Management of epidemic meningococcal meningitis

Transcription

1 Management of epidemic meningococcal meningitis 2008 FOURTH EDITION

2 Médecins Sans Frontières January 2008 All rights reserved for all countries. No reproduction, translation and adaptation may be done without the prior permission of the Copyright owner. ISBN

3 Management of epidemic meningococcal meningitis This edition has been revised by Corinne Danet (MD), Florence Fermon (N), Cathy Hewison (MD) With contributions from Laurence Bonte (L), Menno Goedhart (Log), Véronique Grouzard (N), Myriam Henkens (MD), Jean Rigal (MD), Brigitte Vasset (MD), Francis Varaine (MD) (L) Laboratory technician, (MD) Medical doctor, (N) Nurse, (Log) Logistician English translation updated by Nina Friedman and Caroline Serraf Design and layout by Evelyne Laissu

4

5 Foreword There is a word that designates meningitis in most if not all of the local languages in the African meningitis belt. Populations in this area are familiar with the disease, its severity and its complications. Meningitis outbreaks also occur in other areas, though with less frequency. But wherever it occurs, the disease is always associated with fear, sometimes even panic. Effective treatment and vaccines exist; yet epidemics can reach the scale of national disasters, causing thousands of deaths. The response to an epidemic usually requires sizeable means in order to be effective but above all, it requires an adequate strategy. Responses aim at reducing mortality and minimizing the risk of the outbreak spreading. Various types of response can be selected, based on the epidemiological description and the geographical location of the epidemic. When large epidemics occur, coordination becomes a key factor for an adequate response: an International Coordination Group (ICG) has been in operation since 1997 for that purpose. This guide is designed for health professionals faced with an epidemic of meningococcal meningitis. It is divided into several chapters, which cover: Initial assessment and definition of an outbreak situation, Epidemic response, including case management and vaccination, Evaluation and emergency preparedness. In addition, practical tools are presented in the appendices and on the CD-ROM attached, as well as 1) a film showing how to use the rapid latex agglutination tests for meningitis and the Trans-Isolate medium and 2) a film showing how to organize a mass vaccination campaign in emergency situations. Despite all efforts, it is possible that certain errors may have been overlooked in this manual. Please inform the authors of any errors detected. It is important to remember that, if in doubt, it is the responsibility of the prescribing medical professional to ensure that the doses indicated in this manual conform to the manufacturer s specifications. The authors would be grateful for any comments or criticisms to ensure that this manual continues to evolve and remains adapted to the reality of the field. Comments should be addressed to: Médecins Sans Frontières Medical department 8 rue Saint-Sabin Paris cedex 11 FRANCE Tel: +33 (0) Fax: +33 (0) guide.meningitis@msf.org This manual is also available on the internet at As treatment protocols are constantly changing, medical staff are encouraged to check this website for updates of this edition. 5

6 Table of contents Abbreviations...10 Chapter 1 - Features of meningococcal meningitis epidemics Background...13 Geographic distribution...13 Cycles and seasonality...14 The infectious agent...14 Mode of transmission...16 The role of carriers...16 Age groups at risk...17 Factors influencing the spread of the meningococcus...17 Clinical features...17 Description of epidemics...19 Duration...19 Incidence and attack rates...19 Case fatality ratio (CFR)...20 Key points...20 Chapter 2 - Initial assessment of a meningitis outbreak Confirming the diagnosis...23 Specimen collection...23 Visual inspection of CSF...23 Gram staining...23 Rapid diagnostic tests: latex agglutination tests...24 Culture and sensitivity...24 Determining the type, subtype and clone...24 Epidemiological description...25 Case definition...25 Counting the number of cases and deaths...26 Organizing the data...26 Analysing the data...29 Confirming the existence of an epidemic...29 Comparison with the previous epidemiological situation...31 Analysing the first steps of the response...32 Analysing the local context...32 Initial conclusions...33 Key points...34 Chapter 3- Epidemic management Crisis committees...37 Determining the strategy...38 Free health care...38 Budget estimates...40 Evaluation of the response...40 Key points

7 Chapter 4 - Monitoring Monitoring...43 Demographic data...43 Registration system...43 Reporting data...43 Laboratory surveillance system...44 Data analysis...44 Key points...45 Chapter 5 - Case management Treatment in an epidemic situation...49 First-line treatments...49 Alternatives to oily chloramphenicol or ceftriaxone...51 Supportive therapy...52 Isolation...53 Prophylaxis...53 Case management strategy...55 Case management strategy and supply of medical items...55 Training and supervision...57 Estimating needs...58 Estimated number of cases...58 Number of health facilities to be supplied...58 Bed capacity...58 Key points...59 Chapter 6 - Vaccination Characteristics of meningococcal vaccines...63 The vaccine...63 Presentation...63 Dosage and route of administration...64 Vaccine effectiveness and recommended age for vaccination...64 Contra-indications...65 Adverse effects...65 Vaccine storage and stability...65 Vaccine associations and interactions...66 Vaccination strategies...67 Criteria for launching a mass vaccination campaign...67 Target population...68 Priorities...68 Different approaches...68 Choice of vaccine...69 Prepare a detailed timeframe...70 Preparing the vaccination campaign...71 Vaccine requirements and stock management...71 Storage capacity...71 Stock management...72 Stock control...73 Injection equipment...73 Protection of personnel...74 Cold chain Strategy and equipment...75 Immunization kits

8 Registration and monitoring documents...77 Estimating the vaccination coverage...78 Human resources...79 Composition and tasks of the vaccination team...79 Composition and tasks of the supervision team...80 Team performance...80 Number of teams needed...81 Training and supervision...81 Practical organization of the campaign...82 Logistics and supplies...82 Waste collection and disposal...83 Vaccination sites...85 Practical points...88 Organization of vaccination sessions...89 Key points...90 Chapter 7 - Evaluation Methodology...93 Monitoring of activities...93 Evaluation...93 Evaluation of surveillance...94 Evaluation of case management...95 Evaluation of vaccination activities...98 Chapter 8 - Emergency preparedness Planning emergency preparedness and response to epidemics Surveillance and alert system Laboratory surveillance: confirmation and follow up Case management Vaccination Crisis committee Appendices 1.1 Laboratory examinations Information form for CSF samples Laboratory register Triple-packaging box for shipping biological substances Meningitis register Detection thresholds Example of public information notice Treatment protocol for meningococcal meningitis in an epidemic context Weekly reporting form Meningitis weekly monitoring per district Outbreak monitoring chart Estimating needs for the treatment of meningitis in an epidemic situation (example) Donation forms for treatment kits Standard order for the treatment of 100 cases of complicated meningitis in hospital Tracking the availability of meningitis treatments Tally sheet for meningitis treatment, single dose Standard distribution of population in developing countries Example of vaccination campaign timetable

9 12. Estimated needs - Vaccines and injection supplies for a vaccination campaign against meningitis ICG request form Stock card Cold chain equipment used for mass immunization campaign against meningitis Monitor card Stop!Watch with Freeze tag Estimation of the freezing capacity necessary for a vaccination campaign (example) Immunization kit, 10,000 vaccinations/5 teams Tally sheet for vaccination Daily vaccination summary Summary vaccination by place Summary table per district (example) Job description: vaccination supervisor Estimating the number of vaccination teams needed Estimation of needs for each place of vaccination (example) Record of supplies/equipment per vaccination site Diagnosis confirmation modules References CDRom Appendices 1.2 Information form for CSF samples (pdf) 1.3 Laboratory register (pdf) 2. Meningitis register (word) 4. Public information notice (word) 5. Treatment protocol for meningococcal meningitis in an epidemic context (pdf) 6. Example of weekly reporting form (pdf) 7. Meningitis weekly monitoring per district (pdf) 8. Outbreak monitoring chart (pdf and excel) 9.1 Estimating needs for the treatment of meningitis (excel) 9.2 Donation forms for treatment kits (word) 9.4 Tracking the availability of meningitis treatments (excel) 9.5 Tally sheet for meningitis treatment, single dose (pdf) 11. Vaccination campaign timetable (word) 12. Estimated needs - Vaccines and injection supplies for a vaccination campaign against meningitis (pdf and excel) 13. ICG request form (word and excel) 14. Stock card (pdf) 15.3 Estimation of the freezing capacity necessary for a vaccination campaign (pdf and excel) 17.1 Tally sheet for vaccination (pdf) 17.2,3,4 Summary meningitis vaccination campaign (excel) 18. Job description: vaccination supervisor (word) 19. Estimating the number of vaccination teams needed (excel) Estimation of needs for each place of vaccination and record of supplies/equipment per vaccination site (excel) Videos Rapid latex agglutination tests and Trans-Isolate Organising an emergency mass vaccination 9

10 Abbreviations ADS autodisable syringe C degree centigrade CFR case fatality ratio CSF cerebrospinal fluid g gram ICG International Coordination Group IM intramuscular injection IU international unit IV intravenous injection kg kilogram LP lumbar puncture mg milligram ml millilitre Nm Neisseria meningitidis No. number NGO non-governmental organization NPI National Programme of Immunisation Rx treatment SC subcutaneous injection tab tablet TGV Transport de Germes Vivants/Transport of Live Cultures TI Trans-Isolate UN United Nations UNICEF United Nations Children's Fund WHO World Health Organization 10

11 CHAPTER 1 Features of meningococcal meningitis epidemics Background 13 Description of epidemics 19 Key points 20

12

13 1. Features of meningococcal meningitis epidemics Background Geographic distribution Epidemics of bacterial meningitis are most likely to occur in sub-saharan Africa, in an area known as the "meningitis belt" (or Lapeysonnie s belt ). This epidemic region stretches from the Red Sea to the Atlantic, covering parts of Sudan, Chad, Niger, the Central African Republic, Nigeria, Cameroon, Benin, Burkina Faso, Guinea and Mali (Figure 1). The region at risk tends to include an ever-larger area: epidemics have occurred during the past years in the entire tropical and subtropical zones. Countries spared in the past, such as Rwanda, Zambia, Kenya, Tanzania, Burundi, Uganda, and Democratic Republic of Congo, have all had recent outbreaks. The biggest outbreaks ever reported occurred between 1949 and 1951 (250,000 cases, mainly in Nigeria, Niger, Sudan and Burkina Faso) and between 1995 and 1997 (300,000 cases, mainly in Nigeria, Niger, Burkina Faso, Ghana and Mali). In , an outbreak affected Chad, Sudan (70,000 cases) and Guinea Bissau (2,900 cases). There was also a significant meningitis epidemic in Brazil in 1974 due to meningococci A and C. Figure 1: Meningitis belt. Source: WHO/

14 Background Cycles and seasonality In the meningitis belt, epidemics typically occur in a cyclical manner every 8 to 10 years. The onset is generally in the middle of the dry season (December to February). Outbreaks usually end spontaneously after 3 to 5 months, at the beginning of the rainy season (May-June). However, factors such as population movements or the emergence of a new strain can alter this pattern. Ever shorter intervals between epidemics reflects the constantly changing epidemiology of meningococcal meningitis (Burkina Faso, Niger). The infectious agent Epidemic bacterial meningitis is caused by one particular Gram-negative organism: the meningococcus (Neisseria meningitidis - Nm). Within this species, 12 serogroups have been identified: A, B, C, D, X, Y, Z, W135, 29E, H, I and L. Within each serogroup, there are serotypes, sub-types and clones. For example, A-4 P 1.9 clone III-1 is a meningococcus group A, serotype 4, sub-type P 1.9, clonal complex III-1. With this precise identification of the organism, the spread of an epidemic can be accurately plotted. This technique made it possible to follow the progress of the outbreak that originated in Nepal (clone III-1) and spread through Africa after the pilgrimage to Mecca in Figure 2: Intercontinental spread of meningococcus serogroup A, clonal group III, (Source: WHO) 14

15 1. Features of meningococcal meningitis epidemics Figure 3: Progression of meningococcus serogroup A, clonal group III-1 in Africa, Legend Meningitis belt Geographical progression of meningitis outbreaks Outbreaks 15

16 Background 90% of infections are caused by strains A, B and C. In Africa, meningococcus group A is responsible for the majority of epidemics; more rarely, group C is implicated. In Europe, group B is the predominant cause of endemic cases of meningitis. In the USA, group C is found most often. However, in 2000 and 2001 there were outbreaks of meningococcus W135 in Mecca. In 2002 there was also a large outbreak in Burkina Faso, resulting in more than 10,000 cases. There had never been registered outbreaks of this serogroup before and there is now increasing concern about the importance of this strain in the epidemiology of meningitis in Africa. Attention must also be paid to strain X that is more and more frequently identified. While other pathogens can cause bacterial meningitis, they are not responsible for large outbreaks. The most common pathogens causing non-epidemic meningitis are Haemophilus influenzae (the main cause of meningitis in children under one year of age) and Streptococcus pneumoniae (often associated with other pathologies, such as pneumonia, otitis, etc., responsible for a very high mortality rate). During the course of an epidemic, different organisms may be identified together, with meningococci predominating. Mode of transmission Humans are the only reservoir for this organism. Meningococci harboured by a carrier are spread by respiratory droplets and colonize the naso-pharynx of a susceptible individual. This infection usually goes unnoticed or is heralded by simple pharyngitis. In the majority of cases, an infected person produces protective antibodies and becomes a healthy carrier. In a very small proportion of individuals only, infection spreads via the bloodstream, leading either to meningitis or to meningococcal septicaemia. 16 The role of carriers Healthy carriers play a major role in meningococcal transmission. During the period between epidemics, up to 50% of the population can be healthy carriers without the appearance of a single case of meningitis. During an epidemic, this proportion is variable and can reach 60 to 80%. The carrier state persists for 5 to 15 weeks, and may last as long as 9 to 16 months in some cases. Almost 90% of asymptomatic carriers develop protective antibodies within 7 to 14 days of acquiring the organism. The duration of this natural immunity is unknown. Infants born in endemic regions generally have passive immunity from maternal antibodies. This immune state lasts for the child's first 3 months of life. The level of antibodies then decreases, to reach its minimum at about 5 to 7 months of age. Studies have shown that with endemic exposure to the meningococcus between 2 and 12 years of age the antibody level gradually rises again, to approach adult levels by the age of 13 to 19 years of age.

17 1. Features of meningococcal meningitis epidemics Age groups at risk In the endemic areas, during epidemics, bacterial meningitis is typically a disease of children aged over 6 months, adolescents and young adults. The illness becomes less common in those over the age of 30, with 80-90% of cases occurring in those below this age. However, in the epidemics that occurred outside the meningitis belt, higher attack rates have been reported among those over 30 years of age (e.g. in Uganda and Burundi in 1992 and Guinea in 1993; see page 28). The most at-risk age group should always be determined during the initial assessment. Factors influencing the spread of the meningococcus The epidemiological factors contributing to meningococcal meningitis outbreaks are unclear, and certain among them are of some dispute. However, the following factors are thought to favour an infection by meningococci: The virulence of certain serogroups Alteration of an individual's nasopharyngeal mucosa because of climatic changes, such as cold weather, drought or seasonal winds (e.g. Harmattan winds), or because of a viral infection Immune deficiency Overcrowding: transmission is increased when many people share the same enclosed living space (densely populated urban areas, poor socio-economic conditions, refugee camps). Clinical features Incubation period varies from 2 to 10 days; 3 to 4 days are most common. Adults and children over one year of age Typical meningitic syndrome of sudden onset: Neck stiffness Photophobia Fever up to C Severe headache Nausea, vomiting Purpura, localised or generalised, is typical of meningococcal infection Severe forms: Febrile coma Seizures Purpura fulminans: septic shock, circulatory collapse, necrotic purpura, acute abdominal syndrome. This complication is more frequent in meningococcus group B infections and has a poor prognosis. There may also be more unusual clinical features, related to a particular site of meningococcal colonisation. These include articular, pericardial and bronchopulmonary manifestations. 17

18 Background Children under one year of age The diagnosis is more difficult, with varying disorders: Refusal of eat; gastrointestinal disturbances (diarrhoea, vomiting) Behaviour disorders (drowsiness, feeble or abnormal cry, whining) Abnormal movements (tremors, localised or generalised seizures, upward deviation of the eyes) Tonus disorders (hypotonia, neck stiffness often absent, limp neck) Fever may be absent Bulging fontanelle when not crying, sign that occurs late in the disease with poor prognosis Severe forms: coma, purpura (look systematically for purpura as it is often associated with rapidly evolutive) Sequelae Neurological sequelae are a major problem: it is estimated that 20% of the cured patients will present serious sequelae, including deafness, hemiplegia, facial paralysis, mental retardation, epilepsy. 18

19 Description of epidemics 1. Features of meningococcal meningitis epidemics Duration Epidemics of meningitis last on average for 10 to 14 weeks, the extreme range being from 4 to 20 weeks duration. The peak of the epidemic generally occurs within the 4 weeks after the "epidemic threshold" is reached (see Chapter 2). Figure 4: Meningitis epidemic number of cases and weekly incidence for 100,000 people Khartoum, Sudan, January-April 1988 (Source: MoH) Number of cases Cases/100,000 people, Weeks 0 Incidence and attack rates Meningococcal meningitis is endemic in the countries of the meningitis belt. The background incidence for those countries during non-epidemic years is approximately 20 cases per 100,000 people per year. Typically, an epidemic is defined retrospectively, when a cumulative attack rate of 100 cases per 100,000 people is reported in an area for a period of one year. This figure allows confirmation that an epidemic did actually occur, but it is inappropriate for raising the alarm at the onset of a new outbreak. When an epidemic occurs, in some districts the attack rate can exceed 2,000 cases per 100,000 people (2%). On average, the attack rate is approximately 500 cases per 100,000 people in affected provinces. 19

20 Description of epidemics Case fatality ratio (CFR) The CFR of the disease depends on the quality and rapidity of treatment. Untreated meningococcal meningitis leads to death in 50 to 80% of cases. With appropriate case management the CFR can be reduced to between 8 and 15%. Examples of meningococcal meningitis outbreaks: epidemiological characteristics Country Year Population of affected areas Total number of cases Attack rate/ 100,000 people Total number of deaths CFR (%) NIGER 1991 BURUNDI 1992 GUINEA 1993 NIGERIA 1995/96 MALI 1997 SUDAN 1999 NIGER ,070,160 (2 provinces) 1,604,839 (5 provinces) 1,709,705 (7 districts) 16,000,000 (3 states) 9,190,915 (entire country) 20,738,079 (entire country) 2,682,504 (Maradi region) 4, , , , , , , , , , BURKINA FASO ,472,288 (48/55 districts) 25, , Key points The meningitis belt is the region most at risk. Epidemics usually occur every 8 to 10 years. Neisseria meningitidis group A is the most frequent causative pathogen. Transmission is via respiratory droplets; healthy carriers play a major role. On average, the attack rate is around 500 cases per 100,000 inhabitants in the affected provinces. Meningitis affects mostly the under 30 age group, but it should be systematically confirmed. Outbreaks last 4 to 20 weeks The CFR is approximately 10% during an outbreak (with appropriate case management). Neurological sequelae occur in 20% of cured patients. 20

21 CHAPTER 2 Initial assessment of a meningitis outbreak Confirming the diagnosis 23 Epidemiological description 25 Initial conclusions 33 Key points 34

22

23 2. Initial assessment of a meningitis outbreak Confirming the diagnosis This step is essential in identifying the causative pathogen in order to implement the appropriate measures for prevention and treatment. Only outbreaks caused by meningococcus serogroups A, C and W135 are preventable by immunisation (see Chapter 6). It is imperative to confirm the clinical suspicion of initial cases of meningitis by laboratory tests (see Appendix 1.1). During risk periods and the beginning of an epidemic, LP must be performed and a minimum of 25 CSF samples should be collected in order to obtain a reliable identification of the serogroup(s) involved. Once the serogoup has been confirmed, LP should no longer be done systematically. Laboratory surveillance (serogroup) must be carried out in one or several sentinel districts to determine the evolution of the epidemic. Each sample must be accompanied by a request form which includes relevant clinical details. A register must be set up to record the tests carried out (Gram, latex), the samples sent (TransIsolate), their destination and the results obtained (see Appendix 1.2 and Appendix 1.3). Specimen collection The LP should be performed in an aseptic manner and the CSF collected in a sterile container such as a dry specimen tube or a sterile vial. Visual inspection of CSF In most of the cases, the CSF is cloudy or purulent, but a clear CSF does not exclude meningitis. Note: when purpura is present but a LP is not feasible or is negative, confirmation of the diagnosis can be obtained by direct microscopic examination of the pus or purpura secretions. Gram staining Gram staining identifies certain pathogens but does not allow the identification of the particular serogroup involved. Gram staining can be done in the majority of laboratories in outlying areas. 23

24 Confirming the diagnosis Rapid diagnostic tests: latex agglutination tests These tests are used to identify the different pathogens and serogroups: Neisseria meningitidis groups A and C, W135/Y Neisseria meningitidis group B/Escherichia coli K1 Haemophilus influenzae type b Streptococcus pneumoniae (83 serotypes) Streptococcus agalactiae (group B) In the meningitis belt, latex agglutination tests should be available in the field at the regional level at the beginning of the epidemic season. In other countries, it should be rapidly available in case of epidemic alert. See Appendix 21. Culture and sensitivity At the start of an epidemic, a culture followed by a drug sensitivity test must be carried out to determine the sensitivity of the meningococcus to locally available antibiotics. Determining the type, subtype and clone These tests are carried out in reference laboratories and are reserved for specific epidemiological studies. The CSF is collected on a specific medium (TransIsolate or TGV) in order to transport it to these laboratories (see Appendix 1.1). 24

25 2. Initial assessment of a meningitis outbreak Epidemiological description Case definition It is important to establish a simple case definition for meningitis, based on clinical and biological criteria. SUSPECTED CASE Children under one year of age Fever AND Bulging fontanelle OR Petechial rash Children over one year of age and adults Sudden onset of fever AND Neck stiffness OR Petechial rash PROBABLE CASE SUSPECTED CASE AND Oingoing outbreak OR Cloudy CSF (with or without Gram stain) CONFIRMED CASE SUSPECTED OR PROBABLE CASE AND Positive CSF antigen detection (positive latex agglutination test) OR Positive culture The purpose of a case definition is to permit consistent data collection for the description of the outbreak: number of cases and deaths, age groups at risk, and size and geographical scope of the outbreak. Case definition should be defined by health authorities and agreed upon by all those involved. To ensure reliable monitoring, it must remain consistent throughout the epidemic. Case definition must be simple enough to be used in even the most remote areas. Facing a suspected meningitis case, trained medical personnel should rely on their clinical experience and treat this suspected case, even if the case definition does not seem to fit exactly with the clinical features. 25

26 Epidemiological description This case definition is given as an example. Any case definition is a compromise: it may include patients who are not real cases (resulting in over-estimation because the case definition is not specific enough) or, conversely, exclude patients that are true cases (under-estimation because the case definition is not sensitive enough). In practice, during an outbreak, since only the first 25 cases are confirmed by laboratory examinations, the probable cases represent the basis of the monitoring system. Counting the number of cases and deaths Data collection methods can vary according to the population involved and the existing monitoring system.meningitis cases are sought in the following settings: hospitals, health centres and dispensaries (counting the cases in the register books) more rarely, in villages, by interviewing village leaders or the family members of reported cases, by visiting households, cemeteries, etc. Avoid duplicate notification when patients are transferred (see Appendix 6). When not already in use, a register should be put in place in each dispensary or hospital for essential data recording: name, age, sex, address, date of admission, treatment given, outcome, vaccination status, etc. An example of a specific meningitis register is given in Appendix 2. Recording and notification of cases must go on from the beginning of the epidemic right to its end. Organizing the data Time Data can be recorded chronologically on a graph (epidemic curve), which: can confirm the existence of the epidemic, can follow the course of the epidemic over time, in calendar weeks and not epidemic weeks, to avoid confusion See Appendix 8. 26

27 2. Initial assessment of a meningitis outbreak Figure 5: Meningitis epidemic weekly number of cases and incidence rate; Magaria, Niger, October 1990-April 1991 (Source: Ministry of Health Niger/Epicentre) Number of cases 140 Cases/100,000 people Weeks Cases Attack rate/100,000 people Threshold: 15/100,000 inhabitants Place The geographic distribution of cases or the specific attack rates per area/town/district can be used to identify areas at greatest risk. In addition, the geographical scope of the outbreak can be mapped. Figure 6: Meningitis epidemic, attack rate per 100,000 people by administrative division; Moyo, Uganda, 12 December February 1992 (Source: MSF/MoH Uganda internal report) 27

28 Epidemiological description Population The most important characteristic to be analysed at this stage is age. The mostaffected age group will be identified by estimating age-specific attack rates. This indicator is essential for the definition of the target population for a vaccination campaign. Suggested age groups for purposes of analysis: 0-23 months 2-4 years 5-14 years years years 45 years and up If not feasible, simplified categories can be used (e.g.: 0-23 months, 2-14 years, years, 30 years). Exhaustive recording of age distribution for all cases is often not feasible and is not mandatory: data collected from the most active health facilities can give a good picture of the age distribution in the whole area. 300 Figures 7, 8, 9: Examples Niger, Guinea and Burkina Faso Meningitis epidemic Meningitis epidemic Attack Epidémie rate per de Méningite age. Niger 1991 Attack Epidémie rate per de age. Méningite Guinea 1993 Taux d'attaque par âge. Niger 1991 Taux d'attaque par âge. Guinée Cases/100,000 cas / Cases/100,000 cas / years ans 5-14 years ans ans years >29 > 29 ans years 0-4 years ans 5-14 years ans years ans > >29 years ans Sources: Ministère de la Santé, MSF Sources: Min istère de la Santé, MSF 1200 Meningitis epidemic Attack rate Epidémie per age. de Burkina Méningite Faso 2002 Taux d'attaque (N. Meningitis par âge. Burkina W135) Faso 2002 (N.Meningitis W135) 1000 Cases/100,000 Cas/ months mois 1-4 years ans 5-14 years ans years ans >= years ans Source : Ministère de la Santé 28

29 2. Initial assessment of a meningitis outbreak Analysing the data Analysis of descriptive data and the epidemic curve will help health personnel to identify which groups within the general population are most affected by the epidemic. The main indicators to be calculated per district, region or town are: Incidence rates per week Cumulative attack rates (which include all cases from the start of the epidemic to its end) Case fatality ratio (crude and/or specific according to age group, place) Specific attack rates by age in selected heath facilities Weekly incidence rate Attack rate Number of cases during a given week x 100,000 Population The attack rate is an incidence rate, but this term is used when it relates to a cumulative incidence rate in an epidemic context: Number of new cases during time interval (t) x 100,000 Average population during same time (t) Example: There have been 80 newly recorded cases of meningitis among children aged 5-14 years since the beginning of the outbreak. The total number of children aged 5-14 years in the area is 5,000. The attack rate for meningitis in children aged 5-14 years during this period is: 80/5,000 x 100,000 = 1,600 cases per 100,000 Case fatality ratio Number of deaths due to meningitis during time interval (t) x 100 Number of cases of meningitis notified during time interval (t) Example: Of the 80 children aged 5-14 years who contracted meningitis during the course of the epidemic, 9 died from the disease. The specific CFR for this age group is therefore: 9/80 x 100 = 11.25%. The CFR is an indicator of the quality of case management. Confirming the existence of an epidemic The decision to declare an epidemic will always be a gamble based on the likely progress of the outbreak; however, where there is doubt, it is better to make this decision too early than too late. A meningitis epidemic is defined as an abnormal increase in the number of cases when compared with the usual number observed in a particular area at a particular 29

30 Epidemiological description time of the year. In general, an epidemic occurs against a background of hyperendemic context (meningitis belt); therefore, a distinction has to be made between an impending epidemic and a seasonal increase of cases. Thresholds An epidemic threshold is an incidence rate, expressed weekly, above which an outbreak is likely to occur. Used to define the onset of an outbreak and initiate a response, thresholds are useful tools in endemic regions (see Appendix 3). The ability of any threshold to detect an outbreak can be affected by several factors, such as: Size of the population (administrative level targeted for monitoring); use the administrative divisions (in zones of 30, ,000 people) to calculate the incidence (town, area, etc.). Under-reporting of cases Recent meningitis epidemic or mass vaccination (some acquired immunity) Early or late emergence of cases (before of after the beginning of March for the meningitis belt) Delays in reporting and under-reporting of cases reduce the sensitivity of the threshold. Rumours of an epidemic should be confirmed by field investigation. Endemic regions The epidemic threshold confirms an epidemic and determines immediate action at district and regional level (treatment, immunisation and reinforcing monitoring systems). For populations over 30,000: A threshold of 15 meningitis cases/100,000 people/week is recommended for populations of 30,000 to 100,000 following a study in Burkina Faso, Mali and Togo. An incidence of 10 cases/100,000 people/week provides 100% sensitivity for detecting an emerging epidemic. This lower threshold is less specific but allows a quicker response. This threshold applies only to high risk areas: where there has been no epidemic within the last 5 years. Various factors must be taken into account when evaluating the risk of an epidemic: the early onset of an outbreak at the beginning of the dry season (before March), the immunisation coverage and the population density. For population under 30,000: For smaller populations, one of the two following criteria is used Doubling of the number of cases from one week to the next, for 3 consecutive weeks (e.g. week 1: 1 case, week 2: 2 cases, week 3: 4 cases). 5 cases the same week 30

31 2. Initial assessment of a meningitis outbreak The purpose of an alert threshold is to act as a warning before the onset of an epidemic, and when an outbreak been confirmed in a neighbouring area, this threshold triggers immunisation activities and determines the priority areas. Population over 30,000: 5 cases/100,000/1 week, Population under 30,000: 2 cases in the same week or increase in the number of cases compared to the numbered reported in previous non-epidemic years. In practice, the epidemic threshold is used once; the alert threshold is then used to define operational priorities. Specific situations: in situations such as refugee or displaced people camps, immediate action must be taken, including mass immunization, in the event of 2 confirmed cases of meningococcal meningitis within a week, even if the is no epidemic nearby. Non-endemic regions No epidemic threshold has been established: The situation must be compared with epidemiological data of previous years: a 2-or 3-fold increase in cases compared with a similar period of time in previous years may indicate an epidemic. More than 2 cases within one week can be considered an alert threshold in an institution (jail, orphanage, etc.). Keep in mind that the situation can differ from one village to another within one district. Comparison with the previous epidemiological situation The initial assessment should also provide information on the epidemiological situation in the past. This permits evaluation of the potential risk of the epidemic spreading: if a large outbreak has occurred in the past, the probability that the same region will be affected within 5 years is low. Information about mass vaccination campaigns in previous years will also contribute to estimating the risk and targeting the response: Has the region been affected by an outbreak in recent years? When was the last outbreak? How many cases? What was the CFR? Gather information on the results and evaluation of the epidemic management. Were mass vaccination campaigns implemented? Target? Where? What coverage was achieved? 31

32 Epidemiological description Analysing the first steps of the response The initial assessment should also describe and evaluate the first measures undertaken locally (see Chapter 3): Epidemic management: is there already a crisis committee? If so, what is its composition and how does it function? Was an epidemic declared? Monitoring: case definition, registers, data collection forms, data transmission and feedback, rhythm of collection, transmission and analysis. Laboratory: material available (rapid latex tests, transport medium (TI), capacity of the laboratories, possibility of sending samples to a reference laboratory). Case management: strategy, standard treatment protocol, existing stocks, pending orders, health facilities involved and medical records. Was it decided that treatment would be free-of-charge? Vaccination: strategy, existing stocks, pending orders, cold chain, trained and experienced teams? Analysing the local context Specific information is also important as it may facilitate future responses: Climate: when does the rainy season start? Administrative organization and health system organization Maps, which should include administrative boundaries, health facilities, major towns and villages, and main roads Partners involved: Ministries, NGOs, bilateral co-operation and UN agencies Local events (religious feasts, market days, etc.) and other important characteristics of the local context e.g. large demonstrations Existence of a national response plan Possibilities of purchasing materials locally as well as ways and means of importing medical equipment and vaccines 32

33 2. Initial assessment of a meningitis outbreak Initial conclusions A formal report should conclude the initial assessment. The report should include answers to the following questions: Is it meningococcal meningitis? Which serogroup? Means of diagnosis? Is it an outbreak? Threshold used? Case definition used? What are the incidence rate, attack rate, CFR and age distribution? What is the shape of the epidemic curve? What is the geographic distribution of cases? Is there a particular group of people at risk? What was the epidemiological situation in the previous years? Brief description of national health system and context What are the resources available: human, material, medical, etc.? Are the first response steps adequate? (Who? What? How?) Recommendations: actions to be taken? (Who? How?) Technical support may be needed to strengthen existing capacity in order to provide a quicker and more adequate answer to needs. Technical assistance can be requested for: Investigation and monitoring Case management:organization and supervision of treatment protocols and supplies Mass vaccination campaign: logistical and medical support for planning, organization, supervision and evaluation Evaluation: process (functioning) and results Emergency preparedness: identified needs in training and technical support. In case of future needs, job descriptions for technical staff (international staff) should be discussed and prepared from the beginning. 33

34 Key points Key points Always identify the pathogen on a minimum of 25 CSF samples, then laboratory surveillance of the epidemic s evolution in a few sentinel districts. Describe the size, progress and geographical limits of the outbreak, the groups at risk (age) and the potential range of spreading. Epidemic thresholds are useful tools for identifying affected districts. The CFR is an indicator of the quality of case management. The first steps of the response should be described. A report should conclude the assessment. 34

35 CHAPTER 3 Epidemic management Crisis committees 37 Key points 40

36

37 3. Epidemic management Crisis committees The objective of epidemic management is to ensure that the means correspond to the needs for an efficient response. Epidemic management should be led by a crisis committee at national, provincial and district levels. This committee should include representatives from: The Ministry of Health Reference hospitals and laboratories The National Programme of Immunisation The administrative authority Other sectors NGOs, other agencies (bilateral development agencies, WHO, UNICEF) The composition, terms of reference, frequency of meetings and decisional procedure should be clearly defined. The crisis committee should meet regularly, e.g. daily at the beginning and then once per week. The meetings should be short, with a precise agenda. The minutes of the meetings should be systematically recorded and diffused. Specific technical aspects (laboratory, information) may be delegated to subcommissions. Keep in mind that the health system alone cannot cope with all aspects of a largescale emergency response. The response to a meningitis outbreak requires close coordination between Health and other sectors: representatives of Education, Security, Information, the Military, Customs and so on should participate in the crisis committee when necessary. Examples: Education: schools can be used as vaccination sites; teachers can fill in the vaccination cards Security: policemen may be required to keep order (queues at vaccination sites, etc.) Information: media (radio, newspapers, TV) can be used to inform the population on the availability of drugs, free treatment, date of vaccination campaigns, first signs of the disease, etc. Military: can provide tents for temporary hospitals, logistical support, etc. Customs: can facilitate importation of drugs, vaccines and materials, etc. 37

38 Crisis committees Determining the strategy (see table, following page) The management of the response should be coordinated by the National crisis committee. Experience shows that emergencies such as meningitis outbreaks necessitate strong, centralized management. The teams at regional and district levels are involved in the alert system and in the implementation of the response policy, as defined at the national level. The crisis committee will determine the strategies regarding: Monitoring and follow-up Case management Vaccination Public information The committee will also focus on budget estimates and overall evaluation of the intervention. Free health care Free health care should be defined: what exactly is free? Specific drugs Supportive therapy Consultations Hospitalisations Laboratory testing Others It is important to define who will cover the costs of these acts. 38

39 3. Epidemic management Determining the strategy Monitoring/ Alert system Case management Vaccination Public information Aims To provide data for To reduce the delay between disease To immediately protect the population most To transmit clear and practical decision-making onset and beginning of treatment at risk information to concerned groups Decision-makers will Ensure availability and proper use of drugs Carry out vaccination as early and as quickly as (will facilitate implementation of determine priorities at all levels possible during course of outbreak case management and vaccination) according to these data Key Agree on a standard Define treatment protocols for A mass vaccination campaign: yes or no? Who? steps case definition each facility level General population, health personnel, Treatment protocol for outlying facilities authorities, etc. especially in rural (see Appendix 5) areas Strengthen the Target population? Media that can be used monitorng system Affected age groups = target population All available media Data collection, transmission and analysis Determine priorities for Plan the supply system Where? Identify affected areas What information? case management distribution of kits for each level densely populated areas: urban areas first (see Appendix 4) vaccination regular supplies + supervision (higher transmission risk). Gathering places the disease and its severity public information recentralization at end of outbreak (markets) and refugee camps also a priority treatment possibilities consider threshold and delay vaccination: where, when, who? (children and adults) Ensure regular feedback How? (approach and timeframe) no adverse effects, no contrato all involved start in urban areas indication in pregnancy, etc. determine approaches for rural areas (see below) free of charge Assess neeeds Needs assessment How? specific treatments vaccines, injection equipment local languages hospitalisation capacity (beds) cold chain clear and simple messages Weekly monitoring Weekly monitoring (see Chapter 4) (see Chapter 5) (see Chapter 6) 39

40 Key points Budget estimates The crisis committee must determine budget estimates, taking into account the following costs: Staff costs: salaries, per diems, consultants, etc. Medical supplies: drugs and equipment Vaccination: vaccines, cold chain equipment, injection equipment, kits, logistics equipment National and international freight Staff transportation, including supervision and technical-support visits to outlying areas, vehicle rentals, fuel, etc. Logistics equipment: ropes, tents, megaphones, etc. Administrative materials and stationery: vaccination cards, stamps, tally sheets, paper, pens, training materials, etc. When necessary, food for the staff Communication equipment Evaluation of the response Evaluation is an essential component of any health activity. Its aim is to improve ongoing actions and to formulate recommendations for future responses (see Chapter 7). Evaluation indicators should be formulated at the beginning of the response and necessitate good data-collection procedures (e.g. donation forms, stock cards, patient registers, epidemiological forms, etc.). Right from the start, the evaluation method and information required must be defined and the data forms prepared and distributed. Key points Epidemiological management optimises resources for an efficient response. The crisis committee coordinates the various partners involved and defines and monitors strategies, with 2 main objectives: rapid access to treatment, carefully prioritized, targeted and scheduled vaccination campaigns 40

41 CHAPTER 4 Monitoring Monitoring 43 Key points 45

42

43 4. Monitoring Monitoring Demographic data Demographic data provide the denominators for calculating incidence rates. This has important implications for epidemic management. In many countries, it is difficult to obtain reliable demographic figures. Often, there is no registration; in addition, political or economic reasons may lead to under- or overestimation of specific population groups, and displaced people are sometimes not registered at all. All efforts should be made to obtain the most reliable figures. Data can be obtained from the last census and updated by using annual population growth. Local authorities may have more up-to-date figures than those available at the national level. A consensus with major partners should be reached concerning the population figures to be used for monitoring purposes: once adopted, these figures should be adhered to until the end of the outbreak. Registration system Registers are the basis of any epidemiological investigation. They must be available in each health facility, to provide data related to meningitis cases: name, address, age, sex, date of admission, diagnosis, treatment and outcome (see Appendix 2). Specific meningitis registers can be used. The registers should be kept at the health facility level. The case definition must be standardised, with the same definition being used at all levels of the health-care system (see Chapter 2). Reporting data The monitoring system should be reactivated at the beginning of the meningitis season. Only selected information should be transmitted to higher levels, in order to avoid overloading the monitoring system with irrelevant information. 43

44 Monitoring The necessary information to be forwarded on a routine basis Number of cases and number of deaths At the end of every week, each health facility must forward the number of new cases and deaths due to meningitis for that week (see Appendix 6). Data is usually compiled (see Appendix 7) and analysed at the district level (see Appendix 8) then forwarded to the regional/national level. Zero reporting Even if no cases have been seen during a particular week, this information must be transmitted to health authorities (so-called "zero reporting"). How to report data? Data related to any disease with epidemic potential should be transmitted either by radio, by telephone or by mail (whenever possible) and confirmed later on by a written reporting form. A copy of any oral declaration should be kept by the reporting facility. Every visit to a health facility in an affected region for curative or preventive purposes should be used as an opportunity for gathering data. Laboratory surveillance system With the emergence of outbreaks caused by new menigoccocal strains, it is important to monitor the causative strain throughout the outbreak. To carry out this laboratory testing: Choose hospitals in assected districts per region (sentinel districts). Take 5 to 10 samples per week for latex agglutination tests and culture (TI) for indentification of the serogroup. Data analysis Analysis (time, place and people) should be done at all levels, including outlying areas, to avoid overlooking a possibly very localized epidemic (see Chapter 2). It is an essential tool for the management of the outbreak. At the local level, a simple graph on the dispensary wall, if kept up-to-date every week, will indicate any increase in case numbers and evolution of the CFR. Epidemic and alert thresholds are used as tools for operational decision-making (see Chapter 2). 44

45 4. Monitoring Figure 10: Meningitis incidence rate per week, South Darfur State, Sudan, January-May 1999 (Source: MoH/MSF) Key points Consensus on demographic data is required. Reliable registration and reporting systems are essential. Analyse data on a weekly basis at all levels. The purpose of monitoring is to: signal the start of an epidemic, monitor epidemiological patterns of meningococcal meningitis cases over time, provide quantitative data for decision-makers to adapt the operational response. A routine data collection system is one of the most fundamental components of epidemiological monitoring. Monitor the causative strains in the sentinel districts. 45

46

47 CHAPTER 5 Case management Treatment in an epidemic situation 49 Case management strategy 55 Estimating needs 58 Key points 59

48

49 5. Case management Treatment in an epidemic situation Case management aims at reducing the case fatality ratio and sequelae through reduced delay between onset of the disease and the beginning of treatment. The strategy is to make adequate treatment available in even the most remote areas. Decentralised medical care is essential in order to reduce the delay between the onset of the disease and the beginning of treatment. Case management of patients with meningitis is a heavy burden for any hospital ward. Treatment strategies should therefore be as straightforward and effective as possible. See Appendix 5. First-line treatments 1) Children over 2 years and adults: oily chloramphenicol or ceftriaxone as a single dose Oily chloramphenicol Advantages Single dose IM treatment Excellent diffusion into CSF Resistance in meningococci is rare Preparation very stable Rare adverse effects (when recommended dose is used) Moderate cost Contra-indications, adverse effects, precautions Do not administer in the event of known allergy to chloramphenicol Contra-indicated during pregnancy and breast-feeding May cause agranulocytosis (rare when using the recommended dosage) Do not exceed indicated doses Do not mix with other drugs in the same syringe Presentation and route of administration Oily suspension, 500 mg vial (250 mg/ml, 2 ml), for INTRAMUSCULAR INJECTION ONLY. This preparation must never be administered intravenously. The dose should be divided into 2 deep IM injections administered in 2 different sites (thick product that is difficult to inject). For adults and older children, the injection site should be the upper, outer quadrants of the buttocks. 49

50 Treatment in an epidemic situation Dosage: 100 mg/kg as a single dose, without exceeding 3 g Age 2 5 years 6 9 years years 15 years Dose 1.5 g 2 g 2.5 g 3 g Volume 6 ml 8 ml 10 ml 12 ml Duration Usually a single dose is enough. If there is no clinical improvement or if the patient deteriorates (i.e. repeated seizures, fever > 38.5 C, appearance or aggravation of a reduced level of consciousness or of neurological signs) after 24 hours, administer the same dose of oily chloramphenicol If there is no clinical improvement or if the patient deteriorates 24 hours after this second dose, review the diagnosis. If no other diagnosis has been found, administer ceftriaxone IM for 7 days (100 mg/kg once daily in children and 2 g once daily in adults). Ceftriaxone Advantages Single dose IM treatment in epidemic situation Good diffusion into the CSF Currently no reported meningococcal resistance Treatment of choice in pregnant and brest-feeding women Moderate cost, product widely available The presumptive treatment with a single IM dose of ceftriaxone should not be used in non-epidemic contexts. In non-epidemic contexts, bacterial meningitis (mainly due to S. pneumoniae and H. influenzae) requires a treatment for 7-10 days. The use of a single dose of ceftriaxone in nonepidemic contexts poses a risk for the patient and may have consequences on the sensitivity of the various pathogens to this antibiotic. Contra-indications, adverse effects, precautions Do not administer in the event of known allergy to cephalosporins Administer with caution in the event of allergy to penicillins May cause (rarely): diarrhoea or nausea There is an IM presentation with a solvent containing lidocaine, this must never be used by IV injection. Presentation and route of administration Powder for injection, 1 g vial, for IV injection (+ solvent without lidocaine) The presentation without lidocaine may be administered by IM injection. The volume of solvent (water for infection) to be used is 4 ml per vial of 1 g. Dosage: 100 mg/kg as a single dose, without exceeding 4 g Age 2 5 years 6 9 years years 15 years Dose 1.5 g 2.5 g 3 g 4 g Volume 6 ml 10 ml 12 ml 16 ml Administer half of the dose in each buttock (large quantity to inject). 50

51 5. Case management Duration Usually a single dose is enough If there is no clinical improvement or if the patient deteriorates (i.e. repeated seizures, fever > 38.5 C, appearance or aggravation of a reduced level of consciousness or of neurological signs) after 24 hours, administer the same dose of ceftriaxone. If there is no clinical improvement or if the patient deteriorates 24 hours after this second dose, review the diagnosis. If no other diagnosis has been found, administer ceftriaxone IM for 5 days (100 mg/kg once daily in children and 2 g once daily in adults). 2) Children from 2 to 23 months: ceftriaxone for 7 days Advantages In young children, other pathogens (Haemophilus influenzae, Streptococcus pneumoniae) are common even during an epidemic of meningococcal meningitis. The treatment of choice is ceftriaxone for 7 days. Dosage and duration 100 mg/kg once daily by IM injection for 7 days Weight 4 8 kg 9 15 kg Dose 500 mg 1 g Volume 2 ml 4 ml Administer the dose in one daily injection (small quantity to inject). In outlying areas, ceftriaxone is the best option. When ceftriaxone is not available, oily chloramphenicol may be used in children over 2 months of age: administer one dose of 0.5 g (i.e. 2 ml), then refer in order to provide more adapted treatment. 3) Children under 2 months of age Ceftriaxone is not effective against Listeria, another causative germ before the age of 2 months. In outlying areas, the child must be referred to a hospital. As the clinical features are similar to septicaemia, it is better to treat as such with a combination of antibiotics (ampicillin + gentamicin), see the MSF handbook, Clinical Guidelines. Alternatives to oily chloramphenicol or ceftriaxone ampicillin slow IV: Children: 200 mg/kg/day in 3 or 4 divided doses at regular intervals Adults: 12 g/day in 3 or 4 divided doses at regular intervals Change to oral route as soon as possible to complete at least 7 days of treatment with: amoxicillin PO: Children: 100 mg/kg/day in 2 or 3 divided doses Adults: 5 to 6 g/day in 2 or 3 divided doses 51

52 Treatment in an epidemic situation If the above treatments are not available: aqueous chloramphenicol IV: Children 2 months-1 year: 50 mg/kg/day in 3 or 4 divided doses at regular intervals Children over 1 year: 100 mg/kg/day in 3 or 4 divided doses at regular intervals Adults: 5 to 6 g/day in 3 or 4 divided doses at regular intervals Change to oral route as soon as possible to complete 7 days of treatment with chloramphenicol PO at the same dose. If the above treatments are not available: benzylpenicillin (penicillin G) IV: Children: IU/kg/day in 4 divided doses at 6-hour intervals for 8 to 10 days, depending on the clinical response Adults: 20 MIU/day in 4 divided doses at 6-hour intervals for 8 to 10 days, depending on the clinical response Resistance has recently been recorded. Supportive therapy Fever Tepid sponging, paracetamol or acetylsalycilic acid (aspirin) paracetamol PO Children: 60 mg/kg/day in 3 or 4 divided doses Adults: 3 to 4 g/day in 3 or 4 divided doses or paracetamol IV infusion (only when oral treatment is not possible) Neonates (less than 10 days): 7.5 mg/kg/infusion (0.75 ml/kg/infusion), to be administered over 15 min. Do not exceed 30 mg/kg/day. Infants and children: 15 mg/kg/infusion (1.5 ml/kg/infusion), to be administered over 15 min. Do not exceed 60 mg/kg/day. Adolescents and adults over 50 kg: 1 g/infusion (100 ml/infusion), to be administered over 15 min. Do not exceed 4 g/day. In all events: repeat 2 to 3 times/24 hours if necessary; wait at least 4 hours between 2 infusions. or acetylsalicylic acid (aspirin) PO Children over 8 kg: 50 to 100 mg/kg/day in 3 divided doses; do not exceed 100 mg/kg/day In children, preferably use paracetamol. Adults: 3 to 6 g/day in 3 divided doses; do not exceed 6 g/day In pregnant or breast-feeding women, use paracetamol. Do not use aspirin in patients with purpura. 52

53 5. Case management Seizures diazepam Children: 0.5 mg/kg by rectal route. Use IV route only if technical equipment for ventilation is available (0.3 mg/kg given over 2 to 3 minutes), without exceeding 10 mg Adults: 10 mg by rectal route (or by IV route if technical equipment for ventilation is available). For IV or rectal administration, dilute 10 mg (2 ml) of diazepam in 8 ml of 5% glucose or 0.9% sodium chloride. If seizures do not stop within 5 minutes after the first dose, repeat once Note: for rectal administration, use a syringe without a needle or, even better, cut a nasogastric tube CH 8 (leave 2-3 cm) and place it on the tip of the syringe. Coma Clear airways. Nasogastric feeds with nasogastric tube (beware of risk of pulmonary aspiration). Prevent ocular complications (corneal ulceration) : clean the eyes with 0.9% sodium chloride; close the eyes and protect with a compress. The benefit of dexamethasone (2 to 4 mg IV) to reduce cerebral oedema is controversial and its use must be considered on a case by case basis, especially in children. Skin necrosis A frequent complication of purpura, it must not be neglected and should be treated locally like a burn. Severe cases, including purpura fulminans and septic shock Resuscitation is required: oxygen therapy, restoration of circulating blood volume with modified fluid gelatine or Ringer lactate or sodium chloride 0.9%, as well as the administration of epinephrine (adrenaline) by constant IV drip. Isolation Cases only represent a small proportion of the reservoir. The spread mainly occurs by way of healthy carriers. Patient isolation is thus not justified and not recommended Prophylaxis For many years, sulphonamides were used as chemoprophylaxis for contacts of cases of meningococcal meningitis during epidemics. 53

54 Treatment in an epidemic situation However, as most strains of N. meningitidis are resistant to sulphonamides, they are no longer used for chemoprophylaxis. With regard to rifampicin in mass chemoprophylaxis, use of this drug could lead to the emergence of resistant mycobacteria, thereby compromising the treatment of leprosy and tuberculosis in the area. Chemoprophylaxis is NOT recommended. Vaccination is recommended for close contacts of the patients and, in the event of clinical suspicion, rapid referral to a health facility. 54

55 5. Case management Case management strategy A case management strategy does not only consist in supplying health facilities with treatments. It must also define the type of treatment to distribute, according to the level of the health facility, and ensure a continuous, reliable supply of medicines and equipment adapted to the number of cases. Case management strategy and supply of medical items Treatment kits The organization of medical supplies (drugs, injection equipment, etc.) into kits will facilitate both their transport and stock management, thus reducing risk of shortage. These kits are given to each health facility in affected districts, even to health facilities where no cases have been declared yet. In order to ensure a reliable supply of medical items in peripheral areas, kits must be prepared in advance. 2 types of kits: 1) Kit 5 treatments meningitis single dose (oily chloramphenicol or ceftriaxone and injection equipment), for dispensaries, health centres and hospitals. The single dose treatment (for one case) includes: 6 vials of oily chloramphenicol 500 mg or 4 vials of ceftriaxone 1 g + 2 vials of water for injection 10 ml 3 syringes of 10 ml 3 needles19g; 2 needles 21G; 4 needles 23G 18 tablets of paracetamol 500 mg Remember to also supply, with the first donation, a safety box for the collection and disposal of sharps. With this kit, an optional module is supplied: one treatment meningitis 7 days for children from 2 to 23 months, i.e.: 7 vials of ceftriaxone 1 g + 7 vials of water for injection 10 ml 7 syringes of 10 ml 7 needles19g, 7 needles 23G 2)Complementary kit 10 treatments - complicated meningitis, for hospitals This kit includes antibiotics, complementary treatments and equipment for the management of severe cases in hospitals. See Appendix 9.2. Each kit must be given with the case definition, treatment protocols, and if possible, weekly epidemiological forms (weekly reporting forms). Donation forms are provided (one copy for the health facility, one for the district and one for the donator). Batch numbers must be registered on the donation forms. 55

56 Case management strategy When and where? Peripheral health facilities are supplied with 5 treatments meningitis - single dose kits and the optional module one treatment meningitis 7 days for children 2-23 months. Meningitis in children under two requires specific case management. Patients can be treated as in-patients in a peripheral health facility if there are qualified personnel and adequate resources. If this is not the case, administer the first dose of ceftriaxone and refer to a hospital. With the first donation, provide to each facility at least 1 kit 5 treatments meningitis - single dose and 1 optional module. Subsequent supply will depend on needs. Hospitals and temporary hospitalization units are supplied with 5 treatments meningitis - single dose kits and the complementary kits 10 treatments - complicated meningitis. For each kit delivered, fill out a donation form (see Appendix 9.2). First supply: When the alert threshold is reached, the kits should be delivered by the quickest means possible. Supply all the facilities in the affected region. Supply in priority: hospitals temporary meningitis hospitalization units facilities with the largest number of cases, in priority those with the highest CFR all facilities where cases are registered Then pre-position at least one 5 treatments meningitis - single dose kit (+ an optional module 2-23 months) in health facilities where no cases have been declared yet. Frequency of supply: Set up a supply tracking system. The frequency of supply will depend on the distances, access difficulties, and means available (see Appendix 9.4). At the end of the outbreak: Remaining meningitis-specific treatments/equipment should be centralized at district level, then at regional level in order to avoid them being used to treat other pathologies (especially the kits 5 treatments meningitis - single dose). How many? For each facility, use a supply tracking table to determine the number of treatments required according to the number of treatments available and the number of cases expected per week per facility and the supply frequency. How? Various possibilities: The health staff go to collect the treatments, e.g. at district level. One person is appointed in charge of supply. Transport and health staff must be available to supply each facility and provide the necessary information and/or training. 56

57 5. Case management Training and supervision According to needs (change of protocol, new staff, etc.), it may be necessary to organize training sessions. Training documents, protocols and kits are distributed during these sessions. Supervision visits must be organized in order to answer practical questions and assess case management, stock management and keeping of registers. 57

58 Estimating needs Estimating needs Needs are estimated according to the estimated number of cases and the number of health facilities to be covered. Estimated number of cases In order to evaluate the supplies needed, the estimated number of cases must be calculated at the beginning of an outbreak. The estimate will be based on an average cumulative attack rate of 500 cases/ 100,000 people in an affected area (see Appendix 9.1). Example: INDICATORS CALCUlLATION Population at risk...500,000 Estimated cases (500/100,000)...2,500 Subtract number of cases to date Number of cases estimated until the end of the epidemic...1,900 Add a buffer stock of 25% Total number of treatments to be supplied...2,375 Treatments required for outlying health facilities and hospitals: the proportion of patients requiring hospitalization varies depending on the context (access to health care, etc.); in general 15 to 20 % of cases. Number of health facilities to be supplied This varies according to the health system, the coverage and the personnel in the area concerned. However, experience shows that the estimate calculated above allows treatment to be distributed to all health facilities, even those with no declared cases. Bed capacity Where the caseload is high, temporary meningitis hospitalization units can be set up in outlying areas with the help of one or two nurses from the referral hospital. Any suitable public building, traditional housing or tents can be used. 58

59 5. Case management Key points Meningitis requires emergency medical treatment. The earlier the treatment, the better the chances of cure. Treatment facilities should be as close to patients as possible in order to reduce the delay between the onset of symptoms and treatment. The treatment of choice is oily chloramphenicol or ceftriaxone as a single dose in children over 2 years and adults (indicate each treatment administered on a tally sheet for treatment, see Appendix 9.5). Treatment must be available in all health facilities. Any shortages should be avoided. The distribution of treatment kits ensures that all necessary items are available to provide quality care. No isolation No chemoprophylaxis 59

60

61 CHAPTER 6 Vaccination Characteristics of meningococcal vaccine 63 Vaccination strategies 67 Preparing the vaccination campaign 71 Human resources 79 Practical organization of the campaign 82 Key points 90

62

63 6. Vaccination Characteristics of meningococcal vaccine The vaccine The vaccine is produced by extraction of capsular polysaccharides from certain serogroups, resulting in a synthesized product that induces specific immunity to each serogroup. The only polysaccharides producing acceptable levels of immunity are those extracted from serogroups A, C, Y and W135. The existing group B anti-meningococcal vaccine seems to be poorly immunogenic. Conjugate vaccines provide earlier (usable from the age of 2 years) and longer protection (by the same principle as anti-haemophilus vaccine). A group C anti-meningococcal conjugate vaccine is currently used in routine vaccination in the United Kingdom; a rapid decline in group C meningococcal disease has been observed. A safe and effective single-dose serogroup A conjugate vaccine is currently under investigation. Promising clinical results suggest that it will provide long-term, inexpensive protection, and its large-scale use in the near future appears possible. Presentation Different types of vaccine are available: Polysaccharide vaccines: Bivalent A+C vaccine Trivalent A+C+W135 vaccine (available from ICG) Tetravalent A+C+Y+W135 vaccine (expensive, not available in large quantities) Within the meningitis belt, bivalent A+C vaccine is currently the most commonly used. Conjugate vaccines: Group C conjugate vaccine There are 2 presentations: Multidose vials of lyophilized vaccine to be reconstituted with a specific solvent Single-dose, pre-filled syringe (0.5 ml) Current average price of one dose of meningococcal A+C vaccine (in multidose vials): approximately 0.50 euro Current average price of one dose of meningococcal polysaccharide vaccine A+C+W135 (in multidose vials): 1.00 euro 63

64 Characteristics of meningococcal vaccine Dosage and route of administration 0.5 ml as a single dose by IM or SC injection: Children under 5 years: in the anterolateral thigh Children over 5 years and adults: in the deltoid muscle (outer upper-arm) Vaccine effectiveness and recommended age for vaccination Like all polysaccharide extracts, meningococcal vaccine A+C provokes a typical antigen-antibody reaction (humoral reaction) involving B-cell lymphocytes. The production of B lymphocytes in the bone marrow is not fully mature before the age of 2 years; this explains why the vaccine confers only marginal immunity before this age. The immune response is specific to each serogroup. Antibodies are detected 5 to 8 days after a single injection. Protection lasts 3 to 5 years in adults; this protection diminishes over time. Studies have shown that after 3 years, only 65% of the vaccinated population is protected. Protection diminishes even more quickly in children. Vaccine effectiveness in adults (proportion of population protected among those vaccinated) is 85-90%, decreasing progressively over time. Meningococcal vaccine group A In infants, antibody production can be observed at the age of 3 months with polysaccharide A. In children up to 4-5 years, vaccine effectiveness is lower than in adults. Although it would be justifiable to vaccinate all children over 6 months of age during an epidemic, monovalent A vaccine is not available. Meningococcal vaccine group C The immune response is satisfactory from the age of 2 years, and it increases progressively. The duration of protection is shorter in children under 5 years. Observation shows that children vaccinated before the age of 24 months and receiving a second dose later have a lower immune response than children vaccinated at 2 years and up: until further studies are conducted, the recommendation is to vaccinate only children of 24 months and up. Meningococcal vaccine group W135 The immune response is over 80% in children from the age of 2 years. In practice, bivalent A+C, trivalent A+C+W135 and tetravalent A+C+Y+W135 vaccines should not be administered before the age of 2 years. 64

65 6. Vaccination Contra-indications There is no strict contra-indication for meningococcal vaccination except hypersensitivity to a specific component of the vaccine. Vaccination should be postponed in patients suffering from acute infection (a minor infection is not regarded as contra-indication). Adverse effects Unfrequent and mild, they occur in less than 5% of cases (and are more frequent among children): Erythema at the injection site, lasting 48 hours (in less than 1% of cases) Fever (38 5 C) for 24 to 48 hours (in 0.4 to 2% of cases) There is no risk in vaccinating someone who may be in the incubation period of the infection. Vaccine storage and stability Lyophilised vaccines Lyophilised vaccines are thermostable: They must be stored between +2 C and + 8 C; Freezing at 20 C is no longer recommended, but is not contra-indicated. Close monitoring of the temperature is critical for detecting any breaks in the cold chain: For refrigerators: thermometer, twice-daily monitoring sheet and STOP! Watch card. For transport: thermometer. It is essential that any cold chain problem be carefully noted: successive temperature fluctuations can reduce the efficacy of the vaccine. Any problem should be reported to the person in charge, who will then decide whether or not to use the vaccines. Solvents The solvent is kept at room temperature, however, it must be at the same temperature as the dried powder at the time of reconstitution. The solvent should therefore be put in the refrigerator 12 hours before a vaccination session. Do not freeze. Always use the specific solvent supplied with the powder, manufactured by the same company. Solvent composition varies (phenol or other preservatives), and so might its volume. Always read the manufacturer s instructions before reconstituting. In case of loss of the specific solvent, contact the manufacturer to determine how to proceed. Alternatives are 0.9% sodium chloride solution or water for injection. Use the same volume as the solvent. 65

66 Characteristics of meningococcal vaccine Reconstituted vaccine The reconstituted vaccine is stable if it is stored between + 2 and + 8 C. However, an open vial should not be kept for more than 6 hours. All vials containing the reconstituted vaccine must be destroyed at the end of an immunization session. Vaccine associations and interactions Simultaneous vaccination (at the same time, but with a different syringe and in another injection site) Several studies confirm the clinical and biological effectiveness of meningococcal vaccine when associated with yellow fever vaccine. The few studies concerning association with measles vaccine show a satisfactory response. There is currently no study regarding association with tetanus, poliomyelitis, diphtheria or hepatitis B. Combination with other vaccines (in the same syringe) Such associations are not recommended, as there is a risk of diminishing the vaccine effectiveness. 66

67 6. Vaccination Vaccination strategies To be effective during the course of the outbreak, a mass vaccination campaign must be carried out as early and as quickly as possible. Vaccination campaigns require many personnel and represent a substantial total cost (0.7 to 0.8 euro per person vaccinated). They must not be carried out at the expense of curative activities. The crisis committee needs to define a response strategy that takes into account the human and financial resources that are available and can be mobilized. Criteria for launching a mass vaccination campaign Thresholds and delays If delayed (i.e. about 5 weeks after the epidemic threshold has been crossed or 7 weeks after the alert threshold), a vaccination campaign has a limited degree of effectiveness. Despite the limited impact of a delayed campaign, a large number of cases can still be avoided in densely populated areas. Constraints Preparation time before implementation The preparation time for an emergency vaccination campaign must not exceed one to two weeks. Start of the rainy season In the meningitis belt, the epidemic stops at the outset of the rainy season. The expected start of the rainy season must therefore be taken into account when considering a vaccination campaign. Association with another vaccination Simultaneous administration of several vaccines during a mass vaccination campaign entails additional logistical and organizational constraints. Although possible if necessary, it should not be considered unless another epidemic is also ongoing (e.g. measles or yellow fever) or under special circumstances (refugee camps, displaced populations). The vaccination circuit must be well organised and the vaccination campaign will last longer. Other constraints Accessibility problems (transport and road networks, required time to reach specific places, etc.) and specific events (holidays, religious events, polls, etc.) must also be taken into account when considering a vaccination campaign. 67

68 Vaccination strategies Previous vaccinations Analyse the results of a previous vaccination campaign (if any), focusing on overall coverage and on results by geographical zone and by age groups in the target population. Target population The age group with the highest age-specific attack rate will be the target of the vaccination campaign. Typically, people aged from 2 to 30 years are those most often affected by meningococcus A in the meningitis belt. This represents approximately 65% of the population (see Appendix 10). If the attack rate is high among people over 30 years of age, the entire population must be vaccinated (e.g. in Burundi in 1992 and Guinea in 1993). Under some circumstances (i.e. lack of understanding and popular pressure), it may be difficult to exclude people over 30 years of age (and children below age 2). The decision must take into consideration the country's financial constraints, available stocks of vaccine and current health policy. The objective of a vaccination campaign is 100% coverage of the target population. Priorities Urban and rural zones are to be studied separately. Places where people gather and areas of high population density represent a higher transmission risk. Vaccination should first be organized in population centers of 8,000 inhabitants or more because the risk of transmission is 2 to 4 times higher than in smaller villages. Places where the epidemic threshold has been crossed for less than 5 weeks or the alert threshold has been crossed for less than 7 weeks will be given priority. It is important to analyze the data at the narrowest possible level (that is, at the level of the most remote areas): in a single district, incidence can be high in one zone while still low in neighboring zones. Different approaches Starting a vaccination campaign in urban settings will result in rapidly higher coverage A mass vaccination campaign is the best approach. In urban settings, high coverage rates can be obtained quickly, since access is easy and logistics are simple. At the end of the campaign, maintain one or several sites (according to the town size) for 8 to 10 days in order to receive people who might have been absent during the campaign. Do not forget vaccination in other gathering places, such as refugee camps, jails, military barracks and pilgrimage areas, etc. 68

69 6. Vaccination Examples: In 1993, 80% of the population of Kankan town (Guinea Conakry), i.e. 96,000 people, were vaccinated within 4 days by vaccination teams presenting a total of 18 vaccinators. In 1998, 88% of the target population (6 months - 45 years), i.e. 242,911 people, were vaccinated in Huambo (Angola) in 4 days by teams presenting a total of 36 vaccinators. In rural areas, mass vaccination strategies might combine several approaches Vaccination campaign with mobile teams: This is the most suitable approach for reaching nomadic groups: Mobile teams can be based in a selected village/town for several days, or can go from place to place, following a well-planned circuit; this will require important logistical resources. The vaccination coverage obtained is often lower, and the campaign longer. The campaign should start with priority areas/villages where cases were first declared, in order to avoid panic reactions and needless population movements. Strengthen the vaccination capacity of some health facilities, by adding a vaccination team and providing additional equipment. Target the geographical area: Beyond a certain distance (15 km), the population is harder to reach. Choice of vaccine In each situation, the choice of which vaccine to use is determined on a case-by-case basis, and should take into account all epidemiological and laboratory information available in the country. The choice will depend on the lab results at least 10 Nm-positive samples. To obtain this many positive samples you will need to collect and analyze an average of 20 to 30 CSF samples in the affected district The proportion of Nm W135 required to justify use of the trivalent (ACW135) vaccine is defined according to the number of Nm-positive samples from the affected district. The suggested criteria are as follows: 30% Nm W135 out of 10 to 19 Nm-positive samples 20% Nm W135 out of 20 or more Nm-positive samples The use of trivalent ACW135 vaccine is not justified in the complete absence of laboratory confirmation of Nm W135. Use of the bivalent A+C vaccine is recommended, provided Nm A has been confirmed. If there is a severe epidemic in a district where the requisite minimum number of Nm W135 samples is lacking, trivalent ACW135 vaccine may be justified by one or more confirmed cases of Nm W135 and a Nm W135 epidemic in an adjoining district. 69

70 Vaccination strategies Prepare a detailed timeframe To help visualise and plan the campaign: Analyze the epidemiological situation using the district health map (health care facilities, access route, storage sites, etc.). Include: total population figures, the number of cases and deaths, the weeks over threshold, then add the target population, the optimal duration of the campaign, the number of teams, the existence of a cold chain, etc. Planning must take into account priorities, geographical context and existing means (human, material, logistical, financial, etc) and implementation delays. This planning will be readjusted weekly, based on updated epidemiological data (epidemic trends) and results of the vaccination campaign. 70

71 6. Vaccination Preparing the vaccination campaign After determining the strategy and making an inventory of readily available resources, the crisis committee can proceed with planning the implementation of a vaccination campaign. One of the first steps is to draw up an activity timetable. It should show the various activities listed by category (cold chain, ordering, human resources, supplies, vaccination at the sites, etc.), the name of the person responsible for the activity, and the point in time when the activity should take place. It allows day-to-day monitoring of the campaign. See example, Appendix 11. Vaccine requirements and stock management Estimation of vaccine requirements depends upon: The target population (total population to be vaccinated) The wastage factor (x 1.17): during a vaccination campaign, the loss is estimated at approximately 15%, i.e. if 100 doses are needed to vaccinate 85 people (utilization rate 85%), one should order 117 doses to reach 100 people. A buffer stock, generally estimated at approximately 25%, must always be taken into consideration. See Appendix 12. This first estimate can be adjusted later, based on actual figures coming in from the field (consumption and waste). A mass vaccination campaign in a given site should not start until the entire stock of vaccine required is available. Always order a number of doses and not a number of vials (i.e. ask for 5,000 doses, not 100 vials). This will avoid mistakes due to variable presentations. Storage capacity Because the cold chain must be adequate at each level, it is important to know the volume occupied by the vaccines before organizing transport and storage. Presentations vary according to the manufacturer. Volume per dose can vary from 1.5 to 2.5 cm 3. It is best to verify the volume with the manufacturer. Example: One box of 25 vials of vaccine (each vial containing 50 doses of lyophilized vaccine), measures 2042 cm 3 (16.5 x 16.5 x 7.5 cm) and contains 1250 doses (25 x 50), thus, one dose = 1.6 cm 3. 71

72 Preparing the vaccination campaign Example: Chronological steps for calculating vaccine and storage needs: 1. Estimate the total population... = 50,000 inhabitants 2. Calculate the target population... x 65% = 32,500 people (2-30 years) 3. Target coverage 100%... x 100% = 32,500 people 4. Number of doses to reach coverage... x 1 = 32,500 doses 5. Add wastage factor... x 1.17 = 38,025 doses 6. dd buffer stock... x 1.25 = 47,532 doses Order 47,540 doses 7. Estimate vaccine volume... x 2 cm 3 = 95 litres (in this example, one dose = 2 cm 3 ) Remember: 1 litre = 1,000 cm 3 the solvent occupies the same volume as the vaccine but does not need cold-chain treatment; therefore, it is not included in this step. Ordering vaccines - who should be contacted? The country's central medical stores or the person in charge of the meningitis, if any. The ICG (International Coordinating Group), who manages an emergency stock to deal with possible outbreaks. There is a standard procedure and form for the request (see Appendix 13). The manufacturer can be contacted directly. Prepositioning vaccines before the epidemic season: all countries in the "meningitis belt can preposition a stock of vaccines in the capital city at the start of the season. These vaccines are ordered from the supplier. Stock management Management of the stock should be entrusted to a person with adequate training. This person can be helped by one or more assistants, depending on the workload. The job of each worker must be clearly defined; one worker should be trained so that he might replace the person in charge, if necessary. The timetable and calendar of work (orders, distribution, stock-control activities) will be planned to spread the workload as evenly as possible. 72

73 6. Vaccination Stock control 1) Stock cards The stock card is the main instrument for stock control. For each item (vaccine, solvent, drugs and equipment), a stock card is made out and regularly updated each time the item enters or exits inventory. On this stock card, the following should be noted: The product s International Nonproprietary Name, presentation, number of doses and the batch number (vaccines, solvents, antibiotics). All stock movements (entries, exits, origin, destination) and the date. Orders made and the date. Inventories and the date; if the cards are well kept, the stock column corresponds to the inventory. All irregularities should be investigated. The following can also be included: buffer stock maximum stock other storage locations for this product price per unit The amounts are always recorded in number of doses and never by number of vials. Write only one movement on each line, even if several operations take place the same day. When an order is made, the date, supplier, and amount ordered are recorded, but the stock column does not change. When the order arrives, the amount received is included in the entry column and the stock column is then modified (see Appendix 14). 2) Delivery and order forms Pre-printed order forms make it easier to prepare orders and inventories and to avoid transcription errors. Signed copies of these documents should be kept by the person in charge of distribution, and in each health facility. Injection equipment The safety of injections must be guaranteed, i.e. through: The use of auto-disable syringes Correct injection techniques Appropriate disposal of syringes and needles (safety boxes) 73

74 Preparing the vaccination campaign Equipment required to guarantee safe injections Auto-disable syringes 0.5 ml (fixed needle) This is the standard for a mass vaccination; Auto-disable syringes cannot be reused (allow for 5-10% wastage due to handling errors), thus reducing the risk of exposure to infected blood (hepatitis B and C, HIV). Safety boxes designed for the collection and disposal of used syringes and needles These safety boxes (5 or 15 litres) are waterproof and puncture proof. They must be systematically used in a mass immunization campaign. Instructions on how to fold and use the safety boxes must be clearly marked on the side of the box and must be strictly respected. Temporary or permanent incinerators Key points: the supply of safe injection equipment The injection equipment must be systematically ordered together with the vaccines in order to avoid the use of inappropriate equipment (e. g. reusable syringes). Always order the corresponding number of injection devices when ordering the vaccines. For help in calculating the quantity of injection equipment needed, see Appendix 12. Bundle policy for donors: the purchase must always include the entire package, i.e. vaccines + auto-disable syringes + safety boxes for the collection and elimination of used syringes and needles. Protection of personnel Vaccinators should always wear gloves; the large number of injections they perform at a very brisk pace means there is a high risk of accidental exposure to blood. The personnel in charge of waste collection and disposal, including safety boxes for the collection and disposal of used syringes and needles, should wear thick gloves (e.g. heavy-duty gloves); The protocol for managing accidental exposure to blood (AEB), and the treatment, should be available from the start of the vaccination campaign. In the event of an accident (a cut, a prick through the gloves, or a deeper wound): Let the wound bleed, immediately wash the wound and the surrounding skin with soap and water, rinse, then disinfect the wound with polyvidone iodine 10% or a solution of active chlorine 0.1% or a Dakin solution or 70% ethanol. Minimum contact time of 5 minutes is recommended. 74

75 6. Vaccination An AEB should be declared according to national procedures. Follow the national protocol for medical treatment (for MSF, refer to the MSF Procedures to be followed in case of accidental exposure to blood). Cold chain Strategy and equipment A fixed central refrigeration and deep freezing unit should be set up to supply the teams. The entire cold chain should be totally centralised, including vaccine management, distribution, ice-pack supplies and logistics supplies (including vehicles and fuel management). Select a large town or any central spot that is accessible at all times and permanently supplied with electricity (24 hours), such as a large town. Production of ice is quicker and safer with electrical refrigeration. Assess existing resources and additional needs. Equipment needs for active and passive cold chain are estimated based on: the volume of vaccine to be stocked the cold chain supplies needed at the vaccination sites (cold box, vaccine carriers, ice packs, thermometers). See Appendix Equipment needed Equipment used for: Information required to estimate cold chain needs Passive cold chain Cold boxes Vaccine carriers Thermometers Vaccine transport and storage at the vaccination site Draw up the list of standard equipment per vaccination site Estimate the number of sites Estimate the duration of the campaign Active cold chain Refrigerators Thermometers Monitoring tools (see Appendix 15.2) Freezers Ice packs Vaccine storage Making ice packs Calculate the anticipated volume of vaccine for the campaign Estimate the freezing capacity needed for the duration of the campaign On the basis of this information and the vaccination schedule, estimate the equipment and freezing capacity needed for the campaign. See Appendix There is usually some cold chain equipment on site, which only needs some additional equipment. In some cases, it might be necessary to set up an entire cold chain quickly. 75

76 Preparing the vaccination campaign Before ordering any additional equipment, make an inventory of the equipment available at each level: Check the existing refrigeration (vaccines) and deep-freezing capacity (ice packs) as well as storage capacities. Get an exhaustive, updated list of available equipment in each health facility; note the number, type, brand and fuel required. Make sure that equipment is actually on location and that it functions. Count the number of ice packs and their volume (0.3 litre or 0.4 litre or 0.6 litre). Consider other possible means of refrigeration without neglecting local possibilities: equipment rental factories producing ice (fisheries, businesses, markets, ice cream producers, etc.) Assess availability of electricity generation plants and check their reliability, accessibility and quality. Check power and voltage and possible variations over 24 hours. Draw up a list of existing generators, specifying fuel type (gas, kerosene, etc.). Check all transportation resources (renting, borrowing, etc.). Proper storage is essential to ensuring vaccine quality. Campaigns require very large amounts of ice. Make sure you have a large number of ice packs, so that they can be rotated. When ordering, multiply the anticipated number of ice packs by 2 or 3 (vaccine carrier, RCW25 cold box, etc.). The number of ice packs needed per day during the campaign is estimated based on: The list of standard cold chain equipment per site The number of ice packs needed per day per site (ice packs for cold boxes and vaccine carriers, ice packs for storing reconstituted vaccine and pre-filled syringes) The number of sites to be supplied per day The duration of the campaign. Immunization kits Kits are a useful way to get all the required equipment quickly and at the same time. An immunization kit for the emergency vaccination of 10,000 people has been prepared by MSF, calculated for 5 teams (see Appendix 16). Take into account the estimated delivery time for supplies, which varies from country to country. The immunization kit does not contain vaccines, which must be ordered separately. The kit is split into specific modules and can therefore be ordered as a whole or by module, according to the strategy chosen, the available human resources and local constraints. 76

77 6. Vaccination Registration and monitoring documents Ensure that all the required documents are ready before starting the campaign. Meningitis vaccination cards Using an individual meningitis card for each person vaccinated requires a larger team (for one vaccinator, at least 2 additional people are needed for registration). This can slow down the speed of vaccination. The extra cost of the additional staff and stationery should be considered. Meningitis vaccination cards should thus be used only if there are plans for further evaluation/research (i.e. vaccine effectiveness). In such cases, the specific information related to the research must be recorded: type of vaccine, date, name of person vaccinated. Different models can be used: National Immunization Programme cards If the cards have no specific space for meningitis vaccine, this can be added by hand or by using a stamp labelled meningitis vaccine, with the date. Special cards for meningitis vaccination purposes The date and name of the beneficiary must be recorded on the card; a dating stamp saves time and is easier to read. Daily tally sheets Tally sheets are indispensable for each session, at each vaccination setting, as they document all daily activities. Everyone vaccinated must be tallied on this sheet according to age group: ages 2-4, 5-14, 15-29, 30 and up. Other information to be recorded on the tally sheet: Date, place, vaccination site (if several sites in one place); Name of the team leader: this will help in further control, if necessary; Number of vaccine vials used, in order to calculate the utilization rate; Other information: items received and left over at the end of the day (number of vaccine doses, solvents, syringes, needles, safety boxes, etc.) information specific to the context: tally by particular population groups (e.g. local population, displaced persons, refugees) Tally sheets for each site are compiled every evening, then sent to the coordinator when the campaign is over. See Appendix

78 Preparing the vaccination campaign Vaccination summary forms Using the tally sheets, the supervisor completes the daily vaccination summary and the vaccination summary table by site (see Appendix 17.2 and Appendix 17.3). He estimates the vaccination coverage and the vaccine utilization rate. Estimating the vaccination coverage Number of doses administered x 100 Target population to be vaccinated Vaccine utilization rate Number of doses administered x 100 Number of doses used* * the number of vials opened multiplied by the number of doses per vial Monitoring these results each day allows for adjustment, if needed: at the vaccination site, inform the team of the results, discuss any problems encountered, and readjust (use of equipment, tally sheets, etc.) verify whether or not the vaccination coverage objective has been reached. Depending on the results, readjust: organize additional day(s) for vaccination or change the number of teams at the site, strengthen/adapt the public information, etc. The supervisor calculates the daily figures every evening and discusses the results with the team. Feedback is important and motivating for the teams. Vaccination campaign summary table (e.g., at the district level) Numbers should be compiled in order to: Evaluate the vaccination coverage achieved and analyze the epidemiological situation, with regard to the coverage, at the administrative division level. Provide information to all involved institutions/agencies (health authorities, administration, partners). See Appendix

79 6. Vaccination Human resources A mass immunization campaign requires a lot of human resources. To avoid compromising regular health activities, care must be taken not to monopolize all available resources. Composition and tasks of the vaccination team A core team is formed around each vaccinator. In general, for a quick, smooth flow, the following number of people are required: 2 preparers for 1 vaccinator 2 to 3 registrars for 1 vaccinator 2 recorders for 1 vaccinator. Recording is a key job, since any error in the tally will lead to erroneous interpretation of the vaccination coverage. Security and order must be strictly organized, especially during the first 2 days of immunization at a given site, as this is when there will be the biggest crowds. A vaccination site can accommodate one to three teams, at most. It is not advisable to have more than 3 teams at any one site, as crowd control becomes difficult to manage. The job description for each team member is set out, listing the tasks to be performed. In rural areas, the number of preparers, registrars and recorders is adapted according to the target population and expected performance. Core team for vaccination composition and responsibilities Responsibility Qualification Number Tasks Vaccinator Assistant/Preparer Registrar Recorder Security and information officer Nurses, midwives, health officers Health officers, student nurses Literate people (teachers, administrative agents, etc.) Literate people (teachers, administrative agents, etc.) Volunteers, section chiefs, policemen 1 Clean the skin with water Vaccinate 2 Reconstitute the vaccine Fill the syringes 2 or 3 Prepare vaccination cards Stamp or write the date of vaccination 2 Record number of people vaccinated, by age group, on tally sheet 6 to 8 Inform the population Triage of target population Organize waiting lines Maintain security and order on the site 79

80 Human resources Composition and tasks of the supervision team The supervisor should have a vehicle at his disposal in order to monitor the work being done at the various sites. Composition and tasks of the supervision team Responsibility Qualification Number Tasks Supervisor Health professional 1 Supervise and train team Replace vaccinators, if necessary Compile and analyze vaccination data Send the information to the crisis committee See Job description, Appendis 18. Driver Driver 1 Transport team, equipment, and waste Provide supplies for team Logistician Technician 1 Prepare and set up vaccination sites Provide vaccination teams with supplies Collect, transport, and dispose of waste In urban settings One supervisor can manage 1 to 3 sites. Beyond that number, the quality of monitoring decreases and coordination is more difficult. One logistician assists 1 to 2 supervisors (a maximum of 6 sites at the same time. Daily meetings are necessary to coordinate and transmit information among the local authorities, the vaccination teams and the health official. In rural areas The supervisor s role is more focused on general organization as he is less available at each vaccination site. The logistician can only cover a limited number of teams in terms of site organization, cold chain, and transport. Team performance Under optimal conditions, 1 vaccinator, using auto-disable syringes prepared in advance by 2 preparers and working 6 hours daily, can vaccinate 180 to 240 people per hour (1,000 to 1,500 people per day). Examples: In Burundi in 1992 and Guinea in 1993, perfectly trained teams were able to vaccinate 350 people per hour (without vaccination cards in the Guinea example). These people vaccinated between 8,000 and 10,000 people daily, in 6 to 7 hours. Each vaccinator, using prepared syringes on skin that had already been cleaned, was thus able to inject an average of 6 people per minute. 80

81 6. Vaccination Number of teams needed The number of teams needed is calculated according to the size of the target population to be vaccinated, the expected performance per team, and the desired duration (see Appendix 19). For example: Planning the number of vaccination teams for the town of Nzangwa Vaccinators are expected to perform 1500 vaccinations per day. To vaccinate in 11 days, 6 teams suffice. To vaccinate in 7 days, 10 teams are needed. Choose the optimal duration per site depending on the number of vaccinators and available personnel, and the desired duration. For example: Site/town Target population Expected performance Duration with one team Optimal duration Number of teams needed Nzangwa 100,750 1, Nzangwa 100,750 1, Kibongo 13,000 1, Burenge 52,000 1, Training and supervision Depending on needs, all teams should receive training or have their skills updated prior to the start of the campaign. A practice run should be done before the campaign, involving the entire team, with all the necessary materials and equipment. Job descriptions should be prepared and distributed to all employees, as well as other specific instructions or guidelines, as needed. Vaccination campaigns generally start in urban settings, where supervision is easier. The same teams should then be sent to the rural areas: technical supervision should then be straightforward. 81

82 Practical organization of the campaign Practical organization of the campaign The campaign should start as soon as preparations are complete, the teams are trained and fully supplied with vaccines and equipment. Any delay due to flaws in planning (vaccine shortage, cold chain problems) could lead to disturbances, or even riots, in a population that is anxious to be protected. The MSF film Organizing an emergency mass vaccination is a support tool for preparing the campaign, and can be used for information at all levels and for training vaccination teams. Logistics and supplies The logistics and medical teams work together on the overall planning and organization. Key points discussed in this collaboration are: Evaluation of logistical needs Organization and monitoring of cold chain Organization of supplies: storage, transport Organization of logistics staff scheduling and payroll Planning and organization of transportation (vehicles, drivers, fuel) Choice of the immunization sites and required equipment Preparation of the waste collection and disposal system Set-up of immunization sites Supplying of the immunization sites Organization of the cold chain One person should be in charge of the cold chain. Having only one person responsible for the cold chain allows for strict control of the stocks and their flow (in, out), with precise dates and batch numbers for each entry/exit. This person should be in charge of checking and recording the temperature (one monitoring sheet for each apparatus), distributing vaccines, and freezing ice packs. Make sure that the refrigerators and deep freezers are in good working condition and turned on 24 to 48 hours before receiving the vaccines: the temperature must be between +2 C and +8 C before storing the vaccines. Refrigerate the solvents (refrigerator or cold box) 12 hours before use, so that the solvent will be at the same temperature as the lyophilized vaccine for reconstitution. 82

83 6. Vaccination During a vaccination session, keep the reconstituted vaccines between +2 and +8 C: put them in the foam of a portable vaccine carrier (which is used for this purpose only, and not for storing unreconstituted vaccine), or on an ice pack; do not put the vial in the hole that is in the middle of the ice pack. Preparers should fill the auto-disable syringes in advance. They should keep them on a tray placed on an ice pack inside a thermally insulated bag or a vaccine carrier. Store half-melted ice packs in a cold box: this saves time when re-freezing. As much as possible, try to follow policies and recommendations of the National Immunization Programme, in order to avoid discrepancies and further confusion. Figures 11 and 12: How to keep vaccines cold during a vaccination session Waste collection and disposal This activity should be carefully planned while preparing for the campaign. Vaccination campaigns produce three types of waste: Auto-disable syringes, syringes and needles for dilution Empty vaccine and solvent vials Other waste: gloves, cotton wool, packaging boxes, etc. All waste must be collected daily and: sorted by categories above; gathered at a single site; disposed of quickly. The treatment system should be ready by the time the campaign starts. 83

84 Practical organization of the campaign The different stages of the system are: 1) Sorting Waste must be correctly sorted at each site, by type: syringes and needles in safety boxes. Do not fill boxes beyond the red maximum fill line, as this can prevent closing and result in needle sticks. empty vaccine and solvent vials are collected in a container reserved for this purpose, to facilitate counting and transport. the other non-infectious waste (gloves, etc.) can be thrown into plastic bags that are closed prior to transport. 2) Storage Waste must be stored in specific areas with restricted, monitored access. Waste collection and disposal for vaccination campaigns Type of waste Collection Disposal Sharps Other waste Needles ADS Safety boxes Incineration and burial Vials Boxes (empty cartons, etc.) Crushing and burial Cotton wool Packaging Trash bag Incineration and burial 3) Treatment and disposal Infectious waste (sharps) The method of choice is centralization at a site that has treatment and disposal facilities (hospital, cement works, etc.). Waste is transferred to this site, where it is treated at high temperature and disposed of. If this is not feasible, use on-site treatment and disposal by: burning in a temporary incinerator; this process reduces the volume of waste (see Public health engineering in emergency situation). then burying waste in a secure area. Advantages Disadvantages Centralized disposal Easier monitoring and control A lot of handling Increased exposure risk On-site disposal Little handling Reduced exposure risk Requires a dedicated area and a watchman at each site. Difficult to monitor Choosing the centralized option requires paying particular attention to waste transport: safety boxes for syringe and needle collection and disposal must be transported in a closed container (plastic bucket with cover, metal trunk, etc.) in order to avoid any risk of spilling the sharps. 84

85 6. Vaccination Vaccine and solvent vials should be crushed to prevent re-use, and thrown into a pit dug for this purpose. Non-infectious waste should be burned and buried. The waste area should have a pit for incinerator residue. When the vaccination campaign is over, this pit should be secured by sealing it with concrete, to eliminate any risk of needle stick (needles are not destroyed and thus remain sharp). Transport and storage Reliable transport is essential for conducting activities (deploying vaccination teams, supply, waste collection, supervision, etc.). Transport needs will depend on the campaign strategy (location and number of sites), scheduling (number of teams and duration of vaccination), and the arrangements for storage and supply in the field. Ensuring transport and storage requires significant resources: A central storage facility at the district level, with the stock and cold chain in the same location, is ideal. Set up a rigorous management system with standardized tools. Provide for the necessary staff. Organizing the supply of vaccine and materials to vaccination sites At this stage of organizing a vaccination campaign, you must: estimate the precise needs for each vaccination site (see Appendix 20.1); set up a supply and consumption monitoring tool (see Appendix 20.2). To make it easier to monitor supply, organize it into two modules: an equipment module: designed for one vaccination team and delivered when the vaccination starts; a renewable supplies module: designed for one vaccination team for one day. Each day, the team leader is given a new module (if there is more than enough leftover stock for a day of vaccination, resupply is not necessary). These modules should be prepared ahead of time at the central storage facility (see Appendix 20.2). Vaccination sites Depending on the context (rural or urban area, refugee camps), the team can use schools, places of worship, community rooms, tents, or even the shade of a tree. Avoid using health centres, if possible, in order not to disrupt curative care activities. Criteria for the selection of an appropriate site The area must be accessible to all. Clearly cordoned area (walls, barriers) facilitate triage and security. 85

86 Practical organization of the campaign To prevent jostling, the waiting area should be large and shaded enough to allow a queue at least 50 metres long (using ropes or nets). 2 separate doors (for entry and exit) will avoid confusion and jostling. The area must be organized in such a way that the teams and the people can circulate easily. The area where assistants fill the syringes must be calm, spacious and set apart, but easily accessible by the vaccinators. The site should not be too spacious, because controlling people s movements can then be difficult. Number of sites Immunisation sites should be located according to population density, the size of the zone, accessibility, and available staff and resources. Sites should be set up on main access routes. They should cover all neighborhoods. Warning: The greater the number of sites, the more challenging the logistics (transport, supply, cold chain, etc.). Walkie-talkies, mobile phones, radio, or other communication equipment will facilitate the logistical organization and save on time spent moving around. The average estimate is one site per 15,000 to 20,000 inhabitants. Sites will be chosen according to the town size, the population density in each sector, and the access network. 86

87 6. Vaccination Figure 13: Vaccination site 8 m Exit m m 50 m Entry 1 2 Entry 1 1. Triage zone, age check 2. Information about vaccination (using a megaphone) 3. Preparation of vaccination cards (if necessary) 4. Vaccination posts 5. Recording posts (tally sheets) 6. Syringe preparation posts 7. Supply and storage area Rope 87

88 Practical organization of the campaign Practical points Prepare the site and all the equipment the day before. Organize queues with ropes or tapes. The line must be at least 50 metres long and sufficiently narrow so that people enter one by one. A queue that zig-zags is better than a straight queue for reducing the press of the crowd. If the site is wide, use rope to mark the entire circuit from entry to exit. Vaccination cards are filled out at the entry to the site; tally sheets are filled out right after vaccination. Equipment and materials should be stored in a place accessible to preparers and not accessible to the population. Begin vaccinating once everything is ready, including at least 100 syringes already filled. Provide drinking water in the waiting areas: people may come from remote areas. Open-air sites can be used only in rural areas. Make sure there is enough rope to mark off the various areas, and clearly indicate the circuit. 88

89 6. Vaccination Organization of vaccination sessions Activity Area Equipment Personnel Tasks Waiting shady, spacious area plastic sheeting for shade, shade netting community members inform the population areas drinking water and mugs (security and order) organize queues 1 megaphone + batteries volunteers maintain order Triage after the waiting area ropes +++ community members check age (target population) when entering the stakes (security and order) organize waiting lines, explain the circuit to be lines followed inform the population Registration shady, spacious area tables and chairs literate people (teachers, fill in vaccination cards, first name, surname, age, clearly mark out the vaccination cards and plastic cover administrative staff) date circuit pencils, pens, date stamps explain importance of keeping this document answer any questions Vaccination after registration tables and chairs vaccinators reconstitute the vaccines continues lines / mark cold box and vaccine carrier for vaccines assistants prepare the syringes on a tray circuit if needed, another vaccine carrier for the qualified health assistants clean the skin of people to be vaccinated allow large space for assistants ice packs (to hold syringes and vials) or students trained in inject the vaccine assistants, in quiet 1 thermometer for each cooling device vaccination sort the waste area away from the water + soap + basin for washing hands queues injection equipment, kidney dish, cotton, dressing trays or basins for pre-filled syringes, scissors safety boxes for used syringes / needles, waste bags Storage close to assistants and all the cold-chain equipment for storage and logistics officer (in charge manage the stocks (vaccines, injection equipment) vaccinators transportation of supplies) check the cold chain under shelter all the injection and waste disposal equipment organize a safe waste collection and disposal water container Recording at exit point, near the tables and chairs literate people (teachers, carefully fill in tally sheets according to age group (tally sheets) vaccinator tally sheets + stationery administrative staff) orient vaccinated people towards exit answer questions 89

90 Key points Key points Meningitis outbreaks caused by meningococcus A, C and W135 can be controlled through early vaccination. Vaccination does not prevent subjects from being carriers. Vaccinate in priority the age group and locations with the highest attack rate. Areas of high population density should be vaccinated first. Bundle policy to ensure safe injection: vaccines should always be delivered with the appropriate number of auto-disable syringes and safety boxes for used syringes and needles. A cold chain is crucial to ensure the quality of vaccines. Tally sheets are essential for monitoring of vaccination coverage. Vaccination teams: For 1 vaccinator, a minimum of 12 people is required Specific training of all staff is necessary prior to the campaign A practice run should be done beforehand. Vaccination sites should be carefully selected and organized. Under optimal conditions, one team can vaccinate 180 to 240 people per hour (1,000 to 1,500 people per day). The waste collection and disposal system should be organized before starting the campaign. 90

91 CHAPTER 7 Evaluation Methodology 93 Evaluation of surveillance 94 Evaluation of case management 95 Evaluation of vaccination activities 98

92

93 7. Evaluation Methodology Evaluation of the response includes the monitoring of activities and evaluation of the intervention. Monitoring of activities The monitoring of activities enables correct epidemic management, analysis of results and identification of any problems. It should be carried out from the start to the end of the epidemic on a weekly (monitoring, curative case management) or daily (vaccination activities) basis. Data with which to calculate indicators are routinely collected and analyzed in detail at district level (vaccination coverage, vaccine utilization rate, availability of treatment, etc.). The vaccination tally sheets are filled in every day on the vaccination sites in order to estimate the vaccination coverage. This daily analysis is used to evaluate the results. If the results are not satisfactory, identify the causes (shortage of vaccines or medical supplies, too few teams, lack of public information, poor choice of sites, etc.) and, if necessary, take corrective measures (supply, duration of the campaign on a site, number of teams, public information messages, etc.). Evaluation An evaluation analyses each strategy and response, focusing on several aspects: Effectiveness Accessibility Timeliness Safety and quality Resources mobilized Data are collected during the epidemic, recorded and analyzed at the end of epidemic at district, regional or national level. From the beginning of the intervention: Define the objectives and indicators. Ensure that all the tools are available and that the staff has been trained to use them. Certain information requires field visits and is only measured in selected health facilities or vaccination sites, using appropriate epidemiological sampling methods. These visits must be scheduled during the campaign. A final evaluation report of the intervention should provide constructive recommendations for future epidemic responses. 93

94 Evaluation of surveillance Evaluation of surveillance Indicators Required data Source/tools Method Comments EFFECTIVENESS OF THE INTERVENTION/EFFICIENCY Proportion of health - Number of facilities where case - Case definition available in Visit a sample of health Pay particular attention to facilities with case definition is available the health facility facilities outlying facilities definition - List and level of health facilities - Supervision check-list Expected result: 100% Proportion of health - Number of facilities that send the - Meningitis weekly Exhaustive, for the entire Expected result: 100% facilities that submit weekly reporting form every week monitoring form duration of the epidemic weekly reporting forms - Total number of health facilities - List of health facilities Time required to receive - Date of transmission of the weekly - Meningitis weekly Exhaustive, for the entire Expected result: 1 to 2 weeks weekly reporting forms reporting forms monitoring form duration of the epidemic - Time between the recording and - Weekly reporting form the reception at district level of surveillance data LABORATORY SURVEILLANCE % positive samples - Number of samples collected per - Laboratory register Exhaustive in sentinel type of lab. exam. - Information form for CSF districts, for the entire - Number of positive samples per samples duration of the epidemic type of lab. exam. 94

95 7. Evaluation Evaluation of case management Indicators Required data Source/tools Method Comments EFFECTIVENESS Declared CFR Number of cases and deaths Weekly monitoring forms Analysis of weekly Easily measurable if the declared by administrative unit monitoring forms monitoring system is reliable (region, district, etc.) Expected result: 5 to 15 % Crude and age-specific CFR, Number of cases and deaths per Health facilities - Calculate for each Eliminate bias from unreliable per facility (hospital, health age, per facility, during the consultations/admissions hospital monitoring system centre) epidemic period register - Randomly selected sample of health facilities ACCESSIBILITY Proportion of operational - Number of health facilities - Donation forms Comprehensive analysis For the facilities not supplied, health facilities supplied supplied in each administrative - Stock cards of donation forms and check if they are operational with treatment during unit - Records of treatment list of health facilities Expected result: 100% the epidemic - List and level of health facilities availability Proportion of health facilities - Number of facilities with - Protocol available in the Visit a sample of health Protocol in the national supplied with the treatment treatment protocol available facility facilities language protocol - List and level of health facilities - Supervision check-list Expected result: 100% Proportion of health facilities - Shortage at district stock level? - Stock cards Comprehensive analysis of Systematic analysis at district that experienced a shortage Date? For how long? - Donation forms stock cards, donation level of treatment - Number of facilities that experienced - Supervision check-list forms and records of Expected result: no shortage a shortage of treatment - Records of treatment treatment availability - List and level of health facilities availability Visit a sample of health facilities and check stocks 95

96 Evaluation of case management Indicators Required data Source/tools Method Comments TIMELINESS Time required to supply - Date of first reported cases - Weekly monitoring forms Comprehensive analysis of: Pay particular attention to specific treatments (time - Date of supply of specific - Stock cards - Weekly monitoring forms outlying facilities between the first cases treatment to the health facility - Donation forms - Donation forms declared and the supply of - Records of treatment - Stock cards for specific treatment) availability treatments - Records of treatment availability Time between alert in a - List of supplied health facilities - Weekly monitoring forms Comprehensive analysis of: Pay particular attention to health zone and the supply and date - Stock cards - Weekly monitoring forms outlying facilities of specific treatments to - For each place: date when - Donation forms - Donation forms This indicator is calculated acilities in the district alert/epidemic thresholds were - Records of treatment - Stock cards for specific using the dates when epidemic crossed availability treatments thresholds were crossed. - Records of treatment Expected result: 1 to 2 weeks availability SAFETY AND QUALITY Proportion of cases treated - Number of cases - National protocol In a sample of facilities, Pay particular attention to according to the national - Number of cases treated with the - Supervision check-list analysis of: outlying facilities protocol specific treatment - meningitis register Expected result: 100% - Number of cases treated with the - patient records specific treatment at correct doses or any document describing the treatment received Quality of injections - Number of facilities using safety Supervision check-list Visit of a sample of health Expected result: 100% boxes facilities and observation - Number of hospitals with incinerator 96

97 7. Evaluation Indicators Required data Source/tools Method Comments RESSOURCES Ratio number of treatment - Number of vials distributed - National protocol In a sample of health Expected result: vials/number of cases - Number of vials remaining in stock - Donation forms facilities at the end of Chloramphenicol 6 vials - Number of cases - Records of treatment epidemic Ceftriaxone 4 vials of 1 g availability - Epidemiological data Proportion of patients having - Number of cases - Meningitis register In a sample of health Give out the treatment tally received a 2 nd dose - Number of cases having received - Any document describing facilities at the end of sheets when supplying a second dose the treatment received epidemic treatments - Treatment tally sheets Expected result: < 20 % COST Cost per treated patient - Total cost of curative component - Bill These costs include: drugs Requires preparation with of the intervention - Accounting documents medical equipment, accounting staff - Number of patients treated transportation, staff 97

98 Evaluation of vaccination activities Evaluation of vaccination activities Indicators Required data Source/tools Method Commentss ACCESSIBILITY Vaccine coverage per age - Number of doses administered: - Tally sheets per site - Analysis of data Expected result: group, per place total, per age group, per place - Summary vaccination by collection - in urban settings: 100% - Demographic data and target place - Vaccination coverage - in rural areas: 80% depending population per age group, per - Vaccination cards (if survey) survey (vaccination card on objectives place or history) Proportion of sites that did - Shortage at district level? Date? - Stock cards Analysis of documents At the end of the campaign: experience a shortage of For how long? - Donation forms or Systematic analysis at district vaccines or ADS - Number of facilities that - Record of modules per site Visit to a sample of districts level experienced a shortage and vaccination sites and Pay particular attention to - List of places and vaccination sites checking of stock cards outlying facilities Expected result: 100% EFFECTIVENESS Vaccine efficacy - Standard case definition - Weekly monitoring forms Several methods: To be done by an epidemiologist - Total number of cases - Meningitis register - rapid evaluation method Only if: - Number of cases vaccinated and - case-control study or - doubt on the efficacy of the non vaccinated cohort vaccination - Vaccination coverage In one or several selected - new vaccines places Expected result: depending on vaccines Number of cases prevented - Demographic data - Weekly monitoring forms Pinner s method To be done by an epidemiologist by vaccination - Total number of cases/week - Tally sheets and summary In a sample of places - Number of doses administered of vaccination activities per Separate urban/rural per place site and per place calculation for the district - Vaccination coverage per place - District immunization report - Dates of vaccination campaigns - Results of vaccine coverage studies - Planning of vaccination teams 98

99 7. Evaluation Indicators Required data Source/tools Method Comments TIMELINESS Time between alert and the - For each health zone: date when - Weekly monitoring forms Exhaustive if possible Calculated at the end of start and end of the campaign alert threshold was crossed - Tally sheets and summary Calculate the time for each campaign (when the epidemic is - Dates of the start and end of per site and place place (health zones, For each place, separate urban/ confirmed) campaign in each health zone - District immunization report districts) rural analysis Expected result: 2 to 3 weeks (beginning of the campaign) Number of persons - Duration of the campaign: date - Tally sheets and summary Exhaustive if possible Separate urban/rural analysis vaccinated per day, per team per place (separate urban settings per site and place or in a randomly selected Expected result: and rural areas) - District immunization report sample of places - urban settings: 1000 to Number of doses administered - Planning of vaccination - rural areas: depending on the per place teams context - Number of teams/day/place Specify the number of vaccinators per vaccination site SAFETY/QUALITY Vaccine utilization rate - Number of doses administered - Tally sheets vaccination Exhaustive, for the entire Expected result: 85% - Number of doses used - Stock cards duration of the epidemic (loss 15%) Ratio used ADS/used safety - Number of ADS used - Tally sheets vaccination Exhaustive The number of syringes per box boxes - Number of safety boxes used - Stock cards or in a randomly selected should not exceed the maximum - Team activity reports sample of sites capacity of the safety boxes used - Summary vaccination by Expected result: place - box 5 l: 100 ADS - box 15 l: 400 ADS Proportion of personnel with - Number of personnel with - Accidental exposure to blood - Comprehensive analysis If a questionnaire has been needle-stick injuries during needle-stick injuries during the (AEB) reporting form (if AEB reporting proce- used, the recommended postthe campaign campaign - Specific questionnaire dure is implemented) exposure management can be - Total number of personnel or evaluated - Randomly selected sample of staff (use a questionnaire) 99

100 Evaluation of vaccination activities Indicators Required data Source/tools Method Comments SAFETY/QUALITY Proportion of refrigerators - Number of refrigerators used for - List of refrigerators used to - In a randomly selected - At a minimum, check the cold with updated temperature the campaign store the vaccines used during sample of storage places chain at district level chart - Number of refrigerators with a the campaign or - To be controlled during the updated temperature chart - Temperature charts of these - During supervision visits campaign refrigerators (information included in Expected result: 100 % the supervision check-list) Proportion of vaccination - Total number of sites Supervision check-list Sample of sites During the campaign sites with correct waste - Total number of sites with correct Direct observation in the Expected result: 100 % collection and disposal waste collection and disposal field RESSOURCES Ratio ADS used/number of - Number of ADS used - Tally sheets (information - Global at district level Expected result: the ratio vaccines administered - Number of persons vaccinated included) - In a randomly selected should not be < 1 - Stock cards sample of sites - Team activity reports Proportion of teams with an Number of people per team - Supervision check-list - In a randomly selected The standard composition of adequate number of people qualified to undertake this task sample of sites teams is determined at the or beginning of the campaign - During supervision visits (urban and rural areas) (information included in Expected result: 100 % the supervision check-list) 100

101 7. Evaluation Indicators Required data Source/tools Method Comments COST Global cost of the campaign - Total expenditure for vaccination Expenses accounting for the Expenditure analysis: activities compaign vaccines, equipment for injection, transportation, personnel, cold chain, logistics, etc.) Cost per person vaccinated - Total cost of vaccination activities - Tally sheets Expenditure analysis Requires preparation with (urban/rural) - Activity report accounting staff - Total number of doses administered - Financial report: total Separate urban/rural analysis (urban/rural) expenditure for vaccination activities (urban/rural) Cost per prevented case and - Total cost of vaccination activities - Weekly monitoring forms Expenditure analysis - Qualified person to undertake prevented death vaccination - Tally sheets this task - Number of doses administered - Vaccination campaign report - After the campaign - Calculation of prevented cases (Pinner's method) - Number of vaccination per site SOCIAL MOBILIZATION (efficiency/effectiveness of intervention) Proportion of people - Total number of non-vaccinated Vaccine coverage survey and Vaccine coverage survey At the end of the campaign reporting lack of information persons analysis of reasons for non- Expected result: < 10% as reason for non vaccination - Reasons for non-vaccination vaccination 101

102

103 CHAPTER 8 Emergency preparedness Planning emergency preparedness and response to epidemics 105

104

105 8. Emergency preparedness Planning emergency preparedness and response to epidemics An efficient response to outbreaks requires that emergency response be prepared in advance. It lists the criteria that orient the decisions. It indicates who does what, with what means and when. It defines the activities, decision procedures and responsibilities of all parties. It is divided by activity: Epidemiological surveillance Laboratory surveillance: confirmation of pathogen and monitoring of the evolution in various districts Case management Vaccination Epidemic management It is to be revised before every epidemic season. Surveillance and alert system Reinforce the surveillance system at the start of the dry season: as the dry season approaches each year, an effort should be made to reinforce the system that monitors the number of cases of meningitis. Check that population data are available. Laboratory surveillance: confirmation and follow-up Equipment necessary for LP, rapid latex tests, transport mediums (TI) and triple packaging system for the transport of infectious substances must be available at regional level in order to be distributed if cases are registered in outlying areas (see Appendix 21). Case management Case definitions and treatment protocols should be established and distributed. Security stocks: in a region considered at risk, all health facilities should have a minimum stock of simple treatments and equipment (kit treatment single dose) at the beginning of the meningitis season. 105

106 Planning emergency preparedness and response to epidemics Security stocks at national and regional levels should provide enough treatments for the first month of an outbreak. They are calculated according to the figures of the biggest outbreak in the past years. See Appendix 9.1 Vaccination National security stocks of vaccines can be set up. These stocks should allow the vaccination campaign to begin while awaiting the arrival of supplies ordered. An example of a security stock estimate: In a region of one million inhabitants, the thresholds were passed during the last outbreak in 3 districts within the first month, with a target population of 100,000. It is estimated that a stock of 100,000 doses of vaccines would give a margin of one month before delivery of a new order. Passive and active cold chains should be sufficient for the number of vaccines required for mass vaccination. Vaccination teams should be identified and trained for mass vaccination campaigns. Crisis committee Before a possible outbreak, members of the crisis committee should be identified at national, regional and district levels, and their responsibilities defined. 106

107 Appendices 1.1 Laboratory examinations Information form for CSF samples Laboratory register Triple-packaging box for shipping biological substances Meningitis register Detection thresholds Example of public information notice Treatment protocol for meningococcal meningitis in an epidemic context Weekly reporting form Meningitis weekly monitoring per district Outbreak monitoring chart Estimating needs for the treatment of meningitis in an epidemic situation (example) Donation forms for treatment kits Standard order for the treatment of 100 cases of complicated meningitis in hospital Tracking the availability of meningitis treatments Tally sheet for meningitis treatment, single dose Standard distribution of population in developing countries Example of vaccination campaign timetable Estimated needs - Vaccines and injection supplies for a vaccination campaign against meningitis ICG request form Stock card Cold chain equipment used for mass immunization campaign against meningitis Monitor card Stop!Watch with Freeze tag Estimation of the freezing capacity necessary for a vaccination campaign (example) Immunization kit, 10,000 vaccinations/5 teams Tally sheet for vaccination Daily vaccination summary Summary vaccination by place Summary table per district (example) Job description: vaccination supervisor Estimating the number of vaccination teams needed Estimation of needs for each place of vaccination (example) Record of supplies/equipment per vaccination site Diagnosis confirmation modules 171

108

109 Appendix Laboratory examinations For a better understanding, watch the video on the accompanying CD-ROM. 1 - Collection and storage of CSF 1.1 Collection of CSF samples Collect 1 to 2 sterile 1-ml tubes of CSF, at a minimum (20 drops/tube), depending on the exams to be performed (Gram stain, cell count, latex agglutination, culture). If a culture is planned, reserve one sterile tube for this purpose. Each sample should be accompanied by a patient information form (see Appendix 1.2). It is always better to analyse CSF immediately after collection. If this is not possible, storage times and temperatures will vary (see below). 1.2 Storage of CSF Length of storage Gram staining Latex agglutination test Culture Inoculation of TI medium 8 hours 48 hours 1 hour 1 hour Temperature Room temperature 2-8 C Room temperature Never refrigerate Room temperature Never refrigerate 2 - Gram or methylene blue staining Used to identify Gram-negative and Gram-positive organisms (Gram-negative diplococcus: meningococcus; Gram-negative bacillus: Haemophilus; Gram-positive cocci: pneumococcus). Cannot be used to identify the meningococcal serogroup. 2.1 Equipment Microscope (x 100 objective), immersion oil Centrifuge and sterile centrifuge tubes Slides, Pasteur pipettes Reagents: Methylene blue stain: methylene blue 0.3% solution Gram stain: Hucker Gram kit or crystal violet, alcohol, acetone, Lugol iodine solution, fuchsin or safranine 109

110 Appendix Technique Centrifuge the CSF for 10 minutes. Prepare a smear with the sediment. Leave the smear to dry, then fix. Stain the slide, either with: Methylene blue: by completely covering the slide with methylene blue for 3 minutes, or Gram staining: - Cover the slide completely with crystal violet for 1 minute. - Rinse with water (use filtered water and filter staining solutions through filter paper before use). - Cover with Lugol solution for 1 minute. - Rinse with acetone-alcohol 10%. - Rinse again with water. - Apply diluted fuchsin or safranine for 20 seconds. - Rinse well with water and leave to dry. Examine the slide under the microscope for the presence of meningococci. Examine at least 100 fields before pronouncing a negative result. 2.3 Description of meningococci Figure 14: Gram-negative intracellular diplococci Diplococci: cocci lying side by side (resembling coffee beans) Gram-negative: coloured pink by Gram staining Intracellular: the diplococci are usually inside neutrophils; a few may occasionally be seen outside the cells. 3 - Rapid diagnostic test (latex agglutination test) 3.1 Equipment Kit Pastorex meningitis, BIO-RAD Centrifuge (electric, if possible; otherwise manual) and 100 C water bath Sterile polypropylene centrifuge tubes (able to withstand heating to 100 C), sterile dropper, centrifuge tube rack and wood centrifuge tube holder Sterile water for injection, one syringe, and one needle for reconstituting the R10 positive control Sterile sodium chloride 0.9%, 5-ml vial, for the negative control 110

111 Appendix 1.1 Gloves and safety box for collecting and disposing of syringes and needles A timer See Appendix 21, test and accessories module 3.2 Technique (for Pastorex meningitis, BIO-RAD) CSF processing Heat the CSF by lowering the sterile tube into the water bath (100 C) for 3 minutes; allow the sample to cool to room temperature. Centrifuge the sample for 5 minutes, if possible at 3,000 rpm; save the supernatant. Advantage of heating: heating the sample to 100 C makes more antigenic material available. The sensitivity of the test is thereby increased. Advantage of centrifugation: this separates antigens from other particles that could interfere with the reaction. The lightest antigens will be in the supernatant. The specificity of the test is thereby improved. Heating and centrifugation are essential for good test sensitivity and specificity Agglutination procedure A) Preparing the materials Ten minutes before starting the reaction, remove the reagents from the refrigerator so that they are at room temperature. Adhere very rigourously to the procedure to avoid errors. It is best to arrange the reagents on the table in the order in which they will be used. Each reagent has its own coloured cap. Never mix up the caps, as this can contaminate the reagents. Prepare one card per CSF to be tested. Always perform R2 and R9 negative controls to verify the absence of non-specific agglutination of the CSF. Mix each reagent by inverting the bottle several times. B) Carrying out the reaction Holding the bottle vertically, place one drop of each latex solution on the card supplied (reagent R1 on circle 1, reagent R2 on circle 2, etc.). Then add one drop of the CSF supernatant next to each drop of reagent (Figure 15). Figure 15: Conducting the test (adding drops) Step 1 Step 2 For each circle, mix reagent and CSF with a plastic stirrer; use a fresh stirrer for each circle. Rotate the card gently for 10 minutes. Under daylight, observe if any agglutination of the latex particles has occurred. 111

112 Appendix Interpreting the results Positive result: agglutination appears within the first 10 minutes (for example, agglutination with reagent R8 indicates the presence of meningococcus serogroup Y or serogroup W135. For more precise identification to differentiate between serogroups, send the CSF to the reference laboratory). Negative result: no agglutination after 10 minutes. The suspension is homogenous. In order for the agglutination reaction to be interpretable: there must be only one agglutination per card and agglutination must occur within the first 10 minutes and there must be no agglutination for the R2 and R9 negative controls. The results are non-interpretable if: there are more than one agglutinations on the card (most likely due to handling error or contaminated CSF. In this case, the test must be redone and its validity verified with positive and negative controls) or agglutination occurs beyond the first 10 minutes or agglutination occurs for the R2 and/or R9 negative control(s) 3.3 Using the positive and negative controls The positive (R10) and negative (0.9% sodium chloride) controls are used to validate the performance of the test. Controls should be conducted upon the opening of each kit, then routinely once a week and every time there is doubt about the storage of the kit or a non-interpretable result. Reconstitute the R10 positive control using 1 ml water for injection. Use sterile 0.9% sodium chloride as the negative control. To perform the agglutination test with the controls, use one card for each control, then follow the same procedure as for CSF, but use one drop of control positive or negative in place of the drop of CSF. The positive control must yield a positive agglutination reaction with each of the different reagents except R2 and R9, which should always be negative. The negative control should yield no agglutination reactions. 3.4 Kit specifications, cost and storage conditions Kit Pastorex meningitis BIO-RAD, 25 tests per box, identification of 7 germs, euros 143 (average price) Storage and shelf life: The reagents must be stored in refrigerator between 2 C and 8 C. The reagents must not be frozen. If this happens accidentally, do not use the kit. The shelf life is 15 months. 112

113 Appendix Using Trans-Isolate (TI) medium for transport 4.1 Tests that can be performed Culture and drug sensitivity test Typing, subtyping, and cloning PCR For these 3 tests, the CSF should be sent to a reference laboratory on Trans-Isolate medium. 4.2 Reference laboratories National Institute of Public Health, Dr D. Caugant, Folkehelsa, Geitmyrsvein 75, NO-0403 OSLO, Norway. e.mail: dominique.caugant@fhi.no IIMTSSA, Le Pharo BP 46, Marseille Armée - France. e.mail: imtssa.meningo@free.fr CDC, meningitis and special pathogens branch, 1600 Clifton road, C-09, Atlanta, GA30333, United States. e.mail: BAP4@CDC.GOV. When choosing a transport medium, follow each laboratory's recommendations. The National Institute of Public Health requires Trans-Isolate medium, to be ordered from the Folkehelsa laboratory, Norwegian Institute of Public Health, Geitmyrsvein 75, NO-0403 OSLO, Norway. Fax: Using Trans-Isolate (TI) medium Storage prior to culturing The TI medium should be stored between 2 C and 8 C. It can be used 12 months after the date of manufacture indicated on the bottle Equipment One bottle of Trans-Isolate One triple packaging box + protective container One sterile 1-ml syringe, one sterile 21G needle, and one sterile 19G needle One safety box for needle collection and disposal, and one pair of gloves Technique Take the TI out of the refrigerator to bring it to room temperature 30 minutes before inoculating it. Meningococcus is sensitive to cold; do not inoculate medium that has come straight from the refrigerator. Before use, check the appearance of the medium; if normal, it should: be a clear yellow liquid have no colony growth on the chocolate agar Destroy all medium that shows signs of contamination: cloudiness, presence of colonies on the medium. 113

114 Appendix 1.1 Inoculate the CSF within one hour of collecting the specimen: Remove the inner seal, disinfect the rubber stopper (polyvidone iodine or 70 ethanol) and let it air dry completely. Aspirate 0.1 to 0.5 ml of supernatant with a green 21G needle. Inject the CSF into the TI bottle through the rubber stopper. If the TI will reach the reference laboratory within 24 to 48 hours, store it, as is, at room temperature. If not, ventilate it: It is important to keep the bottles ventilated before shipment in order to allow for growth of the meningococci. To ventilate, after injection, introduce a 19G (beige) needle (the needle should not go down into the CSF). Place a piece of cotton wool into the plastic base of the needle to prevent contamination. Store the TI upright, ventilated with the needle, and away from sunlight, at room temperature. Avoid temperatures above 40 C. Never refrigerate. Prepared in this way, the medium can be stored for a maxium of 3 weeks. Do not culture if: The patient started antibiotic treatment within the 24 hours preceding the LP The CSF was collected more than one hour beforehand or was refrigerated Transport, packaging, and sending Prior to transport, if the medium was ventilated, remove the ventilation needle from the bottle. Protect each TI bottle in a protective container, then in a specific triple package (biological substance category B, UN3373), see Appendix 1.4. Attach the patient information form (see Appendix 1.2). Cold chain should not be used for transport. Once the ventilation needle has been removed for transport, the TI can be stored for one week. Make sure that the necessary information is noted on the lab test log. Notify the reference laboratory that a sample is being sent. 5 - Standard precautions The samples are considered infectious, so use standard precautions: Wash your hands before and after all handling. Wear gloves. Do not recap needles (LP, TI sample); collect them in a safety box designed for the collection of used needles. The safety box should be located as close as possible to the procedure, and the maximum fill level checked. Transport samples in leakproof packaging. Incinerate all contaminated materials (cards, droppers, stirrers, etc.). 114

115 Appendix Information form for CSF samples Name (and type) of health centre: District: Region: Country: Person making request: Contact info (telephone, ): Patient identification Date: / / (dd/mm/year) Last and first name: Date of birth: / / or Age : years Sex: Male Female Residence: Commune: District: Other information: Sample information Date: / / (dd/mm/year) CSF appearance: Tests requested: - Gram stain Yes No - Latex agglutination Yes No - Culture, DST Yes No - Other Yes No If yes, specify: Date transport medium (TI) sent: / / Results (to be filled in by the laboratory) Date TI received: / / Treatment in the 72 hours prior to sample collection Antibiotic: Yes No If yes, specify: Malaria (paracheck +): Yes No If yes, specify: Meningitis vaccination: Yes No If yes, what year? Clinical information Date symptoms began: / / Symptoms on admission: if possible, complete below: Fever Yes No If yes, how high? Chills Yes No Headache Yes No Stiff neck Yes No Vomiting Yes No Seizures Yes No Coma Yes No Obnubilation Yes No Purpura Yes No Other signs Yes No If yes, specify: Date and results of lab tests already done (Gram stain, latex agglutination, etc.): Label tubes with the following information: last name, first name, patient age, sample collection date, health centre. Package samples according to recommendations to avoid contamination. Respect the transport requirements (temperature, time, laboratory information, etc.). 115

116 Appendix Laboratory register Region: District: Health zone: Health centre/hospital: Date 1 Patient s name Address Age Sex CSF Gram appearance 2 stain 3 Result of rapid (latex) test 4 Not done TransIsolate Done Date Date sent Laboratory 5 Results 6 1 Date on which sample was collected 2 Specify: clear, cloudy, or haemorrhagic 3 Specify: Gram + or Gram ; diplococcus or bacillus 4 Specify the microorganism and serogroup 5 Specify the name of the reference laboratory 6 To be completed once the reference laboratory has sent the results

117 Appendix Triple-packaging box for shipping biological substances Box with a triple layer packaging system, ensuring the safe shipping of biological substances. Meets the rules for the transport of Category B infectious substances (infectious substances not capable of causing life-threatening disease in case of exposure). The system consists of three layers of packaging: 1) Primary container: tube or vial containing the sample (TransIsolate) 1b: additional protective container (optional): place the sample (wrapped in absorbent material) inside and close tightly; if necessary, seal the cap with adhesive tape. 2) Secondary container: watertight polyethylene container, designed to protect the primary container from impact. The primary recipient can be wedged firmly with bubble wrap. Absorbent material (gauze or paper towel) should be added in sufficient quantity to completely absorb the liquid in case of breakage. 3) Outer container: reinforced cardboard box, designed to protect the secondary container, with UN3373 labelling. Primary container (TransIsolate) Additional container (with paper towel) Secondary container (with bubble wrap + paper towel) UN 3373 Outer container Leakproof lid for secondary container Before sending: Double check to make sure that all inner packaging is hermetically sealed. Check to make sure that patient information is inside the box (outer container). 117

118 Appendix 1.4 When sending: Verify the recipient s address. Give as much detail as possible (department and name of the person to receive the triple-packaged box). Fill in the required information on the outer container. Attach all necessary shipping documents. Note the information on the shipping log, to facilitate follow-up (reception at lab and transmission of results). Notify the relevant services (laboratory, medical department, logistics unit) that package has been shipped. 118

119 Vaccination (Y/N) andd date Appendix Meningitis register Region: District: Health zone: Health centre/hospital: Date of admission Patient s name Address of residence (town, village) Age Sex Antibiotic treatment (1) Outcome (2) R/D/T/C/ (1) Indicate the name of the antibiotic and the dose administered (e.g.: ceftriaxone 4 g). For the first line treatments (ceftriaxone or oily chloramphenicol), specify if a second dose has been administered. (2) Outcome: R = recovery; D = death; T = transfer; C = complications 119

120 Appendix Detection thresholds 120

121 Appendix 3 121

122 Appendix 3 122

123 Appendix 3 123

124 Appendix Example of public information notice There is a meningitis outbreak in Treatment of patients Adults and children with fever, intense headache, vomiting, stiff neck, may possibly have meningitis and should be seen at the nearest health facility. Infants with fever, that cry abnormally or are floppy, or have tremors or seizures, must be urgently taken to the nearest health facility. Meningitis treatment during the epidemic is free of charge. Vaccination Everyone aged 2 to 30 years should be vaccinated against meningitis. Go to your nearest vaccination point: Vaccinations will take place from (date) from (time) until until The vaccination against meningitis is free of charge. Come and get vaccinated. You only need one injection for protection against meningitis. 124

125 Appendix Treatment protocol for meningococcal meningitis in an epidemic context 1) Case definition Children over one year of age and adults Sudden onset of fever (over 38.5 C) and neck stiffness or petechial rash Children under one year of age Fever over 38.5 C and neurological signs (hypotonia, seizures or bulging fontanelle, etc.) or petechial rash In an epidemic context, patients with these clinical features are probable meningitis cases and should be managed according to the following protocol. 2) Management Age Children under 2 months Children from 2 to 23 months Children over 2 years and adults Pregnant and breastfeeding women Management Refer to hospital if impossible to monitor and treat for 7 days (1) Treatment in health centre possible Antibiotic therapy Refer to hospital ceftriaxone for 7 days ceftriaxone single dose or oily chloramphenicol single dose ceftriaxone single dose Patient information Inform the patient that he must return if there is no improvement 24 hours after the injection. Before transferring a patient, administer a dose of antibiotic. Indicate the treatment administered in the referral letter. (1) Case management in a peripheral facility can only take place if there are qualified staff and adequate means (in-patient ward, guaranteed surveillance and correct administration of treatment, capacity to manage possible complications). 125

126 Appendix 5 3) Antibiotic therapy Children over 2 years and adults a) The first-line treatment of meningococcal meningitis in an epidemic context is either oily chloramphenicol or ceftriaxone as a single dose. oily chloramphenicol IM (500 mg vial ; 250 mg/ml, 2 ml) Children: 100 mg/kg as a single dose Adults: 3 g as a single dose Age 2-5 years 6-9 years years 15 years Dose 1.5 g 2 g 2.5 g 3 g Volume to be injected 6 ml 8 ml 10 ml 12 ml Number of 500 mg-vials Oily chloramphenicol is a thick product that is difficult to inject. The dose should be administered into 2 IM injections (half of the dose in each buttock). Oily chloramphenicol is contra-indicated in pregnant and breast-feeding women. or ceftriaxone IM (1 g vial, to be dissolved in 4 ml of water for injection) Children: 100 mg/kg as a single dose Adults: 4 g as a single dose Age 2-5 years 6-9 years years 15 years Dose 1.5 g 2.5 g 3 g 4 g Volume to be injected 6 ml 10 ml 12 ml 16 ml Number of 1 g-vials 11/2 21/2 3 4 Administer half of the dose in each buttock (large quantity to inject). The solvent of IV ceftriaxone may be used for IM injection, but the solvent of IM presentation contains lidocaine and must never be used for IV injection. b) If there is no clinical improvement: 24 hours after a first dose: administer a second dose of the same antibiotic. 24 hours after a 2 nd dose: review the diagnosis (e.g. malaria test) and/or transfer. c) If condition worsens (deteriorating level of consciousness or worsening of neurological signs) after a first dose or a second dose: transfer. 126

127 Appendix 5 Children from 2 to 23 months a) If the child can be treated on-site (surveillance and treatment for 7 days): ceftriaxone IM: 100 mg/kg once daily for 7 days Weight 4-8 kg 9-15 kg Dose 500 mg 1 g Volume to be injected 2 ml 4 ml Number of 1 g-vials 1/2 1 b) If the facility cannot guarantee surveillance and correct treatment for 7 days: Refer the child and administer one dose of ceftriaxone before transferring (if ceftriaxone is not available, oily chloramphenicol may be used: one IM injection of 500 mg, i.e. 2 ml). Children under 2 months of age Hospitalize. Before transferring, administer one dose of ceftriaxone (100 mg/kg). 4) Management of fever Tepid sponging, paracetamol PO: AGE WEIGHT 0 2 months 4 kg 1 year 8 kg 5 years 15 kg 15 years 35 kg ADULT 1/2 tab 3/4 to 11/2 tab 11/2 to 3 tab 100 mg tab x 3 x 3 x 3 1/4 to 1/2 tab 1/2 to 11/2 tab 500 mg tab 2 tab x 3 x 3 x 3 127

128 Appendix Weekly reporting form Meningitis weekly reporting form Country: District: Town/village: From (Monday) / / To (Sunday) / / Health centre: Hospital: New cases of meningitis (1) Deaths from meningitis Number of patients transferred out (2) Total for the week (1) New cases of meningitis: suspected or probable or confirmed meningitis case, admitted to the health structure during the indicated period. (2) Patients referred to another health structure. The Islamic week starts on Saturday and ends on Friday. Cases should be reported on the day of admission. Deaths should also be reported on the day of death (it is possible to have 0 new diagnosed cases and X number of deaths among patients admitted the week before). If no patient is admitted, write 0, and the same for death: leave no boxes blank. If a patient is transferred to another health facility, do not record this patient on the weekly reporting form: he will be recorded in the referral facility. This form must be filled out every week during the epidemic. A copy must be sent to the district epidemiologist. 128

129 Appendix Meningitis weekly monitoring per district Summary form to be filled in using the information provided in the weekly reporting form (see Appendix 6). Region/district: Reported by: To Monday: / / To Sunday: / / (dd/mm/yy) (dd/mm/yy) Health centre Number of new cases Number of deaths Number of transferred out (1) Total Hospital Number of` new cases (2) Number of deaths Number of transferred out (3) TOTAL Health centre + Hospital (4) (1) Cases transferred to hospital (2) New cases admitted to hospital (patients admitted directly and patients referred from another health facility) (3) Cases referred from health centre (4) Number of new cases health centres + hospitals (including those admitted via referral) 129

130 District Total population Weeks Total Appendix Outbreak monitoring chart Country: Region: District: Year: Number of cases Incidence/100,000 Deaths CFR Number of cases Incidence/100,000 Deaths CFR Number of cases Incidence/100,000 Deaths CFR Number of cases Incidence/100,000 Deaths CFR Number of cases Incidence/100,000 Deaths CFR Number of cases Incidence/100,000 Deaths CFR Number of cases Incidence/100,000 Deaths CFR Total Number of cases Incidence/100,000 Deaths CFR

131 Appendix Estimating needs for the treatment of meningitis in an epidemic situation (example) Needs drugs and medical supplies are estimated according to the estimated number of cases. To estimate these needs, take into account: The estimated cumulative incidence of meningitis for the period to be covered, based on data from previous epidemics. If these data are not available for the district concerned, an incidence of 150 to 300/ inhabitants is a reasonable estimate for a district in the African meningitis belt. The number of declared cases The desired buffer stock The number of complicated cases requiring hospitalization, taking into account access to health care and previous experience. This estimate includes: The treatment of simple cases: oily chloramphenicol 500 mg, 6 vials per treatment or ceftriaxone 1 g, 4 vials per treatment The optional module 7 days ceftriaxone for children 2-23 months. The complementary treatments for complicated hospitalised cases. Example of estimation of needs for the treatment of meningitis in an epidemic situation Expected attack rate/ Buffer stock desired Proportion of hospitalized cases / % 25% % 20% The first order should cover treatment needs for a reasonable period of time, e.g. 4 weeks. The second order will be more precise. Name of the district Lolo Total population Number of estimated cases 228 Number of cases already reported 25 Number of expected cases 203 Buffer stock 51 Needs for the TOTAL number of cases 254 Needs for hospitalized patients 51 kit 5 treatments meningitis-single dose Estimated needs If ceftriaxone 1 g 1015 Water for injection 10 ml

132 Appendix Donation forms for treatment kits DONATION FORM (Kit 5 treatments meningitis single dose ceftriaxone) Médecins Sans Frontières donates to (name of the heath facility): Region: Town: Indicate how many Kit(s) 5 treatments single dose Content of a kit 5 treatments meningitis - single dose: Articles Presentation Quantity Ceftriaxone injectable...1 g vial...20 Water for injection...10 ml ampoule...20 Paracetamol oral mg tablet...90 Syringes...10 ml...15 Needles...19 G...15 Needles...21 G...10 Needles...23 G...20 AND Indicate how many Module(s) one treatment 7 days (2-23 months) Content of a module one treatment of 7 days for children 2-23 months: Articles Presentation Quantity Ceftriaxone injectable...1 g vial...7 Water for injection...10 ml ampoule...7 Syringes...10 ml...7 Needles...19 G...7 Needles...21 G...7 Needles...23 G...7 Other donations (e.g. paracetamol 100 mg tab or 120 mg/5 ml syrup (quantity); safety boxes, etc.): This donation is reserved for the treatment of meningitis only. These treatments must be free of charge for the patients. Date: For Médecins Sans Frontières (signature) For the health facility (signature) This document is signed in triplicate: one copy for the health facility, one for the district health officer, and one for MSF. 132

133 Appendix 9.2 DONATION FORM (Kit 5 treatments meningitis single dose chloramphenicol) Médecins Sans Frontières donates to (name of the heath facility): Region: Town: Indicate how many Kit(s) 5 treatments single dose Content of a kit 5 treatments meningitis - single dose: Articles Presentation Quantity Oily chloramphenicol injectable mg (2 ml) vial...30 Paracetamol oral mg tablet...90 Syringes...10 ml...15 Needles...19 G...15 Needles...21 G...10 Needles...23 G...20 AND Indicate how many Module(s) one treatment 7 days (2-23 months) Content of a module one treatment of 7 days for children 2-23 months: Articles Presentation Quantity Ceftriaxone injectable...1 g vial...7 Water for injection...10 ml ampoule...7 Syringes...10 ml...7 Needles...19 G...7 Needles...21 G...7 Needles...23 G...7 Other donations (e.g. paracetamol 100 mg tab or 120 mg/5 ml syrup (quantity); safety boxes, etc.): This donation is reserved for the treatment of meningitis only. These treatments must be free of charge for the patients. Date: For Médecins Sans Frontières (signature) For the health facility (signature) This document is signed in triplicate: one copy for the health facility, one for the district health officer, and one for MSF. 133

134 Appendix 9.2 DONATION FORM (Complementary kit 10 treatments - complicated meningitis) Médecins Sans Frontières donates to (name of hospital): Region: Town: Indicate how many Complementary kit(s) 10 treatments - complicated meningitis Content of a complementary kit 10 treatments - complicated meningitis: Articles Presentation Quantity Ampicillin injectable mg...15 Ceftriaxone injectable...1 g...80 Dexamethasone injectable...4 mg (4 mg/ml, 1 ml)...3 Diazepam injectable...10 mg (5 mg/ml, 2 ml)...20 Water for injection...10 ml...95 Gentamicine injectable...20 mg (10 mg/ml, 2 ml)...10 Paracetamol injectable (Perfalgan?) mg (10 mg/ml, 50 ml)...8 Glucose 5% and infusion set ml...10 Glucose 5% and infusion set...1 litre...10 Ringer lactate and infusion set...1 litre...2 Amoxicillin oral suspension mg/5 ml...1 Paracetamol oral mg Paracetamol oral mg...50 Polyvidone iodine 10% ml...1 Syringes... 2 ml...15 Syringes...10 ml...80 Needles...19 G...95 Needles...21 G...60 Needles...23 G...45 IV catheters...18 G...15 IV catheters...22 G...10 Scalp vein infusion set...25 G...10 Protective gloves, single use, medium (pair)...30 Protective gloves, single use, large (pair)...20 Safety box (5 litres)...1 Electronic thermometer...1 Cotton 500 g...1 Adhesive tape (roll...1 Other donations (e.g. paracetamol 120 mg/5 ml syrup (quantity), etc.): This donation is reserved for the treatment of meningitis only. These treatments must be free of charge for the patients. Date: For Médecins Sans Frontières (signature) For the hospital (signature) 134 This document is signed in triplicate: one copy for the health facility, one for the district health officer, and one for MSF.

135 Appendix Standard order for the treatment of 100 cases of complicated meningitis in hospital The treatment of 100 cases corresponds to 10 complementary kits 10 treatments complicated meningitis Items Presentation Quantity Ampicillin, injectable mg Ceftriaxone, injectable (for IV injection)...1 g Dexamethasone, injectable...4 mg (4 mg/ml, 1 ml)...30 Diazepam, injectable...10 mg (5 mg/ml, 2 ml) Water for injection...10 ml Gentamicin, injectable...20 mg (10 mg/ml, 2 ml) Paracetamol, injectable (Perfalgan ) mg (10 mg/ml, 50 ml)...80 Glucose 5% + infusion set ml Glucose 5% + infusion set...1 litre Ringer lactate + infusion set...1 litre...20 Paracetamol, oral mg Paracetamol, oral mg Amoxicillin, oral (suspension) mg/5 ml...10 Polyvidone iodine, 10%, bottle ml...10 Syringes...2 ml Syringes...10 ml Needles...19 G Needles...21 G Needles...23 G IV catheters...18 G IV catheters...22 G Scalp vein infusion sets...25 G Protective gloves, non sterile, medium Protective gloves, non sterile, large Safety boxes for collection and disposal of needles (5 litres)...10 Medical thermometers...10 Cotton wool g...10 Adhesive tape, roll

136 Appendix Tracking the availability of meningitis treatments It is important to track the availability of meningitis treatments in order to ensure access to treatment. Every week: Report the number of cases and deaths, as well as the number of treatments supplied to each health facility, using donations forms. Differentiate simple «single dose» treatments from complementary treatments for hospitalised, «complicated cases». The treatment of a simple case requires 6 vials of oily chloramphenicol 500 mg or 4 vials of ceftriaxone 1 g. For each place, the number of treatments available must be more than the number of expected cases for a given period of time. Warning: any availability estimated «negative» indicates that the number of cases has been higher than the number of treatments available for a given period of time. At the end of epidemic: Calculate for each place and for the region: the total number of treatments supplied, the remaining stock, the quantities of treatments used during the epidemic. An Excel document has been designed to facilitate the tracking of treatment availability and to plan deliveries for each health facility providing treatment. 136

137 Appendix 9.4 Availability of meningitis treatments (example) Region: Selama District: Tiwana District: Source: Donation form MSF Treatment simple cases WEEK Health zones Total population Cases Deaths CFR Week 9 Week 10 Number Rx distributed Number Rx available Cases Deaths CFR Number Rx distributed Number Rx available Dan Issa ,5% ,4% 0 4 Danja ,3% ,3% Djiratawa ,0% ,1% 0 11 Gabi ,3% ,2% 0 7 Madaroumfa ,6% ,1% 40 7 Maraka ,5% ,9% N'Yelwa ,3% ,1% Safo ,0% ,1% 0 9 Serkin Yama #DIV/0! ,0% 0 4 Tchizon K ,0% ,0% 0 6 District hospital ,3% ,0% TOTAL #REF! ,9% ,6% Treatment of complicated, hospitalised cases District hospital ,2% ,0%

138 Appendix Tally sheet for meningitis treatment, single dose Tick the antibiotic administered: Oily chloramphenicol Ceftriaxone Region: District: Health zone: From (date) / / To / / Number of first doses administered TOTAL = Number of second doses administered TOTAL = Proportion of patients that have received a second dose No. of patients that have received a 2 nd dose x 100 = No. of patients that have received a 1 st dose 138

139 Appendix Standard distribution of population in developing countries (shown as % of the total population) Children under 5 years of age 0-11 months 4% months 3% months 3% months 3% months 3% Total 16% Total population 0-4 years 16% 5-14 years 27% = 70% years 27% years 16% 45 years 14% Total 100% Example: if the target population is the population aged 2-30 years, the target population represents 63% of the total population. By gender Total females 49.5% Total males 50.5% Females 15 to 44 years old 25.5% Pregnant women 4% Notes: This distribution varies depending on the country and the context. Always use national figures if available. 139

140 Start of epidemic Start of campaign Date D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 D12 D13 D14 D15 D16 D17 End Appendix Example of vaccination campaign timetable Crisis committee - Creation - Meeting - Assessment Epidemiological surveillance - Cases-deaths - Weekly report - Final report and evaluation Vaccines - Estimation of needs - Verification of existing stocks - Orders - Reception and verification - Stock management (cards, batch number) - Vaccine distribution Human resources - Assessment of existing personnel (availability) and estimation of needs - Identification and allocation of personnel - Activity plan (schedule, etc.) - Training - Supervision - Per diem

141 Start of epidemic Start of campaign Date D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 D12 D13 D14 D15 D16 D17 End Appendix 11 Cold chain - Resource and needs assessment - Order - Reception and verification - Distribution and start-up - Monitoring Injection supplies and stationery - Resource and needs assessment - Order - Reception and verification - Distribution according to needs Equipment - Resource and needs assessment - Order - Reception and verification - Distribution Logistics - Assessment of local resources and estimation of needs - Order or local purchase - Reception and verification - Distribution according to needs - Vehicle schedule 141

142 Date D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 D12 D13 D14 D15 D16 D17 End Appendix Start of epidemic Start of campaign Vaccination sites - Identification - Visit - Organization (tables, chairs, etc.) Public information - Creation of public information committee - Committee meeting - Drafting of message - Dissemination of message Vaccination campaign - Preparation of materials - Verification of materials - Supply during vaccination campaign - Waste collection and disposal Evaluation of vaccination activities - Vaccination coverage/age - % loss (vaccines and supplies) - Communication of results - Weekly and final report(s) - Vaccination coverage survey

143 12 - Estimated needs - Vaccines and injection supplies for a vaccination campaign against meningitis (8) Cotton 500 g (9) Appendix 12 Country: Region: District Alert threshold crossed (week) Total population Target population Population already vaccinated Population to be vaccinated (1) x 1.17 (waste) x 1.25 (reserve) (2) Vaccines Injection supplies Volume in Syringes Needles Gloves litres 20 ml 19 G (3) Autodisable syringes 0.5 ml (4) (5) (6) Safety boxes 15 litres (7) Total 143 (1) Population to be vaccinated: target population minus population already vaccinated. (2) Estimated number of vaccines needed: population to be vaccinated multiplied by 1.17 multiplied by 1.25 (25% reserve). (3) Volume of vaccines, in litres: number of doses multiplied by volume estimated for one dose/1000; (1 litre = 1000 cm 3 ). Volume estimated for one dose = 2.5 cm 3 (4) Autodisable syringes: 10% waste. Total number of doses multiplied by 1.1. (5) 20 ml syringes for reconstitution of lyophilised vaccines: 1 syringe for 1 vaccine vial. Total number of doses needed divided by number of doses per vial. (6) 1 needle per vial. Total number of doses needed divided by number of doses per vial. (7) Safety boxes for collection and disposal of needles and syringes, 15 litres: 1 for 400 syringes. Number of autodisable syringes divided by 400. (8) Number of gloves: 1 pair (2 gloves, single use, non sterile) for 250 vaccinations. Total number of autodisable syringes divided by 250 multiplied by 2. (9) 500 g cotton for 500 vaccinations. Total number of autodisable syringes divided by 500. Take available stocks into account.

144 Appendix ICG request form INTERNATIONAL COORDINATING GROUP FOR MENINGITIS VACCINE PROVISION (ICG) APPLICATION FORM TO ACCESS ICG SUPPORT ( outbreak@who.int or fax to ) The International Coordinating Group (ICG) on Vaccine Provision for Epidemic Meningitis Control is a partnership between UNICEF, MSF, IFRC and WHO established to ensure rapid and equal access to vaccines, injection materials and oily chloramphenicol, for emergency outbreak response as well as their optimal use when stocks are limited. The release of these emergency supplies constitute an advance to the countries in outbreak situation, as such their reimbursement is required to maintain ICG stockpiles at constant levels General information Date of Request: Country requesting: Region/State: Affected areas (town/district/division): Requesting agency: Name of person filling the form: Vaccine reception information in the country/region Name Tel. Fax Address Reimbursement/Payment Information: Planned Funding source Name of Contact (if other than above) To activate the ICG process for meningitis vaccine and antibiotic distribution it is essential to provide the following documents (incomplete requests will delay assessment): 1. Essential information in the following forms ( tick the box if attached) : 1.1. Meningitis emergency stockpile application form (pages 2, 3 & 4) 1.2. Annex 1: Epidemiological information (excel sheet 1) 1.3 Annex 2: Laboratory Information (excel sheet 2) 2. Vaccination plan by district (Objective of mass vaccination, targeted zone, planned vaccination date, duration, number of teams, etc. See example attached.) 3. Spot map of the affected areas 144

145 Appendix 13 Meningitis Emergency Stockpile Application Form Country Date I. Epidemiological Information Please include a relevant extract (affected areas and weeks) of the epidemiological national data base or fill out the excel data collection file in ANNEX 1. Brief Summary: Please describe when epidemic threshold 1 was crossed by affected districts/sub-district (town, unit, payam, ward, etc) and the current evolution of this epidemic situation. If applicable also give relevant information for neighbouring districts having crossed the alert threshold. II. Laboratory Information Please fill out the excel data collection table in ANNEX 2 as well as the summary table below Summary How many specimens were tested in total (all methods included)? How many were positive? District/ division/town* Number specimen positive Nm A Number of specimen positive Nm W135 Number of specimen for other Nm serogroup (specify) * Please add rows if necessary 1 Epidemic threshold Population greater than : an incidence of 15 cases per inhabitants per week, in 1 week. However, when the epidemic risk is high (no epidemic for 3 years or alert threshold crossed early in the dry season), the recommended epidemic threshold is 10 cases per inhabitants per week, in 1 week (see reference article for more details). Population less than : 5 cases in 1 week or doubling of the number of cases over a 3-week period (other situations must be evaluated in a case-bycase basis according to the epidemic risk). For operational purposes, when an epidemic is confirmed in a neighbouring area, the alert threshold also serves as the epidemic threshold. Detecting meningococcal meningitis epidemics in highly-endemic African countries, Weekly Epidemiological Record, 22 September 2000, Vol 75, 38, pp , 145

146 Appendix 13 III. Antibiotic Request First line standardized treatment used: Oily chloramphenicol requested to the ICG? Yes No Number of vials available Number of vials requested 2 Is the treatment provided free of charge? Yes No IV. Vaccine Request Age groups targeted for vaccination: from to years of age District/ division/ sub-district/town 1 Week Alert 2 Week Epi 3 Total Population Target population Doses required 4 Total 1 Please add rows if necessary 2 Calendar week when the alert threshold has been reached in this area 3 Calendar week when the epidemic threshold has been reached in this area 4 Note that the total number of vaccine doses needed is calculated with the following formula: Total required doses = number of target population x wastage factor (1.17) If reserve is needed, please indicate and provide justification Type and number of doses of vaccine in stock and requested to control the epidemic Type of vaccine Stock available (doses) Doses requested Bivalent (A/C) Trivalent (A/C/W) Tetravalent (ACYW135)* *Not available through the ICG 2 For calculation of treatment needs, see table 4, page 13 of "Standardized treatment of meningitis in Africa in epidemic and non-epidemic situations" 146

147 Appendix 13 V. Vaccination material Please note that according to WHO recommendations on injection safety, vaccines should be systematically bundled with syringes for administration and reconstitution of the vaccine, as well as safety boxes for their disposal. This policy does not imply that these items must be physically packaged together but that they must ultimately be made available in adequate quantities at the vaccination site or health facility in a timely manner. ( These vaccination materials will be systematically sent by the ICG whenever vaccine is released, shipped by either air or by boat. Transport by boat will only be chosen if the necessary vaccination materials can be made available at the vaccination sites from in-country stocks. The country stocks will then be replenished by the ICG supplies. This will minimize the elevated packing and freight costs of sending these voluminous materials by air, however, delivery delays will be several weeks longer than air transport. In order for the ICG to decide the mode of transport, please provide us information about the availability of autodisable, reconstitution syringes, and incineration boxes in the country. Auto disable syringes (0.5ml) Quantity available in country ( in units) Reconstitution syringes Quantity available in country ( in units) and needles (19G) Incineration boxes (15L) Quantity available in country ( in units) VI. Technical Support Please specify what type of support, if any is needed VII. Reimbursement In order to ensure the sustainability of the revolving stock, the ICG requires a pledge confirmation for replenishment of the stockpile and other supplies. The requesting country or agency is responsible for reimbursing the costs of vaccines, accompanying injection materials (including incineration boxes, auto disable and reconstitution syringes and needles) and oily chloramphenicol. This includes the costs of packaging, freight and insurance. The ICG secretariat (WHO) will issue an invoice within 30 days of shipment. The country or agency should transfer the funds within 30 days of reception of this invoice and in accordance with WHO administrative procedures and regulations. 147

148 Appendix Stock card Name of product: Buffer stock: Maximum stock: Date Origin/Destination In Out Stock Remarks 1 1 Write batch number for vaccines, solvents, vials of chloramphenicol or ceftriaxone. 148

149 Cold chain equipment used for mass immunization campaign against meningitis Ice production capacity volume of storage and ice production performance (external temperature 43 C) Appendix 15.1 Cold chain equipment (ice production) Type of energy Volume required for storage of vaccines at +2 to +8 C (without solvent) in 10-dose vials*** Refrigerator/freezer Sibir V170 *EK (weight: 117 kg) **GE (weight: 97 kg) 55 litres = doses 36 litres *EK: 0.96 kg/24 hours **GE: 1.2 kg/24 hours Refrigerator Vestfrost MK 144 Electricity 220 V Min. required: 8 hours/24 hours Weight: 85 kg 45 litres = doses Refrigerator Vestfrost MK 204 Electricity 220 V Min. required: 8 hours/24 hours Weight: 101 kg Refrigerator Vestfrost MK 304 Electricity 220 V Min. required: 8 hours/24 hours Weight: 127 kg 63 litres = doses 108 litres = doses Freezer Vestfrost MF 214 Electricity 220 V Min. required: 8 hours/24 hours Weight: 84 kg Freezer Vestfrost MF 314 Electricity 220 V Min. required: 8 hours/24 hours Weight: 116 kg * KE = Kerosene/Electricity ** GE = Gas/Electricity *** The number of doses is estimated for a volume per dose of 2.5 cm litres 22.3 kg /24 hours 264 litres 32.4 kg/24 hours 149

150 Monitoring tools Specifications Where to use Thermometer Alcohol, Moeller Refrigerator, cold boxes and vaccine carriers Autonomy of consevation for vaccines (without opening, external temperature 43 C) 114 hours 129 hours 32 hours Thermometer Liquid crystal display Only for cold-chain transport equipment: cold boxes and vaccine carriers STOP! Watch card with Freeze tag French/English Only to monitor fridge temp, which must be monitored twice/day Temperature control chart Monitor twice daily Attached to each batch by the manufacturer on dispatch Appendix Cold chain equipment (transport) Volume required for storage of vaccines (without solvent), 10-dose vials Characteristics Electrolux cold box RCW litres = doses 14 ice packs 0.6 litre Weight: 11 kg Electrolux cold box RCW litres = doses 24 ice packs 0.6 litre Weight: 17 kg Giostyle vaccine carrier 2.6 litres = doses 8 ice packs 0.4 litre Weight: 1.8 kg 3M monitoring card English, French, Spanish (Portuguese and Arabic on special order) Monitors the temperature of vaccines during transport and storage

151 Appendix Monitor card Stop!Watch with Freeze tag Card with temperature indicators, used to monitor the temperature inside a refrigerator. This card provides an additional temperature check, but it is still essential to check the temperature of the refrigerators 2 times daily. Specifications Double-sided card, bilingual English/French, with 2 indicators: A heat-sensitive indicator with 4 windows (A, B, C, D), that gradually turn blue depending on the length of time and the temperature they are exposed to: Windows A, B and C turn blue when the indicator is exposed to temperatures above 10 C. Window D turns blue when the indicator is exposed 2 hours to temperatures above 34 C. A freezing indicator (Freeze-tag ): when the indicator is exposed to temperatures below 0 C for more than one hour, the display will change from the «OK» status to the «ALARM» status. Instructions for use Place the card into the refrigerator 30 minutes (+2 C to +8 C) before activating it. Then activate the card by removing activation tab. The Stop!Watch card has to stay permanently in the refrigerator and must be checked each time the twice daily temperatures are checked. If the windows are blue or if the Freeze tag indicates «alarm»: Note the change on the card and place a new card into the refrigerator. Inform the supervisor who will decide the appropriate action to be taken. Heat-sensitive indicator (windows ABCD) Note on the card: date, if colour changes Freezing indicator date when activated name of facility where vaccines are stored identification of the refrigerator 151

152 Appendix 15.2 Note on the back of the card: inspection date, status of indicators (heat-sensitive and freezing), name of supervisor. 152