Outbreak investigation in vector-borne Diseases
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1 Outbreak investigation in vector-borne Diseases Laurence Marrama Rakotoarivony EU preparedness, SRS EVD programme MediPIET course, Athens, 21 April 2016
2 Learning objectives Understand the reasons to perform an outbreak investigation Identify the objectives of an outbreak investigation Know the steps perform outbreak investigations Understand the specificities of a vector-borne disease investigation
3 Reasons to carry out an outbreak investigation of a vector-borne disease To stop the outbreak; To prevent new outbreaks; To better understand the disease; To implement, evaluate or adapt the surveillance system; To train in outbreak investigation.
4 Objectives an outbreak investigation To confirm that the occurrence of a VBD outbreak; To identify the pathogen and its origin; To identify/confirm the vector and estimate its population dynamics; To appraise the scale of the outbreak (area and population at risk); To identify the factors that affect transmission; To appraise the risk of the outbreak to spread; To identify the best strategy to control the outbreak; To prepare/start the appropriate response.
5 When to investigate an outbreak of a VBD? As soon as possible, as : Public concern is quickly high with vector-borne diseases; The more the disease spreads the more difficult it is to control it; If an outbreak occurs, it means that requirements for disease transmission are met and environmental conditions are favourable; Disease transmission will last as long as the conditions for transmission are favourable (up to several months); There is a risk for disease transmission to continue to spread.
6 10 steps of an outbreak investigation Descriptive phase 1. Confirm the existence of the outbreak of VBD 2. Confirm the diagnosis of the VBD 3. Establish the outbreak investigation team 4. Develop the case definition for the investigation and collect cases 5. Perform a descriptive analysis Analytic phase 6. Generate hypotheses using descriptive findings 7. Test the hypotheses 8. Conduct additional investigations 9. Communicate the findings 10. Propose recommendations for control and prevention measures
7 1. Confirm the existence of the outbreak Definition Outbreak: number of observed cases > expected cases If the disease is absent, 1 locally acquired case = outbreak Source of information + Surveillance of human cases + Travel history data (imported/locally acquired cases) + Vaccination status data + Surveillance of animal cases (according to the disease) + Surveillance of vectors + Monitoring of environmental data (weather ) + Population census
8 1. Confirm the existence of the outbreak Verify that it is not due to an artefact of surveillance Implementation/enhancement of surveillance Increased awareness Change in lab techniques False positive results Rapid increase of the population (migrants from endemic countries ) Accumulation of cases (serology) / difficulty to get the date of infection
9 2. Confirm the diagnosis Diagnosis of VBD is usually based on lab results ( 1 step) Symptoms are often not specific Differential clinical diagnosis is large History of vector bite is difficult to rely on Travel history is essential (but not always simple) Proximity to already confirmed cases (local transmission) Classification confirmed / probable cases based on lab Cross-reaction exists with some lab techniques Co-infection can happen
10 3. The outbreak investigation team The team Multidisciplinary team to cover all aspects of the VBD Epidemiologists Clinician from the peripheral/central level Entomologists Veterinarians Lab personnel / specialist of the pathogen Response Risk communication Administrative staff
11 3. The outbreak investigation team Organise the team Designate a coordinator Clearly define the terms of reference for the team members Plan activities Share responsibility for drafting the final report If the required skills are not available, requested experts, use guides When relevant, team member should be vaccinated or take chemoprophylaxis
12 3. The outbreak investigation team Other preparation activities Gather information about the people/services involved Collect preliminary information (maps, previous investigations ) Prepare mission orders and obtain permits Prepare a budget estimate and ensure funding Prepare necessary equipment for transport, investigation Contact the lab for the analysis of the specimens Determine the communication methods
13 3. The outbreak investigation team Example of tasks organisation for the multidisplinary team (dengue) Clinical epidemiology Entomology Lab / pathogen expertise Response management Describe the situation Is it a VBD outbreak? X X X What is its scale? X X X Evaluate the risks of the disease spreading What factors affect transmission X X X Organize the response What population is at risk? X X X X What vector control measures are required Are resources available for the response and follow-up? X X X X X
14 4. Case definition and search for cases Remember: - Not all VBD infection induce clinical symptoms. - Clinical signs are not specific/other diseases present similar clinical signs. - Atypical cases are possible - As far as possible, all suspected cases should be lab confirmed - A case definition is based on the PROBABILITE to be actually infected (confirmed/probable/possible or conformed/suspected/discarded) It should be balanced in terms of sensitivity and specificity It should be based on the objectives of the investigation
15 4. Case definition and search for cases For the investigation, the case definition: - must be operational (easy to apply) and unique for a specific objective; - must specify the area and the period of investigation; - should include clinical, biological, lab test criteria; - should make it possible to identify the largest possible number of cases in order to find the 1 st case (origin of the outbreak), evaluate its scale and risks of spread - should consider the discarded cases. Example: A [suspected, ] case is a person presenting [clinical/biological/lab result], who is/was resident or has travelled in [place] between [period].
16 4. Case definition and search for cases It is not necessary to identify all cases. However some cases are very important to correctly describe/understand the outbreak: - the first case; - cases with different clinical presentations; - cases infected at different times during the period; - cases infected in different places of the investigation area. Sample of cases as representative as possible of the population of cases
17 4. Case definition and search for cases The transmission of most vector-borne diseases is essentially local (due infection in the local vector population) and it spreads gradually. Emergence of cases in a remote area are due to movement of infected people and, occasionally, to the transportation of infected vectors (by car, trucks ). The most efficient method is the active search of suspected cases around suspected/confirmed cases and question of people about their movement. It requires to gather preliminary information with the local authorities: List of suspected/confirmed cases (lab and clinical team) List & cartography of health care facilities with case reports These data help to define an a priori investigation area and allow operational organisation (teams, transport). This area is refine according to findings.
18 4. Case definition and search for cases A standardized method should be implemented for the investigation: - A data collection sheet to be completed (see next slide) - Interview cases, family, neighbours - Add lab results (possible sequential results) - Prepare the analysis plan (easy, descriptive analysis) Additional information include: - Population at local level - Cases in animal (local data and/or investigation) - Environmental / meteorological data - Information on vectors (local data and/or entomological investigation) - Document with pictures
19 4. Case definition and search for cases Collected information (in parenthesis: reason or analytical value) Unique identifier and contact (avoid duplicates) Age, gender, residence (analysis in terms of place and person) Date of onset (epidemic curve) Clinical signs motivating consultation (diagnosis, differential diagnosis) Vaccination status if relevant (interpretation of lab results) Movement: place, contact with cases (infection place, outbreak dynamics) Date form completed and investigator name (consistency, missing data)
20 5. Descriptive analysis Time Place Person = When have they been infected? = Where have they been infected? = Who has been infected?
21 5. Descriptive analysis: time Number of cases / Incidence rate / Mortality rate Epidemic curve line chart Cases: distribution by date of onset (day, week) Importance et evolution of the outbreak (beginning, peak, length, end) Search of the index case Generate hypotheses source of infection type of transmission (when different types possible) period of infection Routes of dissemination
22 5. Descriptive analysis: time Example: epidemic curve of yellow fever Number of suspected deaths suspects and confirmed cases, identified during the outbreak of Yellow fever (September-December 2001, district of Bambey, Senegal) Number of cases (grey = 1 confirmed case (IgM+), black = 1 suspected death) Weeks September October November December Months
23 5. Descriptive analysis: time Example: epidemic curve of chikungunya, Italy 2007
24 5. Descriptive analysis: place Number of cases by place, specific rate by place Maps (points, areas), bar chart o Place of residence, of work o Other place of exposure (travel, visit to patients ) Identify des areas at risk Generate hypotheses source of infection type de transmission route of dissemination
25 5. Descriptive analysis: place Example: Outbreak of CCHF in Mauritania 10 8 Number Nombre of de cases cas Distribution of cases by place of residence Survivant cases Décédé deaths n = Rosso Keur Macène Rkiz Aleg Maghta Lahjar Tidjikja Moudjeria Mbout Kiffa Boumdeid TRARZA BRAKNA TAGANT GO RGO L ASSABA HEG Tintane
26 5. Descriptive analysis: place Example: Outbreak of Yellow fever, Mali
27 5. Descriptive analysis: place Example: Outbreak of Yellow fever in Senegal
28 5. Descriptive analysis: place Example: Outbreak of chikungunya in Italy
29 5. Descriptive analysis: person Person = individual characteristics Number of cases by age, gender, occupation, specific rates Table, bar chart o Possibility of exposure (at work, during holidays ) Identify the populations at risk Generation of hypotheses source of infection type of transmission Route of dissemination
30 5. Describe mode of transmission It is crucial to identify the possible involved vectors as the collection methods depends on the vector (see ECDC guidelines) the control measures depend for a large part on the vector Collection of vectors will depend on different decisions: which form of the vector will be collected (immature/adult) at what time and how frequently with which method (traps ) how will be done the identification of the species how the vectors will be transported to the lab (for pathogen detection, ) what complementary data will be collected (location, time of collection, method, number of sites prospected, )
31 5. Risk of the disease spreading Collection of information to estimate the risk of spread: Human migration / movement Vector density and infection Population immunity Environmental conditions Trade / transport of goods
32 6. Generate hypotheses Search an hypothesis and discuss it. Question a few cases : questionnaire / open interrogation as complete as possible Index case Place / person / time Type of suspected transmission (Rift valley fever): direct / vector Link between suspected cases and contacts (FHCC)
33 6. Generate hypotheses Transmission chains of CCHF, Nouakchott, Mauritania, 2003 Hospital personnel Family C = Date of infection S = Date of onset P = ID
34 7. Challenge hypotheses with facts Challenge the hypothesis using: clinical observations biological analysis epidemiological studies statistic tests The hypotheses have to be: plausible biologically possible explain the source, transmission mode, infection place
35 8. Perform addition investigations Plan analytical studies Evaluate the alert/surveillance systems Case control or cohort studies Sociological studies (care seeking behaviour ) Travel (patterns, importance, destination ) Environmental studies (breeding sites, weather, climate ) Lab studies (pathogen sequencing, competence tests ) Objectives Analyse of the validity of the information Analyse of presdisposing factors Validate of predictive factors
36 9. Communicate findings Regular communication during the investigation (orally, bulletins ) It forces the investigators to summarize the information, share and discuss findings of the multisciplinary team, and elaborate recommendations. It allows to share results and recommendation with decision-makers and the public. At the end of the investigation, it is required to document the outbreak (evolution over time of outbreaks, surveillance, investigations) It can be used as a training tool and for standardisation.
37 9. Communicate findings Origin of the outbreak Local transmission / imported cases Travel history? Presence / absence of competent vectors Possibility of local direct transmission (i.e. non-vector-borne)? Type of transmission Epidemiological factors Spatial distribution of cases Temporal distribution of cases Distribution of cases by age / gender / occupation Entomological factors (vectors, abundance) Environmental factors (urbanized, rural, climate, land cover )
38 9. Communicate findings Population at risk : (locally, in neighbouring areas, in remote areas) Local transmission Type of transmission Vaccine coverage (evaluation?) Gathering / movement of population Abundance of the vectors (domestic/wild) Predisposing factors Reservoirs Risk of outbreak re-appearing in the coming years Movements of population Persistence of the pathogen in vectors Reservoirs
39 9. Report Example
40 9. Report
41 9. Presentation Example
42 10. Propose recommendations Do wait until the end of the end of the investigation. General actions can be implemented act the beginning and are completed by more specific ones according to the findings. Standard actions to control the outbreak: On the source (ex : isolation of infected people, sanitary measures, ) On the transmission (ex : sanitary measures, vector control measures) On the contact vector-host (ex : use of repellents, ) On the susceptibility of the host (ex : vaccination, prophylaxis)
43 10. Propose recommendations Vector control Vaccination (Tick-borne disease, yellow fever, Japanese encephalitis) Emergency campaign of mass vaccination Planning of mass vaccination campaign Surveillance of adverse events Enhance routine vaccination programmes Sanitary measures/isolation of infectious people (use of bednets) Health education programmes for the population Enhancement/improvement of surveillance Remark: the impact of these recommendations has to be evaluated.
44 Conclusion Dot not forget the reasons and objectives of the investigation: Provide evidence-based recommendations for control and prevention always Understand how / why the outbreak started often Inprove the surveillance of the vector-borne disease often Learn on / train in outbreak investigation often Address a scientific question sometimes
45 References - Adapted from the course of Arbovirology - Investigation of yellow fever epidemics in Africa, field guide: _5F.pdf
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