Pandemics. Dr Tim Healing Dip.Clin.Micro, DMCC, CBIOL, FZS, FRSB. Course Director, Course in Conflict and Catastrophe Medicine

Transcription

1 Pandemics Dr Tim Healing Dip.Clin.Micro, DMCC, CBIOL, FZS, FRSB Course Director, Course in Conflict and Catastrophe Medicine Worshipful Society of Apothecaries of London Faculty of Conflict and Catastrophe Medicine

2 What is an epidemic? The occurrence in a defined region of cases of a disease in the human population in excess of normal expected numbers An equally widespread disease that is stable in terms of how many people are getting sick from it is not an epidemic, it is endemic

3 What is a pandemic? An epidemic of infectious disease that is spreading through human populations across a large area (e.g. a continent) or even worldwide In WHO terms it is occurring in more than one WHO region A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic

4 Why do pandemics occur? Emergence or introduction of a novel disease capable of infecting humans Re-emergence of a disease not seen in human populations for many years Readily transmissible and sustainable No too rapidly lethal Wholly susceptible population Mechanisms to allow spread in human population

5 WHO conditions to declare a pandemic A disease new to a population - or at least a disease that has not surfaced for a long time It must be caused by disease-causing agents that infect humans, leading to serious illness The agents must spread easily and sustainably among humans

6 Why are pandemics potentially damaging to societies? Reduction in the workforce Health services Infrastructure Transport (food, fuel distribution) Power Water supplies Social unrest Security High morbidity Difficult to treat patients adequately High mortality May be difficult to dispose of the dead Legal issues

7 Medical work during a pandemic Many health workers affected Hospitals & health care services overwhelmed Hospital infrastructure damaged Drug, food etc. supplies affected PPE required Dealing with patients is slow and uncomfortable Photos: TDH

8 Basic PPE: good protection against organisms of low virulence (e.g. H1N1) Photo: TDH

9 PPE for dangerous organisms (e.g. H5N1) is much more difficult to work in

10 Minimising the effects of a pandemic The aim is to reduce numbers of cases If not, try to flatten the curve! Same number of cases Longer time Less intense impact on society

11 How can this be achieved? Reduction of potential transmission events: Close/cancel social events, close schools Encourage people to stay at home Try to minimise use of public transport Handwashing Use of masks? Not very effective Can generate false sense of security Try to reduce demands on medical/health care services Encourage home nursing Try to minimise use of medical facilities by those who can be cared for at home free them up for acute cases

12 Minimising effects #2 Epidemiological investigation & surveillance Quarantine of suspect and confirmed cases Inpatient care Other Discourage hoarding Public education/reassurance

13 Organisms particularly associated with pandemics Plague (Yersinia pestis) Plague of Athens (?) [430 BC] Plague of St Justinian [542 AD] Black death [14 th Century] (The most destructive pandemic?) Great plague of London [1665] Cholera [seven pandemics since 1816] Influenza Asiatic [ ] Spanish flu [ ] Asian Flu [ ] Hong Kong [ ] Swine flu [ ]

14 Other pandemic organisms Smallpox devastated the Americas when European settlers first introduced it in the 15th century. Measles Cuba, Killed 66% of the population Honduras Killed 50% of the population Mexico, Central America Killed huge numbers, ravaged the Inca civilization Hawaii 1850s:killed 20% of the population Antonine & Cyprian plagues Probably measles or smallpox. Ravaged the Roman Empire from 165 to 180 AD and in 251 AD HIV/AIDS 20 th century. Killed >25 million people

15 Historical effects of pandemics Antonine plague decline of the Roman empire Plague of Justinian prevented the spread of the Byzantine Empire into Italy, significantly changed the course of European history Smallpox a major factor in the conquest of the Aztec and Incan civilizations by the Spanish Black death created a series of religious, social and economic upheavals, profoundly affected European history

16 Plague pandemics and epidemics There have been 3 major plague pandemics and several damaging local outbreaks The Plague of Justinian (6 th & 7 th centuries) Up to 40% of the population of Constantinople died from the plague. Modern estimates suggest half of Europe's population was wiped out before the plague disappeared in the AD 700s The Black Death (14 th century) originated in or near China may have reduced the world's population from ca. 450 million to million in 1400 Plague returned at intervals with varying virulence and mortality until the 18th century In 1603 plague killed 38,000 Londoners Other notable 17th-century outbreaks were: the Italian Plague ( ), the Great Plague of Seville ( ), the Great Plague of London ( ) the Great Plague of Vienna (1679) The Third Pandemic hit China in the 1890s and devastated India but was confined to limited outbreaks in the west Outbreak in India (1994) caused 700 infections (52 deaths) and triggered a large migration of Indians within India as they tried to avoid the disease

17 The Black Death A massive outbreak of plague that ravaged Europe throughout the 14 th Century Estimated to have killed between 75 to 200 million people in the 14th century alone 45-60% of the entire population of Europe was wiped out Reduced the world's population from ca. 450 million to between 350 & 375 million by 1400 It took 150 years for Europe's population to recover

18 Origin of the pandemic Originated in China Began in 1331 Population of China fell from 120 to 60 million. By the end of 1346 "India was depopulated, Tartary, Mesopotamia, Syria, Armenia were covered with dead bodies". Entered Constantinople in 1347 Reportedly first introduced to Europe at the trading city of Caffa in the Crimea in Fleeing Genoese carried the plague by ship into Sicily and the south of Europe, whence it spread north. Several existing conditions such as war, famine, and weather contributed to the severity of the Black Death.

19 Influenza Characterized by a sudden onset of fever, cough (usually dry), headache, muscle and joint pain, severe malaise sore throat and a runny nose. The cough can be severe and can last 2 or more weeks. Can cause pneumonia Transmitted by aerosols and on the hands (nasal secretions and contact with contaminated surfaces) Seasonal epidemics, resulting in 3-5 million severe cases and 290, ,000 deaths every year* Occasional severe pandemics * WHO Influenza Fact Sheet: Jan 2018

20 Outbreaks: Seasonal Flu. Temperate climates - mainly in winter Tropical regions - throughout the year Worldwide, 3-5 million cases of severe illness, & 250,000 to 500,000 deaths. Estimated global annual attack rate 5% 10% in adults, 20% 30% in children. High-risk groups include the very young, elderly, chronically ill in industrialized countries most deaths >65Y large % of child deaths associated with influenza occur in developing countries

21 Circulating influenza viruses in Northern Hemisphere (to 24/05/2018)

22 Influenza viruses RNA viruses (Orthomyxoviridae) 3 of the 5 strains can affect humans Influenza A Wild aquatic birds are the natural hosts The most virulent human pathogens among the 3 influenza types, cause the most severe disease Subdivided into different serotypes The cause of pandemics Influenza B less common than influenza A. less genetically diverse almost exclusively infects humans Influenza C Infects humans, dogs and pigs least common type, usually only causes mild disease in children

23 Influenza surface antigens Haemagglutinin (HA) - a glycoprotein that binds the virus to the cell that is being infected. At least 16 different HA antigens of which 3 (H1, H2, H3), are found in human flu viruses Viral neuraminidase (NA) - enzyme that enables the virus to be released from the host cell Influenza viruses are characterised by the type of HA and NA that they carry; hence H1N1, H5N1, H3N2 etc.

24 Anti-flu drugs Neuraminidase inhibitors Oseltamivir (Tamiflu), Zanamivir (Relenza) and Peramivir prevent the virus from reproducing by budding from the host cell effective against both influenza A and B M2 inhibitors Amantadine and Rimantadine preventing uncoating of the virus work only against influenza A

25 Epidemiology All age groups can be affected Health care workers are at high risk due to increased exposure and risk further spread to vulnerable individuals People at risk of severe disease or complications are: pregnant women children <59m the elderly individuals with chronic medical conditions individuals with immunosuppressive conditions (e.g. HIV/AIDS, chemotherapy or steroids, malignancy) Incubation period 2-4 days

26 Epidemiology Influenza spreads easily, with rapid transmission in crowded areas including schools and nursing homes. Spread is by: droplet inhalation via contaminated hands Risk of transmission is reduced if people cover their mouth and nose with a tissue when coughing, & wash their hands regularly

27 Treatment Patients not from a high risk group should be managed with symptomatic treatment and should stay at home in order to minimize the risk of infecting others

28 Patients with severe/progressive clinical illness associated with suspected or confirmed influenza virus infection Treat those with severe or progressive clinical illness (pneumonia, sepsis, exacerbation of chronic underlying diseases) with antiviral drugs* Neuraminidase inhibitors (i.e. oseltamivir) (ideally, within 48 hours following symptom onset). Also for patients presenting later in the course of illness. Treat for a minimum of 5 days Do not use corticosteroids unless indicated for other reasons (e.g: asthma etc.). (may prolong viral clearance, cause immunosuppression leading to bacterial or fungal superinfection) *NB. All currently circulating influenza viruses (Jan 2018) are resistant to adamantane antiviral drugs (such as amantadine and rimantadine)

29 Vaccination Good hygiene Prevention Influenza viruses can be inactivated by sunlight, disinfectants and detergents Hand hygiene is an important control measure Isolation Reduce transmission Health education Antiviral drugs

30 Influenza pandemics Pandemic Date Deaths CFR Subtype Asiatic (Russian) x % H3N8(?) Spanish (1918) x 10 6 (Possibly 2.5-5% of the world's population killed) >2.5% H1N1 Asian x % H2N2 Hong Kong x 10 6 <0.1% H3N (Swine flu) , % H1N1

31 WHO Pandemic phases - Influenza PREDOMINANTLY ANIMAL INFECTIONS; FEW HUMAN INFECTIONS PHASE 1: No reports of human infections from influenza viruses circulating naturally among animals and birds. PHASE 2: Some infections in humans from influenza viruses in animals show the virus is a potential pandemic threat. PHASE 3: Sporadic cases or small clusters of infection in people, but not enough to result in sustained human-to-human transmission. SUSTAINED HUMAN-TO-HUMAN TRANSMISSION PHASE 4: The virus is spreading from person to person causing outbreaks at the level of communities, indicating an increased risk but not certainty that it will turn into a pandemic. WIDESPREAD HUMAN INFECTION/PANDEMIC PHASE 5 Human-to-human spread of the virus in at least two countries in one region. Most countries are not yet affected but a pandemic is imminent. Health authorities have little time left to finalise measures to deal with the outbreak. PHASE 6: The virus is spreading in at least two regions, indicating a global pandemic is underway. (No mention of disease severity!)

32 Why is Influenza a cause of pandemics? Drift and Shift Antigenic drift: Mutations cause small changes in the H & N antigens. New strains created some of which are human pathogens May cause an epidemic Strains are similar to old ones & some people immune Reasonably predictable, annual vaccines can be made Antigenic shift Occurs when influenza viruses re-assort (genetic material from different viruses mixes) New antigens - no-one is resistant pandemics can occur Readily transmissible Infective before symptoms appear

33 Spanish Flu Due to a strain of H1N1 Broke out in 1918 Estimated to have infected one third of the world s population Most victims were healthy young adults Possible death toll > 50 million people (3% of world s population)

34 Exceptionally severe infection CFR >2.5%, (CFR in other flu pandemics ca. 0.1%) Unusually it mostly killed young adults. 99% of deaths (in USA) occurred in people <65Y; ca. 50% in 20-40Y pregnant women very vulnerable (in 13 studies, death rate 23% - 71%) 26% of those who survived childbirth lost the child. virus triggers a cytokine storm, which attacks the stronger immune system of young adults. Initially misdiagnosed as dengue, cholera, or typhoid... striking complication was haemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial haemorrhages also occurred". Majority of deaths probably from bacterial pneumonia The virus also killed people directly, by causing massive haemorrhages and pulmonary oedema Good intensive care not available. No vaccines, no antibiotics

35 Fighting the Spanish flu "Physicians tried everything they knew, everything they had ever heard of,..bleeding patients, administering oxygen, developing new vaccines and sera (chiefly against.. Haemophilus influenzae and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success. (National Academies Press: The Threat of Pandemic Influenza: Are We Ready? darwin.nap.edu)

36 Pandemic Influenza A H1N Novel flu strain (Swine flu) Emerged early in 2009 in Mexico, the USA and several other nations Combined genes from human, pig and bird flu Initially appeared quite lethal - many deaths reported WHO declared the outbreak to be a pandemic on June 11 th 2009 Declaration of a Pandemic Level 6 was an indication of spread, not severity, the strain actually having a lower mortality rate than annual flu outbreaks

37 Why was the 2009 pandemic not particularly serious? 1. Virus was not particularly pathogenic 2. Antiviral drugs available 3. Antibiotics available 4. Intensive care facilities effective 5. Vaccine produced rapidly

38 H5N1 Avian flu the pandemic that did not happen (or has not happened yet?) A highly pathogenic virus (HPAI Highly Pathogenic Avian Influenza) Few human cases but high mortality. To end of 2017: 860 lab-confirmed human cases reported from 16 countries with 454 deaths (CFR 52.8%) Mortality pattern rather similar to 1918 outbreak (Max. CFR in 10-39Y age group) H5N1 remains infectious after >30 days at 0 C 6 days at 37 C at ordinary temperatures can survive in the environment for weeks dust containing the virus can be infectious No highly effective treatment, but Oseltamavir (Tamiflu), can inhibit spread of the virus in the body

39 H5N1(HPAI) -transmissibility to humans? An avian virus Most human cases associated with contact with infected poultry Human influenza HAs bind to α2-6 sialic-acid receptors in the human respiratory tract H5N1 HAs bind to α2-3 sialic-acid receptors found in birds These receptors are virtually absent in humans occur only in LRT Because they are present only in the LRT of humans, the virus is not easily expelled by coughing/ sneezing (usual route of transmission) & human to human transmission does not appear to occur NB. - there is evidence that the virus can infect the human GI tract, the brain, the liver and blood cells

40 Other emerging flu strains Over the past two years, H5N1 has been joined by newly detected H5N2, H5N3, H5N6, and H5N8 strains, all of which are currently circulating in different parts of the world. In China, H5N1, H5N2, H5N6, and H5N8 are currently co-circulating in birds together with H7N9 and H10N8

41 Avian influenza A(H7N9) a new Flu First report in humans - Mar 31 st, Chinese authorities notified WHO of 3 confirmed human cases in Shanghai and Anhui (illness onset between Feb 19 th & Mar 15 th, 2013) First reported death - an 87Y man who died on Mar 4 th Total of 1567 lab-confirmed cases of human infection to 02/03/2018. (615 deaths: CFR ca. 40%)

42 Novel virus Avian influenza A H7 viruses normally circulate among birds The new H7N9 virus contains influenza virus genes from multiple origins. May have a greater ability to infect mammals, including humans, than other avian influenza viruses. Contains a gene indicating resistance to amantadine and rimantadine

43 Infection with H7N9 Fever, cough & shortness of breath - may progress to severe pneumonia Can overload the immune system, causing a cytokine storm. Blood poisoning and organ failure can occur Most of the patients with confirmed H7N9 virus infection were critically ill - approximately 20% died of acute respiratory distress syndrome (ARDS) or multiorgan failure * * Li, Q et al. (April 24, 2013). "Preliminary Report: Epidemiology of the Avian Influenza A (H7N9) Outbreak in China". New England Journal of Medicine.

44 Epidemiology Much remains unknown including the animal reservoir(s) & routes of transmission Human infection probably related to exposure to live poultry/contaminated environments: The virus in humans genetically similar to that found in birds & the environment (live bird markets). ca. 75% of human cases have a history of exposure to birds, mostly chickens The virus has been detected in poultry No. of human cases falls after closure of live bird markets Little evidence of sustained human-to-human transmission

45 N.hemisphere: Flu in winter Composition of flu vaccines for N. hemisphere decided in Feb each year After Feb 2014, the genetic make-up and antigenic properties of the main seasonal virus circulating in N. America and Europe (H3N2), changed significantly This greatly reduced the effectiveness of the vaccine Such events are rare (only 4 seasons in the past 25 years).

46 SARS (Severe Acute Respiratory Syndrome) The pandemic that was halted An acute respiratory disease First case - 45Y male in Guandong, China, 16/11/2002 First cases in Hong Kong Feb 2003 Hanoi index case 26/02/2003 Singapore index case 01/03/2003 Canada index case 05/03/2003 Taiwan index case 14/03/2003 Virus identified 22/03/2003 Last pandemic cases July countries involved 8,422 cases and 916 deaths worldwide (CFR = 10.9%) No cases reported since 2004 SARS. Global epidemic curve of probable cases by date of onset

47 Cause A novel Coronavirus (SARS coronavirus - SARS CoV) Probably originated in wildlife & jumped the species barrier Isolated from: Palm civets (Paguma sp.) Raccoon dogs (Nyctereuteus sp.) Ferret badgers (Melogale spp.) Domestic cats Similar viruses found in bats Photo: TDH

48 Spread by: Respiratory droplets Transmission On the hands via the mucous membranes Requires close person to person contact Kissing, hugging, sharing eating / drinking utensils caring for / living with someone with SARS direct contact with respiratory secretions or body fluids of a SARS patient

49 Clinical presentation Incubation period 2-10 days Prodrome: Fever (>38 C) Sometimes Chills and rigors Headache, malaise, myalgia Productive cough & sore throat very rare

50 Clinical presentation & outcome After 3-7 days, lower respiratory phase begins dry, non-productive cough or dyspnea that may be accompanied by or progress to hypoxemia 25% of cases develop respiratory failure Diarrhoea in ca. 70% of cases Other manifestations: liver enzyme changes, lymphopaenia, hypotension, tachycardia, venous thrombosis Overall CFR 10% (varies from <1% for <24Y to 50% for >65Y) Permanent lung damage may occur

51 Treatment Supportive antipyretics oxygen and ventilation as needed. Isolate suspected cases preferably in ve pressure rooms complete barrier nursing precautions Antibiotics for presumptive treatment of atypical pneumonia [Antiviral agents such as oseltamivir or ribavirin & steroids had little effect]

52 Long-time sequelae Include: pulmonary fibrosis osteoporosis femoral necrosis Complete loss of working ability or even self-care ability Some post-sars patients have had severe problems with depression

53 Transmissability: SARS and the Hong Kong Metropole Hotel February 2 nd 2003, a 64-year-old Chinese doctor (had treated cases in Guangdong) arrived in Hong Kong Metropole Hotel (9 th floor - room 911) Feb 15 th - developed symptoms Feb 22 nd - admitted to hospital March 4 th - died Ca. 80% of Hong Kong cases traced back to him Linked to outbreaks in Canada, Singapore & Vietnam Known cases in Australia & Philippines (did not infect others)

54 Controlling the epidemic Epidemiological investigation & surveillance International co-operation Case definitions Defined responsibilities Identification of the cause International co-operation between laboratories Treatment of cases International sharing of results Quarantine of suspect and confirmed cases Advice against un-necessary travel & screening air travellers Reduction of social interaction in affected areas e.g. closure of schools

55

56 Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

57 MERS CoV the new SARS? The Middle East Respiratory Syndrome Coronavirus (MERS- CoV) An enveloped RNA virus Also called SARS-like virus, novel coronavirus or 'Saudi SARS' First known cases spring ,206 lab-confirmed cases including 787 deaths (to end April 2018: [WHO] CFR 35.7%). Most cases male (65.6%) Age 9/12-94 Y (median 49Y)

58 Cases world-wide 27 countries have reported cases Initial (& most ca. 80%) cases in Saudi Arabia (1,831 confirmed cases, 713 deaths) (Saudi MoH, to end April 2018) Concern about risks associated with Hajj pilgrimage

59 Severe disease in: elderly, MERS-CoV the disease immunocompromised, those with chronic diseases (e.g. cancer, chronic lung disease, diabetes) All have respiratory disease Symptoms vary from mild to severe pneumonia Renal failure may occur Atypical symptoms can occur in immunocompromised Supportive care is life saving No approved virus-specific therapy

60 Transmission generally requires close contact Settings where infection has occurred Communities: sporadic cases - unknown exposure Families: contact with infected family members Health care facilities: patients & health care workers Several clusters Connection between cases not fully understood Evidence for limited person-to-person transmission in some clusters Sustained human transmission has not yet been seen** Reservoirs of infection Dromedary camels have been shown to be infected with MERS CoV Taphozous perforatus (Egyptian tomb bat) may be the original source of the virus Epidemiology **The WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Currents 2013 Nov 12

61 Missed cases at least 62% of clinically apparent cases have been missed" Possible that as many as 17,940 infections occurred in both humans and animals between March 2012 and Aug 8, 2013 Cauchemez S, Fraser C, Van Kerkhove MD, et al. Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility. Lancet Infect Dis 2013 Nov 13

62 WHO Director-General Margaret Chan at the annual World Health Assembly (WHA) 2013 "Looking at the overall global situation, my greatest concern right now is the novel coronavirus. These are alarm bells and we must respond. The novel coronavirus is not a problem that any single affected country can keep to itself or manage all by itself. The novel coronavirus is a threat to the entire world.

63 Any Questions?