Global Health Challenges Social Analysis 76: Lecture 12 Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Definitions Epidemic Surveillance and Response Pandemic Influenza Disease Eradication Polio Eradication Campaign Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Epidemic and Endemic Epidemic -- from Greek epi- upon + demos people, is a disease for which the incidence of new cases in a given human population, during a given period, substantially exceeds what is "expected", based on recent experience. Some historically important epidemic diseases – yellow fever, plague, smallpox, cholera, influenza Endemic – a disease is maintained in a population without the introduction of cases from outside the population. Harvard University Initiative for Global Health

Control and Elimination Control: Reduction of disease incidence, prevalence, morbidity or mortality to a locally acceptable level as a result of deliberate efforts. Continued intervention measures are required to maintain the reduction. Elimination of disease: Reduction to zero of the incidence of a specified disease in a defined geographical area as a result of deliberate efforts. Continued intervention measures are required. Harvard University Initiative for Global Health

Elimination and Eradication Elimination of infection: Reduction to zero of the incidence of infection caused by a specified agent in a defined geographical area as a result of deliberate efforts. Continued measures to prevent re-establishment of transmission are required. Eradication: Permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts. Intervention measures are no longer needed. Herd Immunity: when vaccination of a large fraction of a population provides protection to un-vaccinated individuals through decreased disease transmission. Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Definitions Epidemic Surveillance and Response Pandemic Influenza Disease Eradication Polio Eradication Campaign Harvard University Initiative for Global Health

Epidemic Disease Surveillance A key aspect for managing epidemics it to quickly identify a disease outbreak and track trends. All Ministries of Health have a system of notifiable cases of certain disease based on the detection of cases in health facilities. Cases are reported sometimes by paper forms and more recently electronically in selected countries to the central Ministry of Health. Case definitions are based on both clinical signs and symptoms and laboratory criteria for confirmed cases. Ministries of Health report cases to the World Health Organization, weekly, monthly or annually depending on the disease and epidemic. Harvard University Initiative for Global Health

Limitations of Disease Surveillance Systems Facility based data collection only captures a small fraction of cases in the population for most diseases. Poor and excluded groups much less likely to be captured. Weak laboratory systems in many developing countries for confirmation. Speed of transmittal of information from the periphery to the center. Political and economic reasons to suppress information on disease outbreaks. Harvard University Initiative for Global Health

WHO and Epidemic Surveillance and Response International Health Regulations give WHO legal authority to undertake a number of actions related to epidemics including issuing travel bans and other restrictions. Ministries of Health report notifiable cases to the WHO but these are often highly incomplete and politicized – e.g. impact of cholera on tourism, China reluctance to report SARS. To supplement poor reporting, WHO scans local media sources and also receives internet submissions about potential outbreaks. Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Epidemic Response Once a potential outbreak has been identified, national health authorities and WHO with the support of agencies like CDC can respond. Investigation of the source and identification of the agent with laboratory confirmation. Quarantine including travel bans – Canada, China in the case of SARS. Specific responses depending on the agent. In the era of SARS, Avian flu and bioterrorist threats, much greater political and business interest in surveillance and response. Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Definitions Epidemic Surveillance and Response Pandemic Influenza Disease Eradication Polio Eradication Campaign Harvard University Initiative for Global Health

Influenza Virus Composition Type of nuclear material Neuraminidase Hemagglutinin This is a schematic of the influenza virus. As you can see here, it has two surface proteins : hemagglutinin and neuraminidase—or H and N– that our immune systems respond to. The strain information tells you the virus type (A or B), where this particular influenza virus was first isolated, the laboratory strain number, the year it was isolated and the virus subtype (H3N2). A/Beijing/32/92 (H3N2) Virus type Geographic origin Strain number Year of Isolation Virus subtype Harvard University Initiative for Global Health

Influenza Antigenic Changes Structure of hemagglutinin (H) and neuraminidase (N) periodically change: Drift: Minor change, same subtype In 1997, A/Wuhan/359/95 (H3N2) virus was dominant A/Sydney/5/97 (H3N2) appeared in late 1997 and became the dominant virus in 1998 Shift: Major change, new subtype H2N2 circulated in 1957-67 H3N2 appeared in 1968 and replaced H2N2 Pandemic potential The influenza virus undergoes mutations which means that the virus is constantly changing. This process is called DRIFT. Drift affects viruses that already are in worldwide circulation. The process allows influenza viruses to change and re-infect people repeatedly and is the reason virus strains in the vaccine must be updated each year. Much more rarely, the H and N proteins are not modified, but change altogether. When this happens it is called SHIFT, and the result is a virus to which most people have no pre-existing antibody protection. When this happens one of the key conditions for a pandemic to happen has been met. Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Timeline of Emergence of Influenza A Viruses in Humans Avian Influenza H9 H7 Russian Influenza H5 H5 Asian Influenza H1 H3 Spanish Influenza H2 Hong Kong Influenza H1 This illustration depicts the antigenic shifts that occurred during the 20th century. The H1 subtype that circulated starting 1918 was replaced by an H2 subtype in 1957. Of note: when the H1 subtype reappeared in 1977, young persons were disproportionately affected as persons born before 1957 would have had previous exposure to H1 virus. The H5, H7, and H9 subtypes depicted have not caused sustained person-to-person transmission and will be discussed further later on. 1918 1957 1968 1977 1997 2003 1998/9 Harvard University Initiative for Global Health

20th Century Influenza Pandemics 1918-20 – huge mortality concentrated in adult age-groups, mortality ranged from 0.2% of the population in Denmark to 8% in Central Province, India. 1957-58 – much lower mortality 1968-1970 – similar to 1957-58 Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Distributions of median deaths forecasted by a replay of the 1918-20 pandemic in the year 2004 by region and age-group 62.1 Million Global Deaths Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Intervention Options Develop and distribute vaccine Antivirals for prevention and treatment --zanamivir and oseltamivir phosphate Antibiotics for secondary bacterial pneumonia Supportive medical care Travel bans, quarantine Pneumocccal, HiB vaccination? Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Pandemic Vaccine Annual vaccine is trivalent (3 strains), pandemic vaccine will be monovalent. Production using current technologies would likely take 4-5 months  may not be available before 1st pandemic wave There will be vaccine shortages initially 2 doses may be necessary to ensure immunity Although vaccine will begin to be available after 4-5 months it will take time to manufacture enough vaccine for the entire population. In the early phases when limited amounts are available it will be necessary to vaccinate priority groups. It is likely that 2 doses of vaccine will be necessary since the vaccine will protect against a new subtype to which most persons will have no prior immunity. Harvard University Initiative for Global Health

Developing Country Response? Low probability that in setting of a major influenza pandemic vaccine would reach low-income or even middle-income populations. 92% of the likely mortality would be in the developing world. What intervention strategies can be used in these resource poor environments? Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Definitions Epidemic Surveillance and Response Pandemic Influenza Disease Eradication Polio Eradication Campaign Harvard University Initiative for Global Health

Criteria for Eradicability Biological and Technical feasibility – -an effective intervention to interrupt transmission of the agent; - diagnostic tools with sufficient sensitivity and specificity; and - humans are essential for the life cycle of the agent which has no other vertebrate reservoir and does not amplify in the environment. Costs and Benefits – the cost of eradication is warranted by the benefits Societal and Political Support Harvard University Initiative for Global Health

Disease Eradication Efforts Yellow Fever -- launched 1915, mosquito control, failed Yaws – launched 1955, long-acting penicillin, failed Malaria – launched circa 1955, DDT, failed Smallpox – launched 1967, vaccine, last case 1977 Dracunculiasis (Guinea Worm) – launched 1988, water access interventions, on-going Polio – launched 1988, vaccine, ongoing Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Smallpox Caused by a virus transmitted from person to person by respiratory transmission. 10-12 day period of incubation. Fever, aching pains, 2-4 days into illness, rash over face that spreads to rest of body, lesions become pustular. One of causes of major human epidemics. In 1796, Jenner figured out that pustular material from a cowpox lesion (vaccinia virus) would provide protection from smallpox. Commercial production of heat stable freeze-dried vaccine based on the vaccinia virus became available after WWII. Harvard University Initiative for Global Health

Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Smallpox Eradication WHO resolution calling for smallpox eradication around 1959 with little progress over the next 8 years. January 1967 intensified smallpox eradication program launched, at the time estimated 10-15 million cases a year in 44 countries. Major effort with key role played by WHO and US Centers for Disease Control. Last case, Somalia, in 1977. World declared smallpox free in 1980. Harvard University Initiative for Global Health

Why Did Smallpox Eradication Work? Humans only reservoir for the virus. Short period of infectivity 3-4 weeks after onset of skin lesions. Clustered outbreaks due to mechanism of transmission. Vaccine highly effective with long duration effect. Harvard University Initiative for Global Health

Lessons Learned from Smallpox Eradication Smallpox eradication had a very small budget for donor assistance – it had to work primarily using existing health system staff. Operational research on all aspects of control was used to tailor the program strategy to local epidemiological, social and health system conditions. Surveillance including independent monitoring of the effectiveness of vaccination teams. Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Guinea Worm Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Definitions Epidemic Surveillance and Response Pandemic Influenza Disease Eradication Polio Eradication Campaign Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Polio Polio virus transmitted through faecal-oral transmission. Most cases are asymptomatic. 1/200 develop acute flaccid paralysis. 1955- Salk et al developed inactivated polio virus vaccine (IPV) 1961 – Sabin developed live attenuated oral poliovirus vaccine (OPV) Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Polio Control With improved sanitation and widespread use of IPV in high-income countries, incidence fell dramatically. Cuba eliminated polio in the 1960s through mass campaigns using OPV. Pan American Health Organization (PAHO) initiated elimination campaign for the Americas in 1985. Global eradication campaign launched in 1988. Rotary International adopted the campaign and has raised well over $500 million, other donors have contributed more than $3 billion. Harvard University Initiative for Global Health

Polio Eradication Strategy Mass vaccination through National Immunization Days. In poor sanitation environments, each child may need up to 8 doses for permanent immunity. Huge resources (more than US$4 billion?), 20 million plus volunteers, 30% of WHO staff devoted to eradication effort. Steady progress until 2000. Harvard University Initiative for Global Health

Harvard University Initiative for Global Health Setbacks Hispanola outbreak in 1999 found to be due to vaccine derived poliovirus. OPV can mutate back to cause paralysis and can be transmitted human to human. Outbreaks proven with genetic fingerprinting in Egypt, Madagascar, and the Philippines. Post 9/11 not clear countries will be willing to stop immunization even after eradication because of bioterrorist threats. Harvard University Initiative for Global Health

Harvard University Initiative for Global Health

Rumors and Cessation of Vaccination in Kano State, Nigeria Persistent rumors in Muslim communities that polio vaccine was contaminated with HIV and/or would lead the children immunized to be sterile. Kano State, Nigeria stopped vaccination from Jan 1 2004 to September 2004. Outbreak of cases has lead to spread to multiple countries outside of Nigeria. Locus of transmission in Muslim communities in Uttar Pradesh has also led to transmission to other parts of India and other countries. Harvard University Initiative for Global Health

Harvard University Initiative for Global Health

Should the Goal of Eradication be Changed to Elimination or Control? Ongoing cost to poor countries in terms of dollars and staff time is high? Unclear prospect that wild poliovirus transmission can be interrupted given Muslim suspicions in certain countries. OPV paradox – OPV is oral and cheap but OPV has a clear risk of causing vaccine derived outbreaks. Should we switch to control as the goal? If so, how to make this difficult decision? Harvard University Initiative for Global Health