global health challenges social analysis 76: lecture 12

Harvard University Initiative for Global Health

Global Health ChallengesSocial Analysis 76: Lecture 12


DefinitionsDefinitionsEpidemic Surveillance and ResponseEpidemic Surveillance and ResponsePandemic InfluenzaPandemic InfluenzaDisease EradicationDisease EradicationPolio Eradication CampaignPolio Eradication Campaign


Epidemic -- Epidemic -- from Greek from Greek epi-epi- upon + upon + demosdemos people, is a people, is a disease for which the incidence of new cases in a disease for which the incidence of new cases in a given human population, during a given period, given human population, during a given period, substantially exceeds what is "expected", based on substantially exceeds what is "expected", based on recent experience.recent experience.

Some historically important epidemic diseases – yellow Some historically important epidemic diseases – yellow fever, plague, smallpox, cholera, influenzafever, plague, smallpox, cholera, influenza

Endemic – a disease is maintained in a population Endemic – a disease is maintained in a population without the introduction of cases from outside the without the introduction of cases from outside the population. population.

Epidemic and Endemic


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.


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.


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.


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.


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.


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.


Influenza Virus Composition

Type of nuclear material

Virus type

Geographic origin

Strain number

Year of Isolation

Virus subtype

A/Beijing/32/92 (H3N2)

HemagglutininNeuraminidase


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

Influenza Antigenic Changes


Timeline of Emergence of Timeline of Emergence of Influenza A Viruses in HumansInfluenza A Viruses in Humans

1918 1957 1968 1977 19971998/9

2003

H1

H1

H3H2

H7H5H5

H9

SpanishInfluenza

AsianInfluenza

RussianInfluenza

AvianInfluenza

Hong KongInfluenza


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


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


Intervention Options

1) Develop and distribute vaccine

2) Antivirals for prevention and treatment --zanamivir and oseltamivir phosphate

3) Antibiotics for secondary bacterial pneumonia

4) Supportive medical care

5) Travel bans, quarantine

6) Pneumocccal, HiB vaccination?


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


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?


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


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


Caused by a virus transmitted from person to person by Caused by a virus transmitted from person to person by respiratory transmission. respiratory transmission.

10-12 day period of incubation. Fever, aching pains, 2-10-12 day period of incubation. Fever, aching pains, 2-4 days into illness, rash over face that spreads to 4 days into illness, rash over face that spreads to rest of body, lesions become pustular. rest of body, lesions become pustular.

One of causes of major human epidemics. One of causes of major human epidemics.

In 1796, Jenner figured out that pustular material from In 1796, Jenner figured out that pustular material from a cowpox lesion (vaccinia virus) would provide a cowpox lesion (vaccinia virus) would provide protection from smallpox. protection from smallpox.

Commercial production of heat stable freeze-dried Commercial production of heat stable freeze-dried vaccine based on the vaccinia virus became vaccine based on the vaccinia virus became available after WWII. available after WWII.

Smallpox


WHO resolution calling for smallpox eradication around WHO resolution calling for smallpox eradication around 1959 with little progress over the next 8 years. 1959 with little progress over the next 8 years.

January 1967 intensified smallpox eradication program January 1967 intensified smallpox eradication program launched, at the time estimated 10-15 million cases launched, at the time estimated 10-15 million cases a year in 44 countries. a year in 44 countries.

Major effort with key role played by WHO and US Major effort with key role played by WHO and US Centers for Disease Control. Centers for Disease Control.

Last case, Somalia, in 1977. World declared smallpox Last case, Somalia, in 1977. World declared smallpox free in 1980. free in 1980.

Smallpox Eradication


Humans only reservoir for the virus.Humans only reservoir for the virus.

Short period of infectivity 3-4 weeks after onset of skin Short period of infectivity 3-4 weeks after onset of skin lesions.lesions.

Clustered outbreaks due to mechanism of Clustered outbreaks due to mechanism of transmission.transmission.

Vaccine highly effective with long duration effect. Vaccine highly effective with long duration effect.

Why Did Smallpox Eradication Work?


1)1) Smallpox eradication had a very small budget for Smallpox eradication had a very small budget for donor assistance – it had to work primarily using donor assistance – it had to work primarily using existing health system staff. existing health system staff.

2)2) Operational research on all aspects of control was Operational research on all aspects of control was used to tailor the program strategy to local used to tailor the program strategy to local epidemiological, social and health system epidemiological, social and health system conditions. conditions.

3)3) Surveillance including independent monitoring of the Surveillance including independent monitoring of the effectiveness of vaccination teams. effectiveness of vaccination teams.

Lessons Learned from Smallpox Eradication


Guinea WormGuinea Worm


Polio virus transmitted through faecal-oral transmission.Polio virus transmitted through faecal-oral transmission.

Most cases are asymptomatic. 1/200 develop acute Most cases are asymptomatic. 1/200 develop acute flaccid paralysis. flaccid paralysis.

1955- Salk et al developed inactivated polio virus 1955- Salk et al developed inactivated polio virus vaccine (IPV)vaccine (IPV)

1961 – Sabin developed live attenuated oral poliovirus 1961 – Sabin developed live attenuated oral poliovirus vaccine (OPV)vaccine (OPV)

Polio


With improved sanitation and widespread use of IPV in With improved sanitation and widespread use of IPV in high-income countries, incidence fell dramatically.high-income countries, incidence fell dramatically.

Cuba eliminated polio in the 1960s through mass Cuba eliminated polio in the 1960s through mass campaigns using OPV. campaigns using OPV.

Pan American Health Organization (PAHO) initiated Pan American Health Organization (PAHO) initiated elimination campaign for the Americas in 1985.elimination campaign for the Americas in 1985.

Global eradication campaign launched in 1988. Rotary Global eradication campaign launched in 1988. Rotary International adopted the campaign and has raised International adopted the campaign and has raised well over $500 million, other donors have well over $500 million, other donors have contributed more than $3 billion. contributed more than $3 billion.

Polio Control


Mass vaccination through National Immunization Days.Mass vaccination through National Immunization Days.

In poor sanitation environments, each child may need In poor sanitation environments, each child may need up to 8 doses for permanent immunity. up to 8 doses for permanent immunity.

Huge resources (more than US$4 billion?), 20 million Huge resources (more than US$4 billion?), 20 million plus volunteers, 30% of WHO staff devoted to plus volunteers, 30% of WHO staff devoted to eradication effort. eradication effort.

Steady progress until 2000.Steady progress until 2000.

Polio Eradication Strategy


Hispanola outbreak in 1999 found to be due to vaccine Hispanola outbreak in 1999 found to be due to vaccine derived poliovirus. derived poliovirus.

OPV can mutate back to cause paralysis and can be OPV can mutate back to cause paralysis and can be transmitted human to human. Outbreaks proven transmitted human to human. Outbreaks proven with genetic fingerprinting in Egypt, Madagascar, with genetic fingerprinting in Egypt, Madagascar, and the Philippines.and the Philippines.

Post 9/11 not clear countries will be willing to stop Post 9/11 not clear countries will be willing to stop immunization even after eradication because of immunization even after eradication because of bioterrorist threats.bioterrorist threats.

Setbacks


Confirmed AFP/Polio Cases

010002000300040005000600070008000

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

(10/2

4)

Other

Wildtype VirusConfirmed


Rumors and Cessation of Vaccination in Kano State, Nigeria

Persistent rumors in Muslim communities that polio Persistent rumors in Muslim communities that polio vaccine was contaminated with HIV and/or would lead vaccine was contaminated with HIV and/or would lead the children immunized to be sterile. the children immunized to be sterile.

Kano State, Nigeria stopped vaccination from Jan 1 Kano State, Nigeria stopped vaccination from Jan 1 2004 to September 2004. Outbreak of cases has lead 2004 to September 2004. Outbreak of cases has lead to spread to multiple countries outside of Nigeria. to spread to multiple countries outside of Nigeria.

Locus of transmission in Muslim communities in Uttar Locus of transmission in Muslim communities in Uttar Pradesh has also led to transmission to other parts of Pradesh has also led to transmission to other parts of India and other countries. India and other countries.


Nigeria Confirmed AFP/Polio Cases

0

200

400

600

800

1000

1200

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

(10/2

4)


Should the Goal of Eradication be Changed to Elimination or Control?

Ongoing cost to poor countries in terms of dollars and Ongoing cost to poor countries in terms of dollars and staff time is high?staff time is high?

Unclear prospect that wild poliovirus transmission can Unclear prospect that wild poliovirus transmission can be interrupted given Muslim suspicions in certain be interrupted given Muslim suspicions in certain countries. countries.

OPV paradox – OPV is oral and cheap but OPV has a OPV paradox – OPV is oral and cheap but OPV has a clear risk of causing vaccine derived outbreaks. clear risk of causing vaccine derived outbreaks.

Should we switch to control as the goal? If so, how to Should we switch to control as the goal? If so, how to make this difficult decision?make this difficult decision?

global health challenges social analysis 76: lecture 12

Documents

reduction of disease

specified disease

elimination of disease

disease outbreaks

decreased disease transmission

detection of cases

incidence of new cases

confirmed cases