Modeling vaccination
strategies for
developing countries
DIMACS meeting May 17-20, 2004
Annelies Van Rie
Childhood mortality


More than 10 million deaths that occur globally in
children age < 5
2002: millenium goals: reduce childhood mortality by
two thirds by 2015.





1990: 180/1000 in sub-Saharan Africa
1990: 9/1000 in industrialized countries
2000: 175/1000 in sub-Saharan Africa
2000: 6/1000 in industrialized countries
Neonatal disorders and infectious diseases are the
important causes
Global causes of child deaths

Black et al (Lancet, 2003)
prediction for 42 countries
contributing 90% of CH deaths







Neonatal disorders: 33% (29-36)
Diarrhea: 22% (14-30)
Pneumonia: 21% (14-24)
Malaria: 9% (6-13)
AIDS: 3%
Measles: 1% (1-9%)

2000 WHO estimates
prediction for all WHO member
states






Neonatal disorders: 42%
Diarrhea: 13%
Pneumonia: 19%
Malaria: 9%
AIDS: 3%
Measles: 5%
a substantial proportion (24%) are caused by vaccine
preventable infections (Lara Wolfson)
Vaccines for children



Vaccines are one of the grand successes of
the 21st century.
The impact has been substantially larger in
the developed word
Vaccines have been developed to
preferentially address the epidemiology of
infectious diseases in high income countries


Malaria (9%)
Meningococcal (type C scale 2 logs less
compared to type A)
Childhood vaccination:
2 worlds or many more?

Double standard or 1 standard





Rotavirus
Thiomersal
polio
Disease burden in developing countries vs disease
burden in developed countries
How do can we help countries in determining
priorities?


Capacity building (human, laboratory)
Country typology
Black et al. Lancet 2003;361:2226
Barriers to use of existing
childhood vaccines






Lack of disease burden data
Need of cold chain
Poor transportation and storage systems
Inadequate and poorly motivated HCW
Budget constraints
Lack of political will
Obaro et al. Vaccine 2003
Barriers to use of “new”
vaccines



Lack of disease burden data
Budget constraints
Lack of political will
Improving vaccine use in
developing countries (1)

Advocate its use





Generation of local burden of disease data
(disease surveillance systems, regional sentinel
sites)
Demonstration of immunogenicity, efficacy and
safety in the local population
Cost effectiveness data (1 vaccine or
comparisons?)
Inform policy makers, opinion leaders and HCW
Inform the community through mass media
Improving vaccine use in
developing countries (2)

Pay for its use (GAVI)


Immunization Systems Strengthening (ISS)
support –performance/reward based system
New Vaccine Support (NVS) – vaccine provided
for 1st five years
Improving vaccine use in
developing countries (3)



Decrease costs of vaccines (local production)
Develop easy to use vaccines (no cold chain)
Decrease the number of dosages



Pertussis: elimination of 1 childhood dose
Hib : 3 dose instead of 4 in UK
Pneumococcal vaccine: 1 dose instead of 4?
 Italy: 26% coverage 1-year olds plus 31-53% catch up gives
91% reduction in invasive Hib disease (Gallo et al. Vaccine 2002)
 US: largest decrease in invasive disease in 65+ (Whitney at el.
NEJM 2003)

Fractional dose

Hepatitis B: 10-fold dilution with equivalent Ab avidity in
South African study (Lagos et al, Lancet 1998)
Obaro et al. Vaccine 2003
Improving vaccine use in
developing countries (4)

Targeted vaccination


Who to vaccinate?
 Importance of unvaccinated pockets?
 Importance of differences between rural and urban?
 WAIFW differences?
Acquaintance immunization (Cohen et al. Physical Review letters
2003)
Vaccination of randomly selected acquintances of randomly
selected persons
Large Household vaccination (Ball et al. Ann Appl Prob. 1997)
 Vaccinees chosen sequentially from those households with
the largest number of susceptibles


Improving vaccine use in
developing countries (5)

Targeted vaccination

PLACE based vaccination: not WHO but WHERE



Limitation of contact tracing in infectious disease
control
Identification of geographic clustering and high
transmission areas (HTA) for HIV
Role of locations in transmission of infectious disease:
TB transmission in bar, restaurant, dancing hall,
church, crack house, rock concert, prison, shelters in
developing countries, piqueras in Mexico and
shebeens in SA
PLACE






Priorities for Local AIDS Control Efforts
AIDS prevention programs should focus on places where
people with high rates of new sexual partnership formation
meet new sexual partners
Available demographic and epidemiologic contextual data help
to identify places where individuals with highest rates of new
partnership formation meet new partners;
To minimize bias, the method does not primarily rely on selfreported behavior, contact tracing, naming of sexual partners,
or require information about self-reported behavior except to
validate information obtained in other ways;
The method is feasibly implemented in a short period of time
without outside technical experts
The method provides program indicators useful for intervention
monitoring.
Weir et al. Sex Transm Inf 2002
PLACE for HIV and TB (method)




Township in Cape Town, South Africa and in
Kinshasa, Democratic Republic of Congo.
Selection of PLACE venues likely to have a high
HIV incidence of infection based on epidemiological,
socio-demographic and behavioral information via
key informants
site visits, site interviews
Information was on TB symptoms (Cape Town) and
presence of active TB (Kinshasa).
PLACE for HIV and TB (results)


3482 persons interviewed for risk behavior and TB symptoms.
Chronic cough was present in
 Cape Town (221 PLACE venues) :



Kinshasa (63 PLACE venues)




11.5% of 69 male and 8% of 234 female clients
Kinshasa (2 ANC clinics)


15% of 948 men
11% of 245 women
Kinshasa ( 7 STI clinics)


15% of 621 men
12% of 356 women
2.4 % of 1035 pregnant women.
15 (9%) of 163 Kinshasa participants reporting chronic cough,
had active TB confirmed by bacteriological methods
HIV infection: STI > PLACE venues >> ANC
PLACE for HIV and TB (use)

Prevention efforts



Diagnosis



Education
Condom distribution
VCT
TB
Intervention ?



STI syndromatic treatment
TB treatment DOT
HIV treatment DOT
PLACE for VACCINATION


Focus on places where forces of infection are
highest
Use available demographic and
epidemiologic contextual data to identify
areas most likely to have high forces of
infection
Conclusion




To reduce childhood mortality we need action
now
Traditional advocacy methods have been slow
and small in effect
GAVI has sustainability issues
Value of innovative ideas: can modeling help?