This project utilizes ecological and spatial analytical methods to evaluate vaccine efficacy. Conventional vaccine trials often assume that vaccine efficacy is geographically homogeneous. However, spatial variation of ecological factors and disease burden may influence a vaccines protective effect. Ignoring location and ecological differences among vaccine trial participants can affect the vaccine efficacy estimate and ignore possible herd. This project addresses these factors in two vaccine trial settings: 1) cholera vaccine trial in Bangladesh, and 2) malaria vaccine trial in Malawi.
Cholera vaccine trial – Matlab, Bangladesh
In 1985, a community-based, individually randomized oral cholera vaccine trial was conducted in Matlab, Bangladesh. This study uses a geographic information system (GIS) to determine:
- How cholera vaccine efficacy varies spatially in the study area;
- What ecological socio-environmental variables are related to cholera vaccine efficacy (i.e., which variables are effect modifiers);
- How protective efficacy varies with access to treatment facilities (i.e., whether access is a spatial confounder); and
- Whether cholera incidence in the placebo group is related to vaccine coverage rates (i.e., is herd immunity important).
Findings suggest that vaccine efficacy varies spatially in relation to vaccine coverage. Residents living in neighborhoods with higher levels of cholera vaccine coverage experienced lower infection rates regardless of vaccine status.
This research is presently being extended to integrate social networks into a spatial analytical framework for vaccine trial evaluation. The extended study uses social network analysis, participant location data, and remote sensing technologies to determine:
- How cholera vaccine efficacy varies spatially within different spatial and environment contexts;
- How protective efficacy varies within social networks; and
- How spatial and social network information can jointly be used to assess the effectiveness of vaccines.
RTS,S malaria vaccine trial – Lilongwe, Malawi
The University of North Carolina at Chapel Hill (UNC), in collaboration with GlaxoSmithKline (GSK), employed spatial methods to select study participants for a malaria vaccine trial to measure the efficacy of a malaria vaccine (RTS,S/AS01E) against malaria caused by P. falciparum infection. The study is a multi-center Phase III randomized double-blind trial that is currently being implemented among both infants and children across diverse malaria-endemic settings throughout sub-Saharan Africa. The primary goal of the trial is to measure vaccine efficacy against clinical malaria when primary immunization starts at 6-12 weeks or 5-17 months of age.
A secondary goal is to investigate within-site differences in efficacy utilizing “ecological vaccine trial” methods. Study areas may exhibit differences in vector habitat and household ecology that could influence malaria transmission and, therefore, vaccine efficacy. Additional factors such as how frequently an individual is bitten by malaria carrying mosquitoes and whether the design of the house prevents or permits mosquito entry may also influence vaccine efficacy. In Lilongwe, we are attempting to capture these differences by incorporating spatial and ecological data into the study.
Project Team Members
Root, ED; Giebultowicz, S; Ali, M; Yunus, M; Emch, M. (2011) The role of vaccine coverage among social networks in cholera vaccine efficacy. PLoS One. 6(7): e22971. link to article
Ali, M; Emch, M; Yunus, M; Clemens, J. (2009) Modeling spatial heterogeneity of disease risk and evaluation of the impact of vaccination. Vaccine. 27(28): 3724-3729. link to article
Emch, M; Ali, M; Root, ED; Yunus, M. (2009) Spatial and environmental connectivity analysis in a cholera vaccine trial. Social Science and Medicine, 68(4): 631-637. link to article
Ali, M; Emch, M; Yunus, M; Sack, D; Lopez, AL; Holmgren, J; Clemens, J. (2008) Vaccine protection of Bangladeshi infants and young children against cholera: implications for vaccine deployment and person-to-person transmission. The Pediatric Infectious Disease Journal. 27(1): 33-37. link to article
Emch, M; Ali, M; Yunus, M. (2008) Risk areas and neighborhood-level risk factors for Shigella dysenteriae 1 and Shigella flexneri: implications for vaccine development. Health & Place. 14: 96-105. link to article
Ali, M; Goovaerts, P; Nazia, N; Haq, MZ; Yunus, M; Emch, M. (2006) Application of Poisson kriging to the mapping of cholera and dysentery incidence in an endemic area of Bangladesh. International Journal of Health Geographics. 5(45):1-11. link to article
Emch, M; Ali, M; Acosta, C; Yunus, M; Sack, D; Clemens, JD. (2006) Efficacy calculation in randomized trials: global or local measures? Health & Place. 13: 238-248. link to article
Emch, M; Ali, M; Park, JK; Yunus, M; Sack, D; Clemens, JD. (2006) Relationship between neighbourhood-level killed oral cholera vaccine coverage and protective efficacy: evidence for herd immunity. International Journal of Epidemiology. 35: 1044-1050. link to article
Ali, M; Emch, M; von Seidlein, L; Yunus, M; Sack, DA; Holmgren, J; Rao, M; Clemens, JD. (2005) Herd immunity conferred by killed oral cholera vaccines in Bangladesh: A reanalysis. Lancet. Jul 2-8;366(9479):44-9. link to article
Hoffman, I. (P.I.); Emch, M. (CoI); Martinson, F. (CoI); Demster, D. (CoI); Krysiak, R. (CoI); Mofolo, I. (CoI); Sungitsa, M. (CoI) MAL55 Phase III clinical trial for malaria vaccine., PATH Malaria Vaccine Initiative, $6,033,760, 2009-13.
Hoffman, I. (P.I.); Emch, M. (CoI); Martinson, F. (CoI); Miller, W. (CoI); Demster, D. (CoI); Krysiak, R. (CoI); Mofolo, I. (CoI); Sungitsa, M. (CoI) MAL55 Phase III clinical trial for malaria vaccine, PATH Malaria Vaccine Initiative, $287,898, 2008-11.
Emch, M.E. (P.I.); Bearman, P.; Ali, M.; Clemens, J. Integration of Spatial and Social Network Analysis in Vaccine Trials. National Institute of Allergies and Infectious Disease, National Institutes of Health, Award #R03-AI076748, $148,000, 2009-12.
Emch, M.E. (P.I.); Root, E.D.; Bearman, P.; Ali, M.; Clemens, J. Spatial and Social Network Analysis in Vaccine Trials. National Science Foundation, Award # BCS-0924479, $300,183, 2009-13.
Emch, M.E. (P.I.) “Geographical Analysis in Vaccine Efficacy Trials, National Institute of Allergies and Infectious Disease,” National Institutes of Health, 1R03AI53214-01, $116,212, 2003-2005.
Emch, M.E. (P.I.) “Geographical Analysis in Vaccine Efficacy Trials: Spatial Confounders, Effect Modifiers, and Herd Immunity Measurement,” Geography and Regional Science Program, National Science Foundation, Grant # BCS 0323131, $37,936, 2003-2005.
International Centre for Diarrhoeal Disease Research, Bangladesh
International Vaccine Institute