Malaria vaccines: lessons from field trials

Struchiner, Cláudio J.; Halloran, M. Elizabeth; Brunet, Robert C.; Ribeiro, José M. C.; Massad, Eduardo

doi:10.1590/s0102-311x1994000800009

Cited by 14 publications

(10 citation statements)

References 35 publications

(35 reference statements)

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“…Other models of vaccine action would have to be used for more complex distributions of vaccine protection such as threshold effects. We have confined our discussion to estimating the vaccine effect on susceptibility, not on infectiousness, indirect effects, or how the vaccine might change the incubation period (38).…”

Section: Discussionmentioning

confidence: 99%

Estimability and Interpretation of Vaccine Efficacy Using Frailty Mixing Models

Struchiner

1996

American Journal of Epidemiology

101

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The authors consider estimability and interpretation of vaccine efficacy based on time to event data, allowing that some of the population might have a very low probability of acquiring disease, and the rest have partial, possibly continuously distributed, susceptibility. The efficacy parameters of interest in the frailty mixing model include the fraction highly unlikely to acquire the infection or disease due to the vaccine, the degree of partial protection in those still susceptible, and the average protection or summary measure of efficacy under heterogeneity. The efficacy estimates can still be usefully interpreted when the heterogeneity results from heterogeneity in contact patterns, contact rates, or infectiousness of the contacts, as long as these are equal in the vaccinated and unvaccinated groups. A likelihood-based method allows estimation of the efficacy parameters of interest from grouped time to event data. Simulated vaccine studies assuming different levels and distributions of efficacy demonstrate that ignoring heterogeneity in susceptibility or exposure to infection generally results in underestimation of vaccine efficacy as well as incorrect interpretation of the estimates. The approach is also applicable to other covariates affecting susceptibility or exposure to infection in infectious diseases. Exploitation of the dependent happening structure of infectious diseases to obtain a shape for the baseline hazard may help identifiability. The authors recommend fitting several models to time to event data in vaccine studies.

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Section: Discussionmentioning

confidence: 99%

Estimability and Interpretation of Vaccine Efficacy Using Frailty Mixing Models

Struchiner

1996

American Journal of Epidemiology

101

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“…Thus, most efficacy estimates are based on unconditional parameters such as incidence density, hazard rates, or incidence proportion [12]. Measures of vaccine efficacy expressed as functions of the incidence proportion [13] or hazard rates [14] depend on the level of transmission.…”

Section: Introductionmentioning

confidence: 99%

Randomization and baseline transmission in vaccine field trials

Struchiner

Halloran

2006

Epidemiol. Infect.

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In randomized trials, the treatment assignment mechanism is independent of the outcome of interest and other covariates thought to be relevant in determining this outcome. It also allows, on average, for a balanced distribution of these covariates in the vaccine and placebo groups. Randomization, however, does not guarantee that the estimated effect is an unbiased estimate of the biological effect of interest. We show how exposure to infection can be a confounder even in randomized vaccine field trials. Based on a simple model of the biological efficacy of interest, we extend the arguments on comparability and collapsibility to examine the limits of randomization to control for unmeasured covariates. Estimates from randomized, placebo-controlled Phase III vaccine field trials that differ in baseline transmission are not comparable unless explicit control for baseline transmission is taken into account.

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“…Had Guadalupe been sprayed one year later not only might the prevalence of infection have been higher, but the associations between covariates and infection might have been quantitatively different. In an analogous analysis, Struchiner et al demonstrate how estimates of the effect of a vaccine against malaria would change over the course of a malaria epidemic [29] . The authors show that the expected effect of a vaccine decreases over the course of an epidemic, and the same may be true for local risk factors for T. cruzi infection.…”

Section: Discussionmentioning

confidence: 99%

Targeted Screening Strategies to Detect Trypanosoma cruzi Infection in Children

Levy

Kawai²,

Bowman³

et al. 2007

PLoS Negl Trop Dis

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BackgroundMillions of people are infected with Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Anti-trypanosomal drug therapy can cure infected individuals, but treatment efficacy is highest early in infection. Vector control campaigns disrupt transmission of T. cruzi, but without timely diagnosis, children infected prior to vector control often miss the window of opportunity for effective chemotherapy.Methods and FindingsWe performed a serological survey in children 2–18 years old living in a peri-urban community of Arequipa, Peru, and linked the results to entomologic, spatial and census data gathered during a vector control campaign. 23 of 433 (5.3% [95% CI 3.4–7.9]) children were confirmed seropositive for T. cruzi infection by two methods. Spatial analysis revealed that households with infected children were very tightly clustered within looser clusters of households with parasite-infected vectors. Bayesian hierarchical mixed models, which controlled for clustering of infection, showed that a child's risk of being seropositive increased by 20% per year of age and 4% per vector captured within the child's house. Receiver operator characteristic (ROC) plots of best-fit models suggest that more than 83% of infected children could be identified while testing only 22% of eligible children.ConclusionsWe found evidence of spatially-focal vector-borne T. cruzi transmission in peri-urban Arequipa. Ongoing vector control campaigns, in addition to preventing further parasite transmission, facilitate the collection of data essential to identifying children at high risk of T. cruzi infection. Targeted screening strategies could make integration of diagnosis and treatment of children into Chagas disease control programs feasible in lower-resource settings.

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Malaria vaccines: lessons from field trials

Cited by 14 publications

References 35 publications

Estimability and Interpretation of Vaccine Efficacy Using Frailty Mixing Models

Estimability and Interpretation of Vaccine Efficacy Using Frailty Mixing Models

Randomization and baseline transmission in vaccine field trials

Targeted Screening Strategies to Detect Trypanosoma cruzi Infection in Children

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