A Missing Dimension in Measures of Vaccination Impacts

Gomes, M. Gabriela M.; Lipsitch, Marc; Wargo, Andrew R.; Kurath, Gael; Rebelo, Carlota; Medley, Graham F.; Coutinho, António

doi:10.1371/journal.ppat.1003849

Cited by 60 publications

(85 citation statements)

References 16 publications

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“…In this paper we have considered individual heterogeneity in disease risk [9,10], in contrast to other studies that have considered variation in the effect of the vaccine itself [3,4,13]. Although both distributions are likely to affect current measures of vaccine efficacy [16], we wanted to counter a perceived tendency in the research community to explain the observations entirely in light of the latter.…”

Section: Discussionmentioning

confidence: 99%

“…The equations for the rates of change in control individuals (1,2), and their vaccine group analogues (3,4), can be solved analytically. Given that all individuals are non-infected at the beginning of the trial (S c (0) = S v (0) = 1 and I c (0) = I v (0) = 0 ), we have…”

Section: Minimal Model For a Vaccine Trialmentioning

confidence: 99%

“…In line with the rationale that measured discrepancies in vaccine protection arise from differences in frequency of exposure across settings, the identification of a consistent measure might require disentangling efficacy from exposure [3,10]. We have presented a mathematical framework for obtaining such measure.…”

Section: Redefining Vaccine Efficacymentioning

confidence: 99%

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Heterogeneity in disease risk induces falling vaccine protection with rising disease incidence

2016

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This paper is concerned with the analysis of phase 3 vaccine trials. In a randomised controlled trial, a representative sample of a population is given a vaccine and a matched sample is given a placebo. These individuals are followed for a stipulated length of time, while infection (or disease) occurrences are registered. Vaccine efficacy is then calculated to measure the reduction in disease rate (or risk) attributed to the vaccine. Seemingly very reasonable, this procedure often results in the most disparate estimates when conducted in different parts of the world. Here we argue that this is due to cohort selection acting on the trial participants as follows. The more susceptible individuals are infected first, leaving behind a pool whose mean susceptibility decreases over time. As a result infection rates decrease, and this effect is stronger in the control group provided that the vaccine reduces susceptibility. Therefore, any direct measure of vaccine efficacy is expected to decrease as the trial progresses, and this happens faster in settings where the intensity of pathogen exposure is higher. We propose an analytical scheme that takes this phenomenon into account while estimating efficacy more consistently across settings. We provide analytical results concerning the dependence of vaccine efficacy on the intensity of pathogen exposure as well as on the mean and variance of the distribution of disease risk.

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Section: Discussionmentioning

confidence: 99%

Section: Minimal Model For a Vaccine Trialmentioning

confidence: 99%

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Heterogeneity in disease risk induces falling vaccine protection with rising disease incidence

2016

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“…This could also be achieved with a DENV-blocking strain with high protection (measuring absolute protection is tricky, but see Gomes et al 2014;Pessoa et al 2014). If no evolution was expected, continuous DENV transmission could be eliminated in areas where A. aegypti is the only or main vector, which is the case in urban areas; because the wMel-Aedes association is not a natural, and therefore unlikely to be an evolutionary stable one, there is a reason to expect immediate response of the host, if it is evolutionarily perceived as an aggression and if there is variation in the population that can be selected to counter these effects.…”

Section: Host-microorganism Genome Interactions and Long-term Relatiomentioning

confidence: 99%

“…More worrying, a model-based framework to estimate pre-and post-intervention parameters is essentially absent; evaluation of interventions is done through randomized trials, and general conclusions cannot be extracted from them beyond whether the intervention has any success in that particular place and time (but see Gomes et al 2014). Research on this interface could go many ways, with each specific research area informing the others: evolution, ecology, medicine, epidemiology, and modeling of complex systems.…”

Section: Dengue Virus: the Case For Evolutionary Medicine And Evolvinmentioning

confidence: 99%

Host–Symbiont–Pathogen–Host Interactions: Wolbachia, Vector-Transmitted Human Pathogens, and the Importance of Quantitative Models of Multipartite Coevolution

Souto-Maior

2015

Interdisciplinary Evolution Research

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Infectious disease has been recognized for a long time as an important evolutionary force: It created the need for and shaped the evolution of immune systems and influenced reproduction as well as behavior of many host species. Infectious agents themselves also evolve and must have adapted to host strategies to evade infection, to multiple external and internal environments, and to transmission between hosts. Given the pressure to evolve on both sides, coevolution is expected. Evolution is indeed observed when looking at either host, pathogen, or at other microorganisms directly or indirectly involved and is dependent to some degree on all species interacting. Vector-transmitted diseases with high burden to humans such as malaria and dengue fever are some of many examples where parasites evade the immune system of both mosquito and human hosts, thereby maximizing the vector's transmission and persistence. Arthropod hosts such as mosquitos may also be carriers of vertically transmitted endosymbionts, such as the Wolbachia bacterium, that also induce a complex modification of the arthropod's life history traits. This sort of scenario illustrates the need to consider ecological, multipartite, and evolutionary models-the relevance to human health, together with extensive data collection from epidemiological surveillance, provides an opportunity to expand and improve evolutionary theory. Strict definitions apart, the relationship between hosts and parasites is probably almost as old as life itself. The relevance of disease for human health made it of interest already in ancient societies, much earlier than any scientific methods could be applied or were available to investigate their properties or etiology, which was attributed to spirits or other ethereal entities such as "bad air" ("mal aire," Italian words that originated the name "malaria"). With becoming sick being such a widespread and easily recognizable phenomenon, finding out why and how it happened quickly became an obvious research program, which really gained traction with the postulation of the germ theory of infectious diseases by Pasteur (1878, revisited by Absolon et al. 1970) and Koch's postulates (Koch 1880). These and other observations that disease could be transmitted from person to person, from animals, or from foul stuff such as rotting things essentially established that all microorganisms causing disease are horizontally acquired from pathogens' reservoirs-a view which may be valid to a large extent, but is by no means complete. Horizontal transmission implies the pathogen or microorganism can be transmitted from any host carrying it to any non-carrier, while vertical transmission is more restrictive, with transmission from parent to offspring establishing a closely related tracing of host and microorganism lineages. Notwithstanding the fact that many microorganisms were known to be transmitted by different routes and could potentially compete for hosts, the modern population biology study of host-microorganism interactions, especiall...

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Impact of Vaccination and Pathogen Exposure Dosage on Shedding Kinetics of Infectious Hematopoietic Necrosis Virus (IHNV) in Rainbow Trout

2020

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Vaccine efficacy in preventing clinical disease has been well characterized. However, vaccine impacts on transmission under diverse field conditions, such as variable pathogen exposure dosages, are not fully understood. We evaluated the impacts of vaccination on disease‐induced host mortality and shedding of infectious hematopoietic necrosis virus (IHNV) in Rainbow Trout Oncorhynchus mykiss. Fish, in up to three different genetic lines, were exposed to different dosages of IHNV to simulate field variability. Mortality and viral shedding of each individual fish were quantified over the course of infection. As the exposure dosage increased, mortality, number of fish shedding virus, daily virus quantity shed, and total amount of virus shed also increased. Vaccination significantly reduced mortality but had a much smaller impact on shedding, such that vaccinated fish still shed significant amounts of virus, particularly at higher viral exposure dosages. These studies demonstrate that the consideration of pathogen exposure dosage and transmission are critical for robust inference of vaccine efficacy.

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A Missing Dimension in Measures of Vaccination Impacts

Abstract: FCT, PEst, OE/MAT/UI0209/2011, Award Number U54GM088558 from the National Institute of General Medical Science

Cited by 60 publications

References 16 publications

Heterogeneity in disease risk induces falling vaccine protection with rising disease incidence

Heterogeneity in disease risk induces falling vaccine protection with rising disease incidence

Host–Symbiont–Pathogen–Host Interactions: Wolbachia, Vector-Transmitted Human Pathogens, and the Importance of Quantitative Models of Multipartite Coevolution

Impact of Vaccination and Pathogen Exposure Dosage on Shedding Kinetics of Infectious Hematopoietic Necrosis Virus (IHNV) in Rainbow Trout

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