Dataset Information

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines.

ABSTRACT:

Background

Mass drug administration (MDA) of praziquantel has been the intervention of choice against schistosomiasis but with limited success in interrupting the transmission. The development of anti-Schistosoma vaccines is underway. Our objective is to quantify the population-level impact of anti-Schistosoma vaccines when administered alone and in combination with mass drug administration (MDA) and determine factors in vaccine design and public health implementation that optimize vaccination role in schistosomiasis control and elimination.

Methods and findings

We developed a deterministic compartmental model simulation of schistosomiasis transmission in a high-risk Kenyan community, including stratification by age, parasite burden, and vaccination status. The modeled schistosomiasis vaccines differed in terms of vaccine duration of protection (durability) and three biological efficacies. These are vaccine susceptibility effect (SE) of reducing person's susceptibility to Schistosoma acquisition, vaccine mortality effect (ME) of reducing established worm burden and vaccine fecundity effect (FE) of reducing egg release by mature worms. We quantified the population-level impact of vaccination over two decades under diverse vaccination schemes (childhood vs. mass campaigns), with different age-targeting scenarios, different risk settings, and with combined intervention with MDA. We also assessed the sensitivity of our predictions to uncertainties in model parameters. Over two decades, our base case vaccine with 80% SE, FE, and ME efficacies, 10 years' durability, provided by mass vaccination every 10 years, reduced host prevalence, mean intensity, incidence, and patent snail prevalence to 31%, 20 eggs/10-ml sample/person, 0.87 worm/person-year, and 0.74%, from endemic-state values of 71%, 152, 3.3, and 0.98%, respectively. Lower impact was found when coverage did not encompass all potential contaminators, and childhood-only vaccination schemes showed delayed and lower impact. In lower prevalence settings, the base case vaccine generated a proportionately smaller impact. A substantially larger vaccine program effect was generated when MDA + mass vaccination was provided every 5 years, which could be achieved by an MDA-only program only if drug was offered annually. Vaccine impact on schistosomiasis transmission was sensitive to a number of parameters including vaccine efficacies, human contact rates with water, human density, patent snails' rate of patency and lifespan, and force of infection to snails.

Conclusions

To be successful a vaccine-based control strategy will need a moderately to highly effective formulation combined with early vaccination of potential contaminators and aggressive coverage in repeated rounds of mass vaccination. Compared to MDA-only program, vaccination combined with MDA accelerates and prolongs the impact by reducing the acquisition of new worms and reducing egg release from residual worms.

SUBMITTER: Alsallaq RA

PROVIDER: S-EPMC5406007 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines.

Alsallaq Ramzi A RA Gurarie David D Ndeffo Mbah Martial M Galvani Alison A King Charles C

PLoS neglected tropical diseases 20170414 4

<h4>Background</h4>Mass drug administration (MDA) of praziquantel has been the intervention of choice against schistosomiasis but with limited success in interrupting the transmission. The development of anti-Schistosoma vaccines is underway. Our objective is to quantify the population-level impact of anti-Schistosoma vaccines when administered alone and in combination with mass drug administration (MDA) and determine factors in vaccine design and public health implementation that optimize vacci ...[more]

PMID: 28410369

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Project description:Schistosomiasis remains a major cause of morbidity in the world. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission in endemic areas. Despite recent large-scale efforts, such as integrated control programs aimed at limiting schistosomiasis by improving education and sanitation, molluscicide treatment programs and chemotherapy with praziquantel, there has only been limited success. There is an urgent need for complementary approaches, such as vaccines. We demonstrated previously that anti-oxidant enzymes, such as Cu-Zn superoxide dismutase (SOD) and glutathione S peroxidase (GPX), when administered as DNA-based vaccines induced significant levels of protection in inbred mice, greater than the target 40% reduction in worm burden compared to controls set as a minimum by the WHO. These results led us to investigate if immunization of non-human primates with antioxidants would stimulate an immune response that could confer protection as a prelude study for human trials. Issues of vaccine toxicity and safety that were difficult to address in mice were also investigated. All baboons in the study were examined clinically throughout the study and no adverse reactions occurred to the immunization. When our outbred baboons were vaccinated with two different formulations of SOD (SmCT-SOD and SmEC-SOD) or one of GPX (SmGPX), they showed a reduction in worm number to varying degrees, when compared with the control group. More pronounced, vaccinated animals showed decreased bloody diarrhea, days of diarrhea, and egg excretion (transmission), as well as reduction of eggs in the liver tissue and in the large intestine (pathology) compared to controls. Specific IgG antibodies were present in sera after immunizations and 10 weeks after challenge infection compared to controls. Peripheral blood mononuclear cells, mesenteric, and inguinal node cells from vaccinated animals proliferated and produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. All together, these data demonstrate the potential of antioxidants as a vaccine in a non-human primate model.

Project description:The economic impact of schistosomiasis and the underlying tradeoffs between water resources development and public health concerns have yet to be quantified. Schistosomiasis exerts large health, social and financial burdens on infected individuals and households. While irrigation schemes are one of the most important policy responses designed to reduce poverty, particularly in sub-Saharan Africa, they facilitate the propagation of schistosomiasis and other diseases. We estimate the economic impact of schistosomiasis in Burkina Faso via its effect on agricultural production. We create an original dataset that combines detailed household and agricultural surveys with high-resolution geo-statistical disease maps. We develop new methods that use the densities of the intermediate host snails of schistosomiasis as instrumental variables together with panel, spatial and machine learning techniques. We estimate that the elimination of schistosomiasis in Burkina Faso would increase average crop yields by around 7%, rising to 32% for high infection clusters. Keeping schistosomiasis unchecked, in turn, would correspond to a loss of gross domestic product of approximately 0.8%. We identify the disease burden as a shock to the agricultural productivity of farmers. The poorest households engaged in subsistence agriculture bear a far heavier disease burden than their wealthier counterparts, experiencing an average yield loss due to schistosomiasis of between 32 and 45%. We show that the returns to water resources development are substantially reduced once its health effects are taken into account: villages in proximity of large-scale dams suffer an average yield loss of around 20%, and this burden decreases as distance between dams and villages increases. This study provides a rigorous estimation of how schistosomiasis affects agricultural production and how it is both a driver and a consequence of poverty. It further quantifies the tradeoff between the economics of water infrastructures and their impact on public health. Although we focus on Burkina Faso, our approach can be applied to any country in which schistosomiasis is endemic.

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Dataset Information

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines.

Background

Methods and findings

Conclusions

Publications

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines.

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