Protective immunity to
            <i>Schistosoma haematobium</i>
            infection is primarily an anti-fecundity response stimulated by the death of adult worms

Mitchell, Kate; Mutapi, Francisca; Savill, Nicholas J.; Woolhouse, Mark E. J.

doi:10.1073/pnas.1121051109

Cited by 39 publications

(48 citation statements)

References 41 publications

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“…Protective antibody is stimulated by antigens from dying worms and reduces worm fecundity, as suggested by previous comparison of model output with field data [28], and as demonstrated for the leading schistosome vaccine candidate, a 28 kDa glutathione S -transferase [35]. Most of the models used here include an ‘antigen threshold’, a level of cumulative antigen exposure which must be exceeded before a protective antibody response is mounted, as suggested by previous model fitting, but we include models without an antigen threshold which have also been found to fit the data [28].…”

Section: Methodsmentioning

confidence: 69%

“…This model has been fully described previously [28]. Briefly, the model tracks the number of worms an individual harbours between their birth and 34 years of age.…”

Section: Methodsmentioning

confidence: 99%

“…This study suggested that if protective antibody were mainly stimulated by antigens from other life stages (including cercariae, live worms, or eggs) then a boost in antibody would not be seen following treatment [28]. No models have previously looked at long-term effects of MDA upon the dynamics of protective immunity and measured egg output when such immunity is stimulated by dying (rather than live) worms.…”

Section: Introductionmentioning

confidence: 99%

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Predicted Impact of Mass Drug Administration on the Development of Protective Immunity against Schistosoma haematobium

et al. 2014

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Previous studies suggest that protective immunity against Schistosoma haematobium is primarily stimulated by antigens from dying worms. Praziquantel treatment kills adult worms, boosting antigen exposure and protective antibody levels. Current schistosomiasis control efforts use repeated mass drug administration (MDA) of praziquantel to reduce morbidity, and may also reduce transmission. The long-term impact of MDA upon protective immunity, and subsequent effects on infection dynamics, are not known. A stochastic individual-based model describing levels of S. haematobium worm burden, egg output and protective parasite-specific antibody, which has previously been fitted to cross-sectional and short-term post-treatment egg count and antibody patterns, was used to predict dynamics of measured egg output and antibody during and after a 5-year MDA campaign. Different treatment schedules based on current World Health Organisation recommendations as well as different assumptions about reductions in transmission were investigated. We found that antibody levels were initially boosted by MDA, but declined below pre-intervention levels during or after MDA if protective immunity was short-lived. Following cessation of MDA, our models predicted that measured egg counts could sometimes overshoot pre-intervention levels, even if MDA had had no effect on transmission. With no reduction in transmission, this overshoot occurred if protective immunity was short-lived. This implies that disease burden may temporarily increase following discontinuation of treatment, even in the absence of any reduction in the overall transmission rate. If MDA was additionally assumed to reduce transmission, a larger overshoot was seen across a wide range of parameter combinations, including those with longer-lived protective immunity. MDA may reduce population levels of immunity to urogenital schistosomiasis in the long-term (3–10 years), particularly if transmission is reduced. If MDA is stopped while S. haematobium is still being transmitted, large rebounds (up to a doubling) in egg counts could occur.

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Section: Methodsmentioning

confidence: 69%

“…This model has been fully described previously [28]. Briefly, the model tracks the number of worms an individual harbours between their birth and 34 years of age.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predicted Impact of Mass Drug Administration on the Development of Protective Immunity against Schistosoma haematobium

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“…104 Resistance to reinfection is partial, which means that sterile immunity either does not develop or is rare. Studies of resistance to reinfection in human beings suggest that worm death, whether natural or after treatment, leads to release of immunogens that stimulate these protective responses, which then react with antigens expressed by susceptible incoming, migrating schistosomulae.…”

Section: Introductionmentioning

confidence: 99%

Human schistosomiasis

et al. 2014

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Human schistosomiasis—or bilharzia—is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination.

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“…A pattern-oriented mathematical model derived from field-based trends in urinary egg counts and schistosome-specific antibody patterns predicts that, for S. haematobium , the main protective immunity is antifecundity immunity and that, similar to anti-infection immunity, this immunity is dependent on antigen exposure upon death of adult worms [15]. …”

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confidence: 99%

Human Schistosoma haematobium Antifecundity Immunity Is Dependent on Transmission Intensity and Associated With Immunoglobulin G1 to Worm-Derived Antigens

Wilson¹,

Jones²,

Dam³

et al. 2014

The Journal of Infectious Diseases

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BackgroundImmunity that reduces worm fecundity and, in turn, reduces morbidity is proposed for Schistosoma haematobium, a parasite of major public health importance. Mathematical models of epidemiological trends suggest that antifecundity immunity is dependent on antibody responses to adult-worm-derived antigen.MethodsFor a Malian cohort (age, 5–29 years) residing in high-transmission fishing villages or a moderate-transmission village, worm fecundity was assessed using the ratio of urinary egg excretion to levels of circulating anodic antigen, a Schistosoma-specific antigen that is steadily secreted by adult worms. Fecundity was modeled against host age, infection transmission intensity, and antibody responses specific to soluble worm antigen (SWA), tegument allergen-like 1, and 28-kDa glutathione-S-transferase.ResultsWorm fecundity declined steadily until a host age of 11 years. Among children, host age and transmission were negatively associated with worm fecundity. A significant interaction term between host age and transmission indicates that antifecundity immunity develops earlier in high-transmission areas. SWA immunoglobulin G1 (IgG1) levels explained the effect of transmission on antifecundity immunity.ConclusionAntifecundity immunity, which is likely to be protective against severe morbidity, develops rapidly during childhood. Antifecundity immunity is associated with SWA-IgG1, with higher infection transmission increasing this response at an earlier age, leading to earlier development of antifecundity immunity.

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Protective immunity to Schistosoma haematobium infection is primarily an anti-fecundity response stimulated by the death of adult worms

Cited by 39 publications

References 41 publications

Predicted Impact of Mass Drug Administration on the Development of Protective Immunity against Schistosoma haematobium

Predicted Impact of Mass Drug Administration on the Development of Protective Immunity against Schistosoma haematobium

Human schistosomiasis

Human Schistosoma haematobium Antifecundity Immunity Is Dependent on Transmission Intensity and Associated With Immunoglobulin G1 to Worm-Derived Antigens

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