Human Schistosome Infection and Allergic Sensitisation

Several field studies have reported an inverse relationship between the prevalence of helminth infections and that of allergic sensitisation/atopy. Recent studies show that immune responses induced by helminth parasites are, to an extent, comparable to allergic sensitisation. However, helminth products induce regulatory responses capable of inhibiting not only antiparasite immune responses, but also allergic sensitisation. The relative effects of this immunomodulation on the development of protective schistosome-specific responses in humans has yet to be demonstrated at population level, and the clinical significance of immunomodulation of allergic disease is still controversial. Nonetheless, similarities in immune responses against helminths and allergens pose interesting mechanistic and evolutionary questions. This paper examines the epidemiology, biology and immunology of allergic sensitisation/atopy, and schistosome infection in human populations

Helminth parasite proteomics: from experimental models to human infections

Schistosomiasis is a major human helminth infection endemic in developing countries. Urogenital schistosomiasis, caused by S. haematobium, is the most prevalent human schistosome disease in sub-Saharan Africa. Currently control of schistosome infection is by treatment of infected people with the anthelmintic drug praziquantel, but there are calls for continued efforts to develop a vaccine against the parasites. In order for successful vaccine development, it is necessary to understand the biology and molecular characteristics of the parasite. Ultimately, there is need to understand the nature and dynamics of the relationship between the parasite and the natural host. Thus, my studies have focused on molecular characterization of different parasite stages and integrating this information with quantitative approaches to investigate the nature and development of protective immunity against schistosomes in humans. Proteomics has proved a powerful tool in these studies allowing the proteins expressed by the parasite to be characterized at a molecular and immunological level. In this review, the application of proteomic approaches to understanding the human-schistosome relationship as well as testing specific hypotheses on the nature and development of schistosome-specific immune responses is discussed. The contribution of these approaches to informing schistosome vaccine development is highlighted

Similar cellular responses after treatment with either praziquantel or oxamniquine in Schistosoma mansoni infection.

The effect of treatment with either oxamniquine or praziquantel on S.mansoni specific IFN-gamma, IL-4, IL-5 and IL-10 was compared on PBMC which were collected pretreatment, 6 and 18 weeks post treatment. Using sandwich ELISA on the supernatants harvested from the PBMC stimulation by crude S. mansoni SEA and SWAP antigens after 5 days the levels of PBMC proliferation and cytokine production were similar according to treatment with either praziquantel or oxamniquine. Before treatment, infected groups showed low ratios, of IL-4:IFN-gamma, IL-5:IFNgamma and IL-10:IFN-gamma, indicating that IFN-gamma was high in the infected individuals. The general increase in immuno-modulation was observed post-treatment with elevated immune reactivity and cytokine production in both treatment groups. Treatment induced significant increases in levels of IL-4 (p < 0.05), IL-5 (p < 0.0001) and IL-10 (p < 0.05) cytokines 6 and 18 weeks after treatment. There were no significant differences in the increase in IL-4, IL-5 and IL-10 between children treated with praziquantel or oxamniquine. Pre-treatment IFN-gamma and IL-5 levels were positively correlated with infection (p < 0.001), while post treatment IL-4 cytokine levels were negatively correlated with baseline infection status (p < 0.001). The results suggest that treatment-induced immune responses are similar for both common anti-schistosome drugs praziquantel or oxamniquine having similar and immunizing effect

Mainstreaming female genital schistosomiasis to ensure it is not neglected among the neglected tropical diseases

Female genital schistosomiasis (FGS) is a neglected manifestation of Schistosoma haematobium infection, affecting an estimated 56 million women in sub-Saharan Africa. It is characterized by lesions in the genital tract, leading to symptoms like pain, infertility and an increased risk of HIV transmission. Despite its prevalence, FGS remains underdiagnosed and underreported due to limited awareness and diagnostic capabilities. Current knowledge emphasizes the need for integrated approaches combining diagnosis, treatment with praziquantel and education. There are ongoing efforts to integrate FGS services into women’s sexual and reproductive services, yet to date many African countries lack programmatic guidance to achieve this. More comprehensive integration and mainstreaming of FGS prevention, control and treatment across various sectors is needed to ensure intersectoral collaboration and financing of programmes. This review examines the various intervention tools currently available to achieve FGS integration in health systems. These include water, sanitation and hygiene improvements, environmental management, health education and inclusion of preschool-aged children in national schistosomiasis control programmes. Highlighted are also the required diagnostic and therapeutic tools, preventive interventions, effective policy and sustainable funding, all integral to achieving comprehensive FGS mainstreaming

Soluble CD23 Levels are Inversely Associated with Atopy and Parasite-Specific IgE Levels but Not with Polyclonal IgE Levels in People Exposed to Helminth Infection

BACKGROUND: Protective acquired immunity against helminths and allergic sensitisation are both characterised by high IgE antibody levels. Levels of IgE antibodies are naturally tightly regulated by several mechanisms including binding of the CD23 receptor. Following observations that helminth infections and allergic sensitisation may co-present, the current study aims to investigate the relationship between the soluble CD23 (sCD23) receptor, parasite-specific IgE responses and allergic sensitisation in people exposed to the helminth parasite Schistosoma haematobium. METHODS: A cohort of 434 participants was recruited in two villages with different levels of S. haematobium infection in Zimbabwe. Serum levels of the 25-kDa fragment of sCD23 were related to levels of schistosome infection intensity, allergen (house dust mite, HDM) and schistosome-specific IgE, total IgE and skin sensitisation to HDM. RESULTS: sCD23 levels rose significantly with schistosome infection intensity but declined significantly with schistosome-specific IgE levels. Furthermore, sCD23 levels were negatively associated with skin sensitisation and IgE reactivity against HDM, but showed no relationship with total IgE. CONCLUSION: The results are consistent with the suppression of parasite and allergen-specific IgE levels by sCD23. Further mechanistic studies will determine the relevance of this potential regulatory mechanism in the development of helminth-specific immune responses in atopic individuals

What does equitable global health research and delivery look like?:Tackling Infections to Benefit Africa (TIBA) partnership as a case study

There is a current global push to identify and implement best practice for delivering maximum impact from development research in low-income and middle-income countries. Here, we describe a model of research and capacity building that challenges traditional approaches taken by western funders in Africa. Tackling Infections to Benefit Africa (TIBA) is a global health research and delivery partnership with a focus on strengthening health systems to combat neglected tropical diseases, malaria and emerging pathogens in Africa. Partners are academic and research institutions based in Ghana, Sudan, Rwanda, Uganda, Kenya, Tanzania, Zimbabwe, Botswana, South Africa and the UK. Fifteen other African countries have participated in TIBA activities. With a starting budget of under £7 million, and in just 4 years, TIBA has had a verified impact on knowledge, policy practice and capacity building, and on national and international COVID-19 responses in multiple African countries. TIBA’s impact is shown in context-specific metrics including: strengthening the evidence base underpinning international policy on neglected tropical diseases; 77% of research publications having Africa-based first and/or last authors; postgraduate, postdoctoral and professional training; career progression for African researchers and health professionals with no net brain drain from participating countries; and supporting African institutions. Training in real-time SARS-CoV-2 viral genome sequencing provided new national capabilities and capacities that contributed to both national responses and global health security through variant detection and tracking. TIBA’s experience confirms that health research for Africa thrives when the agenda and priorities are set in Africa, by Africans, and the work is done in Africa. Here, we share 10 actionable recommendations for researchers and funders from our lessons learnt