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

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

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

Infection and treatment immunizations for successful parasite vaccines

Since the advent of techniques for the expression of recombinant peptide antigens, the availability of human vaccines for parasitic diseases has been ‘imminent’. Yet vaccines based on recombinant proteins are still largely aspirations, not realities. It is now apparent that vaccine development needs additional knowledge about host protective immune response(s), antigen characteristics, and the delivery required to induce those responses. The most successful immune protection against parasites has been generated by infection and treatment, the induction of protective immunity by truncating the course of an infection with drug treatment. Here, we consider the characteristics of an effective, protective anti-parasite vaccine and propose a conceptual framework to aid parasite vaccine development using malaria and schistosomiasis as examples

Drug metabolism and pharmacokinetics of praziquantel:A review of variable drug exposure during schistosomiasis treatment in human hosts and experimental models

Schistosomiasis control is heavily reliant on the drug praziquantel (PZQ), which is used as preventive chemotherapy as part of national helminth control strategies. Given the heavy reliance on PZQ for mass drug administration, there has been considerable research on the potential of parasites developing resistance to the drug, resulting in decreased drug efficacy. However, there have been comparatively fewer studies of other factors that can potentially alter PZQ efficacy. Here, we investigate whether host PZQ metabolism contributes towards variable cure rates. We evaluate factors that can influence the metabolism of PZQ and the resultant effect on the efficacy of PZQ treatment to determine factors that potentially influence an individual's response to the drug. The literature search was directed at published studies from three online databases: Web of Science, PubMed, and EMBASE. The search terms for the review comprised of ([praziquantel OR PZQ] AND [schistosom* OR bilharzia] AND [pharmaco*]) and included studies evaluating PZQ metabolism. Publications were categorised into pharmacokinetics, drug-drug interactions, pharmacogenetics, and metabolite analysis. Forty publications describing human and experimental studies fitted the inclusion criteria and were subjected to data extraction and analysis. The analyses showed that variable exposure to PZQ was associated with alterations in the liver's capacity to metabolise PZQ and observed drug-drug interactions. Other factors influencing the efficacy of PZQ were brand, formulation, and co-administered food. Although some work has been performed on metabolite identification, there was minimal information on PZQ's metabolic pathway, and no pharmacogenetics studies were identified. The study indicated that in both human and experimental studies alterations in the liver's capacity to metabolise PZQ as well as drug-drug interactions affected systemic levels of PZQ that could result in variable cure rates. The study confirmed previous findings of higher antischistosomal activity of (R)-PZQ enantiomer when administered alone compared to the racemate at the same dose as well as improved efficacy when the drug is administered with food. The study also highlighted the need for more comprehensive studies of the PZQ metabolic pathway and PZQ pharmacogenetic studies in humans

Efficacy of praziquantel has been maintained over four decades (from 1977 to 2018):A systematic review and meta-analysis of factors influence its efficacy

BackgroundThe antihelminthic drug praziquantel has been used as the drug of choice for treating schistosome infection for more than 40 years. Although some epidemiological studies have reported low praziquantel efficacy in cure rate (CR) and/or egg reduction rate (ERR), there is no consistent robust evidence of the development of schistosome resistance to praziquantel (PZQ). There is need to determine factors that lead to variable treatment CR and/or ERR. Therefore, we conducted a systematic review and meta-analysis to review CR and ERR as well as identify their predictors.Methodology/principal findingsIn this systematic review and meta-analysis, a literature review was conducted using Biosis Citation Index, Data Citation Index, MEDLINE, and Web of Science Core Collection all of which were provided through Web of Science. Alongside these, EMBASE, and CAB abstracts were searched to identify relevant articles. Random effect meta-regression models were used to identify the factors that influence CR and/or ERR by considering differences in host characteristics and drug dose. In total, 12,127 potential articles were screened and 146 eligible articles (published from 1979 to 2020) were identified and included for the meta-analysis. We found that there has been no significant reduction in CR or ERR over the study period. The results showed more variability in CR, compared with ERR which was more consistent and remained high. The results showed a positive effect of "PZQ treatment dose" with the current recommended dose of 40 mg/kg body weight achieving 57% to 88% CR depending on schistosome species, age of participants, and number of parasitological samples used for diagnosis, and ERR of 95%.Conclusions/significanceBased on a review of over 40 years of research there is no evidence to support concerns about schistosomes developing resistance to PZQ. These results indicate that PZQ remains effective in treating schistosomiasis

Blind spots in the implementation of point-of-care diagnostics for underserved communities

Point-of-care (POC) diagnostics are particularly important in resource-limited settings. However, to ensure their sustainability, deployment and uptake by underserved communities, systemic, infrastructural, operational and logistical limitations need to be addressed