Comparative evaluation of plasma biomarkers of Schistosoma haematobium infection in endemic populations from Burkina Faso.

Infection with Schistosoma haematobium causes urogenital disease associated with organ disfunction, bleeding, pain, and higher susceptibility to infections and cancer. Timely and accurate diagnosis is crucial for prompt and appropriate treatment as well as surveillance efforts, and the use of plasma biomarkers offers important advantages over parasitological examination of urine, including increased sensitivity and the possibility to use the same specimen for multiple investigations. The present study aims to evaluate the diagnostic performance of different plasma biomarkers in endemic populations from Burkina Faso, West Africa. Schistosoma spp. Circulating Anodic Antigen (CAA), cell free S. haematobium DNA (cfDNA), class M and G antibodies against S. haematobium Soluble Worm Antigen Preparation (SWAP) and Soluble Egg Antigen (SEA) were measured in 406 plasma samples. Results of each biomarker test were compared to those of CAA, a Composite Reference Standard (CRS) and Latent Class Analysis (LCA). An identical proportion of positive samples (29%) was observed as a result of CAA and cfDNA testing, with a substantial agreement (84%, Cohen k = 0.62) between the results of the two tests, and a comparable agreement with the results of CRS and LCA. A higher positivity was observed, as expected, as a result of specific antibody testing (47%-72%), with IgG showing a higher agreement than IgM with the three references. Also, higher IgG levels were observed in current vs past infection, and ROC analysis identified optimal cutoff values for improved testing accuracy. This study provides compelling evidence that can inform the choice of the most appropriate diagnostic plasma biomarker for urogenital schistosomiasis in endemic areas, depending on the purpose, context, and available resources for testing. Either CAA or cfDNA testing can be used for the diagnosis of patients and for epidemiological investigations, even in absence of urine filtration microscopy, whereas anti-SWAP or anti-SEA IgG can be employed for surveillance and integrated monitoring of control interventions against poverty-associated diseases.

Higher gametocyte production and mosquito infectivity in chronic compared to incident Plasmodium falciparum infections.

Plasmodium falciparum gametocyte kinetics and infectivity may differ between chronic and incident infections. In the current study, we assess parasite kinetics and infectivity to mosquitoes among children (aged 5-10 years) from Burkina Faso with (a) incident infections following parasite clearance (n = 48) and (b) chronic asymptomatic infections (n = 60). In the incident infection cohort, 92% (44/48) of children develop symptoms within 35 days, compared to 23% (14/60) in the chronic cohort. All individuals with chronic infection carried gametocytes or developed them during follow-up, whereas only 35% (17/48) in the incident cohort produce gametocytes before becoming symptomatic and receiving treatment. Parasite multiplication rate (PMR) and the relative abundance of ap2-g and gexp-5 transcripts are positively associated with gametocyte production. Antibody responses are higher and PMR lower in chronic infections. The presence of symptoms and sexual stage immune responses are associated with reductions in gametocyte infectivity to mosquitoes. We observe that most incident infections require treatment before the density of mature gametocytes is sufficient to infect mosquitoes. In contrast, chronic, asymptomatic infections represent a significant source of mosquito infections. Our observations support the notion that malaria transmission reduction may be expedited by enhanced case management, involving both symptom-screening and infection detection.

Antibody response to Schistosoma haematobium and other helminth species in malaria-exposed populations from Burkina Faso.

Infection with helminths in sub-Saharan Africa could modulate the immune response towards Plasmodium falciparum as well as susceptibility to malaria infection and disease. The aim of this study is to assess the antibody responses to helminths species in malaria-exposed populations from Burkina Faso. Plasma samples were collected in rural villages inhabited by Fulani, Mossi and Rimaibe communities, and IgG against parasitic helminths were measured by ELISA. The prevalence of IgG against antigens of Strongyloides stercoralis, Wuchereria bancrofti and Schistosoma haematobium (Soluble Egg Antigen, SEA) was 5%, 16% and 63% respectively, in line with estimates of infection prevalence in the region for the three parasites. Anti-SEA IgG prevalence was highest at 10-20 years of age, higher in males than females, and did not show differences between ethnic groups. However, the Fulani showed lower levels of anti-SEA IgG suggesting that lighter S. haematobium infections may occur in the ethnic group known for a marked lower susceptibility to P. falciparum. The present data support the use of serological methods for integrated surveillance of neglected tropical diseases such as soil-transmitted helminths, lymphatic filariasis and bilharzia. Furthermore, as helminth infections might promote downregulation of immune responses against intracellular pathogens, the observation of lower anti-SEA IgG levels in the malaria resistant Fulani population warrants further investigation into the immunological cross-talk between S. haematobium and P. falciparum in this geographical region.

Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants.

Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine.