Scoping a social science agenda for male genital schistosomiasis in sub-Saharan Africa: Posing key questions to frame appropriate research themes

The prevalence of female genital schistosomiasis (FGS) and male genital schistosomiasis (MGS) remains high in low-to-medium income countries, and each has sex-specific disease sequelae with wider detrimental gender and health impacts. Social science research studies on the former outnumber those on the latter. Indeed, in many countries across sub-Saharan Africa (SSA), MGS (as with male reproductive and sexual health issues in general) is overlooked, underappreciated and broadly orphaned within urogenital and intestinal schistosomiasis research and control. Similarly, in those countries where MGS has been reported formally, its psychosocial dimensions and effects remain poorly understood, especially in terms of context-specific cultural and societal factors. In this scoping review, we attempt to better contextualise MGS within men’s sexual and reproductive health and rights (SRHR) and general wellbeing, as it often draws parallels with social science research in FGS. We discuss common psychosocial determinants, highlighting why current surveillance of MGS is particularly poor and the primary health care response to mitigate it is bottlenecked and largely stalled within the wider health system, from both top-down and bottom-up perspectives. Our specific approach remains cognisant of a context of infected households where all members could be suffering from urogenital and/or intestinal schistosomiasis. Looking ahead, we develop and frame a pragmatic social science research agenda to encourage and better explore and assess the detrimental impact of MGS on infected men and boys, considering appropriate ameliorations more holistically within primary care.</p

Precision mapping of hybrid schistosomes in urogenital schistosomiasis: Research lessons learned from stakeholder dialogue, community engagement and household access in two study communities in southern Malawi.

Conducting health research in rural settings of sub-Saharan Africa presents unique challenges and we present our experiences and lessons learned from stakeholder dialogue, community engagement and household mapping strategies for precision mapping of hybrid schistosomes in two study communities of southern Malawi. Targeting to recruit a total sample size of 2400 individuals aged 2 to 45 years, in 2022 we carried out stakeholders’ engagement at district, area and village levels through meetings with representatives from governmental and non-governmental organizations and communities. Community sensitization was achieved through village meetings and public address systems, facilitating local buy-in for a successful Global Positioning System mapping of 1214 households leading to recruitment of a total of 2319 (96.6 %) participants of the 2400 target within a 20-days period. Follow-up surveys in 2023 and 2024 retained 2006 (86.5 %) and 2014 (86.8 %) participants, respectively. Stakeholders and communities were supportive of the study activities and assisted with in kind support. Main challenges in cohort retention were recalcitrant beliefs about disease aetiologies and community displacement following cyclonic flooding. The unfamiliar concept of parasite hybridization and zoonosis in urogenital schistosomiasis required repeated, carefully tailored messaging to build understanding and trust. Our study's experience demonstrates that engaging key stakeholders and community members builds trust, promotes acceptability and ownership, and increases the likelihood of successful implementation of health research activities.</p

Controlled human infection model (CHIM) inoculum production in Malawi using principles of good manufacturing practice

Background Controlled Human Infection Models (CHIM) are an important tool in biomedical research in which pathogens are inoculated into human volunteers to study pathogenesis and test vaccines or treatments. Production of CHIM inoculum, however, presents specific challenges in safety, reproducibility and replication of the desired dose. The principles of Good Manufacturing Practice (GMP) developed for production of medications can be applied to the preparation of CHIM inocula, but licensed GMP facilities are scarce in low resource settings. Methods We applied GMP principles to develop protocols for CHIM inocula production at Liverpool School of Tropical Medicine, UK and subsequently at Malawi-Liverpool Wellcome Programme, Malawi. We used published guidelines to evaluate these protocols and to advise selection, characterisation, manufacture, quality control and storage. We established in-house production of Streptococcus pneumoniae serotypes 3 and 6B for use in Experimental Human Pneumococcal Challenge models. Results The manufacturing process underwent regulatory review in both the UK and Malawi. CHIM inocula production in Malawi was approved by the National Health Sciences Research Committee after written and oral submission. We successfully implemented our procedure and manufactured batch lots of Streptococcus pneumoniae serotype 3 ( n = 2) and serotype 6B (n = 2). We safely, accurately and successfully inoculated participants in CHIM studies and achieved experimental human pneumococcal carriage with both serotype strains. Discussion CHIM inoculum manufacture of pneumococcus was feasible in Malawi. This allowed the Malawi scientific ecosystem to demonstrate scientific and regulatory autonomy as well as having the potential to improve operational efficiency compared to importation of challenge agents.</p

Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae

Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture. Given the demonstrated resistance to the classical insecticides in numerous Anopheles spp., the use of synergists is becoming increasingly pertinent. Tropical plants synthesize diverse phytochemicals, presenting a repository of potential synergists. Methods Extracts prepared from medicinal plants found in Jamaica were screened against recombinant Anopheles gambiae CYP6M2 and CYP6P3, and Anopheles funestus CYP6P9a, CYPs associated with anopheline resistance to pyrethroids and several other insecticide classes. The toxicity of these extracts alone or as synergists, was evaluated using bottle bioassays with the insecticide permethrin. RNA sequencing and in silico modelling were used to determine the mode of action of the extracts. Results Aqueous extracts of Piper amalago var. amalago inhibited CYP6P9a, CYP6M2, and CYP6P3 with IC50s of 2.61 ± 0.17, 4.3 ± 0.42, and 5.84 ± 0.42 μg/ml, respectively, while extracts of Kalanchoe pinnata, inhibited CYP6M2 with an IC50 of 3.52 ± 0.68 μg/ml. Ethanol extracts of P. amalago var. amalago and K. pinnata displayed dose-dependent insecticidal activity against An. gambiae, with LD50s of 368.42 and 282.37 ng/mosquito, respectively. Additionally, An. gambiae pretreated with K. pinnata (dose: 1.43 μg/mosquito) demonstrated increased susceptibility (83.19 ± 6.14%) to permethrin in a bottle bioassay at 30 min compared to the permethrin only treatment (0% mortality). RNA sequencing demonstrated gene modulation for CYP genes in anopheline mosquitoes exposed to 715 ng of ethanolic plant extract at 24 h. In silico modelling showed good binding affinity between CYPs and the plants’ secondary metabolites. Conclusion This study demonstrates that extracts from P. amalago var. amalago and K. pinnata, with inhibitory properties, IC50 < 6.95 μg/ml, against recombinant anopheline CYPs may be developed as natural synergists against anopheline mosquitoes. Novel synergists can help to overcome metabolic resistance to insecticides, which is increasingly reported in malaria vectors

Efficacy of prebiotic, probiotic and synbiotics in improving growth in children under age five years in Africa: a protocol for a systematic review.

Background: Stunting is among main obstacles to human development affecting millions of children worldwide and particularly in the sub-Saharan Africa region. Randomized clinical trials have shown positive effects of prebiotics, probiotics, and synbiotics in improving growth in children and toddlers. However, although the global mobilization to tackle its challenges in their different aspects is visible, it remains to define effective large-scale up interventions and strategies to obtain long lasting impacts. Objective: The objective of this review is to re-evaluate the effectiveness of prebiotics, probiotics, and/or synbiotics on the growth of children in children 0 to 5 years in Africa including recently published studies. Methods: Systematic search will be carried out in Pubmed, science direct, clinicaltrial.org, and google scholar. Both randomized and observational studies that assess the association between prebiotics, probiotics, and synbiotics, and health benefits and growth in children under 5 years of age will be included in the review. PRISMA-P (preferred reporting items for systematic review and meta-analysis protocols) has been used for this protocol, and PRISMA will be used for the systematic review. The Cochrane Risk Assessment Tool will be used to assess the quality of eligible studies. If the compiled data are appropriate and sufficient, we will perform a meta-analysis using RevMan software. Conclusion: This review will provide up-to-date and reliable information on the effectiveness of prebiotics, probiotics, and synbiotics on the growth of children under 5 years of age especially in developing countries. PROSPERO registration number CRD42022343138

Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease

Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately 4 billion people at risk of arthropod-borne viruses (arboviruses). Mosquito populations are geographically expanding into temperate regions and their distribution is predicted to continue increasing. Mosquito symbionts, including fungi, bacteria and viruses, have desirable traits for mosquito disease control including spreading horizontally and vertically through mosquito populations and potentially colonising multiple important vector species. Paratransgenesis, genetic modification of mosquito symbionts with effectors to target the pathogen rather than the vector, is a promising strategy to prevent the spread of mosquito-borne diseases. A variety of effectors can be expressed but venom toxins are excellent effector candidates because they are target specific, potent and stable. However, the only toxins to be explored in mosquito paratransgenesis to date are scorpine and mutated phospholipase A2. To enhance the scope, effectiveness and durability of paratransgenesis, an expanded arsenal of effectors is required. This review discusses other potential toxin effectors for future paratransgenesis studies based on prior in vitro and in vivo antiparasitic and antiviral studies and highlights the need for further research and investment in this area. In terms of mosquito-borne diseases, paratransgenesis strategies have been developed to target Plasmodium. We postulate the potential to apply this principle to target arboviruses using antiviral toxin effectors

Self-reported COVID-19 severity among persons with tuberculosis infection in western Kenya, 2021

Whilst a quarter of the world’s population is estimated to be infected with Mycobacterium tuberculosis, it is unknown whether TB infection (TBI) increases the risk of severe COVID-19, which is relevant in TB-endemic settings, especially where HIV co-infection is also common. A convenience cohort of symptomatic and asymptomatic COVID-19 patients aged 8–80 years in western Kenya was followed daily for 14 days to assess disease progression using the validated inFLUenza-Patient-Reported-Outcome Plus signs and symptom tool. Nasal swabbing for SARS-CoV-2 was conducted to confirm the virus using polymerase chain reaction. QuantiFERON-TB Gold Plus was used to diagnose TBI. HIV status was based on self-reports. Between January 3, 2021, and January 20, 2022, 373 out of 387 participants had conclusive QuantiFERON results. At baseline, 5.9% (22/373) had self-reported severe COVID-19, 33.2% (124/373) had TBI, and 11.1% (38/341) reported being HIV-infected. Median follow-up of the cohort was 105 days (range 0–368). Self-reported severe COVID-19 was experienced by 10 of 124 (8.1%) participants compared with 12 of 249 (4.8%) without TBI (odds ratio [OR] 1.73, 95% CI 0.73-4.12, p = 0.21). HIV was not associated with self-reported severe COVID-19 (OR 3.13, 0.96-8.77, p = 0.039, adjusted OR 2.77, 95%CI 0.84-7.93, p = 0.070), but age ≥ 50 years was associated with self-reported severe COVID-19 (OR 3.73, 1.47-9.07, p = 0.004, adjusted OR 2.91, 95%CI 1.02-7.69, p = 0.035). One participant died of COVID-19 three days after diagnosis, and another participant developed active TB 128 days after his COVID-19 diagnosis and was successfully treated. Both were QuantiFERON positive. Self-reported severe COVID-19 was associated with older age and not TBI. Our finding that increased age was associated with self-reported severe COVID-19 is consistent with findings in multiple settings around the world

Field evaluation of the Bioline Malaria Ag P.f/Pan rapid diagnostic test: causes of microscopy discordance and performance in Uganda

Background Histidine Rich Protein 2 (HRP2)/pan-Lactate Dehydrogenase (pLDH) combination rapid diagnostic tests (RDTs) may address the shortcomings of RDTs that detect HRP2 alone. However, the relative contribution of the possible causes of discordant results (RDT-negative and microscopy-positive) and performance in field settings across Uganda are poorly quantified. Methods This study utilized samples from two cross-sectional surveys conducted in 32 districts at 64 sites across Uganda between November 2021 and March 2023 that enrolled 6354 febrile participants  ≥ two years of age. Discordant samples (negative by HRP2/pLDH RDT and positive by microscopy) underwent quantitative PCR (qPCR) to detect and quantify parasitaemia. Those confirmed to be positive for Plasmodium falciparum at > 1 parasites/microlitre (p/µL) were tested for pfhrp2 and pfhrp3 deletions using digital PCR. Those that were negative or had P. falciparum detected at ≤ 1 p/µL underwent Plasmodium species testing using nested PCR. The performance of the Bioline Malaria Ag P.f/Pan combination RDT was evaluated by comparison with microscopy and qPCR. Results There were 166 (8.4%) discordant samples out of 1988 microscopy positive samples. Of these, 90/166 (54.2%) were confirmed to contain P. falciparum at levels > 1 p/µL, whereas 76/166 (45.8%) were negative or had P. falciparum levels ≤ 1 p/µL. Only one P. falciparum positive sample was confirmed to have a deletion in pfhrp3. The primary reasons for RDT-negative, microscopy-positive discordance in samples testing negative for P. falciparum by PCR were non-falciparum species (37/76, 48.7%) or false positives by microscopy (31/76, 40.8%). The sensitivity of the Bioline Malaria Ag P.f/Pan combination RDT was high (> 91%) using either microscopy or qPCR as the gold standard. However, specificity was low (56.7%) when microscopy was used as the gold standard; it improved to 64.0% when qPCR was used as the gold standard. Conclusion The Bioline Malaria Ag P.f/Pan combination RDT was found to be highly sensitive in Uganda and reliable for ruling out malaria. False negative RDT results were primarily due to low density P. falciparum infections, non-falciparum infections, or incorrect microscopy results. In contrast, false positive RDT results were common, most likely due to persistent HRP2 antigenaemia in this high transmission setting though causes of false positive RDTs were not investigated. The low specificity of HRP2-based RDTs may result in overuse of anti-malarial drugs and missed diagnoses of non-malarial febrile illnesses