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This article discusses the development and evaluation of a PCR-RFLP test for the detection of trypanocidal drug resistance in Trypanosoma congolense, a parasite that causes animal African trypanosomiasis (AAT) in sub-Saharan Africa. AAT affects livestock production and endangers the food supply of rural communities. The test, which detects a single point mutation in the parasite's DNA, was found to be more sensitive than the gold standard test. The use of blood spots or buffy coats on filter paper for sample collection and storage was also explored, offering logistical and economic advantages for large-scale surveys. [Extracted from the article]

Background: The European & Developing Countries Clinical Trials Partnership (EDCTP) is a partnership of European and sub-Saharan African countries that aims to accelerate the development of medical interventions against poverty-related diseases (PRDs). A bibliometric analysis was conducted to 1) measure research output from European and African researchers on PRDs, 2) describe collaboration patterns, and 3) assess the citation impact of clinical research funded by EDCTP. Methodology/Principal Findings: Disease-specific research publications were identified in Thomson Reuters Web of Science using search terms in titles, abstracts and keywords. Publication data, including citation counts, were extracted for 2003–2011. Analyses including output, share of global papers, normalised citation impact (NCI), and geographical distribution are presented. Data are presented as five-year moving averages. European EDCTP member countries accounted for ~33% of global research output in PRDs and sub-Saharan African countries for ~10% (2007–2011). Both regions contributed more to the global research output in malaria (43.4% and 22.2%, respectively). The overall number of PRD papers from sub-Saharan Africa increased markedly (>47%) since 2003, particularly for HIV/AIDS (102%) and tuberculosis (TB) (81%), and principally involving Southern and East Africa. For 2007–2011, European and sub-Saharan African research collaboration on PRDs was highly cited compared with the world average (NCI in brackets): HIV/AIDS 1.62 (NCI: 1.16), TB 2.11 (NCI: 1.06), malaria 1.81 (NCI: 1.22), and neglected infectious diseases 1.34 (NCI: 0.97). The NCI of EDCTP-funded papers for 2003–2011 was exceptionally high for HIV/AIDS (3.24), TB (4.08) and HIV/TB co-infection (5.10) compared with global research benchmarks (1.14, 1.05 and 1.35, respectively). Conclusions: The volume and citation impact of papers from sub-Saharan Africa has increased since 2003, as has collaborative research between Europe and sub-Saharan Africa. >90% of publications from EDCTP-funded research were published in high-impact journals and are highly cited. These findings corroborate the benefit of collaborative research on PRDs. [ABSTRACT FROM AUTHOR]

Background: Human African trypanosomiasis (HAT) is a neglected tropical disease that usually occurs in rural areas in sub-Saharan Africa. It caused devastating epidemics during the 20th century. Sustained, coordinated efforts by different stakeholders working with national sleeping sickness control programmes (NSSCPs) succeeded in controlling the disease and reducing the number of cases to historically low levels. In 2012, WHO targeted the elimination of the disease as a public health problem by 2020. This goal has been reached and a new ambitious target was stated in the WHO road map for NTDs 2021–2030 and endorsed by the 73rd World Health Assembly: the elimination of gambiense HAT transmission (i.e. reducing the number of reported cases to zero). The interruption of transmission was not considered as an achievable goal for rhodesiense HAT, as it would require vast veterinary interventions rather than actions at the public health level. Methodology/principal findings: Data reported to WHO by NSSCPs were harmonized, verified, georeferenced and included in the atlas of HAT. A total of 802 cases were reported in 2021 and 837 in 2022. This is below the target for elimination as a public health problem at the global level (< 2000 HAT cases/year); 94% of the cases were caused by infection with T. b. gambiense. The areas reporting ≥ 1 HAT case/10 000 inhabitants/year in 2018–2022 cover a surface of 73 134 km2, with only 3013 km2 at very high or high risk. This represents a reduction of 90% from the baseline figure for 2000–2004, the target set for the elimination of HAT as a public health problem. For the surveillance of the disease, 4.5 million people were screened for gambiense HAT with serological tests in 2021–2022, 3.6 million through active screening and 0.9 million by passive screening. In 2021 and 2022 the elimination of HAT as a public health problem was validated in Benin, Uganda, Equatorial Guinea and Ghana for gambiense HAT and in Rwanda for rhodesiense HAT. To reach the next goal of elimination of transmission of gambiense HAT, countries have to report zero cases of human infection with T. b. gambiense for a period of at least 5 consecutive years. The criteria and procedures to verify elimination of transmission have been recently published by WHO. Conclusions/significance: HAT elimination as a public health problem has been reached at global level, with seven countries already validated as having reached this goal. This achievement was made possible by the work of NSSCPs, supported by different public and private partners, and coordinated by WHO. The new challenging goal now is to reach zero cases by 2030. To reach this goal is crucial to maintain the engagement and support of donors and stakeholders and to keep the involvement and coordination of all partners. Along with the focus on elimination of transmission of gambiense HAT, it is important not to neglect rhodesiense HAT, which is targeted for elimination as a public health problem in the WHO road map for NTDs 2021–2030. Author summary: Human African trypanosomiasis (HAT), also known as "sleeping sickness, is a neglected tropical disease (NTD) transmitted by the bite of infected tsetse flies mainly affecting rural areas in sub-Saharan Africa. During the 20th century it caused enormous suffering in the endemic areas with a last reported peak in the late 1990s. This situation triggered a successful coordinated control effort that allowed, in 2012, the targeting of elimination of the disease as a public health problem by 2020. This paper follows previous papers to present the achievements towards HAT elimination. Annually reported cases have been kept below 1000 cases per year. HAT surveillance is maintained through active screening in endemic areas but also within a network of health facilities able to detect the disease. The World Health Organization (WHO), as defined in its 2021–2030 road map for NTDs, is now targeting the elimination of transmission of gambiense HAT and the elimination of rhodesiense HAT as a public health problem. The commitment of national health authorities and the international community will be essential to achieve these ambitious targets. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans is responsible for life-threatening infections that primarily affect immunocompromised individuals and has an estimated worldwide burden of 220,000 new cases each year—with 180,000 resulting deaths—mostly in sub-Saharan Africa. Surprisingly, little is known about the ecological niches occupied by C. neoformans in nature. To expand our understanding of the distribution and ecological associations of this pathogen we implement a Natural Language Processing approach to better describe the niche of C. neoformans. We use a Latent Dirichlet Allocation model to de novo topic model sets of metagenetic research articles written about varied subjects which either explicitly mention, inadvertently find, or fail to find C. neoformans. These articles are all linked to NCBI Sequence Read Archive datasets of 18S ribosomal RNA and/or Internal Transcribed Spacer gene-regions. The number of topics was determined based on the model coherence score, and articles were assigned to the created topics via a Machine Learning approach with a Random Forest algorithm. Our analysis provides support for a previously suggested linkage between C. neoformans and soils associated with decomposing wood. Our approach, using a search of single-locus metagenetic data, gathering papers connected to the datasets, de novo determination of topics, the number of topics, and assignment of articles to the topics, illustrates how such an analysis pipeline can harness large-scale datasets that are published/available but not necessarily fully analyzed, or whose metadata is not harmonized with other studies. Our approach can be applied to a variety of systems to assert potential evidence of environmental associations. Author summary: We expand the utility of Natural Language Processing (NLP), backtracking through metabarcodes, utilizing papers that may not mention our subject of interest, C. neoformans, in a departure from usual text analysis methods. We confirm that C. neoformans is associated with decomposing wood which is reinforced by the inferred literature studied here on C. neoformans and its close congeneric relatives. This work demonstrates the potential utility of pairing NLP with single-locus metagenetic data for the study of Neglected Tropical Diseases. While the results of this article are largely confirmatory, we present a novel method to study the ecological niches of rare pathogens that leverages the immense amount of data available to researchers in the NCBI Sequence Read Archive (SRA) combined with a text-mining analysis based on Natural Language Processing. We demonstrate that text processing, noun identification, and verb identification can play an important role in analyzing a large corpus of documents together with metagenetic data. Forging this connection requires access to all of the available ecological 18S ribosomal RNA and Internal Transcribed Spacer NCBI SRA datasets. These datasets use metabarcoding to query taxonomic diversity in eukaryotic organisms, and in the case of the Internal Transcribed Spacer, they specifically target Fungi. The presence of specific species is inferred when diagnostic 18S or ITS gene region sequences are found in the SRA data. We searched for C. neoformans in all 18S and ITS datasets available and gathered all associated journal articles that either cite the SRA data accessions or are cited in the SRA data accessions. Published metagenetic data often have associated metadata including: latitude and longitude, temperature, and other physical characteristics describing the conditions in which the metagenetic sample was collected. These metadata are not always presented in consistent formats, so harmonizing study methods may be needed to appropriately compare metagenetic data as commonly required in metanalysis studies. We present an analysis which takes as input articles associated with SRA datasets that were found to contain evidence of C. neoformans. We apply NLP methods to this corpus of articles to describe the niche of C. neoformans. Our results reinforce the current understanding of C. neoformans's niche, indicating the pertinence of employing an NLP analysis to identify the niche of an organism. This approach could further the description of virtually any other organism that routinely appears in metagenetic surveys, especially pathogens, whose ecological niches are unknown or poorly understood. [ABSTRACT FROM AUTHOR]

Background: The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions. Methods: The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community. Results: In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration). Conclusions: While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission. Author summary: The standard method of control for intestinal worms, a common public health problem in sub-Saharan Africa, is distribution of deworming treatment on a mass scale. These infections are difficult to eliminate as re-infection is common due a combination of people not being treated and high exposure to the parasites through poor access to sanitation and clean water. The Geshiyaro project in Ethiopia has the ambitious goal of breaking the transmission cycle of such infections through treatment in combination with provision of water and sanitation services. The impact of these interventions is being measured using a unique approach, that is, using finger printing to evaluate prevalence of infection with compliance to treatment and access water or sanitation. [ABSTRACT FROM AUTHOR]

Background: Moxidectin is a macrocyclic lactone registered for the treatment of human onchocerciasis. The drug has a good safety profile, large volume of distribution and a long elimination half-life. This paper reports tolerability data from the first use of moxidectin in persons with Wuchereria bancrofti infection. Methods: In this randomized, open-label, masked-observer superiority trial, adults with Wuchereria bancrofti microfilaremia in Côte d'Ivoire were randomized to 1 of 4 treatment arms: ivermectin + albendazole (IA), moxidectin + albendazole (MoxA), ivermectin + diethylcarbamazine (DEC) + albendazole (IDA), or moxidectin + DEC + albendazole (MoxDA). As part of a larger efficacy trial, all participants were closely monitored for 7 days after treatment. Results: One hundred sixty-four individuals were treated, and monitored for treatment emergent adverse events (TEAE). Eighty-seven participants (53%) experienced one or more mild (grade 1) or moderate (grade 2) TEAE. Four participants had transient Grade 3 hematuria after treatment (3 after IDA and 1 after IA). There were no serious adverse events. There were no significant differences in frequency or types of TEAE between treatment groups (IA = 22/41 (53%), MoxA = 24/40 (60%), IDA = 18/41 (44%), MoxDA = 15/42 (36%), p = 0.530). Fifty-nine participants (36%) had multiple TEAE, and 8.5% had a one or more grade 2 (moderate) TEAE. Grade 2 TEAE were more frequent after triple drug treatments (IDA, 14.6%; MoxDA, 9.5%) than after two-drug treatments (IA, 7.3%; MoxA, 2.5%). There was no difference in TEAEs based on baseline Mf counts (OR 0.69 (0.33, 1.43), p-value 0.319). Conclusion: All treatment regimens were well tolerated. We observed no difference in safety parameters between regimens that contained ivermectin or moxidectin. Trial registration: Clinicaltrials.gov, NCT04410406. Author summary: Lymphatic Filariasis (LF) is a mosquito-borne parasitic infection caused predominantly by Wuchereria bancrofti. Infection can lead to significant lymphatic dysfunction, including hydroceles and lymphedema, which can progress to elephantiasis. The World Health Organization's Global Programme to Eliminate LF (GPELF) recommends mass drug administration (MDA) in endemic populations to eliminate the disease. GPELF recommendations for MDA include ivermectin (IVM) plus albendazole (IA) in sub-Saharan Africa where onchocerciasis is present. In 2018 the US Food and Drug Administration approved use of moxidectin for treatment of onchocerciasis. Moxidectin is a macrocytic lactone, similar to IVM, but more lipophilic, with a larger volume of distribution and longer half-life. Onchocerciasis studies found moxidectin to be superior to IVM for clearance of microfiladermia in people with onchocerciasis, with a treatment emergent adverse event (TEAE) profile similar to that of ivermectin. Moxidectin has not yet been studied, alone or in combination with other antihelminthic drugs. This is a safety evaluation of the first trial of moxidectin combination therapy for LF, which shows that moxidectin combination regimens are well tolerated in Wuchereria bancrofti-infected patients, with a TEAE profile comparable to standard ivermectin containing regimens. [ABSTRACT FROM AUTHOR]

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1–27.3°C and 23.6–27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum. Author summary: In this research, we explored the complex interplay between temperature and the transmission risk of schistosomiasis, a parasitic disease currently affecting over two hundred million people, predominantly in SSA. We developed a novel mathematical model accounting for the multiple positive and negative ways temperature affects the free-living stages of the parasite and its obligate, non-human host, i.e., specific species of freshwater snails. Our models show that schistosomiasis transmission risk peaks at temperatures 1–6°C higher than previously estimated. This indicates that the impact of climate change on schistosomiasis transmission might be more extensive than previously thought, affecting a wide geographic range where mean annual temperatures are currently below the optimal temperature. Our model projections are consistent with the observed temperatures in locations of SSA where schistosomiasis is endemic and data on infection prevalence in the human population are available. These findings suggest that the current climate is conducive to schistosomiasis transmission, and future warming could escalate the risk further, emphasizing the need for targeted interventions in these regions. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic disrupted essential health services, including those provided by national neglected tropical disease (NTD) programs. Most mass drug administration (MDA) programs were postponed for 6–12 months following World Health Organization guidance released in April 2020 to temporarily halt NTD programs and launch necessary COVID-19 precautions. While NTD-endemic countries have since resumed MDA activities, it is critical to understand implementers' perspectives on the key challenges and opportunities for program relaunch, as these insights are critical for maximizing gains towards disease control and elimination during public health emergencies. Using data from using online surveys and focus group discussions, this mixed-methods study sought perspectives from Ministry of Health NTD Program Managers and implementing partners from non-governmental organizations working in sub-Saharan Africa. Data analysis revealed that findings converged around several main themes: disruptions for MDA programs included resource shortages due to prioritization of pandemic response, challenges adhering to COVID-19 safety protocols, and community hesitancy due to coronavirus transmission fears. Identified solutions for restarting MDA programs focused on adapting intervention delivery and packaging to minimize disease transmission, embracing technology to optimize intervention planning and delivery, and identifying opportunities to promote program integration between pandemic response strategies and NTD campaign delivery. Findings identifies key challenges due to disruptions to NTD program delivery and provide strategic recommendations for endemic countries to build resilient programs that can continue to perform during and beyond global pandemics. Author summary: In April 2020, global guidelines suspended mass drug administration (MDA) programs used in the control and elimination of neglected tropical diseases (NTDs) due to the ongoing COVID-19 pandemic. While the guidance aimed to reduce the risk of coronavirus exposure and transmission among stakeholders involved in MDA delivery and recipient community members, it risked impeding the gains made by MDA programs towards NTD control and elimination, leaving billions at risk of these infectious diseases. This study summarizes the perspectives of Ministry of Health NTD Program Managers and representatives from non-governmental organizations across sub-Saharan African working in NTDs regarding challenges imposed on MDA programs by the COVID-19 pandemic and identify opportunities to improve planning and implementation during the relaunch of MDA programs. Respondents noted key disruptions for MDA programs, including resource shortages, challenges adhering to COVID-19 safety protocols, and community hesitancy due to coronavirus transmission fears. Specific solutions for restarting MDA programs included adaptations to MDA strategies to incorporate safer, low-contact drug delivery techniques, incorporating technology to optimize MDA planning and delivery, and identifying opportunities to promote integration between NTD campaign delivery and pandemic response strategies. This paper includes suggestions for building resilient programs that can continue to perform in the face of public health emergencies. [ABSTRACT FROM AUTHOR]

Background: Urogenital schistosomiasis and HIV/AIDS infections are widespread in sub-Saharan Africa (SSA) leading to substantial morbidity and mortality. The co-occurrence of both diseases has led to the possible hypothesis that urogenital schistosomiasis leads to increased risk of acquiring HIV infection. However, the available evidence concerning this association is inconsistent. The aim of this study was to systematically review and quantitatively synthesize studies that investigated the association between urogenital schistosomiasis and HIV/AIDS infection. Methods: A systematic review basing on PRISMA guidelines was conducted. It is registered with PROSPERO, number CRD42018116648. We searched four databases, MEDLINE, EMBASE, Global Health and Global Index Medicus for studies investigating the association between urogenital schistosomiasis and HIV infection. Only studies published in English were considered. Results of the association were summarised by gender. A meta-analysis was performed for studies on females using random-effects model and a pooled OR with 95% confidence interval was reported. Results: Of the 993 studies screened, only eight observational studies met the inclusion criteria. Across all studies, the reported unadjusted OR ranged from 0.78 to 3.76. The pooled estimate of unadjusted OR among females was 1.31 (95% CI: 0.87–1.99). Only four of the eight studies reported an adjusted OR. A separate meta-analysis done in the three studies among females that reported an adjusted OR showed that the pooled estimate was 1.85 (95% CI: 1.17–2.92). There were insufficient data to pool results for association between urogenital schistosomiasis and HIV infection in the males. Conclusion: Our investigation supports the hypothesis of an association between urogenital schistosomiasis with HIV/AIDS infection in females. Due to insufficient evidence, no conclusion could be drawn in males with urogenital schistosomiasis. Large-scale prospective studies are needed in future. Author summary: Urogenital schistosomiasis, caused by parasitic trematode Schistosoma haematobium is a significant source of morbidity in sub Saharan Africa. HIV infection caused by a retrovirus is of two subtypes HIV 1 and HIV 2, with subtype HIV 1 being found worldwide and more aggressive, leading to HIV/AIDS. Research on both of these diseases in the same settings, has shown that these diseases cross paths. This has led to the suggestion that there could be a possible association between the two. Here we describe a systematic review that was carried out to determine if there is an association between UGS and HIV/AIDS infections. We searched all published articles available in MEDLINE, EMBASE, Global Health (CABI), and Global Index Medicus before 28th January 2020. We found eight observational studies eligible to be included in the systematic review and no intervention study. Six of these studies were included in the meta-analysis. A summarized meta-analysis of the study findings with adjusted OR showed that there was a likely association between urogenital schistosomiasis and HIV/AIDS infections in females. However, due to limited papers in males, no conclusion could be drawn. [ABSTRACT FROM AUTHOR]

Neglected Tropical Diseases (NTDs) remain endemic to many regions of sub-Saharan Africa (SSA) left behind by socioeconomic progress. As such, these diseases are markers of extreme poverty and inequity that are propagated by the political, economic, social, and cultural systems that affect health and wellbeing. As countries embrace and work towards achieving the Sustainable Development Goals (SDGs), the needs of such vulnerable populations need to be addressed in local and global arenas. The research uses primary qualitative data collected from five NTD endemic counties of Kenya: interviews key informants (n = 21) involved in NTD implementation programs and focus groups (n = 5) of affected individuals. Informed by theories of political ecology of health, the research focuses on post-devolution Kenya and identifies the political, economic, social, and cultural factors that propagate NTDs and their effects on health and wellbeing. Our findings indicate that structural factors such as competing political interests, health worker strikes, inadequate budgetary allocations, economic opportunity, marginalization, illiteracy, entrenched cultural norms and practices, poor access to water, sanitation and housing, all serve to propagate NTD transmission and subsequently affect the health and wellbeing of populations. As such, we recommend that post-devolution Kenya ensures local political, economic and socio-cultural structures are equitable, sensitive and responsive to the needs of all people. We also propose poverty alleviation through capacity building and empowerment as a means of tackling NTDs for sustained economic opportunity and productivity at the local and national level. Author summary: Wellbeing is currently seen as an avenue that shapes, happiness, productivity, environmental awareness, social inclusion, and justice; however, most countries presently adopting wellbeing measures are in the global north. Neglected Tropical Diseases (NTDs) significantly compromise populations' health and well-being in the global south, causing undesirable effects on the personal, social, and economic capabilities of communities living in endemic regions. As countries work towards achieving the Sustainable Development Goals (SDGs), it is paramount that countries in the global south adopt wellbeing measures and, in doing so, capture the lived experiences of individuals experiencing inequities, particularly as these are shaped by NTDs. In sub-Saharan Africa (SSA), political and economic power manifests across different scales, determining human-environmental interaction, distribution of resources, and the transmission of infectious agents. This paper uses a political ecology of health approach to identify the political, economic, social and cultural factors that contribute to NTDs, which are among the world's greatest global health problems. The vast majority of people bearing the burden of NTDs reside in low-income countries. Surprisingly, as the economies of the low-income countries improve to middle-income status, NTDs continue to thrive among sub-populations of low socioeconomic status because of the unequal distribution of economic gains. As a result, NTDs are found in environments characterized by poverty and income inequality, and other inequalities in access to health services, housing, safe water, and sanitation. This paper uses political ecology of health in the primarily biomedical field of NTDs to demonstrate that inequities are embedded within the broad political, socio-cultural, and economic systems that exacerbate NTD infection. The study recommends that NTD endemic countries in SSA formulate policies that enhance equity through capacity building and empowerment in order to enhance population wellbeing. [ABSTRACT FROM AUTHOR]

The neglected tropical diseases (NTDs) affect hundreds of millions of people, predominantly in rural, often difficult-to-access areas, poorly served by national health services. Here, we review the contributions of 4.8 million community-directed distributors (CDDs) of medicines over 2 decades in 146,000 communities in 27 sub-Saharan African countries to control or eliminate onchocerciasis and lymphatic filariasis (LF). We examine their role in the control of other NTDs, malaria, HIV/AIDS interventions, immunisation campaigns, and support to overstretched health service personnel. We are of the opinion that CDDs as community selected, trained, and experienced "foot soldiers," some of whom were involved in the Ebola outbreak responses at the community level in Liberia, if retrained, can assist community leaders and support health workers (HWs) in the ongoing Coronavirus Disease 2019 (COVID-19) crisis. The review highlights the improved treatment coverage where there are women CDDs, the benefits and lessons from the work of CDDs, their long-term engagement, and the challenges they face in healthcare delivery. It underscores the value of utilising the CDD model for strong community engagement and recommends the model, with some review, to hasten the achievement of the NTD 2030 goal and assist the health system cope with evolving epidemics and other challenges. We propose that, based on the unprecedented progress made in the control of NTDs directly linked to community engagement and contributions of CDDs "foot soldiers," they deserve regional and global recognition. We also suggest that the World Health Organization (WHO) and other international stakeholders promote policy and guidance for countries to adapt this model for the elimination of NTDs and to strengthen national health services. This will enhance the accomplishment of some Sustainable Development Goals (SDGs) by 2030 in sub-Saharan Africa. Author summary: Community-directed distributors (CDDs), sometimes known as community health workers (CHWs), have proved to be critical in the delivery of medicines and other tools for the control of neglected tropical diseases (NTDs), prevention of malaria, and other beneficial health interventions. The distributors are the unsung heroes and heroines without whom the health of hundreds of thousands of communities in rural Africa would be worse than it is today. In this paper, we document more than 2 decades (1997–2019) of the contributions of 146,000 communities and 4.8 million CDDs of medicines for NTDs, unpaid or minimally compensated, some have provided 18 years of uninterrupted service. We report on the burden of work and their perspectives of the challenges involved in mass drug administration (MDA) across 27 countries in sub-Saharan Africa. We suggest that they have not been adequately recognised and that harnessing such community human resources could contribute to improving health system's responses to the ongoing Coronavirus Disease 2019 (COVID-19) crisis. We recommend policy measures for a wider application of existing networks of CDDs by countries' health systems to consolidate and accelerate the achievements made as well as for the attainment of the goals set forth in the newly developed World Health Organization (WHO) NTD Roadmap. [ABSTRACT FROM AUTHOR]

Campylobacteriosis disproportionately affects children under five in low-income countries. However, epidemiological and antimicrobial resistance (AMR) information at the children-animal interface is lacking. We hypothesized that Campylobacter is a major cause of enteritis in children in Ethiopia, and contact with animals is a potential source of transmission. The objective of the study was to determine Campylobacter occurrence and its AMR in children under five with diarrhea, backyard farm animals, and companion pets. Stool from 303 children and feces from 711 animals were sampled. Campylobacter was isolated through membrane filtration on modified charcoal cefoperazone deoxycholate agar plates under microaerobic incubation, and the technique showed to be feasible for use in regions lacking organized laboratories. Typical isolates were characterized with MALDI-TOF MS and multiplex PCR. Of 303 children, 20% (n = 59) were infected, with a higher proportion in the 6 to 11-month age group. Campylobacter occurred in 64% (n = 14) of dogs and 44% (n = 112) of poultry. Campylobacter jejuni was present in both a child and animal species in 15% (n = 23) of 149 households positive for Campylobacter. MICs using the gradient strip diffusion test of 128 isolates displayed resistance rates of 20% to ciprofloxacin and 11% to doxycycline. MICs of ciprofloxacin and doxycycline varied between C. coli and C. jejuni, with higher resistance in C. coli and poultry isolates. Campylobacter infection in children and its prevalent excretion from backyard poultry and dogs is a understudied concern. The co-occurrence of C. jejuni in animals and children suggest household-level transmission As resistance to ciprofloxacin and doxycycline was observed, therapy of severe campylobacteriosis should consider susceptibility testing. Findings from this study can support evidence-based diagnosis, antimicrobial treatment, and further investigations on the spread of AMR mechanisms for informed One Health intervention. Author summary: Diarrheal diseases are the second-leading cause of death in children under five years, and Campylobacter is a major global causative agent. However, little attention is given to the accurate isolation, characterization, and AMR assessment of Campylobacter in sub-Saharan Africa. This region has the highest burden of diarrhea but a lack of organized laboratories. This study investigated the presence and AMR of Campylobacter in children and animals using methods with minimal technical challenge. We collected stool samples from 303 children at health centers and 711 animal feces samples from the children's homes in the vicinity of Bahir Dar, Ethiopia. Campylobacter were isolated using membrane filtration-culture. Presumptive isolates were characterized with molecular techniques in Belgium. Membrane filtration culture with a traditional microaerobic incubation system was successful in isolating viable Campylobacter from children with diarrhea and animals. Campylobacter is highly prevalent in children, backyard poultry, and dogs and has shown resistance to ciprofloxacin and doxycycline. The key findings of this study clearly show that Campylobacter infection in children and its occurrence in animals associated with children is a major public health problem. These findings are supportive of clinical decision-making and treatment. Findings from this study are also relevant as a validation of applying the membrane filtration-isolation technique for Campylobacter screening in low-income countries. [ABSTRACT FROM AUTHOR]

Background: Snakebite envenomation inflicts a high burden of mortality and morbidity in sub-Saharan Africa. Antivenoms are the mainstay in the therapy of envenomation, and there is an urgent need to develop antivenoms of broad neutralizing efficacy for this region. The venoms used as immunogens to manufacture snake antivenoms are normally selected considering their medical importance and availability. Additionally, their ability to induce antibody responses with high neutralizing capability should be considered, an issue that involves the immunization scheme and the animal species being immunized. Methodology/Principal findings: Using the lethality neutralization assay in mice, we compared the intrageneric neutralization scope of antisera generated by immunization of horses with monospecific, bispecific/monogeneric, and polyspecific/monogeneric immunogens formulated with venoms of Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp. or non-spitting Naja spp. It was found that the antisera raised by all the immunogens were able to neutralize the homologous venoms and, with a single exception, the heterologous congeneric venoms (considering spitting and non-spitting Naja separately). In general, the polyspecific antisera of Bitis spp, Echis spp, and Dendroaspis spp gave the best neutralization profile against venoms of these genera. For spitting Naja venoms, there were no significant differences in the neutralizing ability between monospecific, bispecific and polyspecific antisera. A similar result was obtained in the case of non-spitting Naja venoms, except that polyspecific antiserum was more effective against the venoms of N. melanoleuca and N. nivea as compared to the monospecific antiserum. Conclusions/Significance: The use of polyspecific immunogens is the best alternative to produce monogeneric antivenoms with wide neutralizing coverage against venoms of sub-Saharan African snakes of the Bitis, Echis, Naja (non-spitting) and Dendroaspis genera. On the other hand, a monospecific immunogen composed of venom of Naja nigricollis is suitable to produce a monogeneric antivenom with wide neutralizing coverage against venoms of spitting Naja spp. These findings can be used in the design of antivenoms of wide neutralizing scope for sub-Saharan Africa. Author summary: Parenteral administration of antivenoms is the core of the current treatment of snakebite envenomations, and there is an urgent need to produce antivenoms of wide neutralizing efficacy for sub-Saharan Africa. The active substance of antivenoms are antibodies (or antibody fragments) purified from plasma of horses or sheep immunized by the repeated injection of snake venoms. Generally, these antibodies can neutralize the venoms used as immunogens and other related venoms. Normally, the venoms used as immunogens are selected considering their medical importance and availability. To complement these criteria with information regarding the immunogenicity of venoms, we compared monospecific, bispecific/monogeneric, and polyspecific/monogeneric antisera towards venoms of Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp. or non-spitting Naja spp, regarding their intrageneric neutralization scope, evaluated by the lethality neutralization assay in mice. We found that the polyspecific antisera against venoms of Bitis spp, Echis spp, Dendroaspis spp, or non-spitting Naja gave the best neutralization profile. On the other hand, the monospecific, bispecific and polyspecific antisera towards venoms of spitting Naja venoms showed a similar performance. This information suggests that polyspecific immunogens could be the best alternative to produce antivenoms with the widest neutralizing coverage against sub-Saharan African snake venoms. [ABSTRACT FROM AUTHOR]

Background: Naja annulifera is a medically important venomous snake occurring in some of the countries in Sub-Saharan Africa. Accidental bites result in severe coagulation disturbances, systemic inflammation and heart damage, as reported in dogs, and death, by respiratory arrest, in humans. Despite the medical importance of N. annulifera, little is known about its venom composition and the pathogenesis of envenomation. In this paper, the toxic, inflammatory and immunogenic properties of N. annulifera venom were analyzed. Methodology/Principal findings: Venom proteomic analysis identified 79 different proteins, including Three Finger Toxins, Cysteine Rich Secretory Proteins, Metalloproteinases, Phospholipases A2 (PLA2), Hyaluronidase, L-amino-acid oxidase, Cobra Venom Factor and Serine Proteinase. The presence of PLA2, hyaluronidase, fibrinogenolytic and anticoagulant activities was detected using functional assays. The venom was cytotoxic to human keratinocytes. In an experimental murine model of envenomation, it was found that the venom induced local changes, such as swelling, which was controlled by anti-inflammatory drugs. Moreover, the venom caused death, which was preceded by systemic inflammation and pulmonary hemorrhage. The venom was shown to be immunogenic, inducing a strong humoral immune response, with the production of antibodies able to recognize venom components with high molecular weight and to neutralize its lethal activity. Conclusions/Significance: The results obtained in this study demonstrate that N. annulifera venom contains toxins able to induce local and systemic inflammation, which can contribute to lung damage and death. Moreover, the venom is immunogenic, an important feature that must be considered during the production of a therapeutic anti-N. annulifera antivenom. [ABSTRACT FROM AUTHOR]

Introduction: Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa (SSA) with Madagascar being among the countries with highest burden of the disease worldwide. Despite WHO recommendations, suggesting treatment of pregnant women after the first trimester, this group is still excluded from Mass Drug Administration programs. Our study, had the objective to measure the prevalence of schistosome infection among pregnant women in Madagascar in order to inform public health policies for treatment in this vulnerable population. Methods: Women were recruited for this cross-sectional study between April 2019 and February 2020 when attending Antenatal Care Services (ANCs) at one of 42 included Primary Health Care Centers. The urine-based upconverting reporter particle, lateral flow (UCP-LF) test detecting circulating anodic antigen was used for the detection of schistosome infections. To identify factors associated with the prevalence of schistosome infection crude and adjusted prevalence ratios and 95% CIs were estimated using mixed-effect Poisson regression. Results: Among 4,448 participating women aged between 16 and 47 years, the majority (70.4%, 38 n = 3,133) resided in rural settings. Overall, the prevalence of schistosome infection was 55.9% (n = 2486, CI 95%: 53.3–58.5). A statistically significant association was found with age group (increased prevalence in 31–47 years old, compared to 16–20 years old (aPR = 1.15, CI 95%: 1.02–1.29) and with uptake of antimalaria preventive treatment (decreased prevalence, aPR = 0.85, CI 95%: 0.77–0.95). No other associations of any personal characteristics or contextual factors with schistosome infection were found in our multivariate regression analysis. Discussion and conclusion: The high prevalence of schistosome infection in pregnant women supports the consideration of preventive schistosomiasis treatment in ANCs of the Malagasy highlands. We strongly advocate for adapting schistosomiasis programs in highly endemic contexts. This, would contribute to both the WHO and SDGs agendas overall to improving the well-being of women and consequently breaking the vicious cycle of poverty perpetuated by schistosomiasis. Author summary: Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa and in Madagascar, where pregnant women are systematically excluded from prevention and control strategies. Our study shows the urgency for adapting public health strategies. We report a high prevalence of schistosome infection among pregnant women in Madagascar. The lack of systematic treatment for this vulnerable group can have a direct impact on the well-being of women and their offspring contributing to the vicious cycle of poverty perpetuated by schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: With more than 1.2 million illnesses and 29,000 deaths in sub-Saharan Africa in 2017, typhoid fever continues to be a major public health problem. Effective control of the disease would benefit from an understanding of the subnational geospatial distribution of the disease incidence. Method: We collated records of the incidence rate of typhoid fever confirmed by culture of blood in Africa from 2000 to 2022. We estimated the typhoid incidence rate for sub-Saharan Africa on 20 km × 20 km grids by exploring the association with geospatial covariates representing access to improved water and sanitation, health conditions of the population, and environmental conditions. Results: We identified six published articles and one pre-print representing incidence rate estimates in 22 sites in 2000–2022. Estimated incidence rates showed geospatial variation at sub-national, national, and regional levels. The incidence rate was high in Western and Eastern African subregions followed by Southern and Middle African subregions. By age, the incidence rate was highest among 5–14 yo followed by 2–4 yo, > 14 yo, and 0–1 yo. When aggregated across all age classes and grids that comprise each country, predicted incidence rates ranged from 43.7 (95% confidence interval: 0.6 to 591.2) in Zimbabwe to 2,957.8 (95% CI: 20.8 to 4,245.2) in South Sudan per 100,000 person-years. Sub-national heterogeneity was evident with the coefficient of variation at the 20 km × 20 km grid-level ranging from 0.7 to 3.3 and was generally lower in high-incidence countries and widely varying in low-incidence countries. Conclusion: Our study provides estimates of 20 km × 20 km incidence rate of typhoid fever across sub-Saharan Africa based on data collected from 2000 through 2020. Increased understanding of the subnational geospatial variation of typhoid fever in Africa may inform more effective intervention programs by better targeting resources to heterogeneously disturbed disease risk. Author summary: Typhoid fever remains a significant health challenge in low- and middle-income nations, especially in sub-Saharan Africa. A comprehensive understanding of the disease's geospatial distribution is pivotal for its control—a gap previous studies overlooked. Addressing this, we undertook a study to chart the incidence of typhoid fever throughout sub-Saharan Africa. Using data from 2000 to 2022, we developed high-resolution maps with a granularity of 20 km by 20 km, detailing the spatial distribution of typhoid incidence. Our findings reveal pronounced disparities in typhoid incidence across different geospatial tiers: from local communities to entire nations and regions. Particularly, Western and Eastern Africa registered the highest incidences, with children aged 5–14 years being the most vulnerable. Distinctively, countries such as South Sudan reported alarmingly high figures, whereas Zimbabwe had notably fewer cases. Such insights are indispensable for health policymakers at local, national, and global levels. Pinpointing the areas hardest hit by typhoid allows for a more strategic allocation of resources and interventions. Armed with this data, we're better positioned to fight typhoid effectively and safeguard lives in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Introduction: Schistosomiasis is a significant public health concern, especially in Sub-Saharan Africa. Conventional microscopy is the standard diagnostic method in resource-limited settings, but with limitations, such as the need for expert microscopists. An automated digital microscope with artificial intelligence (Schistoscope), offers a potential solution. This field study aimed to validate the diagnostic performance of the Schistoscope for detecting and quantifying Schistosoma haematobium eggs in urine compared to conventional microscopy and to a composite reference standard (CRS) consisting of real-time PCR and the up-converting particle (UCP) lateral flow (LF) test for the detection of schistosome circulating anodic antigen (CAA). Methods: Based on a non-inferiority concept, the Schistoscope was evaluated in two parts: study A, consisting of 339 freshly collected urine samples and study B, consisting of 798 fresh urine samples that were also banked as slides for analysis with the Schistoscope. In both studies, the Schistoscope, conventional microscopy, real-time PCR and UCP-LF CAA were performed and samples with all the diagnostic test results were included in the analysis. All diagnostic procedures were performed in a laboratory located in a rural area of Gabon, endemic for S. haematobium. Results: In study A and B, the Schistoscope demonstrated a sensitivity of 83.1% and 96.3% compared to conventional microscopy, and 62.9% and 78.0% compared to the CRS. The sensitivity of conventional microscopy in study A and B compared to the CRS was 61.9% and 75.2%, respectively, comparable to the Schistoscope. The specificity of the Schistoscope in study A (78.8%) was significantly lower than that of conventional microscopy (96.4%) based on the CRS but comparable in study B (90.9% and 98.0%, respectively). Conclusion: Overall, the performance of the Schistoscope was non-inferior to conventional microscopy with a comparable sensitivity, although the specificity varied. The Schistoscope shows promising diagnostic accuracy, particularly for samples with moderate to higher infection intensities as well as for banked sample slides, highlighting the potential for retrospective analysis in resource-limited settings. Trial registration: NCT04505046 ClinicalTrials.gov. Author summary: Assessment of schistosomiasis control programs is a crucial step to understanding the success rate of these control programs. The Schistoscope: an AI-powered automated digital microscope could overcome the limitations of conventional microscopy in endemic resource limited settings as well as in settings lacking microscopy experts. In this study, we carried out an extensive validation of the Schistoscope's diagnostic performance for diagnosis of urogenital schistosomiasis compared to conventional microscopy as well as more accurate diagnostic tests such as real-time PCR and the up-converting particle (UCP) lateral flow (LF) test for the detection of circulating anodic antigen (CAA) on freshly collected urines. We also assessed the performance of the Schistoscope for the diagnosis of schistosomiasis on banked sample slides, using a simple and sustainable storage method, for approximately two years. Having a tool that can prospectively and retrospectively analyse samples in an easy and sustainable way could facilitate schistosomiasis control programs in settings with little or no access to microscopists. Overall, we found the Schistoscope to be as good as conventional microscopy for the diagnosis of schistosomiasis, and given its downstream advantages of digital health, it would serve as a valuable diagnostic/screening tool in resource limited endemic settings. [ABSTRACT FROM AUTHOR]

Snakebite envenomation (SBE) is endemic to sub-Saharan Africa and generally over-represented in rural, remote, and impoverished agricultural communities. While poverty is an established risk factor, little research has been done to investigate the economic consequences of SBE. This cross-sectional, quantitative study aimed to measure out-of-pocket spending and lost income when a household member was bitten by a snake. In 2020, 732 snakebite survivors from Eastern Province (Rwanda) agreed to complete a survey administered by telephone. The survey focused on participant demographics, income, direct medical and non-medical costs, care-seeking decisions, and lost work during convalescence. Our results suggested that patients incurred the highest mean expenses when they sought care from hospitals (11 307 RWF or 12 USD) or traditional healers (5 836 RWF or 6 USD) but that the highest maximum cost was incurred from traditional healers (300 000 RWF or 313 USD). Across all victims, the total amount paid to traditional healers (3.4 million RWF or 3 537 USD) was 4.7 times higher than all other care providers combined. On average, families lost 111 814 RWF (117 USD) per snakebite in direct treatment costs and indirect productivity losses. Many victims sought care from traditional healers despite being eligible for free medical care. Altogether, this study serves as a reminder of the serious physical and financial consequences associated with SBE and provides justification for new investments into SBE prevention and care. Author summary: Snakebite is a life-threatening situation in sub-Saharan Africa, especially for rural and poor populations. Despite being preventable and treatable, it receives little attention from policymakers. The goal of this study was to estimate the financial losses experienced by snakebite victims due to treatment costs and lost work. Interviews with 732 snakebite victims from Eastern Province, Rwanda, indicated that a typical adult lost 12.0% of their annual income due to a single bite. Moreover, caregivers lost time and income when caring for a sick family member. Patients preferentially sought care from traditional healers rather than Community Health Workers, nurses or physicians, even when they qualified for free hospital care. Consequently, victims in our study group paid five times more to traditional healers (3.4 million RWF or 3 537 USD) than to all other care providers combined. Altogether, our analysis suggests that Rwandese lose 7.4 million USD each year in treatment costs and lost work due to snakebite. These results serve as evidence to policymakers that investments to prevention and treatment programs will not only reduce pain and suffering, but also contribute to national goals targeting poverty reduction. [ABSTRACT FROM AUTHOR]

Background: Snakebites is a serious public health issue but remains a neglected tropical disease. Data on antivenom effectiveness are urgently needed in Africa. We assessed effectiveness of Inoserp PAN-AFRICA (IPA), the recommended antivenom available in Cameroon. Methodology/Principal findings: We enrolled 447 patients presenting with snakebite in 14 health facilities across Cameroon. At presentation, cytotoxicity, coagulation troubles and neurotoxicity were graded. We administered two to four vials of antivenom to patients based on hemotoxic or neurotoxic signs. We renewed antivenom administration to patients with persistence of bleedings or neurotoxicity 2 hours after each injection. We defined early improvement as a reduction of the grade of envenomation symptoms 2 hours after first injection. Medium-term effectiveness was investigated looking at disappearance of symptoms during hospitalization. After hospital discharge, a home visit was planned to assess long-term outcomes. Between October 2019 and May 2021, we enrolled 447 (93.7%), including 72% from the savannah regions. The median [IQR] age was 25 [14–40]. Envenomation was diagnosed in 369 (82.6%) participants. The antivenom was administered to 356 patients (96.5%) of whom 256 (71.9%) received one administration. Among these patients, cytotoxic symptoms were observed in 336 (94.4%) participants, coagulation disorders in 234 (65.7%) participants and neurotoxicity in 23 (6.5%) participants. Two hours after the first administration of antivenom, we observed a decrease in coagulation disorders or neurotoxicity in 75.2% and 39.1% of patients, respectively. Complete cessation of bleedings and neurotoxicity occurred in 96% and 93% of patients within 24 hours, respectively. Sequelae have been observed in 9 (3%) patients at the home visit 15 days after hospital admission and 11 (3%) died including one before antivenom injection. Conclusions/Significance: We confirmed good effectiveness of the IPA and highlighted the rapid improvement in bleeding or neurotoxicity after the first administration. Sequential administrations of low doses of antivenom, rigorously assessed at short intervals for an eventual renewal, can preserve patient safety and save antivenom. Trial registration: NCT03326492. Author summary: Snakebite envenomation is a public health issue in all sub-Saharan countries. Their management remains a challenge due to the high cost of antivenom and complex treatment-seeking behavior. The objective of this study was to evaluate the tolerance and effectiveness of a commonly used antivenom in Cameroon, in 14 sites representative of the diversity of common epidemiological situations in sub-Saharan Africa. The treatment protocol was that recommended by the Cameroonian Ministry of Health. We reported in the present manuscript results on antivenom effectiveness. Administration of IPA (at least two vials) was decided in all patients presenting with any symptoms of envenomation (cytotoxicity, bleeding, neurotoxicity) regardless of severity. Two to four vials of antivenom were administered to patients depending on whether they had coagulopathy or neurotoxic disorders, respectively. We repeated the administration of antivenom at the same dose to patients if hemorrhagic or neurotoxic signs persisted 2 hours after each injection. During 20 months, we examined 477 patients and enrolled 447 (94%). Three hundred fifty-six patients presenting envenomation signs have received at least one dose of antivenom. Envenomation was diagnosed in 369 (83%) participants, out of which, 9 (3%) kept sequelae of varying severity, and 11 (3%) died, including one before the antivenom injection. Cytotoxic symptoms were observed in 336 (94.4%) participants, coagulation disorders in 234 (65.7%) participants and neurotoxic syndrome in 23 (6.5%) participants. A single antivenom administration was performed for 256 (71.9%) patients. Two hours after the first administration of antivenom, coagulation disorders and neurotoxicity decreased in 75.2% and 39.1% of patients, respectively. Complete stop bleedings and neurotoxicity occurred in 96% and 93% of patients within 24 hours, respectively. We confirmed the good effectiveness of IPA and highlighted the rapid improvement in bleedings or neurotoxicity after its first administration. [ABSTRACT FROM AUTHOR]

Trypanosomatidae are a dangerous family of Euglenobionta parasites that threaten the health and economy of millions of people around the world. More precisely describing the population biology and reproductive mode of such pests is not only a matter of pure science, but can also be useful for understanding parasite adaptation, as well as how parasitism, specialization (parasite specificity), and complex life cycles evolve over time. Studying this parasite’s reproductive strategies and population structure can also contribute key information to the understanding of the epidemiology of associated diseases; it can also provide clues for elaborating control programs and predicting the probability of success for control campaigns (such as vaccines and drug therapies), along with emergence or re-emergence risks. Population genetics tools, if appropriately used, can provide precise and useful information in these investigations. In this paper, we revisit recent data collected during population genetics surveys of different Trypanosoma species in sub-Saharan Africa. Reproductive modes and population structure depend not only on the taxon but also on the geographical location and data quality (absence or presence of DNA amplification failures). We conclude on issues regarding future directions of research, in particular vis-à-vis genotyping and sampling strategies, which are still relevant yet, too often, neglected issues. [ABSTRACT FROM AUTHOR]

Background: Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and tetanus toxoid (TT). Methods and Findings: 450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their newborns were followed biannually to age 36 months and tested for absolute levels of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood (CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed. Three immunophenotype categories were compared: i) tolerant (those having Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii) sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB recall response to respective parasite antigen); or iii) unexposed (no evidence of maternal infection or CB recall response). Overall, 78.9% of mothers were infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm (33.8%). Antenatal maternal malaria, LF, and hookworm were independently associated with significantly lower Hib-specific IgG. Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination. Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib. Conclusions: There is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria in infants of mothers infected with malaria and/or helminths during pregnancy. These findings highlight the importance of control and prevention of parasitic infections among pregnant women. Author Summary: Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. Prenatal exposure to parasitic infections can generate several potential effects on fetal immune responses and affect functional antibody generation during subsequent vaccination. There is a paucity of data on the detrimental effects of chronic parasitic infections during pregnancy on the response to vaccine from birth to childhood. This paper highlights the overwhelming presence of helminth infection and malaria in pregnant women in rural Kenya. The study shows that the presence of single and multiple antenatal parasitic infections is associated with impaired infant IgG levels against Haemophilus influenzae (Hib) and diphtheria (DT) antigens post-vaccination from birth to 30 months of age. This study found that the response to DT was reduced in malaria-tolerized infants, and the response to Hib was impaired in filarial-tolerized infants; by contrast, the Schistosoma-tolerized group showed no effect. Deworming campaigns must be directed towards pregnant mothers, infants, and young children to improve response to vaccination. [ABSTRACT FROM AUTHOR]

Background: Entamoeba histolytica, Giardia, and Cryptosporidium are common intestinal protozoan parasites that contribute to a high burden of childhood morbidity and mortality. Our study quantified the association between intestinal protozoan parasites and child anthropometric outcomes among children under-5. Methods: We analyzed data from 7,800 children enrolled in the Global Enteric Multicenter Study (GEMS) across seven study sites that were positive for intestinal protozoan parasites between December 2007 and March 2011. Parasites were assessed using stool immunoassays (ELISA). We applied multiple linear regression to test the association between any or concurrent parasite and child anthropometric outcomes: length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-score after 60 days of enrollment. Models were stratified by diarrheal symptoms, driven by the study design, and adjusted for potential covariates. Findings: Among the asymptomatic children, negative associations were observed between Giardia with HAZ [β: -0.13; 95% CI: -0.17, -0.09; p<0.001] and WAZ [β -0.07; 95% CI: -0.11, -0.04; p<0.001], but not WHZ [β: -0.02; 95% CI:-0.06, 0.02; p = 0.36]; Cryptosporidium with WAZ [β: -0.15; 95% CI: -0.22, -0.09; p<0.001] and WHZ [β: -0.18; 95%CI: -0.25, -0.12; p<0.001], but not with HAZ [β: -0.03; 95% CI: -0.09, 0.04; p = 0.40]. For symptomatic children, no associations were found between Giardia and anthropometry; negative associations were found between Cryptosporidium with HAZ [β: -0.17; 95% CI: -0.23, -0.11; p<0.001], WAZ [β: -0.25; 95% CI: -0.31, -0.19; p<0.001] and WHZ [β: -0.23; 95% CI: -0.30, -0.17; p<0.001]. Among the asymptomatic 24–59 months children, Giardia had a negative association with HAZ [β: -0.09; 95% CI: -0.15, -0.04; p = 0.001]. No significant associations were found between E. histolytica with child growth. Conclusions: While some studies have found that Giardia is not associated with (or protective against) acute diarrhea, our findings suggest that it is associated with growth shortfall. This observation underscores the need for preventive strategies targeting enteric protozoan parasites among young children, to reduce the burden of childhood malnutrition. Author summary: Intestinal protozoan parasites such as Entamoeba histolytica, Giardia, and Cryptosporidium are significant causes of childhood morbidity and mortality. A study analyzed data from 7,800 children enrolled in the Global Enteric Multicenter Study (GEMS) across seven study sites who tested positive for these parasites using stool immunoassays. The study aimed to quantify the association between intestinal protozoan parasites and child anthropometric outcomes among children under the age of 5. The results of the study showed negative associations between Giardia and weight-for-age and length/height-for-age among asymptomatic children. Similarly, Cryptosporidium was negatively associated with weight-for-age and weight-for-length/height among asymptomatic children and with weight-for-age, weight-for-length/height, and length/height-for-age among symptomatic children. No significant associations were found between Entamoeba histolytica and child growth. The study findings suggest that while Giardia may not cause acute diarrhea, it is associated with growth shortfall among young children. These observations highlight the need for preventive strategies to target enteric protozoan parasites among young children to reduce the burden of childhood malnutrition. [ABSTRACT FROM AUTHOR]

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. Author Summary: Urogenital schistosomiasis, caused by schistosome blood flukes, infects more than 100 million people in sub-Saharan Africa. Current control efforts involve regularly treating all school-aged children with the drug praziquantel, which kills schistosome worms. Earlier work by our group suggests that protective immunity against schistosomes is mainly stimulated by dying worms, and that in the short term, praziquantel treatment boosts immunity through killing worms. The longer-term impact upon the development of protective immunity is unknown. In this paper, we used a mathematical model which was able to replicate short-term patterns of infection and antibody to predict the long-term changes in antibody and infection levels that would occur during and after a 5-year treatment programme. We found that the longevity of protective immunity was particularly influential. Short-lived protective immunity was associated with levels of protective antibody declining below pre-treatment levels in the long term, and also with an increase in measured infection levels (eggs in urine) to peak above pre-treatment levels after the treatment programme finished. Antibody declines and infection peaks post-treatment were also predicted if treatment programmes reduced schistosome transmission. These results highlight the possible negative consequences of ceasing mass treatment programmes once they have commenced. [ABSTRACT FROM AUTHOR]

Protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) are evolutionary conserved cell signalling enzymes that coordinate cell function. Here we have employed biochemical approaches using 'smart' antibodies and functional screening to unravel the importance of these enzymes to Schistosoma mansoni physiology. Various PKC and ERK isotypes were detected, and were differentially phosphorylated (activated) throughout the various S. mansoni life stages, suggesting isotype-specific roles and differences in signalling complexity during parasite development. Functional kinase mapping in adult worms revealed that activated PKC and ERK were particularly associated with the adult male tegument, musculature and oesophagus and occasionally with the oesophageal gland; other structures possessing detectable activated PKC and/or ERK included the Mehlis' gland, ootype, lumen of the vitellaria, seminal receptacle and excretory ducts. Pharmacological modulation of PKC and ERK activity in adult worms using GF109203X, U0126, or PMA, resulted in significant physiological disturbance commensurate with these proteins occupying a central position in signalling pathways associated with schistosome muscular activity, neuromuscular coordination, reproductive function, attachment and pairing. Increased activation of ERK and PKC was also detected in worms following praziquantel treatment, with increased signalling associated with the tegument and excretory system and activated ERK localizing to previously unseen structures, including the cephalic ganglia. These findings support roles for PKC and ERK in S. mansoni homeostasis, and identify these kinase groups as potential targets for chemotherapeutic treatments against human schistosomiasis, a neglected tropical disease of enormous public health significance. Author Summary: Parasitic blood flukes, also called schistosomes, cause human schistosomiasis, a neglected tropical disease and major public health problem in developing countries, especially sub-Saharan Africa. Sustainable control of schistosomiasis is difficult, mainly because the complex life cycle of the parasite involves a freshwater snail host, and the ability of the parasite to evade the immune response of the human host and to survive for many years. Little is yet known about the cellular mechanisms in schistosomes and how they regulate parasite homeostasis, development and behaviour. In this paper, the nature of intracellular signalling by protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) in schistosomes is studied and these proteins are found to be vital for the coordination of processes fundamental to parasite survival, such as muscular activity and reproductive function. Our results contribute to an understanding of molecular events regulating schistosome function and identify PKCs and ERKs as possible targets for the development of new chemotherapeutic treatments against schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: Human African trypanosomiasis is caused by infection with parasites of the Trypanosoma brucei species complex, and threatens over 70 million people in sub-Saharan Africa. Development of new drugs is hampered by the limitations of current rodent models, particularly for stage II infections, which occur once parasites have accessed the CNS. Bioluminescence imaging of pathogens expressing firefly luciferase (emission maximum 562 nm) has been adopted in a number of in vivo models of disease to monitor dissemination, drug-treatment and the role of immune responses. However, lack of sensitivity in detecting deep tissue bioluminescence at wavelengths below 600 nm has restricted the wide-spread use of in vivo imaging to investigate infections with T. brucei and other trypanosomatids. Methodology/Principal findings: Here, we report a system that allows the detection of fewer than 100 bioluminescent T. brucei parasites in a murine model. As a reporter, we used a codon-optimised red-shifted Photinus pyralis luciferase (PpyRE9H) with a peak emission of 617 nm. Maximal expression was obtained following targeted integration of the gene, flanked by an upstream 5′-variant surface glycoprotein untranslated region (UTR) and a downstream 3′-tubulin UTR, into a T. brucei ribosomal DNA locus. Expression was stable in the absence of selective drug for at least 3 months and was not associated with detectable phenotypic changes. Parasite dissemination and drug efficacy could be monitored in real time, and brain infections were readily detectable. The level of sensitivity in vivo was significantly greater than achievable with a yellow firefly luciferase reporter. Conclusions/Significance: The optimised bioluminescent reporter line described here will significantly enhance the application of in vivo imaging to study stage II African trypanosomiasis in murine models. The greatly increased sensitivity provides a new framework for investigating host-parasite relationships, particularly in the context of CNS infections. It should be ideally suited to drug evaluation programmes. Author Summary: Parasites of the Trypanosoma brucei species complex are the causative agents of human African trypanosomiasis. There is an urgent need for new drugs to treat this debilitating and potentially fatal infection, especially in its late stage, when parasites have entered the central nervous system. Factors which hamper drug development include the limitations of the current murine models for stage II disease. In vivo bioluminescence imaging is a non-invasive technique that can be used to monitor infections in real time and is a powerful new approach for studying drug effectiveness. However, application of this imaging technology to trypanosome infections has been restricted because of lack of sensitivity. In this paper, we have taken a major step to resolve this problem. The enhanced sensitivity in infected mice is based on the high level expression in trypanosomes of a "red-shifted" luciferase variant that greatly improves bioluminescence detection in deep tissue. The system which we have developed should be a widely applicable tool for providing new insights into the infection biology of T. brucei. [ABSTRACT FROM AUTHOR]

Background: There remains a lack of epidemiological data on the geographical distribution of trachoma to support global mapping and scale up of interventions for the elimination of trachoma. The Global Atlas of Trachoma (GAT) was launched in 2011 to address these needs and provide standardised, updated and accessible maps. This paper uses data included in the GAT to describe the geographical distribution and burden of trachoma in Africa. Methods: Data assembly used structured searches of published and unpublished literature to identify cross-sectional epidemiological data on the burden of trachoma since 1980. Survey data were abstracted into a standardised database and mapped using geographical information systems (GIS) software. The characteristics of all surveys were summarized by country according to data source, time period, and survey methodology. Estimates of the current population at risk were calculated for each country and stratified by endemicity class. Results: At the time of writing, 1342 records are included in the database representing surveys conducted between 1985 and 2012. These data were provided by direct contact with national control programmes and academic researchers (67%), peer-reviewed publications (17%) and unpublished reports or theses (16%). Prevalence data on active trachoma are available in 29 of the 33 countries in Africa classified as endemic for trachoma, and 1095 (20.6%) districts have representative data collected through population-based prevalence surveys. The highest prevalence of active trachoma and trichiasis remains in the Sahel area of West Africa and Savannah areas of East and Central Africa and an estimated 129.4 million people live in areas of Africa confirmed to be trachoma endemic. Conclusion: The Global Atlas of Trachoma provides the most contemporary and comprehensive summary of the burden of trachoma within Africa. The GAT highlights where future mapping is required and provides an important planning tool for scale-up and surveillance of trachoma control. Author Summary: In order to target resources and drugs to reach trachoma elimination targets by the year 2020, data on the burden of disease are required. Using prevalence data in African countries derived from the Global Atlas of Trachoma (GAT), the distribution of trachoma continues to be focused in East and West Sub-Saharan Africa, North Africa and a few endemic countries in Central Sub-Saharan Africa. Currently, 129.4 million people are estimated to live in areas that are confirmed to be trachoma endemic and 98 million are known to require access to the SAFE strategy. The maps and information presented in this work highlight the GAT as important open-access planning and advocacy tool for efforts to finalize trachoma mapping and assist national programmes in planning interventions. [ABSTRACT FROM AUTHOR]

There has been little evidence of a decline in the global burden of cholera in recent years as the number of cholera cases reported to WHO continues to rise. Cholera remains a global threat to public health and a key indicator of lack of socioeconomic development. Overall socioeconomic development is the ultimate solution for control of cholera as evidenced in developed countries. However, most research has focused on cross-county comparisons so that the role of individual- or small area-level socioeconomic status (SES) in cholera dynamics has not been carefully studied. Reported cases of cholera in Matlab, Bangladesh have fluctuated greatly over time and epidemic outbreaks of cholera continue, most recently with the introduction of a new serotype into the region. The wealth of longitudinal data on the population of Matlab provides a unique opportunity to explore the impact of socioeconomic status and other demographic characteristics on the long-term temporal dynamics of cholera in the region. In this population-based study we examine which factors impact the initial number of cholera cases in a bari at the beginning of the 0139 epidemic and the factors impacting the number of cases over time. Cholera data were derived from the ICDDR,B health records and linked to socioeconomic and geographic data collected as part of the Matlab Health and Demographic Surveillance System. Longitudinal zero-inflated Poisson (ZIP) multilevel regression models are used to examine the impact of environmental and socio-demographic factors on cholera counts across baris. Results indicate that baris with a high socioeconomic status had lower initial rates of cholera at the beginning of the 0139 epidemic (γ01 = −0.147, p = 0.041) and a higher probability of reporting no cholera cases (α01 = 0.156, p = 0.061). Populations in baris characterized by low SES are more likely to experience higher cholera morbidity at the beginning of an epidemic than populations in high SES baris. Author Summary: Cholera is a bacterial disease usually spread through contaminated water that causes severe diarrhea and dehydration. Modern sewage and water treatment have virtually eliminated cholera in industrialized countries but cholera is still present throughout much of SE Asia, Latin America and sub-Saharan Africa. One of the reasons cholera is still problematic is that genetically distinct forms of the bacteria (often called biotypes) have developed and spread rapidly because the population has no natural immunity to the new biotype. In Bangladesh, the 0139 biotype developed in 1993 and caused a large epidemic. Although it is widely accepted that poor conditions place people at risk for cholera, very few studies have examine what role low socioeconomic status plays in cholera risk, especially during a new epidemic of the disease. In this paper, we explore how local-level socioeconomic status, measured using assets, education and sanitation, affect the severity of the cholera outbreak experienced during the O139 epidemic in Matlab, Bangladesh. We believe our study highlights the importance of improving overall socioeconomic status, not just sanitation and water treatment, in controlling the spread of cholera. [ABSTRACT FROM AUTHOR]

Background: The worldwide neglect of immunotherapeutic products for the treatment of snakebite has resulted in a critical paucity of effective, safe and affordable therapy in many Third World countries, particularly in Africa. Snakebite ranks high among the most neglected global health problems, with thousands of untreated victims dying or becoming permanently maimed in developing countries each year because of a lack of antivenom—a treatment that is widely available in most developed countries. This paper analyses the current status of antivenom production for sub-Saharan African countries and provides a snapshot of the global situation. Methods: A global survey of snake antivenom products was undertaken in 2007, involving 46 current and former antivenom manufacturers. Companies producing antivenom for use in sub-Saharan Africa were re-surveyed in 2010 and 2011. Results: The amount of antivenom manufactured for sub-Saharan Africa increased between 2007 and 2010/11, however output and procurement remained far below that required to treat the estimated 300,000–500,000 snakebite victims each year. Variable potency and inappropriate marketing of some antivenoms mean that the number of effective treatments available may be as low as 2.5% of projected needs. Five companies currently market antivenom for sale in Africa; three others have products in the final stages of development; and since 2007 one has ceased production indefinitely. Most current antivenom producers possess a willingness and capacity to raise output. However inconsistent market demand, unpredictable financial investment and inadequate quality control discourage further production and threaten the viability of the antivenom industry. Conclusion: Financial stimulus is urgently needed to identify and develop dependable sources of high-grade antivenoms, support current and emerging manufacturers, and capitalise on existing unutilised production capacity. Investing to ensure a consistent and sustainable marketplace for efficacious antivenom products will drive improvements in quality, output and availability, and save thousands of lives each year. Author Summary: Antivenom is the only specific treatment for systemic envenoming from snakebite, but remains unavailable to thousands of snakebite victims around the world. A cycle of inconsistent and low market demand, sub-optimal utilisation, rising costs and reduced output of antivenoms have resulted from long term under-investment in procurement and quality regulatory programs. This study provides a contemporary overview of the African antivenom market within the context of the global market. Globally, 35 companies sold at least 4 million vials of antivenom in 2007. Five companies had established African antivenom markets in 2010/11; three other institutions have antivenoms for Africa in development; and another ceased production indefinitely. Between 2007 and 2011, production of sub-Saharan African antivenoms rose from 227,400 to at least 377,500 vials, constituting ∼83,000 effective treatments for moderate envenomings. However, recent reports have identified that some products, which comprise up to 90% of the total antivenom supply in sub-Saharan Africa, may lack efficacy or specificity against relevant snake species. Despite this, revenues from antivenom marketed in sub-Saharan Africa increased from $6.6 million in 2007 to $10.3 million in 2010/11. The average cost of a stated effective treatment in 2010/11 was $124, and the price of antivenom is inversely proportional to the amount produced. Combined unutilised production capacity far exceeds the total projected antivenom needs for Africa. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases, including diseases caused by trypanosomatid parasites such as Trypanosoma brucei, cost tens of millions of disability-adjusted life-years annually. As the current treatments for African trypanosomiasis and other similar infections are limited, new therapeutics are urgently needed. RNA Editing Ligase 1 (REL1), a protein unique to trypanosomes and other kinetoplastids, was identified recently as a potential drug target. Methodology/Principal Findings: Motivated by the urgent need for novel trypanocidal therapeutics, we use an ensemble-based virtual-screening approach to discover new naphthalene-based TbREL1 inhibitors. The predicted binding modes of the active compounds are evaluated within the context of the flexible receptor model and combined with computational fragment mapping to determine the most likely binding mechanisms. Ultimately, four new low-micromolar inhibitors are presented. Three of the four compounds may bind to a newly revealed cleft that represents a putative druggable site not evident in any crystal structure. Conclusions/Significance: Pending additional optimization, the compounds presented here may serve as precursors for future novel therapies useful in the fight against several trypanosomatid pathogens, including human African trypanosomiasis, a devastating disease that afflicts the vulnerable patient populations of sub-Saharan Africa. Author Summary: African sleeping sickness is a devastating disease that plagues sub-Saharan Africa. Neglected tropical diseases like African sleeping sickness cause significant death and suffering in the world's poorest countries. Current treatments for African sleeping sickness either have high costs, terrible side effects, or limited effectiveness. Consequently, new medicines are urgently needed. RNA editing ligase 1 is an important protein critical for the survival of Trypanosoma brucei, the unicellular parasite that causes African sleeping sickness. In this paper, we describe our recent efforts to use advanced computer techniques to identify chemicals predicted to prevent RNA editing ligase 1 from functioning properly. We subsequently tested our predicted chemicals and confirmed that a number of them inhibited the protein's function. Additionally, one of the chemicals was effective at stopping the growth of the parasite in culture. Although substantial work remains to be done in order to optimize these chemicals so they are effective and safe to use in human patients, the identification of these parasite-killing compounds is nevertheless a valuable step towards finding a better cure for this devastating disease. [ABSTRACT FROM AUTHOR]

Background: Recently, a number of Global Health Initiatives (GHI) have been created to address single disease issues in low-income countries, such as poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the effects of such GHIs on local health systems remains scarce. This paper explores positive and negative effects of the Integrated Neglected Tropical Disease (NTD) Control Initiative, consisting in mass preventive chemotherapy for five targeted NTDs, on Mali's health system where it was first implemented in 2007. Methods and Findings: Campaign processes and interactions with the health system were assessed through participant observation in two rural districts (8 health centres each). Information was complemented by interviews with key informants, website search and literature review. Preliminary results were validated during feedback sessions with Malian authorities from national, regional and district levels. We present positive and negative effects of the NTD campaign on the health system using the WHO framework of analysis based on six interrelated elements: health service delivery, health workforce, health information system, drug procurement system, financing and governance. At point of delivery, campaign-related workload severely interfered with routine care delivery which was cut down or totally interrupted during the campaign, as nurses were absent from their health centre for campaign-related activities. Only 2 of the 16 health centres, characterized by a qualified, stable and motivated workforce, were able to keep routine services running and to use the campaign as an opportunity for quality improvement. Increased workload was compensated by allowances, which significantly improved staff income, but also contributed to divert attention away from core routine activities. While the campaign increased the availability of NTD drugs at country level, parallel systems for drug supply and evaluation requested extra efforts burdening local health systems. The campaign budget barely financed institutional strengthening. Finally, though the initiative rested at least partially on national structures, pressures to absorb donated drugs and reach short-term coverage results contributed to distract energies away from other priorities, including overall health systems strengthening. Conclusions: Our study indicates that positive synergies between disease specific interventions and nontargeted health services are more likely to occur in robust health services and systems. Disease-specific interventions implemented as parallel activities in fragile health services may further weaken their responsiveness to community needs, especially when several GHIs operate simultaneously. Health system strengthening will not result from the sum of selective global interventions but requires a comprehensive approach. Author Summary: Prevention of neglected tropical diseases was recently significantly scaled up in sub-Saharan Africa, protecting entire populations with mass distribution of drugs: five different diseases are now addressed simultaneously with a package of four drugs. Some argue however that, similarly to other major control programs dealing with specific diseases, this NTD campaign fails to strengthen health systems and might even negatively affect regular care provision. In 2007, we conducted an exploratory field study in Mali, observing how the program was implemented in two rural areas and how it affected the health system. At the local level, we found that the campaign effects of care delivery differed across health services. In robust and well staffed health centres, the personnel successfully facilitated mass drug distribution while running routine consultations, and overall service functioning benefitted from programme resources. In more fragile health centres however, additional program workload severely disturbed access to regular care, and we observed operational problems affecting the quality of mass drug distribution. Strong health services appeared to be profitable to the NTD control program as well as to general care. [ABSTRACT FROM AUTHOR]

There are remarkably few contemporary, population-based studies of intestinal nematode infection for sub-Saharan Africa. This paper presents a comprehensive epidemiological analysis of hookworm infection intensity in a rural Ugandan community. Demographic, kinship, socioeconomic and environmental data were collected for 1,803 individuals aged six months to 85 years in 341 households in a cross-sectional community survey. Hookworm infection was assessed by faecal egg count. Spatial variation in the intensity of infection was assessed using a Bayesian negative binomial spatial regression model and the proportion of variation explained by host additive genetics (heritability) and common domestic environment was estimated using genetic variance component analysis. Overall, the prevalence of hookworm was 39.3%, with the majority of infections (87.7%) of light intensity (≤1000 eggs per gram faeces). Intensity was higher among older individuals and was associated with treatment history with anthelmintics, walking barefoot outside the home, living in a household with a mud floor and education level of the household head. Infection intensity also exhibited significant household and spatial clustering: the range of spatial correlation was estimated to be 82 m and was reduced by a half over a distance of 19 m. Heritability of hookworm egg count was 11.2%, whilst the percentage of variance explained by unidentified domestic effects was 17.8%. In conclusion, we suggest that host genetic relatedness is not a major determinant of infection intensity in this community, with exposure-related factors playing a greater role. Author Summary: Detailed descriptions of the epidemiology of intestinal nematode infections within affected communities remain of considerable importance for the effective design of disease control programmes. We therefore conducted a parasitological survey of 1,803 individuals living in a rural community in eastern Uganda. Two complementary analytical approaches were used to evaluate causes of variation in intensity of hookworm infection in this community, both of which exploit correlation structures between individuals. Infection intensity was higher among older individuals and was also associated with factors influencing environmental exposure to infection, socio-economic indicators and treatment history. After accounting for these risk factors, spatial correlation remained evident between households less than 82m apart. Focusing further on similarities within households, our results suggest that 11% of variation in infection intensity could be explained by genetic differences between individuals and 18% by unmeasured factors associated with the domestic environment. Taken together, these results suggest that exposure-related factors, rather than host genetics, have the greatest influence on variation in infection intensities. [ABSTRACT FROM AUTHOR]

Although studies on African Trypanosomiases revealed a variety of trypanosome species in the blood of various animal taxa, animal reservoirs of Trypanosoma brucei gambiense and anatomical niches such as skin have been overlooked in most epidemiological settings. This study aims to update epidemiological data on trypanosome infections in animals from human African trypanosomiasis (HAT) foci of Cameroon. Blood and skin snips were collected from 291 domestic and wild animals. DNA was extracted from blood and skin snips and molecular approaches were used to identify different trypanosomes species. Immunohistochemical analyses were used to confirm trypanosome infections in skin snips. PCR revealed 137 animals (47.1%) with at least one trypanosome species in the blood and/or in the skin. Of these 137 animals, 90 (65.7%) and 32 (23.4%) had trypanosome infections respectively in the blood and skin. Fifteen (10.9%) animals had trypanosome infections in both blood and skin snip. Animals from the Campo HAT focus (55.0%) were significantly (X2 = 17.6; P< 0.0001) more infected than those (29.7%) from Bipindi. Trypanosomes of the subgenus Trypanozoon were present in 27.8% of animals while T. vivax, T. congolense forest type and savannah type were detected in 16.5%, 10.3% and 1.4% of animals respectively. Trypanosoma b. gambiense infections were detected in the blood of 7.6% (22/291) of animals. No T. b. gambiense infection was detected in skin. This study highlights the presence of several trypanosome species in the blood and skin of various wild and domestic animals. Skin appeared as an anatomical reservoir for trypanosomes in animals. Despite methodological limitations, pigs, sheep, goats and wild animals were confirmed as potential reservoirs of T. b. gambiense. These animal reservoirs must be considered for the designing of control strategies that will lead to sustainable elimination of HAT. Author summary: Human African Trypanosomiasis (HAT) is a neglected tropical disease affecting some sub-Saharan Africa countries. Although HAT elimination can be considered as achieved in some foci, the interruption of its transmission by 2030 remains a challenge. Animal reservoir and skin-dwelling trypanosomes have emerged as factors that can compromise sustainable elimination of HAT. It is in this light that T. b. gambiense infections and different trypanosome species were identified in blood and skin of domestic and wild animals from two HAT foci of the forest region of Cameroon. For this study, blood and skin snip samples were collected from domestic and wild animals. Molecular tools were used to identify different trypanosome species. Several trypanosome species including trypanosomes of the subgenus Trypanozoon, T. vivax and T. congolense were detected in the blood and skin of several animal taxa. Immuno-histochemical tools confirmed trypanosome infections in the skin. Pigs, sheep, goats and wild animals were confirmed as potential animal reservoirs of T. b. gambiense. Results of this study highlighted the necessity of considering animal reservoirs as well as skin-dwelling trypanosomes in the designing of new control strategies that will lead to the interruption of HAT transmission by 2030. [ABSTRACT FROM AUTHOR]

Cysticercosis is a neglected tropical disease caused by the larval stage of the zoonotic tapeworm (Taenia solium). While there is a clear spatial component in the occurrence of the parasite, no geostatistical analysis of active human cysticercosis has been conducted yet, nor has such an analysis been conducted for Sub-Saharan Africa, albeit relevant for guiding prevention and control strategies. The goal of this study was to conduct a geostatistical analysis of active human cysticercosis, using data from the baseline cross-sectional component of a large-scale study in 60 villages in Burkina Faso. The outcome was the prevalence of active human cysticercosis (hCC), determined using the B158/B60 Ag-ELISA, while various environmental variables linked with the transmission and spread of the disease were explored as potential explanatory variables for the spatial distribution of T. solium. A generalized linear geostatistical model (GLGM) was run, and prediction maps were generated. Analyses were conducted using data generated at two levels: individual participant data and grouped village data. The best model was selected using a backward variable selection procedure and models were compared using likelihood ratio testing. The best individual-level GLGM included precipitation (increasing values were associated with an increased odds of positive test result), distance to the nearest river (decreased odds) and night land temperature (decreased odds) as predictors for active hCC, whereas the village-level GLGM only retained precipitation and distance to the nearest river. The range of spatial correlation was estimated at 45.0 [95%CI: 34.3; 57.8] meters and 28.2 [95%CI: 14.0; 56.2] km for the individual- and village-level datasets, respectively. Individual- and village-level GLGM unravelled large areas with active hCC predicted prevalence estimates of at least 4% in the south-east, the extreme south, and north-west of the study area, while patches of prevalence estimates below 2% were seen in the north and west. More research designed to analyse the spatial characteristics of hCC is needed with sampling strategies ensuring appropriate characterisation of spatial variability, and incorporating the uncertainty linked to the measurement of outcome and environmental variables in the geostatistical analysis. Trial registration: ClinicalTrials.gov; NCT0309339. Author summary: Cysticercosis is a serious, yet neglected disease caused by the larval stage of a zoonotic tapeworm, prevalent in many developing countries, including Burkina Faso. Being able to predict where the disease occurs is essential for running targeted prevention and control activities. In our study, we aimed to describe whether human cysticercosis cases in three provinces in Burkina Faso were clustered, and investigated whether there was a link between this clustering and some land and weather variables. Finally, we aimed to generate high-resolution prediction maps for the occurrence of the infection. We found that there was clustering at 45 meters for the individual- and 28.2 km for the village-level datasets, respectively. Increasing rainfall and proximity to a river were linked with this clustering. The generated prediction maps indicated there were important cysticercosis hotspots in the study area, especially in the extreme south and north-west, where the disease is thought to be more important. Further research should expand the use of spatial techniques to predict the occurrence of cysticercosis, the results of which can aid in the design of intervention programmes. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis and hookworm infection remain public health problems in large parts of sub-Saharan Africa. The epidemiology of schistosomiasis and hookworm was studied in seasonal transmission settings in the northern part of Côte d'Ivoire. Methodology: In August 2018, a cross-sectional study was conducted. Urine and stool samples were collected from 742 individuals aged 6–96 years in 16 localities from four departments in northern Côte d'Ivoire. Urine samples were examined by a filtration method for quantification of Schistosoma haematobium eggs. Stool samples were subjected to duplicate Kato-Katz thick smears and eggs of Schistosoma mansoni and soil-transmitted helminths (STHs) were counted. Additionally, a questionnaire was administered to determine demographic characteristics and to identify risk factors of schistosomiasis and STHs. Malacologic surveys were carried out at water points that are contacted by humans and animals. Principal findings: The prevalence of schistosomiasis was very low. Only two cases of S. mansoni were found (0.3%, 95% confidence interval [CI]: 0.1–1.0%). The distribution of S. haematobium was focal, with cases found only in two departments; Ferkessédougou (5.4%, 95% CI: 2.5–9.9%) and Ouangolodougou (2.7%, 95% CI: 0.9–6.3%). Hookworm was the only STH species observed with a prevalence of 1.5% (95% CI: 0.8–2.8%). A higher risk of S. haematobium infection was observed in males compared to females, but the difference was not statistically significant (2.3% versus 1.3%, odds ratio [OR]: 1.5, 95% CI: 0.8–2.7). Participants aged 16–20 years showed the highest prevalence of S. haematobium. A total of 111 human- and animal-water contact points were identified at 47 water sources. Three potential intermediate host snails of schistosomes were collected; namely, Bulinus forskalii (n = 761), Bulinus truncatus (n = 205), and Biomphalaria pfeifferi (n = 1). Yet, only one specimen of Bu. truncatus was found to be shedding schistosome cercariae. Conclusions/Significance: This study confirms very low transmission of schistosomiasis and hookworm in northern Côte d'Ivoire. The establishment and rigorous implementation of integrated surveillance-response systems could lead to the elimination of schistosomiasis and hookworm in this part of Côte d'Ivoire. Author summary: Schistosomiasis and soil-transmitted helminthiasis, the latter including, hookworms, roundworms, and whipworms, are the most widespread parasitic neglected tropical diseases. As is the case in many sub-Saharan African countries, schistosomiasis and soil-transmitted helminthiasis are endemic in Côte d'Ivoire. Mass drug administration is the mainstay of the global control strategy against schistosomiasis and soil-transmitted helminthiasis and has been implemented in Côte d'Ivoire since 2013. The new road map put forward by the World Health Organization (WHO) for the control of neglected tropical diseases aims to eliminate schistosomiasis and soil-transmitted helminthiasis as a public health problem by 2030. In light of WHO's goals, this study updates prevalence data for schistosomiasis and soil-transmitted helminthiasis and provides a deeper understanding of risk factors that drive transmission in the northern part of Côte d'Ivoire. The findings showed very low prevalence and transmission of schistosomiasis and hookworm. Participants aged 16–20 years and fishermen had the highest prevalence of urogenital schistosomiasis, with both males (2.3%) and females (1.3%) at risk of infection. The results corroborate findings from other investigations in sub-Saharan Africa, which confirm that current efforts to control schistosomiasis and soil-transmitted helminthiasis are successful. Nevertheless, further investment is still needed to reach elimination. In particular, a surveillance-response system would be a valuable tool in a low-prevalence context such as northern Côte d'Ivoire. [ABSTRACT FROM AUTHOR]

Introduction: Estimates suggest that one-third of snakebite cases in sub-Saharan Africa affect children. Despite children being at a greater risk of disability and death, there are limited published data. This study has determined the: population-incidence and mortality rate of hospital-attended paediatric snakebite; clinical syndromes of snakebite envenoming; and predictors of severe local tissue damage. Methods: All children presenting to Kilifi County Hospital, Kenya with snakebite were identified through the Kilifi Health and Demographic Surveillance System (KHDSS). Cases were prospectively registered, admitted for at least 24-hours, and managed on a paediatric high dependency unit (HDU). Households within the KHDSS study area have been included in 4-monthly surveillance and verbal autopsy, enabling calculation of population-incidence and mortality. Predictors of severe local tissue damage were identified using a multivariate logistic regression analysis. Results: Between 2003 and 2021, there were 19,606 admissions to the paediatric HDU, of which 584 were due to snakebite. Amongst young children (≤5-years age) the population-incidence of hospital-attended snakebite was 11.3/100,000 person-years; for children aged 6–12 years this was 29.1/100,000 person-years. Incidence remained consistent over the study period despite the population size increasing (98,967 person-years in 2006; and 153,453 person-years in 2021). Most cases had local envenoming alone, but there were five snakebite associated deaths. Low haemoglobin; raised white blood cell count; low serum sodium; high systolic blood pressure; and an upper limb bite-site were independently associated with the development of severe local tissue damage. Conclusion: There is a substantial burden of disease due to paediatric snakebite, and the annual number of cases has increased in-line with population growth. The mortality rate was low, which may reflect the species causing snakebite in this region. The identification of independent predictors of severe local tissue damage can help to inform future research to better understand the pathophysiology of this important complication. Author summary: The nature of disease caused by snakebite amongst children in rural Africa is poorly understood. All children presenting to Kilifi County Hospital, Kenya with snakebite between 2003 and 2021 were recruited into a study that was nested in an ongoing hospital and community surveillance study. 584 children presented following snakebite and the incidence was 29.1/100,000 person-years amongst children aged 6–12 years. The incidence remained consistent over the course of the study despite the population increasing by over 50%, highlighting that the burden of disease is increasing in-line with population growth. Many children initially sought traditional therapies, which was associated with delayed presentation to hospital. The mortality rate was low, and most children had local, rather than systemic, envenoming. Predictors of severe local envenoming at the time of admission included a high white blood cell count, low haemoglobin, and an upper limb bite site. The findings of this study highlight the need to strengthen strategies to prevent snakebite in children, to overcome barriers to attending hospital, and to develop therapeutics that better treat local envenoming. [ABSTRACT FROM AUTHOR]

Background: Female Genital Schistosomiasis (FGS) is a neglected disease of the genital tract due to the inflammatory response to the presence of Schistosoma haematobium eggs in the genital tract. The WHO has prioritized the improvement of diagnostics for FGS and previous studies have explored the PCR-based detection of Schistosoma DNA on genital specimens, with encouraging results. This study aimed to determine the prevalence of FGS among women living in an endemic district in North-western Tanzania, using PCR on samples collected though cervical-vaginal swabs, and to compare the performance of self-collected and healthcare worker–collected (operator-collected) samples, and the acceptability of the different sampling methods. Methods/Principal findings: A cross-sectional study was conducted involving 211 women living in 2 villages in the Maswa district of North-western Tanzania. Urine, self-collected and operator-collected cervical-vaginal swabs were obtained from participants. A questionnaire was administered, focusing on the comfortability in undergoing different diagnostic procedures. Prevalence of urinary schistosomiasis, as assessed by eggs in urine, was 8.5% (95%CI 5.1–13.1). DNA was pre-isolated from genital swabs and transported at room temperature to Italy for molecular analysis. Prevalence of active schistosomiasis, urinary schistosomiasis, and FGS were 10.0% (95% CI 6.3–14.8), 8.5% (95%CI 5.1–13.1), and 4.7% (95%CI 2.3–8.5), respectively. When real-time PCR was performed after a pre-amplification step, the prevalence of active schistosomiasis increased to 10.4% (95%CI 6.7–15.4), and FGS to 5.2% (95%CI 2.6–9.1). Of note, more cases were detected by self-collected than operator-collected swabs. The vast majority of participants (95.3%) declared that they were comfortable/very comfortable about genital self-sampling, which was indicated as the preferred sampling method by 40.3% of participants. Conclusions/Significance: The results of this study show that genital self-sampling followed by pre-amplified PCR on room temperature-stored DNA is a useful method from both technical and acceptability point of views. This encourages further studies to optimize samples processing, and identify the best operational flow to allow integration of FGS screening into women health programmes, such as HPV screening. Author summary: Female Genital Schistosomiasis (FGS) is a severe debilitating disease of the female genital tract, caused by infection with Schistosoma haematobium, the agent of urogenital schistosomiasis. It is estimated that FGS affects 20–56 million girls and women, especially in sub-Saharan Africa. The diagnosis of FGS is currently difficult, and this disease often remains undiagnosed or is misdiagnosed as sexually transmitted diseases or genital cancer, with dramatic health and social consequences for the affected women. The WHO has prioritized the improvement of diagnostics for FGS. In this study, we applied and compared the performance of two genital sampling methods (self-collected and healthcare worker (operator)-collected cervical-vaginal swab) followed by molecular analysis, and assessed their comparative acceptability among 211 women living in a S. haematobium endemic district in North-western Tanzania. We found that not only self-collection by genital swab was well accepted, and actually the preferred sampling method for a high proportion of participants, but that PCR had higher sensitivity when applied to self-collected samples as compared to operator-collected swabs. Furthermore, we used room temperature-stored DNA, which offered greater ease of sample preservation and transportation after extraction. This encourages further studies to optimize samples processing and identify the best operational flow to allow integration of FGS screening into women health programmes, such as HPV screening. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis. Methods and findings: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with two oral doses of ivermectin (150 μg/kg) separated by at least 6 months prior to treatment with either a single oral dose of ivermectin 150 μg/kg plus albendazole 400 mg (IA), a single oral dose of IDA (IDA1, IA plus diethylcarbamazine (DEC. 6 mg/kg) or three consecutive daily doses of IDA (IDA3). These treatments were tolerated equally well. While adverse events were common (approximately 30% overall), no severe or serious treatment-emergent adverse events were observed. Skin microfilariae were absent or present with very low densities after all three treatments through 18 months, at which time nodules were excised for histological assessment. Nodule histology was evaluated by two independent assessors who were masked regarding participant infection status or treatment assignment. Significantly lower percentages of female worms were alive and fertile in nodules recovered from study participants after IDA1 (40/261, 15.3%) and IDA3 (34/281, 12.1%) than after IA (41/180, 22.8%). This corresponds to a 40% reduction in the percentage of female worms that were alive and fertile after IDA treatments relative to results observed after the IA comparator treatment (P = 0.004). Percentages of female worms that were alive (a secondary outcome of the study) were also lower after IDA treatments (301/574, 52.4%) than after IA (127/198, 64.1%) (P = 0.004). Importantly, some comparisons (including the reduced % of fertile female worms after IDA1 vs IA treatment, which was the primary endpoint for the study) were not statistically significant when results were adjusted for intraclass correlation of worm fertility and viability for worms recovered from individual study participants. Conclusions: Results from this pilot study suggest that IDA was well tolerated after ivermectin pretreatment. They also suggest that IDA was more effective than the comparator treatment IA for killing or sterilizing female O. volvulus worms. No other short-course oral treatment for onchocerciasis has been demonstrated to have macrofilaricidal activity. However, this first study was too small to provide conclusive results. Therefore, additional studies will be needed to confirm these promising findings. Trial registration: The study is registered at Cinicaltrials.gov under the number NCT04188301. Author summary: Why was this study done?: Onchocerciasis is a neglected tropical disease caused by parasitic round worms. The infective worm larvae are transmitted by black flies that breed near rivers in sub-Saharan Africa. The parasites cause severe skin disease with itching and ocular disease; the common name for the infection is "river blindness". WHO has targeted onchocerciasis for elimination and mass drug administration is the key intervention strategy. There is an urgent need for improved treatments to kill or permanently sterilize the adult parasites. This study tested a combination drug treatment that is quite effective for treating other related worm infections. What did the researchers do and find?: We performed a randomized clinical trial that compared a triple drug combination with a standard of care two-drug treatment that is widely used in Africa. We found that the new treatment was as safe as the standard treatment. More importantly, analysis of adult female worms surgically removed from study participants suggested that the new treatment might be more effective than the standard treatment for killing or permanently sterilizing the parasites. However, this first study was too small to provide conclusive results. What do these findings mean?: An improved treatment could improve chances for eliminating onchocerciasis in Africa. Results from this study can be used to better plan follow-up studies to explore the value of this and other new combination treatments for onchocerciasis. [ABSTRACT FROM AUTHOR]

Purpose: The Neglected Tropical Diseases programme since its implementation has improved the lives of many in the tropical and sub-tropical areas. Though witnessed many successes, the programme is continually facing challenges thus, preventing the attainment of various objectives. This study seeks to assess the challenges of implementation of the neglected tropical diseases programme in Ghana. Design/Methodology/Approach: The thematic analysis approach was used to analyze qualitative data collected from 18 key public health managers selected through purposive and snowballing procedures from the national, regional and district levels of Ghana Health Service. Data collection was done through in-depth interviews using semi-structured interview guides in line with the objective of the study. Findings: The Neglected Tropical Diseases Programme though received funding from external sources, faces multiple challenges which cut across financial, human and capital resources to external control. Specifically, inadequate resources, dwindling volunteerism, poor social mobilization, weak governmental commitment and weak monitoring were major challenges to implementation. These factors work individually and in combination to impede effective implementation. Ensuring state ownership, re-structuring implementation approaches to include top-down and bottom-up approaches and building capacity in monitoring and evaluation are recommended in order to meet the programme objectives and ensure sustainability. Originality: This study forms part of an original study on Implementation of the NTDs programme in Ghana. Aside the key issues discussed, it presents first-hand information on major implementation challenges that are relevant to researchers, students, practitioners and the general public and will apply widely to vertically implemented programmes in Ghana. Author summary: Diseases classified as neglected continue to affect the poorest of people across the world especially in the Sub-Saharan Africa region. Although efforts have been made, several barriers continually exist to delay attainment of programme objectives. This study assessed the challenges of implementation of the neglected tropical diseases programme in Ghana from the major state implementation agency (GHS) at the national, regional and district levels. We found the challenges of implementation that acted independently and synergistically to be inadequate resources, dwindling volunteerism, poor social mobilization, weak governmental commitment and weak monitoring and evaluation. [ABSTRACT FROM AUTHOR]

Extensive research has examined why some people have frequent Plasmodium falciparum malaria episodes in sub-Saharan Africa while others remain free of disease most of the time. In contrast, malaria risk heterogeneity remains little studied in regions where P. vivax is the dominant species. Are repeatedly infected people in vivax malaria settings such as the Amazon just unlucky? Here, we briefly review evidence that human genetic polymorphism and acquired immunity after repeated exposure to parasites can modulate the risk of P. vivax infection and disease in predictable ways. One-fifth of the hosts account for 80% or more of the community-wide vivax malaria burden and contribute disproportionally to onward transmission, representing a priority target of more intensive interventions to achieve malaria elimination. Importantly, high-risk individuals eventually develop clinical immunity, even in areas with very low or residual malaria transmission, and may constitute a large but silent parasite reservoir. [ABSTRACT FROM AUTHOR]

Background: Sleeping sickness, or human African trypanosomiasis (HAT), is transmitted by tsetse flies in endemic foci in sub-Saharan Africa. Because of international travel and population movements, cases are also occasionally diagnosed in non-endemic countries. Methodology/Principal findings: Antitrypanosomal medicines to treat the disease are available gratis through the World Health Organization (WHO) thanks to a public-private partnership, and exclusive distribution of the majority of them enables WHO to gather information on all exported cases. Data collected by WHO are complemented by case reports and scientific publications. During 2011–2020, 49 cases of HAT were diagnosed in 16 non-endemic countries across five continents: 35 cases were caused by Trypanosoma brucei rhodesiense, mainly in tourists visiting wildlife areas in eastern and southern Africa, and 14 cases were due to T. b. gambiense, mainly in African migrants originating from or visiting endemic areas in western and central Africa. Conclusions/Significance: HAT diagnosis in non-endemic countries is rare and can be challenging, but alertness and surveillance must be maintained to contribute to WHO's elimination goals. Early detection is particularly important as it considerably improves the prognosis. Author summary: Human African trypanosomiasis, also known as sleeping sickness, is a parasitic disease transmitted by tsetse flies. The infection can be contracted in several endemic areas in sub-Saharan Africa and, unless correctly diagnosed and properly treated, the disease is usually fatal. While the vast majority of cases of sleeping sickness are detected in endemic countries, a few are diagnosed in non-endemic ones, notably in travellers or migrants who have visited or resided in the transmission areas. An accurate and early diagnosis of these exported cases is crucial to improve their prognosis. In this study we reviewed cases of trypanosomiasis detected in non-endemic countries in 2011–2020. The data were gathered by the World Health Organization (WHO) thanks to its exclusive distribution of antitrypanosomal medicines. A total of 49 exported cases of sleeping sickness were detected in the 10 years we studied. Half of them were diagnosed in Europe, 22% in South Africa—a non-endemic country, 14% in North America and 12% in Asia. Only one case was detected in South America. Despite its rarity, travel medicine must maintain alertness on this disease, especially in patients with a history of exposure in endemic areas, with febrile and neuro-psychiatric syndromes and without a clear alternate diagnosis. [ABSTRACT FROM AUTHOR]

Background: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. Methods: We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified with wounds received free care and were invited to participate in the wound management study simultaneously carried out in the survey area. The data were analysed for wound prevalence, stratified by wound and patient characteristics. Results: 3842 HDSS-registered persons were surveyed. Overall wound prevalence derived from combined active and passive case finding was 13.0%. 74.1% (403/544) of patients were below the age of 15 years. Most frequent aetiologies were mechanical trauma (85.3%), furuncles (5.1%), burns (2.9%) and Buruli ulcer (2.2%). Most wounds were acute and smaller than 5 cm2 in size. 22.0% (176/799) of wounds showed evidence of secondary bacterial infection. 35.5% (22/62) of chronic wounds had persisted entirely neglected for years. Buruli ulcer prevalence was 2.3 per 1000 individuals and considerably higher than expected from an annual incidence of 0.01 per 1000 individuals as reported by WHO for Côte d'Ivoire at the time of the study. Conclusions: Skin wounds are highly prevalent in rural West Africa, where they represent a widely neglected problem. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. Trial registration: Registration at ClinicalTrials.gov NCT03957447. Author summary: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified were invited to participate in the wound management study simultaneously carried out in the survey area. We surveyed approximately 4000 HDSS-registered persons and found a high overall wound prevalence (13.0%), predominately in children. Mechanical trauma was the leading cause, followed by furuncles, burns and Buruli ulcer. Most wounds were acute and had a size of less than 5 cm2, but a substantial proportion was large, complicated, or chronic, some of the latter persisting neglected for years. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. [ABSTRACT FROM AUTHOR]

Background: Limited understanding exists about the interactions between malaria and soil-transmitted helminths (STH), their potential geographical overlap and the factors driving it. This study characterised the geographical and co-clustered distribution patterns of malaria and STH infections among vulnerable populations in sub-Saharan Africa (SSA). Methodology/Principal findings: We obtained continuous estimates of malaria prevalence from the Malaria Atlas Project (MAP) and STH prevalence surveys from the WHO-driven Expanded Special Project for the Elimination of NTDs (ESPEN) from Jan 1, 2000, to Dec 31, 2018. Although, MAP provides datasets on the estimated prevalence of Plasmodium falciparum at 5km x 5km fine-scale resolution, we calculated the population-weighted prevalence of malaria for each implementation unit to ensure that both malaria and STH datasets were on the same spatial resolution. We incorporated survey data from 5,935 implementation units for STH prevalence and conducted the prevalence point estimates before and after 2003. We used the bivariate local indicator of spatial association (LISA analysis) to explore potential co-clustering of both diseases at the implementation unit levels among children aged 2–10 years for P. falciparum and 5–14 years for STH, living in SSA. Our analysis shows that prior to 2003, a greater number of SSA countries had a high prevalence of co-endemicity with P.falciparium and any STH species than during the period from 2003–2018. Similar prevalence and distribution patterns were observed for the co-endemicity involving P.falciparum-hookworm, P.falciparum-Ascaris lumbricoides and P.falciparum-Trichuris trichiura, before and after 2003. We also observed spatial variations in the estimates of the prevalence of P. falciparum-STH co-endemicity and identified hotspots across many countries in SSA with inter-and intra-country variations. High P. falciparum and high hookworm co-endemicity was more prevalent in West and Central Africa, whereas high P. falciparum with high A. lumbricoides and high P. falciparum with high T. trichiura co-endemicity were more predominant in Central Africa, compared to other sub-regions in SSA. Conclusions/Significance: Wide spatial heterogeneity exists in the prevalence of malaria and STH co-endemicity within the regions and within countries in SSA. The geographical overlap and spatial co-existence of malaria and STH could be exploited to achieve effective control and elimination agendas through the integration of the vertical control programmes designed for malaria and STH into a more comprehensive and sustainable community-based paradigm. Author summary: Malaria and parasitic worms frequently co-exist among children living in the poorest countries of the world, but little is known about the specific locations of the combined infections involving the two major parasitic diseases and how they interact and change over the years. We used open access data collected by two public registries, that is, the Malaria Atlas Project and Expanded Special Project for the Elimination of NTDs, to understand the overlap of the two diseases in different parts of Africa, where their co-distributions are more predominant. We found significant differences in the distribution patterns of the combined diseases across different parts of Africa, with large concentrations identified in Central and West Africa. For example, double infections with malaria and hookworm were more common in West and Central Africa, whereas malaria and roundworm, and malaria and whipworm were predominantly found in Central Africa. A large collection of the dual infections was also found in some localities within the countries which appeared to have low burden of the two diseases. These findings provide a useful insight into the areas which could be serving as a reservoir to propagating the transmission of the two diseases. The results of this study could also be used to develop and implement integrated control programmes for malaria and parasitic worms, and this could help to achieve the WHO NTD roadmap to ending the neglect to attain Sustainable Development Goals by 2030. [ABSTRACT FROM AUTHOR]

Background: Epilepsy and neurocysticercosis (NCC) prevalence estimates in sub-Saharan Africa are still scarce but show important variation due to the population studied and different screening and diagnosis strategies used. The aims of this study were to estimate the prevalence of epileptic seizures and epilepsy in the sampled population, and the proportion of NCC among people with epilepsy (PWE) in a large cross-sectional study in a rural district of southern Malawi. Methods: We conducted a community-based door-to-door screening study for epileptic seizures in Balaka, Malawi between October and December 2012. Past epileptic seizures were reported through a 15-item questionnaire answered by at least one person per household generating five major criteria. People who screened positive were further examined by a neurologist to establish diagnosis. Patients diagnosed with epilepsy were examined and offered Taenia solium cyst antigen and antibody serological tests, and a CT scan for the diagnosis of NCC. Results: In total, screening information on 69,595 individuals was obtained for lifetime occurrence of epileptic seizures. 3,100 (4.5%) participants screened positive, of whom 1,913 (62%) could be followed-up and underwent further assessment. Lifetime prevalence was 3.0% (95% Bayesian credible interval [CI] 2.8 to 3.1%) and 1.2% (95%BCI 0.9 to 1.6%) for epileptic seizures and epilepsy, respectively. NCC prevalence among PWE was estimated to be 4.4% (95%BCI 0.8 to 8.5%). A diagnosis of epilepsy was ultimately reached for 455 participants. Conclusion: The results of this large community-based study contribute to the evaluation and understanding of the burden of epilepsy in the population and of NCC among PWE in sub-Saharan Africa. Author summary: Epilepsy is more common in low-income and middle-income countries than in high-income countries. One of the reasons for this is that risk factors for acquired epilepsy such as Taenia solium cysticercosis are more common in these countries. In this study we conducted a screening for epileptic seizures among nearly 70,000 people of rural Balaka district of Malawi. We found that around 3 percent of people have ever experienced an epileptic seizure and that 1 percent of people suffer from epilepsy. The screening questionnaire that we used was quite accuracte, and the more criteria for screening positive were fulfilled, the more likely it was that the person has ever experienced an epileptic seizure. Among the patients with epilepsy, around 5% also had neurocysticercosis typical lesions in their brain. [ABSTRACT FROM AUTHOR]

Growing evidence suggests considerable variation in endemic typhoid fever incidence at some locations over time, yet few settings have multi-year incidence estimates to inform typhoid control measures. We sought to describe a decade of typhoid fever incidence in the Kilimanjaro Region of Tanzania. Cases of blood culture confirmed typhoid were identified among febrile patients at two sentinel hospitals during three study periods: 2007–08, 2011–14, and 2016–18. To account for under-ascertainment at sentinel facilities, we derived adjustment multipliers from healthcare utilization surveys done in the hospital catchment area. Incidence estimates and credible intervals (CrI) were derived using a Bayesian hierarchical incidence model that incorporated uncertainty of our observed typhoid fever prevalence, of healthcare seeking adjustment multipliers, and of blood culture diagnostic sensitivity. Among 3,556 total participants, 50 typhoid fever cases were identified. Of typhoid cases, 26 (52%) were male and the median (range) age was 22 (<1–60) years; 4 (8%) were aged <5 years and 10 (20%) were aged 5 to 14 years. Annual typhoid fever incidence was estimated as 61.5 (95% CrI 14.9–181.9), 6.5 (95% CrI 1.4–20.4), and 4.0 (95% CrI 0.6–13.9) per 100,000 persons in 2007–08, 2011–14, and 2016–18, respectively. There were no deaths among typhoid cases. We estimated moderate typhoid incidence (≥10 per 100 000) in 2007–08 and low (<10 per 100 000) incidence during later surveillance periods, but with overlapping credible intervals across study periods. Although consistent with falling typhoid incidence, we interpret this as showing substantial variation over the study periods. Given potential variation, multi-year surveillance may be warranted in locations making decisions about typhoid conjugate vaccine introduction and other control measures. Author summary: There is evidence that typhoid fever incidence may vary over time, but there are few longitudinal studies estimating incidence. This is especially true in Sub-Saharan Africa, where recent estimates show wide variation in incidence across different settings, but very limited longitudinal descriptions from those settings. Incidence estimates were generated using facility-based surveillance data from three study periods that was adjusted for health-seeking behavior established through healthcare utilization surveys performed in the catchment area. In addition to coupling facility-based surveillance data with healthcare utilization data, we utilized a Bayesian statistical methodology in order to estimate incidence and characterize uncertainty around the estimates. Our results demonstrate moderate typhoid incidence in 2007–08 and low incidence during 2012–14 and 2016–18, but with overlapping credible intervals across study periods. Our data are consistent with evidence that endemic typhoid may vary substantially over time. Given potential variation, multi-year surveillance may be warranted in locations making decisions about typhoid conjugate vaccine introduction and other control measures. [ABSTRACT FROM AUTHOR]

Yellow fever virus (YFV) is a flavivirus that frequently causes outbreaks of hemorrhagic fever in Africa and South America and is considered a reemerging public health threat. Accurate diagnosis of yellow fever (YF) disease is critical as one confirmed case constitutes an outbreak and may trigger a mass vaccination campaign. Highly sensitive and specific molecular diagnostics have been developed; however, these assays require maintenance of cold-chain during transport of specimens to prevent the degradation of viral RNA prior to testing. Such cold-chain requirements are difficult to meet in some regions. In this study, we investigated Whatman FTA cards as an alternative stabilization method of YFV RNA for use in molecular diagnosis. Using contrived specimens, linear regression analysis showed that RNA detection from a single 6mm FTA card punch was significantly less sensitive than traditional RNA extraction; however, pooling RNA extracted from two FTA punches significantly lowered the limit of detection to be equal to that of the traditional RNA extraction gold standard. In experiments addressing the ability of FTA card methodology to stabilize YFV RNA at variable temperature, RNA could be detected for more than two weeks following storage at 25°C. Even more promising, YFV RNA was detectable on cards held at 37°C from two days to over two weeks depending on viral input. FTA cards were also shown to stabilize YFV RNA at high humidity if cards were desiccated prior to inoculation. These results support that FTA cards could be cost effective and easy to use in molecular diagnosis of YF, preserving viral RNA to allow for positive diagnoses in situations where maintaining cold-chain is not feasible. Author summary: Yellow fever virus (YFV) is the etiological agent of yellow fever (YF), a hemorrhagic disease endemic to sub-Saharan Africa and tropical regions of South America. Due to the threat YF poses to public health, a single case of constitutes an outbreak, making accurate diagnosis paramount. Viremia during YFV infection is variable and may be quite low depending on disease severity and the timing of sample collection. In addition, viral RNA is highly liable, especially in the hot and humid conditions that accompany YFV transmission season. To reduce RNA degradation, clinical samples are transported to diagnostic laboratories via cold chain. As cold chain is not always reliable or available, the capacity of certain regions to perform the molecular diagnosis of yellow fever is stunted, leading to a delay in diagnosis and outbreak management. Here we optimized a protocol for the incorporation of Whatman FTA cards into the YF molecular diagnostic with the goal of producing a cold chain-independent viral RNA stabilization method. These cards are compact, easy to use and were shown to inactivate YFV and stabilize YFV RNA at high temperature and humidity. The implementation of this protocol in endemic regions could aid in the rapid and accurate diagnosis of YF. [ABSTRACT FROM AUTHOR]

Female genital schistosomiasis (FGS) affects tens of millions of women and girls in sub-Saharan Africa, yet this inequitable threat is often overlooked by advocates in both the neglected tropical disease (NTD) and sexual and reproductive health and rights (SRHR) communities. FGS causes both acute infection and long-term sexual and reproductive health harm to marginalized women and girls, with gender, poverty, and rurality combining to invisibilize the disease. Human rights and gender imperatives can help to galvanize efforts to control and eliminate FGS, as they have for other NTDs. Specifically, international human rights obligations can frame state efforts to address FGS across healthcare settings, upstream social determinants of health, scientific research, and policy implementation. This article analyzes human rights–based approaches to FGS control and elimination efforts, outlining several areas for forward-looking reforms to health policy, programing, and practice. Building from the lessons learned in applying human rights–based approaches to advance progress on other NTDs, this analysis seeks to provide the NTD community with shared understanding around international legal obligations to engage SRHR advocates and draw heightened attention to FGS. Such human rights–based approaches to FGS control and elimination can help to reduce stigma and improve care for the millions of women and girls currently affected by this preventable disease. Author summary: Female genital schistosomiasis (FGS) affects over 56 million women and girls in sub-Saharan Africa alone, yet this inequitable threat is largely ignored by global health advocates, program managers, and policymakers. The lack of international attention undermines efforts to eliminate schistosomiasis globally. International human rights law can help to reverse this neglect and shape the role of the international community in supporting elimination of FGS as a public health problem, as has been done for other neglected tropical diseases (NTDs). This analysis provides the NTD community with shared language around international legal obligations to engage sexual and reproductive health and rights (SRHR) advocates and draw attention to this often overlooked condition. Working together, these two communities can reduce stigma and improve the health and well-being of the millions of marginalized women and girls affected by this preventable disease. [ABSTRACT FROM AUTHOR]

Background: Increasing clinical trial cost and complexity, as well as a high waste of clinical trial investment over the past decades, have changed the way clinical trial quality is managed. Recent evidence has highlighted that the lack of a clear clinical trial quality definition may have contributed to previous inefficiencies. This study aims to support the understanding of what clinical trial quality entails from the perspective of resource-limited settings. Methodology/Principal findings: We conducted 46 semi-structured interviews involving investigators, sponsors, and monitors with experience in conducting clinical trials in 27 countries in sub-Saharan Africa. The questionnaire addressed the overall meaning of clinical trial quality and a conclusive clinical trial quality definition, as well as specific aspects of resource-limited settings across the clinical trial process. We held the interviews either in person, via Skype or by phone. They were recorded and transcribed verbatim, and we performed the analysis using The Framework Method. The analysis of clinical trial quality definitions resulted in 11 elements, which were summarised into a clinical trial quality concept consisting of two components: 1) clinical trial quality building factors (Scientific factors and Moral factors) and 2) promoting factors (Context adaptation; Infrastructure; Partnership; Operational excellence; Quality system). 12 resource-limited settings specific themes were identified. These themes were all categorised under the promoting factors "Context adaptation", "Infrastructure", and "Partnership". Conclusions/Significance: We found that in order to enable comprehensive clinical trial quality management, clinical trial quality should be defined by a multidimensional concept that includes not only scientific and ethical, but also quality-promoting factors. Such a concept is of general relevance and not limited to clinical trials in resource-limited settings, where it naturally carries particular weight. In addition, from the perspective of sub-Saharan Africa, we identified specific categories that appear to be critical for the conduct of clinical trials in resource-limited settings, and we propose respective changes to a particular existing clinical trial quality framework (i.e., INQUIRE). Author summary: In recent decades, the quality management of clinical trials has been criticised for being inefficient and ineffective. This has led to a waste of clinical trial investment and has made it particularly difficult to conduct clinical trials in settings with limited resources. The lack of a universally accepted comprehensive definition of clinical trial quality was suggested as one of the possible causes of inadequate quality management. However, resource-limited countries were not considered in the attempt to create such a definition. In our study, we developed a quality concept based on qualitative interviews from the perspective of investigators, sponsors, and monitors with experience in conducting clinical trials in sub-Saharan Africa. The analysis of these stakeholders' definitions of clinical trial quality has produced a Clinical Trial Quality Concept that includes quality promoting factors (i.e., Context adaptation; Infrastructure; Partnership; Operational excellence; Quality system) in addition to conventional scientific and ethical factors. The results thus support the need for a multidimensional quality concept to reflect clinical trial quality more comprehensively. We recommend the term "Comprehensive Quality Management (CQM)" for this concept. CQM has the potential to serve as a basis for the current revision of quality management principles in international clinical trial guidelines. Furthermore, the sub-Saharan African perspective has highlighted additional considerations compared to the existing comprehensive INQUIRE clinical trial quality framework. Therefore, we propose including the following three points relevant to resource-limited settings in the framework: 1) Communicating potential infrastructural disadvantages to funders, sponsors, and auditors. 2) Preventing potential exploitation of research populations and workforce in low- and middle-income countries by following existing ethical frameworks. 3) Including "Context adaptation" as an additional framework category (i.e., promoting factor). [ABSTRACT FROM AUTHOR]

Background: Tsetse flies are the major vectors of human trypanosomiasis of the form Trypanosoma brucei rhodesiense and T.b.gambiense. They are widely spread across the sub-Saharan Africa and rendering a lot of challenges to both human and animal health. This stresses effective agricultural production and productivity in Africa. Delimiting the extent and magnitude of tsetse coverage has been a challenge over decades due to limited resources and unsatisfactory technology. In a bid to overcome these limitations, this study attempted to explore modelling skills that can be applied to spatially estimate tsetse abundance in the country using limited tsetse data and a set of remote-sensed environmental variables. Methodology: Entomological data for the period 2008–2018 as used in the model were obtained from various sources and systematically assembled using a structured protocol. Data harmonisation for the purposes of responsiveness and matching was carried out. The key tool for tsetse trapping was itemized as pyramidal trap in many instances and biconical trap in others. Based on the spatially explicit assembled data, we ran two regression models; standard Poisson and Zero-Inflated Poisson (ZIP), to explore the associations between tsetse abundance in Uganda and several environmental and climatic covariates. The covariate data were constituted largely by satellite sensor data in form of meteorological and vegetation surrogates in association with elevation and land cover data. We finally used the Zero-Inflated Poisson (ZIP) regression model to predict tsetse abundance due to its superiority over the standard Poisson after model fitting and testing using the Vuong Non-Nested statistic. Results: A total of 1,187 tsetse sampling points were identified and considered as representative for the country. The model results indicated the significance and level of responsiveness of each covariate in influencing tsetse abundance across the study area. Woodland vegetation, elevation, temperature, rainfall, and dry season normalised difference vegetation index (NDVI) were important in determining tsetse abundance and spatial distribution at varied scales. The resultant prediction map shows scaled tsetse abundance with estimated fitted numbers ranging from 0 to 59 flies per trap per day (FTD). Tsetse abundance was found to be largest at low elevations, in areas of high vegetative activity, in game parks, forests and shrubs during the dry season. There was very limited responsiveness of selected predictors to tsetse abundance during the wet season, matching the known fact that tsetse disperse most significantly during wet season. Conclusions: A methodology was advanced to enable compilation of entomological data for 10 years, which supported the generation of tsetse abundance maps for Uganda through modelling. Our findings indicate the spatial distribution of the G. f. fuscipes as; low 0–5 FTD (48%), medium 5.1–35 FTD (18%) and high 35.1–60 FTD (34%) grounded on seasonality. This approach, amidst entomological data shortages due to limited resources and absence of expertise, can be adopted to enable mapping of the vector to provide better decision support towards designing and implementing targeted tsetse and tsetse-transmitted African trypanosomiasis control strategies. Author summary: Tsetse flies are the major vectors of human and animal trypanosomiasis. To support control efforts, there is need to understand the location of these vectors in terms of distribution and abundance. Due to limited resources and unsatisfactory technology, delimiting the extent and magnitude of tsetse coverage remains a challenge. In a bid to overcome these limitations, this study attempted to explore modelling skills that can be applied to inform decision makers about the status of tsetse abundance using limited historical tsetse data and a set of remote-sensed environmental variables. Two regression models; standard Poisson and Zero-Inflated Poisson (ZIP) were fitted and evaluated for superiority. The results indicated the level of responsiveness of each covariate in influencing the vector across the study area. Tsetse abundance was found to be largest at low elevations in areas of high vegetative activity, in game parks, forests and permanently flooded shrubs during the dry season. This approach can be adopted to enable mapping of any tsetse species to provide better decision support towards designing and implementing targeted tsetse and tsetse-transmitted African trypanosomiasis control strategies amidst entomological data shortages due to limited resources and absence of expertise. [ABSTRACT FROM AUTHOR]

The Middle East and Northern Africa, collectively known as the MENA region, are inhabited by a plethora of venomous animals that cause up to 420,000 bites and stings each year. To understand the resultant health burden and the key variables affecting it, this review describes the epidemiology of snake, scorpion, and spider envenomings primarily based on heterogenous hospital data in the MENA region and the pathologies associated with their venoms. In addition, we discuss the venom composition and the key medically relevant toxins of these venomous animals, and, finally, the antivenoms that are currently in use to counteract them. Unlike Asia and sub-Saharan Africa, scorpion stings are significantly more common (approximately 350,000 cases/year) than snakebites (approximately 70,000 cases/year) and present the most significant contributor to the overall health burden of envenomings, with spider bites being negligible. However, this review also indicates that there is a substantial lack of high-quality envenoming data available for the MENA region, rendering many of these estimates speculative. Our understanding of the venoms and the toxins they contain is also incomplete, but already presents clear trends. For instance, the majority of snake venoms contain snake venom metalloproteinases, while sodium channel–binding toxins and potassium channel–binding toxins are the scorpion toxins that cause most health-related challenges. There also currently exist a plethora of antivenoms, yet only few are clinically validated, and their high cost and limited availability present a substantial health challenge. Yet, some of the insights presented in this review might help direct future research and policy efforts toward the appropriate prioritization of efforts and aid the development of future therapeutic solutions, such as next-generation antivenoms. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is one of the widely distributed neglected tropical diseases. It is a serious public health problem in sub-Saharan Africa. The disease is highly prevalent and widely distributed in Ethiopia due to suitable environmental factors and human activities. The prevalence and infection intensity varied from locality to locality in the country. This study aimed to assess the prevalence and intensity of S. mansoni infection and associated risk factors among schoolchildren around Lake Tana. Methods: A school-based cross-sectional study was conducted among 710 schoolchildren from February to April 2021 in eight selected primary schools around Lake Tana. A questionnaire was used to collect data on socio-demographic information and potential risk factors of S. mansoni infection. After collecting socio-demographic information, students were requested to bring about 2grams of stool specimens for parasitological examination. The collected stool samples were processed using a single Kato-Katz and Ritchie's concentration techniques. The data were analyzed using SPSS software version 23 and factors with a p-value < 0.05 were considered as statistically significant. Results: The overall prevalence of S. mansoni was 34.9% (95% CI: 31.4–38.7) among schoolchildren in the study area. The eggs per gram (EPG) of stool ranged from 24 to 1659 with arithmetic and geometric mean values of 138.1 EPG and 85.1 EPG, respectively. The majority of S. mansoni infections (61.4%) were classified as low infection intensity. Among the different determinant factors being male (AOR = 1.74; 95%CI = 1.233–2.457; P-value = 0.002), bathing habits (AOR = 1.494; 95%CI = 1.013–2.199; P-value = 0.043) and students attending at Qunzela primary school (AOR = 10.545; 95%CI = 3.264–34.067; P-value = 0.001), Alabo primary school (AOR = 3.386; 95%CI = 1.084–10.572; P-value = 0.036) were significantly associated with S. mansoni infection. Conclusion: This study revealed that more than one-third of schoolchildren were infected by S. mansoni in the study area. The majority of the infections were classified as low infection intensity. Being male, bathing habits and schools in which students attended were independent explanatory factors for S. mansoni infection. Therefore, integrated control strategies are needed to improve the health conditions of schoolchildren in the study area. Author summary: We conducted a school-based cross-sectional study to assess the prevalence and intensity of Schistosoma mansoni infection and associated risk factors. Stool samples were collected from 681 schoolchildren and processed using Kato-Katz and Ritchie's concentration techniques. Among those students, 238 (34.9%) were infected with S. mansoni. Kato-Katz and Ritchie's concentration detect 220 (92.4%) and 165 (69.3%) of the total positive cases, respectively. Most of the S. mansoni infections were categorized as low infection intensity based on egg per gram of stool. Among the potential risk factors assessed; being male, bathing habits in open water and schools in which students attended were independent predictors for S. mansoni infection. [ABSTRACT FROM AUTHOR]