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Rabies is a lethal zoonotic encephalomyelitis that causes an estimated 59,000 human deaths yearly worldwide. Although developing countries of Asia and Africa bear the heaviest burden, surveillance and disease detection in these countries is often hampered by the absence of local laboratories able to diagnose rabies and/or the difficulties of sample shipment from low-access areas to national reference laboratories. Filter papers offer a convenient cost-effective alternative for the sampling, shipment, and storage of biological materials for the diagnosis of many pathogens including rabies virus, yet the properties of diagnostic tests using this support have not been evaluated thoroughly. Sensitivity and specificity of molecular diagnosis of rabies infection using a reverse transcription followed by a hemi-nested polymerase chain reaction (RT-hn-PCR) either directly on brain tissue or using brain tissue dried on filter paper were assessed on 113 suspected field animal samples in comparison to the direct fluorescent antibody test (FAT) recommended by the World Health Organization as one of the reference tests for rabies diagnosis. Impact of the duration of the storage was also evaluated. The sensitivity and the specificity of RT-hn-PCR i) on brain tissue were 96.6% (95% CI: [88.1-99.6]) and 92.7% (95% CI: [82.4-98.0]) respectively and ii) on brain tissue dried on filter paper 100% (95% CI: [93.8-100.0]) and 90.9% (95% CI: [80.0-97.0]) respectively. No loss of sensitivity of RT-hn-PCR on samples of brain tissue dried on filter paper left 7 days at ambient temperature was detected indicating that this method would enable analyzing impregnated filter papers sent to the national reference laboratory at ambient temperature within a 1-week shipment time. It could therefore be an effective alternative to facilitate storage and shipment of samples from low-access areas to enhance and expand rabies surveillance., Competing Interests: The authors have declared that no competing interests exist.

The article focuses on the improvement of polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) for diminazene resistance detection in trypanosoma congolense. It offers information on the animal African trypanosomiasis and discusses the different techniques for trypanocidal drug resistance diagnosis. It outlines the advantages and disadvantages of the use of Dpll-PCR-RFLP through the use of filter papers . It indicates that the use of filter papers faciliate the large scale survey implementation for trypanocidal drug resistance in African countries affected by the trypanosomiasis using molecular diagnostic tools.

The estimated 50 million nomadic pastoralists in Africa are among the most "hard-to-reach" populations for health-service delivery. While data are limited, some studies have identified these communities as potential disease reservoirs relevant to neglected tropical disease programs, particularly those slated for elimination and eradication. Although previous literature has emphasized the role of these populations' mobility, the full range of factors influencing health service utilization has not been examined systematically. We systematically reviewed empirical literature on health services uptake among African nomadic pastoralists from seven online journal databases. Papers meeting inclusion criteria were reviewed using STROBE- and PRISMA-derived guidelines. Study characteristics were summarized quantitatively, and 10 key themes were identified through inductive qualitative coding. One-hundred two papers published between 1974–2019 presenting data from 16 African countries met our inclusion criteria. Among the indicators of study-reporting quality, limitations (37%) and data analysis were most frequently omitted (18%) We identified supply- and demand-side influences on health services uptake that related to geographic access (79%); service quality (90%); disease-specific knowledge and awareness of health services (59%); patient costs (35%); contextual tailoring of interventions (75%); social structure and gender (50%); subjects' beliefs, behaviors, and attitudes (43%); political will (14%); and social, political, and armed conflict (30%) and community agency (10%). A range of context-specific factors beyond distance to facilities or population mobility affects health service uptake. Approaches tailored to the nomadic pastoralist lifeway, e.g., that integrated human and veterinary health service delivery (a.k.a., "One Health") and initiatives that engaged communities in program design to address social structures were especially promising. Better causal theorization, transdisciplinary and participatory research methods, clearer operational definitions and improved measurement of nomadic pastoralism, and key factors influencing uptake, will improve our understanding of how to increase accessibility, acceptability, quality and equity of health services to nomadic pastoralist populations. Author summary: There are approximately 50 million nomadic pastoralists in Africa for whom there is little data on healthcare access and utilization. This data scarcity presents a challenge to prevent, treat and control neglected tropical diseases and design the health service delivery mechanisms through which these objectives can be met. Examining a range of studies conducted over a 45-year period, we identified supply- and demand-side influences on health services uptake in ten thematic areas. These included physical proximity to, and quality of, health services; monetary and opportunity costs of accessing care; and societal and gender norms governing power dynamics within nomadic pastoralist groups as well as those between them and health care providers. The knowledge, attitudes and practices of health care providers and health seekers also played a role in utilization, as did hegemonic factors including "political will" and varying degrees of social conflict. NTD research topics included guinea worm, lymphatic filariasis, rabies, soil-transmitted helminths, tuberculosis (bovine and human), cholera, and rift valley fever. Studies pertaining to community-directed initiatives and "One Health" approaches offered promising solutions to increase service uptake. We recommend ways to strengthen future research on this subject to improve health service delivery to, and uptake among, nomadic pastoralist populations. [ABSTRACT FROM AUTHOR]

Background: Up to 1.45 billion people currently suffer from soil transmitted helminth infection, with the largest burden occurring in Africa and Asia. Safe and cost effective deworming treatment exists, but there is a debate about mass distribution of this treatment in high prevalence settings. While the World Health Organization recommends mass administration of anthelmintic drugs for preschool and school-aged children in high (>20%) prevalence settings, and several long run follow up studies of an influential trial have suggested large benefits that persist over time, recent systematic reviews have called this recommendation into question. Methods and findings: This paper analyzes the long-term impact of a cluster-randomized trial in eastern Uganda that provided mass deworming treatment to preschool aged children from 2000 to 2003 on the numeracy and literacy skills of children and young adults living in those villages in 2010-2015. This study uses numeracy and literacy data collected seven to twelve years after the end of the deworming trial in a randomly selected subset of communities from the original trial, by an education-focused survey that had no relationship to the deworming study. Building on an earlier working paper which used data from 2010 and 2011 survey rounds, this paper uses an additional four years of numeracy and literacy data (2012, 2013, 2014, and 2015). Aggregating data from all survey rounds, the difference between numeracy scores in treatment versus control communities is 0.07 standard deviations (SD) (95% CI -0.10, 0.24, p = 0.40), the difference in literacy scores is 0.05 SD (95% CI -0.16, 0.27, p = 0.62), and the difference in total scores is 0.07 SD (95% CI -0.11, 0.25, p = 0.44). There are significant differences in program impact by gender, with numeracy and literacy differentially positively affected for girls, and by age, with treatment effects larger for the primary school aged subsample. There are also significant treatment interactions for those living in households with more treatment-eligible children. There is no evidence of differential treatment effects on age at program eligibility or number of years of program eligibility. Conclusions: Mass deworming of preschool aged children in high prevalence communities in Uganda resulted in no statistically significant gains in numeracy or literacy 7-12 years after program completion. Point estimates were positive but imprecise; the study lacked sufficient power to rule out substantial positive effects or more modest negative effects. However, there is suggestive evidence that deworming was relatively more beneficial for girls, primary school aged children, and children living in households with other treated children. Research approval: As this analysis was conducted on secondary data which is publicly available, no research approval was sought or received. All individual records were anonymized by the data provider prior to public release. [ABSTRACT FROM AUTHOR]

Background and Objectives: Trachoma is the most common cause of infectious blindness. Hot, dry climates, dust and water scarcity are thought to be associated with the distribution of trachoma but the evidence is unclear. The aim of this study was to evaluate the epidemiological evidence regarding the extent to which climatic factors explain the current prevalence, distribution, and severity of acute and chronic trachoma. Understanding the present relationship between climate and trachoma could help inform current and future disease elimination. Methods: A systematic review of peer-reviewed literature was conducted to identify observational studies which quantified an association between climate factors and acute or chronic trachoma and which met the inclusion and exclusion criteria. Studies that assessed the association between climate types and trachoma prevalence were also reviewed. Results: Only eight of the 1751 papers retrieved met the inclusion criteria, all undertaken in Africa. Several papers reported an association between trachoma prevalence and altitude in highly endemic areas, providing some evidence of a role for temperature in the transmission of acute disease. A robust mapping study found strong evidence of an association between low rainfall and active trachoma. There is also consistent but weak evidence that the prevalence of trachoma is higher in savannah-type ecological zones. There were no studies on the effect of climate in low endemic areas, nor on the effect of dust on trachoma. Conclusion: Current evidence on the potential role of climate on trachoma distribution is limited, despite a wealth of anecdotal evidence. Temperature and rainfall appear to play a role in the transmission of acute trachoma, possibly mediated through reduced activity of flies at lower temperatures. Further research is needed on climate and other environmental and behavioural factors, particularly in arid and savannah areas. Many studies did not adequately control for socioeconomic or environmental confounders. Author Summary: Trachoma – the leading cause of infectious blindness – is spread through contact with infected persons by hands and towels, and by 'eye-seeking flies.' Trachoma prevalence is high in areas characterised by poverty, inadequate water supply, and poor sanitation. Trachoma is controlled by the SAFE strategy: S = surgery to the upper eyelids; A = antibiotics for active infection; F = facial cleanliness; and E = environmental improvement. In this study we reviewed the scientific literature to assess the extent to which climatic factors (e.g., rainfall, heat, dust, altitude) influence trachoma distribution. A systematic review of the literature found eight papers that measured an association between a climatic factor and trachoma in children or adults. Several studies reported that trachoma is less common at higher altitudes, indicating that temperature may play a role in trachoma transmission. Some studies also reported that trachoma is higher in areas with low rainfall, which is consistent with anecdotal evidence that trachoma is associated with dry environments. [ABSTRACT FROM AUTHOR]

Background: West Nile virus is a mosquito-borne flavivirus which has been posing continuous challenges to public health worldwide due to the identification of new lineages and clades and its ability to invade and establish in an increasing number of countries. Its current distribution, genetic variability, ecology, and epidemiological pattern in the African continent are only partially known despite the general consensus on the urgency to obtain such information for quantifying the actual disease burden in Africa other than to predict future threats at global scale. Methodology and principal findings: References were searched in PubMed and Google Scholar electronic databases on January 21, 2020, using selected keywords, without language and date restriction. Additional manual searches of reference list were carried out. Further references have been later added accordingly to experts' opinion. We included 153 scientific papers published between 1940 and 2021. This review highlights: (i) the co-circulation of WNV-lineages 1, 2, and 8 in the African continent; (ii) the presence of diverse WNV competent vectors in Africa, mainly belonging to the Culex genus; (iii) the lack of vector competence studies for several other mosquito species found naturally infected with WNV in Africa; (iv) the need of more competence studies to be addressed on ticks; (iv) evidence of circulation of WNV among humans, animals and vectors in at least 28 Countries; (v) the lack of knowledge on the epidemiological situation of WNV for 19 Countries and (vii) the importance of carrying out specific serological surveys in order to avoid possible bias on WNV circulation in Africa. Conclusions: This study provides the state of art on WNV investigation carried out in Africa, highlighting several knowledge gaps regarding i) the current WNV distribution and genetic diversity, ii) its ecology and transmission chains including the role of different arthropods and vertebrate species as competent reservoirs, and iii) the real disease burden for humans and animals. This review highlights the needs for further research and coordinated surveillance efforts on WNV in Africa. Author summary: Since its discovery in the African continent in 1937, West Nile virus expansion and invasion into new regions represent a serious concern today for an increasing number of countries worldwide. Although about 80% of infected individuals are asymptomatic, this zoonotic virus is pathogenic for humans other than for some animal species, displaying a range of clinical manifestation spanning from influenza-like symptoms to severe neurological complication and death. This study provides an updated overview on the current knowledge of WNV epidemiology in each African country, summarizing available data on incidence of the infection in humans and animals, the circulating lineages and clades, other than an updated list of the principal arthropod vectors found naturally infected and the availability of vector competence studies. However, this review highlights also the lack of knowledge regarding the occurrence and intensity of circulation of WNV in many African countries. Therefore, considering the sensitivity of WNV transmission system to climate and other environmental changes, along with the increasing level of interconnections among continents due to globalization, the intensification of the research activities on WNV and a promotion of a coordinated surveillance actions across African and European countries would provide the information of utility for a better evaluation of the actual risk of WNV and disease burden at trans-continental scale. [ABSTRACT FROM AUTHOR]

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 123,711 SNPs were detected, of which 22.7% were nonsynonymous and 77.3% were synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (24,007 SNPs; 19.4% of total) and 10 (16,852 SNPs, 13.6% of total). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including merozoite surface protein 1 (MSP1) and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Two genes, MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and MSP3.11 on chromosome 10. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale. Author summary: Plasmodium vivax is the most geographically widespread parasite species that causes malaria in humans. Although it occurs in Africa as a member of a mix of Plasmodium species, P. vivax is dominant in other parts of the world outside of Africa (e.g., Brazil). It was previously thought that most African populations were immune to P. vivax infections due to the absence of Duffy antigen chemokine receptor (DARC) gene expression required for erythrocyte invasion. However, several recent reports have indicated the emergence and potential spread of P. vivax across human populations in Africa. Compared to Southeast Asia and South America where P. vivax is highly endemic, data on polymorphisms in erythrocyte binding gene candidates of P. vivax from Africa is limited. Filling this knowlege gap is critical for identifying functional genes in erythrocyte invasion, biomarkers for tracking the P. vivax isolates from Africa, as well as potential gene targets for vaccine development. This paper examined the level of genetic polymorphisms in a panel of 43 potential erythrocyte binding protein genes based on whole genome sequences and described transmission patterns of P. vivax infections from different study sites in Ethiopia based on the genetic variants. Our analyses showed that chromosomes 9 and 10 of the P. vivax genomes isolated in Ethiopia had the most high-quality genetic polymorphisms. Among all erythrocyte binding protein gene candidates, the merozoite surface proteins 1 and merozoite surface protein 3 showed high levels of polymorphism. MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. The expansion of the Duffy binding protein and merozoite surface protein 3 gene copies was an independent process among the P. vivax lineages in Ethiopia. Various levels of gene flow were observed even at a smaller geographical scale. Our study provided baseline data for future comparison with P. vivax in Duffy negative individuals and help develop a panel of genetic markers that are informative at a micro-geographical scale. [ABSTRACT FROM AUTHOR]

Konzo (caused by consumption of improperly processed cassava, Manihot esculenta) and neurolathyrism (caused by prolonged overconsumption of grass pea, Lathyrus sativus) are two distinct non-infectious upper motor neurone diseases with identical clinical symptoms of spastic paraparesis of the legs. They affect many thousands of people among the poor in the remote rural areas in the central and southern parts of Africa afflicting them with konzo in Ethiopia and in the Indian sub-continent with neurolathyrism. Both diseases are toxico-nutritional problems due to monotonous consumption of starchy cassava roots or protein-rich grass pea seeds as a staple, especially during drought and famine periods. Both foods contain toxic metabolites (cyanogenic glycosides in cassava and the neuro-excitatory amino acid b-ODAP in grass pea) that are blamed for theses diseases. The etiology is also linked to the deficiency in the essential sulfur amino acids that protect against oxidative stress. The two diseases are not considered reportable by the World Health Organization (WHO) and only estimated numbers can be found. This paper analyzes research performance and determines scientific interest in konzo and neurolathyrism. A literature search of over 21 years (from 1990 to 2010) shows that in terms of scientific publications there is little interest in these neglected motorneurone diseases konzo and neurolathyrism that paralyze the legs. Comparison is made with HTLV-1/TSP, an infectious disease occurring mainly in Latin America of which the clinical manifestation is similar to konzo and neurolathyrism and requires a differential diagnosis. Our findings emphasize the multidisciplinary nature of studies on these neglected diseases, which however have not really captured the attention of decision makers and project planners, especially when compared with the infectious HTLV-1/TSP. Konzo and neurolathyrism can be prevented by a balanced diet. [ABSTRACT FROM AUTHOR]

Background: Due to limited diagnostic capacity and availability of point-of-care tests, diagnosis of Clade I mpox in the geographical regions most affected is usually on clinical grounds. This may be complicated due to the similarity between mpox and varicella (chickenpox) lesions. Visual assessment of lesions is also used for determining clinical progress and to assess patient outcomes in clinical trials. However, there has been no investigation into whether clinicians can (i) identify Clade I mpox compared to other viral lesions (ii) differentiate between Clade I mpox lesion stages. Methodology/Principle findings: The objective of this study was to evaluate inter-rater reliability and agreement between clinicians assessing lesions in patients with Clade I mpox. We presented experienced clinicians with 17 images of Clade I mpox or varicella and asked them to independently indicate the most likely diagnosis–mpox or varicella–and to categorise the lesions according to their stage. When selecting the most likely diagnosis, accuracy varied across all images, the inter-rater reliability was poor (κ = 0.223; z = 10.1) and agreement was moderate (Po = 68%). When categorising lesions according to their type, if a single lesion type was present in the image, inter-rater reliability was moderate (κ = 0.671, z = 40.6) and agreement was good (Po = 78%), but when multiple lesion types were shown in an image, both inter-rater reliability (κ = 0.153, z = 10.5) and agreement (Po = 29%) decreased substantially. Conclusions: This study demonstrates that there are presently limitations in using visual assessment to diagnose Clade I mpox and evaluate lesion stage and treatment outcomes, which have an impact on clinical practice, public health and clinical trials. More robust indicators and tools are required to inform clinical, public-health, and research priorities, but these must be implementable in countries affected by mpox. Author summary: Mpox is a zoonotic illness caused by the monkeypox virus (MPXV), for which there are two distinct sub-clades. Clade I is typically found in central Africa and is associated with worse patient outcomes than Clade II. Diagnosis of mpox is most commonly performed using PCR, but in settings with limited laboratory capacity diagnosis is usually performed on clinical grounds taking lesion presentation in to account. Lesion presentation is also used to assess patient outcomes in both clinical and research settings. However, there has been no investigation into whether clinicians can (i) identify Clade I mpox compared to other viral lesions (ii) differentiate between Clade I mpox lesion stages, which has important implications for clinical practice, research and public health. Our study, which presented 16 clinicians with 17 sets of images of Clade I mpox or varicella and asked them to i) provide the most likely diagnosis and ii) categorise the lesions in to their stages, demonstrates that there are presently limitations in using visual assessment to diagnose Clade I mpox and evaluate lesion stage and treatment outcomes. Alternative methods and tools are therefore required that can be easily implemented in affected countries. [ABSTRACT FROM AUTHOR]

Introduction: The Global Strategy to Eliminate Lymphatic Filiariasis (GFELF) through Mass Drug Administration (MDA) has been implemented in Ghana since the year 2000 and transmission has been interrupted in 76 of 98 endemic districts. To improve the MDA in the remaining districts with microfilaria (MF) prevalence above the 1% threshold for the interruption of transmission, there is a need to identify and implement appropriate quality improvement (QI) strategies. This paper describes the use of intervention mapping to select QI strategies to improve an existing evidence-based MDA program in Northern Ghana. Methods: Due to the complexities associated with implementing evidence-based programs (EBP) such as the lymphatic filariasis MDA and variability in the context, an initial assessment to identify implementation bottlenecks associated with the quality of implementation of lymphatic filariasis MDA in the Bole District of Ghana was conducted using a mixed methods approach. Based on the findings of the initial assessment, a context specific QI strategy was designed and operationalized using intervention mapping strategy in terms of seven domains: actor, the action, action targets, temporality, dose, implementation outcomes addressed, and theoretical justification. Results: The initial needs assessment shows that the persistent transmission of lymphatic filariasis in the Bole District is characterized by high levels of refusal to ingest the drug, high levels of reported adverse drug reactions, low MDA coverage at community level, poor adherence to the MDA protocol and non-participants’ responsiveness. Conclusion: This study has shown that it is feasible to develop a context specific QI strategy for an existing evidence-based intervention based on an initial needs assessment through stakeholder participation using the IM approach. However, working (towards) QI requires more time than is usually available in public health service. Sufficient theoretical knowledge of implementation research and experience with technical IM experts must be available. [ABSTRACT FROM AUTHOR]

Background: Toxoplasmosis is a serious endemic zoonotic disease caused by the protozoan parasite Toxoplasma gondii. Toxoplasma infection during pregnancy can result in congenital transmission and serious fetal and neonatal complications. This systematic review and meta-analysis aimed to assess the pooled seroprevalence of T. gondii infection and its determinants among pregnant women in African countries. Methods: All articles reporting the seroprevalence of toxoplasmosis among pregnant women in African countries and published from 2010 to 2023 were searched using various databases. The pooled prevalence of toxoplasmosis was calculated using a random-effect model. The variation between the included studies was assessed using a funnel plot and I2 heterogeneity statistics. To identify the sources of heterogeneity, sub-group analysis was further conducted by country, diagnostic method, and sub-African region. The association of prevalence rates with the socio-economic level and geoclimatic parameters was also explored. Results: In total, 29,383 pregnant women from 60 articles were included for analysis. The pooled T. gondii seroprevalence was 42.89% with high heterogeneity (I2 = 99.4%, P < 0.001). Sub-group analysis revealed variation by country (ranging from 2.62% in Namibia to 80.28% in Congo), diagnostic method used (from 8.66% in studies using a rapid diagnostic test to 55.69% in those using an agglutination test), and sub-African region (from 4.14% in regions of Southern Africa to 53.96 in Central Africa). Cat ownership (OR = 1.58) and the consumption of raw meat (OR = 1.50) and raw vegetables (OR = 1.48) had a statistically significant combined effect on T. gondii seroprevalence. No association was found between T. gondii prevalence and the level of income of the country or geoclimatic parameters. Conclusion: The prevalence of toxoplasmosis infection among pregnant women in Africa is high, particularly in Central and Eastern Africa. The determinants of prevalence are multifactorial. Therefore, efforts should be made to increase the awareness of women concerning the risk factors for toxoplasmosis. Author summary: Toxoplasma gondii is a zoonotic protozoan parasite that infects both humans and animals. T. gondii infection during pregnancy causes congenital transmission and serious fetal and neonatal complications. Estimating the pooled prevalence of toxoplasmosis in high-risk population groups could catch the attention of policymakers and prompt them to develop a policy brief and guidelines to reduce toxoplasmosis sequelae. In this systematic review and meta-analysis, we aimed to assess the pooled seroprevalence of T. gondii infection and its determinants among pregnant women in Africa. All articles reporting recent data on the seroprevalence of toxoplasmosis among pregnant women in African countries were systematically searched using various databases. Sixty articles published from 2010 to 2023 were included for analysis, representing a total of 29,383 pregnant women. The pooled prevalence of toxoplasmosis was 42.89% (95%CI: 36.75–49.03). Cat ownership and the consumption of raw meat and raw vegetables had a statistically significant effect on the seroprevalence of toxoplasmosis among pregnant women in Africa. The infection is more prevalent in countries of Central and East Africa. These findings should increase the awareness of health workers and their understanding of toxoplasmosis among pregnant women and motivate them to conduct integrated community awareness creation activities concerning the risk factors for toxoplasmosis. [ABSTRACT FROM AUTHOR]

Chikungunya can have longstanding effects on health and quality of life. Alongside the recent approval of the world's first chikungunya vaccine by the US Food and Drug Administration in November 2023 and with new chikungunya vaccines in the pipeline, it is important to understand the perspectives of stakeholders before vaccine rollout. Our study aim is to identify key programmatic considerations and gaps in Evidence-to-Recommendation criteria for chikungunya vaccine introduction. We used purposive and snowball sampling to identify global, national, and subnational stakeholders from outbreak prone areas, including Latin America, Asia, and Africa. Semi-structured in-depth interviews were conducted and analysed using qualitative descriptive methods. We found that perspectives varied between tiers of stakeholders and geographies. Unknown disease burden, diagnostics, non-specific disease surveillance, undefined target populations for vaccination, and low disease prioritisation were critical challenges identified by stakeholders that need to be addressed to facilitate rolling out a chikungunya vaccine. Future investments should address these challenges to generate useful evidence for decision-making on new chikungunya vaccine introduction. Author summary: The first vaccine to prevent chikungunya fever has been recently approved in November 2023 by the US FDA and multiple chikungunya vaccine candidates are in different phases of the development pipeline. These will be the first-ever vaccines against an alphavirus and offer new technologies for vaccine development against other viruses of the same family that may cause future epidemics. We interviewed stakeholders from areas at risk of chikungunya outbreaks across Latin America, Asia and Africa, and identified gaps in Evidence-to-Recommendation criteria that should be addressed alongside vaccine introduction. Our findings show that stakeholders from different regions prioritised chikungunya differently, but all stakeholders agreed that the unknown burden of disease, undefined target populations for vaccination and non-specific disease surveillance were challenges that needed to be addressed imminently. To address these gaps, the involvement of stakeholders in all phases of vaccine development and rollout will be crucial to uncover future challenges and to ensure vaccine equity. [ABSTRACT FROM AUTHOR]

African populations of the mosquito Aedes aegypti are usually considered less susceptible to infection by human-pathogenic flaviviruses than globally invasive populations found outside Africa. Although this contrast has been well documented for Zika virus (ZIKV), it is unclear to what extent it is true for dengue virus (DENV), the most prevalent flavivirus of humans. Addressing this question is complicated by substantial genetic diversity among DENV strains, most notably in the form of four genetic types (DENV1 to DENV4), that can lead to genetically specific interactions with mosquito populations. Here, we carried out a survey of DENV susceptibility using a panel of seven field-derived Ae. aegypti colonies from across the African range of the species and a colony from Guadeloupe, French West Indies as non-African reference. We found considerable variation in the ability of African Ae. aegypti populations to acquire and replicate a panel of six DENV strains spanning the four DENV types. Although African Ae. aegypti populations were generally less susceptible than the reference non-African population from Guadeloupe, in several instances some African populations were equally or more susceptible than the Guadeloupe population. Moreover, the relative level of susceptibility between African mosquito populations depended on the DENV strain, indicating genetically specific interactions. We conclude that unlike ZIKV susceptibility, there is no clear-cut dichotomy in DENV susceptibility between African and non-African Ae. aegypti. DENV susceptibility of African Ae. aegypti populations is highly heterogeneous and largely governed by the specific pairing of mosquito population and DENV strain. Author summary: African populations of the mosquito Aedes aegypti are usually thought to be less likely to get infected by flaviviruses compared to Ae. aegypti mosquitoes found outside Africa. While this has been well-demonstrated for Zika virus, it is not clear if the same is true for dengue virus, which is the most common flavivirus in humans. Studying this is complicated by the strain diversity of dengue virus, including four main genetic types, potentially causing different interactions. In this study, we compared several mosquito populations and found that, in general, African mosquitoes were less likely to get infected by dengue virus compared to mosquitoes from outside Africa. However, in some cases, African mosquitoes were just as or even more likely to get infected. The specific strain of dengue virus also influenced how likely African mosquitoes were to get infected, showing that the relationship between African mosquitoes and dengue virus is complex. [ABSTRACT FROM AUTHOR]

Background: It is essential that clinical trial participants are representative of the population under investigation. Using HIV-associated cryptococcal meningitis (CM) as a case study, we conducted a systematic review of clinical trials to determine how inclusive and representative they were both in terms of the affected population and the involvement of local investigators. Methods: We searched Medline, EMBASE, Cochrane, Africa-Wide, CINAHL Plus, and Web of Science. Data were extracted for 5 domains: study location and design, screening, participants, researchers, and funders. Data were summarised and compared over 3 time periods: pre-antiretroviral therapy (ART) (pre-2000), early ART (2000 to 2009), and established ART (post-2010) using chi-squared and chi-squared for trend. Comparisons were made with global disease burden estimates and a composite reference derived from observational studies. Results: Thirty-nine trials published between 1990 and 2019 were included. Earlier studies were predominantly conducted in high-income countries (HICs) and recent studies in low- and middle-income countries (LMICs). Most recent studies occurred in high CM incidence countries, but some highly affected countries have not hosted trials. The sex and ART status of participants matched those of the general CM population. Patients with reduced consciousness and those suffering a CM relapse were underrepresented. Authorship had poor representation of women (29% of all authors), particularly as first and final authors. Compared to trials conducted in HICs, trials conducted in LMICs were more likely to include female authors (32% versus 20% p = 0.014) but less likely to have authors resident in (75% versus 100%, p < 0.001) or nationals (61% versus 93%, p < 0.001) of the trial location. Conclusions: There has been a marked shift in CM trials over the course of the HIV epidemic. Trials are primarily performed in locations and populations that reflect the burden of disease, but severe and relapse cases are underrepresented. Most CM trials now take place in LMICs, but the research is primarily funded and led by individuals and institutions from HICs. Author summary: It is essential that clinical trial participants are representative of the population under investigation. Similarly, research must meaningfully include researchers who are from and/or based in the location where the study is being conducted, both to ensure that the research matches the local need but also to promote equity in research. Using clinical trials in HIV-associated cryptococcal meningitis as a case study, we conducted a systematic review to determine how inclusive and representative trials have been across the course of the HIV epidemic. We identified 39 studies. There was a geographical shift with trials moving from the USA to Africa and Asia over time. We found that recent trials were conducted in areas heavily affected by cryptococcal meningitis, but we did identify geographical areas and patient groups that have been underrepresented. We also found inequality within authorship that was skewed towards male researchers from high-income countries. These findings outline areas for our discipline to focus on. We can also use this study as a benchmark from which to monitor our progress over time. This is a broad methodology that could be adopted and adapted by other research groups. [ABSTRACT FROM AUTHOR]

The documentation of Plasmodium vivax malaria across Africa especially in regions where Duffy negatives are dominant suggests possibly alternative erythrocyte invasion mechanisms. While the transcriptomes of the Southeast Asian and South American P. vivax are well documented, the gene expression profile of P. vivax in Africa is unclear. In this study, we examined the expression of 4,404 gene transcripts belong to 12 functional groups and 43 erythrocyte binding gene candidates in Ethiopian isolates and compared them with the Cambodian and Brazilian P. vivax transcriptomes. Overall, there were 10–26% differences in the gene expression profile amongst geographical isolates, with the Ethiopian and Cambodian P. vivax being most similar. Majority of the gene transcripts involved in protein transportation, housekeeping, and host interaction were highly transcribed in the Ethiopian isolates. Members of the reticulocyte binding protein PvRBP2a and PvRBP3 expressed six-fold higher than Duffy binding protein PvDBP1 and 60-fold higher than PvEBP/DBP2 in the Ethiopian isolates. Other genes including PvMSP3.8, PvMSP3.9, PvTRAG2, PvTRAG14, and PvTRAG22 also showed relatively high expression. Differential expression patterns were observed among geographical isolates, e.g., PvDBP1 and PvEBP/DBP2 were highly expressed in the Cambodian but not the Brazilian and Ethiopian isolates, whereas PvRBP2a and PvRBP2b showed higher expression in the Ethiopian and Cambodian than the Brazilian isolates. Compared to Pvs25, gametocyte genes including PvAP2-G, PvGAP (female gametocytes), and Pvs47 (male gametocytes) were highly expressed across geographical samples. Author summary: Plasmodium vivax malaria is a neglected tropical disease, despite being more geographically widespread than any other form of malaria and causes 132–391 million clinical infections each year. The documentation of P. vivax infections in different parts of Africa where Duffy-negative individuals, who were previously thought to be immune to P. vivax malaria, are dominant suggested that there are alternative pathways for P. vivax to invade human erythrocytes. Experimental approaches to unveil parasite invasion ligands are greatly limited due to a lack of reliable long-term culturing techniques and thus remains largely unexplored. Findings of this study are the first to examine the transcriptomes of African P. vivax and compare such to other geographical isolates with the goal to provide an important baseline for future comparisons of P. vivax transcriptomes in Duffy-negative infections. Our analyses also highlight potential biomarkers for improved gametocyte detection to better monitor the spread of P. vivax malaria. [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]

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]

Capacity building in health research generally, and helminthiasis research particularly, is pivotal to the implementation of the research and development agenda for the control and elimination of human helminthiases that has been proposed thematically in the preceding reviews of this collection. Since helminth infections affect human populations particularly in marginalised and lowincome regions of the world, they belong to the group of poverty-related infectious diseases, and their alleviation through research, policy, and practice is a sine qua non condition for the achievement of the United Nations Millennium Development Goals. Current efforts supporting research capacity building specifically for the control of helminthiases have been devised and funded, almost in their entirety, by international donor agencies, major funding bodies, and academic institutions from the developed world, contributing to the creation of (not always equitable) North-South "partnerships". There is an urgent need to shift this paradigm in disease-endemic countries (DECs) by refocusing political will, and harnessing unshakeable commitment by the countries' governments, towards health research and capacity building policies to ensure long-term investment in combating and sustaining the control and eventual elimination of infectious diseases of poverty. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. This paper discusses the challenges confronting capacity building for parasitic disease research in DECs, describes current capacity building strategies with particular reference to neglected tropical diseases and human helminthiases, and outlines recommendations to redress the balance of alliances and partnerships for health research between the developed countries of the "North" and the developing countries of the "South". We argue that investing in South-South collaborative research policies and capacity is as important as their North-South counterparts and is essential for scaled-up and improved control of helminthic diseases and ultimately for regional elimination. [ABSTRACT FROM AUTHOR]

Background: Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda. Methodology and Principal Findings: The sequence of tests in each algorithm was programmed into a probabilistic model, informed by distributions of the sensitivity, specificity and staging accuracy of each test, constructed based on a literature review. The accuracy of algorithms was estimated in a baseline scenario and in a worst-case scenario introducing various near worst-case assumptions. In the baseline scenario, sensitivity was estimated as 85-90% in all but one algorithm, with specificity above 99.9% except for the Republic of Congo, where CATT serology was used as independent confirmation test: here, positive predictive value (PPV) was estimated at <50% in realistic active screening prevalence scenarios. Furthermore, most algorithms misclassified about one third of true stage 1 cases as stage 2, and about 10% of true stage 2 cases as stage 1. In the worst-case scenario, sensitivity was 75-90% and PPV no more than 75% at 1% prevalence, with about half of stage 1 cases misclassified as stage 2. Conclusions: Published evidence on the accuracy of widely used tests is scanty. Algorithms should carefully weigh the use of serology alone for confirmation, and could enhance sensitivity through serological suspect follow-up and repeat parasitology. Better evidence on the frequency of low-parasitaemia infections is needed. Simulation studies should guide the tailoring of algorithms to specific scenarios of HAT prevalence and availability of control tools. [ABSTRACT FROM AUTHOR]

Konzo is a distinct neurological entity with selective upper motor neuron damage, characterized by an abrupt onset of an irreversible, non-progressive, and symmetrical spastic para/tetraparesis. Despite its severity, konzo remains a neglected disease. The disease is associated with high dietary cyanogen consumption from insufficiently processed roots of bitter cassava combined with a protein-deficient diet. Epidemics occur when these conditions coincide at times of severe food shortage. Up to 1993, outbreaks in poor rural areas in Africa contributed to more than 3,700 cases of konzo. The number of affected people is underestimated. From unofficial reports, the number of cases was estimated to be at least 100,000 in 2000, in contrast to the 6,788 cases reported up to 2009 from published papers. [ABSTRACT FROM AUTHOR]

Background: A research priority for Plasmodium vivax malaria is to improve our understanding of the spatial distribution of risk and its relationship with the burden of P. vivax disease in human populations. The aim of the research outlined in this article is to provide a contemporary evidence-based map of the global spatial extent of P. vivax malaria, together with estimates of the human population at risk (PAR) of any level of transmission in 2009. Methodology: The most recent P. vivax case-reporting data that could be obtained for all malaria endemic countries were used to classify risk into three classes: malaria free, unstable (<0.1 case per 1,000 people per annum (p.a.)) and stable (≥0.1 case per 1,000 p.a.) P. vivax malaria transmission. Risk areas were further constrained using temperature and aridity data based upon their relationship with parasite and vector bionomics. Medical intelligence was used to refine the spatial extent of risk in specific areas where transmission was reported to be absent (e.g., large urban areas and malaria-free islands). The PAR under each level of transmission was then derived by combining the categorical risk map with a high resolution population surface adjusted to 2009. The exclusion of large Duffy negative populations in Africa from the PAR totals was achieved using independent modelling of the gene frequency of this genetic trait. It was estimated that 2.85 billion people were exposed to some risk of P. vivax transmission in 2009, with 57.1% of them living in areas of unstable transmission. The vast majority (2.59 billion, 91.0%) were located in Central and South East (CSE) Asia, whilst the remainder were located in America (0.16 billion, 5.5%) and in the Africa+ region (0.10 billion, 3.5%). Despite evidence of ubiquitous risk of P. vivax infection in Africa, the very high prevalence of Duffy negativity throughout Central and West Africa reduced the PAR estimates substantially. Conclusions: After more than a century of development and control, P. vivax remains more widely distributed than P. falciparum and is a potential cause of morbidity and mortality amongst the 2.85 billion people living at risk of infection, the majority of whom are in the tropical belt of CSE Asia. The probability of infection is reduced massively across Africa by the frequency of the Duffy negative trait, but transmission does occur on the continent and is a concern for Duffy positive locals and travellers. The final map provides the spatial limits on which the endemicity of P. vivax transmission can be mapped to support future cartographic-based burden estimations. Author Summary: Growing evidence shows that Plasmodium vivax malaria is clinically less benign than has been commonly believed. In addition, it is the most widely distributed species of human malaria and is likely to cause more illness in certain regions than the more extensively studied P. falciparum malaria. Understanding where P. vivax transmission exists and measuring the number of people who live at risk of infection is a fundamental first step to estimating the global disease toll. The aim of this paper is to generate a reliable map of the worldwide distribution of this parasite and to provide an estimate of how many people are exposed to probable infection. A geographical information system was used to map data on the presence of P. vivax infection and spatial information on climatic conditions that impede transmission (low ambient temperature and extremely arid environments) in order to delineate areas where transmission was unlikely to take place. This map was combined with population distribution data to estimate how many people live in these areas and are, therefore, exposed to risk of infection by P. vivax malaria. The results show that 2.85 billion people were exposed to some level of risk of transmission in 2009. [ABSTRACT FROM AUTHOR]

Background: Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. Methodology/Principal Findings: This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. Conclusions/Significance: We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths. Author Summary: Elimination of canine rabies has been achieved in some parts of the world, but the disease still kills many thousands of people each year in Africa. Here we counter common arguments given for the lack of effective canine rabies control in Africa presenting detailed data from a range of settings. We conclude that (1) rabies substantially affects public and animal health sectors, hence regional and national priorities for control ought to be higher, (2) for practical purposes domestic dogs are the sole maintenance hosts and main source of infection for humans throughout most of Africa and Asia and sufficient levels of vaccination coverage in domestic dog populations should lead to elimination of canine rabies in most areas, (3) the vast majority of domestic dog populations across sub-Saharan Africa are accessible for vaccination with community sensitization being of paramount importance for the success of these programs, (4) improved local capacity in rabies surveillance and diagnostics will help evaluate the impact of control and elimination efforts, and (5) sustainable resources for effective dog vaccination campaigns are likely to be available through the development of intersectoral financing schemes involving both medical and veterinary sectors. [ABSTRACT FROM AUTHOR]

Background: The morbidity and mortality of extraparenchymal neurocysticercosis (EP-NC) remain high and effectiveness of current medical treatment is suboptimal. Various factors have been implicated in the severity of EP-NC and in the poor response to treatment, but the possible role of host immune and endocrine systems has not yet been examined thoroughly. Methodology/Principal findings: 42 participants with EP-NC before receiving standard treatment and 25 healthy controls were included in the study. Treatment response was assessed by comparing pre/post treatment parasite volumes from 3D MRI. Prior to treatment among participants with EP-NC, specific stimulation induced an increased specific proliferative response accompanied by a significant increase in IL-4, NK, NKT, Bregs and Tregs cells, whereas in healthy controls, specific stimulation induced a significant increase in IL-1β, IL-5, CCL5, IL-6, TNF-α, NK and Bregs cells. Significant differences between participants with EP-NC and healthy controls in the specific inflammatory response were observed. Participants with EP-NC prior to treatment had significantly weaker responses of proinflammatory cytokines (IL-6, TNF-α) and NK cells, and stronger IL-4 response. Anthelmintic treatment did not promote significant peripheral immunological changes at any time, although inflammation was sustained in the cerebrospinal fluid. Serum estradiol concentration significantly decreased after anthelmintic treatment among males, and cortisol correlated negatively with IL-6 and positively with IFN-γ levels. No pre-treatment immunologic or endocrinologic parameters were significantly associated with response to treatment. Conclusion/Significance: Prior to anthelmintic treatment, EP-NC was characterized by low lymphocyte reactivity accompanied by a regulatory response, which may be involved in the lack of peripheral immunological changes during and after treatment, although a central inflammatory response was present. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment. Our findings highlight the need for new anti-inflammatory treatment focused on the central nervous system with less systemic immunosuppressive effects. Author summary: Neurocysticercosis is a central nervous system infection with the helminth Taenia solium in its larval stage. It is a marker of poverty and remains endemic in countries of Latin America, Africa, and Asia. The severity of neurocysticercosis and the prognosis of patients depend on the location of the parasites. Extraparenchymal infection involving the subarachnoid and/or ventricular space is associated with high morbidity and mortality and a suboptimal response to current anthelminthic treatment regimens. We examined peripheral immunological parameters and hormones of 42 participants with extraparenchymal neurocysticercosis before and after treatment, and their associations with subsequent treatment response. Prior to treatment, compared with healthy controls, there was low lymphocyte reactivity with a regulatory response, which may explain the lack of peripheral immunological changes during and after treatment. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment and should be considered in research to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Biomphalaria pfeifferi is the world's most widely distributed and commonly implicated vector snail species for the causative agent of human intestinal schistosomiasis, Schistosoma mansoni. In efforts to control S. mansoni transmission, chemotherapy alone has proven insufficient. New approaches to snail control offer a way forward, and possible genetic manipulations of snail vectors will require new tools. Towards this end, we here offer a diverse set of genomic resources for the important African schistosome vector, B. pfeifferi. Methodology/Principal findings: Based largely on PacBio High-Fidelity long reads, we report a genome assembly size of 772 Mb for B. pfeifferi (Kenya), smaller in size than known genomes of other planorbid schistosome vectors. In a total of 505 scaffolds (N50 = 3.2Mb), 430 were assigned to 18 large linkage groups inferred to represent the 18 known chromosomes, based on whole genome comparisons with Biomphalaria glabrata. The annotated B. pfeifferi genome reveals a divergence time of 3.01 million years with B. glabrata, a South American species believed to be similar to the progenitors of B. pfeifferi which undertook a trans-Atlantic colonization < five million years ago. Conclusions/Significance: The genome for this preferentially self-crossing species is less heterozygous than related species known to be preferential out-crossers; its smaller genome relative to congeners may similarly reflect its preference for selfing. Expansions of gene families with immune relevance are noted, including the FReD gene family which is far more similar in its composition to B. glabrata than to Bulinus truncatus, a vector for Schistosoma haematobium. Provision of this annotated genome will help better understand the dependencies of trematodes on snails, enable broader comparative insights regarding factors contributing to susceptibility/ resistance of snails to schistosome infections, and provide an invaluable resource with respect to identifying and manipulating snail genes as potential targets for more specific snail control programs. Author summary: Biomphalaria pfeifferi is the world's most widely distributed and commonly implicated vector snail for the causative agent of human intestinal schistosomiasis, Schistosoma mansoni. Understanding the basis of host-parasite compatibility relies on functional genomic resources, which will be helpful for developing genetic-based control of schistosomes and their vector snails. Here we report a high-quality, de novo–assembled whole genome for B. pfeifferi (PacBio High-Fidelity long reads), with in-depth gene model annotation for protein-coding and nonprotein-coding genes. Using these enriched molecular data, a divergence date of 3.01 Mya was calculated for B. pfeifferi and B. glabrata, consistent with the idea of Biomphalaria colonization of Africa from South America, and placing an upper boundary on the age of S. mansoni in Africa. The spread of S. mansoni was likely favored by its high degree of compatibility with B. pfeifferi-like snails. In addition, our evidence supports the idea that B. pfeifferi is a preferentially self-crossing species with a more homozygous and smaller genome than related species like B. glabrata known to be preferential out-crossers. Furthermore, several immune-related gene families have expanded differently between B. pfeifferi to B. glabrata. Resources provided here will deepen our general knowledge of molluscan biology, host-parasite co-evolution, vector biology, and genomics. [ABSTRACT FROM AUTHOR]

Background: Snakebite envenoming is a serious and life-threatening medical condition that predominantly affects people living in rural communities across Africa, Asia, and Latin America. As our climate changes, there is a growing concern that negative human–snake interactions will increase. Our ability to prevent and manage snakebite requires effective antivenoms as well as knowledge regarding the prevention and management of snakebite among healthcare workers and affected communities across the globe. This systematic review aims to assess existing levels of knowledge regarding snakebite prevention and management in both healthcare workers and affected communities. Methods: This review was conducted on studies reporting quantitative measurements to evaluate knowledge and practice regarding snakebite prevention and management published in major databases between 1 January 2000 and 31 December 2021. Random effects modelling was used to obtain the pooled proportion. Heterogeneity (I2) was tested, and sensitivity analyses performed. Results: Out of 3,697 records, 16 studies from 12 countries assessing 7,640 participants were included. Four of the studies were ranked as good quality studies, 9 as fair, and 3 as poor. This study results demonstrated that 56% of the study population answered the knowledge question correctly (95% CI 48% to 63%, p < 0.001). High heterogeneity was observed (I2 = 97.29%), with marginal publication bias (Egger's regression test, p = 0.0814). Participants had relatively higher knowledge concerning use of antivenom as preferred treatment, followed by snakebite prevention, knowledge of signs and symptoms of snakebite, knowledge of first-aid, and knowledge of treatment. Participants had lower knowledge relating to types of snakes and the identification of snakes. Conclusion: Adequate knowledge about snakebites and its management among the general population and healthcare workers was 56%. Healthcare workers and communities across Asia showed higher relative knowledge compared to those in Africa and the Middle East. These data suggest that further education is needed in both the general population and among healthcare workers to ensure that appropriate preventative and patient management techniques are being utilised in snakebite endemic regions. Greater local awareness of the risks and appropriate management of snakebite is required to reduce the burden of snakebite mortality and morbidity. [ABSTRACT FROM AUTHOR]

We explore how animal host traits, phylogenetic identity and cell receptor sequences relate to infection status and mortality from ebolaviruses. We gathered exhaustive databases of mortality from Ebolavirus after exposure and infection status based on PCR and antibody tests. We performed ridge regressions predicting mortality and infection as a function of traits, phylogenetic eigenvectors and separately host receptor sequences. We found that mortality from Ebolavirus had a strong association to life history characteristics and phylogeny. In contrast, infection status related not just to life history and phylogeny, but also to fruit consumption which suggests that geographic overlap of frugivorous mammals can lead to spread of virus in the wild. Niemann Pick C1 (NPC1) receptor sequences predicted infection statuses of bats included in our study with very high accuracy, suggesting that characterizing NPC1 in additional species is a promising avenue for future work. We combine the predictions from our mortality and infection status models to differentiate between species that are infected and also die from Ebolavirus versus species that are infected but tolerate the virus (possible reservoirs of Ebolavirus). We therefore present the first comprehensive estimates of Ebolavirus reservoir statuses for all known terrestrial mammals in Africa. Author summary: Identifying the animal hosts of Ebolavirus is crucial to preventing future outbreaks. We gathered exhaustive databases of which species die and which species show evidence of past infection from ebolaviruses in published literature. Our approach allowed us to differentiate which species die from Ebolavirus and which species tolerate the infection after exposure. We found that fruit bats are likely reservoirs as they are exposed to the infection but tolerate the virus, whereas primates do not serve as ideal reservoirs because they succumb to the infection once exposed. We also compared different predictors of infection and conclude that receptors of Ebolavirus best predict infection in bats whereas ecological traits predict infection in primates. [ABSTRACT FROM AUTHOR]

Splenomegaly, an enlargement of the spleen, is a known clinical sign of the parasitic disease, human African trypanosomiasis. This study follows the development of splenomegaly in a group of mice over multiple infection points, using a non-invasive imaging modality, magnetic resonance imaging (MRI). CD-1 mice infected with GVR35 T.b. brucei demonstrated a significant increase in spleen size from day 7 post-infection, with changes in the spleen tracked in individual animals over five time points. At the final time point, the mean spleen weight calculated using the spleen volume from the MR images was compared with the post-mortem gross spleen weight. No significant difference was detected between the two methods (1.62 ± 0.06g using MRI and 1.51 ± 0.04g gross weight, p = 0.554). Haematology and histological analysis were also performed, giving additional insight into splenomegaly for the GVR35 strain of infection. The study demonstrates that MRI is a useful tool when examining changes in organ volume throughout HAT infection and may be applicable in the investigation of a range of conditions where changes in organ volume occur and MRI has not been used previously. Author summary: Although splenomegaly (the enlargement of the spleen) has been explored previously in mice infected with human African trypanosomiasis (HAT), a parasitic disease originating in Africa, it has never been examined in individual mice over time. This study is the first to do this using magnetic resonance imaging (MRI). By scanning mice infected with trypanosomes, we were able to examine how the spleen size and shape changed over the course of the infection. We were also able to show the enlargement in spleen size before the clinical signs became apparent, demonstrating that MRI could be useful for examining changes in the organs in the body following the onset of disease. [ABSTRACT FROM AUTHOR]

The authors reflect on the success of the "PLoS Neglected Tropical Diseases" as an open-access journal for neglected tropical diseases (NTDs). The authors say that the journal has received many article submissions from African countries including Kenya, Uganda, and Ghana, where enormous burden disease was found. The authors state that the journal has kept the high quality of its papers. The authors add that the journal has helped integrate NTDs on the agendas of international agencies.

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]

Introduction: While Shigellae and strains of enterotoxigenic Escherichia coli (ETEC) are important causes of diarrhea-associated morbidity and mortality among infants and young children (<5 years of age), their health impact in older age groups is unclear. We sought to quantify the overall burden of shigellosis and ETEC diarrhea among older children, adolescents, and adults in Africa and South Asia, the two regions with the highest levels of diarrhea-related morbidity and mortality worldwide. Methods: We employed two distinct methodological approaches to estimate the burden of diarrhea due to Shigellae and ETEC among persons ≥5 years of age in the WHO regions of South Asia (SEAR) and Africa (AFR). Under method 1, we conducted a systematic review to identify the median proportion of total deaths due to diarrhea and then applied this figure to the number of all-cause deaths that occurred in 2010 among this age group. To estimate the total number of diarrhea deaths attributable to Shigellae and ETEC, we subsequently applied previously published estimates of the median percentage of diarrhea hospitalizations due to Shigellae and ETEC to the estimated number of diarrhea deaths. For method 2, we applied previously published incidence rates to 2010 population figures and estimated the total number of episodes due to Shigellae and ETEC using published estimates of the average proportion of pathogen-positive outpatients from studies of >4 pathogens. We then estimated the number of pathogen-specific deaths by determining the number of hospitalized patients and applying the case-fatality rate. Results: By method 1, there were 19,451 deaths due to Shigellae and 42,973 due to ETEC in AFR, and 20,691 due to Shigellae and 45,713 due to ETEC in SEAR in 2010. By method 2, there were 15.0 million ETEC episodes and 30.4 million episodes due to Shigellae in AFR, and 28.7 million episodes due to ETEC and 58.1 million episodes due to Shigellae in SEAR in 2010. We were unable to identify published case-fatality rates for ETEC and thus could only estimate Shigellae-related deaths using method 2, by which there were 5,308 and 10,158 Shigellae-related deaths in AFR and SEAR in 2010, respectively. Discussion: Methods 1 and 2 underscore the importance of Shigellae and ETEC as major causes of morbidity and mortality among older children, adolescents, and adults in AFR and SEAR. Understanding the epidemiology of these pathogens is imperative for the development and use of future vaccines and other preventative interventions. Author Summary: We aimed to estimate the burden of diarrhea due to Shigellae and ETEC among persons ≥5 years of age in Africa and South Asia using two methodological approaches. Method 1 employed diarrhea proportionate mortality and published estimates of pathogen-specific hospitalization. Method 2 utilized published incidence rates and case-fatality rates. Method 1 resulted in 19,451 deaths due to Shigellae and 42,973 deaths due to ETEC in AFR, and 20,691 deaths due to Shigellae and 45,713 deaths due to ETEC in SEAR in 2010. Method 2 resulted in 15.0 million episodes due to ETEC and 30.4 million episodes due to Shigellae in AFR, and 28.7 million episodes due to ETEC and 58.1 million episodes due to Shigellae in SEAR in 2010. These figures highlight the importance of Shigellae and ETEC as major causes of morbidity and mortality among older children, adolescents and adults in Africa and South Asia. [ABSTRACT FROM AUTHOR]

Background: Urogenital schistosomiasis remains highly endemic in Africa. Current control is based on drug administration, targeted either to school-age children or to high-risk communities at-large. Urine dipsticks for detection of microhematuria offer an inexpensive means for estimating infection prevalence. However, their diagnostic performance has not been systematically evaluated after community treatment, or in areas with continuing low prevalence. The objective of the present study was to perform meta-analysis of dipstick accuracy for S. haematobium infection in endemic regions, with special attention to performance where infection intensity or prevalence was low. Methodology/Principal Findings: This review was registered at inception with PROSPERO (CRD42012002165). Included studies were identified by computerized search of online databases and hand search of bibliographies and existing study archives. Eligible studies included published or unpublished population surveys irrespective of date, location, or language that compared dipstick diagnosis of S. haematobium infection to standard egg-count parasitology. For 95 included surveys, variation in dipstick sensitivity and specificity were evaluated according to study size, age- and sex-specific participation, region, local prevalence, treatment status, and other factors potentially affecting test performance. Independent of prevalence, accuracy was greater in surveys of school-age children (vs. adults), whereas performance was less good in North Africa, as compared to other regions. By hierarchical ROC analysis, overall dipstick sensitivity and specificity for detection of egg-positive urine were estimated at 81% and 89%, respectively. Sensitivity was lower among treated populations (72%) and in population subgroups having lower intensity infection (65%). When the insensitivity of egg count testing was considered (and diagnosis inferred instead from combined hematuria and egg-count findings), overall dipstick sensitivity/specificity were 82%/97%, with significantly better sensitivity (92%) in high prevalence settings. Conclusions/Significance: This analysis suggests that dipsticks will continue to serve as very useful adjuncts for monitoring community prevalence following implementation of population-based control of urogenital schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: Histoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum (Hcc) and Histoplasma capsulatum var. duboisii (Hcd) causes infection in humans and commonly termed classical or American histoplasmosis and African histoplasmosis, respectively. Histoplasma capsulatum var. farciminosum (Hcf) affects equines. In recent times, there have been heightened sensitization on fungal infections such as histoplasmosis in Africa, aimed at improving awareness among relevant stakeholders, particularly healthcare workers. This effort is expected to be paralleled with increased detection of both classical and African histoplasmosis, which has remained underdiagnosed over the years. In this narrative review, we describe the current perspectives of histoplasmosis in Africa, identify knowledge gaps, and suggest research priorities. Methods: A PubMed, Google Scholar, and Africa Journal Online (AJOL) literature search was conducted for studies on histoplasmosis in Africa between 2000 and 2020. Histoplasmosis essays in medical mycology textbooks were also consulted. This narrative review was prepared from the data gathered. Findings: In the past 2 decades, histoplasmosis in general has seen a relative increase in case detection in some Africa countries, probably attributable to the gradually increasing medical mycology advocacy efforts in Africa. Histoplasmosis cases are dominated by African histoplasmosis mostly in Western and Central Africa, while classical histoplasmosis is more common in Southern and Northern Africa. Although both classical and African histoplasmosis are common in Africa, the latter is more restricted to Africa, and cases outside the continent usually have a travel history to the continent. Despite the clinical and laboratory difference between African histoplasmosis and classical histoplasmosis, it is not straightforward to distinguish them. The typical manifestation of African histoplasmosis is the appearance of lesions affecting the skin, bones, and lymph nodes and unusually linked to human immunodeficiency virus (HIV)/AIDS. By contrast, classical histoplasmosis mostly affects the lungs and is often associated with immunosuppression, mainly HIV/AIDS. The present perspectives of histoplasmosis in Africa highlight unclear details on the true burden, strain diversity, infection route and genetic basis of African histoplasmosis, availability of specie-specific diagnostic tools, and compliance with recommended antifungal therapy. These knowledge gaps represent research questions that require scientific exploration. Conclusions: Despite a subtle increase in identifying histoplasmosis cases in Africa, it remains underdiagnosed and neglected in some parts of the continent. Increasing awareness and training among healthcare workers, bridging diagnostic and therapeutic gaps, and encouraging more research in Africa are crucial to improve the current perspectives of histoplasmosis in Africa. [ABSTRACT FROM AUTHOR]

Introduction: Parasitic infections, especially intestinal protozoan parasites (IPPs) remain a significant public health issue in Africa, where many conditions favour the transmission and children are the primary victims. This systematic review and meta-analysis was carried out with the objective of assessing the prevalence of IPPs among school children in Africa. Methods: Relevant studies published between January 2000 and December 2020 were identified by systematic online search on PubMed, Web of Science, Embase and Scopus databases without language restriction. Pooled prevalence was estimated using a random-effects model. Heterogeneity of studies were assessed using Cochrane Q test and I2 test, while publication bias was evaluated using Egger's test. Results: Of the 1,645 articles identified through our searches, 46 cross-sectional studies matched our inclusion criteria, reported data from 29,968 school children of Africa. The pooled prevalence of intestinal protozoan parasites amongst African school children was 25.8% (95% CI: 21.2%-30.3%) with E. histolytica/ dispar (13.3%; 95% CI: 10.9%-15.9%) and Giardia spp. (12%; 95% CI: 9.8%-14.3%) were the most predominant pathogenic parasites amongst the study participants. While E. coli was the most common non-pathogenic protozoa (17.1%; 95% CI: 10.9%-23.2%). Conclusions: This study revealed a relatively high prevalence of IPPs in school children, especially in northern and western Africa. Thus, poverty reduction, improvement of sanitation and hygiene and attention to preventive control measures will be the key to reducing protozoan parasite transmission. Author summary: Pathogenic intestinal protozoan parasites (IPPs) remain a major public health concern. Studies have documented that, the prevalence rates of protozoan infections are quite high in developing regions, particularly Africa and children are the primary victims. Despite numerous studies have been conducted on IPPs in school children in African countries, data on the burden of these infections in African school children have not yet been synthesised. This systematic review and meta-analysis was conducted to provide continent-wide prevalence of IPPs amongst African school children. Our study found that about 25.8% of the children had one or more species of intestinal protozoan parasites in their faecal specimens. E. histolytica/ dispar and Giardia spp. were the most predominant parasites amongst the study participants. The relatively high prevalence estimate of IPPs amongst African children and the considerable variation in the disease prevalence over the years, between and within countries and regions clearly indicates the needs to improve sanitation and hygiene, paying more attention to preventive control measures as well as poverty reduction which are the key to reducing protozoan parasite transmission. [ABSTRACT FROM AUTHOR]

Background: The awareness of non-malarial febrile illnesses (NMFIs) has been on the rise over the last decades. Therefore, we undertook a systematic literature review and meta-analysis of causative agents of non-malarial fevers on the African continent. Methodology: We searched for literature in African Journals Online, EMBASE, PubMed, Scopus, and Web of Science databases to identify aetiologic agents that had been reported and to determine summary estimates of the proportional morbidity rates (PMr) associated with these pathogens among fever patients. Findings: A total of 133 studies comprising 391,835 patients from 25 of the 54 African countries were eligible. A wide array of aetiologic agents were described with considerable regional differences among the leading agents. Overall, bacterial pathogens tested from blood samples accounted for the largest proportion. The summary estimates from the meta-analysis were low for most of the agents. This may have resulted from a true low prevalence of the agents, the failure to test for many agents or the low sensitivity of the diagnostic methods applied. Our meta-regression analysis of study and population variables showed that diagnostic methods determined the PMr estimates of typhoidal Salmonella and Dengue virus. An increase in the PMr of Klebsiella spp. infections was observed over time. Furthermore, the status of patients as either inpatient or outpatient predicted the PMr of Haemophilus spp. infections. Conclusion: The small number of epidemiological studies and the variety of NMFI agents on the African continent emphasizes the need for harmonized studies with larger sample sizes. In particular, diagnostic procedures for NMFIs should be standardized to facilitate comparability of study results and to improve future meta-analyses. Reliable NMFI burden estimates will inform regional public health strategies. Author summary: Previous systematic reviews have highlighted the research priorities of causative agents for non-malarial febrile illnesses by counting the number of publications attributed to an agent. However, proportional morbidity rates are calculated by dividing the number of cases with a specific disease (numerator) by the total number of diagnosed fever cases (denominator) and are better indicators of the relative importance of aetiological agents in a population. Therefore, we present the leading causes of non-malarial febrile illnesses in African patients in both healthcare and community settings. Preference is given to HIV-negative patients when data could be found. We also determined summary estimates of Brucella spp., Chikungunya virus, Dengue virus, Haemophilus spp., Klebsiella spp., Leptospira spp., non-typhoidal Salmonella spp., typhoidal Salmonella spp., Staphylococcus spp., and Streptococcus spp. The wide array of aetiological agents causing febrile illnesses on the African continent does not only complicate malaria control programs but may also hamper response to epidemic and pandemic illnesses such as Ebola and COVID-19. The harmonisation of diagnostics and study designs will reduce between-study differences, which may result in better estimates of disease burden on the continent and in the different African regions. This information is important for Pan-African surveillance and control efforts. [ABSTRACT FROM AUTHOR]

The article discusses neglected tropical diseases (NTDs) in Africa and the need for research and funding to address these diseases. It highlights the European Foundation Initiative into African Research in Neglected Tropical Diseases (EFINTD), which supports young African researchers in strengthening research capacity in NTDs. The article evaluates the EFINTD fellowship program and its impact on fellows' careers and research outputs. It emphasizes the importance of involving African scientists and communities in priority setting and research for NTDs. The program has had positive effects on fellows and their institutions, including infrastructure development and policy influence. It has also facilitated networking and mentorship opportunities. The fellows recommend extending the senior fellowship duration, providing long-term support for successful fellows, and promoting capacity building and infrastructure development. [Extracted from the article]

Background: Trachoma prevalence surveys provide the evidence base for district and community-wide implementation of the SAFE strategy, and are used to evaluate the impact of trachoma control interventions. An economic analysis was performed to estimate the cost of trachoma prevalence surveys conducted between 2006 and 2010 from 8 national trachoma control programs in Africa. Methodology and Findings: Data were collected retrospectively from reports for 165 districts surveyed for trachoma prevalence using a cluster random sampling methodology in Ethiopia, Ghana, Mali, Niger, Nigeria, Sudan, Southern Sudan and The Gambia. The median cost per district survey was $4,784 (inter-quartile range [IQR] = $3,508-$6,650) while the median cost per cluster was $311 (IQR = $119-$393). Analysis by cost categories (personnel, transportation, supplies and other) and cost activity (training, field work, supervision and data entry) revealed that the main cost drivers were personnel and transportation during field work. Conclusion: Population-based cluster random surveys are used to provide the evidence base to set objectives and determine when elimination targets have been reached for several neglected tropical diseases, including trachoma. The cost of conducting epidemiologically rigorous prevalence surveys should not be a barrier to program implementation or evaluation. [ABSTRACT FROM AUTHOR]

The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated. Author summary: Today's diagnosis of infection with the filarial parasite Onchocerca volvulus mainly depends on the microscopic analysis of skin biopsies and serological testing. The work presented here describes the use of multiple mass spectrometry-based screening methods (metabolomics and lipidomics) to search for biomarkers indicative of infection with Onchocerca volvulus. This resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine as biomarker for O. volvulus. Further evaluation of these biomarkers in a geographically distinct non-endemic population however invalidated the use of urine cis-cinnamoylglycine. These findings are of utmost importance as it not only opens new avenues in the development of non-invasive diagnostic tools for filarial infections, but also emphasizes the need for evaluation and validation of newly discovered biomarkers in different populations from different geographies. [ABSTRACT FROM AUTHOR]

Beside diagnostic uncertainties due to the lack of a perfect gold standard test for Helicobacter pylori infection, the diagnosis and the prevalence estimation for this infection encounter particular challenges in Africa including limited diagnostic tools and specific genetic background. We developed and evaluated the accuracy of an enzyme-linked immunosorbent assay (ELISA) system tailored for H. pylori genetics in Africa (HpAfr-ELISA). Strains belonging to main genetic populations infecting Africans were exploited as sources for whole-cell antigens to establish in-house the ELISA system. A phase II unmatched case-control study explored the diagnostic accuracy of the HpAfr-ELISA using a training set of samples collected from dyspeptic patients from Kinshasa, the Democratic Republic of Congo (DRC) who had been tested with invasive standard tests (i.e., histology, culture, and rapid urease test) in 2017. Then the assay was cross-validated through a community-based survey assessing the prevalence of H. pylori and associated factors in 425 adults from Mbujimayi, DRC in 2018. Bayesian inferences were used to deal with statistical uncertainties of estimates (true prevalence, sensitivity, and specificity) in the study population. At its optimal cut-off-value 20.2 U/mL, the assay achieved an estimated sensitivity of 97.6% (95% credible interval [95%CrI]: 89.2; 99.9%) and specificity of 90.5% (95%CrI: 78.6; 98.5). Consistent outcomes obtained at repeated tests attested the robustness of the assay (negative and positive agreements always > 70%). The true prevalence of H. pylori was estimated 53.8% [95%CrI: 42.8; 62.7%]. Increasing age (adjusted odds ratio [aOR] = 1.0 [95% confidence interval (CI): 1.0; 1.1]; p<0.001), overcrowding households (aOR = 3.2 [95%CI: 2.0; 5.1]; p<0.001), and non-optimal hand hygiene (aOR = 4.5 [95%CI: 2.0; 11.4]; p = 0.001) were independently associated with the H. pylori-seropositivity. The novel ELISA system has demonstrated good diagnostic accuracy and potential usefulness for management and mitigation strategies for H. pylori infection in African settings. Author summary: Enzyme-linked immunosorbent assay (ELISA) systems are useful tools for mass screening of Helicobacter pylori infection but their use encounters important challenges in Africa. This is mainly due to the specific genetic background of African H. pylori that may jeopardize the accuracy of currently available ELISA kits. In this study, we developed a new ELISA system, i.e. HpAfr-ELISA, based on pooled antigens of H. pylori that represent main genetic populations colonizing Africa. This new assay could be validated analytically using training samples collected in H. pylori positive and negative patients from the Democratic Republic of Congo (DRC). Then, the tool was successfully applied to a real-world community-based mass survey aiming at assessing the epidemiology of H. pylori in a rural area of the DRC. The characteristics of the HpAfr-ELISA assay indicated good robustness and high performances for detection of H. pylori. Statistical modeling enabled estimating the true latent prevalence of H. pylori infection and identifying factors predicting the exposition to the infection in the study population. This outcome will be useful for drawing efficient health policies and optimally allocating available resources to fight the H. pylori infection and related complications (e.g., gastric cancer) in the study area and globally in Africa. [ABSTRACT FROM AUTHOR]

Tsetse-transmitted Animal African Trypanosomosis (AAT) is one of the most important constraints to livestock development in Africa. Use of trypanocides has been the most widespread approach for the management of AAT, despite the associated drug resistance and health concerns associated with drug metabolites in animal products. Alternative control measures that target tsetse fly vectors of AAT, though effective, have been hard to sustain in part because these are public goods applied area-wide. The International Centre of Insect Physiology and Ecology (icipe) and partners have developed and implemented a novel tsetse repellent collar (TRC) applied on animals to limit contact of tsetse flies and livestock, thereby reducing AAT transmission. The TRC has now advanced to commercialization. A household-level survey involving 632 cattle keeping households, was conducted in Shimba Hills region of Kwale County, where field trials of the TRC have been previously conducted to assess farmers' knowledge, perception, and practices towards the management of tsetse flies, their willingness to pay (WTP) for the TRC, and factors affecting the WTP. Almost all the respondents (90%) reported that tsetse flies were the leading cattle infesting pests in the area. About 22% of these correctly identified at least four AAT clinical signs, and even though many (68%) used trypanocidal drugs to manage the disease, 50% did not perceive the drug as being effective in AAT management (50%). Few respondents (8%) were aware of the harmful effects of trypanocidal drugs. About 89% of the respondents were aware of icipe TRC, and 30% of them were using the field trial collars during the survey. Sixty-three (63%) of them were willing to pay for the TRC at the same cost they spend treating an animal for AAT. On average farmers were willing to pay KES 3,352 per animal per year. Male educated household heads are likely to pay more for the TRC. Moreover, perceived high AAT prevalence and severity further increases the WTP. Wider dissemination and commercialization of the herd-level tsetse control approach (TRC) should be encouraged to impede AAT transmission and thus enhance food security and farm incomes among the affected rural communities. Besides the uptake of TRC can be enhanced through training, especially among women farmers. Author summary: Animal African Trypanosomosis is a tropical disease that is of economic importance in Sub-Saharan Africa. The livestock sub-sector supports approximately 600 million smallholders in developing countries through employment, income from livestock products, and improving crop productivity through draft power and manure. Efforts to reduce rural poverty and improve food security and nutrition, therefore, require utilizing livestock to their full potential. Trypanosomosis results in anemia, emaciation, productivity loss, and mortality, and remains a leading constraint to livestock development in Africa. To reduce the risks associated with the use of trypanocides, alternative control measures that target the vector- tsetse fly need to be developed and widely disseminated. The International Centre of Insect Physiology and Ecology (icipe) and partners have—developed and implemented a novel tsetse repellent collar that shields animals from getting into contact with the vector, thereby preventing trypanosomosis transmission. The collar has now advanced to a commercialization stage. We conducted community and household-level surveys to assess farmer's knowledge, perception, and practices regarding tsetse pest and trypanosomosis, and their willingness to pay for the novel tsetse repellent collar. We found that the pest is the main cattle production constraint and the cause of the associated disease, although there exists a gap in the identification of the clinical signs of the disease. Besides, most farmers rely on trypanocidal drugs for the treatment of their animals despite their human health and environmental risks. However, the majority were willing to buy the newly developed canvas collar. A male head of a household with a higher level of education is likely to pay more for the novel tsetse repellent collar. Besides, perception of high prevalence and severity of AAT is likely to increase the willingness to pay for the herd-level technology. The findings emphasize the need for wider dissemination and commercialization of the tsetse repellent collar technology to reduce trypanosomosis transmission and hence enhance food security and farm incomes in the affected regions in Africa. [ABSTRACT FROM AUTHOR]

Background: The sand fly Phlebotomus perniciosus is the main vector of Leishmania infantum, etiological agent of zoonotic visceral leishmaniasis in the Western Mediterranean basin. Dogs are the main reservoir host of this disease. The main objective of this study was to determine, under both laboratory and field conditions, if dogs infected with L. infantum, were more attractive to female P. perniciosus than uninfected dogs. Methodology/Principal findings: We carried out a series of host choice experiments and found that infected dogs were significantly more attractive to P. perniciosus than uninfected dogs in the laboratory as well as in the field. Significantly more P. perniciosus fed on infected dogs than on uninfected dogs. However, the fecundity of P. perniciosus fed on infected dogs was adversely impacted compared to uninfected dogs by lowering the number of laid eggs. Phlebotomus perfiliewi, the second most abundant sand fly species in the field site and a competent vector of L. infantum had similar trends of attractivity as P. perniciosus toward infected dogs under field conditions. Conclusions: The results strongly suggest that L. infantum causes physiological changes in the reservoir host which lead to the host becoming more attractive to both male and female P. perniciosus. These changes are likely to improve the chance of successful transmission because of increased contact with infected hosts and therefore, infected dogs should be particularly targeted in the control of zoonotic visceral leishmaniasis in North Africa. Author summary: Zoonotic visceral leishmaniasis is a neglected tropical disease caused by the parasite Leishmania infantum. In the Western Mediterranean basin, Phlebotomus perniciosus and Phlebotomus perfiliewi are the main vectors of L. infantum, and dogs are the main reservoir host of the parasite. In Northern Africa, ZVL affect mostly children less than 5 years. Understanding the chemical ecology governing the relationships between the vector, the parasite and the reservoir host is of major epidemiological importance. Previous studies based on rodent models have shown that the infection with L. infantum enhanced the attractiveness towards Lutzomyia longipaplis, the main vector of ZVL in the Americas. In this study, we reported for the first time that infected dogs are highly attractive to both male and female P. perniciosus under laboratory and filed conditions compared to uninfected dogs. Similar patterns were observed with wild populations of P. perfiliewi. Our results provided strong evidence that the parasite manipulate the reservoir hosts to enhance its transmission success by the vector. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is an emerging, mosquito-borne alphavirus responsible for acute to chronic arthralgias and neuropathies. Although it originated in central Africa, recent reports of disease have come from many parts of the world, including the Americas. While limiting human CHIKV cases through mosquito control has been used, it has not been entirely successful. There are currently no licensed vaccines or treatments specific for CHIKV disease, thus more work is needed to develop effective countermeasures. Current animal research on CHIKV is often not representative of human disease. Most models use CHIKV needle inoculation via unnatural routes to create immediate viremia and localized clinical signs; these methods neglect the natural route of transmission (the mosquito vector bite) and the associated human immune response. Since mosquito saliva has been shown to have a profound effect on viral pathogenesis, we evaluated a novel model of infection that included the natural vector, Aedes species mosquitoes, transmitting CHIKV to mice containing components of the human immune system. Humanized mice infected by 3–6 mosquito bites showed signs of systemic infection, with demonstrable viremia (by qRT-PCR and immunofluorescent antibody assay), mild to moderate clinical signs (by observation, histology, and immunohistochemistry), and immune responses consistent with human infection (by flow cytometry and IgM ELISA). This model should give a better understanding of human CHIKV disease and allow for more realistic evaluations of mechanisms of pathogenesis, prophylaxis, and treatments. Author summary: In humans, CHIKV infections are mostly symptomatic, resulting in fever, viremia, and debilitating joint disease; viremia is present up to 13 days after the onset of fever and peaks at the onset of clinical signs. Previous studies in mice and nonhuman primates (NHPs) have often neglected the mosquito vector, leading to variable viremias and infection of tissues primarily at the sites of CHIKV injection (legs in mice, ankles or spleen/liver in NHPs). This is the first study to demonstrate systemic CHIKV infection caused by infected mosquito bites in humanized laboratory mice. Disease seen with this humanized mouse model mimics human clinical signs and symptoms, with signs of inflammation in muscle and joints due to viral replication. This humanized mouse model provides a basis for assessing human CHIKV pathogenesis, prophylaxis, and treatment, under natural conditions of infection. [ABSTRACT FROM AUTHOR]

Background: Histoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions. Methodology: We conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation. Principal findings: Evidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon. Conclusions: The high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. Author summary: Histoplasmosis is a fungal infection caused by inhalation of spores of the fungus Histoplasma spp. It occurs in specific endemic areas, such as areas of USA, Africa and Latin America. However, the real burden of histoplasmosis remains unknown in many endemic regions. Clinically, histoplasmosis is frequently misdiagnosed as tuberculosis. The current study was carried out to explore the frequency and characteristics of Histoplasma infection in a series of autopsies conducted in the Brazilian Amazon. We found evidence of Histoplasma infection in one-third of the deceased patients. A significant proportion of the cases were disseminated infections, with extensive involvement and severe damage of most organs. All these disseminated infections occurred in HIV-positive patients. Strikingly, histoplasmosis was clinically missed in more than two-thirds of these patients and had an extremely high mortality. In conclusion, the high frequency and mortality of histoplasmosis, together with the frequent misdiagnosis of the disease, highlight the need of implementation of sensitive screening methods for Histoplasma in HIV patients in endemic areas. Additionally, antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. [ABSTRACT FROM AUTHOR]

Paragonimiasis is caused by zoonotic trematodes of Paragonimus spp., found in Asia, the Americas and Africa, particularly in tropical regions. These parasites have a complex, multi-host life cycle, with mammalian definitive hosts and larval stages cycling through two intermediate hosts (snails and freshwater crabs). In Africa, paragonimiasis is particularly neglected, and remains the only human parasitic disease without a fully characterised life cycle. However paragonimiasis has potentially significant impacts on public health in Africa, and prevalence has likely been underestimated through under-reporting and misdiagnosis as tuberculosis due to a similar clinical presentation. We identified the need to synthesise current knowledge and map endemic foci for African Paragonimus spp. together with Poikilorchis congolensis, a rare, taxonomically distant trematode with a similar distribution and morphology. We present the first systematic review of the literature relating to African paragonimiasis, combined with mapping of all reported occurrences of Paragonimus spp. throughout Africa, from the 1910s to the present. In human surveys, numerous reports of significant recent transmission in Southeast Nigeria were uncovered, with high prevalence and intensity of infection. Overall prevalence was significantly higher for P. uterobilateralis compared to P. africanus across studies. The potential endemicity of P. africanus in Cote d'Ivoire is also reported. In freshwater crab intermediate hosts, differences in prevalence and intensity of either P. uterobilateralis or P. africanus were evident across genus and species, suggesting differences in susceptibility. Mapping showed temporal stability of endemic foci, with the majority of known occurrences of Paragonimus found in the rainforest zone of West and Central Africa, but with several outliers elsewhere on the continent. This suggests substantial under sampling and localised infection where potential host distributions overlap. Our review highlights the urgent need for increased sampling in active disease foci in Africa, particularly using molecular analysis to fully characterise Paragonimus species and their hosts. Author summary: Paragonimiasis is a lung disease caused by food-borne zoonotic trematodes of Paragonimus spp., multi-host parasites whose complex life cycle includes primary (snail), secondary (freshwater crab), and mammalian definitive hosts. In Africa, paragonimiasis is a particularly neglected disease, where prevalence has likely been underestimated through under reporting and misdiagnosis as tuberculosis; and it remains the only human parasite without a fully known life-cycle. We present the first systematic review of paragonimiasis in Africa, including 143 publications. In human studies, we uncovered substantial recent transmission in Southeast Nigeria, and recent transmission also in Cote d'Ivoire and Cameroon in endemic foci; significantly higher prevalence of P. uterobilateralis than P. africanus; and evidence supporting the existence of P. africanus in Cote d'Ivoire. In freshwater crab intermediate hosts, prevalence and intensity of either P. uterobilateralis or P. africanus varied across genera and species, suggesting differences in susceptibility. Mapping revealed evidence of temporal stability at endemic foci in rainforest regions; and widespread outliers. Numerous reports of significant recent transmission, particularly in Southeast Nigeria should be heeded by the international NTD research community. Increased studies are urgently needed to ascertain the real distribution and diversity of Paragonimus species in Africa. [ABSTRACT FROM AUTHOR]

Achieving a deeper understanding of the factors controlling the defense responses of invertebrate vectors to the human-infecting pathogens they transmit will provide needed new leads to pursue for control. Consequently, we provide new genomic and transcriptomic insights regarding FReDs (containing a fibrinogen domain) and FREPs (fibrinogen domain and one or two IgSF domains) from the planorbid snail Biomphalaria glabrata, a Neotropical vector of Schistosoma mansoni, causative agent of human intestinal schistosomiasis. Using new bioinformatics approaches to improve annotation applied to both genome and RNA-Seq data, we identify 73 FReD genes, 39 of which are FREPs. We provide details of domain structure and consider relationships and homologies of B. glabrata FBG and IgSF domains. We note that schistosome-resistant (BS-90) snails mount complex FREP responses following exposure to S. mansoni infection whereas schistosome-susceptible (M line) snails do not. We also identify several coding differences between BS-90 and M line snails in three FREPs (2, 3.1 and 3.2) repeatedly implicated in other studies of anti-schistosome responses. In combination with other results, our study provides a strong impetus to pursue particular FREPs (2, 3.1, 3.2 and 4) as candidate resistance factors to be considered more broadly with respect to schistosome control efforts, including involving other Biomphalaria species vectoring S. mansoni in endemic areas in Africa. Author summary: Just as malaria parasites depend on mosquitoes for transmission, Schistosoma trematodes that infect 200+ million people in developing countries depend on freshwater snails to support their development. New control methods targeting schistosomes in the snail host are urgently needed to help break the cycle of transmission. Identification of molecules in snails that confer or facilitate resistance to successful larval development offers one way forward. Building on previous studies and new data, we used a combination of bioinformatics tools to characterize a repertoire of molecules in B. glabrata containing fibrinogen or IgSF domains, or both (the latter molecules called FREPs, first discovered in B. glabrata). We found that snails resistant to schistosomes mount vigorous, multi-component FREP responses following exposure to schistosomes whereas responses of susceptible snails are modest by comparison. Furthermore, for four FREPs repeatedly implicated in snail responses to trematodes, three (FREPs 2, 3.1 and 3.2) exist in distinctive allelic forms in susceptible and resistant snails. We propose that the search for homologous molecules needs to move to the field, to B. glabrata in the Neotropics and to other vector species of Biomphalaria in Africa, to explore the potential of FREPs as resistance factors worthy of development as control agents. [ABSTRACT FROM AUTHOR]

Podoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa are uncertain. We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the environmental suitability and human population at risk of podoconiosis in Africa. Environmental suitability for podoconiosis was predicted in 29 African countries. In the year 2020, the total population in areas suitable for podoconiosis is estimated at 114.5 million people, (95% uncertainty interval: 109.4–123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units (typically second administrative-level units, such as districts) defined by the World Health Organization in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of implementation units with high environmental suitability are located in Angola (80, 4.8%), Cameroon (170, 10.3%), the DRC (244, 14.7%), Ethiopia (495, 29.9%), Kenya (217, 13.1%), Uganda (116, 7.0%) and Tanzania (112, 6.8%). Of the 1,655 environmentally suitable implementation units, 960 (58.0%) require more detailed community-level mapping. Our estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes. Author summary: Podoconiosis is one of the major causes of tropical lymphedema and results in massive swelling of the lower limbs. It is caused by exposure to mineral particle-induced inflammation among genetically susceptible individuals. People affected by the disease often suffer both physical and psychological comorbidities, which can include painful swelling, distress, depression, stigma and discrimination. In spite of its presence among some African countries, its geographical distribution and burden in Africa are uncertain. We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data (elevation, annual precipitation, land surface temperature, vegetation index, and soil characteristics such as clay and silt fraction) and overlaying population figures, we predicted both the environmental suitability as well as the human population at risk for podoconiosis in Africa. Environmental suitability for podoconiosis was predicted in 29 African countries. Our estimates provide key evidence that will help decision-makers to better plan more integrated intervention programmes. [ABSTRACT FROM AUTHOR]

Background: An estimated 59,000 people die from rabies annually, with 99% of those deaths attributable to bites from domestic dogs (Canis lupus familiaris). This preventable Neglected Tropical Disease has a large impact across continental Africa, especially for rural populations living in close contact with livestock and wildlife. Mass vaccinations of domestic dogs are effective at eliminating rabies but require large amounts of resources, planning, and political will to implement. Grassroots campaigns provide an alternative method to successful implementation of rabies control but remain understudied in their effectiveness to eliminate the disease from larger regions. Methodology/Principal Findings: We report on the development, implementation, and effectiveness of a grassroots mass dog rabies vaccination campaign in Kenya, the Laikipia Rabies Vaccination Campaign. During 2015–2017, a total of 13,155 domestic dogs were vaccinated against rabies in 17 communities covering approximately 1500 km2. Based on an estimated population size of 34,275 domestic dogs, percent coverages increased across years, from 2% in 2015 to 24% in 2017, with only 3 of 38 community-years of vaccination exceeding the 70% target. The average cost of vaccinating an animal was $3.44 USD with in-kind contributions and $7.44 USD without in-kind contributions. Conclusions/Significance: The evolution of the Laikipia Rabies Vaccination Campaign from a localized volunteer-effort to a large-scale program attempting to eliminate rabies at the landscape scale provides a unique opportunity to examine successes, failures, and challenges facing grassroots campaigns. Success, in the form of vaccinating more dogs across the study area, was relatively straightforward to achieve. However, lack of effective post-vaccination monitoring and education programs, limited funding, and working in diverse community types appeared to hinder achievement of 70% coverage levels. These results indicate that grassroots campaigns will inevitably be faced with a philosophical question regarding the value of local impacts versus their contributions to a larger effort to eliminate rabies at the regional, country, or global scale. Author summary: Given the importance of mass vaccinations of domestic dogs towards eliminating human rabies in Africa and the site-specific challenges facing such campaigns, additional studies on the development and implementation of such efforts are needed. One mechanism of mass vaccination lies in grassroots efforts that often begin at a very local scale and either develop into larger campaigns, remain local, or cease to persist past several years once interest and funding is exhausted. Here, we discuss the development of a grassroots campaign in Laikipia County, Kenya from its local inception to its development into a county-wide rabies elimination effort. Our results highlight challenges associated with achieving the targeted 70% coverage rate, including a need for consistent and systematic demographic monitoring of dog populations, limitations of the central point method, and logistical and financial challenges facing a volunteer-based effort. Serious political commitment from both the local and national governments are necessary to take the budget beyond what a crowdfunded campaign can raise, including availability and access to quality dog rabies vaccines. Without such outside support and substantial time to grow, grassroots campaigns might be better relegated to raising awareness and vaccinating dogs in small communities to protect those communities directly, without contributing to the broader ecosystem-wide transmission-stopping aim often sought by government human health and veterinary organizations. [ABSTRACT FROM AUTHOR]

Snakebite envenoming is a major neglected tropical disease that affects millions of people every year. The only effective treatment against snakebite envenoming consists of unspecified cocktails of polyclonal antibodies purified from the plasma of immunized production animals. Currently, little data exists on the molecular interactions between venom-toxin epitopes and antivenom-antibody paratopes. To address this issue, high-density peptide microarray (hdpm) technology has recently been adapted to the field of toxinology. However, analysis of such valuable datasets requires expert understanding and, thus, complicates its broad application within the field. In the present study, we developed a user-friendly, and high-throughput web application named "Snake Toxin and Antivenom Binding Profiles" (STAB Profiles), to allow straight-forward analysis of hdpm datasets. To test our tool and evaluate its performance with a large dataset, we conducted hdpm assays using all African snake toxin protein sequences available in the UniProt database at the time of study design, together with eight commercial antivenoms in clinical use in Africa, thus representing the largest venom-antivenom dataset to date. Furthermore, we introduced a novel method for evaluating raw signals from a peptide microarray experiment and a data normalization protocol enabling intra-microarray and even inter-microarray chip comparisons. Finally, these data, alongside all the data from previous similar studies by Engmark et al., were preprocessed according to our newly developed protocol and made publicly available for download through the STAB Profiles web application (http://tropicalpharmacology.com/tools/stab-profiles/). With these data and our tool, we were able to gain key insights into toxin-antivenom interactions and were able to differentiate the ability of different antivenoms to interact with certain toxins of interest. The data, as well as the web application, we present in this article should be of significant value to the venom-antivenom research community. Knowledge gained from our current and future analyses of this dataset carry the potential to guide the improvement and optimization of current antivenoms for maximum patient benefit, as well as aid the development of next-generation antivenoms. Author summary: Millions of people are bitten by venomous snakes each year, resulting in over 100,000 deaths. Currently, such envenomings are treated with animal derived antivenoms that contain undefined antibodies against snake venom toxins that have been raised by the production animal's immune system. To date, our understanding of these antibody toxin interactions is sparse, but with the help of high-density peptide microarray (hdpm) technology this is starting to change. Whilst this technology is very powerful, analysis of the output data is complex and requires expert training. Therefore, in this study, we developed a user-friendly, and high-throughput web application named "Snake Toxin and Antivenom Binding Profiles" (STAB Profiles). Furthermore, we ensured our tool was functional and able to handle large amounts of data by creating an entirely novel and larger than ever hdpm dataset based on all African snake toxin proteins together with eight commercial antivenoms. With these data and our tool, we were able to further our understanding on toxin-antivenom interactions and were able to differentiate the ability of different antivenoms to interact with certain toxins of interest. Ideally, these and future insights can help guide the improvement and optimization of current antivenoms, as well as aid the informed development of next-generation antivenoms. [ABSTRACT FROM AUTHOR]

Africa is the second most populous continent and has perennial health challenges. Of the estimated 181 million school aged children in sub-Saharan Africa (SSA), nearly half suffer from ascariasis, trichuriasis, or a combination of these infections. Coupled with these is the problem of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection, which is a leading cause of death in the region. Compared to the effect of the human immunodeficiency virus on the development of TB, the effect of chronic helminth infections is a neglected area of research, yet helminth infections are as ubiquitous as they are varied and may potentially have profound effects upon host immunity, particularly as it relates to TB infection, diagnosis, and vaccination. Protection against active TB is known to require a clearly delineated T-helper type 1 (Th1) response, while helminths induce a strong opposing Th2 and immune-regulatory host response. This Review highlights the potential challenges of helminth–TB co-infection in Africa and the need for further research. [ABSTRACT FROM AUTHOR]

Background: To counter the increasing global risk of Yellow fever (YF), the World Health Organisation initiated the Eliminate Yellow fever Epidemics (EYE) strategy. Estimating YF burden, as well as vaccine impact, while accounting for the features of urban YF transmission such as indirect benefits of vaccination, is key to informing this strategy. Methods and findings: We developed two model variants to estimate YF burden in sub-Saharan Africa, assuming all infections stem from either the sylvatic or the urban cycle of the disease. Both relied on an ecological niche model fitted to the local presence of any YF reported event in 34 African countries. We calibrated under-reporting using independent estimates of transmission intensity provided by 12 serological surveys performed in 11 countries. We calculated local numbers of YF infections, deaths and disability-adjusted life years (DALYs) lost based on estimated transmission intensity while accounting for time-varying vaccination coverage. We estimated vaccine demand and impact of future preventive mass vaccination campaigns (PMVCs) according to various vaccination scenarios. Vaccination activities conducted in Africa between 2005 and 2017 were estimated to prevent from 3.3 (95% CI 1.2–7.7) to 6.1 (95% CI 2.4–13.2) millions of deaths over the lifetime of vaccinees, representing extreme scenarios of none or maximal herd effects, respectively. By prioritizing provinces based on the risk of urban YF transmission in future PMVCs, an average of 37.7 million annual doses for PMVCs over eight years would avert an estimated 9,900,000 (95% CI 7,000,000–13,400,000) infections and 480,000 (180,000–1,140,000) deaths over the lifetime of vaccinees, corresponding to 1.7 (0.7–4.1) deaths averted per 1,000 vaccine doses. Conclusions: By estimating YF burden and vaccine impact over a range of spatial and temporal scales, while accounting for the specificity of urban transmission, our model can be used to inform the current EYE strategy. Author summary: As large-scale vaccination campaigns are begun or continued with the aim to eliminate yellow fever (YF) epidemics in several countries, estimating disease burden and vaccine impact is timely. We developed two model variants to estimate YF burden in sub-Saharan Africa, each either representing the sylvatic or urban cycle of the disease. Both relied on an ecological niche model fitted to known records of YF in 34 African countries and calibrated using serological survey data. Local numbers of YF infections and deaths were derived while accounting for time-varying vaccination coverage. We estimated vaccine demand and the impact of future preventive mass vaccination campaigns according to various vaccination scenarios. By providing burden and vaccine impact estimates over a range of spatial and temporal scales, and accounting for the specificity of urban transmission, our model can be used to inform the current international strategy to counter the increasing global risk of yellow fever. [ABSTRACT FROM AUTHOR]

Significant reductions in populations of tsetse (Glossina spp) in parts of Zimbabwe have been attributed to increases in temperature over recent decades. Sustained increases in temperature might lead to local extinctions of tsetse populations. Extinction probabilities for tsetse populations have not so far been estimated as a function of temperature. We develop a time-homogeneous branching process model for situations where tsetse live at different levels of fixed temperature. We derive a probability distribution pk(T) for the number of female offspring an adult female tsetse is expected to produce in her lifetime, as a function of the fixed temperature at which she is living. We show that pk(T) can be expressed as a geometric series: its generating function is therefore a fractional linear type. We obtain expressions for the extinction probability, reproduction number, time to extinction and growth rates. The results are valid for all tsetse, but detailed effects of temperature will vary between species. No G. m. morsitans population can escape extinction if subjected, for extended periods, to temperatures outside the range 16°C–32°C. Extinction probability increases more rapidly as temperatures approach and exceed the upper and lower limits. If the number of females is large enough, the population can still survive even at high temperatures (28°C–31°C). Small decreases or increases in constant temperature in the neighbourhoods of 16°C and 31°C, respectively, can drive tsetse populations to extinction. Further study is needed to estimate extinction probabilities for tsetse populations in field situations where temperatures vary continuously. Author summary: Tsetse flies (Glossina spp) are the vectors of the African sleeping sickness. We derived expressions for the extinction probability, and mean time to extinction, of closed populations of G. m. morsitans experiencing different levels of fixed temperature. Temperature plays a key role in tsetse population dynamics: no population of G. m. morsitans can escape extinction at constant temperatures < 16°C or > 32°C. The effect of temperature is more severe if tsetse populations are already depleted. Increasingly high temperatures due to climate change may alter the distribution of tsetse populations in Africa. The continent may witness local extinctions of tsetse populations in some places, and appearances in places hitherto too cold for tsetse. [ABSTRACT FROM AUTHOR]