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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: Endemic areas for soil-transmitted helminthiases often lack the tools and trained personnel necessary for point-of-care diagnosis. This study pilots the use of smartphone microscopy and an artificial neural network-based object detection application named Kankanet to address those two needs. Methodology/Principal findings: A smartphone was equipped with a USB Video Class (UVC) microscope attachment and Kankanet, which was trained to recognize eggs of Ascaris lumbricoides, Trichuris trichiura, and hookworm using a dataset of 2,078 images. It was evaluated for interpretive accuracy based on 185 new images. Fecal samples were processed using Kato-Katz (KK), spontaneous sedimentation technique in tube (SSTT), and Merthiolate-Iodine-Formaldehyde (MIF) techniques. UVC imaging and ANN interpretation of these slides was compared to parasitologist interpretation of standard microscopy.Relative to a gold standard defined as any positive result from parasitologist reading of KK, SSTT, and MIF preparations through standard microscopy, parasitologists reading UVC imaging of SSTT achieved a comparable sensitivity (82.9%) and specificity (97.1%) in A. lumbricoides to standard KK interpretation (97.0% sensitivity, 96.0% specificity). The UVC could not accurately image T. trichiura or hookworm. Though Kankanet interpretation was not quite as sensitive as parasitologist interpretation, it still achieved high sensitivity for A. lumbricoides and hookworm (69.6% and 71.4%, respectively). Kankanet showed high sensitivity for T. trichiura in microscope images (100.0%), but low in UVC images (50.0%). Conclusions/Significance: The UVC achieved comparable sensitivity to standard microscopy with only A. lumbricoides. With further improvement of image resolution and magnification, UVC shows promise as a point-of-care imaging tool. In addition to smartphone microscopy, ANN-based object detection can be developed as a diagnostic aid. Though trained with a limited dataset, Kankanet accurately interprets both standard microscope and low-quality UVC images. Kankanet may achieve sensitivity comparable to parasitologists with continued expansion of the image database and improvement of machine learning technology. [ABSTRACT FROM AUTHOR]

Background: Worldwide, snakebite envenomations total ~2.7 million reported cases annually with ~100,000 fatalities. Since 2009, snakebite envenomation has intermittently been classified as a very important ‘neglected tropical disease’ by the World Health Organisation. Despite this emerging awareness, limited efforts have been geared towards addressing the serious public health implications of snakebites, particularly in sub-Saharan Africa, where baseline epidemiological and ecological data remain incomplete. Due to poverty as well as limited infrastructure and public health facilities, people in rural Africa, including Ghana, often have no other choice than to seek treatment from traditional medical practitioners (TMPs). The African ‘snakebite crisis’ is highlighted here using regionally representative complementary data from a community-based epidemiological and ecological study in the savanna zone of northern Ghana. Methodology and findings: Our baseline study involved two data collection methods in the Savelugu-Nanton District (in 2019 the district was separated into Savelugu and Nanton districts) in northern Ghana, comprising a cross-sectional study of 1,000 residents and 24 TMPs between December 2008 and May 2009. Semi-structured interviews, as well as collection of retrospective snakebite and concurrent rainfall records from the Savelugu-Nanton District Hospital and Ghana Meteorological Authority respectively over 10-years (1999–2008) were used in the study. Variables tested included demography, human activity patterns, seasonality, snake ecology and clinical reports. Complementary data showed higher snakebite prevalence during the rainy season, and a hump-shaped correlation between rainfall intensity and snakebite incidences. Almost 6% of respondents had experienced a personal snakebite, whereas ~60% of respondents had witnessed a total of 799 snakebite cases. Out of a total of 857 reported snakebite cases, 24 (~2.8%) died. The highest snakebite prevalence was recorded for males in the age group 15–44 years during farming activities, with most bites occurring in the leg/foot region. The highest snakebite rate was within farmlands, most severe bites frequently caused by the Carpet viper (Echis ocellatus). Conclusion: The relatively high community-based prevalence of ~6%, and case fatality ratio of ~3%, indicate that snakebites represent an important public health risk in northern Ghana. Based on the high number of respondents and long recording period, we believe these data truly reflect the general situation in the rural northern savanna zone of Ghana and West Africa at large. We recommend increased efforts from both local and international health authorities to address the current snakebite health crisis generally compromising livelihoods and productivity of rural farming communities in West Africa. [ABSTRACT FROM AUTHOR]

Background: Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz. Methods: An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy. Principal findings and conclusions: The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Over recent decades, Salmonella infection research has predominantly relied on murine infection models. However, in many cases the infection phenotypes of Salmonella pathovars in mice do not recapitulate human disease. For example, Salmonella Typhimurium ST313 is associated with enhanced invasive infection of immunocompromised people in Africa, but infection of mice and other animal models with ST313 have not consistently reproduced this invasive phenotype. The introduction of alternative infection models could help to improve the quality and reproducibility of pathogenesis research by facilitating larger-scale experiments. To investigate the virulence of S. Typhimurium ST313 in comparison with ST19, a combination of avian and insect disease models were used. We performed experimental infections in five lines of inbred and one line of outbred chickens, as well as in the alternative chick embryo and Galleria mellonella wax moth larvae models. This extensive set of experiments identified broadly similar patterns of disease caused by the African and global pathovariants of Salmonella Typhimurium in the chicken, the chicken embryo and insect models. A comprehensive analysis of all the chicken infection experiments revealed that the African ST313 isolate D23580 had a subtle phenotype of reduced levels of organ colonisation in inbred chickens, relative to ST19 strain 4/74. ST313 isolate D23580 also caused reduced mortality in chicken embryos and insect larvae, when compared with ST19 4/74. We conclude that these three infection models do not reproduce the characteristics of the systemic disease caused by S. Typhimurium ST313 in humans. [ABSTRACT FROM AUTHOR]

Typhoid fever is endemic across sub-Saharan Africa. However, estimates of the burden of typhoid are undermined by insufficient blood volumes and lack of sensitivity of blood culture. Here, we aimed to address this limitation by exploiting pre-enrichment culture followed by PCR, alongside routine blood culture to improve typhoid case detection. We carried out a prospective diagnostic cohort study and enrolled children (aged 0–4 years) with non-specific febrile disease admitted to a tertiary hospital in Blantyre, Malawi from August 2014 to July 2016. Blood was collected for culture (BC) and real-time PCR after a pre-enrichment culture in tryptone soy broth and ox-bile. DNA was subjected to PCR for invA (Pan-Salmonella), staG (S. Typhi), and fliC (S. Typhimurium) genes. A positive PCR was defined as invA plus either staG or fliC (CT<29). IgM and IgG ELISA against four S. Typhi antigens was also performed. In total, 643 children (median age 1.3 years) with nonspecific febrile disease were enrolled; 31 (4.8%) were BC positive for Salmonella (n = 13 S. Typhi, n = 16 S. Typhimurium, and n = 2 S. Enteritidis). Pre-enrichment culture of blood followed by PCR identified a further 8 S. Typhi and 15 S. Typhimurium positive children. IgM and IgG titres to the S. Typhi antigen STY1498 (haemolysin) were significantly higher in children that were PCR positive but blood culture negative compared to febrile children with all other non-typhoid illnesses. The addition of pre-enrichment culture and PCR increased the case ascertainment of invasive Salmonella disease in children by 62–94%. These data support recent burden estimates that highlight the insensitivity of blood cultures and support the targeting of pre-school children for typhoid vaccine prevention in Africa. Blood culture with real-time PCR following pre-enrichment should be used to further refine estimates of vaccine effectiveness in typhoid vaccine trials. [ABSTRACT FROM AUTHOR]

Background: Podoconiosis, also known as mossy foot or endemic non-filarial elephantiasis, is a preventable form of lower-leg lymphoedema caused by prolonged (typically barefoot) exposure to soil derived from volcanic rocks. Acute adenolymphangitis (also called ‘acute attack’) is a serious complication of podoconiosis resulting in significant symptoms and worsening disability. Despite the well-known morbidity associated with podoconiosis, to date there have been no studies looking at the impact, or burden, of podoconiosis on caregivers. This study explored the experiences and impact of acute attacks on the caregivers of those with podoconiosis in one endemic district of Ethiopia. Methods/Principal findings: This qualitative study was based in Wayu Tuka woreda (district), Oromia, Western Ethiopia. 27 semi-structured interviews of those with podoconiosis and their caregivers were conducted in June 2018. Here we report the findings from the caregiver’s interviews. Data were analysed using NVivo 12. Directed content analysis, a qualitative approach related to thematic analysis, was used to analyse the results. This study highlights a previously unreported impact of acute attacks on the caregivers of those affected by podoconiosis. The findings demonstrate the significant social and financial pressures placed on podoconiosis-affected families which are exacerbated during acute attacks. This study also highlighted the emotional burden experienced by caregivers, the range of care activities placed on them and the limited support available. Conclusions: This study found a significant impact on the caregivers of those with podoconiosis, especially during acute attacks, in in Wayu Tuka woreda. It also highlighted the limited support available to caregivers. Further research is needed to understand whether this impact applies to podoconiosis caregivers across Ethiopia, and beyond, and to establish if there are wider implications of this important consequence of podoconiosis, for example on the economy and caregivers’ mental and physical health. [ABSTRACT FROM AUTHOR]

Background: The Madagascar National Strategic Plan for Malaria Control 2018 (NSP) outlines malaria control pre-elimination strategies that include detailed goals for mosquito control. Primary surveillance protocols and mosquito control interventions focus on indoor vectors of malaria, while many potential vectors feed and rest outdoors. Here we describe the application of tools that advance our understanding of diversity, host choice, and Plasmodium infection in the Anopheline mosquitoes of the Western Highland Fringe of Madagascar. Methodology/Principal findings: We employed a modified barrier screen trap, the QUadrant Enabled Screen Trap (QUEST), in conjunction with the recently developed multiplex BLOOdmeal Detection Assay for Regional Transmission (BLOODART). We captured a total of 1252 female Anopheles mosquitoes (10 species), all of which were subjected to BLOODART analysis. QUEST collection captured a heterogenous distribution of mosquito density, diversity, host choice, and Plasmodium infection. Concordance between Anopheles morphology and BLOODART species identifications ranged from 93–99%. Mosquito feeding behavior in this collection frequently exhibited multiple blood meal hosts (single host = 53.6%, two hosts = 42.1%, three hosts = 4.3%). The overall percentage of human positive bloodmeals increased between the December 2017 and the April 2018 timepoints (27% to 44%). Plasmodium positivity was frequently observed in the abdomens of vectors considered to be of secondary importance, with an overall prevalence of 6%. Conclusions/Significance: The QUEST was an efficient tool for sampling exophilic Anopheline mosquitoes. Vectors considered to be of secondary importance were commonly found with Plasmodium DNA in their abdomens, indicating a need to account for these species in routine surveillance efforts. Mosquitoes exhibited multiple blood feeding behavior within a gonotrophic cycle, with predominantly non-human hosts in the bloodmeal. Taken together, this complex feeding behavior could enhance the role of multiple Anopheline species in malaria transmission, possibly tempered by zoophilic feeding tendencies. [ABSTRACT FROM AUTHOR]

Background: Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa. Methodology/Principal findings: Our market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness. Conclusions/Significance: Clinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms. [ABSTRACT FROM AUTHOR]

Background: The Alliance for the Global Elimination of Trachoma has set the target for eliminating trachoma as a public health problem by 2020. However, challenges remain, including socio-cultural issues. Districts in Northern Tanzania, predominantly inhabited by the Maasai ethnic group, remain endemic for trachoma. We explored socio-cultural factors that may impact the elimination of trachoma. Methods/Findings: This study was nested within a larger ethnographic study of trachoma among Maasai in Northern Tanzania. We used stratified random sampling and semi-structured interviews to examine knowledge and understanding. Interviews were conducted and recorded in Maa, by a native Maa speaking trained interviewer. Transcripts were translated into English. A framework method for a content analysis was used. There was awareness of trachoma and basic symptoms. Yet understanding of etiology and prevention was poor. Trachoma was attributed to pollen, dust, and smoke. Water was recognized as beneficial, but seen as treatment and not prevention. Traditional medicines were most often used for treating conjunctival inflammation, with the most common being a rough leaf used to scratch the inside of the eyelid until it bleeds. Knowledge of mass drug administration (MDA) was inconsistent, although many thought it helped the community, but it was perceived as only for children and the sick. Many participants reported not taking azithromycin and some had no recollection of MDA six months earlier. There was little connection between childhood infection, trichiasis and related blindness. Trichiasis was often seen as a problem of old women, and treated locally by epilation. Conclusion/Significance: Understanding indigenous knowledge may help guide control programs, tailor them to local contexts, address local beliefs and dispel misunderstandings. There is an essential need to understand the social, cultural and political context of the target community to deliver effective programs. Despite limited knowledge, the community recognized trachoma as a public health problem. Results have implications for disease control programs in other marginalized communities. [ABSTRACT FROM AUTHOR]

Background: The world is witnessing mass displacement of populations which could impact global efforts to eliminate neglected tropical diseases such as trachoma. On the African continent, South Sudan has experienced high levels of population displacement. Population based baseline trachoma surveys were conducted among refugee camps in two Sudanese localities hosting South Sudanese refugee populations to determine whether the SAFE strategy was warranted. Methodology/Principal findings: Cross-sectional, multi-stage, cluster-random surveys were conducted within refugee camps in each of two Sudanese localities, Al Salam and Al Jabalain. For survey sampling, multiple camps within each locality were combined to form the sampling frame for that locality. Household water, sanitation and hygiene indicators were assessed, and trachoma signs were graded by trained and certified graders. The prevalence of trachomatous inflammation-follicular (TF) in children aged one to nine years was 15.7% (95%CI: 12.1–20.2) in Al Salam and 10.6% (95%CI: 7.9–14.0) in Al Jabalain. The prevalence of trachomatous trichiasis (TT) in those 15 years above was 2.9% (95%CI: 1.8–4.8) in Al Salam and 5.0% (95%CI: 3.8–6.6) in Al Jabalain. The presence of water and sanitation was high in both survey units. Conclusion/ Significance: Sudan has made progress in reducing the prevalence of trachoma within the country; however, the presence of over one million refugees from a neighboring trachoma hyper-endemic country could impact this progress. These surveys were the first step in addressing this important issue. The results demonstrate that at least three years of mass drug administration with azithromycin and tetracycline is needed in addition to the provision of TT surgical services. Additionally, it highlights that non-endemic or formerly endemic localities may have to adopt new strategies to provide services for refugee populations originating from hyper-endemic regions to ensure elimination of trachoma as a public health problem for all populations. [ABSTRACT FROM AUTHOR]

Background: Recent outbreaks of dengue and other Aedes aegypti-borne arboviruses highlight the importance of a rapid response for effective vector control. Data on insecticide resistance and underlying mechanisms are essential for outbreak preparedness, but are sparse in much of Africa. We investigated the levels and heterogeneity of insecticide resistance and mechanisms of Ae. aegypti from contrasting settings within and around Ouagadougou, Burkina Faso. Methodology/Principal findings: Bioassays were performed on larvae and adults to diagnose prevalence of resistance, and to assess levels where resistance was detected. Investigation of resistance mechanisms was performed using synergist bioassays, knockdown resistance (kdr) target site mutation genotyping and quantitative PCR expression analysis of candidate P450 genes. Larval dose-response assays indicated susceptibility to the organophosphates tested. Adult females were also susceptible to organophosphates, but resistance to carbamates was suspected in urban and semi-urban localities. Females from all localities showed resistance to pyrethroids but resistance prevalence and level were higher in urban and especially in semi-urban areas, compared to the rural population. Environment was also associated with susceptibility: adults reared from larvae collected in tires from the semi-urban site were significantly less resistant to pyrethroids than those collected from large outdoor drinking water containers (‘drums’). Susceptibility to both pyrethroids tested was largely restored by pre-exposure to Piperonyl Butoxide (PBO), suggesting a strong metabolic basis to resistance. The 1534C kdr mutation was nearly fixed in semi-urban and urban areas but was far less common in the rural area, where the 1016I kdr mutation frequency was also significantly lower. P450 gene analysis detected limited over-expression of single candidates but significantly elevated average expression in the semi-urban site compared to both a susceptible laboratory colony, and females from the other collection sites. Conclusions/Significance: Our results reveal pyrethroid resistance and paired kdr mutations in both urban and semi-urban sites at levels that are unprecedented for mainland Africa. The combination of target site and metabolic mechanisms is common in Ae. aegypti populations from other continents but is a worrying finding for African populations. However, organophosphate insecticides are still active against both larvae and adults of Ae. aegypti, providing useful insecticidal options for control and resistance management. [ABSTRACT FROM AUTHOR]

We present a new modeling tool that can be used to maximize the impact of canine rabies management resources that are available at the local level. The model is accessible through a web-based interface that allows for flexibility in the management strategies that can be investigated. Rabies vaccination, sterilization, chemo-contraception, and euthanasia can be specified and limited to specific demographic groups. Additionally, we allowed for considerable complexity in the specification of management costs. In many areas, the costs of contacting additional dogs increases as management effort increases, and this can have important strategic implications. We illustrated the application of the model by examining several alternative management strategies in an area of Mpumalanga Province, South Africa. Our results based on this dog population suggested that puppies should be vaccinated and sterilization would not be optimal if the spatial extent of management is not large (and perhaps not even then). Furthermore, given a sufficient budget, it was evident that vaccination campaigns should be repeated annually. [ABSTRACT FROM AUTHOR]

Forecasting the impacts of climate change on Aedes-borne viruses—especially dengue, chikungunya, and Zika—is a key component of public health preparedness. We apply an empirically parameterized model of viral transmission by the vectors Aedes aegypti and Ae. albopictus, as a function of temperature, to predict cumulative monthly global transmission risk in current climates, and compare them with projected risk in 2050 and 2080 based on general circulation models (GCMs). Our results show that if mosquito range shifts track optimal temperature ranges for transmission (21.3–34.0°C for Ae. aegypti; 19.9–29.4°C for Ae. albopictus), we can expect poleward shifts in Aedes-borne virus distributions. However, the differing thermal niches of the two vectors produce different patterns of shifts under climate change. More severe climate change scenarios produce larger population exposures to transmission by Ae. aegypti, but not by Ae. albopictus in the most extreme cases. Climate-driven risk of transmission from both mosquitoes will increase substantially, even in the short term, for most of Europe. In contrast, significant reductions in climate suitability are expected for Ae. albopictus, most noticeably in southeast Asia and west Africa. Within the next century, nearly a billion people are threatened with new exposure to virus transmission by both Aedes spp. in the worst-case scenario. As major net losses in year-round transmission risk are predicted for Ae. albopictus, we project a global shift towards more seasonal risk across regions. Many other complicating factors (like mosquito range limits and viral evolution) exist, but overall our results indicate that while climate change will lead to increased net and new exposures to Aedes-borne viruses, the most extreme increases in Ae. albopictus transmission are predicted to occur at intermediate climate change scenarios. [ABSTRACT FROM AUTHOR]

Background: Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by infections due to Trypanosoma brucei subspecies. In addition to the well-established environmental and behavioural risks of becoming infected, there is evidence for a genetic component to the response to trypanosome infection. We undertook a candidate gene case-control study to investigate genetic associations further. Methodology: We genotyped one polymorphism in each of seven genes (IL1A, IL1RN, IL4RN, IL6, HP, HPR, and HLA-G) in 73 cases and 250 controls collected from 19 ethno-linguistic subgroups stratified into three major ethno-linguistic groups, 2 pooled ethno-linguistic groups and 11 ethno-linguistic subgroups from three Cameroonian HAT foci. The seven polymorphic loci tested consisted of three SNPs, three variable numbers of tandem repeat (VNTR) and one INDEL. Results: We found that the genotype (TT) and minor allele (T) of IL1A gene as well as the genotype 1A3A of IL1RN were associated with an increased risk of getting Trypanosoma brucei gambiense and develop HAT when all data were analysed together and also when stratified by the three major ethno-linguistic groups, 2 pooled ethno-linguistic subgroups and 11 ethno-linguistic subgroups. Conclusion: This study revealed that one SNP rs1800794 of IL1A and one VNTR rs2234663 of IL1RN were associated with the increased risk to be infected by Trypanosoma brucei gambiense and develop sleeping sickness in southern Cameroon. The minor allele T and the genotype TT of SNP rs1800794 in IL1A as well as the genotype 1A3A of IL1RN rs2234663 VNTR seem to increase the risk of getting Trypanosoma brucei gambiense infections and develop sleeping sickness in southern Cameroon. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) is a zoonotic phlebovirus that can be transmitted to humans or livestock by mosquitoes or through direct contact with contaminated bodily fluids and tissues. Exposure to bodily fluids and tissues varies by types of behaviors engaged for occupational tasks, homestead responsibilities, or use in dietary or therapeutic capacities. While previous studies have included milk exposures in their analyses, their primary focus on livestock exposures has been on animal handling, breeding, and slaughter. We analyzed data from multiple field surveys in Kenya with the aim of associating RVFV infection to raw milk exposures from common animal species. Of those with evidence of prior RVFV infection by serology (n = 267), 77.2% engaged in milking livestock compared to 32.0% for 3,956 co-local seronegative individuals (p < 0.001), and 86.5% of seropositive individuals consumed raw milk compared to 33.4% seronegative individuals (p < 0.001). Individuals who milked and also consumed raw milk had greater odds of RVFV exposure than individuals whose only contact to raw milk was through milking. Increased risks were associated with exposure to milk sourced from cows (p < 0.001), sheep (p < 0.001), and goats (p < 0.001), but not camels (p = 0.98 for consuming, p = 0.21 for milking). Our data suggest that exposure to raw milk may contribute to a significant number of cases of RVFV, especially during outbreaks and in endemic areas, and that some animal species may be associated with a higher risk for RVFV exposure. Livestock trade is regulated to limit RVFV spread from endemic areas, yet further interventions designed to fully understand the risk of RVFV exposure from raw milk are imperative. [ABSTRACT FROM AUTHOR]

Currently, malaria rapid diagnostic tests (RDTs) are widely used for malaria diagnosis, but test performance and the factors that lead to failure of Plasmodium ovale detection are not well understood. In this study, three pLDH-based RDTs were evaluated using cases in China that originated in Africa. The sensitivity of Wondfo Pf/Pan, CareStart pLDH PAN and SD BIOLINE Pf/Pan in P. ovale detection was 70, 55 and 18%, respectively. CareStart was worse at detecting P. o. curtisi (36.5%) than at detecting P. o. wallikeri (75.0%), and SD could not detect P. o. curtisi. The overall detection ratio of all three RDTs decreased with parasite density and pLDH concentration. Wondfo, CareStart and SD detected only 75.0, 78.1 and 46.9% of the P. ovale cases, respectively, even when the parasitemia were higher than 5000 parasites/μL. Subspecies of P. ovale should be considered while to improve RDT quality for P. ovale diagnosis to achieve the goal of malaria elimination. [ABSTRACT FROM AUTHOR]

Background: Seasonal epidemics of bacterial meningitis in the African Meningitis Belt carry a high burden of disease and mortality. Reactive mass vaccination is used as a control measure during epidemics, but the time taken to gain immunity from the vaccine reduces the flexibility and effectiveness of these campaigns. Targeted reactive antibiotic prophylaxis could be used to supplement reactive mass vaccination and further reduce the incidence of meningitis, and the potential effectiveness and efficiency of these strategies should be explored. Methods and findings: Data from an outbreak of meningococcal meningitis in Niger, caused primarily by Neisseria meningitidis serogroup C, is used to estimate clustering of meningitis cases at the household and village level. In addition, reactive antibiotic prophylaxis and reactive vaccination strategies are simulated to estimate their potential effectiveness and efficiency, with a focus on the threshold and spatial unit used to declare an epidemic and initiate the intervention. There is village-level clustering of suspected meningitis cases after an epidemic has been declared in a health area. Risk of suspected meningitis among household contacts of a suspected meningitis case is no higher than among members of the same village. Village-wide antibiotic prophylaxis can target subsequent cases in villages: across of range of parameters pertaining to how the intervention is performed, up to 220/672 suspected cases during the season are potentially preventable. On the other hand, household prophylaxis targets very few cases. In general, the village-wide strategy is not very sensitive to the method used to declare an epidemic. Finally, village-wide antibiotic prophylaxis is potentially more efficient than mass vaccination of all individuals at the beginning of the season, and than the equivalent reactive vaccination strategy. Conclusions: Village-wide antibiotic prophylaxis should be considered and tested further as a response against outbreaks of meningococcal meningitis in the Meningitis Belt, as a supplement to reactive mass vaccination. [ABSTRACT FROM AUTHOR]

Background: Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate. Methodology/Principal findings: In order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses the same reagents as ICT) revealed an overall positivity rate of 1.1% and L. loa microfilaria (Mf) rates of up to 46%. Among the subjects with 0 to 8,000 Mf/ml in day blood, only 0.4% were FTS positive, while 29% of subjects with >8,000 Mf/ml were FTS positive. A Mf density of >8,200 Mf/ml was determined as the cut point at which positive FTS results should be excluded from the analysis. No FTS positive samples were also positive for W. bancrofti antibodies as measured by two different point of care tests that use the Wb123 antigen not found in L. loa. Night blood examination of the FTS positive subjects showed a high prevalence of L. loa Mf with densities up to 12,710 Mf/ml. No W. bancrofti Mf were identified, as confirmed by qPCR. Our results show that high loads of L. loa Mf in day blood are a reliable indicator of FTS positivity, and Wb123 rapid test proved to be relatively specific. Conclusions/Significance: Our study provides a simple day blood-based algorithm for LF mapping in loiasis areas. The results indicate that many districts that were formerly classified as endemic for LF in Cameroon are non-endemic and do not require mass drug administration for elimination of LF. [ABSTRACT FROM AUTHOR]

Background: Most smallholder farmers (SHFs) and marginalized populations (MPs) in Africa, Asia, and Latin America depend on livestock for their livelihoods. However, significant numbers of these animals do not achieve their potential, die due to disease, or transmit zoonotic diseases. Existing vaccines could prevent and control some of these diseases, but frequently the vaccines do not reach SHFs, especially MPs, making it necessary for specific vaccine adoption strategies. Principal findings: Several strategies that have the potential to increase the adoption of animal vaccines by SHFs and MPs have been identified depending on the type of vaccines involved. The strategies differed depending on whether the vaccines were aimed at diseases that cause economic losses, government-controlled diseases, or neglected diseases. The adoption of vaccines for neglected diseases presents a major challenge, because they are mostly for zoonotic diseases that produce few or no clinical signs in the animals, making it more difficult for the farmers to appreciate the value of the vaccines. Strategies can be aimed at increasing the availability of quality vaccines, so that they are produced in sufficient quantity, or aimed at increasing access and demand by SHFs and/or MPs. Some of the strategies to increase vaccine adoption might not provide a definite solution but might facilitate vaccine uptake by decreasing barriers. These strategies are varied and include technical considerations, policy components, involvement by the private sector (local and international), and innovation. Conclusions: Several strategies with the potential to reduce livestock morbidity and mortality, or prevent zoonoses in SHFs communities and MPs through vaccination, require the involvement of donors and international organisations to stimulate and facilitate sustainable adoption. This is especially the case for neglected zoonotic diseases. Support for national and regional vaccine manufacturers is also required, especially for vaccines against diseases of interest only in the developing world and public goods. [ABSTRACT FROM AUTHOR]

Background: Access to an accurate diagnostic test for Buruli ulcer (BU) is a research priority according to the World Health Organization. Nucleic acid amplification of insertion sequence IS2404 by polymerase chain reaction (PCR) is the most sensitive and specific method to detect Mycobacterium ulcerans (M. ulcerans), the causative agent of BU. However, PCR is not always available in endemic communities in Africa due to its cost and technological sophistication. Isothermal DNA amplification systems such as the recombinase polymerase amplification (RPA) have emerged as a molecular diagnostic tool with similar accuracy to PCR but having the advantage of amplifying a template DNA at a constant lower temperature in a shorter time. The aim of this study was to develop RPA for the detection of M. ulcerans and evaluate its use in Buruli ulcer disease. Methodology and principal findings: A specific fragment of IS2404 of M. ulcerans was amplified within 15 minutes at a constant 42°C using RPA method. The detection limit was 45 copies of IS2404 molecular DNA standard per reaction. The assay was highly specific as all 7 strains of M. ulcerans tested were detected, and no cross reactivity was observed to other mycobacteria or clinically relevant bacteria species. The clinical performance of the M. ulcerans (Mu-RPA) assay was evaluated using DNA extracted from fine needle aspirates or swabs taken from 67 patients in whom BU was suspected and 12 patients with clinically confirmed non-BU lesions. All results were compared to a highly sensitive real-time PCR. The clinical specificity of the Mu-RPA assay was 100% (95% CI, 84–100), whiles the sensitivity was 88% (95% CI, 77–95). Conclusion: The Mu-RPA assay represents an alternative to PCR, especially in areas with limited infrastructure. [ABSTRACT FROM AUTHOR]

Effective malaria control strategies require an accurate understanding of the epidemiology of locally transmitted Plasmodium species. Compared to Plasmodium falciparum infection, Plasmodium vivax has a lower asexual parasitaemia, forms dormant liver-stages (hypnozoites), and is more transmissible. Hence, treatment and diagnostic policies aimed exclusively at P. falciparum are far less efficient against endemic P. vivax. Within sub-Saharan Africa, malaria control programmes justly focus on reducing the morbidity and mortality associated with P. falciparum. However, the recent emphasis on malaria elimination and increased accessibility of more sensitive diagnostic tools have revealed greater intricacies in malaria epidemiology across the continent. Since 2010, the number of studies identifying P. vivax endemic to Africa has expanded considerably, with 88 new scientific reports published since a review of evidence in 2015, approximately doubling the available data. There is evidence of P. vivax in all regions of Africa, apparent from infected vectors, clinical cases, serological indicators, parasite prevalence, exported infections, and P. vivax-infected Duffy-negative individuals. Where the prevalence of microscopic parasitaemia is low, a greater proportion of P. vivax infections were observed relative to P. falciparum. This evidence highlights an underlying widespread presence of P. vivax across all malaria-endemic regions of Africa, further complicating the current practical understanding of malaria epidemiology in this region. Thus, ultimate elimination of malaria in Africa will require national malaria control programmes to adopt policy and practice aimed at all human species of malaria. [ABSTRACT FROM AUTHOR]

There is a disease epidemiological transition occurring in Africa, with increasing incidence of noninfectious diseases, superimposed on a health system historically geared more toward the management of communicable diseases. The persistence and sometimes emergence of new pathogens allows for the occurrence of coinfections and comorbidities due to both infectious and noninfectious diseases. There is therefore a need to rethink and restructure African health systems to successfully address this transition. The historical focus of more health resources on infectious diseases requires revision. We hypothesise that the growing burden of noninfectious diseases may be linked directly and indirectly to or further exacerbated by the existence of neglected tropical diseases (NTDs) and other infectious diseases within the population. Herein, we discuss the health burden of coinfections and comorbidities and the challenges to implementing effective and sustainable healthcare in Africa. We also discuss how existing NTD and infectious disease intervention programs in Africa can be leveraged for noninfectious disease intervention. Furthermore, we explore the potential for new technologies—including artificial intelligence and multiplex approaches—for diagnosis and management of chronic diseases for improved health provision in Africa. [ABSTRACT FROM AUTHOR]

Histoplasmosis in Africa has markedly increased since the advent of the HIV/AIDS epidemic but is under-recognised. Pulmonary histoplasmosis may be misdiagnosed as tuberculosis (TB). In the last six decades (1952–2017), 470 cases of histoplasmosis have been reported. HIV-infected patients accounted for 38% (178) of the cases. West Africa had the highest number of recorded cases with 179; the majority (162 cases) were caused by Histoplasma capsulatum var. dubuosii (Hcd). From the Southern African region, 150 cases have been reported, and the majority (119) were caused by H. capsulatum var. capsulatum (Hcc). There have been 12 histoplasmin skin test surveys with rates of 0% to 35% positivity. Most cases of Hcd presented as localised lesions in immunocompetent persons; however, it was disseminated in AIDS patients. Rapid diagnosis of histoplasmosis in Africa is only currently possible using microscopy; antigen testing and PCR are not available in most of Africa. Treatment requires amphotericin B and itraconazole, both of which are not licensed or available in several parts of Africa. [ABSTRACT FROM AUTHOR]

Introduction: Neurological involvement is one of the most important clinical manifestations of syphilis and neurological disease occurs in both early and late syphilis. The impact of HIV co-infection on clinical neurosyphilis remains unclear. The highest prevalence of both syphilis and HIV is in Africa. Therefore it might be expected that neurosyphilis would be an important and not uncommon manifestation of syphilis in Africa and frequently occur in association with HIV co-infection; yet few data are available on neurosyphilis in Africa. The aim of this study is to review data on neurosyphilis in Africa since the onset of the HIV epidemic. Methods: We searched the literature for references on neurosyphilis in Africa for studies published between the 1st of January 1990 and 15th February 2017. We included case reports, case series, and retrospective and prospective cohort and case-control studies. We did not limit inclusion based on the diagnostic criteria used for neurosyphilis. For retrospective and prospective cohorts, we calculated the proportion of study participants who were diagnosed with neurosyphilis according to the individual study criteria. Depending on the study, we assessed the proportion of patients with syphilis found to have neurosyphilis, and the proportion of patients with neurological syndromes who had neurosyphilis. Due to heterogeneity of data no formal pooling of the data or meta-analysis was undertaken. Results: Amongst patients presenting with a neurological syndrome, three studies of patients with meningitis were identified; neurosyphilis was consistently reported to cause approximately 3% of all cases. Three studies on stroke reported mixed findings but were limited due to the small number of patients undergoing CSF examination, whilst neurosyphilis continued to be reported as a common cause of dementia in studies from North Africa. Ten studies reported on cases of neurosyphilis amongst patients known to have syphilis. Studies from both North and Southern Africa continue to report cases of late stage syphilis, including tabes dorsalis and neurosyphilis, in association with ocular disease. Discussion: This is the first systematic review of the literature on neurosyphilis in Africa since the beginning of the HIV epidemic. Neurosyphilis continues to be reported as a manifestation of both early and late syphilis, but the methodological quality of the majority of the included studies was poor. Future well-designed prospective studies are needed to better delineate the incidence and clinical spectrum of neurosyphilis in Africa and to better define interactions with HIV in this setting. [ABSTRACT FROM AUTHOR]

The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for use the clinical management, control and elimination of P. vivax malaria. [ABSTRACT FROM AUTHOR]

Background: Among the Reduviidae family, triatomines are giant blood-sucking bugs. They are well known in Central and South America where they transmit Trypanosoma cruzi to mammals, including humans, through their feces. This parasitic protozoan is the causative agent of Chagas disease, a major public health issue in endemic areas. Because of the medical and economic impact of Chagas disease, the presence of other arthropod-borne pathogens in triatomines was rarely investigated. Methodology/Principal findings: In this study, seven triatomines species involved in the transmission of T. cruzi were molecularly screened for the presence of known pathogens generally associated with arthropods, such as Rickettsia, Bartonella, Anaplasmataceae, Borrelia species and Coxiella burnetii. Of all included triatomine species, only Eratyrus mucronatus specimens tested positive for Bartonella species for 56% of tested samples. A new genotype of Bartonella spp. was detected in 13/23 Eratyrus mucronatus specimens, an important vector of T. cruzi to humans. This bacterium was further characterized by sequencing fragments of the ftsZ, gltA and rpoB genes. Depending on the targeted gene, this agent shares 84% to 91% of identity with B. bacilliformis, the agent of Carrion’s disease, a deadly sandfly-borne infectious disease endemic in South America. It is also closely related to animal pathogens such as B. bovis and B. chomelii. Conclusions: As E. mucronatus is an invasive species that occasionally feeds on humans, the presence of potentially pathogenic Bartonella-infected bugs could present another risk for human health, along with the T. cruzi issue. [ABSTRACT FROM AUTHOR]

This study systematically reviews the literature on the occurrence, incidence and case fatality rate (CFR) of invasive nontyphoidal Salmonella (iNTS) disease in Africa from 1966 to 2014. Data on the burden of iNTS disease in Africa are sparse and generally have not been aggregated, making it difficult to describe the epidemiology that is needed to inform the development and implementation of effective prevention and control policies. This study involved a comprehensive search of PubMed and Embase databases. It documents the geographical spread of iNTS disease over time in Africa, and describes its reported incidence, risk factors and CFR. We found that Nontyphoidal Salmonella (NTS) have been reported as a cause of bacteraemia in 33 out of 54 African countries, spanning the five geographical regions of Africa, and especially in sub-Saharan Africa since 1966. Our review indicates that NTS have been responsible for up to 39% of community acquired blood stream infections in sub-Saharan Africa with an average CFR of 19%. Salmonella Typhimurium and Enteritidis are the major serovars implicated and together have been responsible for 91%% of the cases of iNTS disease, (where serotype was determined), reported in Africa. The study confirms that iNTS disease is more prevalent amongst Human Immunodeficiency Virus (HIV)-infected individuals, infants, and young children with malaria, anaemia and malnutrition. In conclusion, iNTS disease is a substantial cause of community-acquired bacteraemia in Africa. Given the high morbidity and mortality of iNTS disease in Africa, it is important to develop effective prevention and control strategies including vaccination. [ABSTRACT FROM AUTHOR]

A cross sectional serological survey of arboviral infections in humans was conducted on the three islands of the Union of Comoros, Indian Ocean, in order to test a previously suggested contrasted exposure of the three neighboring islands to arthropod-borne epidemics. Four hundred human sera were collected on Ngazidja (Grande Comore), Mwali (Mohéli) and Ndzouani (Anjouan), and were tested by ELISA for IgM and/or IgG antibodies to Dengue (DENV), Chikungunya (CHIKV), Rift Valley fever (RVFV), West Nile (WNV), Tick borne encephalitis (TBEV) and Yellow fever (YFV) viruses and for neutralizing antibodies to DENV serotypes 1–4. Very few sera were positive for IgM antibodies to the tested viruses indicating that the sero-survey was performed during an inter epidemic phase for the investigated arbovirus infections, except for RVF which showed evidence of recent infections on all three islands. IgG reactivity with at least one arbovirus was observed in almost 85% of tested sera, with seropositivity rates increasing with age, indicative of an intense and long lasting exposure of the Comorian population to arboviral risk. Interestingly, the positivity rates for IgG antibodies to DENV and CHIKV were significantly higher on Ngazidja, confirming the previously suggested prominent exposure of this island to these arboviruses, while serological traces of WNV infection were detected most frequently on Mwali suggesting some transmission specificities associated with this island only. The study provides the first evidence for circulation of RVFV in human populations from the Union of Comoros and further suggests that the virus is currently circulating on the three islands in an inconspicuous manner. This study supports contrasted exposure of the islands of the Comoros archipelago to arboviral infections. The observation is discussed in terms of ecological factors that may affect the abundance and distribution of vector populations on the three islands as well as concurring anthropogenic factors that may impact arbovirus transmission in this diverse island ecosystem. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is a zoonotic arboviral disease that is a threat to human health, animal health and production, mainly in Sub-Saharan Africa. RVF virus dynamics have been poorly studied due to data scarcity. On the island of Mayotte in the Indian Ocean, off the Southeastern African coast, RVF has been present since at least 2004. Several retrospective and prospective serological surveys in livestock have been conducted over eleven years (2004–15). These data are collated and presented here. Temporal patterns of seroprevalence were plotted against time, as well as age-stratified seroprevalence. Results suggest that RVF was already present in 2004–07. An epidemic occurred between 2008 and 2010, with IgG and IgM peak annual prevalences of 36% in 2008–09 (N = 142, n = 51, 95% CI [17–55]) and 41% (N = 96, n = 39, 95% CI [25–56]), respectively. The virus seems to be circulating at a low level since 2011, causing few new infections. In 2015, about 95% of the livestock population was susceptible (IgG annual prevalence was 6% (N = 584, n = 29, 95% CI [3–10])). Monthly rainfall varied a lot (2–540mm), whilst average temperature remained high with little variation (about 25–30°C). This large dataset collected on an insular territory for more than 10 years, suggesting a past epidemic and a current inter-epidemic period, represents a unique opportunity to study RVF dynamics. Further data collection and modelling work may be used to test different scenarios of animal imports and rainfall pattern that could explain the observed epidemiological pattern and estimate the likelihood of a potential re-emergence. [ABSTRACT FROM AUTHOR]

Arboviral infections have repeatedly been reported in the republic of Djibouti, consistent with the fact that essential vectors for arboviral diseases are endemic in the region. However, there is a limited recent information regarding arbovirus circulation, and the associated risk predictors to human exposure are largely unknown. We performed, from November 2010 to February 2011 in the Djibouti city general population, a cross-sectional ELISA and sero-neutralisation-based sero-epidemiological analysis nested in a household cohort, which investigated the arboviral infection prevalence and risk factors, stratified by their vectors of transmission. Antibodies to dengue virus (21.8%) were the most frequent. Determinants of infection identified by multivariate analysis pointed to sociological and environmental exposure to the bite of Aedes mosquitoes. The population was broadly naïve against Chikungunya (2.6%) with risk factors mostly shared with dengue. The detection of limited virus circulation was followed by a significant Chikungunya outbreak a few months after our study. Antibodies to West Nile virus were infrequent (0.6%), but the distribution of cases faithfully followed previous mapping of infected Culex mosquitoes. The seroprevalence of Rift valley fever virus was 2.2%, and non-arboviral transmission was suggested. Finally, the study indicated the circulation of Toscana-related viruses (3.7%), and a limited number of cases suggested infection by tick-borne encephalitis or Alkhumra related viruses, which deserve further investigations to identify the viruses and vectors implicated. Overall, most of the arboviral cases' predictors were statistically best described by the individuals' housing space and neighborhood environmental characteristics, which correlated with the ecological actors of their respective transmission vectors' survival in the local niche. This study has demonstrated autochthonous arboviral circulations in the republic of Djibouti, and provides an epidemiological inventory, with useful findings for risk mapping and future prevention and control programs. [ABSTRACT FROM AUTHOR]

Canine rabies can be effectively controlled by vaccination with readily available, high-quality vaccines. These vaccines should provide protection from challenge in healthy dogs, for the claimed period, for duration of immunity, which is often two or three years. It has been suggested that, in free-roaming dog populations where rabies is endemic, vaccine-induced protection may be compromised by immuno-suppression through malnutrition, infection and other stressors. This may reduce the proportion of dogs that seroconvert to the vaccine during vaccination campaigns and the duration of immunity of those dogs that seroconvert. Vaccination coverage may also be limited through insufficient vaccine delivery during vaccination campaigns and the loss of vaccinated individuals from populations through demographic processes. This is the first longitudinal study to evaluate temporal variations in rabies vaccine-induced serological responses, and factors associated with these variations, at the individual level in previously unvaccinated free-roaming dog populations. Individual-level serological and health-based data were collected from three cohorts of dogs in regions where rabies is endemic, one in South Africa and two in Indonesia. We found that the vast majority of dogs seroconverted to the vaccine; however, there was considerable variation in titres, partly attributable to illness and lactation at the time of vaccination. Furthermore, >70% of the dogs were vaccinated through community engagement and door-to-door vaccine delivery, even in Indonesia where the majority of the dogs needed to be caught by net on successive occasions for repeat blood sampling and vaccination. This demonstrates the feasibility of achieving population-level immunity in free-roaming dog populations in rabies-endemic regions. However, attrition of immune individuals through demographic processes and waning immunity necessitates repeat vaccination of populations within at least two years to ensure communities are protected from rabies. These findings support annual mass vaccination campaigns as the most effective means to control canine rabies. [ABSTRACT FROM AUTHOR]

Background: Human infection with Bwamba virus (BWAV) and the closely related Pongola virus (PGAV), as well as Nyando virus (NDV), are important causes of febrile illness in Africa. However, despite seroprevalence studies that indicate high rates of infection in many countries, these viruses remain relatively unknown and unstudied. In addition, a number of unclassified bunyaviruses have been isolated over the years often with uncertain relationships to human disease. Methodology/Principal Findings: In order to better understand the genetic and evolutionary relationships among orthobunyaviruses associated with human disease, we have sequenced the complete genomes for all 3 segments of multiple strains of BWAV (n = 2), PGAV (n = 2) and NDV (n = 4), as well as the previously unclassified Mojuí dos Campos (MDCV) and Kaeng Khoi viruses (KKV). Based on phylogenetic analysis, we show that these viruses populate 2 distinct branches, one made up of BWAV and PGAV and the other composed of NDV, MDCV and KKV. Interestingly, the NDV strains analyzed form two distinct clades which differed by >10% on the amino acid level across all protein products. In addition, the assignment of two bat-associated bunyaviruses into the NDV group, which is clearly associated with mosquito-borne infection, led us to analyze the ability of these different viruses to grow in bat (RE05 and Tb 1 Lu) and mosquito (C6/36) cell lines, and indeed all the viruses tested were capable of efficient growth in these cell types. Conclusions/Significance: On the basis of our analyses, it is proposed to reclassify the NDV strains ERET147 and YM176-66 as a new virus species. Further, our analysis definitively identifies the previously unclassified bunyaviruses MDCV and KKV as distinct species within the NDV group and suggests that these viruses may have a broader host range than is currently appreciated. [ABSTRACT FROM AUTHOR]

Background: Rift Valley fever virus (RVFV) causes outbreaks of severe disease in livestock and humans throughout Africa and the Arabian Peninsula. In people, RVFV generally causes a self-limiting febrile illness but in a subset of individuals, it progresses to more serious disease. One manifestation is a delayed-onset encephalitis that can be fatal or leave the afflicted with long-term neurologic sequelae. In order to design targeted interventions, the basic pathogenesis of RVFV encephalitis must be better understood. Methodology/Principal Findings: To characterize the host immune responses and viral kinetics associated with fatal and nonfatal infections, mice were infected with an attenuated RVFV lacking NSs (ΔNSs) that causes lethal disease only when administered intranasally (IN). Following IN infection, C57BL/6 mice developed severe neurologic disease and succumbed 7–9 days post-infection. In contrast, inoculation of ΔNSs virus subcutaneously in the footpad (FP) resulted in a subclinical infection characterized by a robust immune response with rapid antibody production and strong T cell responses. IN-inoculated mice had delayed antibody responses and failed to clear virus from the periphery. Severe neurological signs and obtundation characterized end stage-disease in IN-inoculated mice, and within the CNS, the development of peak virus RNA loads coincided with strong proinflammatory responses and infiltration of activated T cells. Interestingly, depletion of T cells did not significantly alter survival, suggesting that neurologic disease is not a by-product of an aberrant immune response. Conclusions/Significance: Comparison of fatal (IN-inoculated) and nonfatal (FP-inoculated) ΔNSs RVFV infections in the mouse model highlighted the role of the host immune response in controlling viral replication and therefore determining clinical outcome. There was no evidence to suggest that neurologic disease is immune-mediated in RVFV infection. These results provide important insights for the future design of vaccines and therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. Methods and Findings: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52–2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23–1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04–1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30–2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. Conclusion: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated. [ABSTRACT FROM AUTHOR]

Background: The recent emergence of zoonotic diseases such as Highly Pathogenic Avian Influenza (HPAI) and Severe Acute Respiratory Syndrome (SARS) have contributed to dominant Global Health narratives around health securitisation and pandemic preparedness, calling for greater co-operation between the health, veterinary and environmental sectors in the ever-evolving One Health movement. A decade later, One Health advocates face increasing pressure to translate the approach from theory into action. Methodology/Principal Findings: A qualitative case study methodology was used to examine the emerging relationships between international One Health dialogue and its practical implementation in the African health policy context. A series of Key Informant Interviews (n = 32) with policy makers, government officials and academics in Nigeria, Tanzania and Uganda are presented as three separate case studies. Each case examines a significant aspect of One Health operationalisation, framed around the control of both emerging and Neglected Zoonotic Diseases including HPAI, Human African Trypanosomiasis and rabies. The research found that while there is general enthusiasm and a strong affirmative argument for adoption of One Health approaches in Africa, identifying alternative contexts away from a narrow focus on pandemics will help broaden its appeal, particularly for national or regionally significant endemic and neglected diseases not usually addressed under a “global” remit. Conclusions/Significance: There is no ‘one size fits all’ approach to achieving the intersectoral collaboration, significant resource mobilisation and political co-operation required to realise a One Health approach. Individual country requirements cannot be underestimated, dismissed or prescribed in a top down manner. This article contributes to the growing discussion regarding not whether One Health should be operationalised, but how this may be achieved. [ABSTRACT FROM AUTHOR]

Background: Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a “One Health” perspective to synthesize the published data and identify knowledge gaps. Methods/Principal Findings: We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (≤13%) among cattle except for studies in Western and Middle Africa (18–55%). Small ruminant seroprevalence ranged from 11–33%. Human seroprevalence was <8% with the exception of studies among children and in Egypt (10–32%). Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2–9% of febrile illness hospitalizations and 1–3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts. Conclusions/Significance: C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real yet underappreciated threat to human and animal health throughout Africa. [ABSTRACT FROM AUTHOR]

The article focuses on the epidemics and colonial responses to sleeping sickness in East and Central Africa from 1900 to 1940. It states that the outbreak of the disease was associated to the epizootic of rinderpest introduced in Africa with the Italian invasion of Eritrea in 1889. It says that atoxyl has been tested against the disease by Ayres Kopke in Lisbon, Portugal and by Robert Koch in Uganda.