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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]

Uganda has had repeated outbreaks of Rift Valley fever (RVF) since March 2016 when human and livestock cases were reported in Kabale after a long interval. The disease has a complex and poorly described transmission patterns which involves several mosquito vectors and mammalian hosts (including humans). We conducted a national serosurvey in livestock to determine RVF virus (RVFV) seroprevalence, risk factors, and to develop a risk map that could be used to guide risk-based surveillance and control measures. A total of 3,253 animals from 175 herds were sampled. Serum samples collected were screened at the National Animal Disease Diagnostics and Epidemiology Centre (NADDEC) using a competition multispecies anti-RVF IgG ELISA kit. Data obtained were analyzed using a Bayesian model that utilizes integrated nested Laplace approximation (INLA) and stochastic partial differential equation (SPDE) approaches to estimate posterior distributions of model parameters, and account for spatial autocorrelation. Variables considered included animal level factors (age, sex, species) and multiple environmental data including meteorological factors, soil types, and altitude. A risk map was produced by projecting fitted (mean) values, from a final model that had environmental factors onto a spatial grid that covered the entire domain. The overall RVFV seroprevalence was 11.39% (95% confidence interval: 10.35–12.51%). Higher RVFV seroprevalences were observed in older animals compared to the young, and cattle compared to sheep and goats. RVFV seroprevalence was also higher in areas that had (i) lower precipitation seasonality, (ii) haplic planosols, and (iii) lower cattle density. The risk map generated demonstrated that RVF virus was endemic in several regions including those that have not reported clinical outbreaks in the northeastern part of the country. This work has improved our understanding on spatial distribution of RVFV risk in the country as well as RVF burden in livestock. Author summary: Outbreaks of Rift Valley fever occur periodically in Uganda in livestock and humans. An Initial outbreak was reported in Kabale in March 2016 after a long quiescent period. Factors that trigger these outbreaks have not been fully described, but above-normal precipitation and flooding are known to be important causes. This paper presents a study that was conducted in the country to analyse RVF virus seroprevalence and risk factors for exposure in livestock. The study also mapped spatial distribution of RVFV seroprevalence. Data used in the study were generated from a national cross-sectional serosurvey that involved cattle, sheep and goats. Results obtained showed that the national RVFV seroprevalence was 11.39%, with 95% confidence interval of 10.35–12.51%. Cattle had higher RVFV seroprevalence compared to sheep and goats. Environmental factors that were associated with increased seroprevalence were low precipitation seasonality, haplic planosols, and low cattle density. Prevalence maps generated showed that the southwestern, central and parts of the northeastern regions had higher seroprevalence compared to other regions of the country. These can be used to guide the surveillance of the disease in the country. [ABSTRACT FROM AUTHOR]

Background: Work to control the gambiense form of human African trypanosomiasis (gHAT), or sleeping sickness, is now directed towards ending transmission of the parasite by 2030. In order to supplement gHAT case-finding and treatment, since 2011 tsetse control has been implemented using Tiny Targets in a number of gHAT foci. As this intervention is extended to new foci, it is vital to understand the costs involved. Costs have already been analysed for the foci of Arua in Uganda and Mandoul in Chad. This paper examines the costs of controlling Glossina palpalis palpalis in the focus of Bonon in Côte d'Ivoire from 2016 to 2017. Methodology/Principal findings: Some 2000 targets were placed throughout the main gHAT transmission area of 130 km2 at a density of 14.9 per km2. The average annual cost was USD 0.5 per person protected, USD 31.6 per target deployed of which 12% was the cost of the target itself, or USD 471.2 per km2 protected. Broken down by activity, 54% was for deployment and maintenance of targets, 34% for tsetse surveys/monitoring and 12% for sensitising populations. Conclusions/Significance: The cost of tsetse control per km2 of the gHAT focus protected in Bonon was more expensive than in Chad or Uganda, while the cost per km2 treated, that is the area where the targets were actually deployed, was cheaper. Per person protected, the Bonon cost fell between the two, with Uganda cheaper and Chad more expensive. In Bonon, targets were deployed throughout the protected area, because G. p. palpalis was present everywhere, whereas in Chad and Uganda G. fuscipes fuscipes was found only the riverine fringing vegetation. Thus, differences between gHAT foci, in terms of tsetse ecology and human geography, impact on the cost-effectiveness of tsetse control. It also demonstrates the need to take into account both the area treated and protected alongside other impact indicators, such as the cost per person protected. Author summary: Sleeping sickness is a fatal disease in Africa caused by trypanosomes transmitted by the bite of infected tsetse flies. The World Health Organization has set the absence of new infections as a goal for 2030. To achieve this, screening and treatment of patients is supplemented by tsetse control. Tiny Targets are small insecticide-impregnated panels of blue cloth and black netting which attract and kill tsetse. To maintain the momentum in these last stages of eliminating the disease, it is important to understand the costs of vector control. This paper presents the results of two years' cost monitoring in Bonon, an area covering 130 km2, home to 120,000 people. Since 2016, ~2,000 Tiny Targets have been deployed annually at a cost of USD 471 per km2 per year. Bonon is a degraded forested area and a relatively high number of targets was required as tsetse are present throughout. Nevertheless, the cost comes to only USD 0.5 per person protected per year. Compared to operations using Tiny Targets in Uganda and Chad, the cost was higher per km2 protected, reflecting the need to place targets throughout the area, but low per person protected compared to Chad, highlighting the need to use a range of comparators. [ABSTRACT FROM AUTHOR]

Diagnosing the causative agent of febrile illness in resource-limited countries is a challenge in part due to lack of adequate diagnostic infrastructure to confirm cause of infection. Most febrile illnesses (>60%) are non-malarial, with a significant proportion being zoonotic and likely from animal origins. To better characterize the pathways for zoonotic disease transmission and control in vulnerable communities, adequate information on the communities' experiences and lexicon describing fever, and their understanding and perceptions of risk pathways is required. We undertook an ethnographic study to understand behaviors, exposures, and attitudes toward fever at the community level. Our hope is to better elucidate areas of priority surveillance and diagnostic investment. A focused ethnography consisting of participant observation, informal conversations, 4 barazas (community meetings), and formal ethnographic interviews (13 Focus group discussions and 17 Key informant interviews) was conducted between April and November 2015 in Kasese and Hoima Districts in Uganda. Perception of illness and associated risk factors was heavily influenced by the predominant livelihood activity of the community. The term "fever" referred to multiple temperature elevating disease processes, recognized as distinct pathological occurrences. However, malaria was the illness often cited, treated, or diagnosed both at the health facilities and through self-diagnosis and treatment. As expected, fever is as an important health challenge affecting all ages. Recognition of malarial fever was consistent with a biomedical model of disease while non-malarial fevers were interpreted mainly through ethno etiological models of explanation. These models are currently being used to inform education and prevention strategies and treatment regimens toward the goal of improving patients' outcomes and confidence in the health system. Development of treatment algorithms that consider social, cultural, and economic contexts, especially where human-animal interaction is prevalent, should factor animal exposure and zoonotic illnesses as important differentials. Author summary: Across the tropics malaria prevalence has been steadily declining over the last 15 years. This has revealed the importance of non-malarial febrile illnesses and their link to livestock production. Unlike malaria, managing NMFI in resource limited settings is challenging due to the limited number of diagnostic tools available and communities' health seeking behavior. To develop effective NMFI prevention and management strategies, a comprehensive exploration of the socio-cultural drivers of NMFIs among rural livestock keeping communities is required. Towards this end we conducted a focused ethnographic study in Western Uganda among communities with high human livestock interaction to describe communities' a) perception of the syndrome of fever b), important biosocial pathways associated with febrile illness and c) their management of these febrile illnesses. This paper describes important biosocial drivers of NMFI, highlights important aspects of the cultural epidemiology of NMFIs, and illustrates the unintended consequences of global health policies on the management of NMFIs at the community level. It concludes by proposing important additions to NMFI clinical algorithms that could improve the sensitivity of such tools in areas of limited diagnostic capacities. [ABSTRACT FROM AUTHOR]

Background: Anthrax is a zoonotic disease that can be transmitted to humans from infected animals. During May–June 2017, three persons with probable cutaneous anthrax were reported in Arua District, Uganda; one died. All had recently handled carcasses of livestock that died suddenly and a skin lesion from a deceased person tested positive by PCR for Bacillus anthracis. During July, a bull in the same community died suddenly and the blood sample tested positive by PCR for Bacillus anthracis. The aim of this investigation was to establish the scope of the problem, identify exposures associated with illness, and recommend evidence-based control measures. Methods: A probable case was defined as acute onset of a papulo-vesicular skin lesion subsequently forming an eschar in a resident of Arua District during January 2015–August 2017. A confirmed case was a probable case with a skin sample testing positive by polymerase chain reaction (PCR) for B. anthracis. Cases were identified by medical record review and active community search. In a case-control study, exposures between case-patients and frequency- and village-matched asymptomatic controls were compared. Key animal health staff were interviewed to learn about livestock deaths. Results: There were 68 case-patients (67 probable, 1 confirmed), and 2 deaths identified. Cases occurred throughout the three-year period, peaking during dry seasons. All cases occurred following sudden livestock deaths in the villages. Case-patients came from two neighboring sub-counties: Rigbo (attack rate (AR) = 21.9/10,000 population) and Rhino Camp (AR = 1.9/10,000). Males (AR = 24.9/10,000) were more affected than females (AR = 0.7/10,000). Persons aged 30–39 years (AR = 40.1/10,000 population) were most affected. Among all cases and 136 controls, skinning (ORM-H = 5.0, 95%CI: 2.3–11), butchering (ORM-H = 22, 95%CI: 5.5–89), and carrying the carcass of livestock that died suddenly (ORM-H = 6.9, 95%CI: 3.0–16) were associated with illness. Conclusions: Exposure to carcasses of animals that died suddenly was a likely risk factor for cutaneous anthrax in Arua District during 2015–2017. The recommendations are investigation of anthrax burden in livestock, prevention of animal infections through vaccinations, safe disposal of the carcasses, public education on risk factors for infection and prompt treatment of illness following exposure to animals that died suddenly. Author summary: We are honored to submit an original research article entitled "Cutaneous anthrax associated with handling carcasses of animals that died suddenly of unknown cause: Arua District, Uganda, January 2015–August 2017". Anthrax is a vaccine-preventable disease that can be transmitted to humans from infected animals. Our paper is based on 68 cutaneous anthrax case-patients and cases occurred throughout the three-year period, peaking during dry seasons in Arua District of Uganda. All cases occurred following sudden livestock deaths in the villages. Our findings are based on outbreak investigation which gives a better representation of the actual situation. Our article looks at the scope of the anthrax outbreak, exposures associated with illness, and evidence-based control measures. In this manuscript, we show that exposure to carcasses of animals that died suddenly was a risk factor for cutaneous anthrax in Arua District during 2015–2017. We believe the content and objectives of our work provide knowledge on epidemiology of cutaneous anthrax. [ABSTRACT FROM AUTHOR]

Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec, genus Ledantevirus, family Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas. Serological cross-reactivity as measured by pseudotype-based neutralisation was confined to ledanteviruses, indicating population seropositivity may represent either exposure to LDV or related ledanteviruses. We also describe the discovery of a closely related ledantevirus in blood from the synanthropic rodent Mastomys erythroleucus. Ledantevirus infection is common in Uganda but is geographically heterogenous. Further surveys of patients presenting with acute fever are required to determine the contribution of these emerging viruses to febrile illness in Uganda. Author summary: Understanding the viruses capable of human infection is important for outbreak prevention and early intervention in viral epidemics. Le Dantec virus (LDV) is a member of the viral genus Ledantevirus (Rhabodoviridae) and has previously been isolated only once previously in a child with febrile illness in Senegal in 1965. We detected the genome of LDV in blood sampled from a patient presenting with febrile illness in Western Uganda in 2012. To estimate the extent to which LDV may be causing human infection in the region, we tested stored blood samples collected in 2016 for evidence of antibodies to LDV, revealing that up to 76% of Ugandans in some areas had previously been exposed to either to LDV or a closely related virus. Seroprevalence was highest in Western Uganda, an area of high biodiversity where several other ledanteviruses have been isolated in association with ectoparasites of bats. To investigate potential ecological reservoirs of zoonotic viruses we tested blood from wild rodents inhabiting areas close to human settlements. We detected a new ledantevirus, closely related to LDV, in blood from a wild rodent Mastomys erythroleucus. Our work shows that ledanteviruses are a common cause of human infection in Uganda. [ABSTRACT FROM AUTHOR]

Background: Yellow fever (YF), a mosquito-borne viral hemorrhagic fever, is endemic in Uganda and causes frequent outbreaks. A total of 1.6 million people were vaccinated during emergency mass immunization campaigns in 2011 and 2016. This study explored local perceptions of YF emergency mass immunization among vulnerable groups to inform future vaccination campaigns. Methodology: In this qualitative study, we conducted 43 semi-structured interviews, 4 focus group discussions, and 10 expert interviews with 76 participants. Data were collected in six affected districts with emergency mass vaccination. We included vulnerable groups (people ≥ 65 years and pregnant women) who are typically excluded from YF vaccination except during mass immunization. Data analysis was conducted using grounded theory. Inductive coding was utilized, progressing through open, axial, and selective coding. Principal findings: Participants relied on community sources for information about the YF mass vaccination. Information was disseminated door-to-door, in community spaces, during religious gatherings, and on the radio. However, most respondents had no knowledge of the vaccine, and it was unclear to them whether a booster dose was required. In addition, the simultaneous presidential election during the mass vaccination campaign led to suspicion and resistance to vaccination. The lack of reliable and trustworthy information and the politicization of vaccination campaigns reinforced mistrust of YF vaccines. Conclusions/significance: People in remote areas affected by YF outbreaks rely on community sources of information. We therefore recommend improving health education, communication, and engagement through respected and trusted community members. Vaccination campaigns can never be seen as detached from political systems and power relations. Author summary: Yellow fever is transmitted by mosquitoes in tropical regions of South America and Africa. It can cause severe illness and death. Yellow fever can be prevented with a vaccine. However, people in several affected regions are not vaccinated because the vaccine is expensive and not part of routine immunization. For them, access to the vaccine is only possible during emergency mass vaccination campaigns when an outbreak occurs. In this study, we explored local perceptions of emergency yellow fever mass vaccination among vulnerable groups (people over 65 years and pregnant women) in Uganda to understand better how these people have access to vaccine information, what information reaches affected communities, what motivates people to be vaccinated, and what political motives may influence vaccination programs. Despite extensive campaigns, we found that the information reaching communities varied widely, with people relying heavily on community sources. In addition, the lack of trustworthy information and the politicization of vaccination campaigns increased mistrust of yellow fever vaccines. We also found that informed consent is only possible if the principle of vaccination—protection from disease—is understood. Awareness campaigns should focus on a broad understanding of the importance of immunization. Those involved in organizing campaigns should be aware of the potential impact of politicization on vaccine uptake. [ABSTRACT FROM AUTHOR]

Background: The insecticide-treated baits known as Tiny Targets are one of the cheapest means of controlling riverine species of tsetse flies, the vectors of the trypanosomes that cause sleeping sickness in humans. Models of the efficacy of these targets deployed near rivers are potentially useful in planning control campaigns and highlighting the principals involved. Methods and principal findings: To evaluate the potential of models, we produced a simple non-seasonal model of the births, deaths, mobility and aging of tsetse, and we programmed it to simulate the impact of seven years of target use against the tsetse, Glossina fuscipes fuscipes, in the riverine habitats of NW Uganda. Particular attention was given to demonstrating that the model could explain three matters of interest: (i) good control can be achieved despite the d egradation of targets, (ii) local elimination of tsetse is impossible if invasion sources are not tackled, and (iii) with invasion and target degradation it is difficult to detect any effect of control on the age structure of the tsetse population. Conclusions: Despite its simplifications, the model can assist planning and teaching, but allowance should be made for any complications due to seasonality and management challenges associated with greater scale. Author summary: We produced a simple model of the population dynamics of the riverine tsetse fly, Glossina fuscipes fuscipes, to simulate the field results of controlling this insect for seven years using Tiny Targets, i.e., artificial insecticide-treated baits, in NW Uganda. The model is potentially useful in planning tsetse control and teaching the principles involved. Thus, it confirmed that targets can give good control, even if the targets degrade so much that they need replacement after six months. It showed that reinvasion can limit severely the efficacy of control campaigns and mask the changes in the age structure of the population. We stress the need to consider the possibility of seasonal complications and problems of managing large scale operations. [ABSTRACT FROM AUTHOR]

Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills the adult worm of all Schistosoma species. Nonetheless, re-infections have continued to be detected in endemic areas with individuals living in the same area presenting with varying infection intensities. Our objective was to characterize the transcriptome profiles in peripheral blood of children between 10–15 years with varying intensities of Schistosoma mansoni infection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44 S. mansoni infected (34 high and 10 low by circulating anodic antigen [CAA] level) and 20 uninfected children was sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome. Differential gene expression analysis was done using DESeq2. Principal component analysis revealed clustering of gene expression by gender when S. mansoni infected children were compared with uninfected children. In addition, we identified 14 DEGs between S. mansoni infected and uninfected individuals, 56 DEGs between children with high infection intensity and uninfected individuals, 33 DEGs between those with high infection intensity and low infection intensity and no DEGs between those with low infection and uninfected individuals. We also observed upregulation and downregulation of some DEGs that are associated with fibrosis and its regulation. These data suggest expression of fibrosis associated genes as well as genes that regulate fibrosis in S. mansoni infection. The relatively few significant DEGS observed in children with schistosomiasis suggests that chronic S. mansoni infection is a stealth infection that does not stimulate a strong immune response. Author summary: Schistosomiasis is a neglected tropical disease transmitted via an intermediate snail host through contact with contaminated fresh water. Even with routine Mass Drug Administration for treatment of the infection, re-infections are still common and variations in infection intensity and pathology are still observed in individuals in the same location. These may be due to differences in individuals' response to S. mansoni infection. In this study, we used RNAseq to identify differentially expressed genes associated with S. mansoni infection in children between 10–15 years. We conducted comparisons between phenotypes including infection intensities measured by circulating anodic antigen, wasting by body mass index and stunting by height-for-age Z-score. Our data showed very low numbers of significantly differentially expressed genes in all comparisons. Some of the few differentially expressed genes that were observed were associated with fibrosis which is the cause of pathology in humans and has been observed in late stages of S. mansoni infection in murine studies. [ABSTRACT FROM AUTHOR]

Introduction: Schistosomiasis is a neglected tropical disease (NTD) that is endemic in Uganda, despite several interventions to eliminate it. It is transmitted when people infected with it pass on their waste matter into fresh water bodies used by others, consequently infecting them. Several studies have demonstrated gender and age differences in prevalence of schistosomiasis and NTDs such as lymphatic filariasis and soil transmitted helminths. However, few intersectional gender analysis studies of schistosomiasis have been undertaken. Using the World Health Organisation (WHO)'s intersectional gender analysis toolkit, this study was undertaken to identify which social stratifiers most intersected with gender to influence vulnerability to and access to treatment for schistosomiasis disease, to understand how best to implement interventions against it. Methodology: This was a qualitative study comprising eight focus group discussions (FGDs) of community members, disaggregated by age, sex and location, and 10 key informant interviews with health care providers and community leaders. The Key informants were selected purposively while the community members were selected using stratified random sampling (to cater for age, sex and location). The data was analysed manually to identity key themes around gender, guided by a gender and intersectionality lens. Results: The study established that while the River Nile provided livelihoods it also exposed the community to schistosomiasis infection. Gender relations played a significant role in exposure to and access to treatment for schistosomiasis. Traditional gender roles determined the activities men and women performed in the private and public spheres, which in turn determined their exposure to schistosomiasis and treatment seeking behaviour. Gender relations also affected access to treatment and decision making over family health care. Men and some women who worked outside the home were reported to prioritise their income earning activities over seeking health care, while women who visited the health facilities more regularly for antenatal care and to take sick children were reported to have higher chance of being tested and treated in time, although this was undermined by the irregular and infrequent provision of praziquantel (PZQ) mass drug administration. These gender relations were further compounded by underdevelopment and limited economic opportunities, insufficient health care services, as well as the respondent's age and location. Conclusions: The study concludes that vulnerability to schistosomiasis disease and treatment occurred within a complex web of gender relations, culture, poverty, limited economic opportunities and insufficient health services delivery, which together undermined efforts to eliminate schistosomiasis. This study recommends the following: a) increased public health campaigns around schistosomiasis prevention and treatment; b) more regular PZQ MDA at home and schools; c) improved health services delivery and integration of services to include vector control; d) prioritising NTDs; e) providing alternative economic activities; and f) addressing negative gender norms that promote social behaviours which negatively influence vulnerability, treatment seeking and decision making for health. Author summary: Schistosomiasis is a waterborne NTD endemic to Uganda and many other countries in Africa, Asia and Latin America. Schistosomiasis is one of the prominent NTDs in Uganda, the others being trachoma, onchocerciasis, buruli ulcer, soil-transmitted helminths, and elephantiasis. In Uganda, schistosomiasis only ranks behind malaria among parasitic diseases as a cause of poor health. Schistosomiasis has several socio-economic drivers, which include poverty, limited economic opportunities, poor service delivery and negative socio-cultural and gender norms. Yet the conventional responses to it have often been biomedical, using PZQ MDA. This study applied intersectional gender analysis to study how gender relations intersected with other social stratifiers to shape women's and men's experience of exposure to and treatment of schistosomiasis. It established that traditional gender roles determined the activities men and women performed at home and in public, which in turn determined their exposure to schistosomiasis. Gender roles were also reported in the fishing industry, where men predominantly fished while women processed and sold fish. While men were considered to be the epicentre of infection, women were not any safer since their traditional gender roles of cooking and washing brought them in direct contact with infected water multiple times daily. Gender roles also determined access to prompt health care with men (and some women who worked) prioritising making money instead of treatment, while women who were charged with taking children to hospital had opportunity to be tested and treated in time. Apart from gender differences were other factors such as poverty and limited health care services which compounded gender inequality. For example, the insufficient supply of PZQ undermined women's opportunities to access prompt health care, while long waiting time deterred men and working women from seeking health care. Meanwhile with poverty the community had no alternative means of survival except the River Nile, despite its being infested with schistosomiasis bearing vectors. The study concludes that gender has a significant role to play in understanding and responding to schistosomiasis and makes the several recommendations including: mainstreaming gender in schistosomiasis control strategies; prioritising NTDs elimination in health systems; less vertical programmes in preference of integrated health care services, including in schistosomiasis control; poverty eradication; and more research in intersectional gender analysis in NTDs. [ABSTRACT FROM AUTHOR]

Background: Soil-transmitted helminth (STH) infections are caused by roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura), and hookworms (Necator americanus and Ancylostoma duodenale). In Uganda, baseline surveys conducted during the late 1990s and early 2000s suggested STH infections were common, with prevalence >50% among surveyed schoolchildren. In 2003, a national program was launched with mass preventative chemotherapy (PC) and health education for children 1–14 years old. Little evidence is available to show the impact of national deworming. Methods: We conducted population-based, cross-sectional household surveys in five districts (Buikwe, Kassanda, Kiryandongo, Kisoro, and Rubanda) in March and May 2022. Our primary objective was to estimate STH prevalence by species due to infections of any intensity and infections of moderate-to-heavy intensity among preschool-aged children (PSAC, 1–4 years old), school-aged children (SAC, 5–14 years old), and women of reproductive age (WRA, 15–49 years old). Laboratory technicians used duplicate Kato-Katz microscopy to determine fecal egg count. Results: Overall, 3,352 PSAC; 3,884 SAC; and 1,226 WRA provided stool samples. The prevalence of any infection remained high in Kisoro at or above ~50% within all risk groups. In other districts, the prevalence of any infection ranged from approximately 5 to 16% among PSAC, 6 to 23% among SAC, and 12 to 19% among WRA. Moderate-to-heavy intensity infection prevalence was highest in Kisoro (~15–26%), followed by Rubanda (<5%), and was ≤1% in other districts. A. lumbricoides and T. trichiura infections were largely confined to Kisoro and Rubanda, whereas hookworm was most common in other districts. Conclusions: The STH prevalence has decreased markedly in three districts in Uganda. Based on our findings, the national deworming program should consider decreasing PC distribution frequency in these districts per the World Health Organization guidelines. Efforts are needed to understand why the Kisoro and Rubanda districts did not demonstrate similar gains. Author summary: Intestinal worm infections—formally known as soil-transmitted helminth (STH) infections—are a public health problem that can potentially reduce physical growth, cause anemia, and hinder cognitive development. In Uganda, baseline surveys conducted between 1998 and 2005 indicated that STH infection prevalence was over 50% among school-aged children in most surveyed districts. As a result of these findings, in the early 2000s, the Ugandan Ministry of Health began twice-a-year national deworming campaigns and health education among preschool- and school-aged children. In March and May of 2022, we conducted follow-up surveys in five districts to determine how well the deworming campaigns have reduced infection prevalence in these communities. Among surveyed groups (preschool-aged children, school-aged children, and women of reproductive age), we found that in three of the five surveyed districts, STH prevalence had substantially decreased. In these areas, the national deworming program may consider reducing the frequency of the deworming campaigns from its current twice-a-year schedule. The prevalence remained high in the remaining two districts despite several years of deworming. Further investigation is needed to determine why. [ABSTRACT FROM AUTHOR]

Background: Uganda has active foci of both chronic and acute HAT with the acute zoonotic form of disease classically considered to be restricted to southeast Uganda, while the focus of the chronic form of HAT was confined to the northwest of the country. Acute HAT has however been migrating from its traditional disease focus, spreading rapidly to new districts, a spread linked to movement of infected cattle following restocking. Cattle act as long-term reservoirs of human infective T. b. rhodesiense showing few signs of morbidity, yet posing a significant risk to human health. It is important to understand the relationship between infected cattle and infected individuals so that an appropriate response can be made to the risk posed to the community from animals infected with human pathogens in a village setting. Methodology/Principal Findings: This paper examines the relationship between human T. b. rhodesiense infection and human infective and non-human T. brucei s.l. circulating in cattle at village level in Kaberamaido and Dokolo Districts, Uganda. The study was undertaken in villages that had reported a case of sleeping sickness in the six months prior to sample collection and those villages that had never reported a case of sleeping sickness. Conclusions and Significance: The sleeping sickness status of the villages had a significant effect with higher odds of infection in cattle from case than from non-case villages for T. brucei s.l. (OR: 2.94, 95%CI: 1.38–6.24). Cattle age had a significant effect (p<0.001) on the likelihood of T. brucei s.l. infection within cattle: cattle between 18–36 months (OR: 3.51, 95%CI: 1.63–7.51) and cattle over 36 months (OR: 4.20, 95%CI: 2.08–8.67) had significantly higher odds of T. brucei s. l. infection than cattle under 18 months of age. Furthermore, village human sleeping sickness status had a significant effect (p<0.05) on the detection of T. b. rhodesiense in the village cattle herd, with significantly higher likelihood of T. b. rhodesiense in the village cattle of case villages (OR: 25, 95%CI: 1.2–520.71). Overall a higher than average T. brucei s.l. prevalence (>16.3%) in a village herd over was associated with significantly higher likelihood of T. b. rhodesiense being detected in a herd (OR: 25, 95%CI: 1.2–520.71). Author Summary: Human African trypanosomiasis (HAT) is a fatal parasitic disease of humans. Domestic cattle act as reservoirs for T.b. rhodesiense HAT. In a survey of cattle in Ugandan villages; six that had a reported HAT case in the previous six months, and six which did not, an association was detected between presence of HAT in a village and infection of village cattle with human infective parasites. Village HAT status was significant (p<0.05) for detection of T.b. rhodesiense in the village herd, with significantly greater likelihood of T.b. rhodesiense in herds from case villages (OR:25,95%CI:1.2–520.71). T. brucei s.l. prevalence of over 16.3% in cattle was associated with significantly greater likelihood of T.b. rhodesiense infection within the herd (OR:25, 95%CI:1.2–520.71). Cattle age had a significant effect (p<0.001) on the likelihood of a T. brucei s.l. infection: cattle between 18–36 months (OR:3.51,95%CI:1.63–7.51) and over 36 months (OR:4.20,95%CI:2.08–8.67) had significantly higher rates of T. brucei s.l. than animals under 18 months of age. Cattle are long-term reservoirs of T.b. rhodesiense that will outlive control strategies that do not directly eliminate parasite infection. T.b. rhodesiense and/or elevated T. brucei s.l. prevalence in village herds can serve as an indicator for HAT risk. [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. Author Summary: The One Health movement requires more robust evidence around its practical implementation if it is to truly become a way forwards for addressing health issues at the human, animal and ecosystem interface. The research in this paper discusses some of the recent successes and challenges with both Emerging and Neglected zoonoses in the sub-Saharan Africa context. Through speaking to various human and animal health practitioners and policy makers in Uganda, Nigeria and Tanzania, the authors have created three case studies highlighting the various successes of the approach to date, but also clarifying areas where the approach will take longer to implement, often as a result of the wide institutional and policy changes required in many countries. The authors conclude that whilst the "goodwill" is certainly there, the reality of planning, executing and budgeting for joint interventions – particularly at the national or regional level – proves in many cases more difficult than first thought. It is hoped however that through gaining better insight from those charged with the decision-making in these countries, One Health practitioners will be encouraged to build on the momentum through addressing some of the issues that arise with its implementation. [ABSTRACT FROM AUTHOR]

Introduction: In 2010, the World Health Organization released a new cholera vaccine position paper, which recommended the use of cholera vaccines in high-risk endemic areas. However, there is a paucity of data on the burden of cholera in endemic countries. This article reviewed available cholera surveillance data from Uganda and assessed the sufficiency of these data to inform country-specific strategies for cholera vaccination. Methods: The Uganda Ministry of Health conducts cholera surveillance to guide cholera outbreak control activities. This includes reporting the number of cases based on a standardized clinical definition plus systematic laboratory testing of stool samples from suspected cases at the outset and conclusion of outbreaks. This retrospective study analyzes available data by district and by age to estimate incidence rates. Since surveillance activities focus on more severe hospitalized cases and deaths, a sensitivity analysis was conducted to estimate the number of non-severe cases and unrecognized deaths that may not have been captured. Results: Cholera affected all ages, but the geographic distribution of the disease was very heterogeneous in Uganda. We estimated that an average of about 11,000 cholera cases occurred in Uganda each year, which led to approximately 61–182 deaths. The majority of these cases (81%) occurred in a relatively small number of districts comprising just 24% of Uganda's total population. These districts included rural areas bordering the Democratic Republic of Congo, South Sudan, and Kenya as well as the slums of Kampala city. When outbreaks occurred, the average duration was about 15 weeks with a range of 4–44 weeks. Discussion: There is a clear subdivision between high-risk and low-risk districts in Uganda. Vaccination efforts should be focused on the high-risk population. However, enhanced or sentinel surveillance activities should be undertaken to better quantify the endemic disease burden and high-risk populations prior to introducing the vaccine. Author Summary: Uganda has reported cholera cases to the World Health Organization every year since 1997. Thus, the country may consider the introduction of a WHO-prequalified oral cholera vaccine. This article reviews cholera surveillance data from 1997–2010 with a focus on the 2005–2010 time period to identify high risk populations that may be targeted for preventive vaccination campaigns. We estimated that an average of about 61–182 deaths occur each year. Most cases (81%) occurred in a relatively small number of districts comprising just 24% of Uganda's total population. While there is a clear distinction between low and high-risk districts, sentinel surveillance would help to better quantify the burden in endemic districts. An economic analysis should also be undertaken prior to making a decision to introduce a cholera vaccine. [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. Author Summary: Gambiense human African trypanosomiasis (HAT, sleeping sickness) usually features low prevalence. The two stages of the disease require different treatments, and stage 2 is fatal if untreated. HAT diagnosis must therefore be highly sensitive (i.e., detect as many true cases as possible) and specific (i.e., minimize false positives). HAT diagnostic algorithms are complex and involve several tests to screen for, confirm and stage infection. We analyzed five algorithms used by Médecins Sans Frontières HAT programmes. We combined published data on the accuracy of each test in the algorithm with a computer program that simulates all possible algorithm branches. We found that all algorithms had reasonable sensitivity (85–90%); specificity was high (>99.9%) except for the Republic of Congo, where confirmation did not rely on microscopic evidence, resulting in frequent false positives (but also higher sensitivity). Algorithms misclassified about one third of stage 1 cases as stage 2, but stage 2 classification was highly accurate. The use of serology alone for confirmation merits caution. HAT diagnosis could be made more sensitively by following up serological suspects and repeating microscopic examinations. Computer simulations can help to adapt algorithms to local conditions in each HAT programme, such as the prevalence of infection and operational constraints. [ABSTRACT FROM AUTHOR]

Background: Diverse clinical features have been reported in human African trypanosomiasis (HAT) foci caused by Trypanosoma brucei rhodesiense (T.b.rhodesiense) giving rise to the hypothesis that HAT manifests as a chronic disease in South-East African countries and increased in virulence towards the North. Such variation in disease severity suggests there are differences in host susceptibility to trypanosome infection and/or genetic variation in trypanosome virulence. Our molecular tools allow us to study the role of host and parasite genotypes, but obtaining matched extensive clinical data from a large cohort of HAT patients has previously proved problematic. Methods/Principal Findings: We present a retrospective cohort study providing detailed clinical profiles of 275 HAT patients recruited in two northern foci (Uganda) and one southern focus (Malawi) in East Africa. Characteristic clinical signs and symptoms of T.b.rhodesiense infection were recorded and the degree of neurological dysfunction determined on admission. Clinical observations were mapped by patient estimated post-infection time. We have identified common presenting symptoms in T.b.rhodesiense infection; however, marked differences in disease progression and severity were identified between foci. HAT was characterised as a chronic haemo-lymphatic stage infection in Malawi, and as an acute disease with marked neurological impairment in Uganda. Within Uganda, a more rapid progression to meningo-encephaltic stage of infection was observed in one focus (Soroti) where HAT was characterised by early onset neurodysfunction; however, severe neuropathology was more frequently observed in patients in a second focus (Tororo). Conclusions/Significance: We have established focus-specific HAT clinical phenotypes showing dramatic variations in disease severity and rate of stage progression both between northern and southern East African foci and between Ugandan foci. Understanding the contribution of host and parasite factors in causing such clinical diversity in T.b.rhodesiense HAT has much relevance for both improvement of disease management and the identification of new drug therapy. Author Summary: T. b. gambiense and T. b. rhodesiense cause human African trypanosomiasis (HAT). These parasite subspecies differ in their rate of progression to central nervous system (CNS) infection, and consequently to coma and death. Variation in disease progression and severity has also been documented between northern and southern East African T.b. rhodesiense HAT. However, it is unknown if this is caused by differences in patient susceptibility to infection, genetic variation in parasite virulence, or both, as despite the existence of good molecular tools, previous studies have involved limited numbers of HAT cases. In this paper we present extensive clinical data on T. b. rhodesiense cases and describe robust clinical profiles for three disease foci. Common presenting symptoms were identified. We also describe marked differences in disease progression and severity both between Ugandan and Malawi foci, and between two Ugandan foci (Tororo and Soroti) giving rise to three foci-specific clinical phenotypes ranging from a chronic haemo-lymphatic stage infection in Malawi, to rapid disease progression and neurological dysfunction in Soroti and severe neuropathology in Tororo cases. Most importantly, we have now established clinical focus-specific phenotypes that will be available to supplement host and parasite genetics studies to determine their contribution to HAT disease virulence. [ABSTRACT FROM AUTHOR]

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

This study focused on Oeosophagostomum sp., and more especially on O. bifurcum, as a parasite that can be lethal to humans and is widespread among humans and monkeys in endemic regions, but has not yet been documented in apes. Its epidemiology and the role played by non-human primates in its transmission are still poorly understood. O. stephanostomum was the only species diagnosed so far in chimpanzees. Until recently, O. bifurcum was assumed to have a high zoonotic potential, but recent findings tend to demonstrate that O. bifurcum of non-human primates and humans might be genetically distinct. As the closest relative to human beings, and a species living in spatial proximity to humans in the field site studied, Pan troglodytes is thus an interesting host to investigate. Recently, a role for chimpanzees in the emergence of HIV and malaria in humans has been documented. In the framework of our long-term health monitoring of wild chimpanzees from Kibale National Park in Western Uganda, we analysed 311 samples of faeces. Coproscopy revealed that high-ranking males are more infected than other individuals. These chimpanzees are also the more frequent crop-raiders. Results from PCR assays conducted on larvae and dried faeces also revealed that O. stephanostomum as well as O. bifurcum are infecting chimpanzees, both species co-existing in the same individuals. Because contacts between humans and great apes are increasing with ecotourism and forest fragmentation in areas of high population density, this paper emphasizes that the presence of potential zoonotic parasites should be viewed as a major concern for public health. Investigations of the parasite status of people living around the park or working inside as well as sympatric non-human primates should be planned, and further research might reveal this as a promising aspect of efforts to reinforce measures against crop-raiding. Author Summary: The disease caused by the nodular worm Oesophagostomum bifurcum can be lethal in humans and is thus of major human health significance in certain African regions. There are still gaps in the understanding of the epidemiology of the disease, including the role of non-human primates as reservoirs of the infection. We recently conducted a survey in a community of wild chimpanzees (Pan troglodytes schweinfurthii) in Kibale National Park, Western Uganda. O. stephanostomum is so far the only species previously found in chimpanzees. A total of 311 stool samples was examined and revealed that high-ranking males are more infected than other individuals. These chimpanzees are also the more frequent crop-raiders. Moreover, we reported for the first time molecular evidence for O. bifurcum in addition to O. stephanostomum in chimpanzees. Our results raise public health concerns for a neglected infection in regions where spatial proximity between great apes and humans are increasing because of forest fragmentation. [ABSTRACT FROM AUTHOR]

Background: Mass Drug Administration (MDA) is the main strategy for control of soil-transmitted helminth (STH) infections, with single-dose benzimidazole (albendazole or mebendazole) the principal MDA option. In Mayuge district, Uganda, an MDA programme has been in place for over fifteen years but hookworm infection remains common and there is concern that the effectiveness of single-dose albendazole as currently used for MDA may be sub-optimal. This study aims to assess the efficacy of dual- versus single-dose albendazole, with and without fatty food co-administration against hookworm, the dominant form of STHs in Mayuge district, Uganda. Methodology: This was a 2x2 factorial randomised controlled trial to investigate two interventions simultaneously; 1) dual-dose versus single-dose albendazole, 2) taking albendazole with or without fatty food (200 grams of avocado eaten directly after medication). School children with hookworm infection were randomised in a 1:1:1:1 ratio to the four possible treatment groups. Three weeks after the treatment, stool samples were collected from trial participants to evaluate trial outcomes: cure rate and egg reduction rate (ERR). Principal findings: A total of 225 participants were enrolled, and 222 (98.7%) seen at 3 weeks. The cure rate in the dual-dose group was 96.4% (95% CI: 90.9–99%), higher than 83.9% (95% CI: 75.7–90.2%) in the single-dose group (OR: 5.07, 95% CI:1.61–15.96, p = 0.002). The ERR was 97.6% and 94.5% in the dual-dose group and single-dose drug group, respectively (ERR difference 3.1%, 95% CI: -3.89–16.39%, p = 0.553). The cure rates among participants taking albendazole with and without avocado were 90.1% and 89.1%, respectively, with no statistical difference between the two groups (OR: 1.24, 95% CI: 0.51–3.03, p = 0.622). The ERR was 97.0% and 94.2% in the group receiving albendazole with and without avocado, respectively, and the difference in ERR between the two groups was 2.8% (95% CI -8.63–14.3%, p = 0.629). Conclusions/Significance: In Ugandan school children, dual-dose albendazole improves the cure rate of hookworm compared to single-dose albendazole. However, there was no significant improvement in cure rate or egg reduction rate of hookworm with fatty-food co-administration. Dual-dose albendazole is a feasible alternative for improving drug effectiveness against hookworm infection and minimising drug resistance. Trial registration: PACTR202202738940158. Author summary: Mass Drug Administration (MDA) of single-dose albendazole is the main strategy for control of soil-transmitted helminth infections including hookworm, but these infections remain common in many settings where MDA has been implemented for several years. This study aimed to assess the efficacy of dual-dose versus single-dose albendazole, with and without fatty food co-administration, against hookworm infection in Mayuge district, Uganda. The study was conducted as a randomized controlled trial among school children with hookworm infection. The cure rate was found to be significantly higher in the dual-dose group compared to the single-dose group, with no significant difference in the cure rate or egg reduction rate observed between the groups that took albendazole with or without fatty food. The study suggests that dual-dose albendazole is a feasible alternative for improving drug effectiveness against hookworm infection and minimizing drug resistance. Although the study did not demonstrate any benefit with the use of avocado co-administration against hookworm infection, further exploration is warranted due to the biological rationale for improving albendazole efficacy to treat intraluminal hookworm infection. [ABSTRACT FROM AUTHOR]

Background: Tsetse flies (Glossina) transmit Trypanosoma brucei gambiense which causes Gambian human African trypanosomiasis (gHAT) in Central and West Africa. Several countries use Tiny Targets, comprising insecticide-treated panels of material which attract and kill tsetse, as part of their national programmes to eliminate gHAT. We studied how the scale and arrangement of target deployment affected the efficacy of control. Methodology and principal findings: Between 2012 and 2016, Tiny Targets were deployed biannually along the larger rivers of Arua, Maracha, Koboko and Yumbe districts in North West Uganda with the aim of reducing the abundance of tsetse to interrupt transmission. The extent of these deployments increased from ~250 km2 in 2012 to ~1600 km2 in 2015. The impact of Tiny Targets on tsetse population was assessed by analysing catches of tsetse from a network of monitoring traps; sub-samples of captured tsetse were dissected to estimate their age and infection status. In addition, the condition of 780 targets (~195/district) was assessed for up to six months after deployment. In each district, mean daily catches of tsetse (G. fuscipes fuscipes) from monitoring traps declined significantly by >80% following the deployment of targets. The reduction was apparent for several kilometres on adjacent lengths of the same river but not in other rivers a kilometre or so away. Expansion of the operational area did not always produce higher levels of suppression or detectable change in the age structure or infection rates of the population, perhaps due to the failure to treat the smaller streams and/or invasion from adjacent untreated areas. The median effective life of a Tiny Target was 61 (41.8–80.2, 95% CI) days. Conclusions: Scaling-up of tsetse control reduced the population of tsetse by >80% across the intervention area. Even better control might be achievable by tackling invasion of flies from infested areas within and outside the current intervention area. This might involve deploying more targets, especially along smaller rivers, and extending the effective life of Tiny Targets. Author summary: Gambian human African trypanosomiasis (gHAT) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by tsetse flies (Glossina). Uganda's strategy to eliminate gHAT includes the deployment of Tiny Targets, comprising insecticide-treated panels of cloth which attract and kill tsetse. Our data from a network of monitoring traps assessed how increasing the intervention area from ~250 km2 to ~1600 km2 affected the degree of control. Inspection of deployed targets indicated their effective lifespan. Targets reduced tsetse abundance by >80% beside the rivers where they were deployed but had no clear effect on adjacent rivers where targets were absent. As the intervention area increased, so did the extent of the area controlled. We did not deploy targets along the smaller rivers so that, as expected, the tsetse population was not eliminated. Our findings suggest that the population was sustained at low levels by invasion of tsetse from untreated parts of the drainage system. The average effective life of targets was ~60 days as against the ~180 days for targets deployed in Kenya. This discrepancy is attributable, in part, to the Uganda targets being removed by seasonal floods. While the level of control achieved is already more than sufficient to interrupt transmission of gHAT, even better control would be achieved by increasing the coverage of the drainage system. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the relative effectiveness of tsetse control methods, their costs need to be analysed alongside their impact on tsetse populations. Very little has been published on the costs of methods specifically targeting human African trypanosomiasis Methodology/Principal Findings: In northern Uganda, a 250 km2 field trial was undertaken using small (0.5 X 0.25 m) insecticide-treated targets (“tiny targets”). Detailed cost recording accompanied every phase of the work. Costs were calculated for this operation as if managed by the Ugandan vector control services: removing purely research components of the work and applying local salaries. This calculation assumed that all resources are fully used, with no spare capacity. The full cost of the operation was assessed at USD 85.4 per km2, of which USD 55.7 or 65.2% were field costs, made up of three component activities (target deployment: 34.5%, trap monitoring: 10.6% and target maintenance: 20.1%). The remaining USD 29.7 or 34.8% of the costs were for preliminary studies and administration (tsetse surveys: 6.0%, sensitisation of local populations: 18.6% and office support: 10.2%). Targets accounted for only 12.9% of the total cost, other important cost components were labour (24.1%) and transport (34.6%). Discussion: Comparison with the updated cost of historical HAT vector control projects and recent estimates indicates that this work represents a major reduction in cost levels. This is attributed not just to the low unit cost of tiny targets but also to the organisation of delivery, using local labour with bicycles or motorcycles. Sensitivity analyses were undertaken, investigating key prices and assumptions. It is believed that these costs are generalizable to other HAT foci, although in more remote areas, with denser vegetation and fewer people, costs would increase, as would be the case for other tsetse control techniques. [ABSTRACT FROM AUTHOR]

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

The World Health Organization promotes the SAFE (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements) strategy for trachoma control and prevention. The F&E components of the strategy focus on promotion of healthy hygiene and sanitation behaviors. In order to monitor F&E activities implemented across villages and schools in Malawi, Tanzania, and Uganda, an F&E Monitoring and Evaluation (FEME) framework was developed to track quarterly program outputs and to provide the basis for a pre and post evaluation of the activities. Results showed an increase in knowledge at the school and household levels, and in some cases, an increase in presence of hand/face washing stations. However, this did not always result in a change in trachoma prevention behaviors such as facial cleanliness or keeping compounds free of human feces. The results highlight that the F&E programs were effective in increasing awareness of trachoma prevention but not able to translate that knowledge into changes in behavior during the time between pre and post-surveys. This study also indicates the potential to improve the data collection and survey design and notes that the period of intervention was not long enough to measure significant changes. Author summary: Trachoma control programs promote facial cleanliness, use of latrines, and emphasizes the importance of access to water as means to reduce trachoma transmission. To address these areas, various country ministries and supporting non-governmental organizations (NGOs) support the implementation of tailored behavior change programs. The process and results of evaluating these types of programs in Malawi, Tanzania, and Uganda are described here. The goal of this manuscript is to provide trachoma program managers and supporting NGOs with insights, recommendations, and data collection tools that could be used to support their efforts to conduct monitoring and evaluation of their current or future trachoma prevention activities. [ABSTRACT FROM AUTHOR]

Background: Over 240 million people are infected with schistosomiasis, the majority in sub-Saharan Africa. In Uganda, high infection rates exist in communities on the shores of Lake Victoria. Praziquantel mass drug administration (MDA) delivered by village health teams is the mainstay of schistosomiasis control. However, treatment uptake remains suboptimal, with many people unaware of treatment or thinking it is only for children. Furthermore, people are often rapidly reinfected post-treatment due to continued exposure. In three Schistosoma mansoni high endemicity lake-shore communities in Mayuge district, Eastern Uganda, we investigated the sources of schistosomiasis information, remembered content of information, and the perception of information and related practices towards the control of schistosomiasis. Methods and principal findings: Data were collected from September 2017 to March 2018 using a rapid ethnographic assessment that included transect walks, observations, individual in-depth interviews and focus group discussions. Data were analysed thematically using iterative categorisation. We found that the main sources of schistosomiasis information included health workers at government facilities, village health teams, teachers, and radio programmes produced by the Ministry of Health. These messages described the symptoms of schistosomiasis, but did not mention the side effects of praziquantel treatment. Despite this messaging, the main cause of the disease and transmission was unclear to most participants. The translation of schistosomiasis on the radio into the local language 'ekidada'—meaning swollen stomach, increased, rather than reduced, confusion about the cause(s) of schistosomiasis, due to believed links between ekidada and witchcraft, and prompted a reluctance to engage with treatment or preventative efforts. Conclusion and significance: This study highlights gaps in schistosomiasis messaging. We recommend MDA is complemented by effective, evidence-based messaging on schistosomiasis transmission, prevention, and treatment, that is sensitive to local language and context issues, resulting in clear, concise, and consistent messages, to increase effectiveness. Author summary: Schistosomiasis is a global-health concern causing severe disease, particularly in communities in tropical areas such as Uganda. The parasite is spread in areas with inadequate sanitation and a lack of a safe water supply. Government control efforts focus on mass drug administration for people living in affected areas, with most treatments administered to school-aged children. However, drug uptake is low, and people are rapidly reinfected. In three heavily affected communities on the shores of Lake Victoria, we explored the sources of schistosomiasis information, how messages were relayed to community members, the remembered content of these messages and the way messages were perceived. Common sources of information were health workers at government health facilities, trained village health team members, teachers, and radio programmes. Our findings show that the information shared from the different sources is not consistent and, in some cases, this has caused confusion and prompted a reluctance to engage with treatment or preventative efforts. We propose a framework where there is dialogue between community member representatives, health workers based in the community, and government technical staff to come up with clear, concise, and consistent messages. [ABSTRACT FROM AUTHOR]

Background: Surveillance is an essential component of global programs to eliminate infectious diseases and avert epidemics of (re-)emerging diseases. As the numbers of cases decline, costs of treatment and control diminish but those for surveillance remain high even after the 'last' case. Reducing surveillance may risk missing persistent or (re-)emerging foci of disease. Here, we use a simulation-based approach to determine the minimal number of passive surveillance sites required to ensure maximum coverage of a population at-risk (PAR) of an infectious disease. Methodology and principal findings: For this study, we use Gambian human African trypanosomiasis (g-HAT) in north-western Uganda, a neglected tropical disease (NTD) which has been reduced to historically low levels (<1000 cases/year globally), as an example. To quantify travel time to diagnostic facilities, a proxy for surveillance coverage, we produced a high spatial-resolution resistance surface and performed cost-distance analyses. We simulated travel time for the PAR with different numbers (1–170) and locations (170,000 total placement combinations) of diagnostic facilities, quantifying the percentage of the PAR within 1h and 5h travel of the facilities, as per in-country targets. Our simulations indicate that a 70% reduction (51/170) in diagnostic centres still exceeded minimal targets of coverage even for remote populations, with >95% of a total PAR of ~3million individuals living ≤1h from a diagnostic centre, and we demonstrate an approach to best place these facilities, informing a minimal impact scale back. Conclusions: Our results highlight that surveillance of g-HAT in north-western Uganda can be scaled back without substantially reducing coverage of the PAR. The methodology described can contribute to cost-effective and equable strategies for the surveillance of NTDs and other infectious diseases approaching elimination or (re-)emergence. Author summary: Disease surveillance systems are an essential component of public health practice and are often considered the first line in averting epidemics for (re-)emerging diseases. Regular evaluation of surveillance systems ensures that they remain operating at maximum efficiency; systems that survey diseases of low incidence, such as those within elimination settings, should be simplified to reduce the reporting burden. A lack of guidance on how to optimise disease surveillance in an elimination setting may result in added expense, and/or the underreporting of disease. Here, we propose a framework methodology to determine systematically the optimal number and placement of surveillance sites for the surveillance of infectious diseases approaching elimination. By utilising estimates of geographic accessibility, through the construction of a resistance surface and a simulation approach, we identify that the number of operational diagnostic facilities for Gambian human African trypanosomiasis in north-western Uganda can be reduced by 70% with a minimal reduction in existing coverage, and identify the minimum number of facilities required to meet coverage targets. Our analysis can be used to inform the number and positioning of surveillance sites for diseases within an elimination setting. Passive surveillance becomes increasingly important as cases decline and active surveillance becomes less cost-effective; methods to evaluate how best to engage this passive surveillance capacity given facility capacity and geographic distribution are pertinent for several NTDs where diagnosis is complex. Not only is this a complicated research area for diseases approaching elimination, a well-designed surveillance system is essential for the detection of emerging diseases, with this work being topical in a climate where emerging pathogens are becoming more commonplace. [ABSTRACT FROM AUTHOR]

Mycetoma is considered a neglected tropical disease globally. However, data on its burden and the associated complications in Uganda are limited. Hence we aimed to estimate its burden in Uganda. Firstly, a systematic PubMed search for all studies of any design on mycetoma in Uganda without restriction to the year of publication was conducted. A retrospective review of all the biopsy reports at the Pathology Reference Laboratory, Department of Pathology, Makerere University, Kampala, Uganda from January 1950 to September 2019 was conducted to identify any reports on mycetoma histological diagnosis. During the 70-years study period, 30 cases were identified by the literature review, with 249 additional cases identified by review of biopsy reports (total of 279 cases). The average incidence was estimated at 0.32/100,000 persons and prevalence of 8.32/100,000 persons per decade. However, there was a general decline in the number of cases detected recently. Males and the age group of 21–30 years were the most affected by mycetoma in Uganda, and only 7% of the cases were children. The highest number of cases was recorded from Kampala (n = 30) and Jinja (n = 19) districts. The majority of the cases (68%) were referred from surgical units. The foot was the most affected part of the body (72%). Ten per cent of the cases had bone involvement of which 58% required amputation. Fungi were the most common causative agents (89%) followed by Nocardia species (5%) and Actinomycetes (4%). The index of clinical suspicion of mycetoma was low (45%) with a very large differential diagnosis. Mycetoma is a relatively rare disease in Uganda, mostly caused by fungi, and there is a big gap in data and epidemiological studies. More systematic studies are warranted to define the true burden of mycetoma in Uganda. Author summary: Recently, the World Health Organisation recognized mycetoma, a chronic, progressively destructive morbid inflammatory disease usually of the foot as a neglected tropical disease. However, mycetoma is not a notifiable disease and thus the global burden of the disease remains poorly defined. It is therefore important that any collection of available data on this disease is brought forward to highlight the extent and magnitude of the burden of mycetoma. We retrospectively gathered data on the burden and aetiology of mycetoma in a country (Uganda) within the mycetoma belt based on histological diagnosis and systematic review. We found that fungal pathogens are the most common cause of mycetoma in this region. However, the distribution of the lesions is consistent with global data with the foot being the most affected site. We also noticed that clinicians have low index of clinical suspicion for mycetoma leading to under-diagnosis. Mycetoma is uncommon but not rare in Uganda; more research is obligatory to precisely define the distribution and determinants of the disease as well as primary and secondary preventative measures in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Malaria is endemic in all regions where gambiense or rhodesiense human African trypanosomiasis (HAT) is reported, and both diseases have similarities in their symptomatology. A combined test could be useful for both diseases and would facilitate integration of the screening for gambiense HAT (gHAT) and malaria diagnosis. This study aimed to evaluate a combined prototype rapid diagnostic test (RDT) for gHAT and malaria. Methods: Blood samples were collected in the Democratic Republic of the Congo and in Uganda to evaluate the performance of a prototype HAT/Malaria Combined RDT in comparison to an individual malaria RDT based on Plasmodium falciparum (P.f.) Histidine Rich Protein II (HRP-II or HRP2) antigen (SD BIOLINE Malaria Ag P.f. RDT) for malaria detection and an individual gHAT RDT based on recombinant antigens, the SD BIOLINE HAT 2.0 RDT for HAT screening. Due to the current low prevalence of gHAT in endemic regions, the set of blood samples that were collected was used to evaluate the specificity of the RDTs for gHAT, and additional archived plasma samples were used to complete the evaluation of the HAT/Malaria Combined RDT in comparison to the HAT 2.0 RDT. Results: Frozen whole blood samples from a total of 486 malaria cases and 239 non-malaria controls, as well as archived plasma samples from 246 gHAT positive and 246 gHAT negative individuals were tested. For malaria, the sensitivity and specificity of the malaria band in the HAT/Malaria Combined RDT were 96.9% (95% CI: 95.0–98.3) and 97.1% (95% CI: 94.1–98.8) respectively. The sensitivity and specificity of the SD BIOLINE malaria Ag P.f. RDT were 97.3% (95% CI: 95.5–98.6) and 97.1% (95% CI: 94.1–98.8) respectively. For gHAT, using archived plasma samples, the sensitivity and specificity were respectively 89% (95% CI: 84.4–92.6) and 93.5% (95% CI: 89.7–96.2) with the HAT /malaria Combined RDT, and 88.2% (95% CI: 83.5–92) and 94.7% (95% CI: 91.1–97.2) with the HAT 2.0 RDT. Using the whole blood samples that were collected during the study, the specificity of the HAT/malaria Combined RDT for gHAT was 95.8% (95% CI: 94.3–97.0). Conclusion: The HAT/Malaria Combined prototype RDT was as accurate as the individual malaria or gHAT RDTs. The HAT/Malaria Combined prototype RDT is therefore suitable for both malaria diagnosis and gHAT screening. However, there is a need to assess its accuracy using fresh samples in prospective clinical trials. Author summary: The annual number of reported cases of human African trypanosomiasis (HAT), also known as sleeping sickness (SS), is currently below 1,000 cases worldwide. The Democratic Republic of the Congo (DRC), the most affected country, and Uganda, which shares a border with DRC, are both endemic for gambiense HAT (gHAT). The main strategy to control gHAT is active screening of at-risk individuals, followed by diagnosis and treatment of confirmed cases. However, this strategy and even the passive screening as currently implemented become less efficient with declining incidence, justifying innovative strategies to efficiently detect the remaining cases. All areas where gHAT occurs are also endemic for malaria, presenting an opportunity to integrate gHAT screening activities within malaria control activities. This integration is warranted by the fact that in early disease stage, gHAT patients present with signs and symptoms strikingly similar to those of malaria. In order to use malaria diagnosis as an entry point to screen for gHAT, Standard Diagnostics (SD), Korea (now Abbott Diagnostics, Korea Inc–ADK) made a Combined prototype RDT for both malaria and gHAT, expected to be as accurate as the individual gHAT and malaria RDTs. In this study, we evaluated the accuracy of the Combined prototype RDT using whole blood samples collected in Uganda and DRC, and archived plasma samples collected in DRC, Angola and Central African Republic. We found that the Combined prototype performs just as well as individual RDTs. [ABSTRACT FROM AUTHOR]

Background: Large-scale control of sleeping sickness has led to a decline in the number of cases of Gambian human African trypanosomiasis (g-HAT) to <2000/year. However, achieving complete and lasting interruption of transmission may be difficult because animals may act as reservoir hosts for T. b. gambiense. Our study aims to update our understanding of T. b. gambiense in local vectors and domestic animals of N.W. Uganda. Methods: We collected blood from 2896 cattle and 400 pigs and In addition, 6664 tsetse underwent microscopical examination for the presence of trypanosomes. Trypanosoma species were identified in tsetse from a subsample of 2184 using PCR. Primers specific for T. brucei s.l. and for T. brucei sub-species were used to screen cattle, pig and tsetse samples. Results: In total, 39/2,088 (1.9%; 95% CI = 1.9–2.5) cattle, 25/400 (6.3%; 95% CI = 4.1–9.1) pigs and 40/2,184 (1.8%; 95% CI = 1.3–2.5) tsetse, were positive for T. brucei s.l.. Of these samples 24 cattle (61.5%), 15 pig (60%) and 25 tsetse (62.5%) samples had sufficient DNA to be screened using the T. brucei sub-species PCR. Further analysis found no cattle or pigs positive for T. b. gambiense, however, 17/40 of the tsetse samples produced a band suggestive of T. b. gambiense. When three of these 17 PCR products were sequenced the sequences were markedly different to T. b. gambiense, indicating that these flies were not infected with T. b. gambiense. Conclusion: The lack of T. b. gambiense positives in cattle, pigs and tsetse accords with the low prevalence of g-HAT in the human population. We found no evidence that livestock are acting as reservoir hosts. However, this study highlights the limitations of current methods of detecting and identifying T. b. gambiense which relies on a single copy-gene to discriminate between the different sub-species of T. brucei s.l. Author summary: The decline of annual cases of West-African sleeping sickness in Uganda raises the prospect that elimination of the disease is achievable for the country. However, with the decrease in incidence and the likely subsequent change in priorities there is a need to confirm that the disease is truly eliminated. One unanswered question is the role that domestic animals play in maintaining transmission of the disease. The potential of cryptic-animal reservoirs is a serious threat to successful and sustained elimination of the disease. It is with the intent of resolving this question that we have carried out this study whereby we examined 2088 cattle, 400 pigs and 2184 tsetse for Trypanosoma brucei gambiense, the parasite responsible for the disease. Our study found T. brucei s.l. in local cattle, pigs and tsetse flies, with their respective prevalences as follows, 1.9%, 6.3% and 1.8%. Further analysis to establish identity of these positives to the sub-species level found that no cattle, pigs or tsetse were carrying the pathogen responsible for Gambian sleeping sickness. Our work highlights the difficulty of establishing the absence of a disease, especially in an extremely low endemic setting, and the limitations of some of the most commonly used methods. [ABSTRACT FROM AUTHOR]

Background: Vector-borne diseases are important causes of mortality and morbidity in humans and livestock, particularly for poorer communities and countries in the tropics. Large-scale programs against these diseases, for example malaria, dengue and African trypanosomiasis, include vector control, and assessing the impact of this intervention requires frequent and extensive monitoring of disease vector abundance. Such monitoring can be expensive, especially in the later stages of a successful program where numbers of vectors and cases are low. Methodology/Principal findings: We developed a system that allows the identification of monitoring sites where pre-intervention densities of vectors are predicted to be high, and travel cost to sites is low, highlighting the most efficient locations for longitudinal monitoring. Using remotely sensed imagery and an image classification algorithm, we mapped landscape resistance associated with on- and off-road travel for every gridded location (3m and 0.5m grid cells) within Koboko district, Uganda. We combine the accessibility surface with pre-existing estimates of tsetse abundance and propose a stratified sampling approach to determine the most efficient locations for longitudinal data collection. Our modelled predictions were validated against empirical measurements of travel-time and existing maps of road networks. We applied this approach in northern Uganda where a large-scale vector control program is being implemented to control human African trypanosomiasis, a neglected tropical disease (NTD) caused by trypanosomes transmitted by tsetse flies. Our accessibility surfaces indicate a high performance when compared to empirical data, with remote sensing identifying a further ~70% of roads than existing networks. Conclusions/Significance: By integrating such estimates with predictions of tsetse abundance, we propose a methodology to determine the optimal placement of sentinel monitoring sites for evaluating control programme efficacy, moving from a nuanced, ad-hoc approach incorporating intuition, knowledge of vector ecology and local knowledge of geographic accessibility, to a reproducible, quantifiable one. Author summary: Assessing the impact of vector control programmes requires longitudinal measurements of the abundance of insect vectors within intervention areas. Such monitoring can be expensive, especially in the later stages of a successful program where numbers of vectors and cases of disease are low. Efficient monitoring involves a prior selection of monitoring sites that are easy to reach and produce rich information on vector abundance. Here, we used image classification and cost-distance algorithms to produce estimates of accessibility within Koboko district, Uganda, where vector control is contributing to the elimination of sleeping sickness, a neglected tropical disease (NTD). We combine an accessibility surface with pre-existing estimates of tsetse abundance and propose a stratified sampling approach to determine locations which are associated with low cost (lowest travel time) and potential for longitudinal data collection (high pre-intervention abundance). Our method could be adapted for use in the planning and monitoring of tsetse- and other vector-control programmes. By providing methods to ensure that vector control programmes operate at maximum efficiency, we can ensure that the limited funding associated with some of these NTDs has the largest impact. [ABSTRACT FROM AUTHOR]

In 1994, combined active and passive screening reported 1469 cases from the historic Gambian Human African Trypanosomiasis (gHAT) foci of West Nile, Uganda. Since 2011 systematic active screening has stopped and there has been reliance on passive screening. During 2014, passive screening alone detected just nine cases. In the same year a tsetse control intervention was expanded to cover the main gHAT foci in West Nile to curtail transmission of gHAT contributing to the elimination of gHAT as a public health problem in the area. It is known that sole reliance on passive screening is slow to detect cases and can underestimate the actual true number. We therefore undertook an active screening programme designed to test the efficacy of these interventions against gHAT transmission and clarify disease status. Screening was conducted in 28 randomly selected villages throughout the study area, aiming to sample all residents. Whole blood from 10,963 participants was analysed using CATT and 97 CATT suspects (0.9%) were evaluated with microscopy and trypanolysis. No confirmed cases were found providing evidence that the gHAT prevention programmes in West Nile have been effective. Results confirm gHAT prevalence in the study area of West Nile is below the elimination threshold (1 new case / 10,000 population), making elimination on course across this study area if status is maintained. The findings of this study can be used to guide future HAT and tsetse management in other gHAT foci, where reduced caseloads necessitate a shift from active to passive screening. [ABSTRACT FROM AUTHOR]

Background: Nodding Syndrome was first reported from Tanzania in the 1960s but appeared as an epidemic in Northern Uganda in the 1990s during the LRA civil war. It is characterized by repetitive head nodding, often followed by other types of seizures, developmental retardation and growth faltering with onset occurring in children aged 5–15 years. More than 50 years after the first reports, the aetiology remains unknown and there is still no cure. The recent hypothesis that Nodding Syndrome is caused by onchocerciasis also increases the relevance of onchocerciasis control. Northern Uganda, with its unique socio-political history, adds challenges to the prevention and treatment for Nodding Syndrome. This article aims to show how and why Nodding Syndrome has been politicised in Uganda; how this politicisation has affected health interventions including research and dissemination; and, the possible implications this can have for disease prevention and treatment. Methodology: Ethnographic research methods were used triangulating in-depth interviews, focus group discussions, informal conversations and participant observation, for an understanding of the various stakeholders’ perceptions of Nodding Syndrome and how these perceptions impact future interventions for prevention, treatment and disease control. Principal findings: Distrust towards the government was a sentiment that had developed in Northern Uganda over several decades of war and was particularly linked to the political control and ethnic divisions between the north and south. This coincided with the sudden appearance of Nodding Syndrome, an unknown epidemic disease of which the cause could not be clearly identified and optimal treatment had not clearly been established. Additionally, the dissemination of the inconclusive results of research conducted in the area lacked sufficient community involvement which further fueled this political distrust. Disease perceptions revolved around rumours that the entire Acholi ethnic group of the north would be annihilated, or that international researchers were making money by stealing study samples. This discouraged some community members from participating in research or from accepting the mass drug administration of ivermectin for prevention and treatment of onchocerciasis. Such rumour and distrust led to suspicions concerning the integrity of the disseminated results, which may negatively impact future disease management and control interventions. Conclusions and recommendations: Trust must be built up gradually through transparency and by de-politicising interventions. This can be done by engaging the community at regular intervals during research and data collection and the dissemination of results in addition to involvement during service delivery for prevention and treatment. Maintaining a regular feedback loop with the community will help control rumours, build trust, and improve the preparations for adequate dissemination. [ABSTRACT FROM AUTHOR]

Background: An understudied disease, little research thus far has explored responses to Buruli ulcer and quests for therapy from biosocial perspective, despite reports that people seek biomedical treatment too late. Methods and findings: Taking an inductive approach and drawing on long-term ethnographic fieldwork in 2013–14, this article presents perspectives on this affliction of people living and working along the River Nile in northwest Uganda. Little is known biomedically about its presence, yet ‘Buruli’, as it is known locally, was and is a significant affliction in this region. Establishing a biosocial history of ‘Buruli’, largely obscured from biomedical perspectives, offers explanations for contemporary understandings, perceptions and practices. Conclusions/Significance: We must move beyond over-simplifying and problematising ‘late presentation for treatment’ in public health, rather, develop biosocial approaches to understanding quests for therapy that take into account historical and contemporary contexts of health, healing and illness. Seeking to understand the context in which healthcare decisions are made, a biosocial approach enables greater depth and breadth of insight into the complexities of global and local public health priorities such as Buruli ulcer. [ABSTRACT FROM AUTHOR]

Background: Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples’ knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages. Methods: The study was a community survey done in Luweero, Ibanda and Kamwenge districts that have experienced outbreaks of Ebola and Marburg virus diseases. Quantitative data were collected using a structured questionnaire and triangulated with qualitative participatory epidemiology techniques to gain a communities’ knowledge and attitude towards Ebola and Marburg virus disease. Results: Out of 740 respondents, 48.5% (359/740) were categorized as being knowledgeable about Ebola and Marburg virus diseases, whereas 60.5% (448/740) were having a positive attitude towards control and prevention of Ebola and Marburg virus diseases. The mean knowledge and attitude percentage scores were 54.3 (SD = 23.5, 95%CI = 52.6–56.0) and 69.9 (SD = 16.9, 95%CI = 68.9–71.1) respectively. People educated beyond primary school were more likely to be knowledgeable about Ebola and Marburg virus disease than those who did not attain any formal education (OR = 3.6, 95%CI = 2.1–6.1). Qualitative data revealed that communities describe Ebola and Marburg virus diseases as very severe diseases with no cure and they believe the diseases spread so fast. Respondents reported fear and stigma suffered by survivors, their families and the broader community due to these diseases. Conclusion: Communities in Uganda affected by filovirus outbreaks have moderate knowledge about these diseases and have a positive attitude towards practices to prevent and control Ebola and Marburg viral diseases. The public health sector should enhance this community knowledge gap to empower them more by supplying educational materials for epidemic preparedness in future using appropriate communication channels as proposed by the communities. [ABSTRACT FROM AUTHOR]

Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretroviral therapy (ART). We sampled HIV-infected adults for eight gastrointestinal parasites and correlated parasitic infection with demographic predictors, and clinical and immunologic outcomes. Contrasting with previous studies, we measured parasitic infection with a quantitative, highly sensitive and specific polymerase chain reaction (PCR) method. This cohort study enrolled HIV-infected Ugandans from August-September 2013 in Mbale, Uganda and collected stool and blood samples at enrollment. Real-time PCR quantified stool: Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica, and Giardia intestinalis infection. Generalized linear models assessed relationships between parasitic infection and clinical or demographic data. 35% of participants (71/202) tested positive for ≥1 helminth, mainly N. americanus (55/199, 28%), and 4.5% (9/202) were infected with ≥2 stool parasites. Participants with hookworm infection had lower average CD4+ cell counts (-94 cells/mcL, 95%CI: -141, -48 cells/mcL; p<0.001) after adjustment for sex, CD4+ nadir at clinic entry, and time on ART. The high prevalence of parasitic infection and correlation with decreased CD4+ concentrations highlight the need to re-examine the effects of invasive helminth co-infection in rural, HIV-infected populations in the era of widely available ART. Elucidating the relationship between hookworm infection and immune recovery could provide opportunities for health optimization, e.g. integrated deworming, in these vulnerable populations. [ABSTRACT FROM AUTHOR]

The traditional role of African elders and their connection with the community make them important stakeholders in community-based disease control programmes. We explored elders’ memories related to interventions against sleeping sickness to assess whether or not past interventions created any trauma which might hamper future control operations. Using a qualitative research framework, we conducted and analysed twenty-four in-depth interviews with Lugbara elders from north-western Uganda. Participants were selected from the villages inside and outside known historical sleeping sickness foci. Elders’ memories ranged from examinations of lymph nodes conducted in colonial times to more recent active screening and treatment campaigns. Some negative memories dating from the 1990s were associated with diagnostic procedures, treatment duration and treatment side effects, and were combined with memories of negative impacts related to sleeping sickness epidemics particularly in HAT foci. More positive observations from the recent treatment campaigns were reported, especially improvements in treatment. Sleeping sickness interventions in our research area did not create any permanent traumatic memories, but memories remained flexible and open to change. This study however identified that details related to medical procedures can remain captured in a community’s collective memory for decades. We recommend more emphasis on communication between disease control programme planners and communities using detailed and transparent information distribution, which is not one directional but rather a dialogue between both parties. [ABSTRACT FROM AUTHOR]

Background: Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Since the 1990s, Africa has accounted for the majority of reported human cases. In Uganda, plague cases occur in the West Nile region, near the border with Democratic Republic of Congo. Despite the ongoing risk of contracting plague in this region, little is known about Y. pestis genotypes causing human disease. Methodology/Principal Findings: During January 2004–December 2012, 1,092 suspect human plague cases were recorded in the West Nile region of Uganda. Sixty-one cases were culture-confirmed. Recovered Y. pestis isolates were analyzed using three typing methods, single nucleotide polymorphisms (SNPs), pulsed field gel electrophoresis (PFGE), and multiple variable number of tandem repeat analysis (MLVA) and subpopulations analyzed in the context of associated geographic, temporal, and clinical data for source patients. All three methods separated the 61 isolates into two distinct 1.ANT lineages, which persisted throughout the 9 year period and were associated with differences in elevation and geographic distribution. Conclusions/Significance: We demonstrate that human cases of plague in the West Nile region of Uganda are caused by two distinct 1.ANT genetic subpopulations. Notably, all three typing methods used, SNPs, PFGE, and MLVA, identified the two genetic subpopulations, despite recognizing different mutation types in the Y. pestis genome. The geographic and elevation differences between the two subpopulations is suggestive of their maintenance in highly localized enzootic cycles, potentially with differing vector-host community composition. This improved understanding of Y. pestis subpopulations in the West Nile region will be useful for identifying ecologic and environmental factors associated with elevated plague risk. [ABSTRACT FROM AUTHOR]

Background: Mansonella perstans is a widespread, but relatively unknown human filarial parasite transmitted by Culicoides biting midges. Although it is found in many parts of sub-Saharan Africa, only few studies have been carried out to deepen the understanding of its ecology, epidemiology, and health consequences. Hence, knowledge about ecological drivers of the vector and parasite distribution, integral to develop spatially explicit models for disease prevention, control, and elimination strategies, is limited. Methodology: We analyzed data from a comprehensive nationwide survey of M. perstans infection conducted in 76 schools across Uganda in 2000–2003, to identify environmental drivers. A suite of Bayesian geostatistical regression models was fitted, and the best fitting model based on the deviance information criterion was utilized to predict M. perstans infection risk for all of Uganda. Additionally, we investigated co-infection rates and co-distribution with Wuchereria bancrofti and Plasmodium spp. infections observed at the same survey by mapping geographically overlapping areas. Principal Findings: Several bioclimatic factors were significantly associated with M. perstans infection levels. A spatial Bayesian regression model showed the best fit, with diurnal temperature range, normalized difference vegetation index, and cattle densities identified as significant covariates. This model was employed to predict M. perstans infection risk at non-sampled locations. The level of co-infection with W. bancrofti was low (0.3%), due to limited geographic overlap. However, where the two infections did overlap geographically, a positive association was found. Conclusions/Significance: This study presents the first geostatistical risk map for M. perstans in Uganda. We confirmed a widespread distribution of M. perstans, and identified important potential drivers of risk. The results provide new insight about the ecologic preferences of this otherwise poorly known filarial parasite and its Culicoides vector species in Uganda, which might be relevant for other settings in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: The association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women. Methods: We sampled 1,832 individuals aged 5–90 years from 30 communities in Mayuge District, Uganda. Demographic, village, and parasitological data were collected. Infection risk factors were compared in ordinal logistic regressions. Anaemia and infection intensities were analyzed in multilevel models, and population attributable fractions were estimated. Findings: Household and village-level predictors of Schistosoma mansoni and hookworm were opposite in direction or significant for single infections. S. mansoni was found primarily in children, whereas hookworm was prevalent amongst the elderly. Anaemia was more prevalent in individuals with S. mansoni and increased by 2.86 fold (p-value<0.001) with heavy S. mansoni infection intensity. Individuals with heavy hookworm were 1.65 times (p-value = 0.008) more likely to have anaemia than uninfected participants. Amongst individuals with heavy S. mansoni infection intensity, 32.0% (p-value<0.001) of anaemia could be attributed to S. mansoni. For people with heavy hookworm infections, 23.7% (p-value = 0.002) of anaemia could be attributed to hookworm. A greater fraction of anaemia (24.9%, p-value = 0.002) was attributable to heavy hookworm infections in adults (excluding pregnant women) as opposed to heavy hookworm infections in school-aged children and pregnant women (20.2%, p-value = 0.001). Conclusion: Community-based surveys captured anaemia in children and adults affected by S. mansoni and hookworm infections. For areas endemic with schistosomiasis or hookworm infections, WHO guidelines should include adults for treatment in helminth control programmes. [ABSTRACT FROM AUTHOR]

Background: Animal tungiasis is believed to increase the prevalence and parasite burden in humans. Animal reservoirs of Tunga penetrans differ among endemic areas and their role in the epidemiology of tungiasis had never been investigated in Uganda. Methods and Findings: To identify the major animal reservoirs of Tunga penetrans and their relative importance in the transmission of tungiasis in Uganda, a cross sectional study was conducted in animal rearing households in 10 endemic villages in Bugiri District. T. penetrans infections were detected in pigs, dogs, goats and a cat. The prevalences of households with tungiasis ranged from 0% to 71.4% (median 22.2) for animals and from 5 to 71.4% (median 27.8%) for humans. The prevalence of human tungiasis also varied among the population of the villages (median 7%, range 1.3–37.3%). Pig infections had the widest distribution (nine out of 10 villages) and highest prevalence (median 16.2%, range 0–64.1%). Pigs also had a higher number of embedded sand fleas than all other species combined (p<0.0001). Dog tungiasis occurred in five out of 10 villages with low prevalences (median of 2%, range 0–26.9%). Only two goats and a single cat had tungiasis. Prevalences of animal and human tungiasis correlated at both village (rho = 0.89, p = 0.0005) and household (rho = 0.4, p<0.0001) levels. The median number of lesions in household animals correlated with the median intensity of infection in children three to eight years of age (rho = 0.47, p<0.0001). Animal tungiasis increased the odds of occurrence of human cases in households six fold (OR = 6.1, 95% CI 3.3–11.4, p<0.0001). Conclusion: Animal and human tungiasis were closely associated and pigs were identified as the most important animal hosts of T. penetrans. Effective tungiasis control should follow One Health principles and integrate ectoparasites control in animals. [ABSTRACT FROM AUTHOR]

Background: Sleeping sickness due to Trypanosoma brucei rhodesiense has a wide spectrum of clinical presentations coupled with differences in disease progression and severity across East and Southern Africa. The disease progresses from an early (hemo-lymphatic) stage to the late (meningoencephalitic) stage characterized by presence of parasites in the central nervous system. We hypothesized that disease progression and severity of the neurological response is modulated by cytokines. Methods: A total of 55 sleeping sickness cases and 41 healthy controls were recruited passively at Lwala hospital, in Northern Uganda. A panel of six cytokines (IFN-γ, IL1-β, TNF-α, IL-6, TGF-β and IL-10) were assayed from paired plasma and cerebrospinal fluid (CSF) samples. Cytokine concentrations were analyzed in relation to disease progression, clinical presentation and severity of neurological responses. Results: Median plasma levels (pg/ml) of IFN-γ (46.3), IL-6 (61.7), TGF-β (8755) and IL-10 (256.6) were significantly higher in cases compared to controls (p< 0.0001). When early stage and late stage CSF cytokines were compared, IL-10 and IL-6 were up regulated in late stage patients and were associated with a reduction in tremors and cranioneuropathy. IL-10 had a higher staging accuracy with a sensitivity of 85.7% (95% CI, 63.7%-97%) and a specificity of 100% (95% CI, 39.8%-100%) while for IL-6, a specificity of 100% (95% CI, 47.8%-100%) gave a sensitivity of 83.3% (95% CI, 62.2%-95.3%). Conclusion: Our study demonstrates the role of host inflammatory cytokines in modulating the progression and severity of neurological responses in sleeping sickness. We demonstrate here an up-regulation of IL-6 and IL-10 during the late stage with a potential as adjunct stage biomarkers. Given that both cytokines could potentially be elevated by other CNS infections, our findings should be further validated in a large cohort of patients including those with other inflammatory diseases such as cerebral malaria. Author Summary: Sleeping sickness in east and central Africa is caused by a protozoan parasite, Trypanosoma brucei rhodesiense. About 12.3 million people are at a risk of acquiring the disease that is fatal if untreated. The disease progresses from an early stage with trypanosomes in blood and lymph to a late stage in which trypanosomes enter the central nervous system. Variations in disease presentation, progression and severity of the disease have been reported and cytokines have been proposed as potential players. Before treatment is commenced, disease stage has to be ascertained since treatment for the two stages is different. The currently used staging criteria depends on finding trypanosomes in the cerebrospinal fluids (CSF) and elevation in CSF white blood cells however, this has been found to have low sensitivity. We therefore measured plasma and cerebrospinal fluid cytokine concentrations and determined associations with disease presentation, stage progression and severity of the neurological response. Our study shows that concentrations of specific cytokines are elevated in sleeping sickness patients and have a potential to discriminate between patients in early or late stage of infection. [ABSTRACT FROM AUTHOR]

Free-ranging nonhuman primates are frequent sources of zoonotic pathogens due to their physiologic similarity and in many tropical regions, close contact with humans. Many high-risk disease transmission interfaces have not been monitored for zoonotic pathogens due to difficulties inherent to invasive sampling of free-ranging wildlife. Non-invasive surveillance of nonhuman primates for pathogens with high potential for spillover into humans is therefore critical for understanding disease ecology of existing zoonotic pathogen burdens and identifying communities where zoonotic diseases are likely to emerge in the future. We developed a non-invasive oral sampling technique using ropes distributed to nonhuman primates to target viruses shed in the oral cavity, which through bite wounds and discarded food, could be transmitted to people. Optimization was performed by testing paired rope and oral swabs from laboratory colony rhesus macaques for rhesus cytomegalovirus (RhCMV) and simian foamy virus (SFV) and implementing the technique with free-ranging terrestrial and arboreal nonhuman primate species in Uganda and Nepal. Both ubiquitous DNA and RNA viruses, RhCMV and SFV, were detected in oral samples collected from ropes distributed to laboratory colony macaques and SFV was detected in free-ranging macaques and olive baboons. Our study describes a technique that can be used for disease surveillance in free-ranging nonhuman primates and, potentially, other wildlife species when invasive sampling techniques may not be feasible. Author Summary: Wild nonhuman primates are frequent sources of pathogens that could be transmitted to humans because they are closely genetically related and have intimate contact with humans in many parts of the world. Sampling primates to screen for zoonotic pathogens is logistically challenging because standard invasive sampling techniques, such as the collection of a blood sample or an oral swab, requires field anesthesia. This research describes a non-invasive oral sampling technique that involves distributing a rope for primates to chew on that can be retrieved and screened for pathogens. Oral samples were successfully collected from multiple wild primate species in remote field settings and viruses were detected in those samples. This non-invasive sampling method has the potential for future applications in disease studies examining primates as sources of diseases that could affect humans in remote tropical settings. [ABSTRACT FROM AUTHOR]

Background: Schistosoma mansoni infection is proven to be a major health problem of preschool-age children in sub-Saharan Africa, yet this age category is not part of the schistosomiasis control program. The objective of this study was to compare the impact of single and double dose praziquantel (PZQ) treatment on cure rates (CRs), egg reduction rates (ERRs) and re-infection rates 8 months later, in children aged 1-5 years living along Lake Victoria, Uganda. Methodology/Principal Findings: Infected children (n= 1017) were randomized to receive either a single or double dose of PZQ. Initially all children were treated with a single standard oral dose 40 mg/kg body weight of PZQ. Two weeks later a second dose was administered to children in the double dose treatment arm. Side effects were monitored at 30 minutes to 24 hours after each treatment. Efficacy in terms of CRs and ERRs for the two treatments was assessed and compared 1 month after the second treatment. Re-infection with S. mansoni was assessed in the same children 8 months following the second treatment. CRs were non-significantly higher in children treated with two 40 mg/kg PZQ doses (85.5%; 290/339) compared to a single dose (83.2%; 297/357). ERRs were significantly higher in the double dose with 99.3 (95%CI: 99.2-99.5) compared with 98.9 (95%CI: 98.7-99.1) using a single dose, (P = 0.01). Side effects occurred more frequently during the first round of drug administration and were mild and short-lived; these included vomiting, abdominal pain and bloody diarrhea. Overall re-infection rate 8 months post treatment was 44.5%. Conclusions: PZQ is efficacious and relatively safe to use in preschool-age children but there is still an unmet need to improve its formulation to suit small children. Two PZQ doses lead to significant reduction in egg excretion compared to a single dose. Re-infection rates with S. mansoni 8 months post treatment is the same among children irrespective of the treatment regimen. Author Summary: Intestinal schistosomiasis is a parasitic water borne neglected tropical disease of considerable public health relevance in the tropics and subtropics. In Uganda, approximately 20 million people are at risk of being infected with S. mansoni, which causes intestinal schistosomiasis, and 4 million individuals are estimated to be infected. Currently, schistosomiasis control using PZQ chemotherapy is mainly focusing on school-age children (age 6–19 years) and to those adults considered to have the highest risk of infection. So far preschool-age children are not targeted in schistosomiasis preventive chemotherapy campaigns due to the limited documentation on the safety of PZQ in this age group. However, a number of studies have revealed that children less than 6 years of age get infected with S. mansoni usually through bathing, playing or swimming in schistosome-infested waters and are at higher risk of infection than previously thought. This study compared efficacy of PZQ treatment in terms of CRs and ERRs using a single and double dose among children aged 1–5 years, living along Lake Victoria in eastern Uganda. The effect of the two different regimes on S. mansoni re-infection 8 months post treatment was also assessed. [ABSTRACT FROM AUTHOR]

Tsetse flies transmit trypanosomes, the causative agent of human and animal African trypanosomiasis. The tsetse vector is extensively distributed across sub-Saharan Africa. Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host, parasite and the vector responsible for transmission. Mapping the distribution and abundance of tsetse flies assists in predicting trypanosomiasis distributions and developing rational strategies for disease and vector control. Given scarce resources to carry out regular full scale field tsetse surveys to up-date existing tsetse maps, there is a need to devise inexpensive means for regularly obtaining dependable area-wide tsetse data to guide control activities. In this study we used spatial epidemiological modelling techniques (logistic regression) involving 5000 field-based tsetse-data (G. f. fuscipes) points over an area of 40,000 km2, with satellite-derived environmental surrogates composed of precipitation, temperature, land cover, normalised difference vegetation index (NDVI) and elevation at the sub-national level. We used these extensive tsetse data to analyse the relationships between presence of tsetse (G. f. fuscipes) and environmental variables. The strength of the results was enhanced through the application of a spatial autologistic regression model (SARM). Using the SARM we showed that the probability of tsetse presence increased with proportion of forest cover and riverine vegetation. The key outputs are a predictive tsetse distribution map for the Lake Victoria basin of Uganda and an improved understanding of the association between tsetse presence and environmental variables. The predicted spatial distribution of tsetse in the Lake Victoria basin of Uganda will provide significant new information to assist with the spatial targeting of tsetse and trypanosomiasis control. Author Summary: Trypanosomiasis is a vector-borne disease transmitted to both humans and animals by the tsetse fly. The tsetse vector is distributed across sub-Saharan Africa. Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host, parasite and the vector responsible for transmission. Mapping the distribution and abundance of tsetse flies assists in predicting trypanosomiasis distributions and developing rational strategies for disease and vector control. This study makes available dependable tsetse fly distribution data (maps) for use by decision makers. The approach makes use of modelling techniques involving limited field-sampled tsetse data points distributed across an area of approximately 40,000km2 within the Lake Victoria basin of Uganda. Precipitation, temperature, landcover, normalised difference vegetation index (NDVI, a measure of the amount of green vegetation) and elevation data were used as environmental covariates. We used logistic regression to analyse the relationships between presence of tsetse and the environmental covariates. The results indicated that tsetse are more likely to be present in areas with a greater proportion of riverine vegetation and forest cover. The key outputs are a predicted tsetse distribution map for the Lake Victoria basin of Uganda and an increased understanding of the association between tsetse presence and environmental variables. This will provide a vital resource for the planning and spatial targeting of future tsetse control activities. [ABSTRACT FROM AUTHOR]

Background: While Human African Trypanosomiasis (HAT) is in decline on the continent of Africa, the disease still remains a major health problem in Uganda. There are recurrent sporadic outbreaks in the traditionally endemic areas in south-east Uganda, and continued spread to new unaffected areas in central Uganda. We evaluated the evolutionary dynamics underpinning the origin of new foci and the impact of host species on parasite genetic diversity in Uganda. We genotyped 269 Trypanosoma brucei isolates collected from different regions in Uganda and southwestern Kenya at 17 microsatellite loci, and checked for the presence of the SRA gene that confers human infectivity to T. b. rhodesiense. Results: Both Bayesian clustering methods and Discriminant Analysis of Principal Components partition Trypanosoma brucei isolates obtained from Uganda and southwestern Kenya into three distinct genetic clusters. Clusters 1 and 3 include isolates from central and southern Uganda, while cluster 2 contains mostly isolates from southwestern Kenya. These three clusters are not sorted by subspecies designation (T. b. brucei vs T. b. rhodesiense), host or date of collection. The analyses also show evidence of genetic admixture among the three genetic clusters and long-range dispersal, suggesting recent and possibly on-going gene flow between them. Conclusions: Our results show that the expansion of the disease to the new foci in central Uganda occurred from the northward spread of T. b. rhodesiense (Tbr). They also confirm the emergence of the human infective strains (Tbr) from non-infective T. b. brucei (Tbb) strains of different genetic backgrounds, and the importance of cattle as Tbr reservoir, as confounders that shape the epidemiology of sleeping sickness in the region. Author Summary: Human African Trypanosomiasis (HAT) is a major health problem in Uganda, as there are recurrent sporadic outbreaks of the disease in traditionally endemic areas in south-east Uganda, and continued spread to new unaffected areas in central Uganda. In this study, we evaluate the evolutionary dynamics underpinning the origin of new disease foci and the impact of host species on parasite genetic diversity in Uganda. We found three distinct genetic clusters of T. brucei in Uganda and southwestern Kenya. Clusters 1 and 3 include isolates from central and southern Uganda, while cluster 2 contains mostly isolates from southwestern Kenya. These three clusters are not sorted by subspecies designation (T. b. brucei vs T. b. rhodesiense), host or date of collection. Our results show expansion of the disease to new foci in central Uganda occurred from the northward spread of T. b. rhodesiense. They also confirm the emergence of the human infective strains from non-infective T. b. brucei strains of different genetic backgrounds, and the importance of cattle as Tbr reservoir, as confounders that shape the epidemiology of sleeping sickness in the region. [ABSTRACT FROM AUTHOR]

Background: African trypanosomes constrain livestock and human health in Sub-Saharan Africa, and aggravate poverty and hunger of these otherwise largely livestock-keeping communities. To solve this, there is need to develop and use effective and cheap tsetse control methods. To this end, we aimed at determining the smallest proportion of a cattle herd that needs to be sprayed on the legs, bellies and ears (RAP) for effective Human and Animal African Trypanosomiasis (HAT/AAT) control. Methodology/Principal finding: Cattle in 20 villages were ear-tagged and injected with two doses of diminazene diaceturate (DA) forty days apart, and randomly allocated to one of five treatment regimens namely; no treatment, 25%, 50%, 75% monthly RAP and every 3 month Albendazole drench. Cattle trypanosome re-infection rate was determined by molecular techniques. ArcMap V10.3 was used to map apparent tsetse density (FTD) from trap catches. The effect of graded RAP on incidence risk ratios and trypanosome prevalence was determined using Poisson and logistic random effect models in R and STATA V12.1 respectively. Incidence was estimated at 9.8/100 years in RAP regimens, significantly lower compared to 25.7/100 years in the non-RAP regimens (incidence rate ratio: 0.37; 95% CI: 0.22–0.65; P<0.001). Likewise, trypanosome prevalence after one year of follow up was significantly lower in RAP animals than in non-RAP animals (4% vs 15%, OR: 0.20, 95% CI: 0.08–0.44; P<0.001). Contrary to our expectation, level of protection did not increase with increasing proportion of animals treated. Conclusions/significance: Reduction in RAP coverage did not significantly affect efficacy of treatment. This is envisaged to improve RAP adaptability to low income livestock keepers but needs further evaluation in different tsetse challenge, HAT/AAT transmission rates and management systems before adopting it for routine tsetse control programs. Author Summary: Poverty, hunger and human ill-health aggravated by trypanosomiasis in Sub-Saharan Africa can only be reduced by developing and using cheap and effective tsetse control methods. To further reduce the cost of tsetse control by restricting insecticides to the legs, belly and ears (RAP) we set out to determine the lowest RAP coverage that can effectively control tsetse. Cattle in 20 south-eastern Uganda villages were randomly allocated to 5 treatment groups, ear-tagged for ease of follow-up and treated twice forty days apart with a trypanocide at the beginning of the trial. Cattle in regimens 2–4 received monthly graded RAP (25%, 50% and 75% of village herd respectively), while those in regimens 1 and 5 received no more treatment and deworming once every three months respectively. Molecular techniques were used to check for trypanosome infections, while tsetse apparent density was determined by traps at 161 locations in the district. About 25% RAP coverage was effective at controlling T. brucei s.l. while 50–75% RAP coverage would need to be used for effective T.vivax and T.congolense nagana control. Use of RAP at lower herd coverage is envisaged to reduce its cost, damage to the environment and improve its uptake in resource poor communities. [ABSTRACT FROM AUTHOR]

Background: Whipworms (Trichuris sp.) are a globally distributed genus of parasitic helminths that infect a diversity of mammalian hosts. Molecular methods have successfully resolved porcine whipworm, Trichuris suis, from primate whipworm, T. trichiura. However, it remains unclear whether T. trichiura is a multi-host parasite capable of infecting a wide taxonomic breadth of primate hosts or a complex of host specific parasites that infect one or two closely related hosts. Methods and Findings: We examined the phylogenetic structure of whipworms in a multi-species community of non-human primates and humans in Western Uganda, using both traditional microscopy and molecular methods. A newly developed nested polymerase chain reaction (PCR) method applied to non-invasively collected fecal samples detected Trichuris with 100% sensitivity and 97% specificity relative to microscopy. Infection rates varied significantly among host species, from 13.3% in chimpanzees (Pan troglodytes) to 88.9% in olive baboons (Papio anubis). Phylogenetic analyses based on nucleotide sequences of the Trichuris internal transcribed spacer regions 1 and 2 of ribosomal DNA revealed three co-circulating Trichuris groups. Notably, one group was detected only in humans, while another infected all screened host species, indicating that whipworms from this group are transmitted among wild primates and humans. Conclusions and Significance: Our results suggest that the host range of Trichuris varies by taxonomic group, with some groups showing host specificity, and others showing host generality. In particular, one Trichuris taxon should be considered a multi-host pathogen that is capable of infecting wild primates and humans. This challenges past assumptions about the host specificity of this and similar helminth parasites and raises concerns about animal and human health. Author Summary: Whipworms are a group of gastrointestinal worms that are both common and globally distributed. These parasites are known to stunt development, especially in school-aged children, and therefore hinder economic, social, and intellectual growth. Unfortunately, research on whipworms has lagged behind its effects, at least in part because this parasite infects the world's poorest populations. Currently, a single species of whipworm is assumed capable of infecting both humans and non-human primates. In this study, we tested this assumption by collecting fecal samples from humans and overlapping non-human primate populations containing monkeys and chimpanzees in Western Uganda. Using molecular analyses, we examined patterns of genetic similarity between human and nonhuman primate whipworms. We identified three genetically distinct groups of whipworms that could not be distinguished by microscopic examination of their eggs. One of these groups was found in all nine species of primates examined, including humans. These findings suggest that some varieties of whipworms are indeed transmissible between humans and non-human primates, which raises concerns for both human health and conservation. [ABSTRACT FROM AUTHOR]

Background: Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This 'gold standard' has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings. Method/Principle Findings: In a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive. Conclusions/Significance: Six Kato-Katzs (two/stool from three stools) and/or one POC-CCA are required for M&E or drug-efficacy studies. Although unable to measure egg reduction rates, one POC-CCA appears to be more sensitive than six Kato-Katzs at four-weeks-post-praziquantel (drug efficacy) and six-months-post-praziquantel (M&E). Author Summary: Schistosomiasis is a parasitic disease infecting over 200 million people. It remains a major public health concern despite treatment of over 120 million people in sub-Saharan Africa alone. Accurate diagnostic methods are essential for monitoring drug efficacy and long-term control program success. The World Health Organization recommends two Kato-Katz thick smears (Kato-Katzs) from a single stool for Schistosoma mansoni diagnosis to map prevalence and areas for control interventions. Although highly specific, Kato-Katzs are thought to be insensitive at low egg counts. The recently refined urine point-of-care circulating cathodic antigen test (POC-CCA) has been proposed as a diagnostic alternative for mapping areas for interventions, and potentially for assessing drug efficacy. Over three years we assessed the accuracy of six Kato-Katzs and a single POC-CCA in detecting infections in Ugandan primary-school children at 11 time points with repeated praziquantel treatments. Our results demonstrate that two Kato-Katzs accurately detect S. mansoni infection pre-treatment, but at least three days of two Kato-Katzs per stool or one POC-CCA are required for annual monitoring and treatment evaluation and/or drug-efficacy studies. One POC-CCA may be more sensitive in measuring S. mansoni prevalence than six Kato-Katzs, but its accuracies for rigorous intensity measures are still to be proven. [ABSTRACT FROM AUTHOR]

Background: There is conflicting evidence on the immunologic benefit of treating helminth co-infections ("deworming") in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART. Methodology/Principal Findings: To estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (β = 42.8; 95% CI, −2.1 to 87.7) or after the first year of ART (β = −9.9; 95% CI, −24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (β = 63.0; 95% CI, 6.0 to 120.1) in females. Conclusions/Significance: Empiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit. Author Summary: It is estimated that up to half of all people infected with HIV in sub-Saharan Africa are co-infected with one or more gastrointestinal parasites. These parasitic infections may negatively impact the ability of the immune system to combat the HIV virus, leading to worse clinical outcomes in people with HIV. Therefore, routine, universal, empiric treatment of gastrointestinal parasite infections ("deworming") has been suggested as one strategy for optimizing HIV outcomes in this region. Previous studies have provided conflicting results on whether empiric deworming positively impacts markers of HIV disease progression such as CD4 count and viral load, but all of these studies were performed in HIV-infected individuals not yet on antiretroviral therapy. In this study, we measured the association between receipt of empiric deworming and CD4 count over time in HIV-infected adults taking antiretroviral therapy in southwestern Uganda, an area with a high parasite burden. We found that, overall, there was no significant association between deworming and change in CD4 count; however, when we performed a sub-analysis looking exclusively at females during the first year of ART, deworming was associated with significantly increased CD4 count. These results suggest that empiric deworming may not be an effective generalized strategy for improving HIV treatment outcomes in sub-Saharan Africa; however, the possibility of targeted benefit in specific sub-populations deserves further investigation. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids. Here, we examine the capacity of host and parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni infection. Methods/Principal Findings: We used Exiqon miRNA microarrays to profile miRNA expression in the livers of mice infected with S. mansoni at 7 weeks post-infection. Thirty-three mouse miRNAs were differentially expressed in infected compared to naïve mice (>2 fold change, p<0.05) including miR-199a-3p, miR-199a-5p, miR-214 and miR-21, which have previously been associated with liver fibrosis in other settings. Five of the mouse miRNAs were also significantly elevated in serum by twelve weeks post-infection. Sequencing of small RNAs from serum confirmed the presence of these miRNAs and further revealed eleven parasite-derived miRNAs that were detectable by eight weeks post infection. Analysis of host and parasite miRNA abundance by qRT-PCR was extended to serum of patients from low and high infection sites in Zimbabwe and Uganda. The host-derived miRNAs failed to distinguish uninfected from infected individuals. However, analysis of three of the parasite-derived miRNAs (miR-277, miR-3479-3p and bantam) could detect infected individuals from low and high infection intensity sites with specificity/sensitivity values of 89%/80% and 80%/90%, respectively. Conclusions: This work identifies parasite-derived miRNAs as novel markers of S. mansoni infection in both mice and humans, with the potential to be used with existing techniques to improve S. mansoni diagnosis. In contrast, although host miRNAs are differentially expressed in the liver during infection their abundance levels in serum are variable in human patients and may be useful in cases of extreme pathology but likely hold limited value for detecting prevalence of infection. Author Summary: Schistosomiasis is a chronic disease caused by blood flukes that affects over 200 million people worldwide, of which 90% live in Sub-Saharan Africa. In the field setting schistosomiasis caused by S. mansoni is diagnosed by detection of parasite eggs in stool samples using microscopic techniques. Here we investigate the potential of microRNAs (miRNAs), a class of short noncoding RNAs, to act as biomarkers of S. mansoni infection. We have identified a specific subset of murine miRNAs whose expression is significantly altered in the liver between 6–12 weeks post infection. However their abundance in serum is not significantly different between naïve and S. mansoni-infected mice until twelve weeks post infection and they do not display consistent differential abundance in the serum of infected versus uninfected humans. In contrast, three parasite-derived miRNAs (miR-277, bantam and miR-3479-3p) were detected in the serum of infected mice and human patients and the combined detection of these miRNAs could distinguish S. mansoni infected from uninfected individuals from low and high infection intensity areas with 89%/80% or 80%/90% specificity/sensitivity, respectively. These results demonstrate that miRNAs of parasite origin are a new class of serum biomarker for detecting S. mansoni and likely other helminth infections. [ABSTRACT FROM AUTHOR]

Background: The WHO has established the disability-adjusted life year (DALY) as a metric for measuring the burden of human disease and injury globally. However, most DALY estimates have been calculated as national totals. We mapped spatial variation in the burden of human African trypanosomiasis (HAT) in Uganda for the years 2000–2009. This represents the first geographically delimited estimation of HAT disease burden at the sub-country scale. Methodology/Principal Findings: Disability-adjusted life-year (DALY) totals for HAT were estimated based on modelled age and mortality distributions, mapped using Geographic Information Systems (GIS) software, and summarised by parish and district. While the national total burden of HAT is low relative to other conditions, high-impact districts in Uganda had DALY rates comparable to the national burden rates for major infectious diseases. The calculated average national DALY rate for 2000–2009 was 486.3 DALYs/100 000 persons/year, whereas three districts afflicted by rhodesiense HAT in southeastern Uganda had burden rates above 5000 DALYs/100 000 persons/year, comparable to national GBD 2004 average burden rates for malaria and HIV/AIDS. Conclusions/Significance: These results provide updated and improved estimates of HAT burden across Uganda, taking into account sensitivity to under-reporting. Our results highlight the critical importance of spatial scale in disease burden analyses. National aggregations of disease burden have resulted in an implied bias against highly focal diseases for which geographically targeted interventions may be feasible and cost-effective. This has significant implications for the use of DALY estimates to prioritize disease interventions and inform cost-benefit analyses. Author Summary: Since the 1990s the World Health Organisation has established the disability-adjusted life year (DALY) as a metric for the burden of human disease and injury. However, disease burden has primarily been estimated at the national scale, which does not account for sub-country variations in burden levels. We used the case of human African trypanosomiasis (HAT), a highly focal NTD, in Uganda to calculate and map burden in DALYs. Our results show that HAT burden is highly sensitive to under-reporting estimates, and is particularly high in heavily affected parishes and districts of Uganda. Some districts in southeastern Uganda had HAT burden rates comparable to the national burden rates of major infectious diseases such as malaria and HIV/AIDS. Thus, the spatial scale of burden estimation is crucial, especially for focal diseases such as HAT, and national-level estimates may not reflect the level of impact in afflicted communities. We recommend sub-country burden estimation to identify key areas for prioritization of disease surveillance and targeted interventions. [ABSTRACT FROM AUTHOR]