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BackgroundHuman African trypanosomiasis is a parasitic disease caused by trypanosomes among whichTrypanosoma brucei gambienseis responsible for a chronic form (gHAT) in West and Central Africa. Its elimination as a public health problem (EPHP) is being achieved. Côte d’Ivoire was one of the first countries to be validated by WHO in 2020 and this was particularly challenging as the country still reported around a hundred cases a year in the early 2000s. This article describes the strategies implemented including a mathematical model to evaluate the reporting results and infer progress towards sustainable elimination.MethodsThe control methods used combined both exhaustive and targeted medical surveillance strategies to diagnose and treat cases as well as vector control to reduce the risk of transmission in the most at risk areas. A mechanistic model was used to estimate the number of underlying infections and the probability of elimination of transmission (EoT) between 2000– 2021 in two endemic and two hypo-endemic health districts.ResultsBetween 2015 and 2019, nine gHAT cases were detected in two health districts in which the number of cases/10,000 inhabitants was far below 1, a necessary condition for validating the EPHP. Modelling estimated a slow but steady decline in transmission across the four health districts, bolstered in the two endemic health districts by the introduction of vector control. The decrease in underlying transmission in all health districts corresponds to a high probability that EoT has already occurred in Côte d’Ivoire.ConclusionThis success was achieved through a multi-stakeholder and multidisciplinary one health approach where research has played a major role in adapting tools and strategies to this large epidemiological transition to a very low prevalence. This integrated approach will need to continue to reach the verification of EoT in Côte d’Ivoire targeted by 2025.Author SummarySignificant efforts to controlTrypanosoma brucei gambiensehuman African trypanosomiasis (gHAT) have drastically reduced the prevalence of the disease and elimination of transmission (EoT) is targeted for 2030 by WHO. This reduction was particularly challenging in Côte d’Ivoire as it still faced epidemic episodes in the early 2000s. This large epidemiological transition to very low prevalence necessitated the adaptation and evolution of both medical and vector control strategies described in this article. A mathematical model was also used to retrospectively analyse case reporting results, indicating with high probability that local EoT has already been achieved in the four health districts analysed.With nine gHAT cases detected in two health districts between 2015 and 2019 and less than one case per 10,000 people per year in all health districts at national level over this five-year period, Côte d’Ivoire received validation by WHO of achievement of the elimination of the disease as a public health problem in 2020. These results combined with the modelling offer encouragement regarding reaching the verification of EoT targeted by 2025 in Côte d’Ivoire on condition of maintaining such multidisciplinary one health approach including research activities to continuously adapt it to the epidemiological transition to zero incidence.

Background Riverine species of tsetse (Glossina) transmit Trypanosoma brucei gambiense, which causes Gambian human African trypanosomiasis (gHAT), a neglected tropical disease. Uganda aims to eliminate gHAT as a public health problem through detection and treatment of human cases and vector control. The latter is being achieved through the deployment of ‘Tiny Targets’, insecticide-impregnated panels of material which attract and kill tsetse. We analysed the spatial and temporal distribution of cases of gHAT in Uganda during the period 2010–2019 to assess whether Tiny Targets have had an impact on disease incidence. Methods To quantify the deployment of Tiny Targets, we mapped the rivers and their associated watersheds in the intervention area. We then categorised each of these on a scale of 0–3 according to whether Tiny Targets were absent (0), present only in neighbouring watersheds (1), present in the watersheds but not all neighbours (2), or present in the watershed and all neighbours (3). We overlaid all cases that were diagnosed between 2000 and 2020 and assessed whether the probability of finding cases in a watershed changed following the deployment of targets. We also estimated the number of cases averted through tsetse control. Results We found that following the deployment of Tiny Targets in a watershed, there were fewer cases of HAT, with a sampled error probability of 0.007. We estimate that during the intervention period 2012–2019 we should have expected 48 cases (95% confidence intervals = 40–57) compared to the 36 cases observed. The results are robust to a range of sensitivity analyses. Conclusions Tiny Targets have reduced the incidence of gHAT by 25% in north-western Uganda. Graphical abstract

Human African trypanosomiasis, caused by the gambiense subspecies of Trypanosoma brucei (gHAT), is a deadly parasitic disease transmitted by tsetse. Partners from around the world have stepped up efforts to eliminate the disease, and the Chadian government have had a particular focus on the previously high-prevalence setting of Mandoul. In this study, we evaluate the economic efficiency of the intensified strategies that were put in place from 2014 aimed at interrupting transmission of gHAT, and we make recommendations on the best way forward based on both epidemiological projections and cost-effectiveness. In our analysis we use a dynamic transmission model fit to epidemiological data from Mandoul to evaluate the cost-effectiveness of combinations of active screening, improved passive screening (defined as an expansion of the number of health posts capable of screening for gHAT), and vector control activities (the deployment of Tiny Targets). For cost-effectiveness analyses, our primary outcome is disease burden, denominated in disability-adjusted life-years (DALYs), and costs, denominated in 2020 US$. Although active and passive screening have enabled more rapid diagnosis and accessible treatment in Mandoul, the addition of vector control provided good value-for-money (at less than $750/DALY averted) and substantially increased the probability of reaching the 2030 elimination target for gHAT as set by the World Health Organization. Our transmission modelling and economic evaluations suggests that the gains have been made could be maintained by robust passive screening, and the inclusion of active screening and vector control strategies could be considered for other foci in the country with active transmission. Our analysis speaks to comparative efficiency, and it does not take into account all possible considerations; for instance, any cessation of on-going active screening should first consider that strong surveillance activities will be critical to verify elimination of transmission and to protect against the possible importation of infection from neighbouring endemic foci.Author summaryIn a drive to eliminate human African trypanosomiasis (gHAT or sleeping sickness) from Chad following a peak in 2002, the National Sleeping Sickness Control programme and their partners focused on making substantial changes to interventions within the high prevalence setting of Mandoul. These included the use of vector control starting in 2014 and improved screening in health facilities starting in 2015. To explore whether these interventions were an efficient use of resources we carried out a retrospective analysis using a dynamic transmission model fit to epidemiological data from Mandoul combined with a cost model. Our analysis indicated that active and passive screening have enabled more rapid diagnosis and accessible treatment in Mandoul compared to less ambitious interventions, and furthermore the addition of vector control provided good value-for-money and substantially increased the probability of reaching the 2030 elimination of transmission target for gHAT set by the World Health Organization. Looking forwards, our prospective analysis also considers the health economics of future strategies and, as part of this, concludes that the scaleback of vertical interventions appears cost-effective if passive screening remains robust in Mandoul. This could therefore enable shifting of resources to tackle other remaining foci in Chad.

Aims The migration percentage (MP) is one criterion used for surgery in dislocated or displaced hips in children with cerebral palsy (CP). The MP at which a displaced hip can no longer return to normal is unclear. The aim of this paper was to identify the point of no return of the MP through a large population-based study. Methods All children registered on the Cerebral Palsy Integrated Pathway Scotland surveillance programme undergo regular pelvic radiographs. Any child who had a MP measuring over 35% since the programme’s inception in 2013, in at least one hip and at one timepoint, was identified. The national radiography database was then interrogated to identify all pelvic radiographs for each of these children from birth through to the date of analysis. A minimum of a further two available radiographs following the initial measurement of MP ≥ 35% was required for inclusion. Results A total of 239 children (346 hips) were identified as suitable for analysis at a mean of 6.5 years (2.0 to 14.8) follow-up. In all, 1,485 radiographs taken both prior to and after a hip had a MP ≥ 35% were examined and the MP measured to identify any progression of displacement. Interrogation of the data identified that hips with a MP up to 46% returned to a MP below 40% without intervention, and all hips with a MP equal to or greater than 46% displaced further and the MP did not return to the normal range. Statistical analysis showed the result to be 98% specific with this degree of certainty that hips reaching a MP ≥ 46% would not spontaneously regress. Conclusion These findings are clinically relevant in showing that it may be reasonable to continue to monitor hips with a MP not exceeding 46%. This threshold will also guide referral for further management of a displacing hip. Cite this article: Bone Joint J 2021;103-B(2):411–414.

Background Crimean-Congo Haemorrhagic Fever (CCHF) is a tick-borne viral zoonotic disease distributed across several continents and recognized as an ongoing health threat. In humans, the infection can progress to a severe disease with high fatality, raising public health concerns due to the limited prophylactic and therapeutic options available. Animal species, clinically unaffected by the virus, serve as viral reservoirs and amplifier hosts, and can be a valuable tool for surveillance. Little is known about the occurrence and prevalence of Crimean-Congo Haemorrhagic Fever Virus (CCHFV) in Cameroon. Knowledge on CCHFV exposure and the factors associated with its presence in sentinel species are a valuable resource to better understand transmission dynamics and assess local risks for zoonotic disease emergence. Methods and findings We conducted a CCHFV serological survey and risk factor analysis for animal level seropositivity in pastoral and dairy cattle in the North West Region (NWR) and the Vina Division (VD) of the Adamawa Region in Cameroon. Seroprevalence estimates were adjusted for sampling design-effects and test performance. In addition, explanatory multivariable logistic regression mixed-effects models were fit to estimate the effect of animal characteristics, husbandry practices, risk contacts and ecological features on the serological status of pastoral cattle. The overall seroprevalence was 56.0% (95% CI 53.5–58.6) and 6.7% (95% CI 2.6–16.1) among pastoral and dairy cattle, respectively. Animals going on transhumance had twice the odds of being seropositive (OR 2.0, 95% CI 1.1–3.8), indicating that animal movements could be implicated in disease expansion. From an ecological perspective, absolute humidity (OR 0.6, 95% CI 0.4–0.9) and shrub density (OR 2.1, 95% CI 1.4–3.2) were associated with seropositivity, which suggests an underlying viral dynamic connecting vertebrate host and ticks in a complex transmission network. Conclusions This study demonstrated high seroprevalence levels of CCHFV antibodies in cattle in Cameroon indicating a potential risk to human populations. However, current understanding of the underlying dynamics of CCHFV locally and the real risk for human populations is incomplete. Further studies designed using a One Health approach are required to improve local knowledge of the disease, host interactions and environmental risk factors. This information is crucial to better project the risks for human populations located in CCHFV-suitable ecological niches.

BackgroundVisceral leishmaniasis (VL), also known as kala-azar, is a neglected tropical disease (NTD) that is fatal if not treated early. The WHO targets the elimination of VL as a public health problem in its 2030 NTD road map. However, improving access to VL diagnosis and treatment remains a major challenge in many VL-endemic countries. Kenya is endemic for VL and is among the top 6 high-disease burden countries in the world.MethodsFIND, through its activities in improving the diagnosis of VL and supporting the elimination of the disease in Kenya, has worked with various county ministries of health (MOH) and central MOH over the last couple of years. FIND’s activities in Marsabit county started in 2018. In this work, we present the implementation of activities and the impacts in Marsabit county. We reviewed the data for 2017 and 2019 outbreaks (before and after the implementation of FIND’s activities) and assessed the importance of improving access and community sensitization to VL diagnosis. We assessed the contribution of each facility to the total distance traveled from a perspective of location optimization.ResultsThere was a sharp increase in the number of people tested in the 2017 outbreak compared to the 2019 outbreak. In 2017, 437 people were tested compared to 2,338 in 2019. The county reported 234 and 688 VL cases in 2017 and 2019, respectively. The data revealed a shift in the demographic structures of cases toward the younger population (mean age in 2017 was 17.6 years and 15.3 years in 2019), with more female cases reported in 2019 compared to 2017. In 2017, 44.4% were 10 years of age or under. In 2019, the proportion 10 years or below was 52.2%. The addition of two new diagnosis facilities in 2018 resulted in a decrease in the distance traveled by confirmed VL cases from 28.1 km in 2017 to 10.8 km in 2019. Assessing the impact of facility placement indicated the most optimal facilities to provide VL diagnostic services and minimize the distance traveled by patients. Adding new facilities reduces the travel distance until a point where the addition of a new facility provides no additional impact.ConclusionThe results from this study indicate the need to carefully consider the placement of health facilities in improving access to VL diagnosis and treatment and could serve as an investment case in deciding when to stop adding new facilities in a particular setting. Extending the activities in Kenya to other VL-endemic countries in East Africa will contribute significantly toward the elimination of the disease, addressing the needs of marginalized populations and leaving no one behind.

BackgroundOnchocerciasis (river blindness) is a filarial disease targeted for elimination of transmission. However, challenges exist to the implementation of effective diagnostic and surveillance strategies at various stages of elimination programs. To address these challenges, we used a network data analytics approach to identify optimal diagnostic scenarios for onchocerciasis elimination mapping (OEM).MethodsThe diagnostic network optimization (DNO) method was used to model the implementation of the old Ov16 rapid diagnostic test (RDT) and of new RDTs in development for OEM under different testing strategy scenarios with varying testing locations, test performance and disease prevalence. Environmental suitability scores (ESS) based on machine learning algorithms were developed to identify areas at risk of transmission and used to select sites for OEM in Bandundu region in the Democratic Republic of Congo (DRC) and Uige province in Angola. Test sensitivity and specificity ranges were obtained from the literature for the existing RDT, and from characteristics defined in the target product profile for the new RDTs. Sourcing and transportation policies were defined, and costing information was obtained from onchocerciasis programs. Various scenarios were created to test various state configurations. The actual demand scenarios represented the disease prevalence at IUs according to the ESS, while the counterfactual scenarios (conducted only in the DRC) are based on adapted prevalence estimates to generate prevalence close to the statistical decision thresholds (5% and 2%), to account for variability in field observations. The number of correctly classified implementation units (IUs) per scenario were estimated and key cost drivers were identified.ResultsIn both Bandundu and Uige, the sites selected based on ESS had high predicted onchocerciasis prevalence >10%. Thus, in the actual demand scenarios in both Bandundu and Uige, the old Ov16 RDT correctly classified all 13 and 11 IUs, respectively, as requiring CDTi. In the counterfactual scenarios in Bandundu, the new RDTs with higher specificity correctly classified IUs more cost effectively. The new RDT with highest specificity (99.8%) correctly classified all 13 IUs. However, very high specificity (e.g., 99.8%) when coupled with imperfect sensitivity, can result in many false negative results (missing decisions to start MDA) at the 5% statistical decision threshold (the decision rule to start MDA). This effect can be negated by reducing the statistical decision threshold to 2%. Across all scenarios, the need for second stage sampling significantly drove program costs upwards. The best performing testing strategies with new RDTs were more expensive than testing with existing tests due to need for second stage sampling, but this was offset by the cost of incorrect classification of IUs.ConclusionThe new RDTs modelled added most value in areas with variable disease prevalence, with most benefit in IUs that are near the statistical decision thresholds. Based on the evaluations in this study, DNO could be used to guide the development of new RDTs based on defined sensitivities and specificities. While test sensitivity is a minor driver of whether an IU is identified as positive, higher specificities are essential. Further, these models could be used to explore the development and optimization of new tools for other neglected tropical diseases.

BackgroundIn recent years, an integrated programme of vector control, screening and treatment of gambiense human African trypanosomiasis (gHAT) infections has led to a rapid decline in cases in the Mandoul disease focus of Chad. In this study, we assess whether elimination of transmission has already been achieved in the region despite low-level case reporting, quantify the role of intensified interventions in transmission reduction, and predict the trajectory of gHAT in Mandoul for the next decade under a range of control scenarios.MethodWe utilise human case data (2000–2019) to update a previous model of transmission of gHAT in Mandoul. We also test the updated model, which now has refined assumptions on diagnostic specificity of the current algorithm and an improved fitting method, via a data censoring approach.ResultsWe conclude that passive detection rates have increased due to improvements in diagnostic availability in fixed health facilities since 2015, by 2.1-fold for stage 1 detection, and by 1.5-fold for stage 2. We find that whilst the diagnostic algorithm for active screening is estimated to be highly specific (99.93%, 95% CI: 99.91–99.95%), the high screening level and limited remaining infection means that some recently reported cases might be false positives, especially the ones that were not parasitologically confirmed. We also find that the focus-wide tsetse vector reduction estimated through model fitting (99.1%, 95% CI: 96.1–99.6%) is comparable to the very high reduction previously measured by the decline in catches of tsetse from monitoring traps. In line with previous results, the model suggests that transmission was likely interrupted in 2015 as a result of intensified interventions.ConclusionsWe recommend that additional confirmatory testing is performed in Mandoul in order that the endgame can be carefully monitored now that infection levels are so low. More specific measurement of cases would better inform when it is safe to stop active screening and vector control.

In this study we demonstrate that the adoption of a segmenting and shielding (S&S) strategy could increase scope to partially exit COVID-19 lockdown while limiting the risk of an overwhelming second wave of infection.The S&S strategy has an antecedent in the “cocooning” of infants by immunisation of close family members (Forsyth et al., 2015), and forms a pillar of infection, prevention and control (IPC) strategies (RCN, 2017). We are unaware of it being proposed as a major public health initiative previously.We illustrate the S&S strategy using a mathematical model that segments the vulnerable population and their closest contacts, the “shielders”. We explore the effects on the epidemic curve of a gradual ramping up of protection for the vulnerable population and a gradual ramping down of restrictions on the non-vulnerable population over a period of 12 weeks after lockdown.The most important determinants of outcome are: i) post-lockdown transmission rates within the general population segment and between the general and vulnerable segments; ii) the fraction of the population in the vulnerable and shielder segments; iii) adherence with need to be protected; and iv) the extent to which population immunity builds up in all segments.We explored the effects of extending the duration of lockdown and faster or slower transition to post-lockdown conditions and, most importantly, the trade-off between increased protection of the vulnerable segment and fewer restrictions on the general population.We illustrate how the potential for the relaxation of restrictions interacts with specific policy objectives. We show that the range of options for relaxation in the general population can be increased by maintaining restrictions on the shielder segment and by intensive routine screening of shielders.We find that the outcome of any future policy is strongly influenced by the contact matrix between segments and the relationships between physical distancing measures and transmission rates. These relationships are difficult to quantify so close monitoring of the epidemic would be essential during and after the exit from lockdown.More generally, S&S has potential applications for any infectious disease for which there are defined proportions of the population who cannot be treated or who are at risk of severe outcomes.

The use of network analysis to support livestock disease control in low middle-income countries (LMICs) has historically been hampered by the cost of generating empirical data in the absence of animal movement recording schemes. To fill this gap, methods which exploit freely available demographic and archived molecular data can be used to generate livestock networks based on gravity and phylogeographic modelling techniques, respectively. However, questions remain on the performance of these methods in capturing the topology of empirical networks. Here, we compare output from these network methodologies to a network constructed from either empirical data or randomly generated data. To facilitate this comparison, the spread of infectious diseases was simulated, it is this evaluation that demonstrates their potential utility to inform robust livestock disease control strategies.The molecular network was the closest approximation to the empirical network, both in relation to topological and epidemic characteristics, whereas size of epidemics in the gravity network tended to be larger, better agreement across all three networks was observed when; a) total nodes infected, b) percentage infection take off were compared. These methods consistently identified the same important animal movement and trade hotspots as the empirical networks. We therefore consider this proof-of-concept that demographic data such as censuses and archived molecular data could be repurposed to inform livestock disease management in LMICs.Author summaryLive animal movements in Africa represent a significant risk of transmission and spread of infectious diseases in livestock populations, and therefore, have direct implications on the food security of the continent. Here we explore the potential utility of available data to support control strategies, by comparing movement networks inferred from such data i.e. census and pathogen molecular data using gravity modelling and phylogeography respectively. Their utility is evaluated by comparing their topology and disease spread characteristics to empirical live animal movement. Based on our results, we posit that archived data can be repurposed to support infectious disease control on the African continent.

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 (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.

The migration percentage (MP) is one criterion used for surgery in dislocated or displaced hips in children with cerebral palsy (CP). The MP at which a displaced hip can no longer return to normal is unclear. The aim of this paper was to identify the point of no return of the MP through a large population-based study.All children registered on the Cerebral Palsy Integrated Pathway Scotland surveillance programme undergo regular pelvic radiographs. Any child who had a MP measuring over 35% since the programme's inception in 2013, in at least one hip and at one timepoint, was identified. The national radiography database was then interrogated to identify all pelvic radiographs for each of these children from birth through to the date of analysis. A minimum of a further two available radiographs following the initial measurement of MP ≥ 35% was required for inclusion.A total of 239 children (346 hips) were identified as suitable for analysis at a mean of 6.5 years (2.0 to 14.8) follow-up. In all, 1,485 radiographs taken both prior to and after a hip had a MP ≥ 35% were examined and the MP measured to identify any progression of displacement. Interrogation of the data identified that hips with a MP up to 46% returned to a MP below 40% without intervention, and all hips with a MP equal to or greater than 46% displaced further and the MP did not return to the normal range. Statistical analysis showed the result to be 98% specific with this degree of certainty that hips reaching a MP ≥ 46% would not spontaneously regress.These findings are clinically relevant in showing that it may be reasonable to continue to monitor hips with a MP not exceeding 46%. This threshold will also guide referral for further management of a displacing hip. Cite this article

SummaryRestrictions on mobility are a key component of infectious disease controls, preventing the spread of infections to as yet unexposed areas, or to regions which have previously eliminated outbreaks. However, even under the most severe restrictions, some travel must inevitably continue, at the very minimum to retain essential services. For COVID-19, most countries imposed severe restrictions on travel at least as soon as it was clear that containment of local outbreaks would not be possible. Such restrictions are known to have had a substantial impact on the economy and other aspects of human health, and so quantifying the impact of such restrictions is an essential part of evaluating the necessity for future implementation of similar measures.In this analysis, we built a simulation model using National statistical data to record patterns of movements to work, and implement levels of mobility recorded in real time via mobile phone apps. This model was fitted to the pattern of deaths due to COVID-19 using approximate Bayesian inference. Our model is able to recapitulate mortality considering the number of deaths and datazones (DZs, which are areas containing approximately 500-1000 residents) with deaths, as measured across 32 individual council areas (CAs) in Scotland. Our model recreates a trajectory consistent with the observed data until 1st of July. According to the model, most transmission was occurring “locally” (i.e. in the model, 80% of transmission events occurred within spatially defined “communities” of approximately 100 individuals). We show that the net effect of the various restrictions put into place in March can be captured by a reduction in transmission down to 12% of its pre-lockdown rate effective 28th March. By comparing different approaches to reducing transmission, we show that, while the timing of COVID-19 restrictions influences the role of the transmission rate on the number of COVID-related deaths, early reduction in long distance movements does not reduce death rates significantly. As this movement of individuals from more infected areas to less infected areas has a minimal impact on transmission, this suggests that the fraction of population already immune in infected communities was not a significant factor in these early stages of the national epidemic even when local clustering of infection is taken into account.The best fit model also shows a considerable influence of the health index of deprivation (part of the “index of multiple deprivations”) on mortality. The most likely value has the CA with the highest level of health-related deprivation to have on average, a 2.45 times greater mortality rate due to COVID-19 compared to the CA with the lowest, showing the impact of health-related deprivation even in the early stages of the COVID-19 national epidemic.

BackgroundSurveillance 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 FindingsFor 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 (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.ConclusionsOur 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 SummaryDisease 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.

Graphical abstract, Highlights • Bovine tuberculosis elevated-risk areas historically more extensive than thought. • Cattle movements alone do not explain spread of areas of elevated risk. • For all genotypes, the majority of infection spread is due to local effects. • Similar risk-factors identified within elevated-risk and transitional areas. • Risk factors key to identify incipient elevated-risk areas before incidence rising., Bovine tuberculosis (bTB) is a chronic zoonosis with major health and economic impact on the cattle industry. Despite extensive control measures in cattle and culling trials in wildlife, the reasons behind the expansion of areas with high incidence of bTB breakdowns in Great Britain remain unexplained. By balancing the importance of cattle movements and local transmission on the observed pattern of cattle outbreaks, we identify areas at elevated risk of infection from specific Mycobacterium bovis genotypes. We show that elevated-risk areas (ERAs) were historically more extensive than previously understood, and that cattle movements alone are insufficient for ERA spread, suggesting the involvement of other factors. For all genotypes, we find that, while the absolute risk of infection is higher in ERAs compared to areas with intermittent risk, the statistically significant risk factors are remarkably similar in both, suggesting that these risk factors can be used to identify incipient ERAs before this is indicated by elevated incidence alone. Our findings identify research priorities for understanding bTB dynamics, improving surveillance and guiding management to prevent further ERA expansion.

Gambiense human African trypanosomiasis (g-HAT) is the chronic form of sleeping sickness caused by Trypanosoma brucei gambiense in West and Central Africa, while Trypanosoma brucei rhodesiense causes an acute form in eastern Africa. g-HAT is targeted for elimination as a public health problem by 2020 and 0 transmission by 2030 [1,2]. Control of g-HAT is largely based on identification and treatment of infected individuals, supplemented by control of the tsetse fly vectors [3]. There has been growing evidence that when both tsetse control and case identification activities are carried out simultaneously in the same geographies, elimination of the disease is accelerated [4–6]. Here, we describe how the Trypa-NO! Partnership is using novel and classical tools to drive g-HAT elimination in an integrated approach, progress made, lessons learnt, and future directions.

Background The Democratic Republic of the Congo (DRC) accounts for the majority of the reported gambiense human African trypanosomiasis (HAT) cases. Kongo Central province in the DRC reports a relatively low, yet steady number of cases, and forms a transboundary focus with Angola and the Republic of Congo. This paper describes an intervention aimed at reducing the case burden in Kongo Central by improving passive case detection, complemented with reactive screening. Methodology/Principal findings At the initiation of this programme in August 2015, 620 health facilities were identified and equipped with Rapid Diagnostic Tests (RDTs) for HAT screening. Of these, 603 (97%) reported use of RDTs, and 584 (94%) that continued to use RDTs to the last quarter of 2016 were used in the analysis going forward. Among all health facilities involved, 23 were equipped to confirm HAT by microscopy, and 4 of the latter were equipped to perform molecular testing with loop-mediated isothermal amplification (LAMP). Patients clinically suspected of HAT were tested with an RDT and those with a positive RDT result were referred to the nearest microscopy facility for confirmatory testing. If RDT positive patients were negative by microscopy, they were tested by LAMP, either on fresh blood or blood that was dried on filter paper and transported to a facility performing LAMP. This network of diagnostic facilities reduced the median distance for a patient to travel to a screening facility from 13.7km when the classical card agglutination test for trypanosomiasis (CATT) was used as a screening test in the past, to 3.4km. As a consequence, passive case detection was improved by between 30% and 130% compared to the period before. Furthermore, the proportion of HAT cases detected in early stage disease by passive screening increased from 27% to 64%. Reactive screening took place in 20 villages where cases were reported by passive screening, and in 45 villages in the neighbourhood of these villages. Reactive screening was responsible for detection of 40% of cases, of which, 90% were in first stage of the disease. Conclusions This programme has demonstrated that it is possible to deploy passive screening for HAT at sub-country or country levels in the DRC, and this is made more effective when supplemented with reactive screening. Results and achievements showed an increase in the number of HAT cases detected, the majority of them in early disease, demonstrating that this strategy enables better population coverage and early detection of cases, which is critical in removing the HAT reservoir and interrupting transmission, and could contribute to HAT elimination in regions where it is implemented., Author summary A number of diagnostic tests for HAT have recently been developed, to improve case detection. We report on the use of these technologies in a strategy to increase coverage and early detection of HAT cases in Kongo Central province of DRC. All 620 health facilities in the focus were equipped with RDTs to test patients presenting with symptoms suggestive of HAT. Among these health facilities, 23 were upgraded to perform confirmatory testing, for a final diagnosis. This strategy has reduced the distance a patient travels to a facility screening for HAT, from 13.7km to 3.4km. From August 2015 to December 2016, the proportion of HAT cases detected, adjusted annually, increased by between 30% and 130% compared to the previous two years, and 64% of them were in early stage disease, compared to 27% previously. This strategy has enabled better population coverage, and when supplemented with reactive screening, the identification of local outbreaks and early detection of most cases, which is critical in removing the HAT reservoir and interrupting transmission, thus contributing to elimination of the disease.

Trypanosoma brucei rhodesiense Human African Trypanosomiasis (rHAT) is a zoonotic disease transmitted by tsetse flies from wild and domestic animals. It presents as an acute disease and advances rapidly into a neurological form that can only be treated with melarsoprol, which is associated with a high fatality rate. Bringing diagnostic services for rHAT closer to at-risk populations would increase chances of detecting cases in early stages of disease when treatment is safer and more effective. In Malawi, most of the rHAT cases occur around Vwaza Marsh Wildlife Reserve. Until 2013, diagnosis of rHAT in the region was only available at the Rumphi District Hospital that is more than 60 km away from the reserve. In 2013, Malawi's Ministry of Health initiated a project to enhance the detection of rHAT in five health facilities around Vwaza Marsh by upgrading laboratories and training technicians. We report here a retrospective study that was carried out to evaluate the impact of improving access to diagnostic services on the disease stage at diagnosis and on mortality. Between August 2014 and July 2017, 2014 patients suspected of having the disease were tested by microscopy, including 1267 who were tested in the new facilities. This resulted in the identification of 78 new rHAT cases, of which six died. Compared with previous years, data obtained during this period indicate that access to diagnostic services closer to where people at the greatest risk of infection live promotes identification of cases in earlier stages of infection, and improves treatment outcomes.

Highlights • An analysis of the impacts of Newcastle disease vaccination and husbandry practices on chicken flock productivity in smallholder farms in Uganda. • Productivity was measured by offtake measured by the numbers of chickens consumed, gifted or sold over one year and eggs consumed and sold per week. • · Adjusting for flock size, Newcastle disease vaccination resulted in a 57 % increase in offtake and use of poultry housing a 36 % increase in offtake. • After adjusting for the number of hens, vaccinating against Newcastle disease resulted in an 80 % increase in egg production. • Use of dewormers and feed supplementation had no significant effect., A number of studies have demonstrated the clear beneficial impact that vaccinating against Newcastle disease (ND) can have on reducing the frequency and severity of ND outbreaks. Here we go one step further and analyse the additional benefits in terms of improved production that result from vaccination. Data were collected from a cross sectional survey in Uganda of 593 chicken-rearing smallholders (for the purpose of this study this was defined as a farm with fewer than 75 chickens). Consenting participants were administered a detailed questionnaire covering a range of aspects of chicken production and management. These data were subsequently analysed in a generalised linear model framework with negative binomial error structure and the total offtake over the previous 12 months (chicken sales + chicken consumption + chickens gifted) was included as the dependent variable. Different measures of flock size were tested as independent variables and the model was also offered the district of the flock, ND vaccine adoption, use of poultry housing, provision of supplementary feed and use of dewormers as potential independent variables. We also developed an analogous model for the offtake of eggs (sale and consumption). The total size of the flock (counting chickens of all ages) was the measure of flock size that had the strongest association with offtake and was a significant but weak effect with an incidence rate ratio (IRR) of 1.011 (95 % Confidence intervals (CIs) = 1.007–1.015). ND vaccine adoption had a strong significant positive effect on offtake with an IRR of 1.571 (95 % CIs = 1.363–1.808). Use of a poultry house also had a significant effect (IRR = 1.365, 95 % CIs = 1.193–1.560). In the model of egg production, the number of hens was the demographic determinant with the lowest Akaike Information Criterion (AIC) (IRR = 1.094, 95 % CIs = 1.056–1.136) and ND vaccine adoption had a strong positive effect on egg offtake (IRR = 1.801, 95 % CIs = 1.343–2.412). Vaccinating against ND has a clear beneficial impact on the productivity of the flock, and the livelihoods of smallholder farmers.

Highlights • An assessment of the impacts of anthelminthic drugs on weights of goats in India and Tanzania • Over 56 days, the treated goats in India gained weight at almost twice the rate of non-treated goats. • Over 56 days the treated goats in Tanzania gained 15% more weight than non-treated goats • In both areas, the body condition scores of treated goats also improved relative to non-treated goats., Helminth infections are recognised as a major impediment to the productivity of goats in smallholder production systems. We used a multilevel framework to estimate the impact that administration of locally available anthelminthic drugs can have on the weight gains of goats in smallholder settings in India and Tanzania. We recruited 234 goats from 92 households from Odisha state in India and 253 goats from 15 households from Dodoma region in Tanzania. The goats were non-pregnant adult females, and from each household a minimum of two goats were recruited wherever possible. Each goat was randomly assigned to treatment with a locally available anthelminthic drug, or non-treatment. Each animal was tagged, weighed and had its body condition score (BCS) assessed. Animals were followed up after 28 and 56 days and re-weighed. To account for the local variations in exposure to helminths and for variations between households and herds, the data were analysed in a multilevel mixed model with herd in village as nested random effects. Over the 56 days of study, the non-treated goats in India had gained a mean of 30.64 g per day (a daily gain of 0.23% baseline body weight) and in Tanzania 66.01 g per day (0.33% baseline body weight). From the mixed model, the treated goats in India gained a mean of 25.22 g per day more than non-treated goats, this is significantly greater than the weight gain in non-treated goats (p

Background: Confirmatory diagnosis of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) is based on demonstration of parasites by microscopy. However, the sensitivity of routine microscopy methods is very low, and many cases are missed and left untreated. A clinical study was conducted in the Democratic Republic of the Congo to evaluate the accuracy of improved microscopy methods in diagnosis of HAT. These included examination by fluorescence microscopy (FM) of acridine orange (AO) stained smears of whole blood and smears made following a new procedure for concentrating trypanosomes by selective lysis of red blood cells (RBC). Methodology/Principal Findings: Venous blood was collected from 213 HAT cases, 101 HAT suspects and 95 controls and used to determine the accuracy of four microscopy methods: bright field microscopy of Giemsa-stained thick blood smears, FM of AO-stained thick blood smears, FM of AO-stained thick blood smears prepared after RBC lysis and concentration, and FM of AO-stained thin blood smears prepared after RBC lysis and concentration. The sensitivity of FM using thick blood smears stained with AO was 3 times higher than bright field microscopy using Giemsa-stained thick blood smears [19.7% (95% CI: 14.9% - 25.6%) versus 6.1% (95% CI: 3.6% - 10.2%)]. When the RBC lysis and concentration procedure was included, sensitivity of the test was further enhanced to 23.0% (95% CI: 17.9% - 29.1%) with thick blood smears and 34.3% (95% CI: 28.2% - 40.9%) with thin blood smears. Specificity of all four microscopy methods was 100% (95% CI: 96.1% - 100.0%). However, the miniature anion exchange chromatography technique (mAECT) and capillary tube centrifugation (CTC) method remained more sensitive. Conclusions: These new methods have practical advantages, including shorter staining time, ease of demonstration of parasites, and the possibility of archiving slides. They could, therefore, be alternative methods to improve case detection where concentration procedures such as mAECT or CTC are not performed.

SUMMARYDisease surveillance can be made more effective by either improving disease detection, providing cost savings, or doing both. Currently, cattle herds in low-risk areas (LRAs) for bovine tuberculosis (bTB) in England are tested once every 4 years. In Scotland, the default herd testing frequency is also 4 years, but a risk-based system exempts some herds from testing altogether. To extend this approach to other areas, a bespoke understanding of at-risk herds and how risk-based surveillance can affect bTB detection is required. Here, we use a generalized linear mixed model to inform a Bayesian probabilistic model of freedom from infection and explore risk-based surveillance strategies in LRAs and Scotland. Our analyses show that in both areas the primary herd-level risk factors for bTB infection are the size of the herd and purchasing cattle from high-risk areas of Great Britain and/or Ireland. A risk-based approach can improve the current surveillance system by both increasing detection (9% and 7% fewer latent infections), and reducing testing burden (6% and 26% fewer animal tests) in LRAs and Scotland, respectively. Testing at-risk herds more frequently can also improve the level of detection by identifying more infected cases and reducing the hidden burden of the disease, and reduce surveillance effort by exempting low-risk herds from testing.

Animal health surveillance is necessary to protect human and animal health, rural economies and the environment from the consequences of large-scale disease outbreaks. In Scotland, since the Kinnaird review in 2011, efforts have been made to engage with stakeholders to ensure that the strategic goals of surveillance are better aligned with the needs of the end-users and other beneficiaries. The aims of this study were to engage with Scottish surveillance stakeholders and multidisciplinary experts to inform the future long-term strategy for animal health surveillance in Scotland. In this paper, we describe the use of scenario planning as an effective tool for the creation and exploration of five plausible long-term futures; we describe prioritisation of critical drivers of change (i.e. international trade policy, data sharing philosophies and public versus private resourcing of surveillance capacity) that will unpredictably influence the future implementation of animal health surveillance activities and we present ten participant-developed strategies to support three long-term visions to improve future resilience of animal health surveillance and contingency planning for animal and zoonotic disease outbreaks in Scotland. In the absence of any certainty about the nature of post-Brexit trade agreements for agriculture, participants considered the best investments for long-term resilience to include: data collection strategies to improve animal health benchmarking, user-benefit strategies to improve digital literacy in farming communities and investment strategies to increase veterinary and scientific research capacity in rural areas. This is the first scenario planning study to explore stakeholder beliefs and perceptions about important environmental, technological, societal, political and legal drivers (in addition to epidemiological “risk factors”) and effective strategies to manage future uncertainties for both the Scottish livestock industry and animal health surveillance after Brexit. This insight from stakeholders is important in order to improve uptake and implementation of animal heath surveillance activities and the future resilience of the livestock industry. The conclusions drawn from this study are applicable not only to Scotland, but to other countries and international organizations involved in global animal health surveillance activities.

We characterized the spatiotemporal epidemiology of rabies from January 2009 through March 2014 across the interface between a wildlife reserve and communal livestock farming area in South Africa. Brain tissue from 344 animals of 28 different species were tested for lyssavirus antigen. Of these, 146 (42.4%) samples tested positive, of which 141 (96.6%) came from dogs. Brain samples of dogs were more likely to test positive for lyssavirus antigen if they were found and destroyed in the reserve, compared to samples originating from dogs outside the reserve (65.3% vs. 45.5%; odds ratio (OR) = 2.26, 95% confidence interval (CI) = 1.27–4.03), despite rabies surveillance outside the reserve being targeted to dogs that have a higher index of suspicion due to clinical or epidemiological evidence of infection. In the reserve, dogs were more likely to test positive for rabies if they were shot further from villages (OR = 1.42, 95% CI 1.18–1.71) and closer to water points (OR = 0.41, 95% CI 0.21–0.81). Our results provide a basis for refinement of existing surveillance and control programs to mitigate the threat of spillover of rabies to wildlife populations.

Background Serological tests for gambiense human African trypanosomiasis (gHAT) detect antibodies to antigens on the cell surface of bloodstream trypanosomes. As trypanosomes that cause animal African trypanosomiasis (AAT) also express related antigens, we have evaluated two rapid diagnostic tests (RDTs) on cattle in trypanosomiasis endemic and non-endemic regions, to determine whether gHAT serological tests could also be used to screen for AAT. Methods Two RDTs, 1G RDT, made with native antigens, and p2G RDT, made with recombinant antigens, were tested on 121 cattle in a trypanosomiasis-free region, and on 312 cattle from a rhodesiense HAT and AAT endemic region. A subset of samples from the endemic region were also tested with two immune trypanolysis (TL) tests. The sensitivity of the tests was estimated by evaluating the result of the RDT on samples that were positive by both microscopy and internal transcribed spacer (ITS) PCR, whilst specificity was the result of the RDT on samples that were negative by ITS PCR and microscopy, and others from the non-endemic region. Results The specificity of the p2G RDT on cattle from the non-endemic region was 97.5% (95% CI: 93.0–99.2%), compared to only 57.9% (95% CI: 48.9–66.3%) for 1G RDT. The specificities of 1G RDT, p2G RDT and TL on endemic control cattle were 14.6% (95% CI: 9.7–21.5%), 22.6% (95% CI: 16.4–30.3%) and 68.3% (95% CI: 59.6–75.9%), respectively. The sensitivities of the tests on trypanosome positive samples were 85.1% (95% CI: 79.1–89.7%), 89.1% (95% CI: 83.7–93.0%) and 59.3% (95% CI: 51.8–66.4%), respectively. Among the same samples, 51.7% were positive by both TL and the 1G RDT. Conclusions These serological tests detect cross-reacting antibodies in cattle. The p2G RDT based on recombinant antigens had a high specificity in a non-endemic region, while the 1G RDT had a lower specificity, suggesting cross-reactivity with other pathogens. Electronic supplementary material The online version of this article (10.1186/s13071-017-2487-8) contains supplementary material, which is available to authorized users.

In many countries of the developing world village poultry play a vital role in the rural economy, providing a source of protein and valuable income with relatively small investments. In almost all areas in which village poultry are raised Newcastle disease (ND) is identified as one of the biggest causes of poultry loss, this is often coupled with a lack of knowledge of poultry management practices. Inexpensive and effective vaccines are available that are suitable for use in rural village environments, but in many areas service providers and reliable structures for delivery remain an obstacle to uptake of vaccines. To overcome this, GALVmed has implemented a network for vaccine distribution in which individuals in the villages are trained as vaccinators. The vaccinators purchase ND vaccines from local agro-veterinary stores and sell single doses at market determined prices. Implementation of these networks was preceded by a programme of smallholder sensitisation to increase awareness of diseases and flock management practices. Here we present analysis of the impacts of this scheme on village poultry production. We compare the results of a baseline survey carried out before implementation of the networks, with the results of a survey 16-24 months following implementation. We present results in terms of the uptake of ND vaccine, flock size, consumption of poultry meat, and poultry sales from Gairo district in Tanzania, Mayurbhanj district in India and Banke district in Nepal. In all areas, there was a significant increase in the numbers of flocks that were using ND vaccines, with over 75% uptake in all areas, reaching 98% in India. In all areas flock sizes doubled, the numbers of eggs that were set for hatching and that hatched increased by 25-50% and there was an increase in the frequency with which chicken meat was consumed and chickens were sold. Additionally, farmers reported fewer ND outbreaks, but this is prone to reporting bias and so improvements in production cannot be categorically ascribed to ND vaccination. These results have shown that establishing a market driven approach for the distribution of ND vaccines and community sensitisation on poultry husbandry practices results in a high rate of uptake of the vaccines. The results also suggest a reduction in the number of ND outbreaks and improvements to the livelihoods of rural smallholders.

Introduction The incidence of gambiense human African trypanosomiasis (gHAT) in Uganda has been declining, from 198 cases in 2008, to only 20 in 2012. Interruption of transmission of the disease by early diagnosis and treatment is core to the control and eventual elimination of gHAT. Until recently, the format of available screening tests had restricted screening and diagnosis to central health facilities (passive screening). We describe a novel strategy that is contributing to elimination of gHAT in Uganda through expansion of passive screening to the entire population at risk. Methodology / Principal findings In this strategy, patients who are clinically suspected of having gHAT at primary health facilities are screened using a rapid diagnostic test (RDT), followed by parasitological confirmation at strategically located microscopy centres. For patients who are positive with the RDT and negative by microscopy, blood samples undergo further testing using loop-mediated isothermal amplification (LAMP), a molecular test that detects parasite DNA. LAMP positive patients are considered strong suspects, and are re-evaluated by microscopy. Location and upgrading of facilities to perform microscopy and LAMP was informed by results of georeferencing and characterization of all public healthcare facilities in the 7 gHAT endemic districts in Uganda. Three facilities were upgraded to perform RDTs, microscopy and LAMP, 9 to perform RDTs and microscopy, and 200 to screen patients with RDTs. This reduced the distance that a sick person must travel to be screened for gHAT to a median distance of 2.5km compared to 23km previously. In this strategy, 9 gHAT cases were diagnosed in 2014, and 4 in 2015. Conclusions This enhanced passive screening strategy for gHAT has enabled full coverage of the population at risk, and is being replicated in other gHAT endemic countries. The improvement in case detection is making elimination of the disease in Uganda an imminent possibility.

Classifying, describing and understanding the natural environment is an important element of studies of human, animal and ecosystem health, and baseline ecological data are commonly lacking in remote environments of the world. Human African trypanosomiasis is an important constraint on human well-being in sub-Saharan Africa, and spillover transmission occurs from the reservoir community of wild mammals. Here we use robust and repeatable methodology to generate baseline datasets on vegetation and mammal density to investigate the ecology of warthogs (Phacochoerus africanus) in the remote Luambe National Park in Zambia, in order to further our understanding of their interactions with tsetse (Glossina spp.) vectors of trypanosomiasis. Fuzzy set theory is used to produce an accurate landcover classification, and distance sampling techniques are applied to obtain species and habitat level density estimates for the most abundant wild mammals. The density of warthog burrows is also estimated and their spatial distribution mapped. The datasets generated provide an accurate baseline to further ecological and epidemiological understanding of disease systems such as trypanosomiasis. This study provides a reliable framework for ecological monitoring of wild mammal densities and vegetation composition in remote, relatively inaccessible environments.

Background A major challenge in the control of human African trypanosomiasis (HAT) is lack of reliable diagnostic tests that are rapid and easy to use in remote areas where the disease occurs. In Trypanosoma brucei gambiense HAT, the Card Agglutination Test for Trypanosomiasis (CATT) has been the reference screening test since 1978, usually on whole blood, but also in a 1/8 dilution (CATT 1/8) to enhance specificity. However, the CATT is not available in a single format, requires a cold chain for storage, and uses equipment that requires electricity. A solution to these challenges has been provided by rapid diagnostic tests (RDT), which have recently become available. A prototype immunochromatographic test, the SD BIOLINE HAT, based on two native trypanosomal antigens (VSG LiTat 1.3 and VSG LiTat 1.5) has been developed. We carried out a non-inferiority study comparing this prototype to the CATT 1/8 in field settings. Methodology/Principal Findings The prototype SD BIOLINE HAT, the CATT Whole Blood and CATT 1/8 were systematically applied on fresh blood samples obtained from 14,818 subjects, who were prospectively enrolled through active and passive screening in clinical studies in three endemic countries of central Africa: Angola, the Democratic Republic of the Congo and the Central African Republic. One hundred and forty nine HAT cases were confirmed by parasitology. The sensitivity and specificity of the prototype SD BIOLINE HAT was 89.26% (95% confidence interval (CI) = 83.27–93.28) and 94.58% (95% CI = 94.20–94.94) respectively. The sensitivity and specificity of the CATT on whole blood were 93.96% (95% CI = 88.92–96.79) and 95.91% (95% CI = 95.58–96.22), and of the CATT 1/8 were 89.26% (95% CI = 83.27–93.28) and 98.88% (95% CI = 98.70–99.04) respectively. Conclusion/Significance After further optimization, the prototype SD BIOLINE HAT could become an alternative to current screening methods in primary healthcare settings in remote, resource-limited regions where HAT typically occurs., Author Summary Early diagnosis and treatment of human African trypanosomiasis is essential for safe and effective treatment. The tests used to screen suspected patients and populations at risk are difficult to implement in remote rural settings where the disease occurs. Availability of simple, easy to use, instrument-free rapid diagnostic tests would improve screening and coverage of the population at risk and contribute to elimination of the disease. It would enable technicians with limited training and clinicians in emergency or medical wards to make rapid differential diagnosis for neurological syndromes or malaria-like illnesses. Introduction of such tests in all healthcare facilities in endemic regions would enable early detection of cases, hence reducing the time lost by patients before they get adequate and safe treatment. Treatment delay occurs when such patients attend non-specialized health centres that are unable to perform diagnosis of the disease. We evaluated a prototype rapid diagnostic test for HAT, the SD BIOLINE HAT in Angola, the Democratic Republic of the Congo and the Central African Republic. We show here that the test is as sensitive as the CATT in a 1/8 dilution and less sensitive than CATT on whole blood, although this latter difference was not statistically significant. The prototype RDT is a promising alternative for serodiagnosis of HAT.

SUMMARYHuman campylobacteriosis exhibits a distinctive seasonality in temperate regions. This paper aims to identify the origins of this seasonality. Clinical isolates [typed by multi-locus sequence typing (MLST)] and epidemiological data were collected from Scotland. Young rural children were found to have an increased burden of disease in the late spring due to strains of non-chicken origin (e.g. ruminant and wild bird strains from environmental sources). In contrast the adult population had an extended summer peak associated with chicken strains. Travel abroad and UK mainland travel were associated with up to 17% and 18% of cases, respectively. International strains were associated with chicken, had a higher diversity than indigenous strains and a different spectrum of MLST types representative of these countries. Integrating empirical epidemiology and molecular subtyping can successfully elucidate the seasonal components of human campylobacteriosis. The findings will enable public health officials to focus strategies to reduce the disease burden.

SUMMARYDue to its substantially lower prevalence of bovine tuberculosis (bTB) relative to other areas of Great Britain, Scotland was designated as an officially (bovine) TB-free region in 2009. This paper investigates resultant possibilities for reducing surveillance by developing risk-based alternatives to current 4-year testing of eligible herds. A model of freedom of infection was used to develop strategies that specifically tested herds that are at risk of infection but would probably not be identified by slaughterhouse meat inspection. The performance of current testing is mimicked by testing all herds that slaughter fewer than 25% of their total stock per year and regularly import animals from high-incidence areas of England and Wales or from Ireland. This system offers a cost reduction by requiring 25% fewer herd and animal tests and 25% fewer false positives.

Confirmatory diagnosis of African trypanosomiasis relies on demonstration of parasites in body fluids by bright field microscopy. The parasitaemia in infected patients and animals is usually low, and concentration methods are used to try and increase the chances of seeing parasites. Recently, fluorescence microscopes using light-emitting diodes (LED) have been developed. Since they emit strong light, their use does not require a dark room, making field application a possibility. We have combined LED fluorescence microscopy with lysis of red blood cells (RBC) to improve the sensitivity and speed of detecting trypanosomes. In studies conducted at four centers in Uganda and the Democratic Republic of the Congo, parasitaemic blood was serially diluted and the RBCs lysed using commercial buffer. Samples were then concentrated by centrifugation, and different volumes of the sediment used to make thin and thick smears. Next, these were stained with acridine orange or Giemsa, and examined using an LED microscope under fluorescence or bright light, respectively. Detection of parasites was significantly improved by RBC lysis and concentration, regardless of the staining and microscopy method used. Further improvements were made when smears were prepared using larger volumes of sediment. The best results were obtained with thin smears prepared using 20 μl of sediment and stained with acridine orange. The time taken to see the first parasite was dramatically reduced when smears were examined by LED fluorescence microscopy, compared to bright light. LED fluorescence microscopy was found to be easier and requiring less visual effort than bright field microscopy. These studies demonstrate the potential for incremental improvement in detection of Trypanosoma brucei by combining LED fluorescence microscopy with RBC lysis and concentration. The lysis and concentration method may also be useful in sample preparation for other diagnostic tests for trypanosomiasis.

Anthrax is endemic throughout Africa, causing considerable livestock and wildlife losses and severe, sometimes fatal, infection in humans. Predicting the risk of infection is therefore important for public health, wildlife conservation and livestock economies. However, because of the intermittent and variable nature of anthrax outbreaks, associated environmental and climatic conditions, and diversity of species affected, the ecology of this multihost pathogen is poorly understood. We explored records of anthrax from the Serengeti ecosystem in north-west Tanzania where the disease has been documented in humans, domestic animals and a range of wildlife. Using spatial and temporal case-detection and seroprevalence data from wild and domestic animals, we investigated spatial, environmental, climatic and species-specific associations in exposure and disease. Anthrax was detected annually in numerous species, but large outbreaks were spatially localized, mostly affecting a few focal herbivores. Soil alkalinity and cumulative weather extremes were identified as useful spatial and temporal predictors of exposure and infection risk, and for triggering the onset of large outbreaks. Interacting ecological and behavioural factors, specifically functional groups and spatiotemporal overlap, helped to explain the variable patterns of infection and exposure among species. Synthesis and applications. Our results shed light on ecological drivers of anthrax infection and suggest that soil alkalinity and prolonged droughts or rains are useful predictors of disease occurrence that could guide risk-based surveillance. These insights should inform strategies for managing anthrax including prophylactic livestock vaccination, timing of public health warnings and antibiotic provision in high-risk areas. However, this research highlights the need for greater surveillance (environmental, serological and case-detection-orientated) to determine the mechanisms underlying anthrax dynamics. Keywords: Bacillus anthracis, disease ecology, exposure, infectious disease, multihost, serology, surveillance, susceptibility, zoonosis Introduction Bacillus anthracis (Cohn), the causative agent of anthrax, is a multihost pathogen affecting human, livestock and wildlife populations. The disease has a world-wide distribution, but has declined in many developed countries because of the implementation of livestock vaccination programmes and sanitary measures. However, anthrax is still endemic in Africa, with severe outbreaks causing significant losses in domestic and wild animal populations (Prins & Weyerhaeuser 1987; Shiferaw et al. 2002; Siamudaala 2006; Clegg et al. 2007; Wafula, Patrick & Charles 2008). Non-fatal cutaneous anthrax acquired through contact with infected carcasses or animal products accounts for >95% of all reported human cases globally (World Health Organization 2008). More severe forms, particularly gastrointestinal anthrax because of handling and consumption of inadequately cooked products from infected animals, may also exert a substantial burden that is both underreported and under-diagnosed (Sirisanthana & Brown 2002). Predicting the risk of infection is therefore important from the perspectives of public health, wildlife conservation and livestock economies. Despite the infamous reputation of anthrax, the ecology and transmission of the disease under natural conditions are not well understood (Hugh-Jones & de Vos 2002). The difficulty lies in the intermittent and variable nature of outbreaks, with considerable variation in the species affected, and associated environmental and climatic conditions (Table 1). Table 1 Anthrax outbreaks in Eastern and Southern Africa for which details were available. Predominant species are emboldened, followed by species in which > 5 cases were documented The life cycle of B. anthracis comprises a multiplication phase in the mammalian host and a persistence phase of spores in the soil. Transmission to herbivores largely occurs indirectly, so risk factors are usually associated with exposure to spores, rather than direct animal-to-animal transmission. Survival mechanisms of the pathogen outside the host remain unclear. Bacillus anthracis has been shown to be associated with plant roots (Saile & Koehler 2006), and this is suggested to be an adaptation that increases the likelihood of infecting ungulate hosts (Raymond et al. 2010). Certain environmental factors affect long-term spore survival and thus increase the risk of anthrax (Blackburn et al. 2007). For example, the endemicity of B. anthracis in some areas has been associated with calcium-rich and neutral-to-alkaline soils (van Ness 1971; Dragon et al. 2005; Hugh-Jones & Blackburn 2009), although strain differences exist in soil chemistry preferences (Smith et al. 2000). Strain differences, in fact, may also govern spread in anthrax epidemics (Blackburn et al. 2007; Garofolo et al. 2010). Seasonal incidence patterns suggest climatic factors (precipitation and ambient temperature) play an important role in triggering outbreaks, although these are not consistent between locations (Table 1), and therefore underlying mechanisms are debated. In some African ecosystems, outbreaks have been reported late in the dry season (Prins & Weyerhaeuser 1987; Turnbull et al. 1991; Lindeque & Turnbull 1994; de Vos & Bryden 1996; Shiferaw et al. 2002; Clegg et al. 2007; Muoria et al. 2007), leading to suggestions that transmission may be facilitated by close grazing, nutritional stress and congregation at water holes (Hugh-Jones & de Vos 2002). Elsewhere, outbreaks have been associated with heavy rains (Lindeque & Turnbull 1994; Mlengeya et al. 1998; Wafula, Patrick & Charles 2008; Bellan 2010), which are hypothesized to unearth spores and amplify vector populations (Durrheim et al. 2009; Hugh-Jones & Blackburn 2009; Lewerin et al. 2010). Experimental spore germination and vegetative growth in the rhizosphere provide a mechanism by which bursts of rainfall could spark epidemics (Saile & Koehler 2006). This would parsimoniously explain anthrax occurrences during dry summers in North America and Australia that have been preceded by rains and when animals are often in good body condition (Turner et al. 1999; Hugh-Jones & de Vos 2002; Parkinson, Rajic & Jenson 2003; Hugh-Jones & Blackburn 2009; Epp, Waldner & Argue 2010). Although anthrax infects a wide range of species, outbreaks are typically associated with just a few (Table 1), for example impala Aepyceros melampus, kudu Tragelaphus strepsiceros, buffalo Syncerus caffer and zebra Equus spp. (Prins & Weyerhaeuser 1987; Mlengeya et al. 1998; Clegg et al. 2007; Muoria et al. 2007; Wafula, Patrick & Charles 2008). Even within a single ecosystem, different species may be affected at different times (Lindeque & Turnbull 1994). Reasons for this remain unclear, but could be attributed to host-specific differences in susceptibility and exposure as a result of behavioural and ecological traits as well as differences in pathogen strains. The overall ecological and genetic factors that contribute to environmental persistence of anthrax, and the underlying conditions that initiate outbreaks and underlie patterns of circulation are poorly known. In the Serengeti ecosystem, anthrax has been reported in a variety of species, with sporadic outbreaks occurring in relatively localized endemic foci and mostly affecting a few focal species (Lembo et al. 2011). The ecosystem covers a large area (over 20 000 km2, Sinclair et al. 2008) encompassing a variety of habitats and environmental gradients, which may influence anthrax occurrence. Here, we draw on data gathered opportunistically including serology indicative of exposure and case reports from human, domestic and wild animal populations in the greater Serengeti ecosystem, to explore ecological factors affecting infection patterns in a range of species. Combined, the investigation into environmental and climatic predictors of anthrax and their associations with species-specific patterns of exposure and mortality provides a holistic picture of ecological drivers of anthrax dynamics and identifies priorities for further research in anthrax endemic ecosystems.

Bacillus anthracis, the bacterium that causes anthrax, is responsible for varying death rates among animal species. Difficulties in case detection, hazardous or inaccessible carcasses, and misdiagnosis hinder surveillance. Using case reports and a new serologic assay that enables multispecies comparisons, we examined exposure to and illness caused by B. anthracis in different species in the Serengeti ecosystem in Tanzania during 1996-2009 and the utility of serosurveillance. High seroprevalence among carnivores suggested regular nonfatal exposure. Seropositive wildebeest and buffalo showed that infection was not invariably fatal among herbivores, whereas absence of seropositivity in zebras and frequent detection of fatal cases indicated high susceptibility. Exposure patterns in dogs reflected known patterns of endemicity and provided new information about anthrax in the ecosystem, which indicated the potential of dogs as indicator species. Serosurveillance is a valuable tool for monitoring and detecting anthrax and may shed light on mechanisms responsible for species-specific variability in exposure, susceptibility, and mortality rates.

Controlling an epidemic would be aided by establishing whether particular individuals in infected populations are more likely to transmit infection. However, few analyses have characterised such individuals. Such analyses require both data on who infected whom and on the likely determinants of transmission; data that are available at the farm level for the 2001 Foot and Mouth Disease epidemic in Great Britain. Using these data a putative number of daughter infected premises (IPs) resulting from each IP was calculated where these daughters were within 3 km of the IP. A set of possible epidemiological, demographic, spatial and temporal risk factors were analysed, with the final multivariate generalised linear model (Poisson error term) having 6 statistically significant (p

Background: An understanding of the factors that determine the risk of members of a susceptible population becoming infected is essential for estimating the potential for disease spread, as opposed to just focusing on transmission from an infected population. Furthermore, analysis of the risk factors can reveal important characteristics of an epidemic and further develop understanding of the processes operating. Methods: This paper describes the development of a mixed effects logistic regression model of susceptibility of holdings to foot and mouth disease (FMD) during the 2001 epidemic in Great Britain following the imposition of a national ban on the movements of susceptible animals (NMB). Results: The principal risk factors identified in the model were shorter distances to the nearest infectious seed (a holding infected before the NMB) and the county of the holding (principally Cumbria). Additional risk factors included holdings that are mixed species rather than single species, the surface area of the holding, and the number of cattle within 10 km (all p 0.1). The fit of the model was evaluated using the area under the receiver operator characteristic curve (ROC) and the Hosmer and Lemeshow Chi-squared statistic; the fit was good with both tests (area under the ROC = 0.962 and Hosmer and Lemeshow Chi-squared statistic = 49.98 (p > 0.1)). Conclusions: Holdings at greatest risk of infection can be identified using simple readily available risk factors; this information could be employed in the control of future FMD epidemics. (C) 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

This study assessed the prevalence and zoonotic potential of Shiga toxin-producing Escherichia coli (STEC) sampled from 104 dairy units in the central region of Zambia and compared these with isolates from patients presenting with diarrhoea in the same region. A subset of 297 E. coli strains were sequenced allowing in silico analyses of phylo- and sero-groups. The majority of the bovine strains clustered in the B1 ‘commensal’ phylogroup (67%) and included a diverse array of serogroups. 11% (41/371) of the isolates from Zambian dairy cattle contained Shiga toxin genes (stx) while none (0/73) of the human isolates were positive. While the toxicity of a subset of these isolates was demonstrated, none of the randomly selected STEC belonged to key serogroups associated with human disease and none encoded a type 3 secretion system synonymous with typical enterohaemorrhagic strains. Positive selection for E. coli O157:H7 across the farms identified only one positive isolate again indicating this serotype is rare in these animals. In summary, while Stx-encoding E. coli strains are common in this dairy population, the majority of these strains are unlikely to cause disease in humans. However, the threat remains of the emergence of strains virulent to humans from this reservoir.

This study focused on the use of antibiotics on small, medium and commercial-sized dairy farms in the central region of Zambia and its relationship to antibiotic resistance in Escherichia coli. A stratified random sample of 104 farms was studied, representing approximately 20% of all dairy farms in the region. On each farm, faecal samples were collected from a random sample of animals and a standardised questionnaire on the usage of antibiotics was completed. An E. coli isolate was obtained from 98.67% (371/376) of the sampled animals and tested for resistance to six classes of antibiotics. The estimated prevalence of resistance across the different farming systems was: tetracycline (10.61; 95%CI: 7.40–13.82), ampicillin (6.02; 95%CI: 3.31–8.73), sulfamethoxazole/ trimethoprim (4.49; 95%CI: 2.42–6.56), cefpodoxime (1.91; 95%CI: 0.46–3.36), gentamicin (0.89; 95%CI: 0.06–1.84) and ciprofloxacin (0%). Univariate analyses indicated certain diseases, exotic breeds, location, farm size and certain management practices as risk factors for detection of resistance, whereas multivariate analyses showed an association with lumpy skin disease and a protective effect for older animals (>25 months). This study has provided novel insights into the drivers of antibiotic use and their association with antibiotic resistance in an under-studied region of Southern Africa.

Background Confirmatory diagnosis of visceral leishmaniasis (VL), as well as diagnosis of relapses and test of cure, usually requires examination by microscopy of samples collected by invasive means, such as splenic, bone marrow or lymph node aspirates. This causes discomfort to patients, with risks of bleeding and iatrogenic infections, and requires technical expertise. Molecular tests have great potential for diagnosis of VL using peripheral blood, but require well-equipped facilities and trained personnel. More user-friendly, and field-amenable options are therefore needed. One method that could meet these requirements is loop-mediated isothermal amplification (LAMP) using the Loopamp Leishmania Detection Kit, which comes as dried down reagents that can be stored at room temperature, and allows simple visualization of results. Methodology/Principal findings The Loopamp Leishmania Detection Kit (Eiken Chemical Co., Japan), was evaluated in the diagnosis of VL in Sudan. A total of 198 VL suspects were tested by microscopy of lymph node aspirates (the reference test), direct agglutination test-DAT (in house production) and rK28 antigen-based rapid diagnostic test (OnSite Leishmania rK39-Plus, CTK Biotech, USA). LAMP was performed on peripheral blood (whole blood and buffy coat) previously processed by: i) a direct boil and spin method, and ii) the QIAamp DNA Mini Kit (QIAgen). Ninety seven of the VL suspects were confirmed as cases by microscopy of lymph node aspirates. The sensitivity and specificity for each of the tests were: rK28 RDT 98.81% and 100%; DAT 88.10% and 78.22%; LAMP-boil and spin 97.65% and 99.01%; LAMP-QIAgen 100% and 99.01%. Conclusions/Significance Due to its simplicity and high sensitivity, rK28 RDT can be used first in the diagnostic algorithm for primary VL diagnosis, the excellent performance of LAMP using peripheral blood indicates that it can be also included in the algorithm for diagnosis of VL as a simple test when parasitological confirmatory diagnosis is required in settings that are lower than the reference laboratory, avoiding the need for invasive lymph node aspiration., Author summary Tissue aspiration, either from spleen, bone marrow or lymph node, remains the Gold Standard for parasitological confirmation in patients suspected of visceral leishmaniasis (VL), and is often used for detection of relapses, and as a test of cure. The procedure is invasive, with risks of severe complications, requires skilled personnel to perform, and appropriate facilities to manage severe adverse events, if they occur. These drawbacks can be solved by using sensitive diagnostic test based on peripheral blood. Nucleic acid amplification tests (NAAT) are sensitive for the detection of Leishmania parasites in blood; however, in VL-endemic settings, most NAAT are restricted to well-equipped laboratories. A robust NAAT, Loopamp Leishmania Detection Kit has recently been developed in a collaboration between FIND, Eiken Chemical Co. Ltd., Japan and other partners. We have evaluated this kit in Sudan and obtained a sensitivity of 97.6% and specificity of 99.1%, using DNA obtained from peripheral blood through a simple boil and spin method. Its simplicity and excellent diagnostic performance make this kit ideal for parasitological confirmation of VL in less equipped laboratories.