Specificity of serological screening tests and reference laboratory tests to diagnose gambiense human African trypanosomiasis: a prospective clinical performance study.

BACKGROUND: Serological screening tests play a crucial role to diagnose gambiense human African trypanosomiasis (gHAT). Presently, they preselect individuals for microscopic confirmation, but in future "screen and treat" strategies they will identify individuals for treatment. Variability in reported specificities, the development of new rapid diagnostic tests (RDT) and the hypothesis that malaria infection may decrease RDT specificity led us to evaluate the specificity of 5 gHAT screening tests. METHODS: During active screening, venous blood samples from 1095 individuals from Côte d'Ivoire and Guinea were tested consecutively with commercial (CATT, HAT Sero-K-SeT, Abbott Bioline HAT 2.0) and prototype (DCN HAT RDT, HAT Sero-K-SeT 2.0) gHAT screening tests and with a malaria RDT. Individuals with ≥ 1 positive gHAT screening test underwent microscopy and further immunological (trypanolysis with T.b. gambiense LiTat 1.3, 1.5 and 1.6; indirect ELISA/T.b. gambiense; T.b. gambiense inhibition ELISA with T.b. gambiense LiTat 1.3 and 1.5 VSG) and molecular reference laboratory tests (PCR TBRN3, 18S and TgsGP; SHERLOCK 18S Tids, 7SL Zoon, and TgsGP; Trypanozoon S2-RT-qPCR 18S2, 177T, GPI-PLC and TgsGP in multiplex; RT-qPCR DT8, DT9 and TgsGP in multiplex). Microscopic trypanosome detection confirmed gHAT, while other individuals were considered gHAT free. Differences in fractions between groups were assessed by Chi square and differences in specificity between 2 tests on the same individuals by McNemar. RESULTS: One gHAT case was diagnosed. Overall test specificities (n = 1094) were: CATT 98.9% (95% CI: 98.1-99.4%); HAT Sero-K-SeT 86.7% (95% CI: 84.5-88.5%); Bioline HAT 2.0 82.1% (95% CI: 79.7-84.2%); DCN HAT RDT 78.2% (95% CI: 75.7-80.6%); and HAT Sero-K-SeT 2.0 78.4% (95% CI: 75.9-80.8%). In malaria positives, gHAT screening tests appeared less specific, but the difference was significant only in Guinea for Abbott Bioline HAT 2.0 (P = 0.03) and HAT Sero-K-Set 2.0 (P = 0.0006). The specificities of immunological and molecular laboratory tests in gHAT seropositives were 98.7-100% (n = 399) and 93.0-100% (n = 302), respectively. Among 44 reference laboratory test positives, only the confirmed gHAT patient and one screening test seropositive combined immunological and molecular reference laboratory test positivity. CONCLUSIONS: Although a minor effect of malaria cannot be excluded, gHAT RDT specificities are far below the 95% minimal specificity stipulated by the WHO target product profile for a simple diagnostic tool to identify individuals eligible for treatment. Unless specificity is improved, an RDT-based "screen and treat" strategy would result in massive overtreatment. In view of their inconsistent results, additional comparative evaluations of the diagnostic performance of reference laboratory tests are indicated for better identifying, among screening test positives, those at increased suspicion for gHAT. TRIAL REGISTRATION: The trial was retrospectively registered under NCT05466630 in clinicaltrials.gov on July 15 2022.

Health and economic impacts of Lassa vaccination campaigns in West Africa.

Lassa fever is a zoonotic disease identified by the World Health Organization (WHO) as having pandemic potential. This study estimates the health-economic burden of Lassa fever throughout West Africa and projects impacts of a series of vaccination campaigns. We also model the emergence of "Lassa-X" - a hypothetical pandemic Lassa virus variant - and project impacts of achieving 100 Days Mission vaccination targets. Our model predicted 2.7M (95% uncertainty interval: 2.1M-3.4M) Lassa virus infections annually, resulting over ten years in 2.0M (793.8K-3.9M) disability-adjusted life years (DALYs). The most effective vaccination strategy was a population-wide preventive campaign primarily targeting WHO-classified "endemic" districts. Under conservative vaccine efficacy assumptions, this campaign averted $20.1M ($8.2M-$39.0M) in lost DALY value and $128.2M ($67.2M-$231.9M) in societal costs (International dollars 2021). Reactive vaccination in response to local outbreaks averted just one-tenth the health-economic burden of preventive campaigns. In the event of Lassa-X emerging, spreading throughout West Africa and causing approximately 1.2M DALYs within two years, 100 Days Mission vaccination averted 22% of DALYs given a vaccine 70% effective against disease, and 74% of DALYs given a vaccine 70% effective against both infection and disease. These findings suggest how vaccination could alleviate Lassa fever's burden and assist in pandemic preparedness.

Assessing the importance of demographic risk factors across two waves of SARS-CoV-2 using fine-scale case data.

For the long term control of an infectious disease such as COVID-19, it is crucial to identify the most likely individuals to become infected and the role that differences in demographic characteristics play in the observed patterns of infection. As high-volume surveillance winds down, testing data from earlier periods are invaluable for studying risk factors for infection in detail. Observed changes in time during these periods may then inform how stable the pattern will be in the long term. To this end we analyse the distribution of cases of COVID-19 across Scotland in 2021, where the location (census areas of order 500-1,000 residents) and reporting date of cases are known. We consider over 450,000 individually recorded cases, in two infection waves triggered by different lineages: B.1.1.529 ("Omicron") and B.1.617.2 ("Delta"). We use random forests, informed by measures of geography, demography, testing and vaccination. We show that the distributions are only adequately explained when considering multiple explanatory variables, implying that case heterogeneity arose from a combination of individual behaviour, immunity, and testing frequency. Despite differences in virus lineage, time of year, and interventions in place, we find the risk factors remained broadly consistent between the two waves. Many of the observed smaller differences could be reasonably explained by changes in control measures.

Towards the sustainable elimination of gambiense human African trypanosomiasis in Côte d'Ivoire using an integrated approach.

BACKGROUND: Human African trypanosomiasis is a parasitic disease caused by trypanosomes among which Trypanosoma brucei gambiense is responsible for a chronic form (gHAT) in West and Central Africa. Its elimination as a public health problem (EPHP) was targeted for 2020. 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. METHODS: The control methods used combined both exhaustive and targeted medical screening strategies including the follow-up of seropositive subjects- considered as potential asymptomatic carriers 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) was met between 2000-2021 in two endemic and two hypo-endemic health districts. RESULTS: Between 2015 and 2019, nine gHAT cases were detected in the two endemic health districts of Bouaflé and Sinfra in which the number of cases/10,000 inhabitants was far below 1, a necessary condition for validating EPHP. Modelling estimated a slow but steady decline in transmission across the 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. CONCLUSION: This 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.

Health economic evaluation of strategies to eliminate gambiense human African trypanosomiasis in the Mandoul disease focus of Chad.

Human African trypanosomiasis, caused by the gambiense subspecies of Trypanosoma brucei (gHAT), is a deadly parasitic disease transmitted by tsetse. Partners worldwide have stepped up efforts to eliminate the disease, and the Chadian government has focused on the previously high-prevalence setting of Mandoul. In this study, we evaluate the economic efficiency of the intensified strategy that was put in place in 2014 aimed at interrupting the 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 to control the tsetse vector). 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) which substantially increased the probability of reaching the 2030 elimination target for gHAT as set by the World Health Organization. Our transmission modelling and economic evaluation suggest that the gains that have been made could be maintained by passive screening. Our analysis speaks to comparative efficiency, and it does not take into account all possible considerations; for instance, any cessation of ongoing active screening should first consider that substantial surveillance activities will be critical to verify the elimination of transmission and to protect against the possible importation of infection from neighbouring endemic foci.

A high level estimation of the net economic benefits to small-scale livestock producers arising from animal health product distribution initiatives.

Introduction: A fundamental challenge for charities that facilitate distribution of animal health products to small-scale livestock producers (SSPs) in low and middle income countries (LMICs) is identifying the products and market mechanisms that provide the greatest positive impact for SSPs and estimating their associated impact. This paper describes a pragmatic approach to modeling the impact of market-led product distribution initiatives based on estimating the net economic benefit of administration of animal health products. Methods: The model estimates the economic impact of diseases at the individual animal level for poultry, small ruminants, and cattle. The economic impact of mortality and growth inhibition associated with disease are then estimated in conjunction with the losses averted or recovered by preventing or treating the disease. Economic benefit is estimated in 2014-2017 values and also adjusted to 2023 values. The flexible model structure allows for addition of new geographies, new products, and increased granularity of modeled production systems. Results: Applied to the Global Alliance for Livestock Veterinary Medicines (GALVmed) product distribution initiatives conducted in Africa and South Asia (SA) between 2014 and 2017, the model estimates an adjusted total net economic benefit of 139.9 million USD from sales of vaccines and poultry anthelminthics in these initiatives. Within SSA, the greatest net economic benefit was realized from East Coast fever and Newcastle disease vaccines, while in SA, peste des petits ruminants and Newcastle disease vaccines had the greatest net economic benefits. This translated to an adjusted $37.97 of net economic benefit on average per SSP customer, many of whom were small poultry producers. Discussion: While the model currently estimates impacts from mortality and growth inhibition in livestock, there is the potential to extend it to cover impacts of further initiatives, including interventions targeted at diseases that impact production of milk, eggs, and reproduction.

A modelling assessment of short- and medium-term risks of programme interruptions for gambiense human African trypanosomiasis in the DRC.

Gambiense human African trypanosomiasis (gHAT) is a deadly vector-borne, neglected tropical disease found in West and Central Africa targeted for elimination of transmission (EoT) by 2030. The recent pandemic has illustrated how it can be important to quantify the impact that unplanned disruption to programme activities may have in achieving EoT. We used a previously developed model of gHAT fitted to data from the Democratic Republic of the Congo, the country with the highest global case burden, to explore how interruptions to intervention activities, due to e.g. COVID-19, Ebola or political instability, could impact progress towards EoT and gHAT burden. We simulated transmission and reporting dynamics in 38 regions within Kwilu, Mai Ndombe and Kwango provinces under six interruption scenarios lasting for nine or twenty-one months. Included in the interruption scenarios are the cessation of active screening in all scenarios and a reduction in passive detection rates and a delay or suspension of vector control deployments in some scenarios. Our results indicate that, even under the most extreme 21-month interruption scenario, EoT is not predicted to be delayed by more than one additional year compared to the length of the interruption. If existing vector control deployments continue, we predict no delay in achieving EoT even when both active and passive screening activities are interrupted. If passive screening remains as functional as in 2019, we expect a marginal negative impact on transmission, however this depends on the strength of passive screening in each health zone. We predict a pronounced increase in additional gHAT disease burden (morbidity and mortality) in many health zones if both active and passive screening were interrupted compared to the interruption of active screening alone. The ability to continue existing vector control during medical activity interruption is also predicted to avert a moderate proportion of disease burden.

FAIR data pipeline: provenance-driven data management for traceable scientific workflows.

Modern epidemiological analyses to understand and combat the spread of disease depend critically on access to, and use of, data. Rapidly evolving data, such as data streams changing during a disease outbreak, are particularly challenging. Data management is further complicated by data being imprecisely identified when used. Public trust in policy decisions resulting from such analyses is easily damaged and is often low, with cynicism arising where claims of 'following the science' are made without accompanying evidence. Tracing the provenance of such decisions back through open software to primary data would clarify this evidence, enhancing the transparency of the decision-making process. Here, we demonstrate a Findable, Accessible, Interoperable and Reusable (FAIR) data pipeline. Although developed during the COVID-19 pandemic, it allows easy annotation of any data as they are consumed by analyses, or conversely traces the provenance of scientific outputs back through the analytical or modelling source code to primary data. Such a tool provides a mechanism for the public, and fellow scientists, to better assess scientific evidence by inspecting its provenance, while allowing scientists to support policymakers in openly justifying their decisions. We believe that such tools should be promoted for use across all areas of policy-facing research. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

SCoVMod - a spatially explicit mobility and deprivation adjusted model of first wave COVID-19 transmission dynamics.

Background: Mobility restrictions prevent the spread of infections to disease-free areas, and early in the coronavirus disease 2019 (COVID-19) pandemic, most countries imposed severe restrictions on mobility as soon as it was clear that containment of local outbreaks was insufficient to control spread. These restrictions have adverse impacts on the economy and other aspects of human health, and it is important to quantify their impact for evaluating their future value. Methods: Here we develop Scotland Coronavirus transmission Model (SCoVMod), a model for COVID-19 in Scotland, which presents unusual challenges because of its diverse geography and population conditions. Our fitted model captures spatio-temporal patterns of mortality in the first phase of the epidemic to a fine geographical scale. Results: We find that lockdown restrictions reduced transmission rates down to an estimated 12\% of its pre-lockdown rate. 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. However, poor health associated with deprivation has a considerable association with mortality; the Council Area (CA) with the greatest health-related deprivation was found to have a mortality rate 2.45 times greater than the CA with the lowest health-related deprivation considering all deaths occurring outside of carehomes. Conclusions: We find that in even an early epidemic with poor case ascertainment, a useful spatially explicit model can be fit with meaningful parameters based on the spatio-temporal distribution of death counts. Our simple approach is useful to strategically examine trade-offs between travel related restrictions and physical distancing, and the effect of deprivation-related factors on outcomes.

Seroepidemiology of Crimean-Congo Haemorrhagic Fever among cattle in Cameroon: Implications from a One Health perspective.

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.

Update of transmission modelling and projections of gambiense human African trypanosomiasis in the Mandoul focus, Chad.

BACKGROUND: In recent years, a programme of vector control, screening and treatment of gambiense human African trypanosomiasis (gHAT) infections led to a rapid decline in cases in the Mandoul focus of Chad. To represent the biology of transmission between humans and tsetse, we previously developed a mechanistic transmission model, fitted to data between 2000 and 2013 which suggested that transmission was interrupted by 2015. The present study outlines refinements to the model to: (1) Assess whether elimination of transmission has already been achieved despite low-level case reporting; (2) quantify the role of intensified interventions in transmission reduction; and (3) predict the trajectory of gHAT in Mandoul for the next decade under different strategies. METHOD: Our previous gHAT transmission model for Mandoul was updated using human case data (2000-2019) and a series of model refinements. These include how diagnostic specificity is incorporated into the model and improvements to the fitting method (increased variance in observed case reporting and how underreporting and improvements to passive screening are captured). A side-by-side comparison of fitting to case data was performed between the models. RESULTS: We estimated 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 1.5-fold for stage 2. We find that whilst the diagnostic algorithm for active screening is estimated to be highly specific (95% credible interval (CI) 99.9-100%, Specificity = 99.9%), the high screening and low infection levels mean that some recently reported cases with no parasitological confirmation might be false positives. We also find that the focus-wide tsetse reduction estimated through model fitting (95% CI 96.1-99.6%, Reduction = 99.1%) is comparable to the reduction previously measured by the decline in tsetse catches from monitoring traps. In line with previous results, the model suggests that transmission was interrupted in 2015 due to intensified interventions. CONCLUSIONS: We recommend that additional confirmatory testing is performed in Mandoul to ensure the endgame can be carefully monitored. More specific measurement of cases, would better inform when it is safe to stop active screening and vector control, provided there is a strong passive surveillance system in place.

Estimating the impact of Tiny Targets in reducing the incidence of Gambian sleeping sickness in the North-west Uganda focus.

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.

The epidemiology of bacterial zoonoses in pastoral and dairy cattle in Cameroon, Central Africa.

Previous work identified that bacterial zoonoses (Brucella species, Coxiella burnetii and Leptospira hardjo) were present in Cameroonian pastoral cattle. To assess the characteristics of this zoonotic risk, we analyse seroprevalence of each pathogen and the associated management, herd and environmental factors in Cameroonian pastoral and dairy cattle. Cross-sectional samples included pastoralist herds in the Northwest Region (NWR n = 750) and Vina Division (VD n = 748) and small holder dairy herds in the NWR (n = 60). Exposure to Brucella spp., C. burnetii and L. hardjo were screened for using commercial ELISAs and population adjusted estimates made. In addition, individual, herd and ecological metadata were collected and used to identify risk factors associated with animal-level seropositivity. In the pastoral cattle, seroprevalence to Brucella spp. was relatively low but was higher in the NWR (4.2%, CI: 2.5%-7.0%) than the VD (1.1%: CI 0.5%-2.4%), while L. hardjo seroprevalence was much higher though similar in the NWR (30.7%, CI 26.3%-35.5%) and VD (35.9%, CI 31.3%-40.7%). No differences were noted in C. burnetii seroprevalence between the two study sites (NWR: 14.6%, CI 11.8%-18.0%. VD: 12.4%, 9.6%-15.9%). Compared to pastoral, dairy cattle had lower seroprevalences for L. hardjo (1.7%, CI: 0.0%-4.9%), C. burnetii (0.0%, CI 0.0%-6.0%) but similar for Brucella spp. (5.0%, CI 0.0%-10.6%). Increased odds of Brucella spp. seropositivity were associated with owning sheep or rearing sheep and fencing cattle in at night. Adult cattle had increased odds of being seropositive for both C. burnetii and L. hardjo. Additionally, exposure to C. burnetii was associated with local ecological conditions and L. hardjo was negatively associated with cattle undertaking transhumance. This work highlights that exposure to these 3 important production diseases and occupational zoonoses are widespread in Cameroonian cattle. Further work is required to understand transmission dynamics between humans and livestock to inform implementation of effective control measures.

Segmentation and shielding of the most vulnerable members of the population as elements of an exit strategy from COVID-19 lockdown.

This study demonstrates that an adoption of a segmenting and shielding strategy could increase the scope to partially exit COVID-19 lockdown while limiting the risk of an overwhelming second wave of infection. We illustrate this using a mathematical model that segments the vulnerable population and their closest contacts, the 'shielders'. 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 are explored. Our study shows that the most important determinants of outcome are: (i) post-lockdown transmission rates within the general and between the general and vulnerable segments; (ii) fractions of the population in the vulnerable and shielder segments; (iii) adherence to protective measures; and (iv) build-up of population immunity. Additionally, we found that effective measures in the shielder segment, e.g. intensive routine screening, allow further relaxations in the general population. 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. This strategy 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. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.

Optimising passive surveillance of a neglected tropical disease in the era of elimination: A modelling study.

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.

Hip displacement in children with cerebral palsy.

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.

Development and implementation of a strategy for intensified screening for gambiense human African trypanosomiasis in Kongo Central province, DRC.

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.

Improved Access to Diagnostics for Rhodesian Sleeping Sickness around a Conservation Area in Malawi Results in Earlier Detection of Cases and Reduced Mortality.

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.

A Tool for Prioritizing Livestock Disease Threats to Scotland.

There are a number of disease threats to the livestock of Scotland that are not presently believed to be circulating in the UK. Here, we present the development of a tool for prioritizing resources for livestock disease threats to Scotland by combining a semi-quantitative model of the chance of introduction of different diseases with a semi-quantitative model of disease impact. Eighteen key diseases were identified and then input into a model framework to produce a semi-quantitative estimate of disease priorities. We estimate this through a model of the potential impacts of the infectious diseases in Scotland that is interpreted alongside a pre-existing generic risk assessment model of the risks of incursion of the diseases. The impact estimates are based on key metrics which influence the practical impact of disease. Metrics included are the rate of spread, the disease mitigation factors, impacts on animal welfare and production, the human health risks and the impacts on wider society. These quantities were adjusted for the size of the Scottish livestock population and were weighted using published scores. Of the 18 livestock diseases included, the model identifies highly pathogenic avian influenza, foot and mouth disease in cattle and bluetongue virus in sheep as having the greatest priority in terms of the combination of chance of introduction and disease impact. Disregarding the weighting for livestock populations and comparing equally between industry sectors, the results demonstrate that Newcastle disease and highly pathogenic avian influenza generally have the greatest potential impact. This model provides valuable information for the veterinary and livestock industries in prioritizing resources in the face of many disease threats. The system can easily be adjusted as disease situations evolve.