Gambiense Human African Trypanosomiasis Research Articles

How modelling can help steer the course set by the World Health Organization 2021-2030 roadmap on neglected tropical diseases.

The World Health Organization recently launched its 2021-2030 roadmap, Ending the Neglect to Attain the Sustainable Development Goals , an updated call to arms to end the suffering caused by neglected tropical diseases. Modelling and quantitative analyses played a significant role in forming these latest goals. In this collection, we discuss the insights, the resulting recommendations and identified challenges of public health modelling for 13 of the target diseases: Chagas disease, dengue, gambiense human African trypanosomiasis (gHAT), lymphatic filariasis (LF), onchocerciasis, rabies, scabies, schistosomiasis, soil-transmitted helminthiases (STH), Taenia solium taeniasis/ cysticercosis, trachoma, visceral leishmaniasis (VL) and yaws. This piece reflects the three cross-cutting themes identified across the collection, regarding the contribution that modelling can make to timelines, programme design, drug development and clinical trials.

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

BackgroundIn 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.MethodOur 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.ResultsWe 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.ConclusionsWe 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.Graphical

Two-Year Follow-Up of Trypanosoma brucei gambiense Serology after Successful Treatment of Human African Trypanosomiasis: Results of Four Different Sero-Diagnostic Tests.

Gambiense human African trypanosomiasis (gHAT), also known as gambiense sleeping sickness, is a parasitic infection caused by Trypanosoma brucei gambiense. During the last decades, gHAT incidence has been brought to an all-time low. Newly developed serological tools and drugs for its diagnosis and treatment put the WHO goal of interruption of transmission by 2030 within reach. However, further research is needed to efficiently adapt these new advances to new control strategies. We assessed the serological evolution of cured gHAT patients over a two-year period using four different tests: the rapid diagnostic test (RDT) HAT Sero K-SeT, ELISA/T.b. gambiense, Trypanosoma brucei gambiense inhibition ELISA (iELISA), and the immune trypanolysis test. High seropositive rates were observed in all the tests, although sero-reversion rates were different in each test: ELISA/T.b. gambiense was the test most likely to become negative two years after treatment, whereas RDT HAT Sero-K-SeT was the least likely. iELISA and trypanolysis showed intermediate and comparable probabilities to become negative. Stage 1 patients were also noted to be more likely to become negative than Stage 2 patients in all four serological tests. Our results confirm previous findings that trypanosome-specific antibody concentrations in blood may persist for up to two years, implying that HAT control programs should continue to take the history of past HAT episodes into consideration.

The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020.

BackgroundIn the 20th century, epidemics of human African trypanosomiasis (HAT) ravaged communities in a number of African countries. The latest surge in disease transmission was recorded in the late 1990s, with more than 35,000 cases reported annually in 1997 and 1998. In 2013, after more than a decade of sustained control efforts and steady progress, the World Health Assembly resolved to target the elimination of HAT as a public health problem by 2020. We report here on recent progress towards this goal.Methodology/principal findingsWith 992 and 663 cases reported in 2019 and 2020 respectively, the first global target was amply achieved (i.e. fewer than 2,000 HAT cases/year). Areas at moderate or higher risk of HAT, where more than 1 case/10,000 people/year are reported, shrunk to 120,000 km2 for the five-year period 2016–2020. This reduction of 83% from the 2000–2004 baseline (i.e. 709,000 km2) is slightly below the target (i.e. 90% reduction). As a result, the second global target for HAT elimination as a public health problem cannot be considered fully achieved yet. The number of health facilities able to diagnose and treat HAT expanded (+9.6% compared to a 2019 survey), thus reinforcing the capacity for passive detection and improving epidemiological knowledge of the disease. Active surveillance for gambiense HAT was sustained. In particular, 2.8 million people were actively screened in 2019 and 1.6 million in 2020, the decrease in 2020 being mainly caused by COVID-19-related restrictions. Togo and Côte d’Ivoire were the first countries to be validated for achieving elimination of HAT as a public health problem at the national level; applications from three additional countries are under review by the World Health Organization (WHO).Conclusions/significanceThe steady progress towards the elimination of HAT is a testament to the power of multi-stakeholder commitment and coordination. At the end of 2020, the World Health Assembly endorsed a new road map for 2021–2030 that set new bold targets for neglected tropical diseases. While rhodesiense HAT remains among the diseases targeted for elimination as a public health problem, gambiense HAT is targeted for elimination of transmission. The goal for gambiense HAT is expected to be particularly arduous, as it might be hindered by cryptic reservoirs and a number of other challenges (e.g. further integration of HAT surveillance and control into national health systems, availability of skilled health care workers, development of more effective and adapted tools, and funding for and coordination of elimination efforts).

Monitoring the elimination of gambiense human African trypanosomiasis in the historical focus of Batié, South-West Burkina Faso.

The World Health Organisation has targeted the elimination of human African trypanosomiasis (HAT) as zero transmission by 2030. Continued surveillance needs to be in place for early detection of re-emergent cases. In this context, the performance of diagnostic tests and testing algorithms for detection of the re-emergence of Trypanosoma brucei gambiense HAT remains to be assessed. We carried out a door-to-door active medical survey for HAT in the historical focus of Batié, South–West Burkina Faso. Screening was done using three rapid diagnostic tests (RDTs). Two laboratory tests (ELISA/T. b. gambiense and immune trypanolysis) and parasitological examination were performed on RDT positives only. In total, 5883 participants were screened, among which 842 (14%) tested positive in at least one RDT. Blood from 519 RDT positives was examined microscopically but no trypanosomes were observed. The HAT Sero-K-Set test showed the lowest specificity of 89%, while the specificities of SD Bioline HAT and rHAT Sero-Strip were 92% and 99%, respectively. The specificity of ELISA/T. b. gambiense and trypanolysis was 99% (98–99%) and 100% (99–100%), respectively. Our results suggest that T. b. gambiense is no longer circulating in the study area and that zero transmission has probably been attained. While a least cost analysis is still required, our study showed that RDT preselection followed by trypanolysis may be a useful strategy for post-elimination surveillance in Burkina Faso.

Chemotherapy for second-stage human African trypanosomiasis: drugs in use.

BackgroundHuman African trypanosomiasis, or sleeping sickness, is a severe disease affecting people in the poorest parts of Africa. It is usually fatal without treatment. Conventional treatments require days of intravenous infusion, but a recently developed drug, fexinidazole, can be given orally. Another oral drug candidate, acoziborole, is undergoing clinical development and will be considered in subsequent editions. ObjectivesTo evaluate the effectiveness and safety of currently used drugs for treating second‐stage Trypanosoma brucei gambiense trypanosomiasis (gambiense human African trypanosomiasis, g‐HAT).Search methodsOn 14 May 2021, we searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, BIOSIS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We also searched reference lists of included studies, contacted researchers working in the field, and contacted relevant organizations.Selection criteriaEligible studies were randomized controlled trials that included adults and children with second‐stage g‐HAT, treated with anti‐trypanosomal drugs currently in use.Data collection and analysisTwo review authors extracted data and assessed risk of bias; a third review author acted as an arbitrator if needed. The included trial only reported dichotomous outcomes, which we presented as risk ratio (RR) or risk difference (RD) with 95% confidence intervals (CI). Main resultsWe included one trial comparing fexinidazole to nifurtimox combined with eflornithine (NECT). This trial was conducted between October 2012 and November 2016 in the Democratic Republic of the Congo and the Central African Republic, and included 394 participants. The study reported on efficacy and safety, with up to 24 months' follow‐up. We judged the study to be at low risk of bias in all domains except blinding; as the route of administration and dosing regimens differed between treatment groups, participants and personnel were not blinded, resulting in a high risk of performance bias. Mortality with fexinidazole may be higher at 24 months compared to NECT. There were 9/264 deaths in the fexinidazole group and 2/130 deaths in the NECT group (RR 2.22, 95% CI 0.49 to 10.11; 394 participants; low‐certainty evidence). None of the deaths were related to treatment.Fexinidazole likely results in an increase in the number of people relapsing during follow‐up, with 14 participants in the fexinidazole group (14/264) and none in the NECT group (0/130) relapsing at 24 months (RD 0.05, 95% CI 0.02 to 0.08; 394 participants; moderate‐certainty evidence). We are uncertain whether there is any difference between the drugs regarding the incidence of serious adverse events at 24 months. (31/264 with fexinidazole and 13/130 with NECT group at 24 months). Adverse events were common with both drugs (247/264 with fexinidazole versus 121/130 with NECT), with no difference between groups (RR 1.01, 95% CI 0.95 to 1.06; 394 participants; moderate‐certainty evidence). Authors' conclusionsOral treatment with fexinidazole is much easier to administer than conventional treatment, but deaths and relapse appear to be more common. However, the advantages or an oral option are considerable, in terms of convenience, avoiding hospitalisation and multiple intravenous infusions, thus increasing adherence.

Economic evaluation of disease elimination: An extension to the net-benefit framework and application to human African trypanosomiasis

The global health community has earmarked a number of diseases for elimination or eradication, and these goals have often been praised on the premise of long-run cost savings. However, decision makers must contend with a multitude of demands on health budgets in the short or medium term, and costs per case often rise as the burden of a disease falls, rendering such efforts beyond the cost-effective use of scarce resources. In addition, these decisions must be made in the presence of substantial uncertainty regarding the feasibility and costs of elimination or eradication efforts. Therefore, analytical frameworks are necessary to consider the additional effort for reaching global goals, like elimination or eradication, that are beyond the cost-effective use of country resources. We propose a modification to the net-benefit framework to consider the implications of switching from an optimal strategy, in terms of cost-per-burden averted, to a strategy with a higher likelihood of meeting the global target of elimination or eradication. We illustrate the properties of our framework by considering the economic case of efforts to eliminate the transmission of gambiense human African trypanosomiasis (gHAT), a vector-borne, parasitic disease in West and Central Africa, by 2030.

Prevalence and outcomes of malaria as co-infection among patients with human African trypanosomiasis: a systematic review and meta-analysis

Human African trypanosomiasis (HAT) is endemic in Africa; hence, the possibility of co-infection with malaria among patients with HAT exists. The present study investigated co-infection with malaria among patients with HAT to provide current evidence and characteristics to support further studies. Potentially relevant studies that reported Plasmodium spp. infection in patients with HAT was searched in PubMed, Web of Science, and Scopus. The risk of bias among the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. The pooled prevalence of Plasmodium spp. infection in patients with HAT was quantitatively synthesized using a random-effects model. Subgroup analyses of study sites and stages of HAT were performed to identify heterogeneity regarding prevalence among the included studies. The heterogeneity of the outcome among the included studies was assessed using Cochran’s Q and I2 statistics for consistency. Publication bias was assessed if the number of included studies was 10 or more. For qualitative synthesis, a narrative synthesis of the impact of Plasmodium spp. infection on the clinical and outcome characteristics of HAT was performed when the included studies provided qualitative data. Among 327 studies identified from three databases, nine studies were included in the systematic review and meta-analysis. The prevalence of Plasmodium spp. co-infection (692 cases) among patients with HAT (1523 cases) was 50% (95% confidence interval [CI] = 28–72%, I2 = 98.1%, seven studies). Subgroup analysis by type of HAT (gambiense or rhodesiense HAT) revealed that among patients with gambiense HAT, the pooled prevalence of Plasmodium spp. infection was 46% (95% CI = 14–78%, I2 = 96.62%, four studies), whereas that among patients with rhodesiense HAT was 44% (95% CI = 40–49%, I2 = 98.3%, three studies). Qualitative syntheses demonstrated that Plasmodium spp. infection in individuals with HAT might influence the risk of encephalopathy syndrome, drug toxicity, and significantly longer corrected QT time. Moreover, longer hospital stays and higher treatment costs were recorded among co-infected individuals. Because of the high prevalence of malaria among patients with HAT, some patients were positive for malaria parasites despite being asymptomatic. Therefore, it is suggested to test every patient with HAT for malaria before HAT treatment. If malaria is present, then antimalarial treatment is recommended before HAT treatment. Antimalarial treatment in patients with HAT might decrease the probability of poor clinical outcomes and case fatality in HAT.

Modelling the impact of fexinidazole use on human African trypanosomiasis (HAT) transmission in the Democratic Republic of the Congo.

Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hospital admission for drug administration. Fexinidazole is a new oral treatment for stage 1 and non-severe stage 2 human African trypanosomiasis. The World Health Organization has recently incorporated fexinidazole into its treatment guidelines for human African trypanosomiasis. The treatment does not require hospital admission or a lumbar puncture for all patients, which is likely to ease access for patients; however, it does require concomitant food intake, which is likely to reduce adherence. Here, we use a mathematical model calibrated to case and screening data from Mushie territory, in the Democratic Republic of the Congo, to explore the potential negative impact of poor compliance to an oral treatment, and potential gains to be made from increases in the rate at which patients seek treatment. We find that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern. Reductions in compliance may be offset by increases in the rate at which cases are passively detected. Efforts should therefore be made to ensure good adherence for stage 1 patients to treatment with fexinidazole and to improve access to care.

Trypanosome SL-RNA detection in blood and cerebrospinal fluid to demonstrate active gambiense human African trypanosomiasis infection.

BackgroundSpliced Leader (SL) trypanosome RNA is detectable only in the presence of live trypanosomes, is abundant and the Trypanozoon subgenus has a unique sequence. As previously shown in blood from Guinean human African trypanosomiasis (HAT) patients, SL-RNA is an accurate target for diagnosis. Detection of SL-RNA in the cerebrospinal fluid (CSF) has never been attempted. In a large group of Congolese gambiense HAT patients, the present study aims i) to confirm the sensitivity of SL-RNA detection in the blood and; ii) to assess the diagnostic performance of SL-RNA compared to trypanosome detection in CSF.Methodology/Principal findingsBlood and CSF from 97 confirmed gambiense HAT patients from the Democratic Republic of Congo were collected using PAXgene blood RNA Tubes. Before RNA extraction, specimens were supplemented with internal extraction control RNA to monitor the extraction, which was performed with a PAXgene Blood RNA Kit. SL-RNA qPCR was carried out with and without reverse transcriptase to monitor DNA contamination. In blood, 92/97 (94.8%) HAT patients tested SL-RNA positive, which was significantly more than combined trypanosome detection in lymph and blood (78/97 positive, 80.4%, p = 0.001). Of 96 CSF RNA specimens, 65 (67.7%) were SL-RNA positive, but there was no significant difference between sensitivity of SL-RNA and trypanosome detection in CSF. The contribution of DNA to the Cq values was negligible. In CSF with normal cell counts, a fraction of SL-RNA might have been lost during extraction as indicated by higher internal extraction control Cq values.Conclusions/SignificanceDetection of SL-RNA in blood and CSF allows sensitive demonstration of active gambiense HAT infection, even if trypanosomes remain undetectable in blood or lymph. As this condition often occurs in treatment failures, SL-RNA detection in blood and CSF for early detection of relapses after treatment deserves further investigation.Trial registrationThis study was an integral part of the diagnostic trial "New Diagnostic Tools for Elimination of Sleeping Sickness and Clinical Trials: Early tests of Cure" (DiTECT-HAT-WP4, ClinicalTrials.gov Identifier: NCT03112655).

Modelling to explore the potential impact of asymptomatic human infections on transmission and dynamics of African sleeping sickness.

Gambiense human African trypanosomiasis (gHAT, sleeping sickness) is one of several neglected tropical diseases (NTDs) where there is evidence of asymptomatic human infection but there is uncertainty of the role it plays in transmission and maintenance. To explore possible consequences of asymptomatic infections, particularly in the context of elimination of transmission-a goal set to be achieved by 2030-we propose a novel dynamic transmission model to account for the asymptomatic population. This extends an established framework, basing infection progression on a number of experimental and observation gHAT studies. Asymptomatic gHAT infections include those in people with blood-dwelling trypanosomes, but no discernible symptoms, or those with parasites only detectable in skin. Given current protocols, asymptomatic infection with blood parasites may be diagnosed and treated, based on observable parasitaemia, in contrast to many other diseases for which treatment (and/or diagnosis) may be based on symptomatic infection. We construct a model in which exposed people can either progress to either asymptomatic skin-only parasite infection, which would not be diagnosed through active screening algorithms, or blood-parasite infection, which is likely to be diagnosed if tested. We add extra parameters to the baseline model including different self-cure, recovery, transmission and detection rates for skin-only or blood infections. Performing sensitivity analysis suggests all the new parameters introduced in the asymptomatic model can impact the infection dynamics substantially. Among them, the proportion of exposures resulting in initial skin or blood infection appears the most influential parameter. For some plausible parameterisations, an initial fall in infection prevalence due to interventions could subsequently stagnate even under continued screening due to the formation of a new, lower endemic equilibrium. Excluding this scenario, our results still highlight the possibility for asymptomatic infection to slow down progress towards elimination of transmission. Location-specific model fitting will be needed to determine if and where this could pose a threat.

How modelling can help steer the course set by the World Health Organization 2021-2030 roadmap on neglected tropical diseases

The World Health Organization recently launched its 2021-2030 roadmap, Ending the Neglect to Attain the Sustainable Development Goals, an updated call to arms to end the suffering caused by neglected tropical diseases. Modelling and quantitative analyses played a significant role in forming these latest goals. In this collection, we discuss the insights, the resulting recommendations and identified challenges of public health modelling for 13 of the target diseases: Chagas disease, dengue, gambiense human African trypanosomiasis (gHAT), lymphatic filariasis (LF), onchocerciasis, rabies, scabies, schistosomiasis, soil-transmitted helminthiases (STH), Taenia solium taeniasis/ cysticercosis, trachoma, visceral leishmaniasis (VL) and yaws. This piece reflects the three cross-cutting themes identified across the collection, regarding the contribution that modelling can make to timelines, programme design, drug development and clinical trials.

Modelling to Quantify the Likelihood that Local Elimination of Transmission has Occurred Using Routine Gambiense Human African Trypanosomiasis Surveillance Data.

BackgroundThe gambiense human African trypanosomiasis (gHAT) elimination programme in the Democratic Republic of Congo (DRC) routinely collects case data through passive surveillance and active screening, with several regions reporting no cases for several years, despite being endemic in the early 2000s.MethodsWe use mathematical models fitted to longitudinal data to estimate the probability that selected administrative regions have already achieved elimination of transmission (EOT) of gHAT. We examine the impact of active screening coverage on the certainty of model estimates for transmission and therefore the role of screening in the measurement of EOT.ResultsIn 3 example health zones of Sud-Ubangi province, we find there is a moderate (>40%) probability that EOT has been achieved by 2018, based on 2000–2016 data. Budjala and Mbaya reported zero cases during 2017–18, and this further increases our respective estimates to 99.9% and 99.6% (model S) and to 87.3% and 92.1% (model W). Bominenge had recent case reporting, however, that if zero cases were found in 2021, it would substantially raise our certainty that EOT has been met there (99.0% for model S and 88.5% for model W); this could be higher with 50% coverage screening that year (99.1% for model S and 94.0% for model W).ConclusionsWe demonstrate how routine surveillance data coupled with mechanistic modeling can estimate the likelihood that EOT has already been achieved. Such quantitative assessment will become increasingly important for measuring local achievement of EOT as 2030 approaches.

Strengthening data collection for neglected tropical diseases: What data are needed for models to better inform tailored intervention programmes?

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.

Cost-effectiveness modelling to optimise active screening strategy for gambiense human African trypanosomiasis in endemic areas of the Democratic Republic of Congo

BackgroundGambiense human African trypanosomiasis (gHAT) has been brought under control recently with village-based active screening playing a major role in case reduction. In the approach to elimination, we investigate how to optimise active screening in villages in the Democratic Republic of Congo, such that the expenses of screening programmes can be efficiently allocated whilst continuing to avert morbidity and mortality.MethodsWe implement a cost-effectiveness analysis using a stochastic gHAT infection model for a range of active screening strategies and, in conjunction with a cost model, we calculate the net monetary benefit (NMB) of each strategy. We focus on the high-endemicity health zone of Kwamouth in the Democratic Republic of Congo.ResultsHigh-coverage active screening strategies, occurring approximately annually, attain the highest NMB. For realistic screening at 55% coverage, annual screening is cost-effective at very low willingness-to-pay thresholds (<DOLLAR/>20.4 per disability adjusted life year (DALY) averted), only marginally higher than biennial screening (<DOLLAR/>14.6 per DALY averted). We find that, for strategies stopping after 1, 2 or 3 years of zero case reporting, the expected cost-benefits are very similar.ConclusionsWe highlight the current recommended strategy—annual screening with three years of zero case reporting before stopping active screening—is likely cost-effective, in addition to providing valuable information on whether transmission has been interrupted.

3 Tesla serial magnetic resonance imaging of human African trypanosomiasis (Trypanosoma brucei gambiense) and review of the literature

We report serial magnetic resonance imaging (MRI) findings and follow-up in a case of human African trypanosomiasis (HAT) presenting with limited lesions followed by early and complete resolution. We searched the literature for documented cases and reviewed MRI findings before treatment. A 30-year-old Lebanese man, who had lived in Gabon for six years, presented with a two-year history of rash, anorexia, weight loss, arthralgia, paresthesia, and hypersomnia. Previously, the patient had received corticosteroid therapy for unconfirmed ANCA-associated vasculitis. Physical examination revealed a painless chancre on the left arm located at the site of an old insect bite, enlarged cervical, axillar and inguinal lymph nodes, hepatosplenomegaly and impaired concentration. Blood analysis showed an elevated protein level (90g/L) with hypoalbuminemia (24.2g/L) and elevated IgM (26.4g/L). Bone marrow aspirate and biopsy failed to detect any parasite. Polymerase chain reaction tests on blood and cerebrospinal fluid were positive for Trypanosoma. Serology tests confirmed the diagnosis of HAT due to Trypanosoma brucei gambiense infection. 3T MRI showed lesions in the hypothalamus and basal ganglia, the internal capsule, and the mesencephalon bilaterally. Follow-up MRI showed interval progression of the abnormalities. Treatment with melarsoprol was followed by clinical improvement with regression of the lesions on the three-month MRI, then total resolution at the 10-month follow-up. This case highlights a pattern of mild MRI lesions in T. brucei gambiense HAT with a total and rapid resolution under treatment. The literature review (16 HAT cases with sufficient radiological data, included ours) revealed an MRI pattern of brain lesion distribution that could be helpful for diagnosis and orienting biological tests.

Predicting the impact of COVID-19 interruptions on transmission of gambiense human African trypanosomiasis in two health zones of the Democratic Republic of Congo.

Many control programmes against neglected tropical diseases have been interrupted due to the coronavirus disease 2019 (COVID-19) pandemic, including those that rely on active case finding. In this study we focus on gambiense human African trypanosomiasis (gHAT), where active screening was suspended in the Democratic Republic of Congo (DRC) due to the pandemic. We use two independent mathematical models to predict the impact of COVID-19 interruptions on transmission and reporting and achievement of the 2030 elimination of transmission (EOT) goal for gHAT in two moderate-risk regions of the DRC. We consider different interruption scenarios, including reduced passive surveillance in fixed health facilities, and whether this suspension lasts until the end of 2020 or 2021. Our models predict an increase in the number of new infections in the interruption period only if both active screening and passive surveillance were suspended, and with a slowed reduction—but no increase—if passive surveillance remains fully functional. In all scenarios, the EOT may be slightly pushed back if no mitigation, such as increased screening coverage, is put in place. However, we emphasise that the biggest challenge will remain in the higher-prevalence regions where EOT is already predicted to be behind schedule without interruptions unless interventions are bolstered.

Quantifying epidemiological drivers of gambiense human African Trypanosomiasis across the Democratic Republic of Congo.

Gambiense human African trypanosomiasis (gHAT) is a virulent disease declining in burden but still endemic in West and Central Africa. Although it is targeted for elimination of transmission by 2030, there remain numerous questions about the drivers of infection and how these vary geographically. In this study we focus on the Democratic Republic of Congo (DRC), which accounted for 84% of the global case burden in 2016, to explore changes in transmission across the country and elucidate factors which may have contributed to the persistence of disease or success of interventions in different regions. We present a Bayesian fitting methodology, applied to 168 endemic health zones (∼100,000 population size), which allows for calibration of a mechanistic gHAT model to case data (from the World Health Organization HAT Atlas) in an adaptive and automated framework. It was found that the model needed to capture improvements in passive detection to match observed trends in the data within former Bandundu and Bas Congo provinces indicating these regions have substantially reduced time to detection. Health zones in these provinces generally had longer burn-in periods during fitting due to additional model parameters. Posterior probability distributions were found for a range of fitted parameters in each health zone; these included the basic reproduction number estimates for pre-1998 (R0) which was inferred to be between 1 and 1.14, in line with previous gHAT estimates, with higher median values typically in health zones with more case reporting in the 2000s. Previously, it was not clear whether a fall in active case finding in the period contributed to the declining case numbers. The modelling here accounts for variable screening and suggests that underlying transmission has also reduced greatly-on average 96% in former Equateur, 93% in former Bas Congo and 89% in former Bandundu-Equateur and Bandundu having had the highest case burdens in 2000. This analysis also sets out a framework to enable future predictions for the country.

Trypa-NO! contributes to the elimination of gambiense human African trypanosomiasis by combining tsetse control with "screen, diagnose and treat" using innovative tools and strategies.

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.

Feasibility of community-based control of tsetse: Apilot project using Tiny Targets in the Democratic Republic of Congo.

Gambiense Human African Trypanosomiasis (g-HAT) is a neglected tropical disease caused by trypanosomes transmitted by tsetse flies. 70% of cases in 2019 (604/863) occurred in the Democratic Republic of Congo (DRC). The national programme for g-HAT elimination in DRC includes a large-scale deployment of Tiny Targets which attract and kill tsetse. This intervention is directed by vector-control specialists with small teams, moving in canoes, deploying Tiny Targets along riverbanks where tsetse concentrate. While the targets are deployed in communal areas, and the method is cheap and easy-to-use, local people have little involvement. This study aimed to evaluate if a community-led vector control programme was feasible in the context of DRC’s g-HAT elimination programme. In 2017, a community-led intervention was implemented in three villages in the Kwilu province of DRC. This intervention was evaluated through an Action Research with qualitative data collected through 21 focus group discussions and 289 hours of observation. Also the geographical location and quality of each Tiny Targets were collected (total number deployed = 2429). This research revealed that community-based approach largely worked: people were motivated and proactive, showed a good application of the acquired knowledge resulting in an effective deployment of Tiny Targets. In addition, our study provided evidence that acceptability of the targets by the community can improve deployment quality by reducing target loss and damage. The approach was feasible in places where canoe-based teams could not reach. Against these advantages, a community-based approach was time-consuming and had to adapt to the seasonal and daily rhythms of the community. A community-based approach for tsetse control is technically feasible and recommended but limits to the speed and scale of the approach restraints its application as a standalone strategy in a large-scale national programme aiming to eliminate g-HAT in a short timeframe.