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Since the turn of the century, the global community has made great progress towards the elimination of gambiense human African trypanosomiasis (HAT). Elimination programs, primarily relying on screening and treatment campaigns, have also created a rich database of HAT epidemiology. Mathematical models calibrated with these data can help to fill remaining gaps in our understanding of HAT transmission dynamics, including key operational research questions such as whether integrating vector control with current intervention strategies is needed to achieve HAT elimination. Here we explore, via an ensemble of models and simulation studies, how including or not disease stage data, or using more updated data sets affect model predictions of future control strategies.

Background A clear understanding of the knowledge, attitudes and practices (KAP) of a particular community is necessary in order to improve control of human African trypanosomiasis (HAT).New screening and diagnostic tools and strategies were introduced into South Sudan, as part of integrated delivery of primary healthcare. Knowledge and awareness on HAT, its new/improved screening and diagnostic tools, the places and processes of getting a confirmatory diagnosis and treatment are crucial to the success of this strategy. Methodology A KAP survey was carried out in Yei County, South Sudan, to identify gaps in community KAP and determine the preferred channels and sources of information on the disease. The cross-sectional KAP survey utilized questionnaires, complemented with key informant interviews and a focus group discussion to elicit communal as well as individual KAP on HAT. Findings Most (90%) of the respondents had general knowledge on HAT. Lower levels of education, gender and geographic locations without a history of HAT interventions were associated with incorrect knowledge and/or negative perceptions about the treatability of HAT. Symptoms appearing in the late stage were best known. A majority (97.2%) would seek treatment for HAT only in a health centre. However, qualitative data indicates that existing myths circulating in the popular imagination could influence people’s practices. Seventy-one percent of the respondents said they would offer social support to patients with HAT but qualitative data highlights that stigma still exists. Misconceptions and stigma can negatively influence the health seeking behaviour of HAT cases. In relation to communication, the top preferred and effective source of communication was radio (24%). Conclusion Gaps in relation to KAP on HAT still exist in the community. Perceptions on HAT, specifically myths and stigma, were key gaps that need to be bridged through effective education and communication strategies for HAT control alongside other interventions., Author summary Misconceptions about sleeping sickness, a neglected tropical disease transmitted by tsetse flies, can be a hindrance to effective implementation of control interventions especially in the face of accelerating work to eliminate the disease. Understanding community knowledge, attitudes and practices about sleeping sickness is important in developing appropriate material for educating and sensitizing communities at risk of the disease. We conducted a study to establish community knowledge, attitudes and practices, including preferred channels of disseminating sleeping sickness information. Despite the fact that the community in Yei County knew about the disease, existing myths and stigma have the potential of influencing their health seeking behaviour. The radio, community health workers and village elders were the most preferred sources of sharing information with the community. There is need to develop education and awareness material to address issues of existing myths, potential stigma, treat ability of HAT, importance of testing and treatment, as well as provide information on the new/improved testing and treatment approaches for HAT. In addition, this should be provided through use of preferred and trusted sources of information dissemination, which is critical in uptake of HAT control, management and prevention activities.

New rapid diagnostic tests (RDTs) for screening human African trypanosomiasis (HAT) have been introduced as alternatives to the card agglutination test for trypanosomiasis (CATT). One brand of RDT, the SD BIOLINE HAT RDT has been shown to have lower specificity but higher sensitivity than CATT, so to make a rational choice between screening strategies, a cost-effectiveness analysis is a key element. In this paper we estimate the relative cost-effectiveness of CATT and the RDT when implemented in the Democratic Republic of the Congo (DRC). Data on the epidemiological parameters and costs were collected as part of a larger study. These data were used to model three different diagnostic algorithms in mobile teams and fixed health facilities, and the relative cost-effectiveness was measured as the average cost per case diagnosed. In both fixed facilities and mobile teams, screening of participants using the SD BIOLINE HAT RDT followed by parasitological confirmation had a lower cost-effectiveness ratio than in algorithms using CATT. Algorithms using the RDT were cheaper by 112.54 (33.2%) and 88.54 (32.92%) US dollars per case diagnosed in mobile teams and fixed health facilities respectively, when compared with algorithms using CATT. Sensitivity analysis demonstrated that these conclusions were robust to a number of assumptions, and that the results can be scaled to smaller or larger facilities, and a range of prevalences. The RDT was the most cost-effective screening test in all realistic scenarios and detected more cases than CATT. Thus, on this basis, the SD BIOLINE HAT RDT could be considered as the most cost-effective option for use in routine screening for HAT in the DRC.

Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF)). Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan) showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of “sleeping sickness”. Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity) and stage of disease (92% sensitivity and 81% specificity). A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages) versus control., Author Summary Human African trypanosomiasis, also known as sleeping sickness, is a parasitic disease that affects people in sub-Saharan Africa. There are two stages of the infection. The first stage involves parasites proliferating in the bloodstream following introduction via the bite of an infected tsetse fly. The second, more serious stage, involves parasite invasion and proliferation within the central nervous system causing characteristic disturbances to the patients’ sleep wake patterns and progressive appearance of other neurological signs, including walking disabilities behaviour changes, abnormal movements, incontinence, then ultimately coma and death. Drugs are available to treat both stages of the disease, but the drugs for stage 2 disease have serious side effects and must be administered in hospital settings. Stage determination is thus a key element for disease management. Currently staging involves microscopic evaluation of CSF following a lumbar puncture. Here, we have analysed the metabolome of CSF, blood and urine of patients to seek biomarkers to stage the disease based on these biofluids. CSF and blood fluids were found to have distinctive metabolic biomarkers and when several of these metabolites are combined, a sensitive and robust discriminatory staging test can be developed. Some CSF metabolic markers relate to brain inflammation, whilst others may be related to somnolence associated with the disease in stage 2 patients, which may also help in understanding disease progression. Interestingly, distinctive biomarkers were also found in plasma, potentially abrogating the need for diagnostic lumbar punctures in the future.

Background Diagnosis of human African trypanosomiasis (HAT) remains a challenge both for active screening, which is critical in control of the disease, and in the point-of-care scenario where early and accurate diagnosis is essential. Recently, the first field deployment of a lateral flow rapid diagnostic test (RDT) for HAT, “SD BIOLINE HAT” has taken place. In this study, we evaluated the performance of “SD BIOLINE HAT” and two new prototype RDTs. Methodology/Principal Findings The performance of “SD BIOLINE HAT” and 2 prototype RDTs was tested using archived plasma from 250 Trypanosoma brucei gambiense patients, and 250 endemic controls. As well as comparison of the sensitivity and specificity of each device, the performance of individual antigens was assessed and the hypothetical performance of novel antigen combinations extrapolated. Neither of the prototype devices were inferior in sensitivity or specificity to “SD BIOLINE HAT” (sensitivity 0.82±0.01, specificity 0.97±0.01, 95% CI) at the 5% margins, while one of the devices (BBI) had significantly superior sensitivity (0.88±0.03). Analysis of the performance of individual antigens was used to model new antigen combinations to be explored in development of the next generation of HAT RDTs. The modelling showed that an RDT using two recombinant antigens (rLiTat1.5 and rISG65) would give a performance similar to the best devices in this study, and would also offer the most robust performance under deteriorating field conditions. Conclusions/Significance Both “SD BIOLINE HAT” and the prototype devices performed comparably well to one another and also to the published performance range of the card agglutination test for trypanosomiasis in sensitivity and specificity. The performance of individual antigens enabled us to predict that an all-recombinant antigen RDT can be developed with an accuracy equivalent to “ SD BIOLINE HAT.” Such an RDT would have advantages in simplified manufacture, lower unit cost and assured reproducibility., Author Summary The most prevalent species of trypanosome causing human African trypanosomiasis (HAT), Trypanosoma brucei gambiense, presents a diagnostic challenge. While early diagnosis is essential for effective treatment and also to control transmission, symptoms are non-specific and parasitological diagnosis is laborious and technically difficult. Screening for HAT suspects has until now been done using the card agglutination test for trypanosomiasis (CATT), which requires a cold chain and equipment, making it difficult to deploy. Thus there is an urgent need for sensitive point of care diagnostic tests that are suitable for use in rural areas in terms of stability, simplicity and cost. We describe the evaluation of 3 rapid diagnostic tests (RDTs) for HAT based on lateral flow devices that detect antibodies against defined parasite antigens in blood samples. We demonstrate that the SD BIOLINE HAT RDT currently being deployed in HAT endemic regions, as well as two new prototype devices, are accurate in screening for HAT. By analysing the sensitivity of each of the antigens used in the devices tested, we predict that a highly sensitive RDT based on recombinant antigens can be developed. An all-recombinant antigen RDT offers significant benefits in manufacturing reproducibility and cost, and would dramatically simplify HAT diagnosis.