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Background: The chronic form of human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense and commonly referred to as gambiense-HAT (gHAT) is endemic in 7 of Angola's 18 provinces. Major epidemics of the disease occurred in the country in the 1920s to 1940s and 1990s –mid 2000s, and current estimates are that up to a third of the country's population is at risk of infection. Whereas gHAT was first reported in Angola in 1871, control efforts did not begin until 30 years later in 1901. This case study describes the history of gHAT in Angola, outlines the policies and strategies used in its control, and the intensification efforts being made to accelerate progress towards elimination. Furthermore, it highlights factors that have contributed to recurrent outbreaks of gHAT in the country and key achievements in the push towards elimination. Methods: Literature review was conducted using online databases such as PubMed, Google Scholar, Google, WHO HAT data repository, and the African Union Inter African Bureau for Animal Resources (AU-IBAR), International Scientific Council for Trypanosomiasis Research and Control (ISCTRC) conference proceedings. Data/information not found in these databases was availed through personal communication with colleagues from Instituto de Combate e Controlo das Tripanossomiases (ICCT). The search of databases was conducted using the following terms: "human African trypanosomiasis (HAT) control/elimination in Angola," "sleeping sickness/HAT control in Angola," "HAT epidemics in Angola." Results and conclusion: Overall, the interventions put in place over the years have led to significant reduction in the number of new HAT cases reported annually, from an average of 3,496 (between 1990 and 2006) to an average of 56 cases between 2016 and 2023. This has renewed the hope of achieving elimination of gHAT as a public health problem by 2030. Author summary: Human African trypanosomiasis (HAT), also known as sleeping sickness, is a disease caused by trypanosome parasites transmitted by tsetse flies. HAT presents in 2 forms (chronic or acute) depending on the subspecies of the parasite causing the disease. Angola has the chronic form of HAT and the areas and populations at-risk of HAT are large, resulting in the country experiencing very large epidemics in the past. Through coordinated and sustained control operations, largely supported by the national government, the number of HAT cases reported annually has been bought under control, and the country is progressing towards HAT elimination. This case study is important because it highlights the strategies and policies that have led to sustainable control of HAT in Angola, and key lessons that other national HAT control programs could borrow to achieve a more sustainable and impactful disease control. Among key factors that contributed to sustainable HAT control in Angola and which other national programs could adopt are the following: (1) strong political will and government commitment to fund most HAT control activities; (2) adoption and roll-out of new technologies through the health systems; and (3) partnering with state and non-state actors to sustain control of the disease, particularly in times of internal instability. [ABSTRACT FROM AUTHOR]

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

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. Author summary: Human African tryposonomiasis (HAT), also known as sleeping sickness, is a parasitic disease with over 65 million people estimated to be living at risk of infection. Sleeping sickness consists of two stages: the first one is relatively mild but the second stage is usually fatal if untreated. The World Health Organization has targeted HAT for elimination as a public health problem by 2020 and for elimination of transmission by 2030. Regular monitoring updates indicate that 2020 elimination goals are likely to be achieved. This monitoring relies mainly on case report data that is collected through medical-based control activities—the main strategy employed so far in HAT control. This epidemiological data are also used to calibrate mathematical models that can be used to analyse current interventions and provide projections of potential intensified strategies. We investigated the role of the type and level of aggregation of this HAT case data (staging data and truncated data) on model calibrations and projections. We highlight that the lack of detailed epidemiological information, such as missing stage of disease or truncated time series data, impacts model recommendations for strategy choice: it can misrepresent the underlying HAT epidemiology (for example, the ratio of stage 1 to stage 2 cases) and increase uncertainty in predictions. Consistently including new data from control activities as well as enriching it through cross-sectional (e.g. demographic or behavioural data) and geo-located data is likely to improve modelling accuracy to support planning, monitoring and adapting HAT interventions. [ABSTRACT FROM AUTHOR]

We carried out a study to compare the performance, in terms of sensitivity and specificity, of the new SD BIOLINE® HAT rapid diagnostic test (RDT) with the card agglutination test for trypanosomiasis (CATT) for diagnosis of human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC). Participants were enrolled actively by four mobile teams, and passively at four health facilities in three provinces. Consenting participants were tested concurrently with the RDT and CATT on whole blood. Those found positive by either test were tested with CATT on serial dilutions of plasma, and with a parasitological composite reference standard (CRS). Cases were only the individuals found positive by the CRS, while controls were negative by both CATT and RDT, as well as those that were positive by CATT or RDT, but were negative by the CRS, and had no history of HAT. Over five months, 131 cases and 13,527 controls were enrolled. The sensitivity of the RDT was 92.0% (95% confidence interval (CI) = 86.1–95.5), which was significantly higher than CATT (sensitivity 69.1%; 95% CI = 60.7–76.4). The sensitivity of CATT on plasma at a dilution of 1:8 was 59.0% (95% CI = 50.2–67.2). The specificity of the RDT was 97.1% (95% CIs = 96.8–97.4) while that of CATT was 98.0% (95% CIs = 97.8, 98.2) and specificities of algorithms involving CATT at 1:8 dilution were 99.6% (95% CI = 99.5–99.7). Reproducibility of results was excellent. We concluded that an algorithm in which the SD BIOLINE® HAT RDT is used for screening is optimal for case detection in both passive and active screening settings. However, the lower specificity of the RDT compared to that of CATT would result in a larger number of false positive individuals undergoing confirmatory testing. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: As the reality of eliminating human African trypanosomiasis (HAT) by 2020 draws closer, the need to detect and identify the remaining areas of transmission increases. Here, we have explored the feasibility of using commercially available LAMP kits, designed to detect the Trypanozoon group of trypanosomes, as a xenomonitoring tool to screen tsetse flies for trypanosomes to be used in future epidemiological surveys. Methods and Findings: The DNA extraction method was simplified and worked with the LAMP kits to detect a single positive fly when pooled with 19 negative flies, and the absolute lowest limit of detection that the kits were able to work at was the equivalent of 0.1 trypanosome per ml. The DNA from Trypanosoma brucei brucei could be detected six days after the fly had taken a blood meal containing dead trypanosomes, and when confronted with a range of non-target species, from both laboratory-reared flies and wild-caught flies, the kits showed no evidence of cross-reacting. Conclusion: We have shown that it is possible to use a simplified DNA extraction method in conjunction with the pooling of tsetse flies to decrease the time it would take to screen large numbers of flies for the presence of Trypanozoon trypanosomes. The use of commercially-available LAMP kits provides a reliable and highly sensitive tool for xenomonitoring and identifying potential sleeping sickness transmission sites. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses the various aspects of human African trypanosomiasis (HAT), which is classified in the category of the most neglected tropical diseases. The author talks about the establishment of the East African Trypanosomiasis Research Organization (EATRO) to carry out research and develop technologies for effective control of trypanosomiasis. Also offered are details about trypanosomes.

A critical step before treatment of human African trypanosomiasis (HAT) is the correct staging of the disease. As late stage is established when trypanosomes cross the blood-brain barrier and invade the central nervous system, we hypothesized that matrix metalloproteinases and cell adhesion molecules could indicate, alone or in combination, the disease progression from the first to the second stage of HAT. We measured the levels of MMP-2, MMP-9, ICAM-1, VCAM-1 and E-selectin in the cerebrospinal fluid (CSF) of 63 Trypanosoma brucei gambiense-infected patients (15 stage 1 and 48 stage 2). Staging was based on counting of white blood cells (WBC) and/or parasite detection in CSF. Concentrations were obtained either by ELISA or multiplex bead suspension assays, and results were compared with three known HAT staging markers (CXCL10, CXCL8 and H-FABP). ICAM-1 and MMP-9 accurately discriminated between stage 1 and stage 2 patients with HAT with 95% sensitivity (SE) for 100% specificity (SP), which was better than CXCL10 (93% SE for 100% SP), one of the most promising known markers. Combination of ICAM-1 and MMP-9 with H-FABP provided a panel that resulted in 100% of SE and SP for staging HAT. ICAM-1 and MMP-9, alone or in combination, appeared as powerful CSF staging markers of HAT. Final validation of all newly discovered staging markers on a large multi-centric cohort including both forms of the disease as well as patients with others infections should be performed. [ABSTRACT FROM AUTHOR]