Screening For Human African Trypanosomiasis Research Articles

Conducting active screening for human African trypanosomiasis with rapid diagnostic tests: The Guinean experience (2016-2021).

Strategies to detect Human African Trypanosomiasis (HAT) cases rely on serological screening of populations exposed to trypanosomes. In Guinea, mass medical screening surveys performed with the Card Agglutination Test for Trypanosomiasis have been progressively replaced by door-to-door approaches using Rapid Diagnostic Tests (RDTs) since 2016. However, RDTs availability represents a major concern and medical teams must often adapt, even in the absence of prior RDT performance evaluation. For the last 5 years, the Guinean HAT National Control Program had to combine three different RDTs according to their availability and price: the SD Bioline HAT (not available anymore), the HAT Sero-K-SeT (most expensive), and recently the Abbott Bioline HAT 2.0 (limited field evaluation). Here, we assess the performance of these RDTs, alone or in different combinations, through the analysis of both prospective and retrospective data. A parallel assessment showed a higher positivity rate of Abbott Bioline HAT 2.0 (6.0%, n = 2,250) as compared to HAT Sero-K-SeT (1.9%), with a combined positive predictive value (PPV) of 20.0%. However, an evaluation of Abbott Bioline HAT 2.0 alone revealed a low PPV of 3.9% (n = 6,930) which was surpassed when using Abbott Bioline HAT 2.0 in first line and HAT Sero-K-SeT as a secondary test before confirmation, with a combined PPV reaching 44.4%. A retrospective evaluation of all 3 RDTs was then conducted on 189 plasma samples from the HAT-NCP biobank, confirming the higher sensitivity (94.0% [85.6-97.7%]) and lower specificity (83.6% [76.0-89.1%]) of Abbott Bioline HAT 2.0 as compared to SD Bioline HAT (Se 64.2% [52.2-74.6%]-Sp 98.4% [94.2-99.5%]) and HAT Sero-K-SeT (Se 88.1% [78.2-93.8%]-Sp 98.4% [94.2-99.5%]). A comparison of Abbott Bioline HAT 2.0 and malaria-RDT positivity rates on 479 subjects living in HAT-free malaria-endemic areas further revealed that a significantly higher proportion of subjects positive in Abbott Bioline HAT 2.0 were also positive in malaria-RDT, suggesting a possible cross-reaction of Abbott Bioline HAT 2.0 with malaria-related biological factors in about 10% of malaria cases. This would explain, at least in part, the limited specificity of Abbott Bioline HAT 2.0. Overall, Abbott Bioline HAT 2.0 seems suitable as first line RDT in combination with a second HAT RDT to prevent confirmatory lab overload and loss of suspects during referral for confirmation. A state-of-the-art prospective comparative study is further required for comparing all current and future HAT RDTs to propose an optimal combination of RDTs for door-to-door active screening.

Communities' Perception, Knowledge, and Practices Related to Human African Trypanosomiasis in the Democratic Republic of Congo.

Background: The number of human African trypanosomiasis (HAT) cases in the Democratic Republic of Congo (DRC) has significantly reduced, thanks to more effective drugs and screening tools and regular mass screening. However, this potentially jeopardizes HAT control activities, especially community engagement. Methods: We used an ecological model framework to understand how various factors shape communities’ knowledge, perceptions, and behavior in this low endemicity context. Community members, frontline health providers, and policymakers were consulted using an ethnographic approach. Results: Communities in endemic areas are knowledgeable about causes, symptoms, and treatment of HAT, but this was more limited among young people. Few are aware of new HAT treatment or screening techniques. Participation in mass screening has declined due to many factors including fear and a lack of urgency, given the low numbers of cases. Delays in seeking medical care are due to confusion of HAT symptoms with those of other diseases and belief that HAT is caused by witchcraft. Conclusions: Community members see their role more in terms of vector control than participation in screening, referral, or accepting treatment. We propose recommendations for achieving sustainable community engagement, including development of an information and communication strategy and empowerment of communities to take greater ownership of HAT control activities.

Health work and skills in the last mile of disease elimination. Experiences from sleeping sickness health workers in South Sudan and DR Congo

ABSTRACT Human African trypanosomiasis (HAT) is considered a highly promising candidate for elimination within the next decade. This paper argues that the experiential knowledge of frontline health workers will be critical to achieve this goal. Interviews are used to explore the ways in which HAT workers understand, maintain, and adjust their skills amidst global and national challenges. We contrast two cases: South Sudan where HAT expertise is scattered and has been repeatedly rebuilt, and the Democratic Republic of Congo (DRC) where specialised mobile detection teams have pro-actively tested people at risk for almost a century. We describe HAT careers where skills are built through participation in HAT technology trials and screening programmes; in the DRC expertise is also supported through formal rotations in screening teams and HAT referral centres for new health workers. As cases fade, de-skilling is a real threat as awareness of populations and authorities diminishes and previously vertical programmes evolve, re-configuring professional development and career paths and associated opportunities for HAT practice. To avoid repeating the mistakes of the 1960s, when elimination also seemed close at hand, we need to recognise that the ‘last mile’ of elimination hinges on protecting the fragile expertise of frontline health workers.

Human African trypanosomiasis (HAT) in the Republic of Congo: why the Congolese population is reluctant to screening?

human African trypanosomiasis (HAT) is a neglected tropical infection, and surveillance of the disease relies on community participation in screening. This study aimed to identify the main factors associated with low community uptake of the HAT screening in endemic districts in the Republic of Congo. a cross-sectional survey was carried out during a sensitisation campaign about HAT in the districts of Mpouya, Ngabé and Loudima, which are endemic for the disease. After signing the informed consent form, participants were organized into groups of 10 for focus group discussions (FGDs). A list of questions was used for guiding the discussion, addressing understanding of the disease and reasons for refusing screening. out of 220 recruited individuals (corresponding to 22 FGDs), 58.6% were men. The majority of the respondents described HAT as a rural disease (48.2%) or as a witchcraft (22.3%). Among the clinical signs cited by the participants, sleep disorder (40%) was the most common answer, followed by prolonged fever (19.5%) and madness (14.1%). The main reasons for non-adherence to HAT screening was the fear of lumbar puncture (45.9%) and stigmatisation (22.3%). the findings of this study suggest that more effort should be put into raising awareness of HAT and the benefits of screening amongst the Congolese population, in order to strengthen the national disease control program.

Cost of a new method of active screening for human African trypanosomiasis in the Democratic Republic of the Congo.

BackgroundHuman African trypanosomiases caused by the Trypanosoma brucei gambiense parasite is a lethal disease targeted for eradication. One of the main disease control strategies is active case-finding through outreach campaigns. In 2014, a new method for active screening was developed with mini, motorcycle-based, teams. This study compares the cost of two active case-finding approaches, namely the traditional mobile teams and mini mobile teams, in the two health districts of the Democratic Republic of the Congo.MethodsThe financial and economic costs of both approaches were estimated from a health care provider perspective. Cost and operational data were collected for 12 months for 1 traditional team and 3 mini teams. The cost per person screened and diagnosed was calculated and univariate sensitivity analysis was conducted to identify the main cost drivers.ResultsDuring the study period in total 264,630 people were screened, and 23 HAT cases detected. The cost per person screened was lower for a mini team than for a traditional team in the study setting (US$1.86 versus US$2.08). A comparable result was found in a scenario analysis, assuming both teams would operate in a similar setting, with the cost per person screened by a mini team 15% lower than the cost per person screened by a traditional team (1.86 $ vs 2.14$). The main explanations for this lower cost are that mini teams work with fewer human resources, cheaper means of transportation and do not perform the Capillary Tube Centrifugation test or card agglutination test dilutions.DiscussionActive HAT screening with mini mobile teams has a lower cost and could be a cost-effective alternative for active case-finding. Further research is needed to determine if mini mobile teams have similar or better yields than traditional mobile teams in terms of detections and cases successfully treated.

Performance evaluation of a prototype rapid diagnostic test for combined detection of gambiense human African trypanosomiasis and malaria.

BackgroundMalaria 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.MethodsBlood 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.ResultsFrozen 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).ConclusionThe 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.

Passive Screening and Diagnosis of Sleeping Sickness with New Tools in Primary Health Services: An Operational Research.

IntroductionThe integration of human African trypanosomiasis (HAT) activities into primary health services is gaining importance as a result of the decreasing incidence of HAT and the ongoing developments of new screening and diagnostic tools. In the Democratic Republic of Congo, this integration process faces multiple challenges. We initiated an operational research project to document drivers and bottlenecks of the process.MethodsThree health districts piloted the integration of HAT screening and diagnosis into primary health services. We analysed the outcome indicators of this intervention and conducted in-depth interviews with health care providers, seropositives, community health workers and HD management team members. Our thematic interview guide focused on factors facilitating and impeding the integration of HAT screening.ResultsThe study showed a HAT-RDT-positive rate of 2.2% in Yasa Bonga, 2.9% in Kongolo and 3% in Bibanga, while the proportion of reported seropositives that received confirmatory examinations was 76%, 45.6% and 68%, respectively. Qualitative analyses indicated that some seropositives were unable to access the confirmation facility. The main reasons that were given included distance, RDT rupture, lack of basic screening equipment and financial barriers (additional hospital fees not included in free treatment course), fear of lumbar puncture and the perception of HAT as a disease of supernatural origin.ConclusionPassive screening using HAT RDTs in primary health services inevitably has some limitations. However, regarding the epidemiological context and some obstacles to integrated implementation, this cannot on its own be a relevant alternative to the elimination of HAT by 2020.FundingWe acknowledge the agency that provided financial support for this study, the Belgian Development Cooperation. The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Philippe Mulenga received financial support thanks to a doctoral grant from the Belgian Development Cooperation under the FA4 agreement. Funding for the study and Rapid Service Fees was provided by the Epidemiology and Tropical Diseases Unit of the Institute of Tropical Medicine, Antwerp.

PO 8473 IMPACT OF EBOLA ON SLEEPING SICKNESS IN COASTAL GUINEA: A RETROSPECTIVE ANALYSIS (2012–2017) FROM THE GUINEAN NATIONAL CONTROL PROGRAMME

BackgroundCoastal Guinea harbours the most active human African trypanosomiasis (HAT) foci in West Africa. The Guinean government and its partners are conducting HAT control activities to reduce the burden of this neglected tropical disease and, as set-up by WHO, to eliminate it as a public health problem by 2020. Unfortunately, control efforts were deeply impaired during the Ebola outbreak that struck the country in 2014–2015. The aim of the study was to evaluate the impact of this unprecedented outbreak on HAT screening and care activities and more generally on T. brucei gambiense transmission.MethodsA retrospective analysis of the data collected by the HAT-NCP between 2012 and 2013 (pre-Ebola period) and 2014–2015 (Ebola outbreak) has shown an interruption of active HAT screening activities and a rapid decrease of passive HAT screening activities as the Ebola outbreak was spreading. During the Ebola epidemic, HAT patients were also diagnosed in a later stage of the disease and attendance to post-treatment control visits was also severely affected.ResultsOnly 59 HAT patients were diagnosed and treated during the Ebola outbreak (January 2014–October 2015) as compared to 154 before the outbreak (February 2012–December 2013). This potentially large undiagnosed human reservoir of trypanosomes may have contributed to increased transmission levels. After Guinea was declared free of Ebola virus disease, screening activities (both passive and active) were progressively resumed. In 2016 and 2017, Guinea reported 107 and 140 HAT cases, respectively (almost twice as much as during the pre-Ebola period) and became the second most affected country after the Democratic Republic of the Congo.ConclusionA major lesson taken from the Ebola outbreak is that disruption of medical care may lead to a quick HAT burst in areas of high transmission. Current HAT control measures combining screening and tsetse control interventions will help to stay on course for the elimination goal.

Cost-effectiveness of using a rapid diagnostic test to screen for human African trypanosomiasis in the Democratic Republic of the Congo.

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.

Identification of human African Trypanosomiasis foci using school-going children in post-conflict era in Nwoya District, Northern Uganda: A cross-sectional study

Background: Human African Trypanosomiasis (HAT) is fatal if untreated; the drugs to treat it are toxic making its management difficult and diagnosis complex. Nwoya district has a long history of sleeping-sickness dating back to pre-colonial times. The civil war of 1986-2008 displaced many who upon return complained of cattle and dogs dying of unknown causes alongside increased tsetse flies infestation hence, the needs for the study. Methods: We enrolled local 3,040 pupils and recorded their social-demographic characteristics and access to different domesticated animals/fowls in their homes. Screening for HAT using the card agglutination test for trypanosomiasis (CATT) was performed; positive individuals had their titres determined, followed by microscopy and loop mediated isothermal amplification analysis (LAMP). R was used for analysis where associations were sought between dependent and independent variables. Any factor with P-value <0.05 was taken as statistically significant. Results: HAT serological prevalence of 1.2% (95% CI 0.8-1.6) was obtained, 58.3% being boys while 41.7% were girls with titres ranging from 1:2 - 1:16. Two schools alone, constituted 47% of the CATT positive cases. Pupils who came from homes with dogs were more likely to be CATT/ Trypanosoma brucei gambiense positive; (adjusted odds ratio = 3.12, 95% CI 1.41-6.99 & p=0.005). Conclusions: Though no parasites were detected, with prevalence of CATT positive at 1.2%, active surveillance in the district is still recommended. CATT positive cases needs follow-ups were immune trypanolysis test done to ascertain their exposure.

Identification of human African Trypanosomiasis foci using school-going children in post-conflict era in Nwoya District, Northern Uganda: A cross-sectional study.

Background: Human African Trypanosomiasis (HAT) is fatal if untreated; the drugs to treat it are toxic making its management difficult and diagnosis complex. Nwoya district has a long history of sleeping-sickness dating back to pre-colonial times. The civil war of 1986-2008 displaced many who upon return complained of cattle and dogs dying of unknown causes alongside increased tsetse flies infestation hence, the needs for the study. Methods: We enrolled local 3,040 pupils and recorded their social-demographic characteristics and access to different domesticated animals/fowls in their homes. Screening for HAT using the card agglutination test for trypanosomiasis (CATT) was performed; positive individuals had their titres determined, followed by microscopy and loop mediated isothermal amplification analysis (LAMP). R was used for analysis where associations were sought between dependent and independent variables. Any factor with P-value <0.05 was taken as statistically significant. Results: HAT serological prevalence of 1.2% (95% CI 0.8-1.6) was obtained, 58.3% being boys while 41.7% were girls with titres ranging from 1:2 - 1:16. Two schools alone, constituted 47% of the CATT positive cases. Pupils who came from homes with dogs were more likely to be CATT/ Trypanosoma brucei gambiense positive; (adjusted odds ratio = 3.12, 95% CI 1.41-6.99 & p=0.005). Conclusions: Though no parasites were detected, with prevalence of CATT positive at 1.2%, active surveillance in the district is still recommended.CATT positive cases needs follow-ups were immune trypanolysis test done to ascertain their exposure.

Carbon-Electrode Dielectrophoresis to Concentrate Trypanosoma Brucei

Trypanosoma brucei (T. brucei) is a parasite that causes human African Trypanosomiasis (HAT), commonly known as sleeping sickness. HAT is spread via bite from a Tsetse fly or congenitally, affecting an estimated 60 million people in Sub-Saharan Africa (Chappuis et al., 2005). This translates to a disease burden of 1.78 million disability-adjusted life years (DALY) (Fèvre et al., 2008). Depending on which parasite strain is contracted, T. b. gambiense or T. b. rhodesiense, patients can live 6-7 years or die within 6 months of infection (Centers for Disease Control and Prevention, 2012). Analysis of cerebrospinal fluid and lymph nodes are conclusive diagnostic tests, but are unaffordable and inaccessible in rural, impoverished areas. In these cases, the most relevant form of screening for HAT is the Card Agglutination Trypanosomiasis Test (CATT) (Chappius et al., 2004). This serological test is inexpensive, fast, portable, easy to use, and easy to read. However, current CATTs are limited in sensitivity and specificity: it can only identify T. b. gambiense and produces false positives for other diseases like schistosomiasis and malaria in 5-20% of readings (Inojosa, 2006). The tests also must be stored at low temperatures, which may be a logistical challenge in rural Africa. Hence, there is a need for a test with improved specificity, sensitivity, and that is easily stored while retaining the low cost advantage of the CATT. We propose Dielectrophoresis (DEP) as a rapid way to agglutinate targeted T. brucei strains. DEP is an electric-field technique that can induce motion on only selected targets, which will increase the specificity of the test. We use DEP to rapidly segregate T. brucei from its surroundings and agglutinate it on specific spots to facilitate its detection. To this end, we use microelectrodes made of either titanium or carbon. In particular, we postulate the use of carbon electrodes to enable DEP of T. brucei and thus inexpensive, rapid and specific agglutination assays. The experimental setup includes a microfluidics chip featuring multiple rows of intercalated carbon or titanium electrodes (Martinez-Duarte, 2011). Experimental samples of the animal strain T. brucei brucei were pipetted onto a single electrode array, which was polarized using sinusoidal signals with frequencies between 1kHz to 10 MHz at 1-10 Vpp. The array was monitored to characterize the movement of the parasite around the electrodes. Images taken of the experiments were analyzed to assess the velocity of attachment to the electrode array. Our initial results with both titanium and carbon electrode arrays showed parasite attachment in the range 750 kHz to 2 MHz. By implementing numerical modeling of the electric field of the device, the electric field gradient was simulated as strongest along the curve of the semicircle. This simulation corresponds to the observed location of attraction. Ongoing work is to further characterize specificity of T. brucei movement and to investigate new carbon electrode geometries that will increase the speed of parasitic attachment. Our goal is to eventually create a DEP device with an operational protocol similar to that currently used. We aim to create an inexpensive DEP device that only require batteries for operation. References Chappius, F, et al. “Card agglutination test for trypanosomiasis (CATT) end-Dilution titer and cerebrospinal fluid cell count as predictors of human African Trypanosomiasis (Trypanosoma brucei gambiense) among serologically suspected individuals in southern Sudan.” The American Journal of Tropical Medicine and Hygiene, vol. 71, no. 3, 2004, 313–317. Chappuis, F., et al. “Options for Field Diagnosis of Human African Trypanosomiasis.” Clinical Microbiology Reviews, vol. 18, no. 1, Jan. 2005, pp. 133–146., doi:10.1128/cmr.18.1.133-146.2005. Fèvre, Eric M., et al. “The Burden of Human African Trypanosomiasis.” PLoS Neglected Tropical Diseases, vol. 2, no. 12, 2008, doi:10.1371/journal.pntd.0000333. Inojosa, W. O. “Diagnosing human African trypanosomiasis in Angola using a card agglutination test: observational study of active and passive case finding strategies.” BMJ, vol. 332, 7556, 2006, pp. 1479–1484., doi:10.1136/bmj.38859.531354.7c. Martinez-Duarte, Rodrigo, et al. “A novel approach to dielectrophoresis using carbon electrodes.” Electrophoresis, vol. 32, no. 17, 2011, pp. 2385–2392., doi:10.1002/elps.201100059. “Parasites - African Trypanosomiasis” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 29 Aug. 2012, www.cdc.gov/parasites/sleepingsickness/disease.html. Accessed 15 Nov. 2017.

Impact of the Ebola outbreak on Trypanosoma brucei gambiense infection medical activities in coastal Guinea, 2014-2015: A retrospective analysis from the Guinean national Human African Trypanosomiasis control program.

BackgroundThe 2014–2015 Ebola outbreak massively hit Guinea. The coastal districts of Boffa, Dubreka and Forecariah, three major foci of Human African Trypanosomiasis (HAT), were particularly affected. We aimed to assess the impact of this epidemic on sleeping sickness screening and caring activities.Methodology/Principal findingsWe used preexisting data from the Guinean sleeping sickness control program, collected between 2012 and 2015. We described monthly: the number of persons (i) screened actively; (ii) or passively; (iii) treated for HAT; (iv) attending post-treatment follow-up visits. We compared clinical data, treatment characteristics and Disability Adjusted Life-Years (DALYs) before (February 2012 to December 2013) and during (January 2014 to October 2015) the Ebola outbreak period according to available data. Whereas 32,221 persons were actively screened from February 2012 to December 2013, before the official declaration of the first Ebola case in Guinea, no active screening campaigns could be performed during the Ebola outbreak. Following the reinforcement and extension of HAT passive surveillance system early in 2014, the number of persons tested passively by month increased from 7 to 286 between April and September 2014 and then abruptly decreased to 180 until January 2015 and to none after March 2015. 213 patients initiated HAT treatment, 154 (72%) before Ebola and 59 (28%) during the Ebola outbreak. Those initiating HAT therapy during Ebola outbreak were recruited through passive screening and diagnosed at a later stage 2 of the disease (96% vs. 55% before Ebola, p<0.0001). The proportion of patients attending the 3 months and 6 months post-treatment follow-up visits decreased from 44% to 10% (p <0.0001) and from 16% to 3% (p = 0.017) respectively. The DALYs generated before the Ebola outbreak were estimated to 48.7 (46.7–51.5) and increased up to 168.7 (162.7–174.7), 284.9 (277.1–292.8) and 466.3 (455.7–477.0) during Ebola assuming case fatality rates of 2%, 5% and 10% respectively among under-reported HAT cases.Conclusions/SignificanceThe 2014–2015 Ebola outbreak deeply impacted HAT screening activities in Guinea. Active screening campaigns were stopped. Passive screening dramatically decreased during the Ebola period, but trends could not be compared with pre-Ebola period (data not available). Few patients were diagnosed with more advanced HAT during the Ebola period and retention rates in follow-up were lowered. The drop in newly diagnosed HAT cases during Ebola epidemic is unlikely due to a fall in HAT incidence. Even if we were unable to demonstrate it directly, it is much more probably the consequence of hampered screening activities and of the fear of the population on subsequent confirmation and linkage to care. Reinforced program monitoring, alternative control strategies and sustainable financial and human resources allocation are mandatory during post Ebola period to reduce HAT burden in Guinea.

Predicting the Impact of Intervention Strategies for Sleeping Sickness in Two High-Endemicity Health Zones of the Democratic Republic of Congo.

Two goals have been set for Gambian human African trypanosomiasis (HAT), the first is to achieve elimination as a public health problem in 90% of foci by 2020, and the second is to achieve zero transmission globally by 2030. It remains unclear if certain HAT hotspots could achieve elimination as a public health problem by 2020 and, of greater concern, it appears that current interventions to control HAT in these areas may not be sufficient to achieve zero transmission by 2030. A mathematical model of disease dynamics was used to assess the potential impact of changing the intervention strategy in two high-endemicity health zones of Kwilu province, Democratic Republic of Congo. Six key strategies and twelve variations were considered which covered a range of recruitment strategies for screening and vector control. It was found that effectiveness of HAT screening could be improved by increasing effort to recruit high-risk groups for screening. Furthermore, seven proposed strategies which included vector control were predicted to be sufficient to achieve an incidence of less than 1 reported case per 10,000 people by 2020 in the study region. All vector control strategies simulated reduced transmission enough to meet the 2030 goal, even if vector control was only moderately effective (60% tsetse population reduction). At this level of control the full elimination threshold was expected to be met within six years following the start of the change in strategy and over 6000 additional cases would be averted between 2017 and 2030 compared to current screening alone. It is recommended that a two-pronged strategy including both enhanced active screening and tsetse control is implemented in this region and in other persistent HAT foci to ensure the success of the control programme and meet the 2030 elimination goal for HAT.

From health advice to taboo: community perspectives on the treatment of sleeping sickness in the Democratic Republic of Congo, a qualitative study.

BackgroundSocio-cultural and economic factors constitute real barriers for uptake of screening and treatment of Human African Trypanosomiasis (HAT) in the Democratic Republic of Congo (DRC). Better understanding and addressing these barriers may enhance the effectiveness of HAT control.MethodsWe performed a qualitative study consisting of semi-structured interviews and focus group discussions in the Bandundu and Kasaï Oriental provinces, two provinces lagging behind in the HAT elimination effort. Our study population included current and former HAT patients, as well as healthcare providers and program managers of the national HAT control program. All interviews and discussions were voice recorded on a digital device and data were analysed with the ATLAS.ti software.FindingsHealth workers and community members quoted a number of prohibitions that have to be respected for six months after HAT treatment: no work, no sexual intercourse, no hot food, not walking in the sun. Violating these restrictions is believed to cause serious, and sometimes deadly, complications. These strong prohibitions are well-known by the community and lead some people to avoid HAT screening campaigns, for fear of having to observe such taboos in case of diagnosis.DiscussionThe restrictions originally aimed to mitigate the severe adverse effects of the melarsoprol regimen, but are not evidence-based and became obsolete with the new safer drugs. Correct health information regarding HAT treatment is essential. Health providers should address the perspective of the community in a constant dialogue to keep abreast of unintended transformations of meaning.

Human African Trypanosomiasis Diagnosis in First-Line Health Services of Endemic Countries, a Systematic Review

While the incidence of Human African Trypanosomiasis (HAT) is decreasing, the control approach is shifting from active population screening by mobile teams to passive case detection in primary care centers. We conducted a systematic review of the literature between 1970 and 2011 to assess which diagnostic tools are most suitable for use in first-line health facilities in endemic countries. Our search retrieved 16 different screening and confirmation tests for HAT. The thermostable format of the Card Agglutination Test for Trypanosomiasis (CATT test) was the most appropriate screening test. Lateral flow antibody detection tests could become alternative screening tests in the near future. Confirmation of HAT diagnosis still depends on visualizing the parasite in direct microscopy. All other currently available confirmation tests are either technically too demanding and/or lack sensitivity and thus rather inappropriate for use at health center level. Novel applications of molecular tests may have potential for use at district hospital level.

The Human African Trypanosomiasis Control and Surveillance Programme of the World Health Organization 2000–2009: The Way Forward

One century ago human African trypanosomiasis (HAT), also known as sleeping sickness, was believed to curb the development of colonial territories. As soon as the cause of the disease was clearly identified, colonial authorities established extensive control operations, fearing an unpopulated continent and a shortage of human labour to exploit natural resources. Systematic screening, treatment, and patient follow-up was established in western and central Africa for the gambiense form of the disease while, animal reservoir and vector control was mainly implemented in eastern and southern Africa for the rhodesiense form. By the 1960s, transmission was practically interrupted in all endemic areas, providing evidence that the elimination of the disease as a public health problem was feasible and could be achieved with basic tools. Thereafter, the rarity of cases led to a loss of interest in sustained surveillance, and the risk of re-emergence of the disease was overlooked. Thus in the 1980s the disease re-emerged. By the 1990s, flareups were observed throughout past endemic areas, leading to a worrisome increase in the number of reported cases. At this time, nongovernmental organizations (NGOs) played a crucial role in the control of HAT. However, their interventions were mainly focused on remote and insecure areas. As emergency operators, their policy understandably excluded support to National Sleeping Sickness Control Programmes (NSSCPs), which resulted in (i) the establishment of substitute HAT control systems (ii), the maintenance of a large part of the population at risk out of the umbrella of NGO projects, and (iii) the difficulty for national programmes to sustain control achievements after the NGOs’ withdrawal. Concurrently, bilateral cooperation continued to support NSSCPs in some historically linked countries. Concerning HAT screening, the card agglutination trypanosomiasis test (CATT) for serological screening of populations at risk of HAT gambiense was developed during the 1970s [1], but its large-scale production encountered many problems, hindering its availability [2]; in addition, production of anti-trypanosomal drugs was seriously threatened due to the lower economic return for manufacturers. Research for new diagnostic tools and drugs was scarce [3]. Only eflornithine, initially developed for cancer treatment, was finally registered for the treatment of the gambiense form of the disease in 1990 [4]. But its cost and complex distribution and administration requirements made it inappropriate for the under-equipped peripheral health services in remote rural areas where HAT was prevalent. Only some well-funded NGOs were able to afford the cost of eflornithine treatment. During the 1990s, security constraints due to civil wars and social upheavals complicated HAT control by preventing access to a large number of HAT-endemic areas, leading to difficulties in reaching a large number of affected populations and consequently to a considerable lack of epidemiological information. The World Health Organization (WHO) Expert Committee on HAT Control and Surveillance held in 1995, in consideration of the huge uncertainties between the reported cases and the factual field situation, estimated that the true number of cases was at least 10 times more than reported. Thus from the 30,000 reported cases annually, it was estimated that some 300,000 infected individuals remained ignored in the field [5]. In 1997, the 50th World Health Assembly expressed its concerns about the major recrudescence of cases by adopting a resolution to raise awareness and national and international interest [6]. Subsequently, WHO enhanced its coordinating role and promoted networking with partners, developing a strong advocacy and awareness campaign. As a result, the private sector recognized its responsibility, which led Aventis Pharma and Bayer Health Care to grant in 2001 and 2002 a substantial support to WHO for the control and surveillance of HAT. This support included HAT drug donation and financial contributions that allowed WHO to strengthen its support to diseaseendemic countries (DECs). The importance of the various components of the epidemiology of trypanosomiasis (human, animal, vector control, agricultural activity, and livestock production) and their impact on the development of rural Africa led WHO, in 1995, to promote together with the Food and Agriculture Organization (FAO), the International Atomic Energy Agency (IAEA), and the African Union InterAfrican Bureau for Animal Resources (AUIBAR), an inter-sectoral initiative that ultimately became, in 1997, the Programme Against African Trypanosomiasis (PAAT, http://www.fao.org/ag/againfo/ programmes/en/paat/disease.html). In parallel, African heads of state and governments established during the Afri-

A new format of the CATT test for the detection of Human African Trypanosomiasis, designed for use in peripheral health facilities

To test the reproducibility and thermostability of a new format of the Card-Agglutination Test for Trypanosomiasis (CATT) test for Human African Trypanosomiasis (HAT), designed for use at primary health care facility level in endemic countries. A population of 4217 from highly endemic villages was screened using the existing format of the CATT test (CATT-R250) on whole blood. All those testing positive (220) and a random sample of negatives (555) were retested in the field with the new format (CATT-D10). Inter-format reproducibility was assessed by calculating kappa. All samples testing positive on whole blood with either method were further evaluated in Belgium by CATT titration of serum by two observers, using both old and new format. CATT-D10 test kits were incubated under four temperature regimens (4, 37, 45 degrees C and fluctuating) with regular assessments of reactivity over 18 months. Inter-format reproducibility of CATT-D10 vs. CATT-R250 on whole blood performed by laboratory technicians in the field was excellent with kappa values of 0.83-0.89. Both inter- and intra-format reproducibility assessed by CATT titration were excellent, with 96.5-100% of all differences observed falling within the limits of +/-1 titration step. After 18 months, reactivity of test kits incubated under all four temperature regimens was still well above the minimum threshold considered acceptable. The CATT-D10 is thermostable and can be used interchangeably with the old format of the CATT test. It is highly suitable for use in peripheral health facilities in HAT-endemic countries.

Drug toxicity and cost as barriers to community participation in HAT control in the Democratic Republic of Congo

Active case-finding programmes by mobile teams are the cornerstone of West African Human African Trypanosomiasis (HAT) control. Low attendance rates of screening and low uptake of treatment after diagnosis are major problems. The objectives of this survey were to explore community perception of HAT, to assess acceptability of control activities and to identify barriers amenable to intervention. In September 2004, we conducted 33 focus group discussions with beneficiaries of the HAT control programme among various ethnic groups in two ecological settings (savannah and fluvial) of the Democratic Republic of Congo. The population had a very detailed knowledge and understanding of HAT transmission, utility of screening, symptoms and treatment. Melarsoprol treatment was feared for its side effects. The sudden death of previously asymptomatic people during treatment was attributed to witchcraft, to which one becomes more vulnerable when the diagnosis is disclosed in public. Lack of confidentiality was also a problem because HAT carries a stigma as a mental disease. Lumbar punctures, especially when performed in public, were disliked but less feared. Financial barriers were a major obstacle for many patients. Less toxic drugs, lowering financial barriers and improving confidentiality would have considerable impact on the participation in population screening for HAT.

Efficience de différentes stratégies de détection de la Trypanosomiase Humaine Africaine àT. b. gambiense

Population screening for human African trypanosomiasis (HAT) is often based on a combination of two screening tests: lymph node palpation (LN) and card agglutination test for trypanosomiasis (CATT). This decision analysis compared the efficiency of three alternative detection strategies: screening by LN only, CATT only and their combination (LN and CATT). An HAT detection strategy was defined as the sequence of screening and confirmation. Efficacy was evaluated in terms of lives saved. The cost of screening and confirmation tests was estimated in US$. The different parameters in the decision tree were based on published literature and observations of the HAT control programme in the Democratic Republic of Congo. A sensitivity analysis was carried out on those parameters subject to uncertainty. The cost-effectiveness of a detection strategy based on CATT was US $125 per life saved, compared with US $517 for LN and US $452 for the combined. Marginal cost to add LN to CATT only was between US $1225 and US $5000 per life saved. Sensitivity analysis shows that these results are robust to variation. The CATT strategy was the most efficient. None of the strategies was able to avoid more than 60% of HAT deaths. This moderate efficacy is due to the low sensitivity of the confirmatory (diagnostic) tests. Substantial efficiency gains can be obtained by adopting a CATT only strategy and resources can be better allocated to more sensitive confirmatory tests or to increasing the coverage of populations at risk.