HAT (sleeping sickness) is targeted by WHO for elimination by 2030. The highest prevalence is found in DRC: ~84.5% of global cases were reported there in 2014 (n=3206). Among the endemic provinces in DRC, Kongo Central is one of the smallest. Concentration of HAT cases in Kongo Central extends into neighbouring Angola and RoC, making cross-border collaboration critical for elimination. Since 2014, the three countries have been implementing a project supported and coordinated by the Foundation for Innovative New Diagnostics (FIND), involving characterization of health facilities, capacity building, health facility upgrades, and introduction of novel screening and diagnostic tools.
In the challenging transboundary region of Kongo Central, remote and hard-to-reach populations are often unable to get a reliable diagnosis of HAT, one of the neglected tropical diseases targeted by SDG3. Strengthening diagnostic capacity in three neighbouring countries that share an area of disease concentration (DRC, RoC and Angola) has had a significant impact on disease control, acceleration of HAT elimination, and prevention.
The project was designed to contribute directly to SDG target 3.3.5. Not only are we within reach of sustainable HAT elimination within the SDG 2030 timeframe, we are also on track to hit the WHO interim target of eliminating HAT as a public health problem by 2020.
Work also aligns with SDG target 17.6. The transboundary nature of the project, with training conducted by experts from Makerere University, Uganda, alongside local experts in DRC, is a prime example of South–South and regional cooperation on access to science, technology and innovation, enhancing knowledge sharing on mutually agreed terms.
The project uses a diagnostic algorithm that includes initial testing of patients suspected of having HAT with a rapid diagnostic test (RDT). If the sample is positive, they are referred for confirmatory testing by microscopy. Should a patient be found HAT positive with an RDT but negative by microscopy, a blood sample is dried on a filter paper and transported by motorcycle to a central laboratory for further testing using a molecular test known as LAMP (loop-mediated isothermal amplification). If the LAMP test is positive, the patient is considered a “strong suspect”, and microscopy is repeated. This robust algorithm ensures that no patient goes undiagnosed.
Due to the scale of the programme in a difficult environment, successful implementation requires significant coordination efforts as well as accurate and timely reporting of data. Following a positive RDT result, patients need to travel for confirmatory testing, so coordination between health facilities is critical to ensure follow up.
A key distinguishing feature of the project is the use of a novel RDT, which was co-developed by FIND. HAT RDTs are carried out like pregnancy tests but use a finger-prick blood sample; they are easy to deploy and use in any facility where testing for malaria is conducted (ruling out malaria is also important as symptoms can be similar to those of HAT). Because of this, a person infected with HAT is likely to be tested for the disease the very first time they seek care in a public facility – critical as early diagnosis enables the person to receive treatment before the disease progresses into the brain.
It is cheaper to treat and easier to manage HAT during the early stages of the disease, so finding patients early by bringing screening services closer to where they live is not only good for patients, it is also cost-effective.
This project is supported and coordinated by FIND with funding from the Bill & Melinda Gates Foundation, UK aid from the UK government, the German Federal Ministry of Education and Research through KfW and the Swiss Development Cooperation. The Belgian Technical Cooperation is supporting the national HAT programme of the DRC through the Institute of Tropical Medicine (Belgium), with significant in-kind contributions by the Government of the DRC. Key implementing partners included national HAT control programmes of the DRC, RoC and Angola. Technical partners include Institut National de Recherche Biomédicale in Kinshasa, supported by experts from Makerere University, Uganda.
In the Kongo Central (DRC) region, the project was initiated in 2014 with the characterization of 600 health facilities in the province including training of staff on the selected diagnostic algorithm. Of these, 18 were upgraded to perform confirmatory diagnosis of HAT by microscopy, and an additional 5 to perform both microscopy and the molecular test LAMP. Intensified passive screening was initiated in August 2015 and supplemented with targeted reactive screening – mobile screening teams visited villages that reported cases. A small microscopy team was also sent to actively search for RDT positive patients who did not present themselves for confirmation, and test them on the spot. This brought the number of HAT cases identified during Phase 1 to 136 – the majority of which were in the early stage of disease. This was a clear demonstration that the strategy resulted in early detection of cases.
The data generated in Phase 1 were used to improve the efficiency of the project, by scaling down the number of HAT screening facilities in regions where cases had not been reported over long periods, and to intensify activities in those regions where transmission was considered to be ongoing. This exercise led to a 75% reduction in the number of participating facilities, with 123 facilities screening for HAT using RDTs, 10 using RDTs and performing microscopy, and 4 testing patients with RDTs, microscopy and LAMP.
A further 4 facilities were retained as sentinel sites in regions where scaling down had taken place. This reduced the number of facilities screening for HAT during Phase 2 to 141. The total number of identified cases dropped to 43 in Phase 2.
In RoC, the PNLTHA (Programme National de Lutte contre la Trypanosomiase Humaine Africaine) initiated activities in 2015. After characterization of health facilities, staff from PNLTHA were trained on a new HAT diagnostic algorithm at INRB in DRC. Three facilities were equipped to perform confirmatory testing by microscopy, and one of them to also perform LAMP. The HAT diagnostic algorithm was initiated in 40 health facilities in the region bordering DRC and Angola.
In Angola, initial activities were carried out from October 2016 to June 2017 in the provinces of Cabinda and Zaire – no HAT case was identified. From July 2017 to June 2018, HAT screening was expanded to Uige and Bengo provinces. These activities confirmed the reported absence of disease in Cabinda province.
The project is monitored through review of monthly updates that each country submits to FIND. In addition, a FIND consultant based in Kinshasa maintains regular telephone contacts with programme managers in all three countries, and makes 1-week visits to each of them every 3 months. A FIND project manager also conducts field assessment visits to each country at least twice a year.
In Kongo Central (DRC), during Phase 1 of the project (August 2015 to December 2016), passive screening for HAT was carried out on 45,299 suspected patients and 81 cases were identified. Of these, 53 (65.4%) were in the early stage of the disease. Nearly half of them (39 cases; 48.1%) were referred from RDT facilities that were not screening for HAT before the project started. Reactive screening was carried out on 30,312 people, with 55 cases identified. Of these, 50 (90.9%) were in the early stage of the disease. This brought the number of HAT cases identified during Phase 1 to 136, of which three quarters (103; 75.7%) were in the early stage.
The high number of early-stage cases was also an indication that these were recent infections, meaning that transmission of the disease was ongoing in the province. During the same period, 9 more cases were identified by PNLTHA during their routine activities, bringing the total number of cases during Phase 1 to 145.
During Phase 2 of the project, passive screening of 25,512 patients identified 34 HAT cases, 13 of which were early stage. An additional 9 cases (2 being early stage) were identified by PNLTHA, bringing the total number of cases during Phase 2 to 43. The decreasing proportion of early-stage cases during Phase 2 was a strong indicator that transmission of the disease was declining.
Based on an analysis of the data from Phases 1 and 2, the number of participating facilities in Phase 3 was scaled back to 61. Selection of facilities was done in consultation with PNLTHA DRC after a number of considerations, and ensured that the majority of the at-risk population was within 20km of a facility that was screening for HAT. Preliminary results of the first 6 months of Phase 3 show that the number of HAT cases in Kongo Central province has continued to decline.
In RoC, in 2016, the new HAT diagnostic algorithm was initiated in 54 health facilities. However, soon after initiation of activities, insecurity in Bouenza Province made it difficult to implement activities. Fourteen of the facilities were rendered non-functional while 40 could not be accessed due to insecurity on the roads.
In Angola, people with a positive RDT result continue to be identified although no cases have been confirmed. Two cases were found in Zaire province during Phase 2 of the project, and RDT positive suspects continued to be identified. Reactive screening of 3,738 people using CATT (card agglutination test for trypanosomiasis) in villages where one of the HAT cases was found, identified 79 (2.1%) suspected cases, two of which were confirmed to be HAT.
Use of the RDTs co-developed by FIND radically enhanced HAT screening in Kongo Central. Administering the test requires minimal expertise and training, and can be performed by staff at the smallest healthcare facilities where malaria diagnosis is carried out, as well as by mobile teams. LAMP can be performed by technicians with no specialized training in molecular biology, and be deployed at any district- or microscopy-level laboratory with a reliable electricity supply.
In addition to advanced diagnostics contributing to the success of the project, the willingness and desire of the Ministries of Health from the three countries to work collaboratively together to eliminate HAT in a challenging transboundary region was essential.
A transboundary meeting is held once a year to review progress, share experiences and harmonize activities across the countries. Meeting participants come from the three implementing countries including key stakeholders.
From 2019 onwards, overall coordination of the project will be taken over by the Institute of Tropical Medicine (ITM), Belgium. Day-to-day management will continue to be done by PNLTHA, with some ongoing support from the FIND consultant based in Kinshasa.
The project was designed to be both sustainable and replicable. The project has been cost-effective from the beginning and has demonstrated how limited resources along with knowledge transfer between countries can contribute to both of the above. The ability to scale down the number of facilities screening for the disease was demonstrated while maintaining overall surveillance which shows that the burden of sustaining it decreases with time.
Other African countries including Uganda, Chad and Guinea have adopted a similar approach towards HAT elimination, albeit integrated with control of the tsetse fly vectors of the disease. Uganda is on the brink of achieving elimination, with one indigenous case reported since July 2014. RDTs are now being used for case finding and surveillance in 16 sub-Saharan African countries.
By expanding passive screening to cover the entire province using the existing healthcare system, we are ensuring that the entire at-risk population has access to screening for HAT. The only other way that we believe this could be achieved is through expansion of active screening using a vehicle-based mobile team, which would need a prohibitively high investment (a conservative estimate of between US$1m and US$2m per year), with major logistical challenges. We also found that passive screening was more effective at reaching individuals at greatest risk of infection that are often missed by active screening.
Early diagnosis of HAT is critical: advanced disease requires complicated and risky treatment procedures but will ultimately lead to death in the absence of treatment. However in the early stage of illness, the disease causes non-specific symptoms and generally goes undiagnosed. It is therefore critical that countries have the facilities in place for the early detection of HAT. The longer an infected person remains undetected and without treatment, the higher the chances that he/she could become a source of infection to others. Without breaking transmission, elimination is in jeopardy.
The diagnostic facilities were strategically chosen across Kongo Central to minimize required travel distances: a referred patient had to travel a maximum of 11.2km, while the mean distance for transporting samples for LAMP testing was 33km.
Due to the scale of the programme in a difficult environment, successful implementation requires significant coordination efforts, and accurate and timely reporting of data. Coordination between health facilities is critical to ensure follow up, ensuring that people with a positive RDT result do indeed travel for confirmatory testing must be further addressed through social research and community education.
The project harnessed new technologies to bring diagnostic and screening services closer to patients – and this approach has proved to be instrumental in HAT elimination efforts in support of SDG targets. A remarkable 70% reduction in cases was seen between Phase 1 and Phase 2 in Kongo Central.
The project will also leave a legacy – beyond supporting HAT elimination – of stronger health systems and processes, including procurement of laboratory equipment and consumables, training of personnel, quality assurance and sensitization of communities.
Cost-effectiveness of using a rapid diagnostic test to screen for human African trypanosomiasis in the Democratic Republic of the Congo
Performance of the SD BIOLINE® HAT rapid test in various diagnostic algorithms for gambiense human African trypanosomiasis in the Democratic Republic of the Congo