NEGLECTED TROPICAL DISEASES Human African Trypanosomiasis (HAT)

PROJECT UPDATE: Driving elimination of human African trypanosomiasis in a challenging transboundary region

February 2016

Human African trypanosomiasis (HAT), or sleeping sickness, is a 200 (7326) (7183) parasitic disease transmitted by the bite of a tsetse fly. The disease (8023) has two forms: a chronic form caused by Trypanosoma brucei (5629) 150 gambiense and an acute form caused by Trypanosoma brucei (5647) rhodesiense. Gambiense HAT accounts for more than 95% of all (5595) cases and can last for months to several years without symptoms, 100 (8162) (5983) whereas symptoms of rhodesiense HAT emerge within weeks and (3206) the disease develops rapidly. Both forms can be fatal if left untreated. 50 Sleeping sickness cases

Early diagnosis is a challenge because the chronic form of HAT 0 often shows no signs or symptoms until it is more advanced. The 2006 2007 2008 2009 2010 2011 2012 2013 2014 World Health Organization (WHO) roadmap on 10 neglected tropical Number of HAT cases reported in Kongo Central province, DRC from 2006 compared diseases, which was endorsed by the London Declaration of 2012, to the total for the country (annual national figures in parentheses). The province is a targets HAT for elimination by 2020. good candidate for HAT elimination because its HAT focus is isolated from others in the country, and a relatively small number of cases are reported annually.

The Democratic (DRC) records the highest number of HAT cases globally and accounted for 84.5% of cases reported in 2014 (n=3206). Among the provinces in DRC that are endemic for HAT, Kongo Central (formerly Bas Congo) is one of the smallest, and its HAT focus is isolated from the other foci in the country. Over the past 10 years, only a relatively small number of HAT cases have been reported annually, making it a good candidate for elimination of the disease through intensified control. The outer limits of this HAT focus extend into the neighbouring countries of and the Republic of Congo, making cross-border collaboration critical to achieving the goal of elimination.

Enhanced passive screening for HAT in Kongo Central

Armed with new diagnostic tools co-developed by FIND and partners, HAT screening in Kongo Central has been radically enhanced. HAT RDTs and trainings have been provided to 597 health facilities, which are now conducting the first stage of screening. To confirm disease in HAT suspects, 23 of these 597 facilities have been upgraded and equipped to perform parasitology, including LED fluorescence microscopy (FM), and a select five of them have been in addition equipped with LAMP. These facilities have been strategically chosen across the Kongo Central HAT focus to ensure that distances travelled by referred patients or samples for confirmation are minimised. As a consequence, the distance that a Photo J. Ndung'u / FIND referred patient has to travel has been brought down to 11.2 km, Application of blood from a suspected HAT patient to a filter paper at a while the mean distance for transporting samples for LAMP is 33 km parasitology centre in the DRC. After the sample has dried, it is put into a (see figure on p. 3). plastic pouch and sent to a LAMP centre for further testing. PROBLEM SOLUTION

Twenty-three out of 31 health zones in Kongo Central Three diagnostic tests for sleeping sickness have been province, an area of approximately 33,800 km2, are developed in collaborations between FIND, academic, endemic for HAT, with more than 4.5 million people at industrial and endemic country partners: risk of infection. In recent years, disease surveillance in this vast province has consisted of active screening using CATT by a single mobile team and passive screening at just 36 health facilities. The terrain of the province has SD BIOLINE HAT rapid diagnostic test numerous rivers and is difficult to navigate, meaning that (RDT) the mobile team cannot access most endemic villages (manufactured by Alere/Standard Diagnostics) and health facilities that offer screening are often far from the population at risk. Achieving elimination of HAT in ✓ Simple to use and store (can be Kongo Central requires a cost-effective strategy to deliver stored at 40°C for 2 years) screening services as close as possible to the villages ✓ Inexpensive (50 US cents) where people live, and harmonization of activities with ✓ Very sensitive neighbouring Angola and the Republic of Congo. x Imperfect specificity: 3 in 100 people who do not have HAT test positive for the disease, so positives must be confirmed by other tests

The SD HAT RDT requires minimal expertise and training, and can be performed by staff at the smallest health-care facilities as well as by mobile teams. The RDT kit (pictured above) contains all materials necessary to perform the test.

Primo Star iLED fluorescence microscope (LED FM) Distribution of HAT cases in the DRC 2000-2012. The transboundary (manufactured by Carl Zeiss MicroImaging) region including Kongo Central is shown by the blue circle. (Map from: Lumbala et al. Human African trypanosomiasis in the Democratic Republic of the Congo: disease distribution and risk. International Journal of Health ✓ Low power requirements Geographics 2015 14:20. DOI: 10.1186/s12942-015-0013-9. © World Health Organization/Food and Agriculture Organization of the ✓ Long-lasting light sources United Nations. Used with permission.) ✓ Slides are quick and easy to stain using acridine orange ✓ Versatile – can also be used for malaria and TB ✓ Does not require a dark room x Low sensitivity – microscopy misses many cases

With options for conventional bright field and fluorescence microscopy, the LED FM can be used to perform an extended range of parasitological confirmation tests for HAT. Low electricity requirements mean that it Photo J. Ndung'u / FIND can be powered from solar panels such as Accessibility is a major challenge in most HAT-endemic regions in DRC. these installed at Bangumi Many villages are only accessible by boat, and rivers as well as bad roads are a major hazard. health centre, in Bandundu (see photo on the right).

2 Loop-mediated isothermal amplification (LAMP) of DNA CURRENT STATUS (manufactured by Eiken Chemical Co.) Upgrading of health facilities was initiated in 2014, while implementation of the strategy started in July ✓ Highly sensitive 2015. By the end of October 2015, all 597 facilities ✓ Identifies sleeping sickness cases were participating. From July through November missed by microscopy 2015, 3,609 RDTs were performed and out of 119 ✓ Also works on blood samples (3.3%) positives, 10 (0.4%) were confirmed as cases. dried on filter paper Seven of the 10 cases were initially screened at x Requires reliable power and facilities that were not previously testing for HAT, and a reasonably well equipped lab one of the cases was from Angola. Importantly, seven of the diagnosed cases were in the early or first stage LAMP can be performed by technicians of disease, which is safer and easier to treat than the with no specialized training in late stage when the brain is affected. By comparison, molecular biology. LAMP can be in all of 2014, only 30 cases were detected in Kongo deployed at district- or microscopy- Central by passive screening using the older card level laboratories that have a reliable agglutination test for trypanosomiasis. By the time electricity supply. of this update, samples dried on filter paper from 38 RDT-positive HAT suspects had been tested using LAMP and all were negative.

Screening process

1. Patients with symptoms suggestive of HAT are first tested with a malaria RDT because the symptoms can be similar.

2. If a patient is negative for malaria (or positive for malaria but still symptomatic after malaria treatment), then a HAT RDT is performed.

3. If the HAT RDT is positive, the patient is referred to the nearest facility for parasitological confirmation, including with LED FM.

4. If found positive by microscopy, the patient is staged and treated for HAT. When a patient is negative by microscopy, further testing is required at one of the five facilities equipped to perform LAMP. If the patient is at a facility that does not have LAMP, a blood sample is dried on filter paper and transported to the nearest LAMP facility by a motorcycle belonging to the project.

5. Patients found positive by LAMP are considered as strong HAT suspects and undergo further tests by microscopy because demonstration of parasites by microscopy is required for case confirmation according to WHO guidelines. For HAT screening, 597 facilities have been equipped with HAT RDTs, 23 of these to perform parasitology, including with LED 5 facilities FM, and 5 for parasitology and RDT, LED FM LAMP. They are spread across & LAMP the Kongo Central HAT focus to minimise the distance referred patients or samples have to Negative by Median travel travel for confirmation. The map shows health facilities where parasitology 33km RDT-positive HAT suspects and cases were reported from July 18 facilities through November 2015. RDT & LED FM

Median referral Positive RDT 11.2km

574 facilities RDT only (Left) An illustration of the diagnostic pyramid for HAT being implemented in Kongo Central.

3 HIGHLIGHTS KEY RESULTS

• Project initiated in Kongo Central in 2014 and implementation of new strategy in July 2015. 3,609 people screened for HAT using RDTs • Goal: Implement a cost-effective strategy to enhance from July to November 2015. screening services close to where people live and accelerate elimination of HAT. • All sites were operational by October 2015.

facilities equipped for intensified population 10 cases of HAT confirmed. screening using simple rapid diagnostic tests 597 (RDTs), an increase from 36 sites performing older tests. of the 10 HAT cases were detected using of these facilities upgraded and also equipped 7 RDTs in facilities that were not screening 23 for parasitological confirmation of RDT-positive for HAT before. suspects, including with LED FM.

of the 10 HAT cases were in the first stage of these 23 facilities also equipped with LAMP of disease, which is good news because it is 5 for molecular testing of RDT-positive suspects 7 easier and cheaper to manage. found negative by parasitology.

CHALLENGES

Ensuring that RDT-positive suspects travel for confirmatory testing data. This will be made easier by introduction of an eHealth system is a challenge that still has to be addressed through social research of reporting using mobile phones, targeted for 2016. Furthermore, and community education. Due to the magnitude of the programme achieving and sustaining elimination of the disease requires similar in a difficult environment, successful implementation requires and harmonized activities in cross-border areas in the Republic of significant coordination efforts, and accurate and timely reporting of Congo and Angola, which have now been initiated.

FUNDING

This programme is supported and coordinated by FIND with The Belgian Technical Cooperation is supporting the national funding from the Bill & Melinda Gates Foundation, UK aid from the HAT programme of the DRC through the Institute of Tropical UK government, the German Federal Ministry of Education and Medicine (Belgium), with significant in-kind contributions by the Research through KfW and the Swiss Development Cooperation. Government of the DRC.

FURTHER INFORMATION

More information regarding the diagnosis of HAT is available at: http://www.finddx.org/programs/hat-ond/hat/

Campus Biotech Chemin des Mines 9 - 1202 Geneva - Switzerland T: +41 (0)22 710 05 90 - F: +41 (0)22 710 05 99

4