Use of vector control to protect people from sleeping sickness in the focus of Bonon (Côte d’Ivoire)

Background Gambian human African trypanosomiasis (gHAT) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by tsetse flies (Glossina). In Côte d’Ivoire, Bonon is the most important focus of gHAT, with 325 cases diagnosed from 2000 to 2015 and efforts against gHAT have relied largely on mass screening and treatment of human cases. We assessed whether the addition of tsetse control by deploying Tiny Targets offers benefit to sole reliance on the screen-and-treat strategy. Methodology and principal findings In 2015, we performed a census of the human population of the Bonon focus, followed by an exhaustive entomological survey at 278 sites. After a public sensitization campaign, ~2000 Tiny Targets were deployed across an area of 130 km2 in February of 2016, deployment was repeated annually in the same month of 2017 and 2018. The intervention’s impact on tsetse was evaluated using a network of 30 traps which were operated for 48 hours at three-month intervals from March 2016 to December 2018. A second comprehensive entomological survey was performed in December 2018 with traps deployed at 274 of the sites used in 2015. Sub-samples of tsetse were dissected and examined microscopically for presence of trypanosomes. The census recorded 26,697 inhabitants residing in 331 settlements. Prior to the deployment of targets, the mean catch of tsetse from the 30 monitoring traps was 12.75 tsetse/trap (5.047–32.203, 95%CI), i.e. 6.4 tsetse/trap/day. Following the deployment of Tiny Targets, mean catches ranged between 0.06 (0.016–0.260, 95%CI) and 0.55 (0.166–1.794, 95%CI) tsetse/trap, i.e. 0.03–0.28 tsetse/trap/day. During the final extensive survey performed in December 2018, 52 tsetse were caught compared to 1,909 in 2015, with 11.6% (5/43) and 23.1% (101/437) infected with Trypanosoma respectively. Conclusions The annual deployment of Tiny Targets in the gHAT focus of Bonon reduced the density of Glossina palpalis palpalis by >95%. Tiny Targets offer a powerful addition to current strategies towards eliminating gHAT from Côte d’Ivoire

Revisiting the Immune Trypanolysis Test to Optimise Epidemiological Surveillance and Control of Sleeping Sickness in West Africa

Human African trypanosomiasis (HAT) due to Trypanosoma brucei (T.b.) gambiense is usually diagnosed using two sequential steps: first the card agglutination test for trypanosomiasis (CATT) used for serological screening, followed by parasitological methods to confirm the disease. Currently, CATT will continue to be used as a test for mass screening because of its simplicity and high sensitivity; however, its performance as a tool of surveillance in areas where prevalence is low is poor because of its limited specificity. Hence in the context of HAT elimination, there is a crucial need for a better marker of contact with T.b. gambiense in humans. We evaluated here an existing highly specific serological tool, the trypanolysis test (TL). We evaluated TL in active, latent and historical HAT foci in Guinea, Côte d'Ivoire and Burkina Faso. We found that TL was a marker for exposure to T.b. gambiense. We propose that TL should be used as a surveillance tool to monitor HAT elimination

Untreated Human Infections by Trypanosoma brucei gambiense Are Not 100% Fatal

The final outcome of infection by Trypanosoma brucei gambiense, the main agent of sleeping sickness, has always been considered as invariably fatal. While scarce and old reports have mentioned cases of self-cure in untreated patients, these studies suffered from the lack of accurate diagnostic tools available at that time. Here, using the most specific and sensitive tools available to date, we report on a long-term follow-up (15 years) of a cohort of 50 human African trypanosomiasis (HAT) patients from the Ivory Coast among whom 11 refused treatment after their initial diagnosis. In 10 out of 11 subjects who continued to refuse treatment despite repeated visits, parasite clearance was observed using both microscopy and polymerase chain reaction (PCR). Most of these subjects (7/10) also displayed decreasing serological responses, becoming progressively negative to trypanosome variable antigens (LiTat 1.3, 1.5 and 1.6). Hence, in addition to the “classic” lethal outcome of HAT, we show that alternative natural progressions of HAT may occur: progression to an apparently aparasitaemic and asymptomatic infection associated with strong long-lasting serological responses and progression to an apparently spontaneous resolution of infection (with negative results in parasitological tests and PCR) associated with a progressive drop in antibody titres as observed in treated cases. While this study does not precisely estimate the frequency of the alternative courses for this infection, it is noteworthy that in the field national control programs encounter a significant proportion of subjects displaying positive serologic test results but negative results in parasitological testing. These findings demonstrate that a number of these subjects display such infection courses. From our point of view, recognising that trypanotolerance exists in humans, as is now widely accepted for animals, is a major step forward for future research in the field of HAT

Results of the follow-up of four untreated patients in the Bonon focus in 2009.

<p>All patients were positive to the CATT performed on plasma and trypanosomes were detected either in blood or lymph juice at first diagnosis.</p>1<p>CATT on plasma, considered positive (+) if CATT-P end titres ≥1/8.</p>2<p>Trypanosome in blood and/or lymph juice (+ = presence, − = absence).</p>3<p>trypanolysis test, results are given as follows: Litat 1.3/Litat 1.5/Litat 1.6 (+ = positive TL).</p

Results of the follow-up of seven untreated patients in the Sinfra focus.

<p>All patients were positive to the CATT performed on plasma and trypanosomes were detected either in blood or lymph juice when diagnosed between 1995 and 1996.</p>1<p>Results from Jamonneau et al. (2000).</p>2<p>CATT on plasma, considered positive (+) (i) in presence of a visible agglutination when performed with 5 µl of plasma (1999 and 2004) and (ii) if CATT-P end titres ≥1/8 (2009).</p>3<p>Trypanosome in blood and/or lymph fluid (+ = presence, − = absence).</p>4<p>absence of the patient.</p>5<p>trypanolysis test, results are given as follows: Litat 1.3/Litat 1.5/Litat 1.6 (+ = positive TL).</p

CATT-P and TL results of the 39 treated HAT cases followed up in 2009 in the Sinfra focus.

1<p>HAT patients diagnosed and treated in 1995/1996 as first-stage cases.</p>2<p>CATT on plasma, considered positive (+) if CATT-P end titres ≥1/8.</p>3<p>trypanolysis test, results are given as follows: Litat 1.3/Litat 1.5/Litat 1.6 (+ = positive TL).</p

“Classic” and possible alternative natural progressions of HAT.

<p>Cpl = CATT on plasma, considered positive (Cpl+) if end titres ≥1/8 TL = Trypanolysis test, considered positive (TL+) if positive to at least one variant P = Parasitological investigations in blood and/or lymph fluid (P+ = presence of trypanosome).</p

VAT-specific TL-positive profiles according to study site and HAT status.

<p>Fol/Lor/Bat  =  Folonzo, Loropéni and Batié; nb  =  number; na  =  not available; SUSP, SERO and HAT are defined in the <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000917#s2" target="_blank">Materials and Methods</a> section.</p

Study subjects according to the HAT focus and HAT status.

<p>Fol/Lor/Bat  =  Folonzo, Loropéni and Batié.</p><p>SUSP, SERO and HAT are defined in the <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000917#s2" target="_blank">Materials and Methods</a> section.</p

Results of the medical surveys: sero-prevalence and HAT prevalence.

<p>Fol/Lor/Bat  =  Folonzo, Loropéni and Batié; pos  =  positive.</p><p>CATT-P pos  =  CATT-P end titer ≥1/8.</p