[show abstract][hide abstract] ABSTRACT: Human African Trypanosomiasis (HAT) in West Africa is a lethal, neglected disease caused by Trypanosoma brucei gambiense transmitted by the tsetse Glossina palpalis gambiensis. Although the littoral part of Guinea with its typical mangrove habitat is the most prevalent area in West Africa, very few data are available on the epidemiology of the disease in such biotopes. As part of a HAT elimination project in Guinea, we carried a cross-sectional study of the distribution and abundance of people, livestock, tsetse and trypanosomes in the focus of Boffa. An exhaustive census of the human population was done, together with spatial mapping of the area. Entomological data were collected, a human medical survey was organized together with a survey in domestic animals. In total, 45 HAT cases were detected out of 14445 people who attended the survey, these latter representing 50.9% of the total population. Potential additional carriers of T. b. gambiense were also identified by the trypanolysis test (14 human subjects and two domestic animals). No trypanosome pathogenic to animals were found, neither in the 874 tsetse dissected nor in the 300 domestic animals sampled. High densities of tsetse were found in places frequented by humans, such as pirogue jetties, narrow mangrove channels and watering points. The prevalence of T. b. gambiense in humans, combined to low attendance of the population at risk to medical surveys, and to an additional proportion of human and animal carriers of T. b. gambiense who are not treated, highlights the limits of strategies targeting HAT patients only. In order to stop T. b. gambiense transmission, vector control should be added to the current strategy of case detection and treatment. Such an integrated strategy will combine medical surveillance to find and treat cases, and vector control activities to protect people from the infective bites of tsetse.
[show abstract][hide abstract] ABSTRACT: Most African trypanosome species are sensitive to trypanolytic factors (TLFs) present in human serum. Trypanosome lysis was demonstrated to be associated with apolipoprotein L-I (APOL1). Trypanosoma brucei (T. b.) gambiense and Trypanosoma brucei rhodesiense, the two human infective trypanosome species, have both developed distinct resistance mechanisms to APOL1 mediated lysis. Whereas T. b. rhodesiense resistance is linked with the expression of the serum resistance associated (SRA) protein that interacts with APOL1 inside the parasite lysosome, inhibiting its lytic action; T. b. gambiense resistance is rather controlled by a reduced expression of the parasite HpHb receptor, limiting APOL1 absorption by trypanosomes. Based on this last observation we hypothesised that variation in the host APOL1 environment could significantly alter T. b. gambiense growth and thus resistance/susceptibility to sleeping sickness. To test this hypothesis, we have measured blood APOL1 relative expression in HAT patients, uninfected endemic controls and serologically positive subjects (SERO TL(+)) that are suspected to control infection to parasitological levels that are undetectable by the available test used in the field. All RNA samples were obtained from medical surveys led in the HAT mangrove foci of Coastal Guinea. Results indicate that APOL1 expression is a complex trait dependant on a variety of factors that need to be taken into account in the analysis. Nevertheless, multivariate analysis showed that APOL1 expression levels were significantly higher in both HAT and SERO TL(+) subject as compared to endemic controls (p=0.006). This result suggests that APOL1 expression is likely induced by T. b. gambiense, but is not related to resistance/susceptibility in its human host.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 06/2012; 12(7):1519-23. · 3.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Human African trypanosomiasis (HAT) or sleeping sickness is a major public health problem in sub-Saharan Africa and is due to the kinetoplastid parasite Trypanosoma brucei gambiense in West and Central Africa. The exact role of multiple infections, the basis of clinical diversity observed in patients and the determinism that leads trypanosomes into different body fluids of the host remain opened questions to date. In this paper we investigate, in three Guinean foci, whether strains found in blood, lymph or cerebrospinal fluid (CSF) or in patients at different phase of HAT (phase 1, early phase 2 and late phase 2) are representative of the focus they belong to. Amplifications of parasites directly from body fluids led to substantial amounts of allelic drop outs, especially so for blood and CSF samples, which required data recoding of all homozygous sites into missing data. While controlling for geography, date of sampling and patient's phase of the disease, we found no effect of body fluids in the genetic structure of T. b. gambiense despite the presence of mixed infections. On the contrary, we found that the strains found in patients in different phase of the disease differed genetically, with early phase patients being more likely to be infected with more recent strains than patients at a more advanced phase of the disease. Thus, the combination of date of sampling and patient's status represents a parameter to be controlled for in population genetic structure analyses. Additional studies will also be required to explore further the phenomenon of mixed infections and its consequences.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 07/2011; 11(5):1129-35. · 3.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: At a time when human African trypanosomiasis (HAT) elimination again seems a reachable goal in many parts of sub-Saharan Africa, it is becoming increasingly important to characterise the factors involved in disease resurgence or maintenance to develop sustainable control strategies. In this study conducted in the Forecariah mangrove focus in Guinea, HAT patients and serological suspects (SERO) were identified through mass screening of the population with the Card Agglutination Test for Trypanosomiasis (CATT) and were followed up for up to 2 years. Analysis of the samples collected during the follow-up of HAT patients and SERO was performed with PCR (TBR1/TBR2) and the trypanolysis serological test (TL) in order to clarify the role played by these individuals in the epidemiology of HAT. PCR positivity was higher in TL⁺ than in SERO TL⁻ (50% vs. 18%, respectively). Whereas CATT plasma titres decreased both in treated HAT patients and SERO TL⁻, SERO TL⁺ maintained high CATT titres. Four out of 17 SERO TL⁺ developed HAT during the study. These results strongly suggest that SERO TL⁺ individuals are asymptomatic carriers. In the context where disease prevalence is sufficiently low, treating SERO TL⁺ individual may thus be of crucial importance in order to cut transmission.
Microbes and Infection 05/2011; 13(11):943-52. · 2.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: To provide a better understanding of sleeping sickness transmission and spread in mangrove areas to optimize its control.
In the Forecariah mangrove area, Guinea, 19 sleeping sickness cases and 19 matched controls were followed up in their living areas (at home, in fields and at water points). All occupational sites and pathways were mapped and then placed in their environmental context.
The sleeping sickness cases displayed a significantly broader and more diverse spatial occupation than the controls. They covered double the daily walking distances of controls and had on average two more occupational sites, most of which were located in mangrove forests. Activities with a higher transmission risk (rice culture, attendance of pirogue jetties) were identified as well as high-risk areas and pathways.
An entomological control strategy targeting transmission risk areas is proposed. Its implementation in a control programme would reduce by 86% the efforts needed for a classical vector control programme throughout the area. Medical surveys set up at specific locations, such as pirogue jetties and high-risk paths, should also enable better targeting of the population at highest risk.
Tropical Medicine & International Health 08/2010; 15(8):881-9. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate a modification of the mini anion exchange centrifugation test (mAECT) for the diagnosis of Trypanosoma brucei (T.b.) gambiense human African trypanosomiasis (HAT). To increase its sensitivity, this test uses 350 microl of buffy coat withdrawn from 5 ml of blood instead of blood.
The new protocol was first tested experimentally on serial dilution of trypanosomes and was then further evaluated under field conditions on 57 patients with HAT diagnosed during a medical survey in Guinea.
Experimentally, the use of buffy coats improved mAECT sensitivity at least five fold and enabled to consistently detect parasites in blood at a concentration of 10 trypanosomes/ml. During the field evaluation, more patients tested positive by mAECT-bc (96.5%) than by mAECT-blood (78.9%, chi(2) = 6.93, P = 0.008) and lymph juice examination (77.2%, chi(2) = 7.67, P = 0.005). Furthermore, the number of parasites per collectors was significantly higher (7.2 vs. 2.6, P = 0.001) when buffy coats were used instead of blood.
The use of the mAECT-bc protocol enabled a significant improvement of HAT parasitological diagnosis in Guinea, without any additional costs. It would deserve to be tested in other T.b. gambiense endemic areas.
Tropical Medicine & International Health 05/2010; 15(7):796-9. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Because of its high sensitivity and its ease of use in the field, the card agglutination test for trypanosomiasis (CATT) is widely used for mass screening of sleeping sickness. However, the CATT exhibits false-positive results (i) raising the question of whether CATT-positive subjects who are negative in parasitology are truly exposed to infection and (ii) making it difficult to evaluate whether Trypanosoma brucei (T.b.) gambiense is still circulating in areas of low endemicity. The objective of this study was to assess the value of the immune trypanolysis test (TL) in characterising the HAT status of CATT-positive subjects and to monitor HAT elimination in West Africa.
TL was performed on plasma collected from CATT-positive persons identified within medical surveys in several West African HAT foci in Guinea, Côte d'Ivoire and Burkina Faso with diverse epidemiological statuses (active, latent, or historical). All HAT cases were TL+. All subjects living in a nonendemic area were TL-. CATT prevalence was not correlated with HAT prevalence in the study areas, whereas a significant correlation was found using TL.
TL appears to be a marker for contact with T.b. gambiense. TL can be a tool (i) at an individual level to identify nonparasitologically confirmed CATT-positive subjects as well as those who had contact with T.b. gambiense and should be followed up, (ii) at a population level to identify priority areas for intervention, and (iii) in the context of HAT elimination to identify areas free of HAT.