[Human African trypanosomiasis in Côte d'Ivoire and Burkina Faso: optimization of epidemiologic surveillance strategies]. / La Trypanosomose Humaine Africaine dans l'espace ivoiro-burkinabé : optimisation des stratégies de surveillance épidémiologique.

The objective of this paper was to describe recent data from Burkina Faso and Côte d'Ivoire on Human African Trypanosomosis medical monitoring in order to (i) update the disease situation in these two countries that have been sharing important migratory, economic and epidemiological links for more than a century and (ii) to define the future strategic plans to achieve the goal of a sustainable control/elimination process. Results of active and passive surveillance indicate that all sleeping sickness patients diagnosed these last years in Burkina Faso were imported cases from Côte d'Ivoire. Nevertheless the re-introduction of the parasite is effective and the risk of a resumption of transmission exists. In Côte d'Ivoire, few cases are still diagnosed in several historical foci and the fear exists that the disease could reemerge in these foci or spread to other areas. In order to achieve a sustainable elimination of sleeping sickness in these two countries, control entities have to adapt their strategy to the different epidemiological contexts. At the exception of specific cases, the current disease prevalence no longer justifies the use of expensive medical surveys by exhaustive screening of the population. New disease control strategies, based on the exchange of epidemiological information between the two countries and integrated to the regular national health systems are required to target priority intervention areas. Follow-up in time of both treated patients and serological suspects that are potential asymptomatic carriers of parasite is also important. In parallel, researchers need to better characterize the respective roles of the human and animal reservoir in the maintenance of transmission and evaluate the different control strategies taken by National Control Programs in term of cost/effectiveness to help optimize them.

Human host determinants influencing the outcome of Trypanosoma brucei gambiense infections.

Since first identified, human African trypanosomiasis (HAT) or sleeping sickness has been described as invariably fatal. Increasing data however argue that infection by Trypanosoma brucei gambiense, the causative agent of HAT, results in a wide range of outcomes in its human host and importantly that a number of subjects in endemic areas are apparently able to control infection to low levels, undetectable by the classical parasitological tests used in the field. Thus, trypanotolerance seems to occur in humans as has already been described in cattle or in the rodent experimental models of infection. This review focuses on the description of the diversity of outcomes resulting from T. b. gambiense in humans and on the host factors involved. The consequences/impacts on HAT epidemiology resulting from this diversity are also discussed with regard to implementing sustainable HAT control strategies.

Experimental evaluation of xenodiagnosis to detect trypanosomes at low parasitaemia levels in infected hosts.

In Human African Trypanosomosis (HAT) endemic areas, there are a number of subjects that are positive to serological tests but in whom trypanosomes are difficult to detect with the available parasitological tests. In most cases and particularly in West Africa, these subjects remain untreated, thus posing a fundamental problem both at the individual level (because of a possible lethal evolution of the disease) and at the epidemiological level (since they are potential reservoirs of trypanosomes). Xenodiagnosis may constitute an alternative for this type of cases. The objective of this study was to update the use of xenodiagnosis to detect trypanosomes in infected host characterized by low parasitaemia levels. This was carried out experimentally by infecting cattle and pigs with Trypanosoma congolense and T. brucei gambiense respectively, and by feeding tsetse flies (Glossina morsitans submorsitans and G. palpalis gambiensis, from the CIRDES colonies) on these animals at a time when the observed blood parasitaemia were low or undetectable by the classical microscopic parasitological tests used for the monitoring of infected animals. Our results showed that: i) the G. p. gambiensis colony at CIRDES could not be infected with the T. b. gambiense stocks used; ii) midgut infections of G. m. submorsitans were observed with both T. congolense and T. b. gambiense; iii) xenodiagnosis remains positive even at very low blood parasitaemia for both T. congolense and T. b. gambiense; and iv) to implement T. b. gambiense xenodiagnosis, batches of 20 G. m. submorsitans should be dissected two days after the infective meal. These results constitute a first step toward a possible implementation of xenodiagnosis to better characterize the parasitological status of seropositive individuals and the modalities of parasite transmission in HAT foci.

A geographical approach to identify sleeping sickness risk factors in a mangrove ecosystem.

OBJECTIVES: To provide a better understanding of sleeping sickness transmission and spread in mangrove areas to optimize its control. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Human African trypanosomiasis in mangrove epidemiologic area. Presentation, diagnosis and treatment in Guinea, 2005-2007]. / La trypanosomose humaine africaine en faciès épidémiologique de mangrove. Présentation, déterminants et prise en charge dans le contexte de la Guinée (2005 à 2007).

UNLABELLED: Gambiense human African trypanosomiasis is still assumed to be endemic in many part of West Africa, particularly in Guinea coastal area with mangrove swamp. Diagnosis is usually made during active medical screening or by passive initiative. OBJECTIVES: To describe clinical and epidemiological characteristics of Gambiense human African trypanosomiasis in the coastal area of Guinea. METHODS: Exhaustive and retrospective analysis of all patients attending the trypanosomiasis center in the coastal area of Guinea between January 2005 and December 2007 with a diagnosis of human African trypanosomiasis. RESULTS: A total of 196 patients were recruited for the study. Out of them, 55 % of the 73 patients diagnosed during active screening were classified stage 1 (haemolymphatic stage) or early stage 2 (meningoencephalitic stage). Contrarily, 115 of the 120 diagnosed by passive procedure were classified late stage 2, which features more specific signs and neurological symptoms, and leads to coma and death. More than 90 % of all cases presented cervical lymph nodes with identification of trypanosome on direct examination of fluid puncture. Less than one third of the patients were reexamined three months later. DISCUSSION: In the coastal area of Guinea with mangrove swamp, direct examination of lymph node fluid puncture seems to be the most contributive test for the diagnosis of human African trypanosomiasis. Hence, associating clinical examination of cervical lymph nodes area and direct examination of fluid puncture may allow an early diagnosis of Gambiense human African trypanosomiasis and favor the implementation of efficient therapeutic strategies.

Rearrangements involving repeated sequences within a P element preferentially occur between units close to the transposon extremities.

In a previous report we described rearrangements occurring at a high rate (30% of the progeny of dysgenic flies) within a cluster of 5S genes internal to a P element. These events were characterized as precise amplifications and deletions of 5S units. Here we analyze recombination events within P elements containing two repeated arrays of 5S genes flanking a central white gene. Deletions (50%) and duplications (3%) of the white gene together with various amounts of flanking 5S genes were observed. These recombinations occur preferentially between the most external 5S units of P transposons. Such rearrangements could be favored by interactions between the proteins bound to the P terminal sequences.

Linkage analysis of blood Plasmodium falciparum levels: interest of the 5q31-q33 chromosome region.

There is accumulating evidence for the involvement of genetic factors in the human response to malaria infection, mostly based on results obtained in studies of severe clinical malaria. The role of major gene(s) controlling blood parasitemia levels in human malaria has also been detected by means of segregation analysis. To confirm and to localize such gene(s), we performed a sib-pair linkage analysis investigating the role of five candidate chromosomal regions: 6p21 (HLA-tumor necrosis factor region), 2q13-q21 (genes coding for interleukin-1 alpha and beta), 14q11 (locus coding for the alpha chain of T cell antigen receptor), 7q35 (gene cluster for the beta subunit of T cell receptor), and 5q31-q33, which includes several candidate genes and was recently linked to a locus controlling infection levels by Schistosoma mansoni, denoted as SM1. The analysis was carried out on nine families from a southern Cameroon village, and the phenotype under study was blood infection levels with Plasmodium falciparum. No linkage was found with any of the four markers outside the 5q31-q33 region. A trend in favor of linkage was observed in the distal part of the 5q31-q33 region, especially with the marker D5S636 (P < 0.05 using the Monte Carlo P value), which was the marker that provided the highest evidence for linkage with SM1. These results suggest that a locus influencing P. falciparum levels in malaria could be located in the same genetic region as that containing SM1, indicating that the 5q31-q33 region may be critical in the control of different parasite infections.

Canine visceral leishmaniasis caused by Leishmania infantum in Senegal: risk of emergence in humans?

In the context of global warming and the risk of spreading arthropod-borne diseases, the emergence and reemergence of leishmaniasis should not be neglected. In Senegal, over the past few years, cases of canine leishmaniasis have been observed. We aim to improve the understanding of the transmission cycle of this zoonosis, to determine the responsible species and to evaluate the risk for human health. An epidemiological and serological study on canine and human populations in the community of Mont Rolland (Thiès area) was conducted. The data showed a high seroprevalence of canine leishmaniasis (>40%) and more than 30% seropositive people. The dogs' seroprevalence was confirmed by PCR data (concordance > 0.85, Kappa > 0.7). The statistical analysis showed strong statistical associations between the health status of dogs and seropositivity, the number of positive PCRs, clinical signs and the number of Leishmania isolates. For the first time, the discriminative PCRs performed on canine Leishmania strains clearly evidenced that the pathogenic agent is Leishmania infantum. The results obtained show that transmission of this species is well established in this area. That the high incidence of seropositivity in humans may be a consequence of infection with this species is discussed.

Identification of a novel G245R polymorphism in the IL-2 receptor beta membrane proximal domain associated with human visceral leishmaniasis.

Binding of the interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) triggers a series of intracellular events culminating in lymphocyte proliferation and differentiation. We report here the identification of a novel G245R polymorphism in the membrane proximal domain of the IL-2 receptor beta chain (IL-2Rbeta). Present at a frequency of 7.2%, the IL-2-Rbeta G245R was identified in a population of Eastern Sudan exposed to a severe outbreak of visceral leishmaniasis (VL), a disease associated with a marked depression of T-cell antigen-specific responses. The location of the G245R polymorphism next to the box1/box2 proximal cytokine receptor homology segment and suggestive genetic association with the development of disease (P=0.043), suggest that it may affect Janus kinase (JAK) association and impair growth signal transduction. However, additional genetic association with a synonymous single nucleotide polymorphism (IL2RB+8777T) suggests that other variations of IL2RB or nearby genes participate in the highly significant linkage with VL at 22q12 previously reported for this population.

Sudan: the possible original focus of visceral leishmaniasis.

Fifty-two Leishmania strains, obtained from human patients and dogs in a visceral leishmaniasis focus in Sudan, were characterized by isoenzyme electrophoresis (15 enzymes). The phylogenetic analysis showed that the 7 Leishmania zymodemes obtained hold ancestral positions on the phylogenetic tree, supporting the hypothesis of an East African origin of visceral leishmaniasis.

Genetic control of visceral leishmaniasis in a Sudanese population: candidate gene testing indicates a linkage to the NRAMP1 region.

There is some evidence showing that genetic factors are involved in human susceptibility to parasitic diseases such as schistosomiasis and malaria. Studies have shown that the Nramp1 and H-2 genes are implicated in the control of Leishmania donovani infection in mice. We sought genetic loci involved in the control of susceptibility to visceral disease caused by L. donovani in humans. We studied 37 families with at least two affected sibs living in a village in eastern Sudan, where an outbreak of visceral leishmaniasis occurred between 1995 and 2000. The genetic markers located in five chromosomal regions containing candidate genes were typed: 2q35 (NRAMP1), 5q31-q33 (Th2 cytokine cluster), 6p21 (HLA/TNF-alpha), 6q23 (INFGRI) and 12q15 (INF-gamma). Linkage (multipoint lod-score=1.08; P=0.01) was observed for the 5'(CA) repeat polymorphism in the NRAMP1 promoter. This suggests that genetic variations of this gene affect susceptibility to visceral leishmaniasis in this population.

The sandfly fauna in the visceral-leishmaniasis focus of Gedaref, in the Atbara-River area of eastern Sudan.

Visceral leishmaniasis (VL) is an acute public-health problem in Sudan. Between 1997 and 2000, four, brief entomological surveys were carried out in Barbar El Fugarra, a village in the state of Gedaref, in the Atbara-River area of eastern Sudan. Between 1996 and 1999, 658 cases of VL occurred among the village's population of about 4000. CDC miniature light-traps set inside and outside human dwellings were used to collect a total of 12,745 sandflies, including five species of the genus Phlebotomus and 19 of Sergentomyia. Phlebotomus papatasi and P. orientalis made up 7% and 5% of the collected sandflies, respectively. Seasonal variation was observed in the numbers of P. orientalis, P. papatasi, S. schwetzi and S. magna caught. Almost all (88%) of the sandflies collected were caught inside houses or granaries and there appeared to be particularly large indoor populations of P. orientalis, P. papatasi, S. schwetzi, S. magna and S. clydei. Phlebotomus orientalis could be responsible for the indoor transmission of the parasites causing the local VL, between humans and between humans and local dogs (which have been found infected by some of the Leishmania zymodemes found in humans). The co-occurrence in this focus of P. papatasi and Arvicanthis niloticus, which are known vectors and reservoir hosts, respectively, of L. major, indicates the possibility that outbreaks of human cutaneous leishmaniasis might occur in the area.