[History of an epidemiological route between Ivory Coast and Burkina Faso: the case of the Koudougou sleeping sickness foci]. / Histoire d'un itinéraire épidémiologique entre le Burkina Faso et la Côte d'Ivoire : le cas des foyers de maladie du sommeil de Koudougou.

In the first half of the XXth century, while Upper-Volta (now Burkina Faso) was suffering a terrible epidemic of sleeping sickness, the French colonial administration encouraged the movement of people from Upper-Volta to Ivory Coast to meet their demands for labour. This led to the establishment of Mossi villages, such as those of Koudougou, in the Ivorian forest with populations originating from areas of Upper-Volta that were not only densely populated but also severely affected by sleeping sickness. Since 2000, most cases of sleeping sickness in the Koudougou district of Burkina Faso have been in people originally from Ivory Coast. Who are they? Where did they settle in Burkina Faso? Where do they come from in Ivory Coast? After having retraced the epidemiological history of Koudougou villages in Burkina Faso and Ivory Coast, the history of ten cases of sleeping sickness detected passively at Koudougou hospital since 2000 were analysed. All cases originated from the forest area of Ivory Coast. Understanding the spread of sleeping sickness between Burkina Faso and Ivory Coast will assist in the identification of areas of disease risk.

[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.

[Ivory Coast uprising and returning Burkinabe immigrants: evaluation of the risk for reemergence of sleeping sickness in Burkina Faso]. / Crise ivoirienne et rapatriés burkinabés: évaluation et vérification du risque de réémergence de la maladie du sommeil au Burkina Faso.

Following the sociopolitical unrest that occurred in Ivory Coast in 2002, 360,000 Burkinabe immigrants returned to Burkina Faso that was the epicenter of sleeping sickness last century and is now thought to be free of autochthonous transmission. The purpose of this study was to determine if the massive return of immigrants from human African trypanosomiasis (HAT) endemic areas of Ivory Coast to areas in Burkina Faso where the vector (tsetse fly) is currently present could lead to re-emergence of the disease. Risk areas for re-emergence were identified taking into account the number of returning immigrants, history of the disease, and presence of tsetse flies. Based on these criteria, study was focused on two villages, i.e., Folonzo and Gbalara, located in southern Burkina Faso near the Ivory Coast border. Study in these two villages consisted of characterization of the population (repatriates or not, origin, ...) and medical surveys to assess the presence/absence of the disease. Departure of some returning immigrants from areas including sleeping sickness foci in Ivory Coast (e.g. center west) confirmed the potential risk of re-emergence of the disease. Although no case of sleeping sickness was diagnosed, several serologically positive people were identified and will be followed up. This study failed to demonstrate a clear-cut correlation between massive population movements due to war and reemergence of sleeping sickness. However, this study may have been timed too soon after the return of immigrants to detect reemergence of HAT that could require several years.

[Impact of the dynamics of human settlement on tsetse and trypanosomosis distribution in the Mouhoun river basin (Burkina Faso)]. / Impact de la dynamique de peuplement sur la distribution des glossines et des trypanosomoses dans la boucle du Mouhoun (Burkina Faso).

In Burkina Faso, the Mouhoun river basin (formerly "Black Volta") constitutes a historical focus of Human (HAT) and Animal (AAT) African Trypanosomoses, both transmitted by tsetse flies. Nowadays, HAT seems to have disappeared from this area, while AAT still causes severe economic losses. In order to explain these different epidemiological situations, we undertook a geographical study based on the analysis of aerial pictures between 1952 and 2007, and field surveys to collect medical, entomological, and veterinary data on trypanosomoses. Our results suggest that in this area, landscapes have been dramatically modified as a consequence of population growth, and in turn have had an impact on the number and distribution of tsetse flies. Combined with the historical medical action on HAT which probably led to the disappearance of T. b. gambiense, this environmental degradation and the development of hydrological structures provide explanations for the local disappearance of HAT, and for the maintenance of AAT. It appears necessary to extrapolate these studies to other areas in order to identify the factors explaining the presence/absence of trypanosomoses in the context of human population growth and climatic changes, in order to help to target priority areas for the control of these diseases.

[Population growth and global warming: impacts on tsetse and trypanosomoses in West Africa]. / Impacts des évolutions démographiques et climatiques sur la répartition spatiale des hommes, des tsé-tsé: et des trypanosomoses en Afrique de l'Ouest.

Demographic evolution, climatic change and economical development that happened in West Africa during the XXth century had a lot of consequences on human settlement and landscape. These changes have in turn an impact on the pathogenic system of human and animal trypanosomoses. Since last century, the northern tsetse distribution limit has shifted towards the south, probably due to a decrease in rainfall combined to the impact of human pressure. Sleeping sickness (SS) foci have also shifted from the savannah areas (where there is no more SS) to the forest and mangrove areas of West Africa, but animal trypanosomoses are still present in savannah. We show a decrease of tsetse of the morsitans group as a result of an increase of human densities. On the opposite, tsetse species like Glossina palpalis adapt to high human densities and are found in the biggest urban centres of West Africa. There is a need to promote multidisciplinary studies on this demographic-climatic-vector borne disease topic, especially in Africa to be able to define future areas of presence/absence of these diseases in order to help continental plans of control that have recently begun.

Tsetse elimination: its interest and feasibility in the historical sleeping sickness focus of Loos islands, Guinea.

Guinea is the West African country which is currently the most prevalent for sleeping sickness. The littoral area is the region where most of the recent sleeping sickness cases have been described, especially the mangrove sleeping sickness foci of Dubreka and Boffa where Glossina palpalis gambiensis is the vector. Loos islands constitute a small archipelago 5 km apart from the capital, Conakry. Medical, animal, and entomological surveys were implemented in these islands in Oct-Nov 2006. No pathogenic trypanosomes were found in these surveys. The locally very high tsetse densities (up to more than 100 tsetse/trap/day) linked to pig rearing, constitute a high potential risk for humans (taking into account populations movements with neighboring active sleeping sickness foci of the Guinea littoral, and the history of sleeping sickness on these islands), and for the economically important pig rearing, as well as a danger for tourism. This situation, associated to the possibility of elimination of these tsetse populations due to low possibility of reinvasion, led the National Control Program to launch a tsetse elimination project following an "area wide" strategy for the first time in West Africa, which participates in the global objective of the PATTEC (Pan African Tsetse and Trypanosomosis Eradication Campaign).

Sleeping sickness in West Africa (1906-2006): changes in spatial repartition and lessons from the past.

OBJECTIVE: To review the geography and history of sleeping sickness (Human African trypanosomiasis; HAT) over the past 100 years in West Africa, to identify priority areas for sleeping sickness surveillance and areas where HAT no longer seems active. METHOD: History and geography of HAT were summarized based on a review of old reports and recent publications and on recent results obtained from medical surveys conducted in West Africa up to 2006. RESULTS/CONCLUSIONS: Active HAT foci seem to have moved from the North to the South. Endemic HAT presently appears to be limited to areas where annual rainfall exceeds 1200 mm, although the reasons for this remain unknown. There has also been a shift towards the south of the isohyets and of the northern distribution limit of tsetse. Currently, the most severely affected countries are Guinea and Ivory Coast, whereas the northern countries seem less affected. However, many parts of West Africa still lack information on HAT and remain to be investigated. Of particular interest are the consequences of the recent political crisis in Ivory Coast and the resulting massive population movements, given the possible consequences on HAT in neighbouring countries.

[One century of "sleeping sickness" in West Africa]. / Un siècle de "trypano" en Afrique de l'Ouest. Communication affichée lors des journées du centenaire de la SPE.

This paper summarizes the geography of sleeping sickness disease (or Human African Trypanosomiasis, HAT) over the last 100 years in West Africa, with the objective of identifying today's priority areas for the sleeping sickness surveillance. The history and geography of the disease are based on a bibliographic review of old reports and recent publications on recent results obtained from medical surveys conducted in West Africa up to 2007. This allowed us to situate the historical geography of HAT from the beginning of the 20th century to nowadays. For instance, active HAT foci seem to have moved from the North (savannah area) to the South (forest area) in the last century. Taking into account the limited nature of the information available, endemic HAT presently appears to be limited to areas where annual rainfall is higher than 1,200 mm, although the reasons for this remain unknown. During this period of time there has also been a shift towards the south of the isohyets and of the northern distribution limit of tsetse. Currently the most severely affected countries are Guinea and Ivory Coast, whereas the northern countries seem less affected, but many parts of West Africa still lack information on HAT and remain to be investigated. These observations, put back in the current context of demographic growth and climatic global change, responsible for landscape evolution, political instability and population movements, raise the question of HAT becoming.

Cyclical transmission of Trypanosoma brucei gambiense in Glossina palpalis gambiensis displays great differences among field isolates.

Six sets of teneral Glossina palpalis gambiensis (Diptera: Glossinidae) were fed on mice infected with six different isolates of Trypanosoma brucei gambiense (each mouse was infected with one of the isolates), previously isolated from patients in the sleeping sickness focus of Bonon, Côte d'Ivoire and in Makoua, Congo. All the tsetse flies were dissected 42 days post-infection and midgut and salivary glands were examined for trypanosomes by microscopical examination. No infection was observed with the reference stock whereas each of the five recently isolated trypanosome isolates was able to infect tsetse flies, with rates of infection varying between 9.7 and 18.2% depending on the isolate. Three isolates displayed only immature infections with 9.7, 17.3 and 18% of the flies showing trypanosomes in their midgut. One isolate gave both immature (12.1%) and mature infections (6.1%). Finally, the last isolate involved only mature infections in 9.7% of the Glossina species examined. These substantial differences in the cyclical transmission of T. b. gambiense in the same fly species could have important implications for the epidemiology of the transmission of Human African Trypanosomiasis.

Aparasitemic serological suspects in Trypanosoma brucei gambiense human African trypanosomiasis: a potential human reservoir of parasites?

The serological and parasitological tests used for Trypanosoma brucei gambiense human African trypanosomiasis (HAT) diagnosis have low specificity and sensitivity, respectively, and in the field, control program teams are faced with subjects with positive serology but negative parasitology who remain untreated. The aim of this work was to explore, using PCR tool, the significance of these aparasitemic serological suspects. Since discordant PCR results have been observed earlier with different extraction methods, two DNA extraction methods were compared (the Chelex 100 resin and the DNeasy Tissue kit). The study was conducted on 604 blood samples: 574 from parasitologically confirmed patients, aparasitemic serological suspects and endemic controls collected in Côte d'Ivoire and 30 from healthy volunteers collected in France. No significant differences were observed between the PCR results obtained with the two extraction methods. Concerning PCR, problems of reproducibility and discordances with both serological and parasitological test results were observed, mainly for the aparasitemic serological suspects. In addition to previous results that pointed to the existence of non-virulent or non-pathogenic trypanosome strains and of individual susceptibility leading to long term seropositivity without detectable parasitaemia but positive PCR, the results of this study support the notion of a long lasting human reservoir that may contribute to the maintenance or periodic resurgences of HAT in endemic foci.

Preliminary evaluation of LATEX/T. b. gambiense and alternative versions of CATT/T. b. gambiense for the serodiagnosis of human african trypanosomiasis of a population at risk in Côte d'Ivoire: considerations for mass-screening.

A study was conducted to compare classical card agglutination test for trypanosomiasis (CATT)/T. b. gambiense with CATT-EDTA and LATEX/T. b. gambiense as alternative field tests for serodiagnosis of Human African Trypanosomiasis. The tests were performed on freshly collected blood in an endemic and a low prevalence area in Côte d'Ivoire. Diagnostic performance of each test was assessed using Quantitative Buffy Coat as the parasitological reference and immune trypanolysis as the serological reference test. According to the parasitological data, CATT-EDTA on 10 microl and LATEX/T. b. gambiense on blood diluted 1:4, detecting all confirmed cases with good specificity (respectively 94.6% and 98.1%) yielded better results than the classical CATT did (one false negative and 92.5% specific). However, when immune trypanolysis data and feasibility are taken into account, the classical CATT remains the test of choice for mass screening under the given field conditions.

Comparison of different DNA preparation protocols for PCR diagnosis of Human African Trypanosomosis in Côte d'Ivoire.

During a medical survey the sleeping sickness focus in Bonon, Ivory Coast, PCR with Trypanosoma brucei specific primers (TBR 1-2 from Parasitology 99 (1989) 57) was tested on DNA derived from blood samples. DNA purification using a chelating resin was performed either on whole blood or on the buffy coat prepared in two different ways. The preparation based on whole blood performed better than those using the buffy-coat. Using this first method, the sensitivity was 100% on parasitologically confirmed patients, and the specificity was 92%. However, problems of reproducibility of the technique were pointed out, particularly on samples from serologically positive but apparently aparasitemic individuals. It is suggested that the PCR could help in the diagnosis of Human African Trypanosomosis, but the use of other primers should be investigated.

Inhibition of the DNA amplification of trypanosomes present in tsetse flies midguts: implications for the identification of trypanosome species in wild tsetse flies.

The present study was carried out in order to investigate if there was really a failure of PCR in identifying parasitologically positive tsetse flies in the field. Tsetse flies (Glossina palpalis gambiensis and Glossina morsitans morsitans) were therefore experimentally infected with two different species of Trypanosoma (Trypanosoma brucei gambiense or Trypanosoma congolense). A total of 152 tsetse flies were dissected, and organs of each fly (midgut, proboscis or salivary glands) were examined. The positive organs were then analysed using PCR. Results showed that, regardless of the trypanosome species, PCR failed to amplify 40% of the parasitologically positive midguts. This failure, which does not occur with diluted samples, is likely to be caused by an inhibition of the amplification reaction. This finding has important implications for the detection and the identification of trypanosome species in wild tsetse flies.

[Use of molecular biology in the diagnosis of human African trypanosomiasis]. / Utilisation de la biologie moléculaire dans le diagnostic de la trypanosomose humaine africaine.

Human African trypanosomiasis (HAT), a.k.a. sleeping sickness, is still a major public health problem in sub-Saharan Africa. In West and Central Africa, this vector-borne parasitic disease in caused by Trypanosoma brucei gambiense transmitted by glossidinae. According to the classic model, HAT is characterized by two phases, i.e. the early circulating phase and the later neurological phase. Diagnosis from blood samples in the field and staging from cerebrospinal fluid samples in the laboratory are difficult due to the absence of specific clinical symptoms and fluctuating parasitemia levels. Several recent studies have described the use of the polymerase chain reaction (PCR) technique with primers specific for Trypanosoma brucei s.1 to improve the sensitivity and specificity of conventional test methods. Within the framework of active screening, PCR carried out on blood samples prior to serological tests could be helpful in identifying suspected infection. Although the one-time initial investment is high, expenditures on expendables is lower for PCR than conventional techniques (mAECt: miniature anion exchange column test) while achieving higher sensitivity. For application on cerebrospinal fluid samples, PCR also achieves better sensitivity than conventional techniques and thus can contribute to staging of the disease. Identification of the early or late phase is important for documenting successful therapy and early diagnosis of relapse. Further research will be needed before actual implementation. This is notably the case with regard to specificity since it is still not possible to assert that positive PCR is a sign of active infection by a pathogenic trypanosome in man.

[Role of patient travel in transmission of human African trypanosomiasis in a highly endemic area of the Ivory Coast]. / Représentation spatiale des déplacements des malades dans un foyer de trypanosomose humaine africaine de Côte d'Ivoire.

Human African trypanosomosis (HAT) remains a major public health problem in Subsaharan Africa. The region around the town of Bonon in middle western Côte d'Ivoire is a highly endemic HAT zone. The purpose of this study was to assess the role of travelling of infected patients in transmission of HAT. The study population included a total of 96 patients in whom HAT had been diagnosed actively or passively between 1999 and 2000. Information on each patient's residence and workplaces, i.e. water site, and farm field, was used to calculate the mean distance traveled and mean number of places visited daily by each patient. Findings indicated that both parameters, i.e., distance traveled and number of places visited, were significantly higher for patients living in Bonon than those living in hamlets or homesteads. Based on analysis of patient movements the endemic zone could be divided into three subdivisions with different modes of disease transmission. This study was performed as a preliminary step for a larger investigation designed to allow specific targeting of HAT hot spots based mainly on a geographic information system.

[Settlements, landscapes, and risks of sleeping sickness at the mouth of the Rio Pongo in Guinea-Conakry]. / Peuplements, paysages et risque de maladie du sommeil à l'embouchure du Rio Pongo en Guinée-Conakry.

Seeking to understand how humans, by the settlements they create (among other means), influence the operation of the pathogen system of sleeping sickness, the authors performed a diachronic analysis of the landscape and settlement dynamics by comparing topographic maps from 1957, a satellite image from 2004, and georeferenced censuses from 2009 and 2001. It appears that the extreme mobility of the population between the continent and the islands is the principal cause for the continuation of this disease at the mouth of the Rio Pongo.