Characterizing the Subcortical Structures in Youth with Congenital Heart Disease.

BACKGROUND AND PURPOSE: Congenital heart disease is a leading cause of neurocognitive impairment. Many subcortical structures are known to play a crucial role in higher-order cognitive processing. However, comprehensive anatomic characterization of these structures is currently lacking in the congenital heart disease population. Therefore, this study aimed to compare the morphometry and volume of the globus pallidus, striatum, and thalamus between youth born with congenital heart disease and healthy peers. MATERIALS AND METHODS: We recruited youth between 16 and 24 years of age born with congenital heart disease who underwent cardiopulmonary bypass surgery before 2 years of age (n = 48) and healthy controls of the same age (n = 48). All participants underwent a brain MR imaging to acquire high-resolution 3D T1-weighted images. RESULTS: Smaller surface area and inward bilateral displacement across the lateral surfaces of the globus pallidus were concentrated anteriorly in the congenital heart disease group compared with controls (q < 0.15). On the lateral surfaces of bilateral thalami, we found regions of both larger and smaller surface areas, as well as inward and outward displacement in the congenital heart disease group compared with controls (q < 0.15). We did not find any morphometric differences between groups for the striatum. For the volumetric analyses, only the right globus pallidus showed a significant volume reduction (q < 0.05) in the congenital heart disease group compared with controls. CONCLUSIONS: This study reports morphometric alterations in youth with congenital heart disease in the absence of volume reductions, suggesting that volume alone is not sufficient to detect and explain subtle neuroanatomic differences in this clinical population.

[Ecology of Glossina palpalis VANDERPLANK, 1949 (Diptera: Glossinidae) in mangrove area of Guinea: influence of tides on tsetse densities]. / Écologie de Glossina palpalis gambiensis VANDERPLANK, 1949 (Diptera : Glossinidae) en zone de mangrove de Guinée : influence des marées sur les densités capturées.

The mangrove area on the Guinea littoral constitutes a favourable habitat for transmission of Trypanosoma brucei gambiens, the parasite causing sleeping sickness also called Human African Trypanosmosis (HAT), due the simultaneous presence of the vector (tsetse flies) and the human hosts. In order to assess the influence of the sea tides on the densities of Glossina palpalis gambiensis (Gpg), major vector of HAT in the mangrove, entomological surveys were performed using two transects, according to tides coefficient (great and small) and tide daily fluctuations (high and low). On each transect, 12 biconical traps were deployed through the mangrove to the continent. In total, up to 612 Gpg were caught, giving a density of 2.13 flies/trap/day (f/t/d). Highest captures were recorded during small tides and more tsetse were caught during the dry season than in the wet season. There were significant differences between captures when considering the different biotopes, and highest tsetse densities were recorded at the junction of the river and the channel of the mangrove (6.17±5.24); and in the channels of mangrove (3.50±3.76), during high tides of small coefficients. The results of this study may be used to improve vector control methods.

Tsetse diversity and abundance in Southern Burkina Faso in relation with the vegetation.

The increase of human population, combined with climatic changes, contributed to the modification of spatial distribution of tsetse flies, main vector of trypanosomiasis. In order to establish and compare tsetse presence and their relationship with vegetation, entomological survey was performed using biconical traps deployed in transects, simultaneously with phyto-sociological study, on the Comoe river at its source in the village of Moussodougou, and in the semi-protected area of Folonzo, both localities in Southern Burkina Faso. In Folonzo, the survey revealed a diversity of tsetse with 4 species occurring with apparent densities as follows: Glossina tachinoides (8.9 tsetse/trap/day); G. morsitans submorsitans (1.8 tsetse/trap/day); G. palpalis gambiensis (0.6/trap/day) and G. medicorum (0.15 tsetse/trap/day). In Moussodougou, a highly anthropized area, mainly G. p. gambiensis was caught (2.06 tsetse/trap/day), and rarely G. tachinoides. The phyto-sociological study allowed discrimination of 6 types of vegetation in both localities, with 3 concordances that are riparian forest, shrubby and woody savannah. In Moussodougou, all tsetse were caught in the riparian forest. That was also the case in Folonzo where a great proportion (95 to 99 % following the season) of G. p. gambiensis and G. tachinoides were caught in the gallery, while G. m. submorsitans was occurring as well in the gallery as in the savannah, and G. medicorum in the forest gallery. This study showed that although G. tachinoides and G.p. gambiensis are both riparian, they do not have the same preference in terms of biotope.

[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.

[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.

[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.

ROS-generating NADPH oxidase NOX4 is a critical mediator in oncogenic H-Ras-induced DNA damage and subsequent senescence.

Activated Ras oncogene induces DNA-damage response by triggering reactive oxygen species (ROS) production and this is critical for oncogene-induced senescence. Until now, little connections between oncogene expression, ROS-generating NADPH oxidases and DNA-damage response have emerged from different studies. Here we report that H-RasV12 positively regulates the NADPH oxidase system NOX4-p22(phox) that produces H(2)O(2). Knocking down the NADPH oxidase with small interference RNA decreases H-RasV12-induced DNA-damage response detected by γ-H2A.X foci analysis. Using HyPer, a specific probe for H(2)O(2), we detected an increase in H(2)O(2) in the nucleus correlated with NOX4-p22(phox) perinuclear localization. DNA damage response can be caused not only by H-RasV12-driven accumulation of ROS but also by a replicative stress due to a sustained oncogenic signal. Interestingly, NOX4 downregulation by siRNA abrogated H-RasV12 regulation of CDC6 expression, an essential regulator of DNA replication. Moreover, senescence markers, such as senescence-associated heterochromatin foci, PML bodies, HP1ß foci and p21 expression, induced under H-RasV12 activation were decreased with NOX4 inactivation. Taken together, our data indicate that NADPH oxidase NOX4 is a critical mediator in oncogenic H-RasV12-induced DNA-damage response and subsequent senescence.

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.

Pathologic findings and liver elements in hibernating bats with white-nose syndrome.

Two groups of vespertilionid bats were collected from affected hibernacula. In group 1 (n, 14; pathology and microbiology), the average body weights of all species were at the lower limit of published ranges. Twelve bats (86%) had mycotic growth in the epidermis, hair follicles, and sebaceous glands. Geomyces destructans, with its characteristic curved conidia, was observed microscopically, cultured, and confirmed by polymerase chain reaction. Dermatitis and mural folliculitis was nil to mild. When focally coinfected with Gram-negative bacteria, there was necrosis and pustules. Fat stores were little to abundant in 12 bats (86%) and nil in 2. Thirteen bats (93%) had pulmonary congestion and 7 (50%) had bone marrow granulocytosis. In group 2 (n, 24; liver elements), 3 bats (13%) had potentially toxic lead levels and 1 (4%), potentially toxic arsenic level. There was no evidence of major organ failure or consistent element toxicity.

[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.

Mapping sleeping sickness in Western Africa in a context of demographic transition and climate change.

Human population growth, climate change and economic development are causing major environmental modifications in Western Africa, which will have important repercussions on the epidemiology of sleeping sickness. A new initiative, the Atlas of human African trypanosomiasis (HAT), aims at assembling and geo-referencing all epidemiological data derived from both active screening activities and passive surveillance. A geographic database enables to generate up-to-date disease maps at a range of scales and of unprecedented spatial accuracy. We present preliminary results for seven West African countries (Benin, Burkina Faso, Côte d'Ivoire, Ghana, Guinea, Mali and Togo) and briefly discuss the relevance of the Atlas for future monitoring, control and research activities.

[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.

[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.

[Influence of anthropisation on local vegetation and tsetse abundance in southern Burkina Faso]. / Influence de l'anthropisation sur la végétation locale et l'abondance des tsé-tsé au sud du Burkina Faso.

Entomological and phyto-sociological surveys were undertaken in Folonzo, southern Burkina Faso, along the Comoé river. The purpose of this survey was to compare densities and diversity of tsetse species in a protected versus a non protected area, by the mean of transects going from the river bank to the savannah. A detailed phytological description was made in all the trapping sites. The entomological data were also compared to what was obtained in 1980 in the same trapping sites. The phytogeographical study showed great vegetation homogeneity between transects, particularly in the forest gallery, while savannah showed more heterogeneity. Four tsetse species were caught in the area, with 74% G. tachinoides, 20% G. m. submorsitans, 4% G. p. gambiensis and 2% G. medicorum. There was a significant difference in tsetse densities between the protected and the non-protected area, with in average, four times more tsetse in the protected one. This difference was particularly high for G. m. submorsitans with a ratio of 1/9. This decrease was attributed to the reduction in wildlife density in the non protected area, and can be applied to the situation of the whole country where this tsetse species is of decreasing importance. It is one of the consequences of the increase in human densities, this latter causing much less visible changes in phytological species composition. From the comparison between old (1980) and new data collected on the river bank, we see a general trend of decrease in density, which affects less G. palpalis gambiensis.

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).

[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.

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.

[The impact of war on the evolution of sleeping sickness in west-central Côte d'Ivoire]. / L'impact de la guerre sur l'evolution de la THA dans le centre-ouest de la Côte d'Ivoire.

OBJECTIVE: To evaluate the situation of sleeping sickness in west-central Côte d'Ivoire from 2000 to 2003, in view of the war which broke out in September 2002. METHODS: Active surveys by medical teams and passive case detection. RESULTS: Between 2000 and 2003, 250 patients were diagnosed with sleeping sickness. At first it appeared that sleeping sickness prevalence had fallen since the beginning of political troubles. But this apparent drop was due to poor population coverage. Participation in medical surveys differed according to ethnic group, reflecting land use conflicts between ethnic communities. Such conflicts are common in this area, but have been exacerbated by the war. CONCLUSION: In war, assessing the importance of sleeping sickness by medical surveys only is very difficult. But detection of sleeping sickness cases by passive surveillance increased.

[Human African trypanosomiasis: urban transmission in the focus of Bonon (Côte d'Ivoire)]. / Trypanosomose Humaine Africaine: transmission urbaine dans le foyer de Bonon (Côte d'Ivoire).

Human African trypanosomiasis (HAT) is a vector-borne parasitic disease which has often been considered a rural disease. Population increases in African countries have entailed the spread of urban centres, creating favourable conditions for the appearance of new epidemiological conditions. In Cote d'Ivoire, HAT transmission has been described in the surroundings of towns such as Daloa or Sinfra. In the focus of Bonon, located in central-western Cote d'Ivoire, a medical survey detected 96 patients. The sites visited by the patients every day were geo-referenced and the routes between them recorded. In parallel, an entomological survey of the patients' daily locations enabled the collection of data on the vector. In Bonon, we observed urban cases and tsetse (Glossina palpalis) feeding on men. Trypanosoma brucei gambiense was identified in both man and vector; thus all conditions for possible intra-urban trypanosomosis transmission were met. The consequences of this are discussed regarding the problem of diffusion of the disease.