Association of rs7719175, located in the IL13 gene promoter, with Schistosoma haematobium infection levels and identification of a susceptibility haplotype.

Urinary schistosomiasis is a parasitic disease caused by Schistosoma haematobium helminths. S. haematobium eggs may remain trapped within the bladder or the ureter walls, causing major pathological disorders in the urogenital system. The polymorphism rs1800925(C/T) of the IL13 gene promoter, which is functional, has previously been associated with susceptibility to S. haematobium infection. The aim of this study was to further our understanding and to determine whether, in the 5q31-q33 region, rs1800925 affects infection levels alone or in synergy with other polymorphisms. After sequencing the IL13 promoter and increasing the single-nucleotide polymorphism density, we performed a linkage disequilibrium analysis between rs1800925 and the other markers in a Malian population. Multivariate linear regression analysis and electrophoretic mobility shift assay (EMSA) were performed to characterized markers in linkage disequilibrium with rs1800925. An additional polymorphism, rs7719175, in the IL13 promoter was associated with controlling infection levels in multivariate analysis. The haplotype rs7719175T-rs1800925C was associated with high infection levels. EMSA indicated that rs7719175 affects the binding of transcriptional factors to the promoter region. Polymorphisms rs7719175 and rs1800925 have a synergistic role in the control of infection levels caused by S. haematobium and using them as a haplotype allows a better discrimination between infected subjects.

Microbial biodiversity of natural toothbrushes in Mali.

Different oral hygiene practices are used to overcome endemic diseases such as dental caries and oral infections. In Mali (Africa), natural plant-based toothbrushes are used for eliminating bacterial biofilm. The repertoire of microorganisms associated with natural toothbrushes is unknown. The aim of our study is to study microbial flora in particular the methanogenic archaea associated with natural toothbrushes recently recognized as responsible for periodontitis and peri-implantitis. We investigated the methanogens and bacteria associated with 15 different natural plant toothbrushes collected in Bamako local market (Mali). Microbiological investigations consisted in culturing the bacteria on agar plates and searching archaea using molecular techniques. No archaea were demonstrated by molecular biology but 50 bacterial species, including 33 aero-anaerobic and 17 aerobic species, were isolated from natural toothbrushes. We isolated Pseudomonas sp., Staphylococcus sp. and Klebsiella pneumoniae, which are acknowledged as opportunistic human pathogens. This study has highlighted the likely impact of the use of natural toothbrushes in the spread of potentially pathogenic bacteria in the human oral cavity.

Case report: a rare case of NOMA (cancrum oris) in a Malian woman.

Noma or cancrum oris is a multi-bacterial and opportunistic infection that destroys soft tissue, as well as muscle and bone, and can be fatal. We present a rare case of Noma in a 32-year-old Malian woman, from whom we isolated an Escherichia coli extended-spectrum beta-lactamase.

[Snakebites in the Sudanian and Sahelian zones of Mali: epidemiology, symptoms and treatment]. / Morsures de serpents en zone soudano-sahélienne du Mali epidémiologie, symptomatologie et traitement.

The purpose of this study was to document the epidemiology, symptoms and treatment of snake envenomation in Mali between 2005 and 2006. Data was collected using two methods, i.e., household surveys and retrospective surveys. Household surveys carried out in a village of 597 people showed that the annual average incidence was 164 snakebites per 100,000 inhabitants. Retrospective surveys were conducted in 35 healthcare facilities (5 regional hospitals and 30 district health centers) located in 5 parts of the country. Study periods ranged from 2 to 11 years depending on the location. The mean annual incidence of snakebite including dry-bites without envenomation was 27 per 100,000 inhabitants (range, 15-59). Hospital mortality was 4.7% (67/1433) (range, 2.2-6.7%). The population at risk consisted mainly of working men who accounted for 68.4% (980/1433). Patients between 15 and 30 years accounting for 41.2% (590/1433) of the sample were at highest risk for snakebite (chi2=9.96; p=6.10-3). The frequency of snakebite increased from 9.9% (142/1433) in Mopti in the North to 39.9% (572/1433) in Sikasso in the South (chi2=11.93; p=0,017). Snakebites most frequently occurred during the rainy season (56.6%) but only 0.68% of victims were referred to the health center. Hemorrhagic and inflammatory syndromes were the main complications of envenomation. Treatment was always symptomatic. Antivenom serum requirements ranged from 63 to 200 ampoules per year. Our results show that the frequency of snakebites remains grossly underestimated based on hospital data.

[Immunity in human schistosomiasis: hope for a vaccine]. / L'immunité dans les schistosomoses humaines: perspectives vaccinales.

Schistosomiasis remains a major worldwide public health problem in several endemic areas despite implementation of control measures. Vaccination would be an effective, long-term treatment option for future control of schistosomiasis. Although several parasite antigens have been identified as schistosomiasis vaccine candidates, major hurdles must still be overcome to develop a vaccine suitable for clinical trials in the field. Better understanding of immune responses to Schistosoma infection in both animal models and humans suggests that development of a vaccine is possible. The purpose of this review is to summarize the mechanisms of protective immunity against Schistosoma infection and to provide perspective on the development of a vaccine.

A STAT6 gene polymorphism is associated with high infection levels in urinary schistosomiasis.

Th2-mediated immunity is critical for human defence against schistosome, and susceptibility to infection is controlled by a major genetic locus, mapped on the 5q31-q33 region comprising the genes IL4, IL5 and IL13. We have reported an association between the rs1800925 polymorphism in the IL13 promoter and infection levels in a Dogon population (693 subjects in Ségué and 148 in Boul), where Schistosoma haematobium is endemic. In the same population, we investigated whether other polymorphisms in genes involved in type 2 cytokine immune response could affect susceptibility to schistosome infection. By logistic regression analysis, we found an association between a single-nucleotide polymorphism (SNP) in the STAT6 gene (rs324013) and infection levels (P=0.04). We confirmed this association in analyses restricted to subjects under 20 years age and living in Boul, the village with the highest levels of infection (P=0.005). We detected an additive effect of the rs324013 and rs1800925 polymorphisms (P=0.011). These SNPs were not strongly correlated with any other tested markers surrounding the two genes. Furthermore, electrophoretic mobility shift assay has shown that both polymorphisms affect transcription factor binding. These results are consistent with the Th2 cytokine pathway enhancing resistance to schistosome infection in humans.

Installing biosafety level 3 containment laboratories in low- and middle-income countries: challenges and prospects from Mali's experience.

In Mali, the incidence of tuberculosis (TB) is estimated at 56 cases per 100 000 people, with a prevalence of multidrug-resistant TB in new cases of 1.7% (range, 0.3-3.1%) and in retreatment cases of 17% (range, 4.4-30%). Appropriate biosafety conditions for performing routine TB culture and antimicrobial susceptibility testing have been lacking. In 2015, a biosafety level 3 (BSL3) laboratory set up in a shipping container was donated to the Malian Ministry of Health and Public Hygiene to provide capacity for TB testing. This laboratory is now managed by Malian laboratory staff and is processing samples at the national level. We explain the necessary steps for establishing and running a BSL3 laboratory. Despite the acute need for functioning and sustainable BSL3 laboratories, low- and middle-income countries are faced with a complex process and must overcome many challenges.

P. falciparum malaria prevalence among blood donors in Bamako, Mali.

AIM: Malaria parasite is usually transmitted to humans by Anopheles mosquitoes but it can also be transmitted through blood transfusion. Usually malaria transmission is low in African urban settings. In West Africa where the P. falciparum is the most predominant malaria species, there are limited measures to reduce the risk of blood transfusion malaria. The aim of this study was to evaluate the prevalence of P. falciparum malaria carriage among blood donors in the National Blood Center of Bamako, capital city of Mali. METHODS: The study was conducted using a random sample of 946 blood donors in Bamako, Mali, from January to December 2011. Screening for malaria was performed by thick smear and rapid diagnostic test (RDT). Blood group was typed by Beth-Vincent and Simonin techniques. RESULTS: The frequency of malaria infection was 1.4% by thick smear and 0.8% by the RDT. The pick prevalence of P. falciparum malaria was in rainy season, indicating a probable high seasonal risk of malaria by blood transfusion, in Mali. The prevalence of P. falciparum infection was 2% among donors of group O the majority being in this group. CONCLUSION: There is a seasonal prevalence of malaria among blood donors in Bamako. A prevention strategy of transfusion malaria based on the combination of selection of blood donors through the medical interview, promoting a voluntary low-risk blood donation and screening all blood bags intended to be transfused to children under 5, pregnant women and immune-compromised patients during transmission season using thick smear will reduce the risk of transfusion malaria in Mali.

[Mobile laboratories for rapid deployment and their contribution to the containment of emerging diseases in Sub-Saharan Africa, illustrated by the example of Ebola virus disease]. / Laboratoires mobiles et leur contribution dans l'endiguement de pathologies émergentes en Afrique subsaharienne illustrée par l'exemple de la maladie à virus Ebola.

The Ebola virus, which became a global health concern in 2014, is an example of an emerging pathogen. Ebola virus disease can only be diagnosed in biosafety level 3 and 4 laboratories, which provide the security required to avoid exposure of both the staff and the environment to the pathogen. These laboratories are often far from the site of outbreaks, which may occur in rural areas or border regions (when the disease is imported from a neighboring country). Rapidly deployable laboratory units can bring the diagnosis closer to the outbreak site and thus significantly shorten the time to delivery of results, thus facilitating epidemic containment. Here we report our experience from the first months of implementation in Mali of a mobile laboratory unit of the same type as the European mobile labs and we describe the workflow in the laboratory as well as the training of its Malian staff. Based on our experience and the reports of other projects, we propose a framework in which these mobile laboratory units can strengthen epidemiological surveillance and contribute to containing outbreaks of emerging diseases in sub-Saharan Africa.

Community pyrimethamine-sulfadoxine use and prevalence of resistant Plasmodium falciparum genotypes in Mali: a model for deterring resistance.

Pyrimethamine-sulfadoxine (PS, Fansidar; Hoffman-LaRoche, Basel, Switzerland) is now the first-line antimalarial therapy in parts of Africa with high rates of chloroquine-resistant Plasmodium falciparum. With PS resistance increasing and no suitably inexpensive and effective third antimalarial drug available, strategies for delaying the spread of PS resistance in Africa are needed. Community PS usage was measured in two Malian villages, one rural and one periurban, and prevalence of pyrimethamine-resistant P. falciparum genotypes was determined at these sites and two urban sites. The prevalence of resistant genotypes was 22.6% (n = 84) in the periurban village where PS was available from multiple sources and large stocks of PS were observed, and 13.5% (n = 89) and 23.4% (n = 77) in a large town and a city, respectively, where PS is widely available. No pyrimethamine-resistant genotypes (n = 58) were detected in Kolle, a rural village with a community-supported dispensary and clinic where PS is used sparingly and no PS was available in pharmacies or markets. The high rates of pyrimethamine resistant genotypes concurrent with higher PS usage argue for a policy of judicious PS use in Mali and in similar settings. A possible model for slowing the spread of drug-resistant malaria is illustrated by the example of the Kolle clinic.

Seasonality, malaria, and impact of prophylaxis in a West African village I. Effect of anemia in pregnancy.

The importance of malaria as a cause of anemia in pregnancy in endemic areas remains controversial. The prevalence of anemia in pregnant women following the dry (May) and the rainy (November) seasons was compared in two successive years in Bougoula village (region of Sikasso, Mali). Phase I (1992) was observational and included 172 pregnant women and 208 controls. In Phase II (1993, 174 pregnant women and 206 controls), malaria prophylaxis with proguanil (200 mg/day) and chloroquine (300 mg/week) was offered to pregnant women. A strong seasonal variation in the prevalence of moderate to severe anemia in pregnant women (hematocrit < 30%) occurred in Phase I (dry season = 8.7%, rainy season = 41.2%). This variation was present only in women of parity lower than five, and paralleled variation in parasitemia. In Phase II, the seasonal variation of anemia was suppressed in women under malaria prophylaxis (presence of antimalarial metabolites in urine), and the overall prevalence of moderate to severe anemia in pregnancy decreased by 55.5% (22.8-74.3%). We conclude that malaria is the major cause of anemia in pregnancy in this region. A high priority should be given to prevention of malaria in pregnancy.

[Transmission of schistosomiasis in an urban population and prevalence of intestinal helminthiasis in Bamako, Mali ]. / Transmission de la schistosomose urbaine et prévalence des helminthoses intestinales à Bamako, Mali.

Parasitological, malacological and anthropological studies were performed to assess the prevalence of Schistosoma haematobium and S. mansoni in schoolchildren living in the suburban area of Bamako. A total of 1017 schoolchildren aged 6-14 years were selected in two different areas between September 1997 and December 1999. In Djikoroni, the prevalence of S. haematobium and S. mansoni was 80.7% (339/420) and 22.8% (85/372) respectively. There was no significant difference of prevalence and intensity of infection with S. haematobium between schools, gender and age (p > 0.05), whereas, those of S. mansoni were higher in the vicinity of (+/- 100 m from) major sites where infected Biomphalaria pfeifferi were found (p < 0.001). In Niomirambougou, S. haematobium was prevalent in 46.7% (279/597) and S. mansoni in 28.2% (134/475). Boys and children aged 11-14 years were more infected (p < 0.001). Associated intestinal helminths (Hymenolepis nana, Necator americanus and Ascaris lumbricoides) were relatively scarce (prevalence < 1%). The prevalences of schistosome infected snails intermediate host were relatively high, 49.3% (100/203) in B. pfeifferi, 20.6% (88/138) in B. truncatus and 24.1% (7/29) in B. globosus. We recorded a total of 2514 water contacts about which 1130 in December and 1384 in January. Most of the children, 42.9% (1077/2511) were attracted to water bodies for bathing, swimming and playing, suggesting the lack of recreational facilities in these areas. Developing local control programmes in schools located in the vicinity of water bodies would contribute to break the parasite transmission cycle in Bamako.

[Echographic morbidity due to Schistosoma haematobium in a peripheral district of Bamako in Mali, Missabougou]. / Morbidité échographique due à Schistosoma haematobium dans un quartier périphérique de4 Bamako au Mali, Missabougou.

Frequency of urologic lesions was evaluated in 408 children from 6-15 years old in a suburban area of Bamako district in Mali, Missabougou; 65.2% from children were infected by Schistosoma haematobium, 13% by Schistosoma mansoni and 0.2% by Schistosoma intercalatum. Urologic lesions have been demonstrated in 223 cases among which 66 cases of urinary bladder lesions, 108 cases of hydronephrosis and 49 cases of mixed lesions. In order of the frequency we had the following uropathic lesions: wall thickening, wall irregularities, localised hypertrophies and hydronephrosis. We did not found any lesions in 185 children. Infection due to S. haematobium did not varied significantly in spite of age group, sex, schooling of children or the profession of the parents. Lesions were strongly correlated with age group (47.8 and 61.3% in 6-9 and 10-15 years old respectively) (p < 0.01) and with intensity of infection as measured by urinary egg counts (p = 0.0017).

[Epidemiology of malaria in a village of Sudanese savannah in Mali (Bancoumana). Anti-TRAP and anti-CS humoral immunity response]. / Epidémiologie du paludisme dans un village de savane soudanienne du Mali (Bancoumana). 1. Réponse immunitaire humorale anti-TRAP et anti-CS.

Vaccine development research is an important component of malaria control strategies. Thrombospondin related anonymous protein (TRAP) and the circumsporozoite (CS) protein are two antigens of sporozoite surface. Immune response to these two antigens may contribute to the development of anti-sporozoite vaccine. Recent studies suggest that antibodies anti-TRAP may partially block sporozoites penetration in hepatocyte, and thereby reducing malaria morbidity. We carried out a study to assess the seroprevalence of anti-TRAP and anti-CS antibodies and to identify a possible role of these antibodies on malaria morbidity in children 1-9 years old living in a rural hyperendemic village. We performed 5 cross sectional surveys and a longitudinal follow up in 1993 and 1994. During each cross sectional study, children were examined for fever and splenomegaly; all febrile children received thick film examination, and serologic analysis was performed in one third of these, randomly selected. The results show that the seroprevalence of anti-TRAP and anti-CS varied with age and season (p < 0.05). Association between the prevalence of anti-TRAP and splenomegaly was observed during two cross sectional surveys (June and October 1993). The presence of anti-TRAP antibody was associated with Plasmodium falciparum infection at the beginning of the transmission season (June 1993 and July 1994). A negative association between the level of anti-TRAP title and parasitemia was observed (March and October 1994). These findings suggest no clear evidence of the protective role of anti-TRAP antibodies in uncomplicated malaria, possibly due to the limited persistence of these antibodies under natural situations.

[Epidemiology of malaria in a village of Sudanese savannah area in Mali (Bancoumana). 2. Entomo-parasitological and clinical study ]. / Epidémiologie du paludisme dans un village de savane soudanienne du Mali (Bancoumana). 2. Etude entomo-parasitologique et clinique.

We carried out five cross sectional surveys between 1993 and 1994 to assess the epidemiology of malaria in the village of Bancoumana, located in the Sudanese savannah areas of Mali. Each survey included a collection of entomological, clinical, parasitological and immunological data. The study population involved 1600 children from six months to 9 years of age. The main vector was Anopheles gambiae s.l., man bite rate and entomological inoculation rate were maximum respectively in August (peak of the transmission season) and October (end of transmission season). Plasmodium. falciparum was the main parasite species observed. Spleen enlargement rate, parasite rate, gametocyte rate and parasite density varied significantly with age and season. The parasite rate, gametocyte rate and parasite density were significantly low in October 1994 compared with October 1993 while the entomologic parameter did not show any variation over the two years. This reduction of parasitologic index between 1993 and 1994 may be related to an increase of anti-malarial drug use in the population. Our results show that malaria is hyperendemic in the village of Bancoumana.

[Reinfection with Schistosoma haematobium and mansoni despite repeated praziquantel office treatment in Niger, Mali]. / Réinfections par Schistosoma haematobium et mansoni à l'office du Niger au Mali malgré la prise répétée de praziquantel.

The dynamics of reinfection by Schistosoma haematobium and Schistosoma mansoni after repeated treatment with praziquantel (40 mg/kg body weight, single dose) was studied in a cohort of schoolchildren living in an endemic area. A total of 214 urine and 220 stool samples were collected and examined at three different times, i.e., February 1989, July 1989 and February 1990. Mass chemotherapy was administered at the beginning of study (February 89). Treatment was repeated in children with positive tests at each subsequent sampling. Prevalence rates were 55.1 p. 100, 3.7 p. 100, and 35.0 p. 100 for Schistosoma haematobium and 62.7 p. 100, 46.3 p. 100 and 73.1 p. 100 for Schistosoma mansoni in February 1989, July 1989 and February 1990 respectively (p < 0.001). From July 1989 to February 1990, reinfection was observed in 84.5 p. 100 of children by Schistosoma haematobium versus 57.8 p. 100 by Schistosoma mansoni. The risk of reinfection by Schistosoma haematobium was higher in children between the ages of 7 and 10 years than in children between the ages of 11 and 15 years (p < 0.001), The incidence of intense Schistosoma haematobium egg excretion rose from 0 p. 100 in July 1989 to 6.0 p. 100 in February 1990. The incidence of intense Schistosoma mansoni excretion in February 1990 was 4.5 p. 100. The reinfection rate at 7 months was over 50 p. 100 for both parasite species despite repeated treatment. This finding demonstrates that additional measures such as proper sanitation and vector control are needed to control human schistosomiasis in irrigated rice paddies.

[Sickle cell anemia and transfusion safety in Bamako, Mali. Seroprevalence of HIV, HBV and HCV infections and alloimmunization belonged to Rh and Kell systems in sickle cell anemia patients]. / Sécurité transfusionnelle et drépanocytose à Bamako, Mali. Séroprévalence des infections à VIH, VHB, VHC et allo-immunisation anti-Rh et Kell chez les drépanocytaires.

Red cell transfusion is one of the main treatments in sickle cell disease. However there are potential risks of blood transfusions. In order to propose strategies to improve blood safety in sickle cell disease in Mali, we conducted a prospective study of 133 patients with sickle cell anemia recruited at the sickle cell disease research and control center of Bamako, November 2010 to October 2011. The study aimed to determine the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections by serum screening and the frequency of red cell alloimmunization before and after blood transfusion. The diagnosis of sickle cell syndrome was made by HPLC, the detection of markers of viral infection was performed by ELISA, and the diagnosis of alloimmunization was conducted by the Indirect Coombs test. Prevalence of viral infections observed at the time of enrolment of patients in the study was 1%, 3% and 1% respectively for HIV, HBV and HCV. Three cases of seroconversion after blood transfusion were detected, including one for HIV, one for HBV and one another for HCV in sickle cell anemia patients. All these patients had received blood from occasional donors. The red cell alloimmunization was observed in 4.4% of patients. All antibodies belonged to Rh system only. Blood transfusion safety in sickle cell anemia patients in Mali should be improved by the introduction of at least the technique for detecting the viral genome in the panel of screening tests and a policy of transfusions of blood units only from regular blood donors.

[Prevalence and risk factors of hepatitis C virus infection in chronic hemodialysis patients at the University Hospital of Point G, Bamako, Mali]. / Prevalence et facteurs associes au portage du virus de l'hepatite virale C chez les hemodialyses chroniques au CHU du Point G, Bamako, Mali.

The objective of this prospective study conducted in November 2008, was to determine the prevalence and the factors associated with Hepatitis C Virus (HCV) infection in chronic hemodialysis patients. The study was carried out in the hemodialysis unit of the university teaching hospital of Point G. Serum samples were tested for anti-HCV antibody, anti-HIV antibody and HBs Ag using enzyme immunoassay methods (ELISA) at the laboratory of immunology of the National Blood Transfusion Service of Bamako. The following parameters were assessed: initial nephropathy, duration of the dialysis, history of blood transfusion, number of blood units transfused since the beginning of the dialysis, history of nosocomial exposure. A total of 66 patients were enrolled. The mean age of the patients was 42,27±14, 8 years, with a male to female sex-ratio of 1,44. Anti-HCV antibodies were found in 13 chronic hemodialysis patients, leading to a prevalence of 19,7%. A significant association was found between the bearing of HCV and the duration of the dialysis. These results indicate that hepatitis C is frequent in the chronic hemodialysis patients of the university teaching hospital of Point G, and that the duration of dialysis constitutes the main factor associated with the contamination by the HCV.

HIV, HCV, HBV and syphilis rate of positive donations among blood donations in Mali: lower rates among volunteer blood donors.

Good data on background seroprevalence of major transfusion transmitted infections is lacking in Mali. We gathered data on the rate of positive donations of human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) and syphilis among blood donations in Mali for calendar year 2007. Donations with repeatedly reactive results on screening enzyme immunoassay (EIA) were considered to be seropositive. Rate of positive donations per blood unit collected was 2.6% for HIV, 3.3% for HCV, 13.9% for hepatitis B surface antigen (HBsAg) and 0.3% for syphilis. For HIV, HBsAg and syphilis, rate of positive donations was significantly (p<0.001) higher among donations from replacement donors than those from volunteer donors, while HCV rate of positive donations was similar in the two groups. Rate of positive donations was also significantly (p<0.0001) lower in blood units from regular than from first-time donors. These data reinforce WHO recommendations for increasing the number of regular, volunteer blood donors in Africa.