Salt in stools is associated with obesity, gut halophilic microbiota and Akkermansia muciniphila depletion in humans.

BACKGROUND/OBJECTIVES: High salt intake has been linked to several diseases including obesity and an increased risk of death; however, fecal salinity and the ability of salt to alter the gut microbiota, which was recently identified as an instrumental factor for health and disease, remains poorly explored. METHODS/SUBJECTS: We analyzed the fecal samples of 1326 human individuals for salinity by refractometry, 572 for gut microbiota by culturomics, and 164 by 16S rRNA-targeted metagenomics. Geographical origin, age, gender, and obesity were tested as predictors of fecal salinity and halophilic diversity. All halophilic isolates were characterized by taxonogenomics and their genome sequenced. RESULTS: Fecal salinity was associated with obesity independently of geographical origin, gender, and age. The first 2 human-associated halophilic archaeal members were isolated along with 64 distinct halophilic species, including 21 new species and 41 known in the environment but not in humans. No halophiles grow in less than 1.5% salinity. Above this threshold, the richness of the halophilic microbiota was correlated with fecal salinity (r = 0.58, p < 0.0001). 16S metagenomics linked high fecal salinity to decreased diversity (linear regression, p < .035) and a depletion in anti-obesity Akkermansia muciniphila and Bifidobacterium, specifically B. longum and B. adolescentis. Genomics analysis suggested that halophilic microbes are not only transient passengers but may be residents of the human gut. CONCLUSIONS: High salt levels are associated with alteration of the gut microbial ecosystem and halophilic microbiota, as discovered during this study. Further studies should clarify if the gut microbiota alterations associated with high salt levels and the human halophilic microbiota could be causally related to human disease, such as obesity.

High dermatophyte contamination levels in hairdressing salons of a West African suburban community.

Tinea capitis is a dermatophyte infection of scalp is commonly spread by currently infected patients, asymptomatic carriers or by fomites, such as hairdressing tools. However, studies on the risk factors of Tinea capitis remain scarce. The aim of this study was to evaluate the dermatophytes contamination level of the hairdressing tools to which hairdressing salon customers are exposed in Sirakoro-Méguétana, a suburb of Bamako, the capital city of Mali. A total of 41 hairdressing tools were sampled in five hairdressing salons. Two anthropophilic dermatophytes species, Microsporum audouinii (53.3%) and Trichophyton soudanense (46.7%), were cultured from 30 (73.2%) samples. This first study, addressing hairdressing salons dermatophyte contamination, revealed a strikingly high contamination of hairdressing tools with dermatophyte propagules, which exposes hairdressing salons customers to an important dermatophytosis risk. The sterilisation of hairdressing tools is central to preventing dermatophytoses spreading. Appropriate community information and hairdressers training should be implemented in this view.

Fc gamma receptor IIa-H131R polymorphism and malaria susceptibility in sympatric ethnic groups, Fulani and Dogon of Mali.

It has been previously shown that there are some interethnic differences in susceptibility to malaria between two sympatric ethnic groups of Mali, the Fulani and the Dogon. The lower susceptibility to Plasmodium falciparum malaria seen in the Fulani has not been fully explained by genetic polymorphisms previously known to be associated with malaria resistance, including haemoglobin S (HbS), haemoglobin C (HbC), alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Given the observed differences in the distribution of FcγRIIa allotypes among different ethnic groups and with malaria susceptibility that have been reported, we analysed the rs1801274-R131H polymorphism in the FcγRIIa gene in a study of Dogon and Fulani in Mali (n = 939). We confirm that the Fulani have less parasite densities, less parasite prevalence, more spleen enlargement and higher levels of total IgG antibodies (anti-CSP, anti-AMA1, anti-MSP1 and anti-MSP2) and more total IgE (P < 0.05) compared with the Dogon ethnic group. Furthermore, the Fulani exhibit higher frequencies of the blood group O (56.5%) compared with the Dogon (43.5%) (P < 0.001). With regard to the FcγRIIa polymorphism and allele frequency, the Fulani group have a higher frequency of the H allele (Fulani 0.474, Dogon 0.341, P < 0.0001), which was associated with greater total IgE production (P = 0.004). Our findings show that the FcγRIIa polymorphism might have an implication in the relative protection seen in the Fulani tribe, with confirmatory studies required in other malaria endemic settings.

Different patterns of Toll-like receptor 2 polymorphisms in populations of various ethnic and geographic origins.

Upon the invasion of the host by microorganisms, innate immunity is triggered through pathogen recognition by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are the best-studied class of PRRs, and they recognize specific pathogen-associated molecular patterns (PAMPs) from various microorganisms. A large number of studies have shown that genetic variation in TLRs may influence susceptibility to infections. We assessed the genetic variation of TLR2, which encodes one of the most important TLRs, in various populations around the globe and correlated it with changes in the function of the molecule. The three best-known nonsynonymous TLR2 polymorphisms (1892C>A, 2029C>T, and 2258G>A) were assessed in different populations from the main continental masses: Romanians, Vlax-Roma, Dutch (European populations), Han Chinese (East Asia), Dogon, Fulani (Africa), and Trio Indians (America). The 2029C>T polymorphism was absent in both European and non-European populations, with the exception of the Vlax-Roma, suggesting that this polymorphism most likely arose in Indo-Aryan people after migration into South Asia. The 1892C>A polymorphism that was found exclusively in European populations, but not in Asian, African, or American volunteers, probably occurred in proto-Indo-Europeans. Interestingly, 2258G>A was present only in Europeans, including Vlax-Roma, but at a very low frequency. The differential pattern of the TLR2 polymorphisms in various populations may explain some of the differences in susceptibility to infections between these populations.

[Place of malaria among febrile illnesses in two ethnic tribes living in sympatry in Mali from 1998 to 2008]. / Place du paludisme dans les syndromes fébriles dans deux groupes ethniques vivant en sympatrie au Mali de 1998 à 2008.

In Africa, malaria is responsible for 25-40% of all outpatient visits and 20-50% of all hospitalizations. In malaria-endemic areas, individuals do not behave the same toward the outcome of clinical malaria. The aim of this study is to determine the prevalence of malaria in the locality among the different ethnic groups, evaluate the place of malaria among febrile illnesses, and assess the relationship between fever and parasite density of Plasmodium falciparum. Studies on susceptibility to malaria between the Fulani and Dogon groups in Mali were conducted in Mantéourou and the surrounding villages from 1998 to 2008. We carried out six cross-sectional studies during the malaria transmission and longitudinal surveys (July to December depending on the year) during the 10-year duration. In longitudinal studies, clinical data on malaria and other diseases frequently observed in the population were recorded. It appears from this work that malaria is the leading cause of febrile syndromes. We observed a significant reduction in malaria morbidity in the study population from 1998 to 2008. The pyrogenic threshold of parasitaemia was 1,000 parasites/mm(3) of blood in the Dogon and 5,000 parasites/mm(3) of blood in the Fulani.We have also found that high parasitical densities were not always associated with fever. Malaria morbidity was higher among the Dogon than in Fulani. The immunogenetic factors might account for this difference in susceptibility to malaria between Fulani and Dogon in the area under study. With regard to this study, it is important to take into account the ethnic origin of subjects when interpreting data of clinical and malarial vaccine trials.

[Humoral immune anti-Plasmodium falciparum AMA1 and MSP1 response in two ethnic groups living in sympatry in Mali]. / Réponse humorale anti-Plasmodium falciparum AMA1 et MSP1 dans deux groupes ethniques vivant en sympatrie au Mali.

Fulani of Mali are known for their lower susceptibility to Plasmodium falciparum malaria than their neighbours, the Dogon, despite similar transmission conditions. However, the mechanisms underlying these differences are poorly understood, particularly those concerning antigenspecific immune responses. The Apical Membrane Antigen 1 (AMA1) and the Merozoite Surface Antigen 1 (MSP1) are two malaria vaccine candidates, which play a pivotal role during the invasion of parasites into erythrocytes, and in the case of AMA1, of hepatocytes. Therefore, we analyzed the level of anti-AMA1 and anti-MSP1 antibodies (FVO and 3D7 alleles), by using ELISA (Enzyme Linked Immuno Sorbent Assay) to investigate whether there are differences between the two ethnic groups. Our results show that the splenic rate, the level of anti-AMA1 and anti-MSP1 were significantly higher in Fulani compared to Dogon; while the parasite rate was lower in Fulani group compared to Dogon. Our results suggest that the lower susceptibility of Fulani to malaria could be due to the higher specific humoral responses against AMA1 and MSP 1 in Fulani's ethnic group compared to Dogon.

[Relationship between malaria and anemia in two ethnic groups living in sympatry in Mali]. / Relation entre l'anémie et le paludisme dans deux groupes ethniques vivant en sympatrie au Mali.

Studies performed in Burkina Faso and Mali showed differences in susceptibility to malaria between the Fulani and other sympatric ethnic groups, the Mossi and Dogon. We carried out a longitudinal survey and three cross-sectional studies from 2003 to 2005 in order to assess the prevalence of anemia in Dogon and Fulani. The distribution of the study population by sex was comparable between the two ethnic groups (p = ns). The Fulani are mainly cattle breeders and the Dogons, farmers. They were exposed to similar entomological inoculation rates, and studies on "knowledge, attitude, and practices" showed no difference between the two ethnic groups. The cross-sectional studies were performed during the intense malaria transmission season (in September 2003 and 2005) and during the dry season (in March 2004). Longitudinal clinical follow-up studies were performed from August to December 2005 using the WHO 28 days in vivo test, after administration of a curative dose of antimalarial drugs to patients with mild malaria. During the cross-sectional studies, both Fulani men and women had significantly lower hemoglobin levels than their Dogon counterparts; this difference was most evident in the women (in 2005: 9.4 g/dl in Fulani vs 10.7 g/dl in Dogon, p = 0.0002). Clinical longitudinal follow-up data showed that Fulani children aged 10-14 years have lower hemoglobin levels than Dogon children. At day 0, the mean of hemoglobin level was 9.6 g/dl in Dogon children vs. 8.7 g/dl in Fulani children (p = 0.01). At day 28, after malaria treatment, we also observed a significant difference in hemoglobin levels in children (10.6 g/dl in Dogon vs 9.3 g/dl in Fulani, p < 0.001). A stronger association between anemia and spleen enlargement was found in the Fulani (53.2% with spleen enlargement) than in the Dogon (32.9%) [p = 0.005]. The Fulani suffer more from anemia than the Dogon, despite their lower susceptibility to malaria. The difference in anemia between Dogon and Fulani must be further investigated to determine possible factors involved in malaria susceptibility.

[Epidemiology of cutaneous leishmaniasis in five villages of Dogon country, Mali]. / Épidémiologie clinique et parasitologique de la leishmaniose cutanée dans cinq villages du Pays Dogon, Mali.

The epidemiology of the cutaneous leishmaniasis (CL) with Leishmania major is poorly documented in Mali. Following reports of CL in the tourist areas of the Dogon country (Bandiagara Escarpment), a joint French and Malian bio-clinical team conducted a field study from 16 to 27 January, 2010. The population of 5 villages has been examined by a dermato-infectiologist and cases were selected by visual inspection of skin lesions. Smears and biopsies (from the lesions) and venous blood were obtained from suspected cases of CL. Diagnosis was performed by light microscopy, in vitro cultures, serology and molecular biology. Fifty patients with skin lesions have been examined. Twenty-one have been suspected as CL. At least one sample was obtained from 18 patients. The lesions were predominantly old, more or less scarring and secondary infected. A skin smear was performed for 15 patients, a skin biopsy for 14 patients: smears and cultures were all negative. The PCR (Leishmania spp.) made on 14 biopsies was positive for 12 patients (86%). The low amount of amplified DNA obtained did not allow the sequencing and identification of the species of Leishmania. Western blot (WB) serology was positive in 11 cases out of 12 (92%). This investigation showed the presence of cutaneous leishmaniasis in Bandiagara. A further investigation is required during transmission period (September-October) to confirm the presence of Leishmania major epidemic in Dogon country.

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.

Association of HLA alleles with Plasmodium falciparum severity in Malian children.

Pre-erythrocytic immunity to Plasmodium falciparum malaria is likely to be mediated by T-cell recognition of malaria epitopes presented on infected host cells via class I and II major histocompatibility complex (MHC) antigens. To test for associations of human leukocyte antigen (HLA) alleles with disease severity, we performed high-resolution typing of HLA class I and II loci and compared the distributions of alleles of HLA-A, -B, -C and -DRB1 loci in 359 Malian children of Dogon ethnicity with uncomplicated or severe malaria. We observed that alleles A*30:01 and A*33:01 had higher frequency in the group of patients with cerebral disease compared to patients with uncomplicated disease [A*30:01: gf = 0.2031 vs gf = 0.1064, odds ratio (OR) = 3.17, P = 0.004, confidence interval (CI) (1.94-5.19)] and [A*33:01: gf = 0.0781 vs gf = 0.0266, 4.21, P = 0.005, CI (1.89-9.84)], respectively. The A*30:01 and A*33:01 alleles share some sequence motifs and A*30:01 appears to have a unique peptide binding repertoire compared to other A*30 group alleles. Computer algorithms predicted malaria peptides with strong binding affinity for HLA-A*30:01 and HLA-A*33:01 but not to closely related alleles. In conclusion, we identified A*30:01 and A*33:01 as potential susceptibility factors for cerebral malaria, providing further evidence that polymorphism of MHC genes results in altered malaria susceptibility.

[Neuromeningeal cryptococcosis in Mali]. / La cryptococcose neuro-méningée au Mali.

Cryptococcal meningitis is the most common fatal central nervous system infection in AIDS patients in Sub-Saharan Africa. The purpose of this prospective study conducted from March 2003 to February 2004 in the internal medicine and infectious diseases departments of the Point G University Hospital Center was to investigate the clinical, prognostic and epidemiological profile of Cryptococcus neoformans infection in patients hospitalized for brain and meningeale infection (BMI). Diagnosis of neuromeningeal cryptococcosis (NMC) was based on positive identification of Cryptococcus by direct exam of the cebrospinal fluid (CSF) after India ink staining and/or culture on Sabouraud medium without actidione. During the study period, a total of 569 patients were hospitalized including 235 (41.3%) with HIV infection. Overall C. neoformans was identified in 14 patients. Median patient age was 39 +/- 8 years. There was a male preponderance with a sex ratio of 1.8 (9 men/5 women). Patients with BMI were HIV-positive in 85.7% of cases (n=12) and HIV-negative in 14.3% (n=2). The overall and HIV-specific prevalence of BMI was 2.5% and 5.1% respectively. The CD4 lymphocyte count was between I and 49 cells/mm3 in 64.3% of cases. The main clinical symptoms were cephalea in 85.7% of cases, altered consciousness in 50% and nausea/vomiting in 35.7%. Neurological manifestations (hemiparesis and cranial nerve deficit) were noted in 14.3%. HIV infection is the main purveyor of NMC in Mali. The actual incidence of cryptococcosis is unclear due to the poor sensitivity of diagnostic techniques. This study highlights diagnostic difficulties related to clinical polymorphism and poor technical facilities. Agglutination testing of blood and CSF is recommended, but mortality remains.

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.

Maternal country of origin, breast milk characteristics and potential influences on immunity in offspring.

Breast milk contains pro- and anti-inflammatory cytokines and chemokines with potential to influence immunological maturation in the child. We have shown previously that country of birth is associated with the cytokine/chemokine profile of breast milk. In this study we have investigated how these differences in breast milk affect the cellular response of cord blood mononuclear cells (CBMCs) and intestinal epithelial cells (IECs, cell line HT-29) to microbial challenge. Ninety-five women were included: 30 from Mali in West Africa, 32 Swedish immigrants and 33 native Swedish women. CBMCs or IECs were stimulated in vitro with breast milk, alone or in combination with lipopolysaccharide (LPS) or peptidoglycan (PGN). Breast milk in general abrogated the LPS-induced down-regulation of surface CD14 and Toll-like receptor (TLR)-4 expression on CB monocytes, while inhibiting the PGN-induced TLR-2 up-regulation. However, breast milk from immigrant women together with LPS induced a lower CBMC release of interleukin (IL)-6 (P = 0·034) and CXCL-8/IL-8 (P = 0·037) compared with breast milk from Swedish women, while breast milk from Swedish women and Mali women tended to increase the response. The same pattern of CXCL-8/IL-8 release could be seen after stimulation of IECs (HT-29). The lower CBMC and IEC (HT-29) responses to microbial compounds by breast milk from immigrant women could be explained by the fact that breast milk from the immigrant group showed a divergent pro- and anti-inflammatory content for CXCL-8/IL-8, transforming growth factor-ß1 and soluble CD14, compared to the other two groups of women. This may have implications for maturation of their children's immune responses.

[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.

[Obstacles to laboratory diagnosis of malaria in Mali--perspectives]. / Problématique du diagnostic biologique du paludisme au Mali--perspectives.

Rapid accurate laboratory diagnosis is necessary for effective malaria management. In Mali, meeting this prerequisite is impeded by underuse of laboratory diagnosis by clinicians, absence of qualified laboratory facilities in some locations, and poor continuous professional education of laboratory technicians. The twofold aim of this investigation was to perform quality control of thick smear readings made by laboratory technicians in 1998 and 1999 and to study the feasibility and diagnostic value of two rapid diagnostic tests (RDT), i.e., ParaSight and OptiMAL, in comparison with the thick smear technique in the period from 1998 to 2003. Quality control of thick smear readings indicated a 56% false positive rate with 49.3% concordance between laboratory technician readings and the reference centre. Trials using RDT showed that the OptiMAL test was more efficient with 97.2% sensibility, 95.4% specificity and 93% concordance in comparison with thick smear. A program of training, refresher courses, and regular didactic supervision (quality control) for laboratory technicians has been set up in Mali under the sponsorship of the "Fondation Mérieux" (ACTION BIOMALI) and the President's Malaria Initiative (PMI). These institutions provide funding for training as well as equipment and consumables in all public medical laboratories in Mali. The thick smear method is still being used as the reference technique, but use of RDT is to be implemented at all levels of the health care pyramid.

[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.

[Development of anti-malarial vaccines and need for clinical trials in accordance with international standards in South Africa]. / Le développement de vaccins antipaludiques et la nécessité des essais cliniques conformes aux normes internationales en Afrique.

In the 20th century malaria remains a major problem of public health in sub-Saharan Africa. This haemosporidium discovered in Africa by Laveran in 1880, kills one child every 30 seconds which amounts to three "tsunami" flowing each year into the African continent. The current international solidarity raises new hopes as regards the possibility to suppress the morbidity effects on the population's health condition. In order to be efficient, today's strategies (impregnated mosquito nets, intermittent preventive treatments, artemisinin based combination therapy) should reach at least 80% of the targeted population (pregnant women and children). By 2025, the uncontrolled urbanization of the African population and the social disorders will make a new population a target for malaria. The new data of functional genomics and proteonics open new avenues of research for new mechanisms, new therapeutics and vaccine targets and new tools of diagnosis and prognosis. The current candidate vaccines of the first generation have allowed the development of African competences in clinical trials of international standard. Although they represent scientific advances they will not resolve the problem of public health. Research on candidate vaccines of 2nd and 3rd generation remains a challenge for the international scientific community. Africa should play a determining role in this process. Scientific information on the field remains essential for these generations of new anti-malarial vaccines. The ethical aspects regarding those clinical trials and actions of public health and research remain an universal necessity Deontology and ethics are two complementary approaches for the good practice of medicine and research of a good practitioner. For the protection and advantages of the patient and/or volunteer of the research are the cornerstones of the ethical approach. The scientific quality of a research protocol submitted to an independent research ethics committee and the volunteer 's informed consent are universal ethical obligations. For the quality of ethics observance in a country reflects best the quality of the efficiency of its research system and its democracy.

[Neuromeningeal cryptococcosis in non-HIV patients to CHU ward of Point G in Bamako (Mali): 3 case report]. / Cryptococcose neuroméningée chez des patients VIH négatif au CHU du Point G de Bamako (Mali): à propos de trois observations cliniques.

We report 3 clinical observations of neuromeningeal cryptococcosis which occurred without any immunodepression related to HIV infection. Our patients were male. They did not present any particular medical history indicating a diagnosis of cryptococcosis. Nevertheless we found a professional exposure to the risk of inhalation of C. neoformans capsules. The diagnosis was based on presence of encapsulated yeast of Cryptococcus in the direct exam by China ink and culture on Sabouraud medium. CD4 lymphocytic count was done in two patients (case 1:899 cells/mm3; case 2:347 cells/mm3). Idiopathic lymphocytopenia was noted in one case. Co-morbidity of 5. pneumoniae meningitis was reported in one patient (case 3). Treatment was based on injectable amphotericin B in monotherapy (case 1), followed by perfusion of fluconazole cure (case 2). Case 3 was treated by perfusion of amphotericin B associated with ceftriaxone (case 2). No secondary prophylactic treatment was administered. Evolution was favorable after follow-up of 5 years (case 1) and of 4 years (case 2). The third patient died during hospitalization.