Bacterial Infection in the Sickle Cell Population: Development and Enabling Factors.

The high frequency of bacterial infections represents a major threat to public health. In developing countries, they are still responsible for significant morbidity and mortality in pediatric populations with sickle cell disease, particularly in children under 5 years of age. Indeed, they have an increased susceptibility to bacterial infections due to their immune deficiency. This susceptibility is even greater for pneumococcal and salmonella infections. In addition, the underdevelopment of some countries and socio-economic factors increases this condition. This review examines the common and specific factors leading to infections in people with sickle cell disease in different types of developed and undeveloped countries. The threat of bacterial infections, particularly those caused by S. pneumoniae and Salmonella, is of increasing concern due to the rise in bacterial resistance to antibiotics. In light of this disturbing data, new strategies to control and prevent these infections are needed. Solutions could be systematic penicillin therapy, vaccinations, and probabilistic antibiotic therapy protocols.

Competitive fitness of Mycobacterium tuberculosis in vitro.

Background: While, bacteria resistance mutations can affect competitive fitness, given our multidrug-resistant (MDR) prevalence, we conducted this study to determine the impact of MDR on the competitive fitness of Mycobacterium tuberculosis (MTB) complex MDR strains. We conducted a cross-sectional study at the University Clinical Research Center (UCRC) from January to December 2017. New TB patients over aged of 18 were recruited at University teaching hospital and health reference centers of Bamako in USTTB Ethical committee approved protocols. Methods: MDR and drug-susceptible (wild-type [WT]) MTB strains (T1 and Beijing) and MTB H37Rv were competed on solid media in UCRC's Tuberculosis Laboratory. Competitive and individual cultures were incubated for 14 days at 37°C with 7% CO2. Number of generation, generation time, and relative competitive fitness (W) of the strains were calculated. Data were analyzed with Epi-Info 7.1.5.2 software (CDC). P value was considered significant when it was <0.05. Scientific calculator (CS-82TL) was used for competitive fitness parameters calculations. Results: We performed 24 competitive cultures and 10 individual cultures. In individual cultures, strains' generation number was for Beijing (WT: 4.60 and mutant MR: 4.40), T1 (WT: 2.69 and MR: 2.37), and H37Rv: 2.91. Generation number of WT strains was less than those of MDR strains in both individual and competitive culture. Relative competitive fitness was below 1 (W<1) in 83.3%. Conclusion: MDR strains were less competitive than WT strains in 83.3% of cases. Resistant mutation impacts bacteria fitness.

Prevalence and Diversity of the Thermotolerant Bacterium Bacillus cytotoxicus among Dried Food Products.

HIGHLIGHTS: Bacillus cytotoxicus was found in all tested potato flakes but at loads lower than 102 CFU/g. B. cytotoxicus was observed in other potato-containing products and in millet flour. B. cytotoxicus isolates (n = 57) fell into six RAPD patterns and 11 plasmid profiles. A large proportion of B. cytotoxicus isolates contained small and/or large plasmids.

Very high prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in bacteriemic patients hospitalized in teaching hospitals in Bamako, Mali.

The worldwide dissemination of extended-spectrum beta-lactamase producing Enterobacteriaceae, (ESBL-E) and their subset producing carbapenemases (CPE), is alarming. Limited data on the prevalence of such strains in infections from patients from Sub-Saharan Africa are currently available. We determined, here, the prevalence of ESBL-E/CPE in bacteriemic patients in two teaching hospitals from Bamako (Mali), which are at the top of the health care pyramid in the country. During one year, all Enterobacteriaceae isolated from bloodstream infections (E-BSI), were collected from patients hospitalized at the Point G University Teaching Hospital and the pediatric units of Gabriel Touré University Teaching Hospital. Antibiotic susceptibility testing, enzyme characterization and strain relatedness were determined. A total of 77 patients had an E-BSI and as many as 48 (62.3%) were infected with an ESBL-E. ESBL-E BSI were associated with a previous hospitalization (OR 3.97 95% IC [1.32; 13.21]) and were more frequent in hospital-acquired episodes (OR 3.66 95% IC [1.07; 13.38]). Among the 82 isolated Enterobacteriaceae, 58.5% were ESBL-E (20/31 Escherichia coli, 20/26 Klebsiella pneumoniae and 8/15 Enterobacter cloacae). The remaining (5 Salmonella Enteritidis, 3 Morganella morganii 1 Proteus mirabilis and 1 Leclercia adecarboxylata) were ESBL negative. CTX-M-1 group enzymes were highly prevalent (89.6%) among ESBLs; the remaining ones being SHV. One E. coli produced an OXA-181 carbapenemase, which is the first CPE described in Mali. The analysis of ESBL-E relatedness suggested a high rate of cross transmission between patients. In conclusion, even if CPE are still rare for the moment, the high rate of ESBL-BSI and frequent cross transmission probably impose a high medical and economic burden to Malian hospitals.

Prevalence of ESBL-producing Enterobacteriaceae isolated from blood cultures in Mali.

INTRODUCTION: The increasing frequency of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is becoming a serious public health concern. This study sought to determine ESBL frequency in Enterobacteriaceae isolated from patients' blood cultures in two university teaching hospitals of Bamako, Mali. METHODOLOGY: During a three-month period, the presence of Enterobacteriaceae from blood cultures of patients admitted to the university teaching hospitals of Bamako was evaluated. The microbial identifications were initially performed with an API 20E gallery and VITEK2 locally in Mali, and then confirmation in France was performed with a mass spectrometry MALDI-TOF in the bacteriology laboratory of the university teaching hospital of Bichat. Antibiotic susceptibility profiles were determined by the diffusion method as recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). RESULTS: The isolated species were K. pneumoniae (14/40; 35.0%), E. coli (11/40; 27.5%), and E. cloacae (9/40; 22.5%). Of the strains isolated, 21/34 (61.8%) had an ESBL phenotype, including 10/14 (71.4%) K. pneumoniae, 8/11 (72.7%) E. coli, and 3/9 (33.3%) E. cloacae. Resistances associated with ESBL strains of K. pneumoniae, E. coli, and E. cloacae were as follows: gentamicin (10/10, 100%; 6/8, 75%; 2/3, 67%, respectively), amikacin (2/10, 20%; 0/8, 0%; 0/3, 0%, respectively), ofloxacin (8/10, 80%; 7/8, 87%; 3/3, 100%, respectively), and cotrimoxazole (10/10, 100%; 6/8, 75%; 3/3, 100%, respectively). CONCLUSION: Almost two-thirds (61.8%) of Enterobacteriaceae isolated from our blood cultures were ESBL producers. Only susceptibilities to carbapenems and to amikacin were fully conserved within the strains.

Efficacy of Adjunctive Tofacitinib Therapy in Mouse Models of Tuberculosis.

The global tuberculosis (TB) epidemic and the spread of multi- and extensively-drug resistant strains of Mycobacterium tuberculosis (M.tb) have been fueled by low adherence to following lengthy treatment protocols, and the rapid spread of HIV (Human Immunodeficiency Virus). Persistence of the infection in immunocompetent individuals follows from the ability of M.tb to subvert host immune responses in favor of survival within macrophages. Alternative host-directed strategies are therefore being currently sought to improve treatment efficacy and duration. In this study, we evaluated tofacitinib, a new oral Janus kinase (JAK) blocker with anti-inflammatory properties, in shortening tuberculosis treatment. BALB/c mice, which are immunocompetent, showed acceleration of M.tb clearance achieving apparent sterilization after 16 weeks of adjunctive tofacitinib therapy at average exposures higher than recommended in humans, while mice receiving standard treatment alone did not achieve clearance until 24 weeks. True sterilization with tofacitinib was not achieved until five months. C3HeB/FeJ mice, which show reduced pro-inflammatory cytokines during M.tb infection, did not show improved clearance with adjunctive tofacitinib therapy, indicating that the nature of granulomatous lesions and host immunity may influence responsiveness to tofacitinib. Our findings suggest that the JAK pathway could be explored further for host-directed therapy in immunocompetent individuals.

West African female sex workers in Mali: reduction in HIV prevalence and differences in risk profiles of sex workers of differing nationalities of origin.

BACKGROUND: Female sex workers (FSW) in Mali are highly vulnerable to HIV. Their prevalence in 2009 was 9 times higher (24.2%) than that among pregnant women (2.7%). METHODS: Four Integrated HIV/sexually transmitted infection (STI) Surveillance and Behavioral Surveys among FSW in Mali (2000, 2003, 2006, and 2009) tracked demographic characteristics, behavior, and HIV and STI prevalence. Logistic regression using generalized estimating equations to control for the cluster effect identified factors associated with HIV-positive serostatus adjusting for potential confounding. RESULTS: Of 2430 FSW, 40.8% were Nigerian, 36.8% were Malian, and 22.4% were from other neighboring countries. Between 2003 and 2009, HIV prevalence dropped from 44.14% to 28.49% (P < 0.0001) among Malians, from 21.33% to 12.71% (P = 0.0082) among Nigerians, and from 43.42% to 33.67% (P = 0.0442) among "others." Between 2000 and 2009, condom availability increased (89.18%-99.3%; P < 0.0001) as did HIV testing (40%-75%; P < 0.0001). Consistent condom use with clients improved for Malians (72.3%-81.5%; P = 0.0092), but not among Nigerians (92.7%-90.94%; P = 0.8240) and "others" (88.9%-88.48%; P = 0.8452). Consistent condom use with boyfriends was low and improved only for Nigerians (9.8%-28.4%; P = 0.0003). Factors associated with HIV prevalence in the multivariate model were older age, study year (2003 and 2006), nationality, lack of education, mobility, STI symptoms, gonorrhea prevalence, and younger age at first sex. CONCLUSIONS: This study documents progress in the fight against HIV among FSW in Mali. The different vulnerabilities to HIV found for different nationality FSW should be considered in programming and future research.

Antiretroviral treatment outcome in HIV-1-infected patients routinely followed up in capital cities and remote areas of Senegal, Mali and Guinea-Conakry.

INTRODUCTION: Access to antiretroviral treatment (ART) becomes more and more effective in resource-limited settings (RLS). However, this global effort would be even more profitable if the access to laboratory services especially in decentralized settings was strengthened. We report the virological outcome and HIV-1 drug resistance in three West African countries using dried blood spots (DBS) samples. METHODS: We included HIV-1-infected adults on ART ≥6 months and followed up in capital cities and decentralized sites in Senegal, Mali and Guinea-Conakry. Patients were consecutively enrolled and DBS were collected in field conditions and kept at ambient temperature before transfer to the reference laboratory. Viral load (VL) was quantified using the NucliSENS EasyQ HIV-1 v1.2. Genotyping of HIV-1 pol gene was performed using in-house protocol. RESULTS: Of the 407 participants, 119, 152 and 136 were from Senegal, Mali and Guinea-Conakry, respectively. The median treatment duration was 36 months [IQR: 6-136]. Virological failure (VF) (VL≥3log10 copies/mL) was observed in 26% (95% confidence interval (CI), 18-35; n=31), 11% (95% CI, 6-17; n=16) and 24% (95% CI, 17-32; n=33) of patients in Senegal, Mali and Guinea-Conakry, respectively (p=0.001). Of samples presenting VL≥3log10 copies/mL (n=80), 70 were successfully genotyped. At least one drug resistance mutation (DRM) was detected in the following proportions: 70% (95% CI, 50-86; n=19), 93% (95% CI, 68-100; n=14) and 68% (95% CI, 48-84; n=19) in Senegal, Mali and Guinea-Conakry, respectively (p=0.22). Twenty-six per cent (26%; 95% CI, 16-38; n=18) of patients in VF harboured wild-type viruses, which is likely indicative of weak adherence. Phylogenetic analysis showed the predominance of CRF02_AG subtype (73%; 95% CI, 61-83; n=51). CONCLUSIONS: We describe the ART outcome in capital and rural settings of Senegal, Mali and Guinea-Conakry. Our results in all of the three countries highlight the need to reinforce the ART adherence in order to minimize the occurrence of drug resistance. In addition, these findings provide additional evidence that the use of DBS as a sampling support could assist virological monitoring of patients on ART in remote areas.

[Follow-up of children born to HIV seropositive mothers in Mali]. / Suivi des nourrissons nés de mères séropositives au VIH au Mali.

INTRODUCTION: The rate of mother-to-child transmission without perinatal antiretroviral treatment is 30 to 40%. Antiretroviral treatment of new-borns from HIV infected mother has proved effective in reducing rates of mother-to child transmission. Our aim was to follow newborns of HIV infected mothers for 18 months in three of preventive mother to child transmission (PMTCT) health centres in Bamako and one in Koulikoro. METHODS: This was a longitudinal study with follow-up of a cohort of newborns from HIV-positive mothers over an 18-month period. Follow-up was based on clinical, laboratory and psychosocial parameters for 18 months. A questionnaire was used to collect data. All analyses were performed using ACCESS version 3 software. RESULTS: A total of 157 HIV-infected mothers and 161 children were included. Artificial feeding was performed in 93.2% of children. Antiretroviral prophylaxis was received by 89.8% of children and 100% of mothers. 72.67% (117/161) of the children were followed for 18 months, 3.4% were infected by HIV, 20% were lost to follow-up and 9.31% died. During follow-up, 68.2% of women shared information about their status with their husbands; 83.2% of husbands performed an HIV screening test and 58.4% presented positive HIV serology. CONCLUSION: Clinical, laboratory and psychosocial follow-up can be performed at PMTCT sites and may contribute to a reduction of mother-to-child transmission.

Molecular characterization of invasive meningococcal isolates from countries in the African meningitis belt before introduction of a serogroup A conjugate vaccine.

BACKGROUND: The serogroup A conjugate meningococcal vaccine, MenAfriVac, was introduced in mass vaccination campaigns in December 2010 in Burkina Faso, Mali and Niger. In the coming years, vaccination will be extended to other African countries at risk of epidemics. To document the molecular characteristics of disease-causing meningococcal strains circulating in the meningitis belt of Africa before vaccine introduction, the World Health Organization Collaborating Centers on Meningococci in Europe and United States established a common strain collection of 773 isolates from cases of invasive meningococcal disease collected between 2004 and 2010 from 13 sub-Saharan countries. METHODOLOGY: All isolates were characterized by multilocus sequence typing, and 487 (62%) were also analyzed for genetic variation in the surface antigens PorA and FetA. Antibiotic susceptibility was tested for part of the collection. PRINCIPAL FINDINGS: Only 19 sequence types (STs) belonging to 6 clonal complexes were revealed. ST-5 clonal complex dominated with 578 (74.8%) isolates. All ST-5 complex isolates were remarkably homogeneous in their PorA (P1.20,9) and FetA (F3-1) and characterized the serogroup A strains which have been responsible for most epidemics during this time period. Sixty-eight (8.8%) of the 773 isolates belonged to the ST-11 clonal complex which was mainly represented by serogroup W135, while an additional 38 (4.9%) W135 isolates belonged to the ST-175 complex. Forty-eight (6.2%) serogroup X isolates from West Africa belonged to the ST-181 complex, while serogroup X cases in Kenya and Uganda were caused by an unrelated clone, ST-5403. Serogroup X, ST-181, emerged in Burkina Faso before vaccine introduction. CONCLUSIONS: In the seven years preceding introduction of a new serogroup A conjugate vaccine, serogroup A of the ST-5 clonal complex was identified as the predominant disease-causing strain.

Superiority of 3 over 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine for the prevention of malaria during pregnancy in mali: a randomized controlled trial.

BACKGROUND: In 2003, Mali introduced intermittent preventive therapy in pregnancy (ITPp) with sulfadoxine-pyrimethamine (SP) for the control of malaria in pregnancy, consisting of 2 doses of SP given in the 2nd and 3rd trimester. This widely used regimen, although very effective, leaves many women unprotected from malaria during the last 4-to-8 weeks of gestation, which is a pivotal period for fetal weight gain. The aim of the study was to compare the efficacy and safety of 3-dose versus 2-dose IPTp-SP for the prevention of placental malaria and associated low birth weight (LBW). METHODS: We conducted a parallel-group, open-label, individually randomized controlled superiority trial involving 814 women of all gravidity, enrolled from April 2006 through March 2008. All women were seen at least 3 times and received either 2 (n = 401) or 3 (n = 413) doses of IPTp-SP. The primary endpoint measured was placental malaria, LBW, preterm births, and maternal anemia were secondary endpoints, and severe maternal skin reactions and neonatal jaundice were safety endpoints. RESULTS: Among the 96% of study subjects who were followed up until delivery, the prevalence of placental malaria was 2-fold lower in the 3-dose group (8.0%) than in the 2-dose group (16.7%); the adjusted prevalence ratio (APR) was 0.48 (95% confidence interval [CI], 0.32-0.71). LBW and preterm births were also reduced; the prevalence of LBW was 6.6% in the 3-dose group versus 13.3% in the 2-dose group (APR, 0.50; 95% CI, 0.32-0.79), and the prevalence of preterm births was 3.2% versus 8.9% (APR, 0.37; 95% CI, 0.19-0.71). No significant reductions in maternal anemia or differences in safety endpoints were observed. CONCLUSIONS: Adding a third dose of ITPp-SP halved the risk of placental malaria, LBW, and preterm births in all gravidae, compared with the standard 2-dose regimen, in this area of highly seasonal transmission with low levels of SP resistance. CLINICAL TRIALS REGISTRATION: ISRCTN 74189211.

[Cholera epidemics in Mali between 1995 and 2004]. / Les epidémies de choléra au Mali de 1995 & 2004.

INTRODUCTION: Cholera represents a public health problem in developing countries like Mali. AIM: This work aims to describe the characteristics of the cholera epidemics which occurred in Mali between 1995 and 2004. METHOD: A retrospective survey was conducted within the Division of the fight against the diseases of epidemic potential and the Institute of Public Health and Research of the Ministry of Health of Mali. Individual medical records tracking the follow-up of patients as well as the registers of these structures were used as sources to collect data for the study. RESULTS: There were 12,176 cases of cholera recorded, including 1,406 deaths, from 1995 to 2004. Cholera outbreaks in Mali have been a regular occurrence every year since 2001. The regions of Mopti and Segou seem to be the most impacted by these epidemics. The lethal rates were higher than 1% at the time of each of these epidemics during this period. Vibrio cholerae O: 1, biotype El Tor were responsible for the epidemics, and the serotype Ogawa was prevalent. CONCLUSION: Cholera epidemics have been constant in Mali since the beginning of the 21st century in spite of the efforts which have been made to prevent and control them. A rigorous analysis of the factors which support this persistence and appropriate measures are essential to reverse cholera in this country.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae in a Malian orphanage.

We show high rates of extended-spectrum beta-lactamase-producing Enterobacteriaceae carriage among the staff and children at an orphanage in Bamako, Mali. Enterobacteriaceae colonized in 100% and 63%, respectively, of the 38 children and 30 adults studied. Use of antimicrobial drugs appeared excessive and inappropriate; decontamination and hygiene protocols were also questioned.

[The movement of wild poliovirus in West Africa: the Malian case]. / Circulation des poliovirus sauvages en Afrique de l'Ouest: l'exemple du Mali.

The objective of this study was to examine the evolution of the movement patterns and trends of the wild poliovirus in Mali through surveillance of acute flaccid paralysis. A retrospective descriptive study was conducted between 1 January 1998 and 31 December 2005 on 1,002 cases of acute flaccid paralysis (AFP) investigated across the country. Reports made to the National Center for Immunization (CNI) of children under 15 years suffering from AFP were included as part of the epidemiological surveillance. The isolation of the poliovirus was done with stool examinations carried out at the Pasteur Institute in Abidjan. Among 1,002 cases of AFP, 156 stool samples were positive for enteroviruses including 59 cases of poliovirus (31 cases of polio vaccine and 28 cases of wild poliovirus), a frequency of 2.3%. Children 0 to 5 years of age were most affected by AFP (59.78%). Paralysis of the legs represented the most frequently affected zone (69.56%). The Mopti region was most heavily affected are with 11 cases of the 28 cases of wild poliovirus, of which boys were most affected (71.43%). Despite the efforts made so far in the fight against polio, wild poliovirus continues to circulate and spread in Mall and the West African sub-region. All countries in West Africa and on the African continent must reach a sufficient level of vaccination coverage in order to eradicate the wild strain like industrialized countries have.

The measles campaign in West and Central Africa: remembering the future.

The rainy season was once the harbinger of measles and child deaths in Western Africa, but measles has now become so uncommon that some younger West African doctors have never seen a single case. A series of successful measles campaigns were carried out in the late eighties through the early part of this century in West Africa--these campaigns have almost eliminated measles in Mali, the thirtieth poorest country in the world. This article provides a retelling of the measles campaigns that were carried out in West Africa during that time period for young doctors and vaccine researchers. The power of vaccination to stop an endemic disease from killing between 5 and 20% of children under the age of five living in rural villages in West and Central Africa is recalled, and the importance of vaccination for the improvement of human life is considered deserving of renewed emphasis.

Activité antibactérienne et antalgique de deux recettes traditionnelles utilisées dans le traitement des infections urinaires et la cystite au Mali

Pour la prise en charge des infections urinaires et la cystite, les plantes médicinales constituent une source de nouvelles molécules à activité antimicrobienne économiquement accessibles pour faire face à l'apparition de phénomènes de résistance des germes aux antibiotiques. Les infections urinaires et la cystite sont très répandues et constituent une préoccupation importante de santé publique dans les pays en développement: Environ 50% des femmes développent au moins une fois une infection symptomatique des voies urinaires dans leur vie. L'infection urinaire est, par ordre de fréquence, la première des maladies infectieuses non épidémiques. Le but de notre étude est de trouver dans la pharmacopée malienne des plantes dotées de propriétés antibactériennes et antalgiques. Cinq recettes et leurs plantes utilisées en médecine traditionnelle pour la prise en charge des infections urinaires et de la cystite ont été sélectionnées, sur la base de résultats d'enquêtes ethnobotaniques. Des extraits des recettes et leurs plantes ont été testés pour leur activité antibactérienne sur des germes responsables des infections urinaires et de la cystite. Les extraits des recettes contenant Stylosanthes erecta P. Beauv (Fabaceae) ont démontré une activité antibactérienne contre les souches cliniques de Escherichia coli, responsable de 75 à 80 % des infections urinaires. Les mêmes extraits ont démontré une activité antalgique contre la douleur provoquée par l'acide acétique chez les souris. Les propriétés antibactériennes et antalgiques peuvent être bénéfiques dans la prise en charge des infections urinaires et de la cystite

Evaluation of urban measles mass campaigns for children aged 9-59 months in Mali.

There are an estimated 234,000 cases of measles and 13,851 measles-related deaths per year in Mali. In 1998 and 1999, 548,309 children aged 9-59 months were vaccinated against measles during mass campaigns in urban centers across Mali. After the first campaign, measles incidence decreased by 95% in districts encompassing vaccinated urban centers and by 41% in nonvaccinated districts. There was no shift in the proportion of cases by age group in vaccinated centers. Measles in vaccinated districts after the campaign was likely related to persistent transmission in age groups not targeted for vaccination and among children living in nonvaccinated districts. The second campaign (1999) did not change the incidence of measles in vaccinated compared with nonvaccinated centers. Urban mass measles vaccination probably did not affect overall measles transmission in Mali. Mass vaccination of all children in Mali, targeting a larger age group, will be necessary to reach measles control objectives.