Scientific writing quality of theses in Medicine and Pharmacy at the University of Bamako (Mali).

AIM: To describe the scientific editorial quality of practice theses defended at the Faculties of Medicine and Pharmacy of Bamako (Mali), during the period 2016-2018. METHODS: This was a cross-sectional study conducted on practice theses in health science, defended between 2016 and 2018, and the electronic version of which was available at the libraries of the Faculties of Medicine and Pharmacy in Bamako. An adjusted STROBE grid was used to measure a scientific editorial conformity score for 18 iso-weighted items of the IMRaD structure (i.e. a total of 18 points). In this way, the scientific editorial quality of practice theses in health sciences was judged to be highly conform (14-18 points), fairly conform (9-13 points), poorly conform (5-8 points), or not conform (<5 points). An ordinal logistic regression model was used to identify determining factors independently associated with the scientific editorial quality of the health sciences practice thesis, with a significance level of 5%. RESULTS: A total of 534 practice theses in health sciences were included in this study, whose scientific editorial quality was judged to be highly or fairly conform (12.2%), poorly conform (43.1%) or not conform (44.8%). These standards scientific editorial conformity, which was higher in a "Medicine" thesis than in a "Pharmacy" thesis (ORa=2.45; IC95% [1.62-3.27], p<=0.05), was attributed to the supervisor's membership of a research structure (ORa=2.88; IC95% [1.6-3.2]; p<0.05). CONCLUSION: The research methodology profile of the practice health sciences thesis supervisor and the thesis section are associated with scientific editorial standard with the IMRaD.

A New Sequence Type of Neisseria meningitidis Serogroup C Associated With a 2016 Meningitis Outbreak in Mali.

In 2016, Mali reported a bacterial meningitis outbreak consisting of 39 suspected cases between epidemiologic weeks 9 and 17 with 15% case fatality ratio in the health district of Ouéléssebougou, 80 kilometers from the capital Bamako. Cerebrospinal fluid specimens from 29 cases were tested by culture and real-time polymerase chain reaction; 22 (76%) were positive for bacterial meningitis pathogens, 16 (73%) of which were Neisseria meningitidis (Nm). Of the Nm-positive specimens, 14 (88%) were N meningitidis serogroup C (NmC), 1 was NmW, and 1 was nongroupable. Eight NmC isolates recovered by culture from the outbreak were characterized using whole genome sequencing. Genomics analysis revealed that all 8 isolates belonged to a new sequence type (ST) 12446 of clonal complex 10217 that formed a distinct clade genetically similar to ST-10217, a NmC strain that recently caused large epidemics of meningitis in Niger and Nigeria. The emergence of a new ST of NmC associated with an outbreak in the African meningitis belt further highlights the need for continued molecular surveillance in the region.

Phylogenetic relationships and regional spread of meningococcal strains in the meningitis belt, 2011-2016.

BACKGROUND: Historically, the major cause of meningococcal epidemics in the meningitis belt of sub-Saharan Africa has been Neisseria meningitidis serogroup A (NmA), but the incidence has been substantially reduced since the introduction of a serogroup A conjugate vaccine starting in 2010. We performed whole-genome sequencing on isolates collected post-2010 to assess their phylogenetic relationships and inter-country transmission. METHODS: A total of 716 invasive meningococcal isolates collected between 2011 and 2016 from 11 meningitis belt countries were whole-genome sequenced for molecular characterization by the three WHO Collaborating Centers for Meningitis. FINDINGS: We identified three previously-reported clonal complexes (CC): CC11 (n = 434), CC181 (n = 62) and CC5 (n = 90) primarily associated with NmW, NmX, and NmA, respectively, and an emerging CC10217 (n = 126) associated with NmC. CC11 expanded throughout the meningitis belt independent of the 2000 Hajj outbreak strain, with isolates from Central African countries forming a distinct sub-lineage within this expansion. Two major sub-lineages were identified for CC181 isolates, one mainly expanding in West African countries and the other found in Chad. CC10217 isolates from the large outbreaks in Nigeria and Niger were more closely related than those from the few cases in Mali and Burkina Faso. INTERPRETATIONS: Whole-genome based phylogenies revealed geographically distinct strain circulation as well as inter-country transmission events. Our results stress the importance of continued meningococcal molecular surveillance in the region, as well as the development of an affordable vaccine targeting these strains. FUND: Meningitis Research Foundation; CDC's Office of Advanced Molecular Detection; GAVI, the Vaccine Alliance.

Triplex real-time PCR assay for the detection of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae directly from clinical specimens without extraction of DNA.

This study presents a triplex real-time PCR assay that allows for the direct detection of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in one reaction without DNA extraction, with similar sensitivity and specificity to singleplex assays. This approach saves time, specimen volume and reagents while achieving a higher testing throughput.

Triplex Real-Time PCR without DNA Extraction for the Monitoring of Meningococcal Disease.

Detection of Neisseria meningitidis has become less time- and resource-intensive with a monoplex direct real-time PCR (drt-PCR) to amplify genes from clinical specimens without DNA extraction. To further improve efficiency, we evaluated two triplex drt-PCR assays for the detection of meningococcal serogroups AWX and BCY. The sensitivity and specificity of the triplex assays were assessed using 228 cerebrospinal fluid (CSF) specimens from meningitis patients and compared to the monoplex for six serogroups. The lower limit of detection range for six serogroup-specific drt-PCR assays was 178⁻5264 CFU/mL by monoplex and 68⁻2221 CFU/mL by triplex. The triplex and monoplex showed 100% agreement for six serogroups and the triplex assays achieved similar sensitivity and specificity estimates as the monoplex drt-PCR assays. Our triplex method reduces the time and cost of processing CSF specimens by characterizing six serogroups with only two assays, which is particularly important for testing large numbers of specimens for N. meningitidis surveillance.

The Establishment and Diversification of Epidemic-Associated Serogroup W Meningococcus in the African Meningitis Belt, 1994 to 2012.

Epidemics of invasive meningococcal disease (IMD) caused by meningococcal serogroup A have been eliminated from the sub-Saharan African so-called "meningitis belt" by the meningococcal A conjugate vaccine (MACV), and yet, other serogroups continue to cause epidemics. Neisseria meningitidis serogroup W remains a major cause of disease in the region, with most isolates belonging to clonal complex 11 (CC11). Here, the genetic variation within and between epidemic-associated strains was assessed by sequencing the genomes of 92 N. meningitidis serogroup W isolates collected between 1994 and 2012 from both sporadic and epidemic IMD cases, 85 being from selected meningitis belt countries. The sequenced isolates belonged to either CC175 (n = 9) or CC11 (n = 83). The CC11 N. meningitidis serogroup W isolates belonged to a single lineage comprising four major phylogenetic subclades. Separate CC11 N. meningitidis serogroup W subclades were associated with the 2002 and 2012 Burkina Faso epidemics. The subclade associated with the 2012 epidemic included isolates found in Burkina Faso and Mali during 2011 and 2012, which descended from a strain very similar to the Hajj (Islamic pilgrimage to Mecca)-related Saudi Arabian outbreak strain from 2000. The phylogeny of isolates from 2012 reflected their geographic origin within Burkina Faso, with isolates from the Malian border region being closely related to the isolates from Mali. Evidence of ongoing evolution, international transmission, and strain replacement stresses the importance of maintaining N. meningitidis surveillance in Africa following the MACV implementation. IMPORTANCE Meningococcal disease (meningitis and bloodstream infections) threatens millions of people across the meningitis belt of sub-Saharan Africa. A vaccine introduced in 2010 protects against Africa's then-most common cause of meningococcal disease, N. meningitidis serogroup A. However, other serogroups continue to cause epidemics in the region-including serogroup W. The rapid identification of strains that have been associated with prior outbreaks can improve the assessment of outbreak risk and enable timely preparation of public health responses, including vaccination. Phylogenetic analysis of newly sequenced serogroup W strains isolated from 1994 to 2012 identified two groups of strains linked to large epidemics in Burkina Faso, one being descended from a strain that caused an outbreak during the Hajj pilgrimage in 2000. We find that applying whole-genome sequencing to meningococcal disease surveillance collections improves the discrimination among strains, even within a single nation-wide epidemic, which can be used to better understand pathogen spread.

Immunization Coverage Surveys and Linked Biomarker Serosurveys in Three Regions in Ethiopia.

OBJECTIVE: Demographic and health surveys, immunization coverage surveys and administrative data often divergently estimate vaccination coverage, which hinders pinpointing districts where immunization services require strengthening. We assayed vaccination coverage in three regions in Ethiopia by coverage surveys and linked serosurveys. METHODS: Households with children aged 12-23 (N = 300) or 6-8 months (N = 100) in each of three districts (woredas) were randomly selected for immunization coverage surveys (inspection of vaccination cards and immunization clinic records and maternal recall) and linked serosurveys. IgG-ELISA serologic biomarkers included tetanus antitoxin ≥ 0.15 IU/ml in toddlers (receipt of tetanus toxoid) and Haemophilus influenzae type b (Hib) anti-capsular titers ≥ 1.0 mcg/ml in infants (timely receipt of Hib vaccine). FINDINGS: Coverage surveys enrolled 1,181 children across three woredas; 1,023 (87%) also enrolled in linked serosurveys. Administrative data over-estimated coverage compared to surveys, while maternal recall was unreliable. Serologic biomarkers documented a hierarchy among the districts. Biomarker measurement in infants provided insight on timeliness of vaccination not deducible from toddler results. CONCLUSION: Neither administrative projections, vaccination card or EPI register inspections, nor parental recall, substitute for objective serological biomarker measurement. Including infants in serosurveys informs on vaccination timeliness.

Development of Real-Time PCR Methods for the Detection of Bacterial Meningitis Pathogens without DNA Extraction.

Neisseria meningitidis (Nm), Haemophilus influenzae (Hi), and Streptococcus pneumoniae (Sp) are the lead causes of bacterial meningitis. Detection of these pathogens from clinical specimens using traditional real-time PCR (rt-PCR) requires DNA extraction to remove the PCR inhibitors prior to testing, which is time consuming and labor intensive. In this study, five species-specific (Nm-sodC and -ctrA, Hi-hpd#1 and -hpd#3 and Sp-lytA) and six serogroup-specific rt-PCR tests (A, B, C, W, X, Y) targeting Nm capsular genes were evaluated in the two direct rt-PCR methods using PerfeCTa and 5x Omni that do not require DNA extraction. The sensitivity and specify of the two direct rt-PCR methods were compared to TaqMan traditional rt-PCR, the current standard rt-PCR method for the detection of meningitis pathogens. The LLD for all 11 rt-PCR tests ranged from 6,227 to 272,229 CFU/ml for TaqMan, 1,824-135,982 for 5x Omni, and 168-6,836 CFU/ml for PerfeCTa. The diagnostic sensitivity using TaqMan ranged from 89.2%-99.6%, except for NmB-csb, which was 69.7%. For 5x Omni, the sensitivity varied from 67.1% to 99.8%, with three tests below 90%. The sensitivity of these tests using PerfeCTa varied from 89.4% to 99.8%. The specificity ranges of the 11 tests were 98.0-99.9%, 97.5-99.9%, and 92.9-99.9% for TaqMan, 5x Omni, and PerfeCTa, respectively. PerfeCTa direct rt-PCR demonstrated similar or better sensitivity compared to 5x Omni direct rt-PCR or TaqMan traditional rt-PCR. Since the direct rt-PCR method does not require DNA extraction, it reduces the time and cost for processing CSF specimens, increases testing throughput, decreases the risk of cross-contamination, and conserves precious CSF. The direct rt-PCR method will be beneficial to laboratories with high testing volume.

Strategies for Coordination of a Serosurvey in Parallel with an Immunization Coverage Survey.

A community-based immunization coverage survey is the standard way to estimate effective vaccination delivery to a target population in a region. Accompanying serosurveys can provide objective measures of protective immunity against vaccine-preventable diseases but pose considerable challenges with respect to specimen collection and preservation and community compliance. We performed serosurveys coupled to immunization coverage surveys in three administrative districts (woredas) in rural Ethiopia. Critical to the success of this effort were serosurvey equipment and supplies, team composition, and tight coordination with the coverage survey. Application of these techniques to future studies may foster more widespread use of serosurveys to derive more objective assessments of vaccine-derived seroprotection and monitor and compare the performance of immunization services in different districts of a country.

[Study of the impact of breeding sites on the infectivity of P. falciparum gametocytes to An. gambiae s.l in malaria-endemic area of Nanguilabougou.-Mali]. / Etude de l'impact des gites larvaires sur l'infectivite des gametocytes de Plasmodium Falciparum chez Anopheles Gambiae s.l en zone d'endemie palustre de Nanguilabougou - Mali.

Numerous studies have shown the influence of some bacteria colonizing the breeding sites on the development of the parasite in Anopheles malaria vectors. The aim of this study was to evaluate the impact of the breeding sites of Plasmodium falciparum on the gametocytes infectivity of Anopheles gambiae sl using the membrane feeding method. We carried out an experimental infestation study from September 2010 to January 2011 in a village located in the southern savanna of Mali. Cross sectional surveys were conducted to collect larvae and to select gametocyte carriers. Female offspring of L3 and L4 stage larvae were used for the experimental infestation. The gametocyte carriers were children aged within 4 to 12 years. Bacteria identified in breeding water of larvae and adult mosquitoes were: Escherichia coli, Salmonella spp, Klebsiella oxytoca, Pseudomonas spp, Staphylococcus spp, Shigella sp. The oocyst load of infected mosquitoes did not significantly vary according to the samples (F = 1.517, P = 0.230). Low infection rates (5.4% and 2.8%) were observed in the larval bedding and in mosquitoes containing K. oxytoca and Shigella. The blood feeding rates (62.4%; 60.9%; 67.7%) and mortality (66.4%; 64.9%; 61.9%) of An. gambiae did not significantly vary depending on the breeding sites [(P = 0.15); (P = 0.22)].

De nombreuses études ont montré l'influence de certaines bactéries vivant dans les gites larvaires sur le développement du parasite chez les anophèles vecteurs du paludisme. Le but du présent travail consistait à étudier l'impact des gites larvaires sur l'infectivité des gamétocytes de Plasmodium falciparum chez Anopheles gambiae s.l par la technique d'infestation sur membrane. Pour réaliser ce travail, une étude d'infestation expérimentale a été conduite de septembre 2010 à janvier 2011 dans un village de savane sud soudanienne du Mali. Des passages transversaux ont été effectués pour la collecte des larves et la sélection des porteurs de gamétocytes. Les femelles issues des larves de stades L3 et L4 ont été utilisées pour les séances d'infestation expérimentale. Les enfants porteurs de gamétocytes étaient âgés de 4 à 12 ans. Les bactéries identifiées dans l'eau des gites chez les larves et les adultes de moustiques étaient : Escherichia coli, Salmonella s.p., Klebsiella oxytoca, Pseudomonas s.p., Staphylococcus s.p., Shigella sp. La charge oocystique des moustiques infectés n'avait pas varié de façon significative en fonction des gites (F=1,517 ; P=0,230). De faibles taux d'infection (5,4% et 2,8%) ont été observés dans les gites et chez les moustiques contenant K. oxytoca et Shigella. Le taux d'engorgement (62,4% ; 60,9% ; 67,7%) et le taux de mortalité (66,4% ; 64,9% ; 61,9%) d'An. gambiae n'ont pas varié significativement en fonction des gites larvaires,[(P= 0,15) ; (P= 0,22)].

[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.

North-South exchange and professional development: experience from Mali and France.

BACKGROUND: Developing countries are facing the challenge of developing a family practice culture in a context in which clinical practice remains strongly associated with hospital practice. To what extent can professional exchange between GPs from North and South fuel novel professional identities in family practice? OBJECTIVES: Assess to what extent a North-South professional exchange programme involving rural GPs from Mali and France affected practice development and professional identity formation of Malian GPs. METHODS: Qualitative analysis of 19 exchanges between rural GPs from Mali and France based on (i) interviews; (ii) retrospective report analysis; (iii) field observation of three exchanges; (iv) workshop with Malian GPs; and (v) workshop with French GPs. RESULTS: Malian GPs reported increased self-esteem, increased concern for doctor-patient communication and innovations in practice organization. Although Malian participants considered a transfer from France's general practice irrelevant, the experience was thought provoking. The interpersonal and professional interaction was crucial. The Malian Rural Doctors Association provided a platform to capitalize on individual experiences in a process of collective professional identity construction. Costs of the programme were kept low, limiting possible side expectations of participants. CONCLUSIONS: North-South professional exchange can contribute to professional development. Exchange programmes should be designed as mutual learning processes, rather than unilateral assistance or transfer of practice models. Southern family practitioners are likely to improve primary care to individuals and families, while Northern GPs can draw lessons from the community perspective of primary health care in the South. Recruitment and preparation of participants are crucial, as well as collective reflection upon return.