Assessing the accuracy of health facility typology in representing the availability of health services: a case study in Mali.

INTRODUCTION: Using health facility types as a measure of service availability is a common approach in international standards for health system policy and planning. However, this proxy may not accurately reflect the actual availability of specific health services. OBJECTIVE: This study aims to evaluate the reliability of health facility typology as an indicator of specific health service availability and explore whether certain facility types consistently provide particular services. DESIGN: We analysed a comprehensive dataset containing information from 1725 health facilities in Mali. To uncover and visualise patterns within the dataset, we used two analytical techniques: Multiple Correspondence Analysis and Between-Class Analysis. These analyses allowed us to quantitatively measure the influence of health facility types on the variation in health service provisioning. Additionally, we developed and calculated a Consistency Index, which assesses the consistency of a health facility type in providing specific health services. By examining various health facilities and services, we sought to determine the accuracy of facility types as indicators of service availability. SETTING: The study focused on the health system in Mali as a case study. RESULTS: Our findings indicate that using health facility types as a proxy for service availability in Mali is not an accurate representation. We observed that most of the variation in service provision does not stem from differences between facility types but rather within facility types. This suggests that relying solely on health facility typology may lead to an incomplete understanding of health service availability. CONCLUSIONS: These results have significant implications for health policy and planning. The reliance on health facility types as indicators for health system policy and planning should be reconsidered. A more nuanced and evidence-based understanding of health service availability is crucial for effective health policy and planning, as well as for the assessment and monitoring of health systems.

Master's degree in sexual and reproductive health: enhancing career development opportunities for midwives in Mali.

BACKGROUND: Midwives' contribution to improving outcomes for women and newborns depends on factors such as quality of pre-service training, access to continuing professional development, and the presence of an enabling work environment. The absence of opportunities for career development increases the likelihood that health professionals, including midwives, will consider leaving the profession due to a lack of incentives to sustain and increase motivation to remain in the field. It also limits the opportunities to better contribute to policy, training, and research. This study aimed to assess the influence of a Master in Sexual and Reproductive Health (SRH) at the INFSS on midwives' career progression in Mali. METHODS: This mixed methods study was conducted using an online questionnaire, semi-structured interviews, and a document review. The study participants included graduates from two cohorts (N = 22) as well as employers, managers, and teachers of the graduates (N = 20). Data were analysed according to research questions, comparing, and contrasting answers between different groups of respondents. RESULTS: The study revealed that graduates enrolled in the programme primarily to improve their knowledge and skills in management and public health. The graduates' expected roles are those of programme and health project manager and participation in planning and monitoring activities at national or sub-national level. The managers expected the programme to reflect the needs of the health system and equip midwives with skills in management and planning. The Master enhanced opportunities for graduates to advance their career in fields they are not usually working in such as management, research, and supervision. However, the recognition of the master's degree and of the graduates' profile is not yet fully effective. CONCLUSION: The master's degree in SRH is a capacity building programme. Graduates developed skills and acquired advanced knowledge in research and management, as well as a postgraduate degree. However, the master programme needs to be better aligned with health system needs to increase the recognition of graduates' skills and have a more positive impact on graduates' careers.

Protocol for a parallel group, two-arm, superiority cluster randomised trial to evaluate a community-level complementary-food safety and hygiene and nutrition intervention in Mali: the MaaCiwara study (version 1.3; 10 November 2022).

BACKGROUND: Diarrhoeal disease remains a significant cause of morbidity and mortality among the under-fives in many low- and middle-income countries. Changes to food safety practices and feeding methods around the weaning period, alongside improved nutrition, may significantly reduce the risk of disease and improve development for infants. We describe a protocol for a cluster randomised trial to evaluate the effectiveness of a multi-faceted community-based educational intervention that aims to improve food safety and hygiene behaviours and enhance child nutrition. METHODS: We describe a mixed-methods, parallel group, two-arm, superiority cluster randomised controlled trial with baseline measures. One hundred twenty clusters comprising small urban and rural communities will be recruited in equal numbers and randomly allocated in a 1:1 ratio to either treatment or control arms. The community intervention will be focussed around an ideal mother concept involving all community members during campaign days with dramatic arts and pledging, and follow-up home visits. Participants will be mother-child dyads (27 per cluster period) with children aged 6 to 36 months. Data collection will comprise a day of observation and interviews with each participating mother-child pair and will take place at baseline and 4 and 15 months post-intervention. The primary analysis will estimate the effectiveness of the intervention on changes to complementary-food safety and preparation behaviours, food and water contamination, and diarrhoea. Secondary outcomes include maternal autonomy, enteric infection, nutrition, child anthropometry, and development scores. A additional structural equation analysis will be conducted to examine the causal relationships between the different outcomes. Qualitative and health economic analyses including process evaluation will be done. CONCLUSIONS: The trial will provide evidence on the effectiveness of community-based behavioural change interventions designed to reduce the burden of diarrhoeal disease in the under-fives and how effectiveness varies across different contexts. TRIAL REGISTRATION: ISRCTN14390796. Registration date December 13, 2021.

Impact of extramural DAIT/NIAID pharmacy programs, research pharmacist scientist oversight on study performance, and lessons learned.

PURPOSE: Over the past two decades, the involvement of a Pharmacist Scientist in clinical settings has improved patient safety, decreased medication errors, and enabled successful conduct of clinical trials and faster product development [1-5]. The impact of an oversight by a Pharmacist Scientist on clinical trial performance and execution in terms of Pharmacy and Investigational Product (IP)-related deviations has not been evaluated by a sponsor. METHODS: This was a retrospective observational study conducted by the Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID). We assessed the association of the number of Pharmacy and Investigational Product (IP)-related deviations with Pharmacist oversight and use of DAIT Pharmacy/ Pharmaceutical services in two groups: Intervention Group (IG) and the Control Group (CG). RESULTS: We evaluated monitoring data from 116 studies conducted between 2006 through 2020. Forty-one eligible clinical trials were included and analyzed: 13 trials were in the IG with Pharmacist oversight and use of Pharmacy Services; 28 trials were in the CG with no Pharmacist oversight and zero to partial use DAIT Pharmacy/ Pharmaceutical Services. The evaluation revealed the expected risk of having a pharmacy and IP-related deviations were 2.94 times higher (95% CI 1.28, 6.67, = 0.01) in trials not having Pharmacist oversight and zero to partial use of Pharmaceutical/ Pharmacy Program services. This significant finding was associated with having Pharmacist oversight when adjusting for study size (# of sites and patients needed), anticipated study duration, design complexity, and whether recruitment was completed or not. CONCLUSION: We found a statistically significant association between Pharmacist Scientist involvement and oversight from protocol development to study execution and a reduction in Pharmacy and IP-related deviations.

Genome-wide association study of leprosy in Malawi and Mali.

Leprosy is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae. Despite recent improvements in disease control, leprosy remains an important cause of infectious disability globally. Large-scale genetic association studies in Chinese, Vietnamese and Indian populations have identified over 30 susceptibility loci for leprosy. There is a significant burden of leprosy in Africa, however it is uncertain whether the findings of published genetic association studies are generalizable to African populations. To address this, we conducted a genome-wide association study (GWAS) of leprosy in Malawian (327 cases, 436 controls) and Malian (247 cases, 368 controls) individuals. In that analysis, we replicated four risk loci previously reported in China, Vietnam and India; MHC Class I and II, LACC1 and SLC29A3. We further identified a novel leprosy susceptibility locus at 10q24 (rs2015583; combined p = 8.81 × 10-9; OR = 0.51 [95% CI 0.40 - 0.64]). Using publicly-available data we characterise regulatory activity at this locus, identifying ACTR1A as a candidate mediator of leprosy risk. This locus shows evidence of recent positive selection and demonstrates pleiotropy with established risk loci for inflammatory bowel disease and childhood-onset asthma. A shared genetic architecture for leprosy and inflammatory bowel disease has been previously described. We expand on this, strengthening the hypothesis that selection pressure driven by leprosy has shaped the evolution of autoimmune and atopic disease in modern populations. More broadly, our data highlights the importance of defining the genetic architecture of disease across genetically diverse populations, and that disease insights derived from GWAS in one population may not translate to all affected populations.

Adoption of harmonisation policy for the midwives' training programme in Mali: A policy analysis.

West Africa is engaged in a process of harmonising health workers' training programmes as a means to regulate regional training standards and thus improve their quality. There is currently a lack of documented information regarding the adoption of these revised training programmes. In 2012 a harmonised programme, the WAHO competency-based curriculum, was introduced in Mali for training midwives. The present study explores the barriers and facilitators of the adoption of this programme and how the content, context, process, and actor-related factors influenced this. We used a qualitative research design consisting of document analysis (n = 25) and semi-structured interviews (n = 21) with policymakers, students, and those in charge of implementing the training programme. Information was collected on education and training policies, the context and process of the harmonised curriculum development, its adoption, and the actors involved in the adoption strategy, along with their role. The study shows that the adoption of the harmonised curriculum in Mali offered midwives an opportunity to attain a higher standard of training and level of qualification than before. It also displayed both the government's and the public school's willingness and commitment to improve maternal and child health through enhancing midwives' training standards. The most salient factors that influenced adoption were the lack of available resources, and the lack of involvement of, and coordination with, relevant actors for successful policy adoption. Mali's experience of adopting the harmonisation policy of training curricula demonstrates the need for the authorities to collaborate with relevant actors for information dissemination and in the adoption process. It also demonstrates the need for finding innovative ways to secure and diversify funding opportunities, as well as establish a supervisory body for health worker training.

Impact of Three-Year Intermittent Preventive Treatment Using Artemisinin-Based Combination Therapies on Malaria Morbidity in Malian Schoolchildren.

Previous studies have shown that a single season of intermittent preventive treatment in schoolchildren (IPTsc) targeting the transmission season has reduced the rates of clinical malaria, all-cause clinic visits, asymptomatic parasitemia, and anemia. Efficacy over the course of multiple years of IPTsc has been scantly investigated. METHODS: An open, randomized-controlled trial among schoolchildren aged 6-13 years was conducted from September 2007 to January 2010 in Kolle, Mali. Students were included in three arms: sulphadoxine-pyrimethamine+artesunate (SP+AS), amodiaquine+artesunate (AQ+AS), and control (C). All students received two full doses, given 2 months apart, and were compared with respect to the incidence of clinical malaria, all-cause clinic visits, asymptomatic parasitemia, and anemia. RESULTS: A total of 296 students were randomized. All-cause clinic visits were in the SP+AS versus control (29 (20.1%) vs. 68 (47.2%); 20 (21.7%) vs. 41 (44.6%); and 14 (21.2%) vs. 30 (44.6%); p < 0.02) in 2007, 2008, and 2009, respectively. The prevalence of asymptomatic parasitemia was lower in the SP+AS compared to control (38 (7.5%) vs. 143 (28.7%); and 47 (12.7%) vs. 75 (21.2%); p < 0.002) in 2007 and 2008, respectively. Hemoglobin concentration was significantly higher in children receiving SP+AS (11.96, 12.06, and 12.62 g/dL) than in control children (11.60, 11.64, and 12.15 g/dL; p < 0.001) in 2007, 2008, and 2009, respectively. No impact on clinical malaria was observed. CONCLUSION: IPTsc with SP+AS reduced the rates of all-cause clinic visits and anemia during a three-year implementation.

Career mobility of maternal care providers in Mali: a mixed method study on midwives and obstetric nurses.

BACKGROUND: An important strategy to reduce maternal and child mortality in Mali is to increase the number of deliveries assisted by qualified personnel in primary care facilities, especially in rural areas. However, placements and retention of healthcare professionals in rural areas are a major problem, not only in Mali but worldwide, and are a challenge to the health sector. The purpose of this study was to map the mobility of midwives and obstetric nurses during their work lives, in order to better understand their career paths and the role that working in rural areas plays. This article contributes to the understanding of career mobility as a determinant of the retention of rural health professionals. METHODS: A mixed method study was conducted on 2005, 2010, and 2015 cohorts of midwives and obstetric nurses. The cohorts have been defined by their year of graduation. Quantitative data were collected from 268 midwives and obstetric nurses through questionnaires. Qualitative data had been gathered through semi-structured interviews from 25 midwives and stakeholders. A content analysis was conducted for the qualitative data. RESULTS: Unemployment rate was high among the respondents: 39.4% for midwives and 59.4% for obstetric nurses. Most of these unemployed nurses and midwives are working, but unpaid. About 80% of the employed midwives were working in urban facilities compared to 64.52% for obstetric nurses. Midwives were employed in community health centers (CSCom) (43%), referral health centers (CSRef) (20%), and private clinics and non-governmental organizations (NGO) (15%). The majority of midwives and obstetric nurses were working in the public sector (75.35%) and as civil servants (65.5%). The employment status of midwives and obstetric nurses evolved from private to public sector, from rural to urban areas, and from volunteer/unpaid to civil servants through recruitment competitions. Qualitative data supported the finding that midwives and obstetric nurses prefer to work as civil servant and preferably in urban areas and CSRef. CONCLUSION: The current mobility pattern of midwives and obstetric nurses that brings them from rural to urban areas and towards a civil servant status in CSRef shows that it is not likely to increase their numbers in the short term in places where qualified midwives are most needed.

Rural pipeline and willingness to work in rural areas: Mixed method study on students in midwifery and obstetric nursing in Mali.

The availability and retention of healthcare professionals in rural areas and remote areas is a challenge to the health sector worldwide. Attracting people who are most likely to be interested in rural practice can be conducive to the sustainable availability of health services in rural areas where health facilities are typically understaffed and existing professionals often underqualified. This article aims to contribute to the rural pipeline evidence, and reports on the findings of a study that investigated the career choices of midwifery and obstetric nurse students in Mali. The article enquires into the relationship between their intention to practice in rural areas and the different components of the rural pipeline. A mixed method study using a survey, semi-structured interviews, and document analysis was conducted from October to December 2017 on third-year midwifery and obstetric nurse students and school-managers. Descriptive statistics and bivariate analysis were performed for quantitative data, and content analysis was carried out for the qualitative data. Key findings suggest that students prefer urban locations for living and for work. The intention to work in rural areas seems to be influenced by the current living situation (currently living in a rural area) or having attended secondary school or professional training in rural areas.

Differential infectivity of gametocytes after artemisinin-based combination therapy of uncomplicated falciparum malaria.

BACKGROUND: Most malaria-endemic countries use artemisinin-based combination therapy (ACT) as their first-line treatment. ACTs are known to be highly effective on asexual stages of the malaria parasite. Malaria transmission and the spread of resistant parasites depend on the infectivity of gametocytes. The effect of the current ACT regimens on gametocyte infectivity is unclear. OBJECTIVES: This study aimed to determine the infectivity of gametocytes to Anopheles gambiae following ACT treatment in the field. METHODS: During a randomised controlled trial in Bougoula-Hameau, Mali, conducted from July 2005 to July 2007, volunteers with uncomplicated malaria were randomised to receive artemether-lumefantrine, artesunate-amodiaquine, or artesunate-sulfadoxine/pyrimethamine. Volunteers were followed for 28 days, and gametocyte carriage was assessed. Direct skin feeding assays were performed on gametocyte carriers before and after ACT administration. RESULTS: Following artemether-lumefantrine treatment, gametocyte carriage decreased steadily from Day 0 to Day 21 post-treatment initiation. In contrast, for the artesunate-amodiaquine and artesunate-sulfadoxine/pyrimethamine arms, gametocyte carriage increased on Day 3 and remained constant until Day 7 before decreasing afterward. Mosquito feeding assays showed that artemether-lumefantrine and artesunate-amodiaquine significantly increased gametocyte infectivity to Anopheles gambiae sensu lato (s.l.) (p < 10-4), whereas artesunate-sulfadoxine/pyrimethamine decreased gametocyte infectivity in this setting (p = 0.03). CONCLUSION: Different ACT regimens could lead to gametocyte populations with different capacity to infect the Anopheles vector. Frequent assessment of the effect of antimalarials on gametocytogenesis and gametocyte infectivity may be required for the full assessment of treatment efficacy, the potential for spread of drug resistance and malaria transmission in the field.

The WHO recommendation of home fortification of foods with multiple-micronutrient powders in children under 2 years of age and its effectiveness on anaemia and weight: a pragmatic cluster-randomized controlled trial.

OBJECTIVE: To assess under real community settings the effectiveness of the WHO strategy of home fortification of foods (HFF) with multiple-micronutrient powders on Hb change, anaemia and weight in children. DESIGN: A pragmatic cluster-randomized controlled trial. SETTING: Forty villages in the Nioro Circle in Mali and 722 children aged 6-23 months were randomized to the intervention or control group. The intervention consisted of a daily dose of multiple-micronutrient powder for 3 months; in the control group, no supplement was given. In both groups, mothers received group education on child complementary feeding. Changes in weight, Hb concentration and anaemia were assessed as primary outcomes at baseline and 3 months. The HFF effect was determined using regression analyses and quantile regression with standard errors taking account of the cluster design. SUBJECTS: Children aged 6-23 months. RESULTS: Overall prevalence of anaemia in the sample was high: 90 %. HFF provided a modest but statistically significant Hb change v. no intervention (0·50 v. 0·09 g/dl, P=0·023). Prevalence of anaemia changed little: 91·3-85·8 % (P=0·04) in the intervention group v. 88·1-87·5 % % (P=0·86) in the control group. Proportion of severe anaemia was reduced by 84 % (from 9·8 to 1·6 %) in the intervention group, but increased in the control group (from 8·5 to 10·8 %). No effect was observed on weight. CONCLUSIONS: The WHO HFF strategy to fight anaemia showed a modest change on Hb concentration and significantly reduced the rate of severe anaemia.

[Midwives' intention to leave primary level care services in Mali]. / Intention de quitter les services de premier niveau chez les sages-femmes et infirmières-obstétriciennes au Mali.

BACKGROUND: Mali is a country with a high rate of maternal and neonatal deaths and a low density of human resources for health. The health system faces understaffing and inequitable distribution of available resources. Health staff are reluctant to take positions and stay in first level care services. This study examines midwives and obstetric nurses' intention to leave their current positions in first level structures and management factors that influence this intention. METHODS: A cross-sectional mixed method study was conducted with 220 midwives and obstetric nurses in 46 primary healthcare services of three health regions. Questionnaires and interview guide were used. Descriptive statistics and bi-varied analyses tested the links between managerial practices, demographic characteristics and intention to leave. A thematic analysis of the qualitative data examined the factors underlying the intention to leave. RESULTS: Nearly half of midwives and obstetric nurses in primary healthcare services had the intention to leave their current positions. This intention to leave is more marked among midwives who have very little attraction for first-level service. Age, type of structure and area of assignment are strongly associated with the intention to leave. Managerial practices that differ according to locations and type of structures seem to influence the intention to leave. CONCLUSION: There is a high intention to leave their position among midwives and obstetric nurses in first level services. Managerial practices seem to have more influences on the intention to leave in rural areas and among obstetric nurses.

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

Phase 1 randomized controlled trial to evaluate the safety and immunogenicity of recombinant Pichia pastoris-expressed Plasmodium falciparum apical membrane antigen 1 (PfAMA1-FVO [25-545]) in healthy Malian adults in Bandiagara.

BACKGROUND: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel(®) was assessed in malaria-experienced Malian adults. The malaria vaccine, PfAMA1-FVO [25-545] is a recombinant protein Pichia pastoris-expressed AMA-1 from Plasmodium falciparum FVO clone adsorbed to Alhydrogel(®), the control vaccine was tetanus toxoid produced from formaldehyde detoxified and purified tetanus toxin. METHODS: A double blind randomized controlled phase 1 study enrolled and followed 40 healthy adults aged 18-55 years in Bandiagara, Mali, West Africa, a rural setting with intense seasonal transmission of P. falciparum malaria. Volunteers were randomized to receive either 50 µg of malaria vaccine or the control vaccine. Three doses of vaccine were given on Days 0, 28 and 56, and participants were followed for 1 year. Solicited symptoms were assessed for seven days and unsolicited symptoms for 28 days after each vaccination. Serious adverse events were assessed throughout the study. The titres of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed. RESULTS: Commonest local solicited adverse events were the injection site pain and swelling more frequent in the PfAMA1 group. No vaccine related serious adverse events were reported. A significant 3.5-fold increase of anti-AMA-1 IgG antibodies was observed in malaria vaccine recipients four weeks after the third immunization compared to the control group. CONCLUSION: The PfAMA1 showed a good safety profile. Most adverse events reported were of mild to moderate intensity. In addition, the vaccine induced a significant though short-lived increase in the anti-AMA1 IgG titres. Registered on www.clinicaltrials.gov with the number NCT00431808.

[Endoscopic contribution in the dilatation of caustic esophagus stenosis]. / Apport des moyens endoscopiques dans la dilatation des sténoses caustiques de l'œsophage.

INTRODUCTION: The aim of this work was to present the contribution of the endoscopy in the management of esophageal dilatation for caustic esophageal stenosis (CES). METHODS: This was a descriptive and prospective study in the thoracic surgery department at the Hospital of Mali. A total of 46 cases of CES is recorded and divided into 4 groups according to the topography of the esophageal lesions. For the different methods of dilatation the number of performed endoscopic support was determined to understand the contribution of endoscopic means in the success of dilatation for CES. The outcome, complications and mortality in the two methods were compared. RESULTS: Fibroscopy was used in 41.30% of patients with Savary Guillard dilators and in 47.82% of patients with Lerut dilators. Video laryngoscopy was used in 58.69% of patients who underwent dilatation with Lerut dilators. The passage of the guide wire was performed in 39.13% under video laryngoscopy and 58.68% under fibroscopy. In comparison of the two methods, there is a significant difference in the occurrence of complications (p=0.04075), general anesthesia (p=0.02287), accessibility (p=0.04805) and mortality (p=0.00402). CONCLUSION: The CES is a serious disease and under evaluated in Mali. The endoscopies contribute significantly to the success of esophageal dilatation for caustic stenosis in the different methods we used.

Conflict, displacement and sexual and reproductive health services in Mali: analysis of 2013 health resources availability mapping system (HeRAMS) survey.

OBJECTIVE: Little is known specifically about the effects of conflict and displacement on provision of sexual and reproductive health (SRH) services. We aimed to understand the association between levels of conflict and displacement and the availability of SRH services in post-conflict Mali. METHODS: A national assessment was conducted between April and May 2013 employing Health Systems Availability Mapping System (HeRAMS). Data from 1581 primary care facilities were analysed, focusing on SRH services. Descriptive analyses and multivariable logistic regression models were used to examine the availability of SRH services by different levels of conflict and displacement. FINDINGS: Of 1581 facilities, 1551 had data available to identify the details of service provision. The majority of the facilities were part of the public sector (79.1 %), identified as basic community primary care facilities (71.9 %). Overall 15.7 % of the facilities were in the zones under occupation, 40.3 % in the areas with high concentration of displaced population and 44 % in areas with low concentration of displaced populations. Between zones of low concentration of displaced populations and under occupation the likelihood of service availability varied between OR: 2.9 (95 % CI 2.0-4.4) for basic emergency obstetric care and OR: 41.7 (95 % CI 20.4-85.3) for family planning. All of the services within the three domains of SRH were more likely to be available in the low and high concentration displaced population areas compared to the facilities in the under occupation zones, after adjusting for other facility-related variables. CONCLUSION: Areas with high concentration of displaced population had less service availability, and areas formerly under occupation had the least service availability. This suggests that those living in conflict areas, and many of those who are internally displaced, have poor access to essential SRH interventions. The systematic measurement of the availability of health services, including SRH, is feasible and can contribute to recovery planning in post-conflict and humanitarian settings.

Genetic determinants of anti-malarial acquired immunity in a large multi-centre study.

BACKGROUND: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. METHODS: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. RESULTS: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. CONCLUSION: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.

Urban schistosomiasis and associated determinant factors among school children in Bamako, Mali, West Africa.

BACKGROUND: Schistosomiasis is classically described as a rural disease that occurs in areas with poor sanitary conditions. However, over recent decades, there has been an expansion of schistosomiasis foci towards urban areas faced with a rapid and disordered urbanization. In Bamako, Mali, the impact of environmental change on vector-borne diseases such as schistosomiasis is not well known. This study sought to identify the presence of schistosomiasis transmission hotspots in Bamako. Using this perspective, we aimed to describe the risk factors of the endemization and maintenance of schistosomiasis. MATERIALS AND METHODS: A cross-sectional study was carried out in the six municipalities (communes) in Bamako. Environmental information was obtained from earth observation satellites in order to maximize ecological contrasts. Twenty-nine blocks of 200 m x 200 m were identified. We selected a school inside or nearest to each block for urine and stool samples examination. The study cohort was school children aged between eight and 15 years. The Kato-Katz technique and filtration were used for Schistosoma mansoni and S. haematobium ova research in stools and urine, respectively. The schools and snail breeding sites were georeferenced. Four malacological surveys were conducted between October 2011 and February 2012. Bivariate analysis was used to identify independent predictors of being infected with schistosomiasis. RESULTS: The prevalence rate of S. haematobium was 14.7% (n = 1,761) and that of S. mansoni 1.5% (n = 1,491). Overall, the urinary form was endemic in 76.6% of schools. The infection significantly varied between the municipalities (p < 0.001). It was also more prevalent on the left side of the Niger River than the right side (17.4% vs. 9.5% respectively; p < 0.001). The vicinity to snail breeding sites (OR = 3.677; 95% IC [2.765-4.889]; p < 10 (-3) ) and parents' occupations (OR = 7.647; 95% IC [2.406-24.305]; p < 0.001) were the most important risk factors associated with S. haematobium infection exposure. Biomphalaria pfeifferi, Bulinus truncatus, and B. globosus were the intermediate hosts captured. The schistosome natural infection rates (SNIRs), which were low or nil in October and November, rose to 2.8% in January and 8.3% in February for B. pfeifferi and B. truncatus, respectively. CONCLUSION: Our findings show that there is a high transmission risk for schistosomiasis in Bamako. Appropriate integrated control measures need to be introduced to control the transmission of this disease in the study area.

Efficacy of sulphadoxine-pyrimethamine + artesunate, sulphadoxine-pyrimethamine + amodiaquine, and sulphadoxine-pyrimethamine alone in uncomplicated falciparum malaria in Mali.

BACKGROUND: Plasmodium falciparum resistance to artemisinin has been reported in South-East Asia. Long half-life drugs are increasingly being used for malaria prevention. The potential spread of parasite resistance to these regimens is real and makes regular efficacy surveillance a priority. METHODS: From August to December 2004 and July to December 2005, a randomized open label trial of sulphadoxine-pyrimethamine (SP) + artesunate (AS) versus SP + amodiaquine (AQ), and SP alone, was conducted in two villages of Mali. PCR was used to distinguish new infections from recrudescent P. falciparum infections. Patients were followed for 28 days to assess treatment efficacy. RESULTS: Overall 912 children aged between six to 59 months, with uncomplicated P. falciparum malaria were recruited. Baseline characteristics were similar in the three treatment arms. Crude ACPRs were 94.9%; 98.6% and 93.5% for SP + AS; SP + AQ and SP alone arms respectively (SP + AS versus SP + AQ, p = 0.01; SP + AS versus SP, p = 0.5; SP + AQ versus SP, p = 0.001). After PCR adjustment, cACPRs were 99%; 100% and 97.2% for SP + AS; SP + AQ and SP alone arms, respectively (SP + AS versus SP + AQ, p = 0.25; SP + AS versus SP, p = 0.12; SP + AQ versus SP, p = 0.007). CONCLUSION: Sulphadoxine-pyrimethamine + amodiaquine therapy was as efficacious as sulphadoxine-pyrimethamine + artesunate, but more efficacious than sulphadoxine-pyrimethamine alone in the treatment of uncomplicated P. falciparum malaria in Mali.

Biosensor for selective detection of E. coli in spinach using the strong affinity of derivatized mannose with fimbrial lectin.

Escherichia coli (E. coli) contamination in foods and water resources represents a major threat for human health and the environment. This work exploits the strong affinity of mannose-containing oligosaccharides with the fimbrial lectin of E. coli to design novel biosensors. Modified carbohydrate ligands were synthesized by introducing phenyl residues and aliphatic chains to mannose via reductive amination in order to increase both the affinity and selectivity to E. coli compared to other pathogenic bacteria. The synthesized ligands include p-thiolphenyl aminomannose (PTAM), p-carboxyphenyl aminomannose (PCAM), 1-deoxy-1-aminomannopyranoside (DAMP), glucosamine and low molecular weight chitosan bonded to mercapto undecanoic acid. The structures of the ligands were confirmed using (1)H NMR and 1H, (13)C, COZY NMR, and ESI/MS. The ligands were immobilized onto gold electrodes and SPR surfaces using-mercaptoundecanoic acid with glycine as deactivating agent. Two detection mechanisms were tested: (i) metal-enhanced electrochemical detection (MED) and (ii) label-free surface plasmon resonance (SPR) detection. The introduction of phenyl residues and aliphatic side groups to the mannose-containing oligosaccharides produced extremely high affinity for E. coli with detection limit of 1 cfu/mL. The relative selectivity of these ligands for E. coli, Citrobacter freundii, Staphylococcus epidermidis were 100%, 2.6% and 8.6% respectively. The biosensors were validated using spinach leaves at 3.0 cfu/mL. The work provides a generic biosensor for other pathogenic bacteria by enabling multivalent binding, immediate recognition for pathogens as well as inhibition of bacterial growth.