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.

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.

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.

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.

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.

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.

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.

The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma.

In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10(-8), per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10(-14)) and rs12617313 (P = 7.48 × 10(-12)), both highly correlated with rs9679290 (r(2) > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r(2) < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10(-9), per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants.

Coproduced, arts interventions for nurturing care (0-5 years) in low-income and middle-income countries (LMICs): a realist review.

OBJECTIVES: Community-based arts interventions have the potential to support contextually relevant nurturing care programmes and policies that adapt to different settings. Understanding the distinctive features of using the arts in local, culturally specific ways in low/middle-income countries (LMICs); how this varies by context; and gaining a better understanding of the perspectives on desirable outcomes for communities is important evidence that this review generates. DESIGN: We conducted a realist review of papers that covered outcomes related to child health or development (0-5 years) AND arts-based approaches AND community-based, participatory approaches AND based in LMICs using a range of databases and other networks. A coding framework was developed covering context, intervention, outcomes, mechanisms, study, sustainability, transferability and scalability. RESULTS: The included papers reported 18 unique interventions. Interventions covered 14 countries, with evidence lacking for South America, Arab countries and parts of Africa. Lead authors came from mostly clinical science-based disciplines and from institutions in a different country to the country/countries studied. Intended outcomes from interventions included clinical, health systems/organisation, changes in practices/behaviours/knowledge/attitudes, and wider social and educational goals. We identified three demi-regularities (semi-predictable patterns or pathways of programme functioning): participatory design based on valuing different sources of expertise; dynamic adaptation of intervention to context; and community participation in arts-based approaches. CONCLUSIONS: Our findings suggest that arts-based, nurturing care interventions have greater potential when they include local knowledge, embed into existing infrastructures and there is a clear plan for ongoing resourcing of the intervention. Studies with better documentation of the lessons learnt, regarding the intervention delivery process and the power dynamics involved, are needed to better understand what works, for whom and in which contexts.

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.

Hygiene intervention reduces contamination of weaning food in Bangladesh.

OBJECTIVE: This study was conducted to measure the impact of a hygiene intervention on the contamination of weaning food in Bangladesh. METHODS: Sixty households were selected: 30 study and 30 control households. Samples of weaning food were collected from all the 60 households at baseline and examined for faecal coliforms (FC), faecal streptococci (FS) and Clostridium perfringens (CP) following standard procedures. After cooking, food samples were collected on three occasions before feeding. Following Hazard Analysis Critical Control Point (HACCP) procedures, critical control points were determined. The mothers in the 30 study households were then trained for 4 weeks in how to attain the control point conditions. Then, again the food samples were collected and analysed. RESULTS: At baseline, weaning foods from study and control households were heavily contaminated with FC and FS. The FC and FS counts were 1.84 log(10) and 1.92 log(10) colony-forming unit (cfu)/g, respectively, in the study households, and 0.86 log(10) and 1.33 log(10)  cfu/g, respectively, in the control households in the first feeding. After the intervention, the FC and FS counts in study households had dropped to 0.10 log(10) and 0.09 log(10)  cfu/g, respectively, a statistically significant reduction (P < 0.001). Monitoring the sustainability of the behaviour change after 3 months showed that the mothers were maintaining food hygiene. CONCLUSIONS: A hygiene intervention following the HACCP approach reduced the weaning food contamination significantly. Awareness building among mothers about weaning food hygiene could be an important intervention for preventing weaning food-related diarrhoea in Bangladesh.

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.

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.

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.

Increase in EPI vaccines coverage after implementation of intermittent preventive treatment of malaria in infant with Sulfadoxine -pyrimethamine in the district of Kolokani, Mali: results from a cluster randomized control trial.

BACKGROUND: Even though the efficacy of Intermittent Preventive Treatment in infants (IPTi) with Sulfadoxine-Pyrimethamine (SP) against clinical disease and the absence of its interaction with routine vaccines of the Expanded Immunization Programme (EPI) have been established, there are still some concerns regarding the addition of IPTi, which may increase the work burden and disrupt the routine EPI services especially in Africa where the target immunization coverage remains to be met. However IPTi may also increase the adherence of the community to EPI services and improve EPI coverage, once the benefice of strategy is perceived. METHODS: To assess the impact of IPTi implementation on the coverage of EPI vaccines, 22 health areas of the district of Kolokani were randomized at a 1:1 ratio to either receive IPTi-SP or to serve as a control. The EPI vaccines coverage was assessed using cross-sectional surveys at baseline in November 2006 and after one year of IPTi pilot-implementation in December 2007. RESULTS: At baseline, the proportion of children of 9-23 months who were completely vaccinated (defined as children who received BGG, 3 doses of DTP/Polio, measles and yellow fever vaccines) was 36.7% (95% CI 25.3% -48.0%). After one year of implementation of IPTi-SP using routine health services, the proportion of children completely vaccinated rose to 53.8% in the non intervention zone and 69.5% in the IPTi intervention zone (P <0.001).The proportion of children in the target age groups who received IPTi with each of the 3 vaccinations DTP2, DTP3 and Measles, were 89.2% (95% CI 85.9%-92.0%), 91.0% (95% CI 87.6% -93.7%) and 77.4% (95% CI 70.7%-83.2%) respectively. The corresponding figures in non intervention zone were 2.3% (95% CI 0.9% -4.7%), 2.6% (95% CI 1.0% -5.6%) and 1.7% (95% CI 0.4% - 4.9%). CONCLUSION: This study shows that high coverage of the IPTi can be obtained when the strategy is implemented using routine health services and implementation results in a significant increase in coverage of EPI vaccines in the district of Kolokani, Mali.

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.

Transglutaminase-1 gene mutations in autosomal recessive congenital ichthyosis: summary of mutations (including 23 novel) and modeling of TGase-1.

Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of rare cornification diseases. Germline mutations in TGM1 are the most common cause of ARCI in the United States. TGM1 encodes for the TGase-1 enzyme that functions in the formation of the cornified cell envelope. Structurally defective or attenuated cornified cell envelop have been shown in epidermal scales and appendages of ARCI patients with TGM1 mutations. We review the clinical manifestations as well as the molecular genetics of ARCI. In addition, we characterized 115 TGM1 mutations reported in 234 patients from diverse racial and ethnic backgrounds (Caucasion Americans, Norwegians, Swedish, Finnish, German, Swiss, French, Italian, Dutch, Portuguese, Hispanics, Iranian, Tunisian, Moroccan, Egyptian, Afghani, Hungarian, African Americans, Korean, Japanese and South African). We report 23 novel mutations: 71 (62%) missense; 20 (17%) nonsense; 9 (8%) deletion; 8 (7%) splice-site, and 7 (6%) insertion. The c.877-2A>G was the most commonly reported TGM1 mutation accounting for 34% (147 of 435) of all TGM1 mutant alleles reported to date. It had been shown that this mutation is common among North American and Norwegian patients due to a founder effect. Thirty-one percent (36 of 115) of all mutations and 41% (29 of 71) of missense mutations occurred in arginine residues in TGase-1. Forty-nine percent (35 of 71) of missense mutations were within CpG dinucleotides, and 74% (26/35) of these mutations were C>T or G>A transitions. We constructed a model of human TGase-1 and showed that all mutated arginines that reside in the two beta-barrel domains and two (R142 and R143) in the beta-sandwich are located at domain interfaces. In conclusion, this study expands the TGM1 mutation spectrum and summarizes the current knowledge of TGM1 mutations. The high frequency of mutated arginine codons in TGM1 may be due to the deamination of 5' methylated CpG dinucleotides.

Modelling malaria incidence with environmental dependency in a locality of Sudanese savannah area, Mali.

BACKGROUND: The risk of Plasmodium falciparum infection is variable over space and time and this variability is related to environmental variability. Environmental factors affect the biological cycle of both vector and parasite. Despite this strong relationship, environmental effects have rarely been included in malaria transmission models.Remote sensing data on environment were incorporated into a temporal model of the transmission, to forecast the evolution of malaria epidemiology, in a locality of Sudanese savannah area. METHODS: A dynamic cohort was constituted in June 1996 and followed up until June 2001 in the locality of Bancoumana, Mali. The 15-day composite vegetation index (NDVI), issued from satellite imagery series (NOAA) from July 1981 to December 2006, was used as remote sensing data.The statistical relationship between NDVI and incidence of P. falciparum infection was assessed by ARIMA analysis. ROC analysis provided an NDVI value for the prediction of an increase in incidence of parasitaemia.Malaria transmission was modelled using an SIRS-type model, adapted to Bancoumana's data. Environmental factors influenced vector mortality and aggressiveness, as well as length of the gonotrophic cycle. NDVI observations from 1981 to 2001 were used for the simulation of the extrinsic variable of a hidden Markov chain model. Observations from 2002 to 2006 served as external validation. RESULTS: The seasonal pattern of P. falciparum incidence was significantly explained by NDVI, with a delay of 15 days (p = 0.001). An NDVI threshold of 0.361 (p = 0.007) provided a Diagnostic Odd Ratio (DOR) of 2.64 (CI95% [1.26;5.52]).The deterministic transmission model, with stochastic environmental factor, predicted an endemo-epidemic pattern of malaria infection. The incidences of parasitaemia were adequately modelled, using the observed NDVI as well as the NDVI simulations. Transmission pattern have been modelled and observed values were adequately predicted. The error parameters have shown the smallest values for a monthly model of environmental changes. CONCLUSION: Remote-sensed data were coupled with field study data in order to drive a malaria transmission model. Several studies have shown that the NDVI presents significant correlations with climate variables, such as precipitations particularly in Sudanese savannah environments. Non-linear model combining environmental variables, predisposition factors and transmission pattern can be used for community level risk evaluation.

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.