Complete HLA genotyping of type 1 diabetes patients and controls from Mali reveals both expected and novel disease associations.

HLA genotyping was performed on 99 type 1 diabetes (T1D) patients and 200 controls from Mali. Next-generation sequencing of the classical HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1 loci revealed strong T1D association for all loci except HLA-C and -DPA1. Class II association is stronger than class I association, with most observed associations predisposing or protective as expected based on previous studies. For example, HLA-DRB1*03:01, HLA-DRB1*09:01, and HLA-DRB1*04:05 predispose for T1D, whereas HLA-DRB1*15:03 is protective. HLA-DPB1*04:02 (OR = 12.73, p = 2.92 × 10-05 ) and HLA-B*27:05 (OR = 21.36, p = 3.72 × 10-05 ) appear highly predisposing, although previous studies involving multiple populations have reported HLA-DPB1*04:02 as T1D-protective and HLA-B*27:05 as neutral. This result may reflect the linkage disequilibrium between alleles on the extended HLA-A*24:02~HLA-B*27:05~HLA-C*02:02~HLA-DRB1*04:05~HLA-DRB4*01:03~HLA-DQB1*02:02~HLA-DQA1*02:01~HLA-DPB1*04:02~HLA-DPA1*01:03 haplotype in this population rather than an effect of either allele itself. Individual amino acid (AA) analyses are consistent with most T1D association attributable to HLA class II rather than class I in this data set. AA-level analyses reveal previously undescribed differences of the HLA-C locus from the HLA-A and HLA-B loci, with more polymorphic positions, spanning a larger portion of the gene. This may reflect additional mechanisms for HLA-C to influence T1D risk, for example, through expression differences or through its role as the dominant ligand for killer cell immunoglobulin-like receptors (KIR). Comparison of these data to those from larger studies and on other populations may facilitate T1D prediction and help elucidate elusive mechanisms of how HLA contributes to T1D risk and autoimmunity.

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Mali.

OBJECTIVE: Limited information is available regarding youth-onset diabetes in Mali. We investigated demographic, clinical, biochemical, and genetic features in new diabetes cases in children and adolescents. RESEARCH DESIGN AND METHODS: The study was conducted at Hôpital du Mali in Bamako. A total of 132 recently-diagnosed cases <21 years were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, glutamic acid decarboxylase-65 (GAD-65) and islet antigen-2 (IA2) autoantibodies) were assessed. DNA was genotyped for HLA-DRB1 using high-resolution genotyping technology. RESULTS: A total of 130 cases were clinically diagnosed as type 1 diabetes (T1D), one with type 2 diabetes (T2D), and one with secondary diabetes. A total of 66 (50.8%) T1D cases were males and 64 (49.2%) females, with a mean age at diagnosis of 13.8 ± 4.4 years (range 0.8-20.7 years) peak onset of 15 years. 58 (44.6%) presented in diabetic ketoacidosis; with 28 (21.5%) IA2 positive, 76 (58.5%) GAD-65 positive, and 15 (11.5%) positive for both autoantibodies. HLA was also genotyped in 195 controls without diabetes. HLA-DRB1 genotyping of controls and 98 T1D cases revealed that DRB1*03:01, DRB1*04:05, and DRB1*09:01 alleles were predisposing for T1D (odds ratios [ORs]: 2.82, 14.76, and 3.48, p-values: 9.68E-5, 2.26E-10, and 8.36E-4, respectively), while DRB1*15:03 was protective (OR = 0.27; p-value = 1.73E-3). No significant differences were observed between T1D cases with and without GAD-65 and IA2 autoantibodies. Interestingly, mean C-peptide was 3.6 ± 2.7 ng/ml (1.2 ± 0.9 nmol/L) in T1D cases at diagnosis. CONCLUSIONS: C-peptide values were higher than expected in those diagnosed as T1D and autoantibody rates lower than in European populations. It is quite possible that some cases have an atypical form of T1D, ketosis-prone T2D, or youth-onset T2D. This study will help guide assessment and individual management of Malian diabetes cases, potentially enabling healthier outcomes.

Management of type 1 diabetes in low- and middle-income countries: Comparative health system assessments in Kyrgyzstan, Mali, Peru and Tanzania.

AIMS: To describe and compare the health system responses for type 1 diabetes in Kyrgyzstan, Mali, Peru and Tanzania. METHODS: The Rapid Assessment Protocol for Insulin Access, a multi-level assessment of the health system, was implemented in Kyrgyzstan, Mali, Peru and Tanzania using document reviews, site visits and interviews to assess the delivery of care and access to insulin. RESULTS: Despite the existence of noncommunicable or diabetes strategies and Universal Health Coverage policies including diabetes-related supplies, this has not necessarily translated into access to insulin or diabetes care for all. Insulin and related supplies were often unavailable and unaffordable. Across the four countries test strips and insulin, when paid for by the individual, represented respectively 48-82% and 25-36% of total costs. Care was mainly delivered at tertiary-level hospitals by specialists. Only Kyrgyzstan had data collection systems integrated into the Ministry of Health structure. In addition, issues with healthcare worker training and education and empowerment of people with diabetes were present in these health systems. CONCLUSIONS: People with type 1 diabetes in these countries face different barriers, including the cost of insulin and care. Given the renewed attention to diabetes on the global health agenda tailored health system responses for type 1 diabetes are needed. Insulin should be prioritized as it is the foundation of type 1 diabetes care, but other elements of care and support need to be fostered by different actors.

The role of non-governmental organizations in strengthening healthcare systems in low- and middle-income countries: Lessons from Santé Diabète in Mali.

Non-governmental organizations play a vital part in the achievement of the Sustainable Development Goals as defined by the United Nations. These Goals also include targets related to noncommunicable diseases. However, non-governmental organizations have played a limited role in this area despite such diseases causing the bulk of morbidity and mortality worldwide. Through their activities, non-governmental organizations should aim to strengthen health systems, yet they often only support these for a single disease. Mali, like many other low- and middle-income countries, is facing an increasing burden of diabetes and a health system not adapted to address this challenge. Santé Diabète, a non-governmental organization based in Mali since 2003, has been working specifically on diabetes, and has developed a wide range of activities to improve the national health system. This paper describes changes in the diabetes environment in Mali between 2004 and 2018 based on two health system assessments carried out using a Rapid Assessment Protocol. Over this period, the health system was strengthened with regard to financing and access to medical products. Leadership and governance, service delivery and health workforce were all improved but still partially rely on sustained support from Santé Diabète. The key lesson from this study is that to be effective in changing the management of noncommunicable diseases in a low- and middle-income country, non-governmental organizations need to play a variety of roles, many of which may change over time.

Rapid increases in observed incidence and prevalence of Type 1 diabetes in children and youth in Mali, 2007-2016.

AIMS: Determine incidence, prevalence and mortality of Type 1 diabetes (T1D) in children and youth <25 years (y) in Mali during the first 10 years of the Santé Diabète/Life for a Child program. METHODS: Data were collected from the prospective program register. Diagnosis of T1D was clinical, based on presentation, clinical features, immediate requirement for insulin, and no suggestion of other diabetes types. RESULTS: Total of 460 cases were diagnosed with T1D <25 years in 2007-2016. Male-to-female ratio was 1.04:1. Peak age at onset was 15-16 years (range 1.1-24 years). T1D incidence <25 years per 100,000 population/year increased from 0.12 in 2007 to 0.74 in 2016 (an 18% annualized increase, p < 0.001). Incidence peaked at 0.80 in 2014, the year after an education campaign was conducted. Incidence <15 years rose from 0.12 to 0.35 per 100,000/year in 2007 and 2016, respectively, (14% annualized increase, p < 0.001). There was a steep, consistent increase in prevalence (per 100,000) from 0.43 in 2007 to 2.90 in 2016 (p < 0.001). Prevalence <15 years was 0.34/100,000 in 2007 and 1.02/100,000 by 2016 (p < 0.001). Overall crude mortality rate was 30.0/1000 patient years, equating to a standardized mortality rate of 9.0, with vital status known for 99.8% of cases. CONCLUSION: Known incidence and prevalence of diabetes in Mali increased rapidly from 2007 to 2016, contemporaneous with the introduction and development of the Santé Diabète/Life for a Child program. Improved diagnosis and care resulting in lower mortality are likely contributors. True incidence may still be underestimated, with some cases still dying undiagnosed and full study ascertainment being uncertain.

[Determinants of home delivery in two neighborhoods in Commune V of Bamako]. / Comparaison des determinants de l'accouchement a domicile dans deux quartiers en Commune V de Bamako.

OBJECTIVE: The objective was to study the determinants of home delivery in the Commune V Health District of Bamako. MATERIALS AND METHODS: We conducted an analytical cross-sectional study among women who delivered at home, in two neighborhoodsofSabalibougou and Badalabougou, from March 2015 to February 2016, and who were admitted at the Maternity of the Commune V Referral Health Center during the same period. Two groups of women from two neighborhoods were compared. The data were entered and analyzed using EpiInfo 3.5.3. We presented the Odds Ratios and confident intervals. RESULTS: The frequency of home delivery was 16.18%. The age group 35 years and over were the most represented in both Sabalibougou with 80.75% and Badalabougou with 19.42%.In Sabalibougou, compared to Badalabougou, we found 0.49 times fewer women in school (p = 0.01); 8.92 times more women with gainful occupation (p = 10-8); 3.5 times more partners with non-gainful occupation (p = 10-6); 4.59 times more risk to give birth at home (p = 10-8); 3 times more risk not to perform antenatal care (p = 0.0002); 3.26 times more appreciation of the high cost of delivery care (p = 10-4) and 3.03 times more lack of financial support (p=3*10-4). CONCLUSION: The frequency of home delivery was higher in Sabalibougou. The determinants of this phenomenon were: the low level of schooling, the low socioeconomic level, the non-use of antenatal care, theperceived high cost of delivery care.

OBJECTIF: L'objectif était d'étudierles déterminants de l'accouchement à domicile en Commune V de Bamako. MATÉRIELS ET MÉTHODES: Nous avons mené une étude transversale analytique chez les femmes qui ont accouchées à domicile, dans les quartiers de Sabalibougou et Badalabougou, de Mars 2015 en Février 2016 et reçues à la maternité du Centre de Santé de Référence de la Commune V pendant la même période. Les deux quartiers ont été comparés. Les données ont été saisies et analysées sur EpiInfo 3.5.3, avec présentation des Odds Ratios et intervalles de confiance. RÉSULTATS: La fréquence de l'accouchement à domicile était de 16,18%.La tranche d'âge 35 ans et plus était la plus représentée à Sabalibougou (80,75%) et à Badalabougou (19,42%). Nous avons trouvéà Sabalibougou, comparé à Badalabougou, 0,49 fois moins de femmes scolarisées (p=0,01) ;8,92 fois plus de femmes avec activité rémunératrice (p=10-8) ;3,5 fois plus de partenaires avec activité non rémunératrice (p=10-6) ; 4,59 fois plus de risque d'accoucher à domicile (p=10-8) ; 3 fois plus de risque de ne pas réaliser de consultation prénatale (p=0,0002) ;3,26 fois plus d'appréciation du coût de l'accouchement élevé (p=10-4) et3,03 fois plus de manque de moyens (p=3*10-4). CONCLUSION: La fréquence de l'accouchement à domicile était plus élevée à Sabalibougou.Les déterminants étaient : l'absence de scolarisation, lemanque de moyens financiers, l'absence de réalisation de consultation prénatale, le coût jugé élevé de l'accouchement.

[Contribution of therapeutic education on the psychological level of diabetic patients in the medical department of the Hospital Mali 2018]. / Apport de l'education therapeutique sur le niveau psychologique des malades diabetiques au service de medecine de l'Hopital du Mali 2018.

AIMS: The management of patients with diabetes is done with a focus on the "biological" component in relation to other determinants of health, namely the psychosocial aspect. This work aimed to study the contribution of therapeutic education to the psychological level of patients. METHOD: a cross-sectional study, carried out in the medical department of the Mali Hospital during the first half of 2018, which concerned all 115 patients hospitalized during this period. RESULTS: Among these patients, 52.20% were over 50 years old, with 52.2% female versus 47.8% male. Depression was found in 64.31% of patients, patients who never received a Therapeutic Education constituted 67.83%, the correlation was significant between the psychological level of the patient and his participation in a therapeutic education with a correlation coefficient r = 0.518 and a level p <0.001. CONCLUSION: Educating a patient can help him cope with and manage his illness. However, this education is complex because it is a real training leading to a transfer of skills from the caregiver to the care.

OBJECTIF: la prise en charge des malades atteints de diabète se fait en mettant l'accent prioritairement sur la composante « biologique ¼ par rapport aux autres déterminants de la santé à savoir l'aspect psychosocial. Ce travail avait pour objectif d'étudier l'apport de l'éducation thérapeutique sur le niveau psychologique des patients. MÉTHODE: une étude transversale, réalisée dans le service de médecine de l'Hôpital du Mali durant le premier semestre 2018 et qui a concernée tous les 115 malades hospitalisés pendant cette période. RÉSULTATS: parmi ces malades, 52,20% avaient plus de 50 ans, avec 52,2 % de sexe féminin contre 47,8% pour le sexe masculin. La dépression a été constatée chez 64,31% des patients, les patients qui n'ont jamais reçu d'Education Thérapeutique constituaient 67,83%, la corrélation était significative entre le niveau psychologique du patient et sa participation à une éducation thérapeutique avec un coefficient de corrélation r= 0,518 et un niveau p<0,001. CONCLUSION: éduquer un patient permet de l'aider à supporter sa maladie et à bien la gérer. Cependant, cette éducation est complexe parce qu'il s'agit d'une véritable formation devant aboutir à un transfert de compétences du soignant vers le soigné.

Structured peer-led diabetes self-management and support in a low-income country: The ST2EP randomised controlled trial in Mali.

OBJECTIVES: Our objective was to evaluate the effectiveness of peer-led self-management education in improving glycaemic control in patients with type 2 diabetes in a low-income country (Mali). METHODS: We conducted an open-label randomised controlled trial. A total of 151 adults (76% women, mean age 52.5) with type 2 diabetes (HbA1c≥8%), treated in the diabetes consultation units of two secondary health centres in Bamako, were allocated to peer-led structured patient education (n = 76) or conventional care alone (n = 75). The intervention group received 1 year of culturally tailored structured patient education (3 courses of 4 sessions) delivered in the community by five trained peer educators. Both groups underwent conventional diabetes monitoring and follow-up. Primary outcome was the mean absolute change in HbA1c from baseline to 12 months. RESULTS: 177 education sessions were delivered to the intervention group. Patient attrition was 8%. From baseline to 12 months, the decrease in HbA1c levels was 1.05% (SD = 2.0; CI95%: 1.54;-0.56) in the intervention group compared with 0.15% (SD = 1.7; CI95%: -0.56; 0.26) in the control group, p = 0.006. Mean BMI change was -1.65 kg/m2 (SD = 2.5; CI95%: -2.25; -1.06) in the intervention group and +0.05 kg/m2 (SD = 3.2; CI95%: -0.71; 0.81) in the control group, p = 0.0005. Mean waist circumference decreased by 3.34 cm (SD = 9.3; CI95%: -5.56;-1.13) in the intervention group and increased by 2.65 cm (SD = 10.3; CI95%: 0.20; 5.09) in the control group, p = 0.0003. CONCLUSIONS: Peer-led structured patient education delivered over 1 year to patients with poorly controlled type 2 diabetes in Mali yielded substantial improvements in glycaemic control and anthropometric parameters. This is of importance for the scaling up of efficient interventions in low-resource settings in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT01485913.

Diabetes in an emergency context: the Malian case study.

BACKGROUND: The World Health Organization proposes 6 building blocks for health systems. These are vulnerable to challenges in many contexts. Findings from a 2004 assessment of the health system in Mali for diabetes care found many barriers were present for the management and care of this condition. Following this assessment different projects to strengthen the healthcare system for people living with diabetes were undertaken by a local NGO, Santé Diabète. CASE DESCRIPTION: In March 2012, following a Coup in Bamako, the northern part of Mali was occupied and cut-off from the rest of the country. This had a major impact on the health system throughout the country. Due to the lack of response by humanitarian actors, Santé Diabète in close collaboration with other local stakeholders developed a humanitarian response for patients with diabetes. This response included evacuation of children with Type 1 diabetes from northern regions to Bamako; supplies of medicines and tools for management of diabetes; and support to people with diabetes who moved from the north to the south of the country. DISCUSSION: It has been argued that diabetes is a good tracer for health systems and based on Santé Diabète's experience in Mali, diabetes could also be used as a tracer in the context of emergencies. One lesson from this experience is that although people with diabetes should be included as a vulnerable part of the population they are not considered as such. Also within a complex emergency different "diabetes populations" may exist with different needs requiring tailored responses, such as internally displaced people versus those still in conflict areas. From Santé Diabète's perspective, the challenge was changing the ways it operated from a development NGO to an emergency NGO. In this role it could rely on its knowledge of the local situation and its function as part of the post-conflict situation. CONCLUSION: The lessons learnt from this experience by Santé Diabète in Mali may be useful for other NGOs and the humanitarian response in general in addressing the challenge of managing non communicable diseases and diabetes in conflict and disaster situations in countries with weak health systems.

[Diabetes, a public health challenge for Mali]. / Le diabète, un enjeu de santé publique au Mali.

Mali has a high proportion of people with diabetes, a situation which has significantly worsened since war broke out at the beginning of 2013. A nongovernmental organisation, Santé Diabète, is carrying out wide-scale action in order to improve access to care and the follow-up of people with diabetes in Mali.