Neuropathic pain in Mali: The current situation, comprehensive hypothesis, which therapeutic strategy for Africa?

INTRODUCTION: According to the taxonomy of the International Association for the Study of Pain (IASP 2011), neuropathic pain (NeuP) is defined as "pain caused by a lesion or disease of the somatosensory nervous system". NeuP is currently well-defined clinically, despite a high degree of etiological variation, and it has become a significant public health problem. This work aimed to study the situation regarding NeuP in current practice in Mali, as well as to analyze the therapeutic environment of the patients. METHODOLOGY: This was a retrospective and cross-sectional study, carried out in two phases: (1) compilation of the files of patients according to the ICD-11, over a period of 24 months (2) a second prospective phase regarding the Knowledge, Attitudes, and Practices (KAP) of general practitioners and neurologists in regard to NeuP. The focus of the first phase of the study was the files of the patients who had undergone a consultation at the Gabriel Touré UHC. The second phase of the study focused on the general practitioners (Community Health Centers (comHC) of Bamako) and neurologists (Malian or not). RESULTS: Over the period of the study, 7840 patients were seen in consultation in the Department of Neurology, of whom 903 for NeuP, thus amounting to a NeuP frequency of 11.5%. Women accounted for 58.9% (532/903), with a sex ratio of 1.4. Using a comparative normal law, the difference in frequency was statistically significant between males and females (p < 10-7) and between two age groups (p ã€ˆ10-3). The 49-58 years of age group was represented the most. Diabetic NeuP (21%), lumbar radiculopathies (14%), HIV/AIDS NeuP (13%), and post-stroke NeuP (11%) were the most represented. The survey among the carers revealed: a need for training, a low level of compliance with the therapeutic guidelines, and the use of traditional medicine by the patients. DISCUSSION/CONCLUSION: This work confirms that NeuP is encountered frequently in current practice, and its optimal management will involve specific training of carers and improvement of access to the medications recommended in this indication. In light of this issue, we revisit the debate regarding the concept of essential medications and the relevance of taking into account effective medications for the treatment of NeuP.

Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis.

Janus kinase (JAK) inhibitors are used to treat rheumatoid arthritis (RA). We assessed the effects of tofacitinib on bone density and bone markers in association with clinical and laboratory parameters in RA. Tofacitinib stabilized bone density and resulted in a positive balance of bone turnover. INTRODUCTION: Janus kinase (JAK) inhibitors emerged as new therapeutic options in rheumatoid arthritis (RA). We have little information on how it affects areal and volumetric bone mineral density (BMD) and bone turnover markers. The aim of this study was to assess the effects of 1-year tofacitinib therapy on bone metabolism in RA. METHODS: Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) levels, as well as serum levels of sclerostin, osteocalcin (OC), P1NP, DKK-1, OPG, RANKL, and 25-hydroxy-vitamin D3. Areal and volumetric BMD were assessed by DXA and peripheral quantitative CT (QCT), respectively. RESULTS: Twenty-six patients (13 on each arm) completed the study. Tofacitinib was clinically effective by suppressing DAS28, CRP, and HAQ. This was accompanied by the attenuation of further bone loss. Tofacitinib therapy significantly increased OC, OPG, and vitamin D3, while decreased CTX levels (p < 0.05). Age and multiple bone markers (OC, CTX, P1NP, RANKL) inversely correlated with L2-4 and femoral neck BMD by DXA. CRP, DAS28, and RANKL inversely determined volumetric BMD by QCT. Age, CRP, anti-CCP, and DKK-1 influenced the effects of tofacitinib therapy on BMD changes. CONCLUSIONS: One-year tofacitinib treatment stabilized BMD in RA patients and resulted in a positive balance of bone turnover as indicated by bone biomarkers. Further studies are needed to evaluate the potential beneficial effects of JAK inhibitors on inflammatory bone loss.

Diabetic polyneuropathy with/out neuropathic pain in Mali: A cross-sectional study in two reference diabetes treatment centers in Bamako (Mali), Western Africa.

INTRODUCTION: Diabetic polyneuropathy (DPN) with or without neuropathic pain is a frequent complication of diabetes. This work aimed to determine the prevalence of diabetic polyneuropathy, to describe its epidemiological aspects, and to analyze the therapeutic itinerary of patients with DPN. METHODS: This was a cross-sectional, descriptive study performed synchronously over six months at two major follow-up sites for patients with diabetes in Mali. DPN was diagnosed based on the Michigan Neuropathy Screening Instrument (MNSI). The neuropathic nature of the pain and the quality of life of patients were evaluated by the DN4 and the ED-5D scale, respectively. We used three (3) different questionnaires to collect data from patients (one at inclusion and another during the follow-up consultation) and from the caregivers of patients with DPN. RESULTS: We included 252 patients with diabetes, and DPN was found to have a healthcare facility-based prevalence of 69.8% (176/252). The sex ratio was approximately three females for every male patient. The patients were mostly 31 to 60 years of age, 83% had type 2 diabetes, and 86.9% had neuropathic pain Approximately half of the patients (48.3%) had autonomic neuropathy and they reported moderate to intense pain, which was mainly described as a burning sensation. The patients exhibited impaired exteroceptive and proprioceptive sensations in 51.7% of cases. The patients smoked tobacco in 3.4% of cases, while 36.6% of the patients were obese and had dyslipidemia. The caregivers clearly indicated that appropriate medications were not readily accessible or available for their patients with DPN. CONCLUSION: The healthcare facility-based prevalence of DPN with or without neuropathic pain was high in our cohort. These inexpensive and easy-to-use tools (MNSI, DN4) can be used to adequately diagnose DPN in the African context. In Mali, screening and early treatment of patients at risk of DPN should allow for a reduction of the burden of the disease, while caregivers need to be adequately trained to manage DPN.

Etiology of hepatocellular carcinoma in West Africa, a case-control study.

Hepatocellular carcinoma (HCC) is a leading cause of cancer in West Africa where HBV infection is endemic. However, limited information is available on other risk factors such as alcohol use, HCV and HIV infection. A case-control study was conducted in referral hospitals of Abidjan (Cote d'Ivoire), Bamako (Mali) and Lome (Togo). Cases were matched with controls on age, gender and participating site. The diagnosis of HCC relied on the combination of one or more space-occupying lesions suggestive of an HCC on a standardized abdominal ultrasound and an α-fetoprotein level ≥400 ng/ml. HIV, HBV and HCV serology were performed. Hazardous alcohol use was assessed using the AUDIT questionnaire. A conditional logistic regression model was used to measure odds ratio (OR) with their 95% confidence intervals (CI). A total of 160 cases and 320 controls were included. Cases were predominantly men (80.0%) with a median age of 47 years (IQR 38-57). Hazardous alcohol use (OR = 4.5 [CI 1.1-18.5]), HBV infection (OR = 62.5 [CI 20.5-190.7]) and HCV infection OR = 35.9 [CI 10.0-130.3]) were independently associated with HCC. Combining the effect of HBV infection and alcohol, HBV-infected hazardous drinkers had an OR = 149.8 (CI 13.5-1 667.0), HBV mono-infected had an OR = 57.4 (CI 18.8-175.3) (ref: HBV-negative). Aside the independent association of alcohol use and HBV and HCV infection with HCC, a synergic effect between alcohol use and HBV infection was identified. Timely screening and care of HBV infection and hazardous drinking might prevent a significant number of HCC in West Africa.

L'epilepsie en milieu scolaire : enquete chez les enseignants de la ville de Kati au Mali et revue de la litterature

Introduction La prevalence de l'epilepsie en Afrique subsaharienne est elevee. Nous avons mene une etude transversale et descriptive dans l'ensemble des ecoles primaires de la ville de Kati (200 000 habitants). Les enseignants furent interviewes de maniere exhaustive a l'aide de questionnaires portant; d'une part; sur les connaissances; attitudes et pratiques des enseignants en matiere d'epilepsie et; d'autre part; sur leurs avis sur les consequences psychologiques; sociales pour l'enfant epileptique et les incidences sur sa scolarite.Resultats Nous avons interroge 92 enseignants (60 hommes et 32 femmes). L'age moyen des enseignants etait de 30 ans. La majorite d'entre eux avait une experience professionnelle de plus de 5 ans. Environ 38% des enseignants attribuaient la maladie a une cause surnaturelle. Plus de 39% des enseignants pensaient que l'epilepsie etait contagieuse et 61% pensaient que l'epilepsie etait incurable. 79% interdisaient systematiquement la pratique du sport a l'enfant epileptique. Environ 55% pensaient que l'enfant epileptique avait des capacites cognitives inferieures a celles de l'enfant non epileptique et 88% affirmaient que l'enfant epileptique etait incapable d'avoir une scolarite normale. 59% trouvaient que l'eleve epileptique etait victime de stigmatisation et de marginalisation. Devant une crise; 68% renvoyaient l'enfant au domicile.Conclusion Ce travail fait apparaitre un besoin de formation des enseignants en matiere d'epilepsie. Les donnees actuelles sur la frequence de l'epilepsie en milieu scolaire justifient une attention particuliere des services de sante et de ceux de l'education nationale sur la scolarisation de l'enfant epileptique

[Modalities of stroke management in Mali (West Africa): a survey of practices]. / Modalites de prise en charge des accidents vasculaires cerebraux au Mali (Afrique de l'Ouest): une enquete de pratiques.

The upsurge and the impact of stroke in terms of mortality and morbidity in Africa are well documented. But their current stroke management modalities remain to be evaluated. METHODS: This study investigated the modalities of healthcare practitioners working in structures involved in stroke management in seven of the eight regions and the capital city of Bamako. A questionnaire was sent out to all potential participants identified in the designated areas, whereas the relevant medical personnel were systematically enrolled to take part. 149 practitioners (90%) including 68 general practitioners, 12 specialists, and 69 residents responded to the questionnaire. Six CT-scan, 15 echocardiographs, and 21 electrocardiographs were available. The team directly involved in patient management included six neurologists, seventeen cardiologists, six neurosurgeons, 86 physical therapists, three orthophonists, and two ergotherapists. Hemiplegia was the revealing symptom of stroke in 61.1% of cases. Almost all infrastructures and the personnel are located in a geographic area representing less than 10% of the country, where only 14 % of the population live. These findings emphasize the lack and unequal distribution of resources allocated to stroke management. CONCLUSION: Problems related to stroke in Mali need a re-organization of patient management networks. An initial and continued training of health practitioners should be implemented.

La haute incidence des AVC en Afrique et leur gravité en termes de mortalité est bien documentée. Mais les modalités actuelles de leur prise en charge restent à évaluer. L'objectif de ce travail était d'analyser les modalités de prise en charge et l'offre de soins pour les AVC, au Mali. Il s'agissait d'une enquête de santé publique auprès des prescripteurs exerçant dans des structures impliquées dans la prise en charge AVC dans 7 des 8 régions existantes et du district de Bamako. Un questionnaire a été adressé à tous les intervenants potentiels recensés de ces territoires, tandis que les plateaux techniques et les personnels ont été systématiquement recensés.Au cours de ce travail 149 prescripteurs sollicités ont répondu au questionnaire (90%). Il s'agissait de 68 médecins généralistes, 12 médecins spécialistes, 69 internes. Sur le plan de la logistique, la presque totalité de ce plateau technique et du personnel se trouvent sur une aire géographique qui représente moins de 10% du territoire national et n'abrite que 14% de la population. Ces données témoignent de l'insuffisance et de l'inégale répartition des ressources allouées à la prise en charge des AVC.

Modalites de prise en charge des accidents vasculaires cerebraux au Mali (Afrique de l'Ouest) : une enquete de pratiques

La haute incidence des AVC en Afrique et leur gravite en termes de mortalite est bien documentee. Mais les modalites actuelles de leur prise en charge restent a evaluer. L'objectif de ce travail etait d'analyser les modalites de prise en charge et l'offre de soins pour les AVC; au Mali. Il s'agissait d'une enquete de sante publique aupres des prescripteurs exercant dans des structures impliquees dans la prise en charge AVC dans 7 des 8 regions existantes et du district de Bamako. Un questionnaire a ete adresse a tous les intervenants potentiels recenses de ces territoires; tandis que les plateaux techniques et les personnels ont ete systematiquement recenses. Au cours de ce travail 149 prescripteurs sollicites ont repondu au questionnaire (90). Il s'agissait de 68 medecins generalistes; 12 medecins specialistes; 69 internes. Sur le plan de la logistique; la presque totalite de ce plateau technique et du personnel se trouvent sur une aire geographique qui represente moins de 10du territoire national et n'abrite que 14 de la population. Ces donnees temoignent de l'insuffisance et de l'inegale repartition des ressources allouees a la prise en charge des AVC

Low prevalence of detectable HIV plasma viremia in patients treated with antiretroviral therapy in Burkina Faso and Mali.

BACKGROUND: Sub-Saharan Africa has seen dramatic increases in the numbers of people treated with antiretroviral therapy (ART). Although standard ART regimens are now universally applied, viral load measurement is not currently part of standard monitoring protocols in sub-Saharan Africa. METHODS: We describe the prevalence of inadequate virological response (IVR) to ART (viral load >or= 500 copies/mL) and identify factors associated with this outcome in 606 HIV-positive patients treated for at least 6 months. Recruitment took place in 7 hospitals and community-based sites in Bamako and Ouagadougou, and information was collected using medical charts and interviews. RESULTS: The overall prevalence of IVR in treatment-naive patients was 12.3% and 24.4% for pretreated patients. There were no differences in rates of IVR according to ART delivery sites and time on treatment. Patients living farther away [odds ratio (OR) = 2.48; 95% confidence interval (CI) 1.40 to 4.39], those on protease inhibitor or nucleoside reverse transcriptase inhibitor regimens (OR = 3.23; 95% CI 1.79 to 5.82) and those reporting treatment interruptions (OR = 2.36; 95% CI 1.35 to 4.15), had increased odds of IVR. Immune suppression (OR = 3.32, 95% CI 1.94 to 5.70) and poor self-rated health (OR = 2.00; 95% CI 1.17 to 3.41) were also associated with IVR. CONCLUSIONS: Sufficient expertise and dedication exist in public hospital and community-based programs to achieve rates of treatment success comparable to better-resourced settings.

Characterization of drug resistance in antiretroviral-treated patients infected with HIV-1 CRF02_AG and AGK subtypes in Mali and Burkina Faso.

BACKGROUND: In a multicentred cohort of patients on antiretroviral therapy (ART) in Burkina Faso and Mali, we analysed the prevalence of HIV drug resistance mutations in patients failing a modified directly observed therapy (mDOT) protocol. METHODS: Patients on ART >6 months and with viral load (VL) >500 copies/ml were enrolled in a mDOT protocol. Genotypic resistance testing was performed on pre- and post-mDOT plasma samples of patients who still had VL >500 copies/ml after mDOT. RESULTS: Eight hundred and one patients from seven sites participated in the study. One hundred and thirteen patients (14.1%) had VL >500 copies/ml. Most patients were treated with lamivudine along with zidovudine or stavudine and efavirenz or nevirapine. Genotypes were available for 46 patients. The predominant HIV-1 subtypes were CRFO2_AG in 26 (56.5%) and AGK/K/AK in 12 (26.1%) patients. The prevalence of drug resistance mutations by class were as follows for nucleoside reverse transcriptase inhibitors: 1841/V (82.6%), 215Y/F (32.6%), 219E/Q (19.6%), 70R (19.6%), 67N (21.7%), 41L (15.2%) and 151M(2.2%). For non-nucleoside reverse transcriptase inhibitors the prevalence was: 103N (50%) and 181C/I (19.6%). Phylogenetic analysis showed that, although the genetic distances were small among isolates, there was no clustering of a particular subtype in a specific region and that the high prevalence of AGK subtype in our drug-resistant population was not due to a circulating resistant strain. CONCLUSION: Although CRFO2_AG is the dominant clade in the Burkina Faso/Mali region, isolates with subtype K reverse transcriptase were frequent in our cohort. Drug resistance mutation pathways in subtype K reverse transcriptase need to be further evaluated in a larger cohort of non-B HIV-infected individuals.

Urinary disease in 2 Dogon populations with different exposure to Schistosoma haematobium infection: progression of bladder and kidney diseases in children and adults.

BACKGROUND: Schistosoma haematobium infection causes severe urinary disease and considerable mortality. The factors that determine disease progression from mild to severe stages are not fully understood. METHODS: Here we describe a cross-sectional epidemiological study of kidney and bladder diseases in 2 Dogon populations with different exposure to S. haematobium infection. RESULTS: Early and high exposure resulted in more-severe disease, especially among young subjects, without clear evidence of a more-rapid development of immunity. Nevertheless, 50%-60% of subjects of all age classes in both villages showed no evidence of disease. Kidney and bladder disease peaked biphasically among young subjects and adults >25 years old. The first peak corresponded with infections of maximum intensity, whereas the second peak occurred among adults with infections of very low intensity. Kidney disease was correlated with circulating anodic antigen concentration in serum, whereas bladder disease was correlated with egg count and eosinophil cationic protein concentration in urine. Kidney and bladder disease did not correlate. Severe kidney disease was more frequent in certain families. CONCLUSIONS: The frequency of urinary disease is increased by infections acquired early during life, is regulated by strong clinical immunity in certain subjects, and may be dependent on hereditary factors. Kidney and bladder disease may involve different mechanisms of pathogenesis, which may differ between children and adults.

[African histoplasmosis (Histoplasma capsulatum var. duboisii): a case report from Mali]. / Histoplasmose africaine à Histoplasma capsulatum var. duboisii. A propos d'un cas au Mali.

We report a case of disseminated African histoplasmosis with lymph node and digestive involvement in a 19-year-old man living in the Kayes district of Mali. The patient, HIV-seronegative and not otherwise immunocompromised, presented voluminous cervical and axillary adenopathies as well as retrosternal and mesenteric tumor lesions. Direct examination of biopsy tissue showed numerous specimens of Histoplasma capsulatum var. duboisii. Because direct fungal techniques are the easiest and the most effective method of diagnostic investigation, no cultures were performed. Intolerance to therapy with amphotericin b and ketoconazole led its rapid replacement by surgical treatment: partial excision of the abdominal lesions led to partial remission of the symptoms.

Analysis of the 5q31-q33 locus shows an association between IL13-1055C/T IL-13-591A/G polymorphisms and Schistosoma haematobium infections.

Millions of humans are exposed to schistosome infections, which cause severe kidney and liver disease and 280,000 deaths annually. Th2-mediated immunity is critical to human defenses against this pathogen and susceptibility to infection is controlled by a major genetic locus that includes IL4, IL5, and IL13 genes. These observations led us to evaluate whether certain polymorphisms in IL4, IL5, or IL13 determine schistosome infection. The study was performed in two Dogon villages where Schistosoma haematobium is endemic. Schistosome infections were evaluated by counting eggs and measuring worm Ags in urine. Genetic polymorphisms were determined by restriction enzyme analysis or by primer extension and denaturing high-performance liquid chromatography analysis. Associations were tested using family-based association tests and logistical regression analysis. The alleles IL13-1055C (p = 0.05) and IL13-591A (p = 0.01) are shown, by family-based association test, to be preferentially transmitted to children with the 10% highest infections. A logistic regression analysis that included IL13-1055 G/G, G/T and T/T genotypes, age, gender, and village of residency, applied to the whole study population, showed that subjects bearing the IL13-1055T/T genotype were on average much less infected than individuals with other genotypes. Previous studies on asthma indicated that the IL13-1055T allele increased gene transcription, which is in agreement with the fact that this cytokine enhances resistance to infection by schistosome in humans.

[Case-control study of hepatitis C HBs Ag and antivirus antibodies in chronic hepatopathies]. / Etude de l'antigène HBs et des anticorps antivirus de l'hépatite C au cours des hépatopathies chroniques.

The aim of this study is to establish the prevalence of hepatitis C HBs Ag and of anti-virus antibodies in chronic hepatopathies. The prospective case-control study was carried out on 91 patients who needed to be treated for chronic hepatopathies and 92 occasional blood donors. The search for hepatitis C HBs Ag and anti-virus antibodies was done using third generation ELISA screening. At the end of the study, HBs Ag was found in 54% of the patients vs. 4.3% of the control (p=0.0006). The two markers were present more frequently in cirrhosis than in hepatocellular carcinoma (HCC) and their association was more frequent in the case of cirrhosis. In Mali, hepatitis B and C viruses play an important part in chronic hepatopathies.

The metabolic and hormonal effects of continuous subcutaneous insulin infusion therapy in diabetic children.

To find out whether the concurrent metabolic and hormonal abnormalities are corrected when normoglycaemia is achieved, two groups of diabetic children (newly-diagnosed and chronically-treated) were treated with insulin pumps. Fasting levels of metabolites, lipids and hormones were measured before and after 8 to 10 days of pump treatment and the immediate postprandial hormonal and metabolic changes after a test-meal were also measured. Restoration of normoglycaemia was accompanied by correction of multiple metabolic abnormalities including the normalisation of fasting plasma free insulin, growth hormone, free fatty acid, triglyceride and total cholesterol levels. Plasma glucagon, however, decreased below normal, and significant hypoketonaemia developed in newly-diagnosed diabetic children. The fall in (VLDL + LDL)-cholesterol levels was accompanied by a substantial increase in HDL2-cholesterol concentration in newly-diagnosed diabetic children, whereas pump-treatment resulted in a decrease of the HDL3-cholesterol subfraction in chronically-treated diabetic children. The postprandial blood glucose and free insulin profiles were similar to that of control subjects, but there was an "abnormal" postmeal fall in plasma glucagon and free fatty acid levels. These changes together with the fasting hypoglucagonaemia and hypoketonaemia indirectly suggest that optimal glycaemic control is only achievable at the expense of "increased insulin action" despite the failure to detect peripheral hyperinsulinaemia. Furthermore, the restoration of normoglycaemia and the simultaneous normalisation of the metabolic and endocrine milieu is not entirely possible with this mode of therapy.

Food-induced thermogenesis in obese children.

In 11 obese children aged 12.5 (+/- 0.7) years with normal glucose tolerance and 7 lean, control children aged 11.9 +/- 0.7 years the preload resting energy expenditure and thermogenic response to a standardised meal was measured by indirect calorimetry. Preload energy expenditure was higher in obese children when expressed in absolute terms than in controls, but was not different when corrected for lean body weight. Four children with obesity of recent onset had lower food-induced thermogenesis and insulin response then seven overweight children with long-standing obesity. Food-induced thermogenesis and insulin response showed a significant positive correlation. It is concluded that food-induced thermogenesis is reduced in the early phase of childhood obesity but increased in the later phase when hyperinsulinaemia develops, pointing towards an important role of insulin in food-induced thermogenesis.

Absence of responses in energy metabolism and respiratory quotient to carnitine infusion in premature infants.

Plasma levels of total, free and acylcarnitine, as well as oxygen consumption and respiratory quotient were determined in premature infants maintained at neutral temperature. The effects on these parameters of intravenous infusion of 24 mg/kg/day carnitine were studied. Total, free and acylcarnitine increased and the acyl/free carnitine ratio decreased significantly during the four-hour study period. Resting heat production and respiratory quotient remained practically unchanged throughout the study period, indicating that in the face of carnitine sufficiency exogenous carnitine did not influence whole body heat production and substrate utilization pattern in premature infants. Further examinations in carnitine depleted infants will be required to clarify the regulatory role of carnitine in neonatal fatty acid metabolism and non-shivering thermogenesis.

Blood levels of total carnitine and lipid utilization with and without carnitine supplementation in newborn infants.

Postnatal changes of the plasma carnitine level were compared in orally and parenterally fed newborn infants. As expected, in contrast to the increasing plasma level of carnitine in infants fed with human milk, a gradual and significant fall was observed during parenteral feeding. Next, the effect of carnitine supplementation on the elimination rate of an Intralipid load was tested. The increased disappearance rate of triglycerides associated with the exogenously administered carnitine suggested an increased lipid utilization during the carnitine supplemented period of parenteral nutrition.