Enhancing Pharmacovigilance in Côte d'Ivoire: Impact of GSK's Training and Mentoring Pilot Project in the Abidjan Region.

INTRODUCTION: Pharmacovigilance (PV) in sub-Saharan Africa relies on passive surveillance but underreporting of adverse events (AEs) by health care professionals (HCPs) is a major challenge. A PV enhancement project was implemented to address this in Côte d'Ivoire. OBJECTIVE: To improve safety surveillance of medicines through PV training and mentoring of HCPs in selected health care facilities (HCFs). METHODS: This collaborative project between national PV stakeholders, GSK, and PATH was implemented from September 2018 to February 2020 in Abidjan region, Côte d'Ivoire. Trained PV focal points provided training and regular mentoring of HCPs. Key performance indicator (KPI) categories for AE reporting were the volume of AE reports, efficiency of report transmission and data entry, quality of reports, and quality of the central (Vigilance Unit) response to AE reports. RESULTS: Overall, 1427 HCPs at 91 HCFs were trained. In the 8 months before implementation, 33 AE reports were received versus 85 after 3 months and 361 after 18 months of implementation (71 [83.5%] and 278 [77.0%], respectively, from Abidjan). The KPIs with the highest proportions were: AE reports received centrally (100%), complete AE reports (69.0%), AE reports entered into the local PV database within 48 h (99.6%), and AE reports entered into the global database, VigiBase (86.7%). Report notification within 72 h, causality assessment, and serious AE reporting had proportions below 20%; feedback to reporters was provided for only 0.4% of reports. CONCLUSION: Regular PV trainings and mentoring improved AE reporting in Côte d'Ivoire but further enhancement is required to improve passive safety surveillance.

Medicines and vaccines should be safe and effective for use in the general population. Health care professionals therefore have the responsibility to continuously monitor medicinal products and report any unwanted medical occurrence (adverse event). Training and mentoring of health care professionals can improve adverse event reporting. In Côte d'Ivoire, a training and mentoring project was implemented by GSK, PATH (a non-governmental organisation), and the Ministry of Health, with the objective of increasing adverse event reporting. Over the period of 18 months, 1427 health care professionals from 91 health care facilities in the Abidjan region received training and mentoring. Between January and August 2018, before the project began, 33 adverse event reports were submitted at the central level (to the country's Vigilance Unit), with 11 (33.3%) from the Abidjan region. From September to December 2018, the first three months of project implementation, 85 reports were received, with 71 (83.5%) coming from the Abidjan region. This number increased to 361 by the end of the 18-month project, with 278 (77.0%) coming from the Abidjan region. Training of health care professionals therefore improved adverse event reporting, mainly from the Abidjan region but also nationwide. Assessments of the efficiency of adverse event reporting and the quality of adverse events reports received by the Vigilance Unit showed promising results, although there was room for improvement. Lessons learned from this project can flexibly serve the needs of other countries with less functional systems for reporting adverse events associated with medicinal products.

[Antimalaria therapy of chronic renal failure]. / Paludothérapie chez l'insuffisant rénal chronique.

INTRODUCTION: The treatment of uncoded malaria (malaria) remains very delicate in chronic renal failure which is associated with immunity abnormalities which weaken the uremic subject and create a vicious morbid circle. OBJECTIVE: Describe the malaria treatment profile of the chronic renal failure patient with malaria. METHODOLOGY: This was a retrospective study of patients with chronic renal failure presenting with diagnosed simple malaria admitted to the nephrology departments of the university hospital centers of Treichville and Yopougon from October 1, 2018 to February 28, 2019 and having given their informed consent verbal. RESULTS: We identified 278 chronic renal failure patients, 40 (14.4%) of whom had malaria. The mean age was 42±13 years with a male predominance (sex-ratio: 1.1). The clinical signs were hyperthermia (70%), diffuse pain (67.5%) and headache (37.5%). Chronic renal failure was discovered at stage 5 in 87.5% of cases and 85% started chronic dialysis using a dialysis using a hemodialysis catheter (94%). Malaria was confirmed by a thick drop (66%) and a Quantitative Buffy Coast Malaria Test (44%). There was severe anemia with an average hemoglobin level of 7.1±1.9g/dL and thrombocytopenia (38.4%). Malaria was first treated with artemether (67%) or artesunate (25%) intramuscularly (67.5%) or intravenously (25%). The average duration of treatment with artemether was 3 days and artesunate 4.5 days±1.1. Seventy-eight percent of the patients had an injectable antimalarial without oral relay. The clinical course was favorable in 77%. Diabetes was a factor influencing patient evolution. CONCLUSION: This study reveals a misuse of antimalarials because the national recommendations for the treatment of malaria were not respected. The presence of anemia would make the parenteral routes preferable.

Artemisinin-Based Combination Therapy Synergized with Medicinal Plants to Induce Musculotoxic Effects.

INTRODUCTION: Multivisceral, neurological, hepatic, and renal damage has been witnessed following the use of artemisinin-based combination therapy (ACT) and herbal medicine. These multiple organ damages make us think of muscle damage. The objective was to study the myotoxicity of the combination of ACTs with medicinal plants. MATERIALS AND METHODS: Muscle cells (RD cells) were brought into contact with preparations of antimalarial drugs and/or antimalarial herbs. The following drugs were used: artesunate 100 mg/amodiaquine 270 mg (ASAQ) and artemether 80 mg/lumefantrine 480 mg (AL); plant Sida acuta (PSA) and plant Enantia polycarpa (PEP) at 10 µg/ml. After 5 days of incubation, the cells were counted by using a hemocytometer with trypan blue solution. RESULTS: Artesunate/amodiaquine caused a significant drop in the number of muscle cells, compared to the control, between D2 and D4 (p < 0.001). There was also a significant difference between the control and artemether/lumefantrine between D2 (p < 0.01) and D4 (p < 0.001) and between the control and the Sida acuta plant, on D2 (p < 0.001), D4 (p < 0.001), and D5 (p < 0.05). In tubes treated with ASAQ and Sida acuta, cell mortality was over 30%. Finally, statistically significant cell destruction in the tubes treated with the combination of antimalarial drugs and traditional plants compared to those of the control was observed from D2 (p < 0.001). CONCLUSION: Artemisinin-based combination therapy remains effective and well tolerated. But its combination with medicinal plants induced myotoxic effects. This toxicity would appear to be of the additive type. Further studies should be able to better elucidate the mechanism of this toxicity.

Preventive Beneficial Effect of an Aqueous Extract of Phyllanthus amarus Schum. and Thonn. (Euphorbiaceae) on DOCA-Salt-Induced Hypertension, Cardiac Hypertrophy and Dysfunction, and Endothelial Dysfunction in Rats.

This study investigated the preventive effect of an aqueous extract of the whole plant of Phyllanthus amarus (AEPA) on blood pressure, cardiac, and endothelial function in the deoxycorticosterone acetate (DOCA) salt-induced hypertensive rat model. Male Wistar rats were assigned into 5 groups receiving either vehicle (control and DOCA salt), DOCA salt combined with AEPA at 100 or 300 mg/kg, or AEPA (100 mg/kg) alone for 5 weeks. In addition, DOCA salt-treated rats were allowed free access to water containing 1% NaCl. Systolic blood pressure, left ventricle parameters, vascular reactivity of primary mesenteric artery rings, the vascular level of oxidative stress, and the level of target proteins were determined, using respectively tail-cuff sphygmomanometry, echocardiography, organ chambers, dihydroethidium staining, and immunofluorescence methods. After 5 weeks, AEPA treatments (100 or 300 mg/kg per day) significantly prevented the increase in systolic blood pressure in DOCA salt-treated rats, respectively, by about 24 and 21 mm Hg, improved cardiac diastolic function, and reduced significantly the increased posterior and septum diastolic wall thickness and the left ventricle mass in hypertensive rats. Moreover, the DOCA salt-induced endothelial dysfunction and the blunted nitric oxide- and endothelium-dependent hyperpolarization-mediated relaxations in primary mesenteric artery were improved after the AEPA treatments. AEPA also reduced the level of vascular oxidative stress and the expression level of target proteins (eNOS, COX-2, NADPH oxidase subunit p22) in DOCA salt rats. Altogether, AEPA prevented hypertension, improved cardiac structure and function, and improved endothelial function in DOCA salt rats. Such beneficial effects seem to be related, at least in part, to normalization of the vascular level of oxidative stress.

Comparative Antidiabetic Activity of Aqueous, Ethanol, and Methanol Leaf Extracts of Persea americana and Their Effectiveness in Type 2 Diabetic Rats.

Native to Mexico, Persea americana Mill. (avocado) is a fruit tree whose different parts (leaf, bark, roots, and stone) are used in traditional medicine especially against diabetes mellitus. The aim of this study was to investigate the beneficial effects of 28-day treatment with aqueous, ethanolic, and methanolic leaf extracts on glucose homeostasis in type 2 diabetic mellitus using Wistar rats. Type 2 diabetes was induced with nicotinamide (120 mg/kg, i.p.) and streptozotocin (65 mg/kg, i.p.). After 28 days of treatment, histopathological examination of the pancreas, kidneys, liver, and muscle (tibialis anterior) were realized. Biochemical markers were determined and an intestinal absorption test of D-glucose was performed. All extracts (100 mg/kg/day, p.o.) significantly (p < 0.001) reduced blood glucose level at the 28th day of treatment with a more pronounced effect for methanolic extract. The treatments were well tolerated and induced a restoration of T-CHOL and HDL-C levels compared to the control group. Methanolic extract reduced the AIP (atherogenic index of plasma) by 45%. Histopathological analyzes of the pancreas showed regeneration of islets of Langerhans. Methanolic extract was the most effective in preventing intestinal glucose uptake up to 60.90% in relation to metformin. These results justify the use of this plant in traditional medicine against type 2 diabetes. However, other complementary studies should be done to identify the molecules responsible for this activity and their signaling voice.

Ethanol Extract of Leaves of Cassia siamea Lam Protects against Diabetes-Induced Insulin Resistance, Hepatic, and Endothelial Dysfunctions in ob/ob Mice.

Despite long traditional utilization and some reports on the antihyperglycemic and antihyperlipidemic action of Cassia siamea, the mechanisms involved have not been investigated yet. Thus, the objective of the present study was to investigate whether and how oral administration of the ethanolic extract of Cassia siamea Lam leaves (LECS) improves glucose and insulin homoeostasis, liver damage, and endothelial dysfunction in an experimental model of type 2 diabetes, the leptin-deficient ob/ob mice. Oxidative stress and protein expression of insulin-dependent and insulin -independent signaling pathways were studied. Obese ( ob/ob) vs. control (ob/+) mice were treated daily with intragastric administration of either vehicle or LECS (200 mg/kg, per day) for 4 weeks. Fasting blood glucose, body weight, food intake, glucose and insulin tolerance, oxidative stress, and liver damage as well as vascular complications with respect to endothelial dysfunction were examined. Administration of LECS in obese mice significantly reduced blood glucose and insulin levels, improved glucose tolerance and insulin sensitivity, and restored the increase of circulating AST and ALT without modification of body weight and food intake. These effects were associated with increased activity of both insulin and AMPK pathways in the liver and skeletal muscles. Of particular interest, administration of LECS in obese mice completely prevented the endothelial dysfunction resulting from an increased NO· and decreased reactive oxygen species (ROS) production in the aorta. Altogether, oral administration of LECS remarkably attenuates features of type 2 diabetes on glucose, hepatic inflammation, insulin resistance, endothelial function, and vascular oxidative stress, being as most of these effects are related to insulin-dependent and insulin-independent mechanisms. Therefore, this study points for the therapeutic potential of Cassia siamea in correcting both metabolic and vascular alterations linked to type 2 diabetes.

[Evaluation of the knowledge of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine in Ivory Coast]. / Évaluation de la connaissance du traitement préventif intermittent au cours de la grossesse (TPIg) par la sulfadoxine-pyriméthamine en Côte d'Ivoire.

In 2006, because of the chloroquine-resistance and following the World Health Organization (WHO) recommendations, Côte d'Ivoire adopted a new policy for the prevention of malaria during pregnancy by intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, its implementation remains limited. Objectives of this study were to evaluate the knowledge of the TPIp-SP regimen and prescribers opinion concerning this protocol. It was a knowledge attitude and pratices (KAP) cross-sectional descriptive study. We used a two-stage stratified sounding. The study took place in 12 health facilities in the health region of Abidjan 2 from march to august 2016 and involved 187 health professionals. We performed descriptive analysis, univariate and bivariate comparative analysis. The study found that half of the prescribers surveyed actually knew the ITPp program (SP - 3 doses - 2nd and 3rd trimesters). Knowledge was better among practitioners with more than 5 years of exercise (P=0.011) and at the level of first contact of health institution (P=0.001). Half of the prescribers were in favor of applying the protocol. The level of knowledge of prescribers has changed little in 2016 compared to 2008 for physicians (Pr (|Z|<|z|)=0.4861) or midwives Pr (|Z|<|z|)=0.4786). Prescribers remained faithful to the old 2-dose protocol. The opinion on the protocol was better in 2016 compared to 2008 Pr (Z

The acute diuretic effect of an ethanolic fraction of Phyllanthus amarus (Euphorbiaceae) in rats involves prostaglandins.

BACKGROUND: Phyllanthus amarus (Schum & Thonn), a plant belonging to the family of Euphorbiaceae is used in Ivorian traditional medicine to treat cardiovascular disorders such as hypertension. However, although this plant has been described as a diuretic agent, the underlying mechanism remains unclear. Therefore, the aim of the present study was to investigate the mechanism action of diuretic effects of an ethanolic fraction of Phyllanthus amarus (EFPA) in rats. METHODS: Effects of EFPA on urinary excretion were carried out for doses ranging from 5 to 80 mg/kg given by intraperitoneal injection (i.p.) and compared with that induced by furosemide (5 mg/kg) after 8 h. Thereafter, the diuretic activity of EFPA was also evaluated in the presence of indomethacin (5 mg/kg, i.p.) in order to determine the involvement of prostaglandins, after 24 h. RESULTS: Between 5 and 80 mg/kg, EFPA induced a significant urinary excretion. The profile of urinary excretion showed that after 2 h, the highest dose of 80 mg/kg induced a urinary volumetric excretion (UVE), which was similar to that induced by furosemide. After 24 h, EFPA at 10 mg/kg increased significantly UVE, Na+ (43 mEq) and Cl¯ (97 mEq) urinary excretions without promoting kaliuresis. In rats pretreated with indomethacin, the urinary excretion and the natriuretic response of EFPA were significantly reduced. CONCLUSION: Altogether, this study has shown that EFPA promotes a significant urinary excretion of water and Na+, confirming its diuretic activity. Moreover, the increased diuresis could be attributed, at least in part, to the involvement of prostaglandins.

[Hepatonephritis during the treatment of malaria by the therapeutic combinations from a pharmacovigilance database]. / Hépatonéphrites au cours du traitement du paludisme par les combinaisons thérapeutiques à partir d'une base de données de pharmacovigilance.

INTRODUCTION: Prior studies have shown an association between the onset of hepatonephritis and the use of arteminisin-based combination therapy (ACT) during the treatment of uncomplicated malaria. The objective of this study was to identify the risk factors of hepatonephritis occurrence because of the uncertainty regarding the appearance and the aggravation of this syndrome. METHODS: A case-non case study was carried out on 428 notifications of pharmacovigilance extracted from the database of the clinical pharmacology department of the teaching hospital of Cocody from 2008 to 2012. Twenty-two cases of hepatonephritis were identified. Univariate analysis and multivariate logistic regression were performed to identify the risk factors and an adjusted odds ratio (AOR) was calculated for each factor. The cut-off for significant association was set at 0.05. RESULTS: The average age of cases was comparable with that of non-cases (34.04±3.68 years versus 33.94±3.92 years) with a median duration of therapy of 5 days and 6 days respectively. Male (AOR: 6.71; P<0.0001), toxic antecedents, traditherapy (AOR: 6.25; P<0.0001), consumption of CTA (AOR: 1.25; P<0.0001), betalactam (AOR: 0.46; P<0.0001), fluoroquinolone and self-medication (AOR: 2.89; P<0.0001) would be the majors risk factors associated with hepatonephritis onset. The risk increased with the number of antimalarial drugs taken. The evolution towards the offset was less frequent (AOR: 0.078; P<0.02). CONCLUSION: The risk factors of hepatonephritis were the consumption of malarial drugs and connected molecules, self-medication and misuse. The outcome was generally unfavourable. Both the general population and health professionals should be trained on the good use of the antimalarial drugs.

Dengue: etiology of acute febrile illness in Abidjan, Côte d'Ivoire, in 2011-2012.

BACKGROUND: The burden of dengue in Africa is not well understood. A prospective study was conducted in Abidjan, Côte d'Ivoire from December 2011 to December 2012 to estimate the proportion of dengue and malaria cases among febrile patients during a period when dengue was not known to be circulating in the region, and to describe the clinical and virological characteristics of laboratory-diagnosed dengue cases. METHODS: Blood samples were taken from febrile patients (body temperature ≥ 38°C) at two study sites. Patients with fever lasting more than 7 days, with fever of known origin and with jaundice were excluded. Thick blood film tests, ELISA for anti-dengue IgM and reverse transcription-PCR (RT-PCR) were performed. RESULTS: A total of 812 patients were enrolled (51.7% male [48.3% female]; 46.4% aged <10 years) of whom 796 (98.0%) provided IgM ELISA and RT-PCR data, and 807 (99.4%) had thick blood film results. Three (0.4%) patients had laboratory-diagnosed dengue (one with DENV-3 serotype), none of whom were diagnosed clinically, and 234 (28.8%) had confirmed malaria. CONCLUSIONS: This study suggests that dengue virus circulates in Abidjan outside an epidemic and that there should be an increase in awareness of dengue as a possible diagnosis in cases of undifferentiated fever. These results stress the importance of implementing laboratory capacity to assess dengue burden in Africa.

Sodium and blood pressure in Africa.

In the pathophysiology of hypertension, the profile hemodynamic is modified by the relation between the increased sodium intake and blood pressure (BP) level. An increased sodium diet is related not only on the amount of fluid volume within the organism but also to the elasticity of the cardiovascular system. In humans, age and salt excess reduced elasticity is linked to BP level and to stiffness material within the vascular wall of larges arteries. Actions of vasoactives hormones such as angiotensin II, antidiuretic hormone, and aldosterone are also linked. The purpose of this article is : (i) to report existing work in Africa relating to "salt and hypertension", (ii) to determine the characteristic of hypertension among black populations, and for epidemiologic study in Ivory Coast, (iii) to determine the various characteristics of hypertension, prevention of cardiovascular risk, and to show usual antihypertensive drugs for reduce rigidity and vascular fibrosis.

The chronic oral administration of arginine aspartate decreases secretion of IGF-1 and IGFBP-3 in healthy volunteers.

To investigate the effect of chronic oral arginine aspartate on the growth hormone (GH), GH-releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) secretions in healthy volunteers. Twenty-three healthy non-athlete volunteer males were administered arginine aspartate (30 g) orally once daily at 21:00 h for 21 consecutive days. Subjects were hospitalized on days 0, 1, 3, 5, 7, 14 and 21 of treatment. At each hospitalization, concentrations of GHRH, GH, IGF-1 and IGFBP-3 were measured over 4 h after arginine aspartate intake. GH, IGF-1 and IGFBP-3 concentrations were also determined over 12 h at days 0, 1 and 21. Compared with day 1, 4 h GH levels dropped at day 5 and subsequently rose to levels not significantly different from initial ones. The latter was substantiated by 12 h GH levels that did not significantly change from days 1 to 21. GHRH levels were not statistically different, although there was a trend in median values that seemed to inversely mirror those of GH. This dynamic over the course of the study for GH and GHRH was accompanied by a general decrease in IGF-1 and IGFBP-3. In healthy volunteers, a chronic oral treatment with 30 g/day arginine aspartate is followed by a decrease in IGF-1 and IGFBP-3 secretions.

[Clinical trials using medicinal plants: bibliographical review and methodological analysis]. / Essais cliniques des medicaments à base de plantes: revue bibliographique.

BACKGROUND: The importance of traditional medicine, one of the fundamentals of the cultural heritage of African, Asian and South American peoples, is evident in that such medicine is practised by more than 80% of these populations. METHODS: To analyse the methodology of clinical trials using medicinal plants, we reviewed articles published on this topic between 1980 and 2000. RESULTS: Forty-eight clinical trials were identified. Most were carried out in developed countries. Standard methodological principles were applied in almost all the trials: randomisation (85.4%), comparison (87.5%) versus placebo (95.2%), and blinded design (81.3%). The duration of the studies was short. Sample sizes were generally small, ranging from 30 to 99 subjects; statistical tests were used in 90% of the trials. Adverse effects were infrequently collected. CONCLUSION: Most clinical trials included in this survey were conducted in accordance with WHO guidelines. Respect for methodological principles and the implementation of a legislative framework are important in obtaining credibility and international recognition of the traditional pharmacopoeia.