BackgroundIn many malaria-endemic, sub-Saharan African countries, existing pharmacovigilance systems are not sufficiently operational to document reliably the safety profile of anti-malarial drugs. This study describes the implantation of a community-based pharmacovigilance system in Côte d’Ivoire and its use to document the safety of ASAQ Winthrop® (artesunate–amodiaquine).MethodsThis prospective, longitudinal, descriptive, non-comparative, non-interventional study on the use of artesunate–amodiaquine in real-life conditions of use was conducted in seven Community Health Centres of the Agboville district in Côte d’Ivoire. Twenty trained Health Centre employees and 70 trained community health workers were involved in data collection in the field. All patients with suspected uncomplicated falciparum malaria, seeking treatment at one of the participating Health Centres, and treated with artesunate–amodiaquine could be enrolled. Two visits were planned, one for inclusion at the Health Centre and a second at home, performed by a community health worker 3–10 days after the inclusion visit. Administration of artesunate–amodiaquine was unsupervised. Adverse events (AEs) were documented at the home visit or during any unexpected visit to the Health Centre or to the hospital and coded and adjudicated by a local pharmacovigilance committee. Symptoms suggestive of hepatic failure, severe neutropaenia, extrapyramidal disorders and retinopathy were considered a priori as AEs of special interest.ResultsSome 15,228 malaria episodes in 12,198 patients were evaluated; 2545 AEs were documented during 1978 malaria episodes (13.0%). The most frequently observed events were asthenia (682 cases), vomiting (482 cases) and somnolence (174 cases). Most reported AEs were of mild or moderate intensity and resolved without corrective treatment. One-hundred and five (105) AEs reported during 100 episodes (0.7%) were considered as serious. Three serious cases of transient extrapyramidal disorders, identified as AEs of special interest were reported in three patients.ConclusionThe fixed dose artesunate–amodiaquine combination ASAQ Winthrop® for the unsupervised treatment of uncomplicated falciparum malaria under real-life conditions of care in Côte d’Ivoire is well tolerated. The study emphasizes the interest of involving properly trained community health workers to collect pharmacovigilance data in the field in order to document rare AEs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1655-1) contains supplementary material, which is available to authorized users.
Airway hyperresponsiveness is a main feature of asthma, and several lines of evidence suggest that tachykinins might be involved in the pathogenesis of airway hyperresponsiveness in rodents. We conducted a study designed to describe an original model of airway hyperresponsiveness induced by citric acid administered as aerosol to guinea pigs, and to investigate the effects of the nonpeptide neurokinin1 (NK1) and neurokinin2 (NK2)-receptor antagonists, SR 140333 and SR 48968, respectively, on the development of this airway hyperresponsiveness. Animals received thiorphan 1 mg/kg intraperitoneally and 30 min later were exposed to an aerosol of citric acid 0.4 M for 1 h. After 24 h, the animals were anesthetized and ventilated. Airway hyperresponsiveness was evidenced by significant shifts to the left of dose-response curves for intravenous acetylcholine (ACh) without a change in maximum responses to ACh. Exposure to citric acid induced an airway hyperresponsive that was abolished by chronic pretreatment with capsaicin (120 mg/kg, 5 d before citric acid exposure). SR 48968 1 mg/kg intraperitoneally, given once at 30 min before the citric acid exposure, inhibited airway hyperresponsiveness, whereas SR 140333 1 mg/kg or codeine 30 mg/kg given under similar conditions did not. The inhibition of airway hyperresponsiveness by SR 48968 did not result from functional antagonism, since SR 48968 did not affect ACh-induced bronchoconstriction, nor did it result from inhibition of tachykinin, which could have been released under the influence of ACh in hyperresponsive animals, since SR 48968 given after the exposure to aerosolized citric acid failed to inhibit airway hyperresponsiveness. In conclusion, these results show that inhaled citric acid can induce the development of an airway hyperresponsiveness in the guinea pig through a release of tachykinins, and also demonstrate that NK2-receptor stimulation plays a predominant role in the development of airway hyperresponsiveness.
Background While antiretroviral treatment (ART)-related adverse drug reactions (ADR) are documented in industrialized countries, there is no pre-existing surveillance system dedicated to ADR monitoring in most African countries. We assessed knowledge towards pharmacovigilance among ART prescribers and available capacity of HIV clinics to conduct ADR monitoring in Abidjan, Côte d’Ivoire. Methods A questionnaire was administered to ART prescribers, to assess their knowledge towards the occurrence of ADRs. A retrospective ADR survey was also conducted, based on a data query of treatment modification/interruptions in three HIV clinics. Clinical monitors went back to medical charts to review and validate the reasons of the treatment modification/interruptions. Results Of the 81 ART prescribers interviewed, 25 (31%) declared not grading ADRs and 12 (14.8%) declared notifying ADRs to the national regulatory authorities. Among 5,252 adult ART-treated patients who attended the participating clinics in 2008, 599 treatment modifications were identified. Reasons for treatment modification/interruptions identified in the electronic database were documented in the medical charts in 554 (92.5%) cases, ADR accounting for 273 (45.5%) cases. Toxicity related to ART was graded in only 58 (21%) cases in the medical charts. Discussion This study describes challenges limiting the implementation of reliable pharmacovigilance activities in HIV clinics in Côte d’Ivoire. The lack of knowledge of ART prescribers concerning ADR grading does not support the spontaneous reporting of ADRs. Using treatment modification/interruptions for ADR monitoring appears feasible but improvements are needed to respond to key questions related to drug toxicities in the context of ART scale up in Africa.
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