Adverse events following immunization reported with COVID-19 vaccines in Burkina Faso: Analysis of spontaneous reports / Manifestations post-vaccinales indésirables rapportées avec les vaccins anti-COVID-19 au Burkina Faso : analyse des notifications spontanées

The rapid deployment of COVID-19 vaccines to a large proportion of the population requires a focus on safety. However, few studies have assessed the safety of COVID-19 vaccines in Africa. In Burkina Faso, this issue has not yet been addressed. The objective of this study was to contribute to the description of the characteristics of adverse events following immunization (AEFIs) related to COVID-19 vaccines in Burkina Faso. This was a cross-sectional descriptive retrospective study of spontaneous reports of COVID-19 vaccine-related AEFIs recorded in VigiBase® between June 2021 and November 2022 in Burkina Faso. Individual case safety reports (ICSRs) were extracted from VigiBase® using the Anatomical Therapeutic Chemical level 2 (ATC2) code. The proportion of ICSRs according to the reporter's qualification, the reporting rate, the time taken to submit and record ICSRs, and the completeness score were calculated. A total of 973 ICSRs concerned COVID-19 vaccines and represented 32.6% of all 2,988 reports in VigiBase®. Overall, 82.0% of the reporters were nurses/midwives, 7.8% were physicians, 6.7% were pharmacists, and 3.4% were patients. The median time between the onset of AEFIs and the submission of the report to the Pharmacovigilance Center was 180 days (IQR: 136; 281). The median registration time was 188 days (IQR: 149; 286). The mean ICSR completeness score was 0.8 (standard deviation = 0.1). The overall AEFI reporting rate was 27.8 per 100,000 vaccine doses. The AEFI reporting rates for the ChAdOx1-nCoV-19, JNJ 78436735, Elasomeran, Tozinameran, and HB02 vaccines were 454.2, 17.4, 11.0, 10.2, and 0.4 per 100,000 vaccine doses, respectively. The majority of AEFIs were systemic in nature (90.1%). Headache (21.2%), fever (19.4%), and myalgia (11.0%) were the most frequently reported AEFIs. Eighteen cases (1.8%) of serious AEFIs (9 hospitalizations, 4 life threatening, 3 temporary disabilities, and 2 others unspecified) were reported. The majority of AEFIs reported were systemic in nature and mild. However, there have been reports of serious AEFIs. The overall AEFI reporting rate was low. There is a need to strengthen the monitoring of these vaccines to better organize strategies to optimize the adherence of the population of Burkina Faso.

Le déploiement rapide des vaccins anti COVID-19 sur une grande partie de la population nécessite de mettre l'accent sur la sécurité. Cependant, peu d'études ont évalué la sécurité des vaccins anti COVID-19 en Afrique. Au Burkina Faso, cette question n'a pas encore été abordée. La présente étude avait pour objectif de contribuer à la description des caractéristiques des manifestations post-vaccinales indésirables (MAPI) liées aux vaccins anti COVID-19 au Burkina Faso. Il s'est agi d'une étude transversale rétrospective ayant porté sur les notifications de MAPI liées aux vaccins anti COVID-19 enregistrées dans VigiBase® entre juin 2021 et novembre 2022 au Burkina Faso. Les cas individuels de rapports de sécurité (CIRS) ont été extraits de VigiBase® à l'aide du code Anatomical Therapeutic Chemical niveau 2 (ATC2). La proportion de CIRS selon la qualification du notificateur, le taux de notification, le délai de transmission et d'enregistrement des CIRS et le score d'exhaustivité ont été calculés. Au total 973 CIRS concernaient les vaccins anti COVID-19 et représentaient 32,6 % des 2 988 rapports enregistrés dans VigiBase®. La répartition des notifications en fonction de la qualification du notificateur a montré que 82,0 % étaient des infirmiers/sage femmes, 7,8 % des médecins, 6,7 % des pharmaciens et 3,4 % des patients. Le délai médian entre l'apparition des MAPI et la transmission du rapport au Centre de pharmacovigilance était de 180 jours (IQR : 136 ; 281). Le délai médian d'enregistrement était de 188 jours (IQR : 149 ; 286). Le score d'exhaustivité moyen des CIRS était de 0,8 (écart type = 0,1). Le taux global de notifications des MAPI était de 27,8 pour 100 000 doses de vaccins. Les taux de notification des MAPI pour les vaccins ChAdOx1-nCoV-19, JNJ 78436735, Elasomeran, Tozinameran et HB02 étaient de 454,2 ; 17,4 ; 11,0 ; 10,2 et 0,4 pour 100 000 doses, respectivement. La majorité des MAPI était de manifestation systémique (90,1 %). Les céphalées (21,2 %), la fièvre (19,4 %) et les myalgies (11,0 %) étaient les MAPI les plus fréquemment notifiés. Dix-huit cas (1,8 %) de MAPI graves (9 hospitalisations, 4 mises en jeu du pronostic vital, 3 incapacités temporaires et 2 autres non précisés) ont été rapportés. La majorité des cas notifiés dans le cadre de la surveillance des MAPI était de manifestation systémique et de nature bénigne. Néanmoins, des cas de MAPI graves ont été notifiés. Le taux global de notification des MAPI était faible. Il est nécessaire de renforcer la surveillance de ces vaccins pour mieux organiser les stratégies visant à optimiser l'adhésion de la population burkinabé.

Monitoring of adverse drug reactions during seasonal malaria chemoprevention campaigns in children aged 3­59 months in Burkina Faso / Surveillance des effets indésirables lors des campagnes de la chimioprévention du paludisme saisonnier chez les enfants de 3-59 mois au Burkina Faso

Introduction: Seasonal malaria chemoprevention (SMC) by mass administration of sulfadoxine pyrimethamine + amodiaquine (SPAQ) reduces the burden of malaria in children aged 3­59 months. The occurrence of adverse drug reaction (ADR) may affect the success of this intervention. There are few studies of SMC adverse event surveillance in sub-Saharan Africa, particularly in Burkina Faso, a highly endemic country. Our main objective was to characterize the ADRs reported during SMC campaigns in Burkina Faso. Secondly, we evaluated the performance of the pharmacovigilance integrated into the SMC program in order to support safe administration of SMC. Method: This was a retrospective descriptive study of SMC individual case safety reports recorded in VigiBase® in Burkina Faso from 2014 to 2021. We used the P-method for the analysis of preventable serious adverse drug reactions and WHO criteria for assessing the performance of pharmacovigilance integrated into the SMC program. Results: A total of 1,105 SMC individual case safety reports were registered in VigiBase® for 23,311,453 doses of SPAQ given between 2014 and 2021. No pharmacovigilance signal was detected. The number of serious cases was 101, of which 23 (22.8%) were preventable. In 38.1% of children, the occurrence of ADRs led to discontinuation of SMC treatment. Vomiting was the most frequently reported adverse drug reaction (48.0%). The proportion of children whose treatment was discontinued due to vomiting was 42.7%, while the proportion of treatment discontinuation for other ADRs was 32.8% (p = 0.01). The SMC program contributed at 46.2% to the national pharmacovigilance database. The reporting rate was 0.03 per 1,000 exposed children in 2021. The median completeness score of the ICSRs was 0.7 (IQR: 0.5­0.7), and the median time to register the ICSRs in VigiBase® was 204 (IQR: 143­333) days. Conclusions: Post-drug administration vomiting may interfere with the purpose of SMC. Measures to manage this adverse drug reaction should be taken to improve the success of the SMC program. Based on the information on reporting time and reporting rate, spontaneous reporting should be supported by active surveillance, including cohort event monitoring, in Burkina Faso.

Introduction: La chimioprévention du paludisme saisonnier (CPS) par l'administration en masse de la sulfadoxine-pyriméthamine + amodiaquine (SPAQ) permet de réduire le fardeau du paludisme chez les enfants de 3-59 mois. La survenue d'effets indésirables (EI) pourrait nuire au succès de cette intervention. Il existe peu d'études sur la surveillance des EI de la CPS en Afrique subsaharienne et plus particulièrement au Burkina Faso, pays de forte endémicité palustre. Notre objectif principal était de caractériser les effets indésirables notifiés au cours des campagnes CPS au Burkina Faso. Secondairement, nous avons évalué la performance de la pharmacovigilance intégrée au programme de CPS dans le but de soutenir la sécurité d'administration de la CPS. Méthodes: Nous avons réalisé une analyse rétrospective à visée descriptive des rapports d'effets indésirables de la CPS enregistrés dans VigiBase® entre le 1er janvier 2014 et le 31 décembre 2021. Nous avons utilisé la P-method pour l'analyse de l'évitabilité des effets indésirables graves et les critères de l'OMS pour évaluer la performance de la pharmacovigilance intégrée au programme de CPS. Résultats: Au total, 1 105 cas individuels de rapports de sécurité de la CPS ont été analysés dans VigiBase® pour 23 311 453 doses administrées. Aucun signal de pharmacovigilance n'a été détecté. Le nombre des cas graves était de 101, dont 23 (22,8 %) évitables. Chez 38,1 % des enfants, la survenue des EI a occasionné l'arrêt de l'administration du traitement de la CPS. Le vomissement était l'effet indésirable le plus fréquemment rapporté (48,0 %). La proportion d'enfants dont le traitement a été arrêté pour motif de vomissement était de 42,7 %, tandis que la proportion d'arrêts de traitement pour les autres EI était de 32,8 % (p=0,01). La pharmacovigilance de la CPS a contribué à 46,2 % à l'alimentation de la base de données nationale de pharmacovigilance. Le taux de notification était de 0,03 pour 1 000 enfants exposés en 2021. Le score d'exhaustivité médian des rapports était de 0,7 (P25-P75 : 0,5-0,7) et le délai médian d'enregistrement des rapports dans VigiBase® était de 204 (P25-P75 : 143-333) jours. Conclusions: Les vomissements peuvent nuire à l'objectif de la CPS. Des mesures de gestion de cet effet indésirable doivent être prises pour améliorer le succès de la CPS. Au regard des informations sur le délai de notification et le taux de notification, la notification spontanée devrait être soutenue par une surveillance active, notamment une « cohort event monitoring ¼ au Burkina Faso.

Adverse Drug Reactions to Antiretroviral Therapy: Frequency, Type, and Risk Factors in Children in Mali.

OBJECTIVE: The aim of our study was to evaluate the frequency, type, and risk factors associated with adverse drug reactions (ADRs) in HIV-positive children with adherence to antiretroviral therapy (ART) at the Unit of Care and Accompaniment for People Living With HIV (USAC) of Bamako. METHODS: A cross-sectional study was conducted at USAC of Bamako from May 1, 2014, to July 31, 2015. We included children aged 1 to 14 years with at least 6 months of ARV treatment initiated at USAC, with or without ADRs. Data collection was based on information collected from parents and clinical/biological assessments. RESULTS: Median age of participants was 36 months and female sex was predominant (54.8%). Poor adherence during the study was observed in 15% of cases. Of patients in the study, 52% had a CD4 count less than 350 cells/mm3 at the time of adverse events. In bivariate analysis, we found that participants with adherence to ART tended to be younger than those with non-adherence to ART (36 vs 72 months, p = 0.093). In multivariable analysis, prophylactic treatment was the only factor marginally associated with ART adherence in HIV patients (p = 0.09). No other adverse biological effects or clinical conditions were associated with ART adherence in this study. CONCLUSIONS: In this study we found that ADRs were frequent in HIV-positive patients but less frequent in ART-adherent HIV-positive children. Therefore, it is essential to regularly monitor children receiving ARVs to detect and treat the complications associated with these therapies according to ART adherence.

Surveillance des effets indésirables lors des campagnes de la chimioprévention du paludisme saisonnier chez les enfants de 3-59 mois au Burkina Faso.

INTRODUCTION: Seasonal malaria chemoprevention (SMC) by mass administration of sulfadoxine pyrimethamine + amodiaquine (SPAQ) reduces the burden of malaria in children aged 3-59 months. The occurrence of adverse drug reaction (ADR) may affect the success of this intervention. There are few studies of SMC adverse event surveillance in sub-Saharan Africa, particularly in Burkina Faso, a highly endemic country. Our main objective was to characterize the ADRs reported during SMC campaigns in Burkina Faso. Secondly, we evaluated the performance of the pharmacovigilance integrated into the SMC program in order to support safe administration of SMC. METHOD: This was a retrospective descriptive study of SMC individual case safety reports recorded in VigiBase® in Burkina Faso from 2014 to 2021. We used the P-method for the analysis of preventable serious adverse drug reactions and WHO criteria for assessing the performance of pharmacovigilance integrated into the SMC program. RESULTS: A total of 1,105 SMC individual case safety reports were registered in VigiBase® for 23,311,453 doses of SPAQ given between 2014 and 2021. No pharmacovigilance signal was detected. The number of serious cases was 101, of which 23 (22.8%) were preventable. In 38.1% of children, the occurrence of ADRs led to discontinuation of SMC treatment. Vomiting was the most frequently reported adverse drug reaction (48.0%). The proportion of children whose treatment was discontinued due to vomiting was 42.7%, while the proportion of treatment discontinuation for other ADRs was 32.8% (p = 0.01). The SMC program contributed at 46.2% to the national pharmacovigilance database. The reporting rate was 0.03 per 1,000 exposed children in 2021. The median completeness score of the ICSRs was 0.7 (IQR: 0.5-0.7), and the median time to register the ICSRs in VigiBase® was 204 (IQR: 143-333) days. CONCLUSIONS: Post-drug administration vomiting may interfere with the purpose of SMC. Measures to manage this adverse drug reaction should be taken to improve the success of the SMC program. Based on the information on reporting time and reporting rate, spontaneous reporting should be supported by active surveillance, including cohort event monitoring, in Burkina Faso.

Detection of Falsified Antimalarial Sulfadoxine-Pyrimethamine and Dihydroartemisinin-Piperaquine Drugs Using a Low-Cost Handheld Near-Infrared Spectrometer.

Falsified drugs are of serious concern to public health worldwide, particularly for developing countries where quality control of drugs is inefficient. In law enforcement against such fake medicines, there is a need to develop reliable, fast, and inexpensive screening methods. In this work, the ability of an innovative low-cost handheld near-infrared spectrometer to identify falsifications among two antimalarial fixed dose combination tablets, dihydroartemisinin/piperaquine and sulfadoxine/pyrimethamine, has been investigated. Analyzed samples were collected in Burkina Faso mainly in rural transborder areas that could be infiltrated by illicit drugs. A principal component analysis was applied on the acquired near-infrared spectra to identify trends, similarities, and differences between collected samples. This allowed to detect some samples of dihydroartemisinin/piperaquine and sulfadoxine/pyrimethamine which seemed to be falsified. These suspicious samples were semiquantitatively analyzed by thin-layer chromatography using Minalab® kits. Obtained results allowed to confirm the falsifications since the suspected samples did not contain any of the expected active pharmaceutical ingredients. The capacity of the low-cost near-infrared device to identify specifically a brand name of dihydroartemisinin/piperaquine or sulfadoxine/pyrimethamine has been also studied using soft independent modelling of class analogy (SIMCA) in the classical and data driven versions. The built models allowed a clear brand identification with 100% of both sensitivity and specificity in the studied cases. All these results demonstrate the potential of these low-cost near-infrared spectrometers to be used as first line screening tools, particularly in resource limited laboratories, for the detection of falsified antimalarial drugs.

In Vitro Antioxidant and Anticancer Properties of Various E. senegalensis Extracts.

Although Erythrina senegalensis is a plant widely used in traditional medicine in sub-Saharan Africa, its biological properties have been poorly investigated to date. We first characterized by conventional reactions the composition of several stem bark extracts and evaluated in acellular and cellular assays their pro- or antioxidant properties supported by their high phenolic and flavonoid content, particularly with the methanolic extract. The pro- or antioxidant effects observed did not correlate with their IC50 concentrations against five cancer cell lines determined by MTT assay. Indeed, the CH2Cl2 extract and its ethyl acetate (EtOAc) subfraction appeared more potent although they harbored lower pro- or antioxidant effects. Nevertheless, at equipotent concentration, both extracts induced ER- and mitochondria-derived vacuoles observed by fluorescent microscopy that further led to non-apoptotic cell death. LC coupled to high resolution MS investigations have been performed to identify chemical compounds of the extracts. These investigations highlighted the presence of compounds formerly isolated from E. senegalensis including senegalensein that could be retrieved only in the EtOAc subfraction but also thirteen other compounds, such as 16:3-Glc-stigmasterol and hexadecanoic acid, whose anticancer properties have been previously reported. Nineteen other compounds remain to be identified. In conclusion, E. senegalensis appeared rich in compounds with antioxidant and anticancer properties, supporting its use in traditional practice and its status as a species of interest for further investigations in anticancer drug research.

Design and Implementation of a Computerized Management System for Adverse Drug Reactions at the Sourô SANOU University Hospital (CHUSS) in Bobo-Dioulasso, Burkina Faso.

Pharmacovigilance is the science and activities related to the detection, evaluation, understanding and prevention of adverse drug reactions or any other possible drug-related problems. In our tropics, this discipline is in an embryonic state. The availability of a management system capable of responding to pharmacovigilance activities is the main objective of our study. The coding was done on the DJANGO Framework. Signal detection was done using the ROR method. We designed three modules which are the notification module, the analysis module and the statistics module. This study has allowed us to launch the basis for a computerization of the pharmacovigilance information system and partly meets our objective. However, it could lead to the integration of the dictionary of adverse effects such as MedDRA as well as the International Classification of Medicines (ATC, EphMRA).

Systematic Review of Potential Anticancerous Activities of Erythrina senegalensis DC (Fabaceae).

The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant Erythrina senegalensis, focusing on compounds harboring activities against cancer models detailed in depth herein at both in vitro and in vivo preclinical levels. The review was conducted through Pubmed and Google Scholar. Nineteen out of the forty-two secondary metabolites isolated to date from E. senegalensis displayed interesting in vitro and/or in vivo antitumor activities. They belonged to alkaloid (Erysodine), triterpenes (Erythrodiol, maniladiol, oleanolic acid), prenylated isoflavonoids (senegalensin, erysenegalensein E, erysenegalensein M, alpinumisoflavone, derrone, warangalone), flavonoids (erythrisenegalone, senegalensein, lupinifolin, carpachromene) and pterocarpans (erybraedine A, erybraedine C, phaseollin). Among the isoflavonoids called "erysenegalensein", only erysenealenseins E and M have been tested for their anticancerous properties and turned out to be cytotoxic. Although the stem bark is the most frequently used part of the plant, all pterocarpans were isolated from roots and all alkaloids from seeds. The mechanisms of action of its metabolites include apoptosis, pyroptosis, autophagy and mitophagy via the modulation of cytoplasmic proteins, miRNA and enzymes involved in critical pathways deregulated in cancer. Alpinumisoflavone and oleanolic acid were studied in a broad spectrum of cancer models both in vitro and in preclinical models in vivo with promising results. Other metabolites, including carpachromen, phaseollin, erybraedin A, erysenegalensein M and maniladiol need to be further investigated, as they display potent in vitro effects.

Plaidoyer pour un renforcement du système de pharmacovigilance au Burkina Faso.

Large-scale deployment of new medicines has been observed over the last two decades in many Sub-Saharan Africa countries faced with major public health issues such as malaria and HIV/AIDS. However, some of these medicines may be responsible for varying degrees of toxicity, with adverse drug reactions leading to decreased compliance or even discontinuation of treatment. Pharmacovigilance systems therefore had to be set up in these countries, such as in Burkina Faso, West Africa, which initiated the organization of pharmacovigilance activities in 2008. Despite this progress, the systems in place have not yet achieved a sufficient level of performance to deal with drug-related health issues, highlighting the need for further actions. Pharmacovigilance in Burkina Faso can be strengthened at multiple levels: pre-service and in-service training of health workers; the establishment of active surveillance based on sentinel sites; informing the public and raising awareness; and strengthening national coordination.

Pharmacovigilance systems in developing countries: an evaluative case study in Burkina Faso.

BACKGROUND: Burkina Faso, like other Sub-Saharan African countries, has recently experienced a large-scale deployment of new medicines for the prevention and treatment of notable diseases of public health interest, including malaria, HIV/AIDS and meningitis. This new context rendered the implementation of pharmacovigilance necessary in order to monitor and establish the safety and effectiveness of these medicines. In 2008, the Ministry of Health of Burkina Faso, West Africa, launched a formal pharmacovigilance system to respond to this need. OBJECTIVE: The aim of this study was to evaluate the early-stage pharmacovigilance system of Burkina Faso through a comprehensive and system-based approach with the prospect of identifying areas for improvements. METHODS: We conducted a descriptive cross-sectional study in Burkina Faso. Sixteen key informants from the National Drug Authority (NDA), public health programmes (PHPs) and hospitals were interviewed. Study participants were selected based on a convenience sampling in the NDA, three teaching hospitals, two regional hospitals and six PHPs. Data were collected using the Indicator-based Pharmacovigilance Assessment Tool (IPAT), a metric instrument recently designed and validated by 'Management Sciences for Health', a US non-profit organization. The evaluation also involved the collection and review of relevant pharmacovigilance-related documentation in the institutions assessed. A scoring system was used for the quantification of assessment results. RESULTS: The NDA of Burkina Faso, the institution statutorily in charge of pharmacovigilance, achieved a performance score of 70 %. The basic structures for pharmacovigilance activities were in place; however, the lack of specific laws dedicated to pharmacovigilance, the lack of national guidelines and standard operating procedures on pharmacovigilance, and the insufficient coordination of pharmacovigilance stakeholders in the country were identified as the main weaknesses. Safety data collected thus far have not led to the identification of local drug-related risks; yet, relevant external safety alerts are monitored and acted upon. In 2010, 31 marketing authorizations were modified to include new safety information; seven others were suspended and the corresponding medicines were withdrawn from the national market. In PHPs, pharmacovigilance activities were not formalized, and in hospitals, pharmacovigilance structures were still under development. CONCLUSION: Relevant interventions aimed at strengthening the legal framework and structures for pharmacovigilance activities, and improving the coordination of stakeholders countrywide, should be undertaken as soon as possible. Such an investment is necessary before the national pharmacovigilance system is able to collect its own data, generate signals, evaluate and manage local medicine-related risks and then become a genuine tool for public health.