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.

Challenges and lessons learned from four years of planning and implementing pharmacovigilance enhancement in sub-Saharan Africa.

Pharmacovigilance (PV) systems in many countries in sub-Saharan Africa (SSA) are not fully functional. The spontaneous adverse events (AE) reporting rate in SSA is lower than in any other region of the world, and healthcare professionals (HCPs) in SSA countries have limited awareness of AE surveillance and reporting procedures. The GSK PV enhancement pilot initiative, in collaboration with PATH and national PV stakeholders, aimed to strengthen passive safety surveillance through a training and mentoring program of HCPs in healthcare facilities in three SSA countries: Malawi, Côte d'Ivoire, and Democratic Republic of Congo (DRC). Project implementation was country-driven, led by the Ministry of Health via the national PV center or department, and was adapted to each country's needs. The implementation phase for each country was scheduled to last 18 months. At project start, low AE reporting rates reflected that awareness of PV practices was very low among HCPs in all three countries, even if a national PV center already existed. Malawi did not have a functional PV system nor a national PV center prior to the start of the initiative. After 18 months of PV training and mentoring of HCPs, passive safety surveillance was enhanced significantly as shown by the increased number of AE reports: from 22 during 2000-2016 to 228 in 18 months to 511 in 30 months in Malawi, and ~ 80% of AE reports from trained healthcare facilities in Côte d'Ivoire. In DRC, project implementation ended after 7 months because of the SARS-CoV-2 pandemic. Main challenges encountered were delayed AE report transmission (1-2 months, due mainly to remoteness of healthcare facilities and complex procedures for transmitting reports to the national PV center), delayed or no causality assessment due to lack of expertise and/or funding, negative perceptions among HCPs toward AE reporting, and difficulties in engaging public health programs with the centralized AE reporting processes. This pilot project has enabled the countries to train more HCPs, increased reporting of AEs and identified KPIs that could be flexibly replicated in each country. Country ownership and empowerment is essential to sustain these improvements and build a stronger AE reporting culture.

Enhancing Pharmacovigilance in Sub-Saharan Africa Through Training and Mentoring: A GSK Pilot Initiative in Malawi.

INTRODUCTION: Pharmacovigilance (PV) systems to monitor drug and vaccine safety are often inadequate in sub-Saharan Africa. In Malawi, a PV enhancement initiative was introduced to address major barriers to PV. OBJECTIVE: The objective of this initiative was to improve reporting of adverse events (AEs) by strengthening passive safety surveillance via PV training and mentoring of local PV stakeholders and healthcare providers (HCPs) at their own healthcare facilities (HCFs). METHODS: An 18-month PV training and mentoring programme was implemented in collaboration with national stakeholders, and in partnership with the Ministry of Health, GSK and PATH. Two-day training was provided to Expanded Programme on Immunisation coordinators, identified as responsible for AE reporting, and four National Regulatory Authority representatives. Abridged PV training and mentoring were provided regularly to HCPs. Support was given in upgrading the national PV system. Key performance indicators included the number of AEs reported, transmission of AE forms, completeness of reports, serious AEs reported and timeliness of recording into VigiFlow. RESULTS: In 18 months, 443 HCPs at 61 HCFs were trained. The number of reported AEs increased from 22 (January 2000 to October 2016) to 228 (November 2016 to May 2018), enabling Malawi to become a member of the World Health Organization Programme for International Drug Monitoring. Most (98%) AE report forms contained mandatory information on reporter, event, patient and product, but under 1% were transmitted to the national PV office within 48 h. CONCLUSION: Regular PV training and mentoring of HCPs were effective in enhancing passive safety surveillance in Malawi, but the transmission of reports to the national PV centre requires further improvement.

When a medicine or vaccine is made available for use, healthcare organisations maintain regular surveillance to confirm that the medicinal product is safe and effective. The efficiency of this surveillance depends mainly on the healthcare system and medical practices in place in each country. An important element is an effective procedure for identifying and reporting any unwanted medical occurrences (adverse events) after taking a medicinal product. In countries where regular safety surveillance has not been maintained, it is important to train and mentor healthcare providers on the need to be aware of adverse events and the importance of adhering to safety reporting procedures. GSK and partners conducted a pilot project in Malawi with the aim of improving adverse event reporting by training and mentoring healthcare providers. Training sessions and continuous mentoring were conducted over 18 months, involving 443 healthcare providers at 61 healthcare facilities. There was a large increase in the number of adverse events reported: from 22 in the 16-year period before the project started to 228 during the 18-month project period. This project showed that the training and mentoring programme for healthcare providers was effective in increasing the number of adverse events reported. This enabled Malawi to join the World Health Organization's international safety reporting scheme. Other countries facing similar challenges in safety surveillance systems could benefit from a similar approach.

Introducing new vaccines in low- and middle-income countries: challenges and approaches.

INTRODUCTION: The number of new vaccine introductions (NVIs) in low and middle-income countries (LMICs) has markedly increased since 2010, raising challenges to often overstretched and underfunded health care systems. AREAS COVERED: We present an overview of some of these challenges, focusing on programmatic decisions, delivery strategy, information and communication, pharmacovigilance and post-licensure evaluation. We also highlight field-based initiatives that may facilitate NVI. EXPERT COMMENTARY: Some new vaccines targeting populations other than infants require alternative delivery strategies. NVIs impact upon existing supply chain management, in particular vaccines with novel characteristics. A lack of understanding about immunization and misconceptions may be detrimental to NVI, as well as insufficient or poorly trained health care workforce. Many barriers exist to achieving good vaccination coverage. Real-world evaluation of vaccine safety, effectiveness and impact in LMICs may be limited by lack of robust demographic and disease epidemiology data, as well as limited health care and surveillance infrastructure. A thorough planning phase is crucial to define the most suitable delivery strategy based on the vaccine's and country's specificities. A communication plan and social mobilization are essential. Implementation research and innovative approaches applied to logistics, delivery, communication and program evaluation can facilitate NVI.

Persistence of Rabies Virus-Neutralizing Antibodies after Vaccination of Rural Population following Vampire Bat Rabies Outbreak in Brazil.

BACKGROUND: Animal control measures in Latin America have decreased the incidence of urban human rabies transmitted by dogs and cats; currently most cases of human rabies are transmitted by bats. In 2004-2005, rabies outbreaks in populations living in rural Brazil prompted widespread vaccination of exposed and at-risk populations. More than 3,500 inhabitants of Augusto Correa (Pará State) received either post-exposure (PEP) or pre-exposure (PrEP) prophylaxis. This study evaluated the persistence of rabies virus-neutralizing antibodies (RVNA) annually for 4 years post-vaccination. The aim was to evaluate the impact of rabies PrEP and PEP in a population at risk living in a rural setting to help improve management of vampire bat exposure and provide additional data on the need for booster vaccination against rabies. METHODOLOGY/PRINCIPAL FINDINGS: This prospective study was conducted in 2007 through 2009 in a population previously vaccinated in 2005; study participants were followed-up annually. An RVNA titer >0.5 International Units (IU)/mL was chosen as the threshold of seroconversion. Participants with titers ≤0.5 IU/mL or Equivalent Units (EU)/mL at enrollment or at subsequent annual visits received booster doses of purified Vero cell rabies vaccine (PVRV). Adherence of the participants from this Amazonian community to the study protocol was excellent, with 428 of the 509 (84%) who attended the first interview in 2007 returning for the final visit in 2009. The long-term RVNA persistence was good, with 85-88.0% of the non-boosted participants evaluated at each yearly follow-up visit remaining seroconverted. Similar RVNA persistence profiles were observed in participants originally given PEP or PrEP in 2005, and the GMT of the study population remained >1 IU/mL 4 years after vaccination. At the end of the study, 51 subjects (11.9% of the interviewed population) had received at least one dose of booster since their vaccination in 2005. CONCLUSIONS/SIGNIFICANCE: This study and the events preceding it underscore the need for the health authorities in rabies enzootic countries to decide on the best strategies and timing for the introduction of routine rabies PrEP vaccination in affected areas.

Rotavirus surveillance in urban and rural areas of Niger, April 2010-March 2012.

Knowledge of rotavirus epidemiology is necessary to make informed decisions about vaccine introduction and to evaluate vaccine impact. During April 2010-March 2012, rotavirus surveillance was conducted among 9,745 children <5 years of age in 14 hospitals/health centers in Niger, where rotavirus vaccine has not been introduced. Study participants had acute watery diarrhea and moderate to severe dehydration, and 20% of the children were enrolled in a nutrition program. Of the 9,745 children, 30.6% were rotavirus positive. Genotyping of a subset of positive samples showed a variety of genotypes during the first year, although G2P[4] predominated. G12 genotypes, including G12P[8], which has emerged as a predominant strain in western Africa, represented >80% of isolates during the second year. Hospitalization and death rates and severe dehydration among rotavirus case-patients did not differ during the 2 years. The emergence of G12P[8] warrants close attention to the characteristics of associated epidemics and possible prevention measures.

Prevalence of Bordetella infection in a hospital setting in niamey, niger.

Bordetella pertussis still poses an important health threat in developing countries. In Niger, notified pertussis cases are few despite the low diphtheria-tetanus-pertussis/pentavalent vaccine coverage. We aimed to estimate the prevalence of B. pertussis in children aged <5 years consulting at a pediatric ward. A 5-month study in 2011 recruited 342 children with respiratory symptoms at the National Hospital of Niamey. Nasopharyngeal aspirates were tested by culture and real-time polymerase chain reaction. Overall, 34 (11.2%) of the 305 available nasopharyngeal aspirates tested by real-time polymerase chain reaction were positive for a Bordetella spp., with an estimated prevalence of 8.2 cases per 1000 children aged <5. None was notified to the surveillance network. A single specimen was positive on culture. This study, the first to provide laboratory-confirmed data on pertussis in Niger, highlights the need to sensitize health care personnel to actively notify clinical cases and to integrate laboratory diagnosis in the existing surveillance system.