Lessons Learned From Enhancing Vaccine Pharmacovigilance Activities During PsA-TT Introduction in African Countries, 2010-2013.

BACKGROUND: The rollout of the group A meningococcal vaccine, PsA-TT, in Africa's meningitis belt countries represented the first introduction of a vaccine specifically designed for this part of the world. During the first year alone, the number of people who received the vaccine through mass vaccination campaigns was several hundredfold higher than that of subjects who participated in the closely monitored clinical trials. Implementation of a system to identify rare but potentially serious vaccine reactions was therefore a high priority in the design and implementation of those campaigns. METHODS: National authorities and their technical partners set up effective vaccine pharmacovigilance systems, including conducting active surveillance projects. RESULTS: Implementation of national expert advisory groups to review serious adverse events following immunization in all countries and active monitoring of conditions of interest in 3 early-adopter countries did not identify particular concerns with the safety profile of PsA-TT, which had already provided tremendous public health benefits. CONCLUSIONS: Lessons learned from this experience will help to improve preparations for future vaccine introductions in resource-poor settings and capitalize on such efforts to advance vaccine safety systems in the future.

Active Surveillance for Adverse Events After a Mass Vaccination Campaign With a Group A Meningococcal Conjugate Vaccine (PsA-TT) in Mali.

BACKGROUND: The monovalent meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed for use in the "meningitis belt" of sub-Saharan Africa. Mali was 1 of 3 countries selected for early introduction. As this is a new vaccine, postlicensure surveillance is particularly important to identify and characterize possible safety issues. METHODS: The national vaccination campaign was phased from September 2010 to November 2011. We conducted postlicensure safety surveillance for PsA-TT in 40 government clinics from southern Mali serving approximately 400 000 people 1-29 years of age. We conducted analyses with individual-level data and population-level data, and we calculated rates of adverse events using the conditional exact test, a modified vaccine cohort risk interval method, and a modified self-controlled case series method for each outcome of interest, including 18 prespecified adverse events and 18 syndromic categories. RESULTS: An increased rate of clinic visits for fever within 3 days after vaccination was found using multiple methods for all age groups. Although other signals were found with some methods, complete assessment of all other prespecified outcomes and syndromic categories did not reveal that PsA-TT was consistently associated with any other health problem. CONCLUSIONS: No new safety concerns were identified in this study. These results are consistent with prelicensure data and other studies indicating that PsA-TT is safe. The approach presented could serve as a model for future active postlicensure vaccine safety monitoring associated with large-scale immunization campaigns in low-income countries.

Adverse events following immunization during mass vaccination campaigns at first introduction of a meningococcal A conjugate vaccine in Burkina Faso, 2010.

MenAfriVac™ is a new meningococcal A conjugate vaccine developed to prevent meningitis outbreaks in Africa. It was first introduced during the last quarter of 2010 in three West African countries. We report on the monitoring of adverse events following immunization (AEFI) in Burkina Faso where more than 11 million people aged 1-29 years were vaccinated. Vaccine pharmacovigilance relied on stimulated passive AEFI surveillance countrywide and active surveillance for 12 clinical conditions in one sentinel district (Ziniaré) with 97,715 people eligible for vaccination. All AEFI occurring during the 10 days of mass campaign or the 42 subsequent days were to be notified. Serious AEFI were submitted to a national expert committee (NEC) for causality assessment. A total of 11,466,950 people were vaccinated with 1471 vaccinees reported to have experienced at least one AEFI (12.83 cases per 100,000). 1444 AEFI were minor; the most common of which were fever, headache, gastro-intestinal disorders and local reactions (2-7 cases per 100,000). Of 27 serious AEFI reported, four cases were classified by the NEC as related to vaccine (1 case per 3 million vaccinated) including one case each of exanthematous pustulosis, angioedema, bronchospasm and severe vomiting. Active surveillance identified 71 cases of the 12 conditions of interest. Convulsions, urticaria and bronchospasm were more frequently reported. Attack rates for those conditions were similar to the baseline rates recorded in the same population, over the same time period, a year earlier. With the exception of convulsions in the days following vaccination the distribution of time intervals between vaccination and the occurrence of symptoms did not reveal any temporal clustering. The monitoring of AEFI of MenAfriVac™ in Burkina Faso did not suggest special concern regarding the vaccine safety. However, reported possible hypersensitivity reactions to vaccine components would require further review to rule out any anaphylactic reaction.

Monitoring adverse events following immunization with a new conjugate vaccine against group A meningococcus in Niger, September 2010.

INTRODUCTION: MenAfriVac is a new conjugate vaccine against Neisseria meningitidis serogroup A, the major cause of meningitis outbreaks in sub-Saharan Africa. In Niger, the MenAfriVac introduction campaign was conducted in the District of Filingue, during September 2010, targeting 392,211 individuals aged 1-29 years. We set up an enhanced spontaneous surveillance system to monitor adverse events following immunization (AEFI) during the campaign period and 42 days thereafter. METHODS: All the 33 health centres of the district have been designated as surveillance units, which reported AEFIs on a daily basis to the health district headquarters. Health care workers were instructed to screen patients presenting with predefined conditions of interest and patients spontaneously presenting at units or at vaccination posts with complaints after vaccination. Cases were classified as serious (resulting in death, hospitalization or long-term disability) or minor. A National Expert Committee was established to determine if serious cases were causally associated with the vaccine. RESULTS: In total, 356,532 vaccine doses were administered. During 61 days of monitoring, 82 suspected AEFIs were reported: 16 severe and 66 minor. The cumulative incidence was of 23.0 per 100,000 doses. Among severe cases, 14 were classified as coincidences, one urticaria complicated by respiratory distress was classified as a probable vaccine reaction, and one death was unclassifiable because post-mortem information was unavailable. The number of units that reported at least one case was 19/33 (57.6%). CONCLUSIONS: Although these results are limited by underreporting of cases, we did not identify safety concerns with MenAfriVac. The lessons learned from this experience should be used to reinforce the national pharmacovigilance system in Niger to make it complaint with international standards. In order to do so, we recommend using a lighter system for routine; and conducting regular training and supervisory activities to increase its acceptance among local health workers.