Introduction and Rollout of a New Group A Meningococcal Conjugate Vaccine (PsA-TT) in African Meningitis Belt Countries, 2010-2014.

BACKGROUND: A group A meningococcal conjugate vaccine (PsA-TT) was developed specifically for the African "meningitis belt" and was prequalified by the World Health Organization (WHO) in June 2010. The vaccine was first used widely in Burkina Faso, Mali, and Niger in December 2010 with great success. The remaining 23 meningitis belt countries wished to use this new vaccine. METHODS: With the help of African countries, WHO developed a prioritization scheme and used or adapted existing immunization guidelines to mount PsA-TT vaccination campaigns. Vaccine requirements were harmonized with the Serum Institute of India, Ltd. RESULTS: Burkina Faso was the first country to fully immunize its 1- to 29-year-old population in December 2010. Over the next 4 years, vaccine coverage was extended to 217 million Africans living in 15 meningitis belt countries. CONCLUSIONS: The new group A meningococcal conjugate vaccine was well received, with country coverage rates ranging from 85% to 95%. The rollout proceeded smoothly because countries at highest risk were immunized first while attention was paid to geographic contiguity to maximize herd protection. Community participation was exemplary.

The Safety of PsA-TT in Pregnancy: An Assessment Performed Within the Navrongo Health and Demographic Surveillance Site in Ghana.

BACKGROUND: Group A meningococcal disease occurs in large epidemics within the meningitis belt of Africa that includes northern Ghana. Major epidemics in the meningitis belt have infection rates ranging from 100 to 800 per 100 000 population. In 2012, a group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), was introduced into the region in large campaigns. METHODS: We report here on the safety of this vaccine when used in pregnant women in the Navrongo region of Ghana. RESULTS: Rates of events in 1730 immunized pregnant women and their infants were compared to the rates of the same events in pregnant women who did not receive the vaccine during the campaign and also to women who were pregnant in the prior year. CONCLUSIONS: We found no evidence of any safety concerns when this vaccine was administered during pregnancy.

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.

MenAfriVac as an Antitetanus Vaccine.

BACKGROUND: The group A meningococcal conjugate vaccine, PsA-TT, uses tetanus toxoid (TT) as a carrier protein (PsA-TT). TT as a carrier protein in other conjugate vaccines is known to be immunogenic and generates a robust anti-TT response. METHODS: Clinical studies in Africa assessed whether PsA-TT generated tetanus serologic responses when tested in African populations (toddlers to adults). Second, the high acceptance of PsA-TT mass immunization campaigns in the 1- to 29-year age group meant that a sizeable fraction of women of reproductive age received PsA-TT. Incidence data for neonatal tetanus were reviewed for countries with and without PsA-TT campaigns to check whether this had any impact on the incidence. RESULTS: PsA-TT generated robust tetanus serologic responses in 1- to 29-year-olds, similar to those expected after a booster dose of TT. Neonatal cases of tetanus fell by 25% in countries that completed PsA-TT campaigns in 1- to 29-year-olds. CONCLUSIONS: Although these data are not yet definitive, they are consistent with the hypothesis that improved community immunity to tetanus as a result of the PsA-TT campaigns may be having an impact on the incidence of neonatal tetanus in sub-Saharan Africa. CLINICAL TRIALS REGISTRATION: ISRCTN17662153 (PsA-TT 001); ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN46335400 (PsA-TT 003a); ISRCTN82484612 (PsA-TT 004); CTRI/2009/091/000368 (PsA-TT 005); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007).

Risk Assessment and Meningococcal A Conjugate Vaccine Introduction in Africa: The District Prioritization Tool.

BACKGROUND: A group A meningococcal (MenA) conjugate vaccine has progressively been introduced in the African meningitis belt since 2010. A country-wide risk assessment tool, the District Prioritization Tool (DPT), was developed to help national stakeholders combine existing data and local expertise to define priority geographical areas where mass vaccination campaigns should be conducted. METHODS: DPT uses an Excel-supported offline tool that was made available to the countries proposed for immunization campaigns. It used quantitative-qualitative methods, relying predominantly on evidence-based risk scores complemented by expert opinion. RESULTS: DPT was used by most of the countries that introduced the group A conjugate vaccine. Surveillance data enabled the computation of severity scores for meningitis at the district level (magnitude, intensity, and frequency). District data were scaled regionally to facilitate phasing decisions. DPT also assessed the country's potential to conduct efficient preventive immunization campaigns while paying close attention to the scope of the geographic extension of the campaigns. The tool generated meningitis district profiles that estimated the number of vaccine doses needed. In each assessment, local meningitis experts contributed their knowledge of local risk factors for meningitis epidemics to refine the final prioritization decisions. CONCLUSIONS: DPT proved to be a useful and flexible tool that codified information and streamlined discussion among stakeholders while facilitating vaccine distribution decisions after 2011. DPT methodology may be tailored to prioritize vaccine interventions for other diseases.

Public Health Impact After the Introduction of PsA-TT: The First 4 Years.

BACKGROUND: During the first introduction of a group A meningococcal vaccine (PsA-TT) in 2010-2011 and its rollout from 2011 to 2013, >150 million eligible people, representing 12 hyperendemic meningitis countries, have been vaccinated. METHODS: The new vaccine effectiveness evaluation framework was established by the World Health Organization and partners. Meningitis case-based surveillance was strengthened in PsA-TT first-introducer countries, and several evaluation studies were conducted to estimate the vaccination coverage and to measure the impact of vaccine introduction on meningococcal carriage and disease incidence. RESULTS: PsA-TT implementation achieved high vaccination coverage, and results from studies conducted showed significant decrease of disease incidence as well as significant reduction of oropharyngeal carriage of group A meningococci in vaccinated and unvaccinated individuals, demonstrating the vaccine's ability to generate herd protection and prevent group A epidemics. CONCLUSIONS: Lessons learned from this experience provide useful insights in how to guide and better prepare for future new vaccine introductions in resource-limited settings.

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.

Serogroup A meningococcal conjugate (PsA-TT) vaccine coverage and measles vaccine coverage in Burkina Faso--implications for introduction of PsA-TT into the Expanded Programme on Immunization.

BACKGROUND: A new serogroup A meningococcal conjugate vaccine (PsA-TT, MenAfriVac™) has been developed to combat devastating serogroup A Neisseria meningitis (MenA) epidemics in Africa. A mass immunization campaign targeting 1-29 year olds was conducted in Burkina Faso in December 2010. Protection of subsequent infant cohorts will be necessary through either introduction of PsA-TT into the routine Expanded Programme on Immunization (EPI) or periodic repeat mass vaccination campaigns. OBJECTIVES: To inform future immunization policy for PsA-TT vaccination of infants through a comparison of PsA-TT campaign vaccination coverage and routine measles-containing vaccine (MCV) coverage in Burkina Faso. METHODS: A national survey was conducted in Burkina Faso during December 17-27, 2011 using stratified cluster sampling to assess PsA-TT vaccine coverage achieved by the 2010 nationwide immunization campaign among 2-30 year olds and routine MCV coverage among 12-23 month olds. Coverage estimates and 95% Confidence Intervals (CI) were calculated, reasons for non-vaccination and methods of campaign communication were described, and a multivariable analysis for factors associated with vaccination was conducted. RESULTS: National overall PsA-TT campaign coverage was 95.9% (95% CI: 95.0-96.7) with coverage greater than 90% all 13 regions of Burkina Faso. National overall routine MCV coverage was 92.5% (95% CI: 90.5-94.1), but ranged from 75.3% to 95.3% by region. The primary predictor for PsA-TT vaccination among all age groups was a head of household informed of the campaign. PsA-TT vaccination was more likely in residents of rural settings, whereas MCV vaccination was more likely in residents of urban settings. CONCLUSION: Overall national vaccination rates in Burkina Faso were similar for PsA-TT and MCV vaccine. The regions with MCV coverage below targets may be at risk for sub-optimal vaccination coverage if PsA-TT is introduced in EPI. These results highlight the need for assessments of routine vaccination coverage to guide PsA-TT immunization policy in meningitis belt countries.