Safety profile from data obtained from campaigns in Burkina Faso, Mali and Niger

GACVS received updated data on vaccine safety from campaigns to introduce MenAfriVac meningococcal A conjugate vaccine in the 3 countries (Burkina Faso, Mali and Niger) where the vaccine was introduced during December 2010. Previously, data presented from 7 phase I and phase II clinical trials at 5 sites (the Gambia, Ghana, India, Mali and Senegal), and from the pilot introduction of the vaccine in September 2010, had not indicated any cause for concern about the safety of this lyophilized vaccine. The pilot phase was followed by introduction of the vaccine into all 62 districts in Burkina Faso, 20 districts in Mali and 11 districts in Niger, covering a total population of almost 18 million: 10.7 million in Burkina Faso, 4.5 million in Mali and 2.7 million in Niger. Following a recommendation made by GACVS prior to the December 2010 rounds, an active surveillance component has been included in 1 district in Burkina Faso in addition to the enhanced passive surveillance system already in place.

Passive surveillance revealed a total of 1807 AEFIs, including 44 serious events, reported from 18.4 million people vaccinated in the 3 countries during introduction. This corresponds to a reporting rate of 9.8 AEFIs per 100 000 people vaccinated. Fever (39.2%) and local reactions (28.4%) were most commonly reported. Based on a review by national expert committees in each country, only 3/44 serious AEFIs were classified as possibly or probably related to vaccination (1 case each of acute exanthematous pustulosis, bronchospasm, and vomiting). In addition, during the pilot phase another 4 serious events were classified as possibly or probably related to vaccination (bronchospasm, meningitis-like syndrome, vomiting, and urticaria). Active surveillance for 12 pre-identified syndromes was conducted for 52 days (10 days during the vaccination campaign and 42 days after) in 16 health-care facilities in which approximately 100 000 people had been vaccinated. A total of 71 episodes of these syndromes were investigated, of which the most common were convulsion (32 cases), urticaria (18) and bronchospasm (14). The national expert committee of Burkina Faso classified these cases as coincidental. For the 3 most frequent syndromes, the distribution of the intervals between vaccination and the occurrence of symptoms did not reveal any temporal clustering.

A total of 2022 pregnant women vaccinated in Burkina Faso and Mali are also being followed to collect data on AEFIs and pregnancy outcomes.

GACVS concluded that the data from surveillance during the introduction of MenAfriVac do not indicate any reasons for concern about the vaccine’s safety. However, reports of bronchospasm and urticaria may suggest hypersensitivity reactions to vaccination, and the committee recommended that a more in-depth review of these cases be made to rule out anaphylaxis.

GACVS recognized that it would not be practical to conduct widespread active surveillance but highlighted the need for AEFI surveillance to continue as the vaccine becomes more widely available, so that additional information about its safety profile can be obtained.

Full report of GACVS meeting of 15-16 June 2011, published in the WHO Weekly Epidemiological Record on 22 July 2011

The Committee was updated on vaccine safety data relating to the introduction of MenAfriVac vaccine collected in the 3 early-adopter countries (Burkina Faso, Mali and Niger) during September 2010. The data previously presented from 7 clinical trials from 5 sites (Gambia, Ghana, India, Mali and Senegal), involving 4614 participants, did not identify any unexpected safety issues with this lyophilized meningitis A conjugate vaccine.⁵ During the initial phase, 4 districts in the 3 countries were selected for vaccine introduction. Spontaneous AEFI reporting was stimulated during preparatory training activities and supported by national AEFI review committees in all 3 countries.

A total of 215 reports of AEFI, including 34 serious adverse events, were received after 1.04 million people were vaccinated. Based on a review by national expert committees, only 1 serious AEFI (an anaphylactic reaction) was classified as related to vaccination. So far, these data do not suggest that there should be any special concern about safety. However, GACVS had concerns about the completeness of ascertainment of AEFI. Data were collected largely through existing passive surveillance systems, and could not be compared to background rates of occurrence of the conditions of interest in the same populations.

Based on GACVS’s recommendations, the 3 countries have developed a modified postmarketing surveillance plan for the next phase of vaccine introduction in order to generate additional data on safety. The Committee recognized that it would not be practical to adopt a large-scale active surveillance approach and therefore recommended giving priority to enhancing existing surveillance systems. Active surveillance, focusing on selected syndromes of interest, will be conducted in sentinel sites that have adequate infrastructure.

The Committee also addressed precautions from the package insert recommending that the vaccine should not be administered during pregnancy unless there is definite risk of group A meningococcal disease, and lactating women should not be given the vaccine since it is not known whether it is excreted in breast milk. The Committee noted that this kind of precautionary statement has also been used for other inactivated vaccines, including other meningococcal conjugate vaccines, and is not based on any known risks to these groups. Given the clear benefits of the vaccine, the increased risk of disease in the geographical area and past experiences using similar vaccines in comparable conditions, GACVS supported WHO’s technical guidance that MenAfriVac should be offered to pregnant and lactating women residing in the meningitis belt during any stage of pregnancy or lactation. A plan should be developed to follow up vaccinated pregnant women in antenatal or obstetric clinics, and to monitor pregnancy outcomes by making appropriate comparisons with unvaccinated pregnant women.

GACVS highlighted the importance of developing a robust postmarketing surveillance plan for any new vaccine before it is introduced. Furthermore, GACVS emphasized the importance of considering whether to conduct studies in specific groups during the product development stage, especially those groups which may be at higher risk of disease from vaccination.

GACVS concluded that the data for MenAfriVac vaccine had identified no safety concerns regarding the use of this vaccine. However, GACVS emphasized the need for additional effective postmarketing surveillance to provide more complete information about the safety profile of the vaccine, including its effects in specific groups, especially pregnant women.

⁵ See No. 30, 2010, pp. 285–291.

Full report of GACVS meeting of 8-9 December 2010, published in the WHO Weekly Epidemiological Record on 28 January 2011