Mamoudou H. Djingarey

Impact of the serogroup A meningococcal conjugate vaccine, MenAfriVac, on carriage and herd immunity.

BACKGROUND The conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, was first introduced in mass vaccination campaigns of 1-29-year-olds in Burkina Faso in 2010. It is not known whether MenAfriVac has an impact on NmA carriage. METHODS We conducted a repeated cross-sectional meningococcal carriage study in a representative portion of the 1-29-year-old population in 3 districts in Burkina Faso before and up to 13 months after vaccination. One district was vaccinated in September 2010, and the other 2 were vaccinated in December 2010. We analyzed 25 521 oropharyngeal samples, of which 22 093 were obtained after vaccination. RESULTS In October-November 2010, NmA carriage prevalence in the unvaccinated districts was comparable to the baseline established in 2009, but absent in the vaccinated district. Serogroup X N. meningitidis (NmX) dominated in both vaccinated and unvaccinated districts. With 4 additional sampling campaigns performed throughout 2011 in the 3 districts, overall postvaccination meningococcal carriage prevalence was 6.95%, with NmX dominating but declining for each campaign (from 8.66% to 1.97%). Compared with a baseline NmA carriage prevalence of 0.39%, no NmA was identified after vaccination. Overall vaccination coverage in the population sampled was 89.7%, declining over time in 1-year-olds (from 87.1% to 26.5%), as unvaccinated infants reached 1 year of age. NmA carriage was eliminated in both the vaccinated and unvaccinated population from 3 weeks up to 13 months after mass vaccination (P = .003). CONCLUSIONS The disappearance of NmA carriage among both vaccinated and unvaccinated populations is consistent with a vaccine-induced herd immunity effect.

Epidemic meningitis due to Group A Neisseria meningitidis in the African meningitis belt: a persistent problem with an imminent solution.

Epidemic meningitis in Africa remains an important and unresolved public health problem. Bacteriologic and epidemiologic data collected over the past 30 years have consistently established the importance of Group A Neisseria meningitidis as the dominant etiologic agent. The meningococcal Group A capsule is the major virulence factor; it is a polysaccharide comprised of a repeating unit of partly O-acetylated alpha-1,6-linked N-acetylmannosamine phosphate. Meningitis epidemics occur annually during the dry season (January to May) and stop with the first rains. Until now, control of these meningitis epidemics has relied on a reactive vaccination strategy with polysaccharide vaccines that is logistically complicated and has not put an end to recurrent epidemics. A meningococcal A conjugate vaccine (MenAfriVac) has been developed and tested in Phase II clinical trials in Africa. The vaccine has been shown to be safe and to generate a sustained immunologic response with functional antibody 20 times higher than that seen with polysaccharide vaccine. Widespread use of such a vaccine is likely to generate herd immunity and to put an end to Group A meningococcal epidemics.

Serogroup A meningococcal conjugate vaccination in Burkina Faso: analysis of national surveillance data

BACKGROUND An affordable, highly immunogenic Neisseria meningitidis serogroup A meningococcal conjugate vaccine (PsA-TT) was licensed for use in sub-Saharan Africa in 2009. In 2010, Burkina Faso became the first country to implement a national prevention campaign, vaccinating 11·4 million people aged 1-29 years. We analysed national surveillance data around PsA-TT introduction to investigate the early effect of the vaccine on meningitis incidence and epidemics. METHODS We examined national population-based meningitis surveillance data from Burkina Faso using two sources, one with cases and deaths aggregated at the district level from 1997 to 2011, and the other enhanced with results of cerebrospinal fluid examination and laboratory testing from 2007 to 2011. We compared mortality rates and incidence of suspected meningitis, probable meningococcal meningitis by age, and serogroup-specific meningococcal disease before and during the first year after PsA-TT implementation. We assessed the risk of meningitis disease and death between years. FINDINGS During the 14 year period before PsA-TT introduction, Burkina Faso had 148 603 cases of suspected meningitis with 17 965 deaths, and 174 district-level epidemics. After vaccine introduction, there was a 71% decline in risk of meningitis (hazard ratio 0·29, 95% CI 0·28-0·30, p<0·0001) and a 64% decline in risk of fatal meningitis (0·36, 0·33-0·40, p<0·0001). We identified a statistically significant decline in risk of probable meningococcal meningitis across the age group targeted for vaccination (62%, cumulative incidence ratio [CIR] 0·38, 95% CI 0·31-0·45, p<0·0001), and among children aged less than 1 year (54%, 0·46, 0·24-0·86, p=0·02) and people aged 30 years and older (55%, 0·45, 0·22-0·91, p=0·003) who were ineligible for vaccination. No cases of serogroup A meningococcal meningitis occurred among vaccinated individuals, and epidemics were eliminated. The incidence of laboratory-confirmed serogroup A N meningitidis dropped significantly to 0·01 per 100 000 individuals per year, representing a 99·8% reduction in the risk of meningococcal A meningitis (CIR 0·002, 95% CI 0·0004-0·02, p<0·0001). INTERPRETATION Early evidence suggests the conjugate vaccine has substantially reduced the rate of meningitis in people in the target age group, and in the general population because of high coverage and herd immunity. These data suggest that fully implementing the PsA-TT vaccine could end epidemic meningitis of serogroup A in sub-Saharan Africa. FUNDING None.

Effectively introducing a new meningococcal A conjugate vaccine in Africa: The Burkina Faso experience

A new Group A meningococcal (Men A) conjugate vaccine, MenAfriVac™, was prequalified by the World Health Organization (WHO) in June 2010. Because Burkina Faso has repeatedly suffered meningitis epidemics due to Group A Neisseria meningitidis special efforts were made to conduct a country-wide campaign with the new vaccine in late 2010 and before the onset of the next epidemic meningococcal disease season beginning in January 2011. In the ensuing five months (July-November 2010) the following challenges were successfully managed: (1) doing a large safety study and registering the new vaccine in Burkina Faso; (2) developing a comprehensive communication plan; (3) strengthening the surveillance system with particular attention to improving the capacity for real-time polymerase chain reaction (PCR) testing of spinal fluid specimens; (4) improving cold chain capacity and waste disposal; (5) developing and funding a sound campaign strategy; and (6) ensuring effective collaboration across all partners. Each of these issues required specific strategies that were managed through a WHO-led consortium that included all major partners (Ministry of Health/Burkina Faso, Serum Institute of India Ltd., UNICEF, Global Alliance for Vaccines and Immunization, Meningitis Vaccine Project, CDC/Atlanta, and the Norwegian Institute of Public Health/Oslo). Biweekly teleconferences that were led by WHO ensured that problems were identified in a timely fashion. The new meningococcal A conjugate vaccine was introduced on December 6, 2010, in a national ceremony led by His Excellency Blaise Compaore, the President of Burkina Faso. The ensuing 10-day national campaign was hugely successful, and over 11.4 million Burkinabes between the ages of 1 and 29 years (100% of target population) were vaccinated. African national immunization programs are capable of achieving very high coverage for a vaccine desired by the public, introduced in a well-organized campaign, and supported at the highest political level. The Burkina Faso success augurs well for further rollout of the Men A conjugate vaccine in meningitis belt countries.

Resurgence of Ebola virus disease in Guinea linked to a survivor with virus persistence in seminal fluid for more than 500 days

We report on an Ebola virus disease (EVD) survivor who showed Ebola virus in seminal fluid 531 days after onset of disease. The persisting virus was sexually transmitted in February 2016, about 470 days after onset of symptoms, and caused a new cluster of EVD in Guinea and Liberia.

Baseline Meningococcal Carriage in Burkina Faso before the Introduction of a Meningococcal Serogroup A Conjugate Vaccine

ABSTRACT The serogroup A meningococcal conjugate vaccine MenAfriVac has the potential to confer herd immunity by reducing carriage prevalence of epidemic strains. To better understand this phenomenon, we initiated a meningococcal carriage study to determine the baseline carriage rate and serogroup distribution before vaccine introduction in the 1- to 29-year old population in Burkina Faso, the group chosen for the first introduction of the vaccine. A multiple cross-sectional carriage study was conducted in one urban and two rural districts in Burkina Faso in 2009. Every 3 months, oropharyngeal samples were collected from >5,000 randomly selected individuals within a 4-week period. Isolation and identification of the meningococci from 20,326 samples were performed by national laboratories in Burkina Faso. Confirmation and further strain characterization, including genogrouping, multilocus sequence typing, and porA-fetA sequencing, were performed in Norway. The overall carriage prevalence for meningococci was 3.98%; the highest prevalence was among the 15- to 19-year-olds for males and among the 10- to 14-year-olds for females. Serogroup Y dominated (2.28%), followed by serogroups X (0.44%), A (0.39%), and W135 (0.34%). Carriage prevalence was the highest in the rural districts and in the dry season, but serogroup distribution also varied by district. A total of 29 sequence types (STs) and 51 porA-fetA combinations were identified. The dominant clone was serogroup Y, ST-4375, P1.5-1,2-2/F5-8, belonging to the ST-23 complex (47%). All serogroup A isolates were ST-2859 of the ST-5 complex with P1.20,9/F3-1. This study forms a solid basis for evaluating the impact of MenAfriVac introduction on serogroup A carriage.

Benefits of using vaccines out of the cold chain: delivering meningitis A vaccine in a controlled temperature chain during the mass immunization campaign in Benin.

Highlights • The first field use of MenAfriVacs new label allowed the vaccine to be kept at up to 40 °C for up to 4 days.• 155,000 people were vaccinated using the CTC approach in the Meningitis A campaign in northern Benin in 2012.• 98.7% of supervisors and 100% of vaccinators would prefer to conduct their next campaign using CTC.• They saw CTC benefits as: more people vaccinated, no need to return to health centre every night, reduced logistic burden.• Taking advantage of the flexibility offered by CTC opens the door for the implementation of new immunization strategies.

Predictors of Immunity after a Major Serogroup W-135 Meningococcal Disease Epidemic, Burkina Faso, 2002

BACKGROUND The African meningitis belt undergoes recurrent epidemics caused by Neisseria meningitidis serogroup A. During 2002, Burkina Faso documented the first large serogroup W-135 (NmW-135) meningococcal disease epidemic. To understand the emergence of NmW-135, we investigated meningococcal carriage and immunity. METHODS Immediately after Burkina Fasos epidemic, we conducted a cross-sectional survey of meningococcal carriage and seroprevalence in an epidemic and a nonepidemic district. We identified predictors of elevated NmW-135 serum bactericidal activity (SBA), a functional correlate of protection, using multivariate logistic regression. RESULTS The NmW-135 carriage rate was 25.2% in the epidemic district and 3.4% in the nonepidemic district (P<.0001). Compared with residents of the nonepidemic district, those of the epidemic district had higher geometric mean titers of NmW-135 SBA (P<.0001). NmW-135 SBA titers>or=1:8, an estimated protective threshold, were observed in 60.4% and 34.0% of residents of the epidemic and nonepidemic district, respectively (P=.0002). In a multivariate model, current NmW-135 carriage, age, and residence in the epidemic district were independent predictors of having an NmW-135 SBA titer>or=1:8. CONCLUSIONS Extensive NmW-135 carriage and transmission in the epidemic area caused residents to acquire natural immunity. Serial carriage and seroprevalence surveys could establish the duration of immunity in the population. The persistent circulation of NmW-135 underscores the potential for periodic NmW-135 epidemics in Africa.

Neisseria meningitidis serogroup W, Burkina Faso, 2012.

In 2010, Burkina Faso became the first country to introduce meningococcal serogroup A conjugate vaccine (PsA-TT). During 2012, Burkina Faso reported increases in Neisseria meningitidis serogroup W, raising questions about whether these cases were a natural increase in disease or resulted from serogroup replacement after PsA-TT introduction. We analyzed national surveillance data to describe the epidemiology of serogroup W and genotyped 61 serogroup W isolates. In 2012, a total of 5,807 meningitis cases were reported through enhanced surveillance, of which 2,353 (41%) were laboratory confirmed. The predominant organism identified was N. meningitidis serogroup W (62%), and all serogroup W isolates characterized belonged to clonal complex 11. Although additional years of data are needed before we can understand the epidemiology of serogroup W after PsA–TT introduction, these data suggest that serogroup W will remain a major cause of sporadic disease and has epidemic potential, underscoring the need to maintain high-quality case-based meningitis surveillance after PsA–TT introduction.

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.