Molecular insights into meningococcal carriage isolates from Burkina Faso 7 years after introduction of a serogroup A meningococcal conjugate vaccine.

In 2010, Burkina Faso completed the first nationwide mass-vaccination campaign of a meningococcal A conjugate vaccine, drastically reducing the incidence of disease caused by serogroup A meningococci. Since then, other strains, such as those belonging to serogroups W, X and C, have continued to cause outbreaks within the region. A carriage study was conducted in 2016 and 2017 in the country to characterize the meningococcal strains circulating among healthy individuals following the mass-vaccination campaign. Four cross-sectional carriage evaluation rounds were conducted in two districts of Burkina Faso, Kaya and Ouahigouya. Oropharyngeal swabs were collected for the detection of Neisseria meningitidis by culture. Confirmed N. meningitidis isolates underwent whole-genome sequencing for molecular characterization. Among 13 758 participants, 1035 (7.5 %) N. meningitidis isolates were recovered. Most isolates (934/1035; 90.2 %) were non-groupable and primarily belonged to clonal complex (CC) 192 (822/934; 88 %). Groupable isolates (101/1035; 9.8 %) primarily belonged to CCs associated with recent outbreaks in the region, such as CC11 (serogroup W) and CC10217 (serogroup C); carried serogroup A isolates were not detected. Phylogenetic analysis revealed several CC11 strains circulating within the country, several of which were closely related to invasive isolates. Three sequence types (STs) were identified among eleven CC10217 carriage isolates, two of which have caused recent outbreaks in the region (ST-10217 and ST-12446). Our results show the importance of carriage studies to track the outbreak-associated strains circulating within the population in order to inform future vaccination strategies and molecular surveillance programmes.

Meningococcal carriage 7 years after introduction of a serogroup A meningococcal conjugate vaccine in Burkina Faso: results from four cross-sectional carriage surveys.

BACKGROUND: In the first 2 years after a nationwide mass vaccination campaign of 1-29-year-olds with a meningococcal serogroup A conjugate vaccine (MenAfriVac) in Burkina Faso, carriage and disease due to serogroup A Neisseria meningitidis were nearly eliminated. We aimed to assess the long-term effect of MenAfriVac vaccination on meningococcal carriage and herd immunity. METHODS: We did four cross-sectional studies of meningococcal carriage in people aged 9 months to 36 years in two districts of Burkina Faso between May 2, 2016, and Nov 6, 2017. Demographic information and oropharyngeal swabs were collected. Meningococcal isolates were characterised using whole-genome sequencing. FINDINGS: Of 14 295 eligible people, 13 758 consented and had specimens collected and laboratory results available, 1035 of whom were meningococcal carriers. Accounting for the complex survey design, prevalence of meningococcal carriage was 7·60% (95% CI 5·67-9·52), including 6·98% (4·86-9·11) non-groupable, 0·48% (0·01-0·95) serogroup W, 0·10% (0·01-0·18) serogroup C, 0·03% (0·00-0·80) serogroup E, and 0% serogroup A. Prevalence ranged from 5·44% (95% CI 4·18-6·69) to 9·14% (6·01-12·27) by district, from 4·67% (2·71-6·64) to 11·17% (6·75-15·59) by round, and from 3·39% (0·00-8·30) to 10·43% (8·08-12·79) by age group. By clonal complex, 822 (88%) of 934 non-groupable isolates were CC192, all 83 (100%) serogroup W isolates were CC11, and nine (69%) of 13 serogroup C isolates were CC10217. INTERPRETATION: Our results show the continued effect of MenAfriVac on serogroup A meningococcal carriage, for at least 7 years, among vaccinated and unvaccinated cohorts. Carriage prevalence of epidemic-prone serogroup C CC10217 and serogroup W CC11 was low. Continued monitoring of N meningitidis carriage will be crucial to further assess the effect of MenAfriVac and inform the vaccination strategy for future multivalent meningococcal vaccines. FUNDING: Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.

Evaluation of pneumococcal meningitis clusters in Burkina Faso and implications for potential reactive vaccination.

BACKGROUND: To better understand how to prevent and respond to pneumococcal meningitis outbreaks in the meningitis belt, we retrospectively examined Burkina Faso's case-based meningitis surveillance data for pneumococcal meningitis clusters and assessed potential usefulness of response strategies. METHODS: Demographic and clinical information, and cerebrospinal fluid laboratory results for meningitis cases were collected through nationwide surveillance. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination; strains were serotyped using PCR. We reviewed data from 2011 to 2017 to identify and describe clusters of ≥ 5 confirmed pneumococcal meningitis cases per week in a single district. We assessed whether identified clusters met the 2016 WHO provisional pneumococcal meningitis outbreak definition: a district with a weekly incidence of >5 suspected meningitis cases/100,000 persons, >60% of confirmed meningitis cases caused by Streptococcus pneumoniae, and >10 confirmed pneumococcal meningitis cases. RESULTS: Twenty pneumococcal meningitis clusters were identified, with a maximum weekly incidence of 7 cases and a maximum duration of 4 weeks. Most identified clusters (15/20; 75%) occurred before nationwide introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013. Most cases were due to serotype 1 (74%), 10% were due to PCV13 serotypes besides serotype 1, and 8 clusters had >1 serotype. While 6 identified clusters had a weekly incidence of >5 suspected cases/100,000 and all 20 clusters had >60% of confirmed meningitis cases due to S. pneumoniae, no cluster had >10 confirmed pneumococcal meningitis cases in a single week. CONCLUSIONS: Following PCV13 introduction, pneumococcal meningitis clusters were rarely detected, and none met the WHO provisional pneumococcal outbreak definition. Due to the limited cluster size and duration, there were no clear instances where reactive vaccination could have been useful. More data are needed to inform potential response strategies.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis, Burkina Faso, 2016-2017.

BACKGROUND: In 2013, Burkina Faso introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine childhood immunization program, to be administered to children at 8, 12, and 16 weeks of age. We evaluated the impact of PCV13 on pneumococcal meningitis. METHODS: Using nationwide surveillance, we gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination; strains were serotyped using PCR. We compared annual incidence (cases per 100 000) 4 years after PCV13's introduction (2017) to average pre-PCV13 incidence (2011-2013). We adjusted incidence for age and proportion of cases with CSF tested at national laboratories. RESULTS: In 2017, pneumococcal meningitis incidence was 2.7 overall and 10.5 (<1 year), 3.8 (1-4 years), 3.5 (5-14 years), and 1.4 (≥15 years) by age group. Compared to 2011-2013, PCV13-serotype incidence was significantly lower among all age groups, with the greatest decline among children aged <1 year (77%; 95% confidence interval [CI], 65%-84%). Among all ages, the drop in incidence was larger for PCV13 serotypes excluding serotype 1 (79%; 95% CI, 72%-84%) than for serotype 1 (52%; 95% CI, 44%-59%); incidence of non-PCV13 serotypes also declined (53%; 95% CI, 37%-65%). In 2017, 45% of serotyped cases among all ages were serotype 1 and 12% were other PCV13 serotypes. CONCLUSIONS: In Burkina Faso, meningitis caused by PCV13 serotypes continues to decrease, especially among young children. However, the concurrent decline in non-PCV13 serotypes and short pre-PCV13 observation period complicate evaluation of PCV13's impact. Efforts to improve control of serotype 1, such as switching from a 3 + 0 schedule to a 2 + 1 schedule, may improve overall control of pneumococcal meningitis in this setting.

Implementation of an intensive adherence intervention in patients with second-line antiretroviral therapy failure in four west African countries with little access to genotypic resistance testing: a prospective cohort study.

BACKGROUND: The decision about whether to switch to third-line antiretroviral therapy (ART) in patients with treatment failure on second-line therapy is difficult in settings with little access to genotypic resistance testing. In this study, we used a standardised algorithm including a wide range of adherence-enhancing interventions followed by a new viral load measurement to decide whether to switch to third-line therapy in this situation. The decision, made on the basis of effectiveness of the adherence reinforcement to drive viral resuppression, did not use genotypic resistance testing. METHODS: In this prospective cohort study, adults in four west African countries with treatment failure of a boosted protease inhibitor ART regimen were offered nine adherence reinforcement interventions, and followed up for 64 weeks. We measured viral load at week 12 and used the results to decide ART treatment at week 16: if successful resuppression (plasma HIV-1 RNA <400 copies per mL or had decreased by ≥2 log10 copies per mL compared with baseline), patients continued the same second-line regimen; otherwise they switched to a third-line regimen based on ritonavir-boosted darunavir and raltegravir. The primary endpoint was virological success at week 64 (plasma HIV-1 RNA <50 copies per mL). After study termination we did genotypic resistance testing on frozen plasma samples collected at baseline, and retrospectively determined the appropriateness of the week 16 decision on the basis of the baseline genotypic susceptibility score. FINDINGS: Between March 28, 2013, and May 11, 2015, of the 198 eligible participants, five died before week 16. Of the 193 remaining, 130 (67%) reached viral resuppression and continued with second-line ART, and 63 (33%) switched to third-line ART at week 16. Post-study genotypic resistance testing showed that the baseline genotypic susceptibility score was calculable in 166 patients, of whom 57 (34%) had a score less than 2. We retrospectively concluded that the week 16 decision was appropriate in 145 (75%) patients. At week 64, four patients (2%) were lost to follow-up, ten (5%) had died, and 101 (52%) had a viral load less than 50 copies per mL. INTERPRETATION: Poor adherence is the first problem to tackle in patients for whom second-line ART is failing when resistance tests are not routinely available and is effectively a manageable problem. Lack of access to genotypic resistance testing should not be an obstacle to the prescription of third-line ART in patients who do not achieve viral resuppression after adherence reinforcement. FUNDING: French Agency for Research on AIDS and Viral Hepatitis.

Molecular characterization of invasive meningococcal isolates in Burkina Faso as the relative importance of serogroups X and W increases, 2008-2012.

BACKGROUND: Neisseria meningitidis serogroup A disease in Burkina Faso has greatly decreased following introduction of a meningococcal A conjugate vaccine in 2010, yet other serogroups continue to pose a risk of life-threatening disease. Capsule switching among epidemic-associated serogroup A N. meningitidis strains could allow these lineages to persist despite vaccination. The introduction of new strains at the national or sub-national levels could affect the epidemiology of disease. METHODS: Isolates collected from invasive meningococcal disease in Burkina Faso between 2008 and 2012 were characterized by serogrouping and molecular typing. Genome sequences from a subset of isolates were used to infer phylogenetic relationships. RESULTS: The ST-5 clonal complex (CC5) was identified only among serogroup A isolates, which were rare after 2010. CC181 and CC11 were the most common clonal complexes after 2010, having serogroup X and W isolates, respectively. Whole-genome phylogenetic analysis showed that the CC181 isolates collected during and after the epidemic of 2010 formed a single clade that was closely related to isolates collected in Niger during 2005 and Burkina Faso during 2007. Geographic population structure was identified among the CC181 isolates, where pairs of isolates collected from the same region of Burkina Faso within a single year had less phylogenetic diversity than the CC181 isolate collection as a whole. However, the reduction of phylogenetic diversity within a region did not extend across multiple years. Instead, CC181 isolates collected during the same year had lower than average diversity, even when collected from different regions, indicating geographic mixing of strains across years. The CC11 isolates were primarily collected during the epidemic of 2012, with sparse sampling during 2011. These isolates belong to a clade that includes previously described isolates collected in Burkina Faso, Mali, and Niger from 2011 to 2015. Similar to CC181, reduced phylogenetic diversity was observed among CC11 isolate pairs collected from the same regions during a single year. CONCLUSIONS: The population of disease-associated N. meningitidis strains within Burkina Faso was highly dynamic between 2008 and 2012, reflecting both vaccine-imposed selection against serogroup A strains and potentially complex clonal waves of serogroup X and serogroup W strains.

Early impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis-Burkina Faso, 2014-2015.

OBJECTIVES: We evaluate early impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in Burkina Faso. METHODS: Nationwide surveillance gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination, and strains serotyped using PCR. We compared incidence (cases per 100,000) in the early post-PCV13 period (2014 and 2015) to average pre-PCV13 incidence (2011-2013). RESULTS: In 2015, age-specific pneumococcal meningitis incidences were 8.7 (<1 year), 2.4 (1-4 years), 6.5 (5-14 years), and 2.6 (≥15 years). Compared to 2011-2013, PCV13-serotype incidence among all ages decreased by 32% (95%CI: 23%-39%), with significant decreases among children aged <1 year (76%; 95%CI: 64%-84%) and 1-4 years (58%, 95%CI: 40%-71%). Among all ages, incidence of PCV13 serotypes besides serotype 1 decreased (68%; 95%CI: 59%-75%), but serotype 1 incidence did not. Incidence of non-PCV13 serotypes also decreased (47%; 95%CI: 29%-60%). Among children aged <1 year, serotypes 12F/12A/12B/44/46 (17%), 1 (12%), and 5 (10%) predominated. CONCLUSIONS: Following PCV13 introduction, PCV13-serotype meningitis incidence in young children significantly decreased. PCV13 impact on serotype 1 and disease in older children and adults requires continued monitoring.

Nationwide Trends in Bacterial Meningitis before the Introduction of 13-Valent Pneumococcal Conjugate Vaccine-Burkina Faso, 2011-2013.

BACKGROUND: Following introduction of Haemophilus influenzae type b vaccine in 2006 and serogroup A meningococcal conjugate vaccine in 2010, Streptococcus pneumoniae (Sp) became the leading cause of bacterial meningitis in Burkina Faso. We describe bacterial meningitis epidemiology, focusing on pneumococcal meningitis, before 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the pediatric routine immunization program in October 2013. METHODS: Nationwide population-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Sp infections are confirmed by culture, real-time polymerase chain reaction (rt-PCR), or latex agglutination, and CSF serotyped using real-time and conventional PCR. We calculated incidence rates in cases per 100,000 persons, adjusting for age and proportion of cases with CSF tested at national reference laboratories, and case fatality ratios (CFR). RESULTS: During 2011-2013, 1,528 pneumococcal meningitis cases were reported. Average annual adjusted incidence rates were 26.9 (<1 year), 5.4 (1-4 years), 7.2 (5-14 years), and 3.0 (≥15 years). Overall CFR was 23% and highest among children aged <1 year (32%) and adults ≥30 years (30%). Of 1,528 cases, 1,036 (68%) were serotyped: 71% were PCV13-associated serotypes, 14% were non-PCV13-associated serotypes, and 15% were non-typeable by PCR. Serotypes 1 (45%) and 12F/12A/12B/44/46 (8%) were most common. Among children aged <1 year, serotypes 5 (15%), 6A/6B (13%) and 1 (12%) predominated. CONCLUSIONS: In Burkina Faso, the highest morbidity and mortality due to pneumococcal meningitis occurred among children aged <1 year. The majority of cases were due to PCV13-associated serotypes; introduction of PCV13 should substantially decrease this burden.