Immunogenicity and Reactogenicity of 13-Valent Pneumococcal Conjugate Vaccine Among Infants, Toddlers, and Children in Western Burkina Faso: Results From a Clinical Trial of Alternative Immunization Schedules.

BACKGROUND: Many African countries have introduced pneumococcal conjugate vaccine (PCV) into their routine immunization program to reduce the burden of morbidity and death that results from Streptococcus pneumoniae infection, yet immunogenicity and reactogenicity data from the region are limited for the 2 available PCV products. METHODS: We conducted a randomized trial of 13-valent PCV (PCV13) in Bobo-Dioulasso, Burkina Faso. Infants received 3 doses of PCV at 6, 10, and 14 weeks of age or at 6 weeks, 14 weeks, and 9 months of age; toddlers received 2 doses 2 months apart or 1 dose beginning at 12 to 15 months of age; and children received 1 dose between 2 and 4 years of age. We measured each participant's serotype-specific serum immunoglobulin G concentration and opsonophagocytic activity before and after vaccination. For each age group, we compared immune responses between study arms and between the standard schedule in our study and the PCV13-licensing trials. RESULTS: In total, 280 infants, 302 toddlers, and 81 children were assigned randomly and underwent vaccination; 268, 235, and 77 of them completed follow-up, respectively. PCV13 resulted in low reactogenicity in all the study arms. The vaccine elicited a strong primary immune response in infants after 2 or more doses and in children aged 1 to 4 years after 1 dose. Infants who received a booster dose exhibited a robust memory response. Immunogenicity was higher than or comparable to that observed in the PCV13-licensing trials for a majority of serotypes in all 3 age groups. CONCLUSIONS: PCV13 has a satisfactory immunogenicity and reactogenicity profile in this population. Our findings will help support decision making by countries regarding their infant and catch-up vaccination schedules.

Antipneumococcal seroprevalence and pneumococcal carriage during a meningococcal epidemic in Burkina Faso, 2006.

BACKGROUND: To better understand the high incidence of pneumococcal meningitis in the African meningitis belt, we conducted a pneumococcal seroprevalence study during a meningococcal meningitis epidemic in Western Burkina Faso, March 2006. METHODS: In 3 villages experiencing epidemics, we included 624 healthy persons (1-39 years) by cluster sampling. We determined pneumococcal serum immunoglobulin G (IgG) antibody concentrations against 12 serotypes contained in 13-valent pneumococcal conjugate vaccine, and evaluated determinants for IgG ≥ 0.35 µg/mL by multivariate logistic regression. RESULTS: The percentage of subjects with serotype-specific IgG concentrations ≥0.35 µg/mL increased with age and was similar for the different serotypes: it was 20%-43% among 1-4-year-olds and 56%-90% among 20-39-year-olds. Prevalence of IgG ≥ 0.35 µg/mL against serotype 1 was up to 71% after age 10 years. During multivariate analyses, determinants of IgG concentrations ≥0.35 µg/mL varied by serotype; for 5 and 6 serotypes, respectively, female sex (around 2-fold increased odds) and cigarette smoking (about 5-fold reduced odds) predicted elevated titers. CONCLUSIONS: Despite a substantially higher historical pneumococcal meningitis incidence in Burkina Faso, the general population has an antibody seroprevalence against 12 pneumococcal serotypes similar to that reported from the United Kingdom. The role of putatively protective antibody seroprevalence in preventing pneumococcal meningitis in the meningitis belt requires more thorough evaluation.

Seroprevalence of bactericidal, specific IgG antibodies and incidence of meningitis due to group A Neisseria meningitidis by age in Burkina Faso 2008.

BACKGROUND: We investigated serological correlates of protection against Neisseria meningitidis serogroup A (NmA) in Burkina Faso before the introduction of NmA conjugate vaccine. METHODOLOGY/PRINCIPAL FINDINGS: We collected blood from a representative sample (N = 1022) of Bobo-Dioulasso residents. Sera were evaluated for serum bactericidal antibody (SBA) activity against NmA strains of immunotype L11 (F8238) and L10 (3125) and NmA-specific IgG. Seroprevalence was compared to the age-specific NmA meningitis incidence in Bobo-Dioulasso during March 2007-February 2008. Meningococcal carriage was evaluated in a subset (N = 538). Geometric mean titres (GMT)/concentrations (GMC) of SBA and NmA-specific IgG increased with age, peaking around age 20 years. Overall, 70% of our sample had NmA-specific IgG ≥2 ug/mL. Meningitis incidence was highest in those aged <6 months and 5-19 years. No NmA carriers were found. Compared to the reference strain SBA, GMTs were higher against a locally isolated strain and around 40-fold lower against Dutch strain 3125. CONCLUSIONS/SIGNIFICANCE: This study provides estimates of natural immunity to NmA, according to a variety of antibody measures, which will be helpful in ascertaining antibody persistence after MenAfriVac™ introduction. Age-specific seroprevalence of reference strain SBA titres most likely reflects exposure to meningococci and consecutive reactive immunity. We could not define any serological correlate of protection.

Pneumococci in the African meningitis belt: meningitis incidence and carriage prevalence in children and adults.

BACKGROUND: The development of optimal vaccination strategies for pneumococcal conjugate vaccines requires serotype-specific data on disease incidence and carriage prevalence. This information is lacking for the African meningitis belt. METHODS: We conducted hospital-based surveillance of acute bacterial meningitis in an urban and rural population of Burkina Faso during 2007-09. Cerebrospinal fluid was evaluated by polymerase chain reaction for species and serotype. In 2008, nasopharyngeal swabs were obtained from a representative population sample (1 month to 39 years; N = 519) and additional oropharyngeal swabs from 145 participants. Swabs were evaluated by culture. RESULTS: Annual pneumococcal meningitis incidence rates were highest among <6-month-old (58/100,000) and 15- to 19-year-old persons (15/100,000). Annual serotype 1 incidence was around 5/100,000 in all age groups. Pneumococcal carriage prevalence in nasopharyngeal swabs was 63% among <5-year-old children and 22% among ≥5-year-old persons, but adding oropharyngeal to nasopharyngeal swabs increased the estimated carriage prevalence by 60%. Serotype 1 showed high propensity for invasive disease, particularly among persons aged ≥5 years. CONCLUSIONS: Serotype 1 causes the majority of cases with a relatively constant age-specific incidence. Pneumococcal carriage is common in all age groups including adults. Vaccination programs in this region may need to include older target age groups for optimal impact on disease burden.

Study of a localized meningococcal meningitis epidemic in Burkina Faso: incidence, carriage, and immunity.

BACKGROUND: To better understand localized meningococcal meningitis epidemics, we evaluated a serogroup A (NmA) epidemic in Burkina Faso by surveillance, carriage, and seroprevalence studies. METHODS: During March-April 2006, cerebrospinal fluid samples from patients suspected to have meningitis in 3 epidemic villages were analyzed by culture or polymerase chain reaction. We assessed meningococcal carriage and serogroup-specific serum bactericidal antibody titers with baby rabbit complement (rSBA) in a representative population sample (N = 624; age range, 1-39 years). A serogroup A/C polysaccharide vaccine campaign occurred in parallel. RESULTS: Cumulative incidence of Nm meningitis was 0.45% and varied among villages (0.08%-0.91%). NmA carriage prevalence was 16% without variation by vaccination status. NmA carriage and anti-NmA seroprevalence varied by village and incidence. In the 2 villages with highest incidence and seroprevalence, presence of rSBA titers ≥8 was associated with NmA carriage (odds ratio [OR], 9.33 [95% confidence interval {CI}, 1.90-45.91]) and vaccination ≤4 days earlier (OR, 0.10 [95% CI, .03-.32]). Visibly purulent or Nm meningitis was significantly associated with recent flulike symptoms and exposure to kitchen smoke (risk ratios >15). CONCLUSIONS: A surge of NmA carriage may be involved in the development of meningococcal epidemics and rapidly increase anti-NmA seroprevalence. Flulike infection and kitchen smoke may contribute to the strength of epidemics.