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Streptococcus pneumoniae serotype 1 burden in the African meningitis belt: exploration of functionality in specific antibodies.

ABSTRACT: Streptococcus pneumoniae serotype 1 (Sp1) constitutes an important cause of seasonal endemic meningitis in all age groups in the African meningitis belt. Despite a higher meningitis incidence, the Burkinabé population has an Sp1-specific antibody seroprevalence similar to that reported in the United Kingdom (UK). We aimed to establish whether the opsonophagocytic activity (OPA) of pneumococcal IgG naturally present in Burkina Faso differs from that seen in individuals in the UK and to compare the OPAs generated by natural and vaccine-induced immunity. Samples collected from pneumococcal vaccine-naive Burkinabé and UK subjects were matched for age (1 to 39 years) and anti-Sp1 IgG level, analyzed for OPA to 3 S. pneumoniae serotypes (1, 5, and 19A), and compared to postvaccine samples. Furthermore, the Burkinabé samples were assessed for IgG avidity and serotype-specific IgM concentrations. One hundred sixty-nine matched serum samples from both populations were selected. A greater proportion of Burkinabé subjects aged 1 to 19 years had functional Sp1 activity (OPA ? 8) compared to UK subjects (12% versus 2%, P < 0.001); however, the proportions were similar among adults (9%). The correlation between Sp1 IgG concentration and OPA was good (P < 0.001), but many individuals had nonfunctional IgG, which was not related to avidity. While the Sp1 IgM concentrations correlated with OPA, not all of the function in serum samples with low IgG could be attributed to IgM. Finally, vaccine-induced Sp1-specific IgG was more functional than equivalent amounts of naturally occurring IgG. In conclusion, despite a substantially higher pneumococcal meningitis incidence, no decreased functional immunity to Sp1 could be evidenced in the Burkinabé population compared to that in the population from the UK. Furthermore, the naturally induced antibodies were less functional than vaccine-induced antibodies.

SUBMITTER: Blumental S

PROVIDER: S-EPMC4375351 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Streptococcus pneumoniae serotype 1 burden in the African meningitis belt: exploration of functionality in specific antibodies.

Blumental S S Moïsi J C JC Roalfe L L Zancolli M M Johnson M M Burbidge P P Borrow R R Yaro S S Mueller J E JE Gessner B D BD Goldblatt D D

Clinical and vaccine immunology : CVI 20150204 4

Streptococcus pneumoniae serotype 1 (Sp1) constitutes an important cause of seasonal endemic meningitis in all age groups in the African meningitis belt. Despite a higher meningitis incidence, the Burkinabé population has an Sp1-specific antibody seroprevalence similar to that reported in the United Kingdom (UK). We aimed to establish whether the opsonophagocytic activity (OPA) of pneumococcal IgG naturally present in Burkina Faso differs from that seen in individuals in the UK and to compare th ...[more]

PMID: 25651921

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Project description:BackgroundStreptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV) targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD) caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention.Methods and findingsCases with suspected IPD had blood or cerebrospinal fluid (CSF) collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal meningitis, accounting for 20.4% (45/221; 95% CI 15%-26%) of cases. Ninety eight percent (45/46) of these serotype-2 strains were isolated from meningitis cases, yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI 3.4-256.3). The serotype-2 strains had three closely related pulsed field gel electrophoresis types.ConclusionsS. pneumoniae serotype-2 was found to possess an unusually high potential for causing meningitis and was the leading serotype-specific cause of childhood meningitis in Bangladesh over the past decade. Persisting disease occurrence or progressive spread would represent a major potential infection threat since serotype-2 is not included in PCVs currently licensed or under development.

Project description:BackgroundPneumococcal conjugate vaccine strategies in GAVI-eligible countries are focusing on infant immunization but this strategy may not be optimal in all settings. We aimed to collect all available population based data on pneumococcal meningitis throughout life in the African meningitis belt and then to model overall meningitis risk to help inform vaccine policy.MethodsAfter a systematic review of literature published from 1970 through the present, we found robust population-based Streptococcus pneumoniae (Sp) meningitis data across age strata for four African meningitis belt countries that included 35 surveillance years spanning from 1970 to 2005. Using these data we modeled disease risk for a hypothetical cohort of 100,000 persons followed throughout life.ResultsSimilar to meningococcal meningitis, laboratory-confirmed pneumococcal meningitis was seasonal, occurring primarily in the dry season. The mean annual Sp meningitis incidence rates were 98, 7.8 to 14, and 5.8 to 12 per 100,000 among persons <1, 1 through 19, and 20 to 99 years of age, respectively, which (in the absence of major epidemics) were higher than meningococcal meningitis incidences for persons less than 1 and over 20 years of age. Mean Sp meningitis case fatality ratios (CFR) among hospitalized patients ranged from 36-66% depending on the age group, with CFR exceeding 60% for all age groups beyond 40 years; depending on the age group, Sp meningitis mortality incidences were 2 to 12-fold greater than those for meningococcal meningitis. The lifetime risks of pneumococcal meningitis disease and death were 0.6% (1 in 170) and 0.3% (1 in 304), respectively. The incidences of these outcomes were highest among children age <1 year. However, the cumulative risk was highest among persons age 5 to 59 years who experienced 59% of pneumococcal meningitis outcomes. After age 5 years and depending on the country, 59-79% of meningitis cases were caused by serotype 1.ConclusionsIn the African meningitis belt, Sp is as important a cause of meningitis as Neisseria meningitidis, particularly among older children and working age adults. The meningitis belt population needs an effective serotype 1 containing vaccine and policy discussions should consider vaccine use outside of early childhood.

Dataset Information

Streptococcus pneumoniae serotype 1 burden in the African meningitis belt: exploration of functionality in specific antibodies.

Publications

Streptococcus pneumoniae serotype 1 burden in the African meningitis belt: exploration of functionality in specific antibodies.

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