Streptococcus pneumoniae serotype-2 childhood meningitis in Bangladesh: a newly recognized pneumococcal infection threat

Abstract

Background: Streptococcus 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 findings: Cases 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.

Conclusions: S. 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.

Figure 1. Cases of Pneumococcal Meningitis by Leading Serotypes Detected According to Culture or Non-Culture Methods.

This depicts the percentage of meningitis cases <5 years by the leading serotypes identified by culture (A) and non-culture (B) detection methods. In brackets, (N), under the year along the x axis indicates the total number of serotype detected in that year. The number above each serotype-2 solid black bar in the histogram represents the number of isolates.

Figure 2. Age Distribution of Serotype-2 Pneumococcal Meningitis Cases Compared to All Other Serotypes.

This depicts the frequency by age of the serotype-2 compared to non serotype 2 pneumococcal meningitis cases in children <5 years. The median and interquartile ranges were 3 months (1 to 4) and 7 months (4 to 9) respectively.

Figure 3. Restriction Fragments Generated by Pulsed-Field Gel Electrophoresis.

Showing banding patterns of serotype 2 representing 3 different pulsetypes, A (N = 36), B (N = 4)& C (N = 1), detected from Sma1 digested genomic DNA.

Figure 4. Depiction of eBURST analysis of the serotype 2 data available on

http://www.mlst.net/ . This is a depiction of an eBURST analysis of the serotype 2 data available on http://www.mlst.net/. The founding sequence type (ST) of the only clonal complex is ST 74, marked by the dark blue node. For the Bangladeshi isolates, the majority (n = 23) belonged to ST 74. The two other sequence types 5083 (n = 3) and 5199 (n = 15) were single and double locus variants of sequence type 74 respectively. The relative proportions are reflected in the light blue and light pink circles around the respective nodes. Epidemiological data recorded on http://www.mlst.net indicates CC 74 is the dominant lineage recorded among those MLST and they originate mainly from West Africa.