Streptococcus pneumoniae Serotypes Associated with Death, South Africa, 2012-2018

Abstract

The Streptococcus pneumoniae polysaccharide capsule plays a role in disease severity. We assessed the association of serotype with case-fatality ratio (CFR) in invasive pneumococcal disease (IPD) and meningitis in South Africa, 2012-2018 (vaccine era), using multivariable logistic regression by manual backward elimination. The most common serotypes causing IPD were 8 and 19A. In patients <15 years of age, serotypes associated with increased CFR in IPD, compared with serotype 8 and controlling for confounding factors, were 11A, 13, 19F, 15A, and 6A. None of these serotypes were associated with increased CFR in meningitis. Among IPD patients >15 years of age, serotype 15B/C was associated with increased CFR. Among meningitis patients of all ages, serotype 1 was associated with increased CFR. PCV13 serotypes 1, 3, 6A, 19A, and 19F should be monitored, and serotypes 8, 12F, 15A, and 15B/C should be considered for inclusion in vaccines to reduce deaths caused by S. pneumoniae.

Keywords: South Africa; Streptococcus; Streptococcus pneumoniae; Switzerland; bacteria; case-fatality ratio; meningitis/encephalitis; mortality; polysaccharide capsule; serotype; streptococci.

Figure 1

Flow diagram of cases included in the analysis of patients with IPD in South Africa, 2012–2018. Asterisk (*) indicates that cases were not typed for 1 of the following reasons: the case was identified by the laboratory information system data audits, n = 651; the sample was positive for pneumococcal antigen detection but nonviable upon culture, n = 14; the isolate was not received and thus serotyping not possible, n = 379; or sample was nonviable and PCR negative, n = 81. Dagger (†) indicates that samples for which Quellung did not yield a valid result were prepared for PCR confirmation and serotyping if PCR positive. If the multiplex PCR was negative for all 38 detectable serotypes, then the sample was excluded from analysis. IPD, invasive pneumococcal disease.

Figure 2

Number of isolates per serotype in invasive pneumococcal disease patients in South Africa, 2012–2018. A) Total number of isolates; serotype 8 was the most commonly isolated (507, 12%). Black dots indicate most common serotypes in patients <15 years of age; arrowheads indicate most common serotypes in patients >15 years of age. B) Number of isolates per serotype per year of the 4 most common serotypes in the prevaccine era (1, 19A, 3, and 4) (9), the 4 most common in the vaccine era (8, 19A, 12F, and 3), and 6A and 19F. The 7-valent pneumococcal conjugate vaccine was introduced in 2009, 13-valent in 2011.

Figure 3

In-hospital outcome per serotype of IPD patients <15 years of age, South Africa, 2012–2018. Numbers above bars indicate number of cases per serotype. Asterisk (*) indicates serotypes significantly associated with increased in-hospital death upon multivariable analysis compared to serotype 8. IPD, invasive pneumococcal disease.

Figure 4

In-hospital outcome per serotype of IPD patients >15 years of age, South Africa, 2012–2018. Numbers above bars indicate number of cases per serotype. Asterisk (*) indicates serotypes significantly associated with increased in-hospital death upon multivariable analysis compared to serotype 8. IPD, invasive pneumococcal disease.

Figure 5

In-hospital outcome per serotype of meningitis patients <15 years of age, South Africa, 2012–2018. A case was defined as a meningitis case if the attending doctor diagnosed it as meningitis, regardless of the specimen type (cerebrospinal fluid, blood, or other) that was taken. Numbers above bars indicate number of cases per serotype. Asterisk (*) indicates serotypes significantly associated with increased in-hospital death upon multivariable analysis compared to serotype 8. IPD, invasive pneumococcal disease.

Figure 6

In-hospital outcome per serotype of meningitis patients >15 years of age, South Africa, 2012–2018. A case was defined as a meningitis case if the attending doctor diagnosed it as meningitis, regardless of the specimen type (cerebrospinal fluid, blood, or other) that was taken. Numbers above bars indicate number of cases per serotype. Asterisk (*) indicates serotypes significantly associated with increased in-hospital death upon multivariable analysis compared to serotype 8. IPD, invasive pneumococcal disease.