Streptococcus pneumoniae serotype epidemiology among PCV-10 vaccinated and unvaccinated children at Gertrude’s Children’s Hospital, Nairobi County: a cross-sectional study

Introduction

Streptococcus pneumoniae (SPn) is a highly invasive, Gram-positive, extracellular bacterial pathogen (Mitchell & Mitchell, 2010). It is a major cause of morbidity and mortality globally, causing more deaths than any other infectious disease (Jones et al., 2010). SPn is classified into serogroups (denoted by numbers and letters, e.g. 18c, 23f) (Kellogg et al., 2001). There are over 90 known serotypes and the prevalence of different serotypes varies by regions of the world (Hackel et al., 2013). Different serotypes exhibit differing potentials to cause disease and may cause different syndromes in different age groups (Harboe et al., 2009).

Some strains also have a greater potential to develop antibiotic resistance (Song et al., 2012). The 13 most common serotypes of SPn pneumonia cause 80–93% of serious pneumococcal disease in children (Johnson et al., 2010). According to the World Health Organization (WHO) and UNICEF Global Action Plan for the Prevention and Control of Pneumonia, pneumonia kills more children than any other illness in the world (WHO & UNICEF, 2009). Given the high burden of under-five mortality associated with pneumonia, control efforts are critical to achieving Sustainable Development Goal 3 (Colglazier, 2015).

WHO and UNICEF estimates indicate that over 800,000 children under 5 years of age die from pneumococcal disease each year (O’Brien et al., 2009). In Kenya, an estimated one in every five children under 5 years of age dies from this disease every year (WHO, 2013).

SPn vaccines protect against several severe forms of pneumococcal disease, such as meningitis, pneumonia and bacteremia (Feldman & Anderson, 2014). These vaccines will not protect against these conditions if they are caused by agents other than SPn or from other strains of SPn that are not contained in the vaccine (Moffitt & Malley, 2011). The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Kenya Expanded Program on Immunization (KEPI) in February 2011 with a 2+1 schedule (at 6, 10, 14 weeks) without catch-up vaccinations (Hammitt et al., 2014). The vaccine covers 1, 4, 5, 6b, 7f, 9V, 14, 18c, 19f and 23f SPn serotypes.

Currently over 90 different serotypes have been identified, six of them very recently (Weinberger et al., 2011). Various SPn serotypes with antigenic similarities are classified under the same groups (9A, 9L, 9N and 9V) while those lacking antigenic similarities are given numbers only (1, 2, 3, 4 and 5). The degree of interaction (cross-reactivity) between various SPn groups may vary. For instance, serotypes 6A and 6B have identical chemical composition except for one of the bonds between two sugars yet they are highly cross-reactive but serotypes 19F and 19A are less reactive.

Pneumococcal conjugate (PCVs) and polysaccharide (PPVs) vaccines are designed according their virulence mechanisms and how they generally interact with the human immune system (Castañeda-Orjuela et al., 2012). The WHO has advised that all children ≤5 years should be immunized against pneumococcal disease and continuous surveillance done to keep out the disease especially in the developing world (Vandenbos et al., 2013). The need for continuous surveillance has been exacerbated by the acute emergence of multi-drug resistant SPn strains and escalated child mortality and morbidity due to pneumococcal disease, despite the availability of PCVs and PPVs. (Väkeväinen et al., 2010). This study therefore sought to establish the SPn serotypes among vaccinated and unvaccinated children ≤5 years of age in Nairobi County, Kenya.

Methods

Results

Out of n=206 (100%) of the subjects sampled, n=97 (47.1%) were male and n=109 (52.9%) were female. In total, 68 (33.0%) of the children studied were within the age bracket of 6–12 months, 47 (22.8%) were between the ages of 13–24 months, 46 (22.3%) were between the ages of 25–36 months, 17 (8.3%) were between the ages of 37 and 48 months and 28 (13.6%) were between the ages of 49 and 60 months. Out of the total number of subjects (n=206) sampled, 20.39% (n=42) were found to be carriers of SPn; 52% (n=22) of the SPn carriers had received the recommended dose of PCV-10 immunization, while 48% (n=20) had not. All isolates (n=42; 20% of subjects) contained non-vaccine-type SPn serotypes, while n=1 (0.49% of the subjects) of the serotypes were untypeable (Table 1). In total, 18 different SPn serotypes were found in this population. They include: 28F (8 instances), 6A (5 instances), 3 (4 instances), 23B (3 instances), 20 (3 instances), 23A (3 instances), 19B (2 instances), 17F (2 instances), 7C (2 instances), 11A (2 instances), 35F (1 instance), 15B (1 instance), untypeable (1 instance), 48 (1 instance), 35B (1 instance), 21 (1 instance), 39 (1 instance) and 13 (1 instance).

Various serotypes were found to be prevalent in different age groups. For instance, out of the 42 serotypes found, 9 (23.53%) were prevalent among children at 6–12 months of age (n=16). They include: 28F (4 instances), 11A (2 instances), 23A (2 instances), 3 (2 instances), 6A (2 instances), 17F (1 instance), 35F (1 instance), 7C (1 instance) and untypeable (1 instance). There were 7 (16.67%) serotypes prevalent among children at 13–24 months (n=8), including: 20 (2 instances), 21 (1 instance), 39 (1 instance), 28F (1 instance), 35B (1 instance), 17F (1 instance) and 13 (1 instance). There were 8 (19%) serotypes found among children of 25–36 months of age (n=12), including: 23B (3 instances), 19B (2 instances), 3 (2 instances), 20 (1 instance), 28F (1 instance), 7C (1 instance), 23A (1 instance) and 48 (1 instance). There were 3 (7%) serotypes prevalent among children at 37–48 months old (n=4), including: 6A (2 instances), 15B (1 instance) and 28F (1 instance).

There were 2 (4.76% of the total) serotypes prevalent among children at 49–60 months (n=2): 6A (1 instance) and 28F (1 instance) (Table 2). Out of the 42 isolates (found in 20.39% of subjects), serotype 28F was the most prevalent (3.88% of the total), followed by 6A (2.43%), 3 (1.94%) and 20, 23A and 23B all at 1.46% (n=3). Each of the serotypes 7C, 11A, 17F and 19B represented 0.97% (n=2) of the total serotypes, while serotypes: 13, 21, 39, untypeable, 48, 15B, 35B and 35F represented 0.49% (n=1) each of the total serotypes found (Figure 1 and Figure 2). In total 51% (n=106) of the total sampled subjects were confirmed to have received a full dose of the PCV-10 vaccination as per the recommended schedule of immunization at 6, 10 and 14 weeks. Approximately 11% (n=12) of the immunized children were carriers of SPn in their nasopharyngeal region; 10% (n=10) of the non-immunized group were also carriers (Table 3). Serotypes 28F (5 instances), 23A (3 instances), 6A (3 instances), 17F (2 instances), 11A (1 instance), 3 (1 instance), 35F (1 instance), 48 (1 instance), 13 (1 instance), 35 (1 instance) and 7C (1 instance) were prevalent among the 9.71% (n=20) of the total sample group that had not received PCV-10 immunization. Serotypes 3 (3 instances), 28F (3 instances), 23B (3 instances), 20 (3 instances), 19B (2 instances), 6A (2 instances), 21 (1 instance), 11A (1 instance), 7C (1 instance), untypeable (1 instance), 15B (1 instance) and 39 (1 instance) were prevalent among the 10.68% (n=22) of the total sample group that received immunization (Table 4).

Figure 1. Serotype distribution in the Streptococcus pneumoniae (SPn) isolates.

This figure shows the prevalence of various SPn serotypes among PCV-10-vaccinated and –unvaccinated children.

Figure 2. Streptococcus pneumoniae (SPn) serotype distribution by PCV-10 vaccination status.

Discussion

This study found that 20.39% of all children studied, from both the PCV-10 vaccinated and unvaccinated groups, were carriers of SPn. While this is a significant reduction from the pre-vaccine era, it is still high compared to malaria, diarrhea and HIV/AIDS (Feikin et al., 2010). In total, n=41 of the serotypes found were non-vaccine type (in 19.90% of the subjects), with one additional untypeable serotype. This is a very important finding as it explains the high level of child morbidity and mortality due to pneumococcal disease despite the availability of PCV-10.

While these findings agree partially with those of Jacobs et al. (2008), where a significant decrease in the vaccine type SPn serotypes found in isolates was observed, a 97.6% (n=41) decrease is, at the very least, surprising. This trend may be attributed to the increased level of antimicrobial misuse by a greater percentage of the study population (Domenech de Cellès et al., 2011). 10-valent pneumococcal conjugate vaccine contains 10 different serotypes, which include: 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F (Slotved et al., 2016). None of these 10 serotypes was found in the study population yet this is the vaccine currently included in KEPI, targeting the same population.

Streptococcus pneumoniae carriage decreased with age as 11.65% (n=24) were obtained from children aged between 6–24 months and 8.74% (n=18) from children >24 months. The study results demonstrated a linear relationship between child age and SPn carriage. A similar study done elsewhere reported findings that partly agree with this and partly disagrees (Hill et al., 2008). The former being attributable to development of SPn-specific IgG antibodies due to vaccination and during that window before most children start attending school (Corscadden et al., 2013). Unlike findings from a study by de Paz et al. (2015), serotype 28F was the most prevalent and was present in all five age groups profiled. This is a likely scenario of serotype replacement as SPn attempts to evade the action of the immune system and eventually shares the resistant genes within the microbial community, especially in the nasopharyngeal region (Donati et al., 2010).

Serotypes 28F, 6A, 11A, 3 and 7C were prevalent in both vaccinated and unvaccinated children, whereas serotypes 23A, 17F, 35F, 48, 13, 35B and 23B, 20, 19B, 21, untypeable, 15B, 39 were found among unvaccinated and vaccinated groups respectively. There exists different antigenic features between and within various strains of SPn (Song et al., 2012). While the majority, if not all, pneumococcal serotypes are capable of causing disease, the frequency with which they are isolated varies (Kalin, 1998). In this case, vaccination would only be partially effective and, if so, due to inter-strain antigenic characteristics.

While trying to evade the action of the immune system, SPn has a tendency to exchange resistant genes and other antigenic correlates at the nasopharyngeal region (Johnston et al., 2014). Resistance to antimicrobial agents is occasioned by among other factors, misuse of antibiotics (Dinsbach, 2012). This is largely due to a lack of properly enforced antibiotic use regulations by the authorities.

Data availability

Dataset 1. List of basic demographic information for each subject, with the size of the optochin clearance zone and serotype of Streptococcus pneumoniae, if found. DOI: http://doi.org/10.5256/f1000research.14387.d207458 (Walekhwa et al., 2018).