Version Changes
Revised. Amendments from Version 1
After receiving reviews from the three proposed peer reviewers, I have made corrections to include their concerns as follows:
Changed description of Streptococcus pneumoniae from “highly invasive” to “friendly gram positive inhabitant of the human upper respiratory tract” in paragraph 1.
Edited the use of the abbreviation “SP n” to “ S. pneumoniae” across the text.
Reviewed paragraphs 1 & 5 to remove noted repetitions and inconsistencies regarding the exact number of S. pneumoniae serotypes
I changed the previous wording of the conclusion in the abstract from “Kenyan children currently using PCV-10 vaccine are not protected” to “these results therefore highlight the importance of monitoring and evaluation to provide epidemiological information to determine the effectiveness of PCV10 in Kenya’s Public health services”
Reviewed the paper to indicate that the evaluation was done after introduction of PCV-10 in 2010 and also reviewed the methodology section to make it a summarized version of what is in the main text.
Abstract
Background: Serotype replacement and emergence of multidrug resistant S. pneumoniae has exacerbated the need for continuous regional serotype surveillance especially in the developing world. We investigated S. pneumoniae serotypes circulating among vaccinated and unvaccinated children ≤5 years in Nairobi County post PCV10 era.
Methods: A total of 206 vaccinated and unvaccinated children attending Gertrude’s Children’s Hospital (GCH) were recruited for this study. Nasopharyngeal swabs collected using Copan Flocked Swabs were the main study specimen. Culturing and isolation of S. pneumoniae was done on BA with gentamicin and BA plates respectively at the GCH main laboratory. Serotyping was done using the Quellung reaction at the KEMRI-Wellcome Trust, Kilifi.
Results: Out of the 206 subjects sampled, 20.39% (42) were found to be carriers of S. pneumoniae. About 52% (n=22) of the S. pneumoniae carriers had received the recommended dose of PCV-10, while 48% (n=20) of the carriers had not. Almost all (n=41; 19.90% of subjects) isolates contained non-vaccine type S. pneumoniae serotypes, while n=1 of the serotypes (in 0.49% of subjects) were untypeable. Serotypes 28F, 6A, 11A, 3 and 7C were prevalent in both vaccinated and unvaccinated children, whereas serotypes 23A, 17F, 35F, 48, 13 and 35B, and 23B, 20, 19B, 21, untypeable, 15B and 39 were found among unvaccinated and vaccinated groups, respectively.
Conclusions: All S. pneumoniae serotypes isolated from the subjects sampled were non PCV-10 vaccine type. These results therefore highlight the importance of monitoring and evaluation to provide epidemiological information to determine the effectiveness of PCV10 in Kenya’s Public health services.
Keywords: Streptococcus pneumoniae, serotypes, Nairobi, Quellung reaction, Optochin test, Bile solubility
Introduction
Streptococcus pneumoniae is a friendly gram positive inhabitant of the human upper respiratory tract but can be highly invasive in some conditions ( Mitchell & Mitchell, 2010). It is a major cause of morbidity and mortality globally as it kills more children than any other illness ( Jones et al., 2010). Streptococcus pneumoniae is classified into serogroups (denoted by numbers and letters, e.g. 18c, 23f) ( Kellogg et al., 2001). There are over 90 known serotypes whose distribution and occurrence vary geographically across the globe ( 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 than others ( Song et al., 2012). The 13 most common serotypes of S. pneumoniae 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 in the developing world ( O’Brien et al., 2009). In Kenya, an estimated one in every five children less than 5 years of age dies from this disease every year ( WHO, 2013).
S. pneumoniae 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 S. pneumoniae or from strains not included 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 serotypes.
Various S. pneumoniae 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 S. pneumoniae 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 to 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 S. pneumoniae 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 S. pneumoniae serotypes among vaccinated and unvaccinated children ≤5 years of age in Nairobi County, Kenya.
Methods
Study Location
This study was conducted among children ≤5 years attending the outpatient department of Gertrude's Children’s Hospital in Nairobi County between May 2017 and February 2018. Subjects were clinically assessed by a physician and those who presented with pneumococcal disease symptoms recommended to the study nurse for recruitment. Gertrude's Children’s Hospital is the largest standalone health care facility specializing in pediatric care in East and Central Africa. The hospital is accredited by the Joint Commission on International Accreditation (JCIA). S. pneumoniae isolation and stocking was done at Gertrude's Children’s Hospital Main Laboratory and capsular serotyping done at KEMRI Wellcome Trust, Kilifi, Kenya.
Study Design
This was a descriptive cross-sectional study. S. pneumoniae serotype epidemiology among PCV-10 vaccinated and unvaccinated children between 6 months and 5 years of age was measured. Children who had no history of any chronic disease and whose parents or legal guardians consented to the study were systematically recruited. Children whose parents or legal guardians declined to give consent and those with any known immunosuppressive conditions were excluded from the study.
Sample Size Determination
To determine the minimum sample size, the formula developed by Chow et al. (2007) was used, with a prevalence rate of 16% ( Agweyu et al., 2014).
Where n= desired minimal sample size; z= standard normal deviation (1.96, from the tailed normal table); p̂= prevalence rate; and m= the desired degree of accuracy at a 95% confidence level of 0.05. This gave a sample size of 206.
Identification of S. pneumoniae
Nasopharyngeal swabs were per nasally collected using Copan flocked swabs and temporarily suspended in Armies medium for transportation to the main laboratory. Each swab was inoculated onto a selective gentamicin with 5% sheep blood agar (BA) plate. All swabs were plated within 24 h of collection. The plates were incubated at 37°C in a 5% CO 2 atmosphere and examined at 16–24 h and then again at 40–48 h for growth of S. pneumoniae. Isolates were identified as S. pneumoniae by colony morphology (Mucoid, draughtsman appearance, α-haemolysis) and susceptibility to optochin (positive, ≥14 mm zone of inhibition; negative, <14 mm zone of inhibition). Plates with colonies akin to S. pneumoniae morphological features but with optochin clearance zones below 14 mm were further subjected to solubility in bile salts (positive, bile soluble; negative, bile insoluble).
The isolation of a single colony indicated carriage. Single colonies were picked using sterile inoculating loops and evenly plated on BA. After 24–48 h, enough inoculum was stocked in brain heart infusion (BHI) agar with 5% sheep blood (Ultralab East Africa, Ltd), gently vortexed and stored at –70°C for serotyping.
Serotyping of S. pneumoniae
Capsular serotyping was done using the Quellung reaction test. Frozen vials containing S. pneumoniae stocks stored at -70°C were thawed at room temperature for about 30 minutes. A loopful of the stored S. pneumoniae cells were suspended in 50 µl PBS and gently vortexed. Subsequently, 10 µl of the suspended cells were added on to a glass slide and mixed with 5 µl pooled antisera (Statens Serum Institute, cat. No.16744). The glass slide was swirled gently while observing for any agglutination reaction until a positive reaction was observed with various pooled antisera. The process was repeated with individual groups under various antisera pools.
After that, 10 µl of the suspended cells in PBS were added to a glass slide and mixed with various S. pneumoniae serotype-specific antisera included in the antisera pools that gave a positive reaction. This was done until a positive reaction with the particular serotype specific antisera was observed. Those serotypes that did not belong to any pool were typed directly until a positive agglutination reaction was observed. The cells/PBS/serotype-specific antisera mixture on the glass slide were covered with a cover slip and observed under a phase contrast microscope with a ×100 objective lens with oil emulsion.
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 S. pneumoniae; 52% (n=22) of the S. pneumoniae 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 S. pneumoniae serotypes, while n=1 (0.49% of the subjects) of the serotypes were untypeable ( Table 1). In total, 18 different S. pneumoniae 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).
Table 1. Overall Streptococcus pneumoniae Carriage of Vaccine Type and Non-Vaccine Type Serotypes.
| All children | Vaccinated
children |
Unvaccinated
children |
||||
|---|---|---|---|---|---|---|
| N | % | N | % | N | % | |
| Overall S. pneumoniae carriage | 42 | 20.39 | 22 | 10.68 | 20 | 9.71 |
| Proportion of S. pneumoniae Serotypes | count | % | count | % | count | % |
| PCV10 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 |
| Non PCV10 serotypes | 41 | 19.90 | 41 | 19.90 | 41 | 19.90 |
| Non typeable | 1 | 0.49 | 1 | 0.49 | 1 | 0.49 |
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 S. pneumoniae 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).
Table 2. S. pneumoniae Serotype Distribution by Age.
| All | 6–12 Months | 13–24
Months |
25–36
Months |
37–48
Months |
49–60
Months |
|
|---|---|---|---|---|---|---|
| Numbers with carriage (n) | 42 | 16 | 8.00 | 12 | 4 | 2 |
| Carriage (%) | 20.39 | 23.53 | 17.02 | 26.09 | 23.53 | 7.14 |
| Number of different serotypes seen | 18 | 9 | 7 | 8 | 3 | 2 |
| Serotypes seen | 28F (8) | 28F (4) | 20 (2) | 23B (3) | 6A (2) | 6A (1) |
| 6A (5) | 11A (2) | 21 (1) | 19B (2) | 15B (1) | 28F (1) | |
| 3 (4) | 23A (2) | 39 (1) | 3 (2) | 28F (1) | ||
| 23B (3) | 3 (2) | 28F (1) | 20 (1) | |||
| 20 (3) | 6A (2) | 35B (1) | 28F (1) | |||
| 23A (3) | 17F (1) | 17F (1) | 7C (1) | |||
| 19B (2) | 35F (1) | 13 (1) | 23A (1) | |||
| 17F (2) | 7C (1) | 48 (1) | ||||
| 7C (2) | untypeable (1) | |||||
| 11A (2) | ||||||
| 35F (1) | ||||||
| 15B (1) | ||||||
| untypeable (1) | ||||||
| 48 (1) | ||||||
| 35B (1) | ||||||
| 21 (1) | ||||||
| 39 (1) | ||||||
| 13 (1) |
S. pneumoniae serotypes as found in children at varying age groups
Figure 1. Percentage S. pneumoniae Serotype Distribution.
Figure 2. S. pneumoniae Serotype Distribution by PCV-10 Vaccination Status.
Table 3. S. pneumoniae Serotype Distribution by PCV-10 Vaccination Status.
| Unvaccinated
(100/206) |
Vaccinated
(106/206) |
||||
|---|---|---|---|---|---|
| Serotype | n | % | Serotype | n | % |
| 28F | 5 | 5 | 3 | 3 | 2.83 |
| 23A | 3 | 3 | 28F | 3 | 2.83 |
| 6A | 3 | 3 | 23B | 3 | 2.83 |
| 17F | 2 | 2 | 20 | 3 | 2.83 |
| 11A | 1 | 1 | 19B | 2 | 1.89 |
| 3 | 1 | 1 | 6A | 2 | 1.89 |
| 35F | 1 | 1 | 21 | 1 | 0.94 |
| 48 | 1 | 1 | 11A | 1 | 0.94 |
| 13 | 1 | 1 | 7C | 1 | 0.94 |
| 35B | 1 | 1 | Untypeable | 1 | 0.94 |
| 7C | 1 | 1 | 15B | 1 | 0.94 |
| 39 | 1 | 0.94 | |||
Table 4. S. pneumoniae carriage by Vaccination Status.
| Child Immunization Status | S. pneumoniae | n | % |
|---|---|---|---|
| PCV-10 Immunized | NGR | 84 | 40.78 |
| S. pneumoniae | 22 | 10.68 | |
| Non PCV10-Immunized | NGR | 80 | 38.83 |
| S. pneumoniae | 20 | 9.71 | |
| Total | N/A | 206 | N/A |
NGR, no growth observed; SP n, Streptococcus pneumoniae; NA, not applicable
Copyright: © 2019 Walekhwa M et al.
Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).
Discussion
This study found that 20.39% of all children studied, from both the PCV-10 vaccinated and unvaccinated groups, were carriers of S. pneumoniae. 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 agree with those of ( Jacobs et al. (2008), where a significant decrease in the vaccine type S. pneumoniae 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 percent 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.
S. 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 S. pneumoniae 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 S. pneumoniae-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 S. pneumoniae 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 exist different antigenic features between and within various strains of S. pneumoniae ( Song et al., 2012). While the majority, if not all, S. pneumoniae 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, S. pneumoniae 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 lack of properly enforced antibiotic use regulations by the authorities.
Data availability
The data referenced by this article are under copyright with the following copyright statement: Copyright: © 2019 Walekhwa M et al.
Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication). http://creativecommons.org/publicdomain/zero/1.0/
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).
Acknowledgements
Special thanks to Prof. Anthony Scott, Dr. Claire Gordon and Ms. Angela Karani of Kemri Wellcome Trust, Kilifi for their professional input. The laboratory and technical team: Ann Karanu, Elizabeth Mbithe, Shadrack Mutua and Alfred Too. Your technical input was amazing! The Gertrude's Hospital clinical and laboratory team (Linet Okose, Barasa Kasili, Charles Muia, Lilive Njagi, Carolyne Thumbi, and Peninah Chege), you made this possible. Thanks to Japheth Wambani Rapando for the review of my work.
Funding Statement
The study was in part funded by the National Commission of Science Technology & Innovation (NACOSTI) Kenya. Ref Nos. NACOSTI/RCD/ST & I/7TH CALL/PhD/148.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
[version 2; referees: 2 approved
References
- Agweyu A, Kibore M, Digolo L, et al. : Prevalence and correlates of treatment failure among Kenyan children hospitalised with severe community-acquired pneumonia: a prospective study of the clinical effectiveness of WHO pneumonia case management guidelines. Trop Med Int Health. 2014;19(11):1310–20. 10.1111/tmi.12368 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Castañeda-Orjuela C, Alvis-Guzmán N, Velandia-González M, et al. : Cost-effectiveness of pneumococcal conjugate vaccines of 7, 10, and 13 valences in Colombian children. Vaccine. 2012;30(11):1936–1943. 10.1016/j.vaccine.2012.01.031 [DOI] [PubMed] [Google Scholar]
- Chow S, Wang H, Shao J: Sample Size Calculations in Clinical Research. New York. 2 nded. Taylor & Francis Group.2007. Reference Source [Google Scholar]
- Colglazier W: SUSTAINABILITY. Sustainable development agenda: 2030. Science. 2015;349(6252):1048–50. 10.1126/science.aad2333 [DOI] [PubMed] [Google Scholar]
- Corscadden KJ, Kirkham LA, Thornton RB, et al. : High pneumococcal serotype specific IgG, IgG1 and IgG2 levels in serum and the middle ear of children with recurrent acute otitis media receiving ventilation tubes. Vaccine. 2013;31(10):1393–1399. 10.1016/j.vaccine.2012.12.078 [DOI] [PubMed] [Google Scholar]
- de Paz HD, Selva L, Muñoz-Almagro C: Pneumococcal Vaccination and Consequences. Streptococcus Pneumoniae. 2015;41–57. 10.1016/B978-0-12-410530-0.00003-X [DOI] [Google Scholar]
- Domenech de Cellès M, Opatowski L, Salomon J, et al. : Intrinsic epidemicity of Streptococcus pneumoniae depends on strain serotype and antibiotic susceptibility pattern. Antimicrob Agents Chemother. 2011;55(11):5255–5261. 10.1128/AAC.00249-11 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dinsbach NA: Antibiotics in dentistry: Bacteremia, antibiotic prophylaxis, and antibiotic misuse. Gen Dent. 2012;60(3):200–207; quiz 208–9. [PubMed] [Google Scholar]
- Donati C, Hiller NL, Tettelin H, et al. : Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species. Genome Biol. 2010;11(10):R107. 10.1186/gb-2010-11-10-r107 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feikin DR, Jagero G, Aura B, et al. : High rate of pneumococcal bacteremia in a prospective cohort of older children and adults in an area of high HIV prevalence in rural western Kenya. BMC Infect Dis. 2010;10:186. 10.1186/1471-2334-10-186 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feldman C, Anderson R: Review: Current and new generation pneumococcal vaccines. J Infect. 2014;69(4):309–25. 10.1016/j.jinf.2014.06.006 [DOI] [PubMed] [Google Scholar]
- Hackel M, Lascols C, Bouchillon S, et al. : Serotype prevalence and antibiotic resistance in Streptococcus pneumoniae clinical isolates among global populations. Vaccine. 2013;31(42):4881–4887. 10.1016/j.vaccine.2013.07.054 [DOI] [PubMed] [Google Scholar]
- Hammitt LL, Akech DO, Morpeth SC, et al. : Population effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and non-typeable Haemophilus influenzae in Kilifi, Kenya: Findings from cross-sectional carriage studies. Lancet Glob Health. 2014;2(7):e397–e405. 10.1016/S2214-109X(14)70224-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harboe ZB, Thomsen RW, Riis A, et al. : Pneumococcal serotypes and mortality following invasive pneumococcal disease: A population-based cohort study. PLoS Med. 2009;6(5):e1000081. 10.1371/journal.pmed.1000081 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill PC, Cheung YB, Akisanya A, et al. : Nasopharyngeal Carriage of Streptococcus pneumoniae in Gambian Infants: A Longitudinal Study. Clin Infect Dis. 2008;46(6):807–814. 10.1086/528688 [DOI] [PubMed] [Google Scholar]
- Jacobs MR, Good CE, Beall B, et al. : Changes in serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae strains in Cleveland: a quarter century of experience. J Clin Microbiol. 2008;46(3):982–990. 10.1128/JCM.02321-07 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson HL, Deloria-Knoll M, Levine OS, et al. : Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: The pneumococcal global serotype project. PLoS Med. 2010;7(10): pii: e1000348. 10.1371/journal.pmed.1000348 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnston C, Campo N, Bergé MJ, et al. : Streptococcus pneumoniae, le transformiste. Trends Microbiol. 2014;22(3):113–9. 10.1016/j.tim.2014.01.002 [DOI] [PubMed] [Google Scholar]
- Jones RN, Jacobs MR, Sader HS: Evolving trends in Streptococcus pneumoniae resistance: Implications for therapy of community-acquired bacterial pneumonia. Int J Antimicrob Agents. 2010;36(3):197–204. 10.1016/j.ijantimicag.2010.04.013 [DOI] [PubMed] [Google Scholar]
- Kalin M: Pneumococcal serotypes and their clinical relevance. Thorax. 1998;53(3):159–162. 10.1136/thx.53.3.159 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kellogg JA, Bankert DA, Elder CJ, et al. : Identification of Streptococcus pneumoniae revisited. J Clin Microbiol. 2001;39(9):3373–3375. 10.1128/JCM.39.9.3373-3375.2001 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mitchell AM, Mitchell TJ: Streptococcus pneumoniae: virulence factors and variation. Clin Microbiol Infect. 2010;16(5):411–8. 10.1111/j.1469-0691.2010.03183.x [DOI] [PubMed] [Google Scholar]
- Moffitt KL, Malley R: Next generation pneumococcal vaccines. Curr Opin Immunol. 2011;23(3):407–13. 10.1016/j.coi.2011.04.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- O’Brien KL, Wolfson LJ, Watt JP, et al. : Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 2009;374(9693):893–902. 10.1016/S0140-6736(09)61204-6 [DOI] [PubMed] [Google Scholar]
- Slotved HC, Dalby T, Hoffmann S: The effect of pneumococcal conjugate vaccines on the incidence of invasive pneumococcal disease caused by ten non-vaccine serotypes in Denmark. Vaccine. 2016;34(6):769–774. 10.1016/j.vaccine.2015.12.056 [DOI] [PubMed] [Google Scholar]
- Song JH, Dagan R, Klugman KP, et al. : The relationship between pneumococcal serotypes and antibiotic resistance. Vaccine. 2012;30(17):2728–37. 10.1016/j.vaccine.2012.01.091 [DOI] [PubMed] [Google Scholar]
- Väkeväinen M, Soininen A, Lucero M, et al. : Serotype-specific hyporesponsiveness to pneumococcal conjugate vaccine in infants carrying pneumococcus at the time of vaccination. J Pediatr. 2010;157(5):778–83.e1. 10.1016/j.jpeds.2010.04.071 [DOI] [PubMed] [Google Scholar]
- Vandenbos F, Gal J, Radicchi B: [Vaccination coverage against influenza and pneumococcus for patients admitted to a pulmonary care service]. Rev Mal Respir. 2013;30(9):746–751. 10.1016/j.rmr.2013.02.009 [DOI] [PubMed] [Google Scholar]
- Walekhwa M, Muturi M, Gunturu R, et al. : Dataset 1 in: Streptococcus pneumoniae serotype epidemiology among PCV-10 vaccinated and unvaccinated children at Gertrude’s Children’s Hospital, Nairobi County: a cross-sectional study. F1000Research. 2018. 10.5256/f1000research.14387.d207458 [DOI] [PMC free article] [PubMed] [Google Scholar]
- WHO : Pneumonia Factsheet. WHO Media Centre. 2013;1–2. [Google Scholar]
- WHO & UNICEF : Global Action Plan for Prevention and Control of Pneumonia (GAPP) Technical Consensus statement. B World Health Organ. 2009;86(5):1–23. Reference Source [DOI] [PMC free article] [PubMed] [Google Scholar]