Secondary Logo

Journal Logo

Vaccine Reports

Temporal Changes in Pneumococcal Colonization in a Rural African Community With High HIV Prevalence Following Routine Infant Pneumococcal Immunization

Nzenze, Susan A. MB ChB, MPH*†; Shiri, Tinevimbo MSc, PhD*†; Nunes, Marta C. PhD*†; Klugman, Keith P. MB BCh, FCPath, PhD†‡§; Kahn, Kathleen MB BCh, MPH, PhD¶‖**; Twine, Rhian BSc; de Gouveia, Linda MTech† ††; von Gottberg, Anne MB BCh, FCPath(Micro)† ††; Madhi, Shabir A. MBBCh, FCPaeds, MMed, PhD. Can*† ††

Author Information
The Pediatric Infectious Disease Journal: November 2013 - Volume 32 - Issue 11 - p 1270-1278
doi: 10.1097/01.inf.0000435805.25366.64


Colonization of the nasopharynx by Streptococcus pneumoniae, although usually asymptomatic, may be associated with pneumococcal disease particularly within the first 2 months of acquisition of new pathogenic serotypes.1 At the time of illness, the same serotype colonizing the nasopharynx is identifiable from diseased sites.1,2

Immunization of children with pneumococcal conjugate vaccine (PCV) decreases their risk of acquisition of vaccine serotypes, particularly serotypes traditionally associated with a high prevalence of asymptomatic nasopharyngeal (NP) colonization during childhood (ie, 6A, 6B, 9V, 19A, 19F and 23F).1,3,4 Routine 7-valent PCV (PCV7) childhood immunization in industrialized settings has been associated with reduced NP acquisition of the vaccine serotypes among vaccinated children, which in turn has resulted in reduced transmission of these serotypes to unvaccinated individuals.5,6 Consequently, reductions in the incidence of vaccine serotype invasive pneumococcal disease (IPD) among vaccinated and unvaccinated individuals have been observed in settings with low prevalence of HIV infection.7–9 A decline in vaccine serotype IPD has also been observed among PCV-unvaccinated HIV-infected adults following childhood PCV7 immunization in the United States,10,11 which has partly been offset by an increase in nonvaccine serotype IPD of greater magnitude compared with among healthy HIV-uninfected adults.10,11

In Africa, a study from The Gambia recently reported significant decline in vaccine serotype colonization among unvaccinated adolescents and adults following childhood PCV7 immunization, which included a targeted catch-up campaign of children aged up to 3 years.12 This study finding may have been confounded by the prolonged time period (3 years) between when the prevaccination survey was undertaken relative and when PCV immunization was initiated. In addition, widespread community-wide intervention with azithromycin between sampling periods may have confounded the study interpretation in attributing the changes in the prevalence of pneumococcal colonization solely to PCV immunization. Consequently, it was unclear whether the unexpectedly, lower prevalence of nonvaccine serotype colonization observed among adults following PCV childhood immunization compared with the prevaccine period was due to PCV immunization of young children or due to widespread use of azithromycin prophylaxis in the community. In addition, the possibility of natural temporal fluctuations of circulating pneumococcal serotypes may have contributed to differences in serotype-specific pneumococcal colonization, including the lower prevalence of nonvaccine serotype colonization, following childhood immunization with PCV.12

To our knowledge, there are no published data on the impact of infant PCV7 immunization in the absence of catch-up campaign of older children and on NP pneumococcal colonization in rural African communities with a high prevalence of HIV infection. We aimed to determine the effect of infant PCV immunization on the epidemiology of NP colonization in different age groups in a rural African community with high prevalence of HIV infection.


Study Setting and Study Population

South Africa introduced PCV7 (Prevnar; Pfizer, New York, NY) into the national, public-funded childhood immunization program from April 2009. The vaccine is administered in a 2-dose primary series at 6 and 14 weeks of age, followed by a third-dose at age 9 months. PCV7 was substituted with 13-valent PCV (Prevnar-13; Pfizer) from May 2011. No catch-up campaign of any child older than 6 weeks, at the time of initiation of the PCV immunization program, if they had already received any other childhood vaccine recommended from 6 weeks of age onward, was offered during the course of this study.

Two cross-sectional studies, spaced 2 years apart, were undertaken in a rural health and sociodemographic surveillance site (HDSS), in the Agincourt subdistrict in Mpumalanga province, rural northeast South Africa. The Agincourt HDSS, established in 1992, covers an area of approximately 402 km2 and shares a border with Mozambique (Fig., Supplemental Digital Content 1, The HDSS includes an annual update of all vital events (births, deaths, in- and out-migrations) in all households in 27 villages. About a third of the population is composed of Mozambican immigrants.13 The prevalence of HIV infection among individuals aged >15 years in the HDSS was 37.4% in 2011. ART rollout increased from 1503 to 5667 patients in 2009 and 2011, respectively.14 Details of the surveyed population are summarized in Table 1. Those characteristics that could have influenced the prevalence of pneumococcal NP colonization and that differed between the 2 sampling periods at a significance level of P < 0.1 were adjusted when estimating the relative risk of pneumococcal carriage in periods 1 and 2.

Comparison of Prevalence of all Pneumococci, Vaccine Type (VT), Nonvaccine Type (NVT) and Nontypeable Serotypes by Age and Gender in Periods 1 and 2

Study Sampling Framework and Procedure

The initial survey (period 1) was undertaken from May to October 2009 (ie, immediately upon introduction of PCV into the immunization program). A subsequent (period 2) survey was undertaken from May to October 2011. Based on the annual census update of the 27 villages in the HDSS, children <2 years of age were identified and linked to their parent household for potential study participation in each village. Villages were then randomly selected for the order of sampling, with the number of villages approached continuing until the target sample size was achieved. A household was included if in addition to the listed child there was at least 1 individual older than 12 years who agreed to participate in the study. The Agincourt HDSS definition for a household, also used in this study, was “a group of people who resided and ate together including temporary migrants (ie, a household member who is away for >6 months per year but retains a significant link to the rural/sending household), who ate with them on return.” Meetings were held with community members, traditional and civic leaders, to explain the study. A questionnaire was administered at the time of swab collection. No HIV testing was performed, but self-reported HIV infection status was collected.

Sample Size Calculation

Because there were no prior data on the prevalence of pneumococcal NP colonization in this setting, the estimated prevalence of vaccine serotype colonization among adults in 2009 was based on data from Navajo Indian populations (4%)15 and an African population in Malawi16 in the absence of PCV immunization. Vaccine serotype colonization in South African adults was expected to be greater than that in Navajo Indians because a higher prevalence of colonization had been reported among HIV-infected Malawian women (11.4% versus 5.9% in HIV-uninfected women).16 We postulated that the prevalence of vaccine serotype colonization would be 10% among adults in 2009. We calculated the need to enroll 611 adults in each survey period to detect at least a 45% reduction in vaccine serotype colonization between periods 1 and 2 with 80% power. Based on the actual observed prevalence of vaccine serotype colonization among adults in period 1 (3.0%), we recalculated the sample size for period 2 and targeted enrolling at least 1783 adults to provide 80% power to detect a 50% reduction in vaccine serotype colonization compared with period 1.

Determination of Bacterial Colonization

Sampling of the pharynx was undertaken by trained medical study staff at the households. NP swabs were performed using an aluminum-shafted, Dacron swab (Medical Wire and Equipment Co. Ltd., Corsham, Wiltshire, England), as described.17 In addition, an oropharyngeal swab was collected in adults. Specimens were placed in skimmed milk, tryptose, glycerol and glucose broth transport media, transported in a cooler box and then stored at −70°C within 6 hours of sampling. Samples were shipped intermittently to the Centre for Respiratory Diseases and Meningitis laboratory at the National Institute for Communicable Diseases in Johannesburg on dry ice and stored at −70°C until processed by routine microbiological methodologies. Serotyping was undertaken by the Quellung method using serogroup and factor-specific antisera (Statens Serum Institut Copenhagen, Denmark). Presumptive pneumococcal isolates that did not exhibit the Quellung reaction with serogroup-specific, factor-specific and all-pooled antisera were categorized as nontypeable once pneumococcal identification was confirmed with lytA polymerase chain reaction.18 Where >1 distinct morphological colony type was present, each colony was serotyped. Serotypes 6A, 6B, 6C and 6D were distinguished only using the relevant antisera and without any additional molecular typing.

Definitions and Statistical Analysis

For all statistical analysis, individuals older than 12 years were categorized as adolescents/adults and those ≤12 years as children. Multiple, simultaneous serotype colonization in the same individual were considered as independent events if they differed in stratification by vaccine serotype, nonvaccine serotype or being nontypeable when measuring the prevalence of colonization. Vaccine serotypes refers to serotypes in PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F); nonvaccine serotypes refers to any other pneumococcal serotypes and excluded nontypeable isolates. Comparison of the prevalence of pneumococcal NP colonization and serotype distribution between the 2 periods was performed using χ2 or Fisher’s exact tests where appropriate. Log-binomial regression models were used to estimate the risk ratios for pneumococcal carriage in period 1 versus period 2, adjusting for potential risk factors for colonization, including age, gender, fuel used for cooking in the household, presence of a child attending day care in the household and household structure (ie, the presence of any child <5 years and any individual between 6 and 18 years of age in the household). In addition, generalized linear mixed models were developed to adjust for potential correlation among subjects from the same household plus all the other risk factors used in the log-binominal regression models. Statistical analyses were performed with STATA 12 (StataCorp, College Station, TX) and SAS version 9.2 software (SAS Institute, Inc., Cary, NC).


This study was approved by the Human Research Ethics Committee (Medical; Ethics Number M090014) at the University of the Witwatersrand and the Mpumalanga Department of Health Ethics Committee. Informed written consent was obtained from participants ≥18 years, and parental/guardian consent was obtained for younger participants. Children between 8 and <18 years age also provided verbal assent for study participation.


A total of 577 and 1079 households were recruited in periods 1 and 2, respectively. This included 994 and 1781 adults/adolescents and 1016 and 1877 children in the 2 respective periods. Characteristics of the sampled households are summarized in the Table (Supplemental Digital Content 2, Differences between households in the 2 periods included a higher proportion of children who used electricity for cooking in period 2 (34.2% versus 29.3%; P = 0.032), higher mean number of children <5 years of age within households in period 2 and consequently an older mean age of children enrolled in period 1 (Table, Supplemental Digital Content 2,

Temporal Changes in the Prevalence of Pneumococcal Colonization

In period 1, 83.0% of children aged <2 years were colonized, including 28 who carried 2 serotypes, resulting in a total of 359 pneumococcal isolates (Table 1). The prevalence of vaccine serotype colonization was 45.1% in children aged <2 years in period 1 (Table 1). In 2- to 5-year-old children, overall colonization was 80.2%, including 17 children who were colonized by 2 serotypes that resulted in 236 isolates. The prevalence of vaccine serotype and nonvaccine serotype colonization in the 2- to 5-year age group was 35.5% and 45.8%, respectively, in period 1 (Table 1). Among 6- to 12-year-old children, 60.0% were colonized, including 13 with 2 serotypes, resulting in 199 pneumococcal isolates identified. The prevalence of vaccine serotype was 19.0% among the 6- to 12-year age group, which was lower than that among the <2-year age group (P < 0.0001), while the prevalence of nonvaccine serotype colonization (42.6%) was similar to that in the youngest age group (P = 0.32; Table 1). Overall, the prevalence of colonization in adolescents and adults was 22.8%, 10.7% and 5.1% among the age groups of 13–18 years, 19–45 years and >45 years, respectively (Table 1). In addition, the prevalence of vaccine serotype colonization was 5.7%, 3.0% and 1.7% in the respective above-specified adolescent and adult age groups (Table 1). Females who were primary caregivers to the children had similar overall prevalence of pneumococcal colonization [compared with other adolescents/adults; 10.2% (49/478) versus 8.4% (19/225); P = 0.45] but higher prevalence of vaccine serotypes [3.8% (18/478) versus 1.3% (3/225); P = 0.06] in period 1.

In period 2, 666 (73.4%) children <2 years of age were colonized, including 47 in whom 2 serotypes were identified, which resulted in 713 pneumococcal isolates. The overall prevalence of pneumococcal colonization was 11.6% lower in period 2 compared with that in period 1 (P = 0.0002) in the <2-year age group (Table 1). This was dominantly due to a 50.0% decrease in vaccine serotype colonization [ARR 0.50, 95% confidence interval (CI): 0.42–0.59], while there was a 35.0% increase in the prevalence of nonvaccine serotype colonization by period 2 (P = 0.0001). Among 2- to 5-year-old children, although there was a 21% reduction in vaccine serotype colonization, the prevalence of overall and nonvaccine serotype colonization remained unchanged in period 2 compared with that in period 1 (Table 1).

Among older age groups, lower prevalence of vaccine serotype colonization in period 2 compared with that in period 1 was evident in children aged 6–12 years (ARR 0.66, 95% CI: 0.48–0.92), a similar trend was observed in the 13- to 18-year age group (ARR 0.49, 95% CI: 0.17–1.39) and significantly lower prevalence was observed in the 19- to 45-year age group (ARR 0.36, 95% CI: 0.18–0.74). The prevalence of nonvaccine serotype colonization remained unchanged comparing period 2 with period 1 in the 6- to 12-year age group, whereas reductions of 45.0% and 54.0% were observed in the 13- to 18-year and 19- to 45-year age groups, respectively (Table 1). Overall, pneumococcal colonization declined by 17%, 46% and 52% among the age groups of 6–12 years, 13–18 years and 19–45 years, respectively. The prevalence of pneumococcal colonization among the primary caregivers declined to 5.4% (58/1067; P = 0.001) overall, 0.94% (10/1067; P ≤ 0.001) for vaccine serotypes but remained unchanged among non-caregivers [8.3% (58/696) overall and 2.01% for VT in period 2; P = 0.9 and 0.4, respectively].

Limiting the analysis to those villages only sampled during both periods resulted in similar findings compared with those found when analyzing the entire study cohorts (data not shown). Also using generalized linear mixed models adjusting for potential intra-household clustering had no effect on the observed results (Table, Supplemental Digital Content 3,

Serotype-specific Colonization by Age Group Over 2 Periods

Among children aged 0–12 years, the dominant colonizing serotypes in period 1 were 19F (14.2%), 6B (10.2%), 6A (9.3%), 23F (8.9%), 15 (7.6%), 19A (5.0%) and 14 (4.3%) in decreasing order of frequency (Table 2). The prevalence of colonization was significantly lower in period 2 among children <2 years for serotypes 6B, 18C, 19F and 23F. There were, however, no significant changes in the prevalence of colonization by individual vaccine serotype in older children and particularly those in 2–5 years of age where vaccine serotypes remained dominant (Table 2).

Serotype Distribution by Age Group in Each of the Survey Periods

Nonvaccine serotypes that showed significant increase among children aged <2 years from period 1 compared with period 2 included serogroup 15 (ie, serotypes 15A, 15B, 15C combined), which increased from 5.8% to 12.2% (P < 0.0001), serotypes 16F and serotypes 11A (Table 2). The dominant serotypes in descending order among colonized children <2 years in period 2 included 6A (12.3%), 15B (7.6%), 19A (6.3%), 16F (5.8%), 11A (3.2%) and 15A (2.8%). The prevalence of colonization by serotypes 6A and 19A remained unchanged between the study periods in children and adults. Among the individuals >12 years, a significant increase in serogroup 15 from 3.3% to 10.6% (P = 0.02) was also observed (Table 2).

HIV and Pneumococcal Colonization

HIV infection status in periods 1 and 2 was volunteered by 505 and 1320 adults and 165 and 631 children, respectively. In period 1, adolescent/adults who self-reported as being HIV-infected had a trend toward higher prevalence of overall colonization (8/40, 20.0%) compared with HIV-uninfected individuals (55/465, 11.8%; P = 0.13). This difference was significant in period 2 when 10.4% (14/135) of self-reported HIV-infected individuals were colonized compared with 5.1% (60/1185) of reportedly HIV-uninfected adolescents/adults (P = 0.01). Vaccine serotype colonization was also greater in adolescents/adults reported to be HIV-infected compared with HIV-uninfected individuals in period 1 [10.0% (4/40) versus 3.2% (15/465); P = 0.054] and period 2 [3.0% (4/135) versus 1.0% (12/1185); P = 0.011]. There were no differences in the prevalence of overall or vaccine serotype colonization among children aged <12 years in period 1 or period 2 when stratified by self-reporting HIV status.

Effect of the Number of PCV Doses Received on Carriage in Vaccine Recipients

A total of 386 (51.5%) of 749 children, <2 years of age in period 2 who had verifiable immunization records at hand, were fully vaccinated. Fifty percent (347/692) of the children aged 9 months to 2 years were fully vaccinated with 3 doses of PCV, while 31.9% (221/692) had received 2 doses and 17.9% (124/692) had only received a single dose. Fully vaccinated 9-month- to 2-year-old children had a lower prevalence of vaccine serotype colonization (59/347, 17.0%) compared with those who had only received 2 (56/221, 25.3%; P = 0.02) or a single PCV7 dose (37/124, 29.8%; P = 0.002). In 3- to 9-month-old children, there was no difference in vaccine serotype colonization between partially vaccinated (ie, only received one PCV7 dose; 27.8%) and those who had received both scheduled PCV7 doses (28.1%, P = 0.979). Overall, in a logistic regression model, adjusting for age, there was an inverse relationship between the number of doses of PCV received and the vaccine serotype colonization (odds ratio 0.69, 95% CI: 0.56–0.87), indicating that incompletely vaccinated children were more likely to carry vaccine serotypes compared with fully vaccinated children.


To our knowledge, this is the first report on the temporal association of infant PCV immunization on the epidemiology of NP pneumococcal colonization among children and adults in a rural African setting with high HIV prevalence. Our study indicated that the prevalence of vaccine serotype colonization in the <2- and 2- to 5-year age groups were almost similar at the time of initiation of the PCV immunization program; nevertheless, a vaccination program limited to immunization at 6 weeks, 14 weeks and 9 months of age was associated with reduction in vaccine serotype colonization in all study age groups, including the 2- to 5-year-old unvaccinated children. Notably, a reduction in vaccine serotype colonization was observed with 51.5% of the targeted population having been fully vaccinated based on their age group. This suggests that despite a high prevalence of vaccine serotype colonization among older children in resource poor, rural settings, children <2 years of age are likely the primary source of transmission of vaccine serotypes in the community and that an indirect effect of PCV immunization can be realized within 2 years of initiating the PCV immunization program, even without a catch-up campaign of older children and with a fairly modest level of vaccine coverage of the target population. A higher level of fully vaccinated coverage may have been associated with even a greater magnitude of reduction in colonization by vaccine serotypes among unvaccinated individuals compared with what was observed in our setting.

The findings of our study corroborate that of clinical trials in which the direct and indirect effect of PCV in children reduced colonization among vaccinated and unvaccinated individuals.6,15,19–24 There are also few observational ecological studies where this has now been reported, including those from The Gambia,12 United Kingdom,25 The Netherlands,26 United States among Native Americans, Alaska27 and the general US population28,29 and in Australasia.30 The results of our study, nevertheless, are unique as we evaluated a national immunization program with no catch-up campaign of older children as undertaken elsewhere,12,25,26,28–30 and also it was undertaken in a setting of high underlying HIV positivity among adults and with only modest levels of age-appropriate PCV7 coverage.

The prevalence of pneumococcal colonization was generally high in our study population, which is similar to that reported in a few other African countries.12,31 Notably, the prevalence of pneumococcal colonization in children <2 years of age (83.8%) was comparable with that in 3- to 5-year-old children (81.4%) and also high (60%) in the 6- to 12-year age group at the time of PCV7 introduction. In contrast, the prevalence of pneumococcal colonization in children from developed countries peaks at 40–50% at approximately 2 years of age and is subsequently followed with reduction from around 5 years of age to adult levels of ≤10%.4 While our study suggests that young infants are the main source of pneumococcal transmission to adolescents and older adults, the more modest reduction (21%) in vaccine serotype colonization in the 2- to 5-year age group possibly indicates some ongoing transmission of vaccine serotypes among this age group, who are also more likely to intermingle in the community and in playgroups or day-care centers. Although 2- to 5-year-old children are at lower risk of IPD compared with <2-year-old children,32 they do however remain at risk of developing acute otitis media and other mucosal infections that itself may warrant catch-up campaigns in this age group in the presence of only modest reduction in vaccine serotype colonization with immunization only directed at young infants. Our study is unable to establish whether there is any added benefit of a PCV catch-up campaign of older children in accelerating the timing and magnitude of indirect effect as postulated.33 Nevertheless, we identified an indirect effect on vaccine serotype NP colonization materialized within similar timelines and magnitude, in the absence of a catch-up campaign, compared with settings where catch-up campaigns have been implemented.12

There is limited information on pneumococcal NP colonization in settings with high prevalence of HIV, including conflicting data on whether infants born to HIV-infected mothers have higher rates of pneumococcal NP colonization compared with children born to HIV-uninfected mothers.34,35 In addition, no difference in the prevalence of pneumococcal colonization has been observed between HIV-infected and HIV-uninfected PCV-unvaccinated children,36,37 similar to that identified in our study. Although limited to self-reports only, the prevalence of HIV positivity among children in our study (3%) was similar to that recorded in a separate HIV survey undertaken in the area in 2007 (4.4%; 95% CI: 2.79–5.97).38 HIV-infected women reportedly have a higher prevalence and rate of overall and vaccine serotype pneumococcal colonization,16,35,39 as well as an increased risk of vaccine serotype IPD.33 The heightened risk of vaccine serotype colonization in HIV-infected women was corroborated by our study, despite, probable under reporting of HIV positivity status among adults in our study, ie, 10% compared with 23.9% for the general adult-population in the 2011 HIV-survey.40 Such underreporting in our study would have biased our results toward underestimating the effect of HIV positivity on the prevalence of pneumococcal colonization.

The likelihood of infant PCV immunization having an indirect protective effect against vaccine serotype IPD among HIV-infected women, including high HIV prevalence settings such as ours, was alluded to by a decrease in vaccine serotype colonization among 19- to 45-year-old HIV-infected women, which was of a greater magnitude compared with reportedly HIV-uninfected individuals. This reduction in vaccine serotype colonization among HIV-infected adults also lessened an earlier theoretical concern of ours, that HIV-infected women could remain a potential reservoir for vaccine serotype colonization and transmission in settings such as ours despite PCV in children. Caregivers, which included mothers, had higher vaccine serotype carriage than non-caregivers in period 1, which declined significantly in period 2. The close contact between caregivers and young children may explain the high carriage among caregivers in period 141,42 and the early herd immunity among caregivers in period 2.

While the increase in nonvaccine serotype colonization was anticipated among the age group eligible to have been vaccinated (ie, <2 years old),5,6,20,43 there was an unexpected decrease in nonvaccine serotype colonization among all age groups >12 years old. The reasons for this decline in nonvaccine serotype colonization following the introduction of infant PCV immunization remain to be explored further. To our knowledge, there is only one similar observation of decline in nonvaccine serotype and overall colonization among adults, which was reported from The Gambia, which as mentioned could have been, in part, attributed to intercurrent azithromycin prophylaxis between sampling periods.12 The only other studies, to our knowledge, which evaluated the effect of childhood PCV immunization on the epidemiology of NP colonization among adults was among Navajo Indians in United States15,44 and Alaskan Natives.27 Among Navajo Indians, no changes were observed in nonvaccine serotype colonization among adults postintroduction of childhood PCV7 immunization, despite an increase among childhood age groups who had been targeted for vaccination, while among Alaskan Natives there was an increase in nonvaccine serotype colonization among adults.27 The lack of an increase in nonvaccine serotype colonization among adults in the era of childhood PCV immunization may relate to most nonvaccine serotype strains being less efficient in colonizing healthy adults. This does not, however, explain the decline in nonvaccine serotype colonization observed among adults in our study.

Possible reasons as to why nonvaccine serotype colonization may have declined among individuals >12 years in our setting remain unclear. This may reflect coincidental temporal changes in circulation of these nonvaccine serotypes, although a similar decline would then possibly have been expected among younger children, unless the longer duration of pneumococcal colonization in children had masked this.1 A further possible explanation for the decline in nonvaccine serotype colonization among adults may include an increase in ART coverage in HIV-infected adults with AIDS, which has previously been associated with a lower risk of pneumococcal colonization following at least 1 year of ART.39 Other hypothetical reasons include that increased transmission of nonvaccine serotypes to adults may result in robust anamnestic responses against the nonvaccine serotypes. This could possibly reduce the acquisition and/or duration and subsequently likelihood of detection of these nonvaccine serotypes in adults. Such an anamnestic response may also be cross-protective against other nonvaccine serotypes to which they were already colonized. Despite the decrease in overall nonvaccine serotype among adults, serogroup 15 was an exception in having increased prevalence of colonization in children (5.8% versus 12.2%) as well as in adolescents/adults (3.3% versus 10.6%). This increase in serogroup 15 colonization, dominantly associated with serotype 15B, warrants ongoing monitoring in relation to changes in invasive disease due to this serogroup, especially in settings such as ours where serogroup 15 had contributed to 2–3% IPD among children and adults prior to PCV introduction.45–47 In addition, a trend toward a higher incidence of serotype 15A IPD in placebo recipients was observed in the phase III efficacy trial in South Africa, particularly among HIV-infected children.48 The importance of serogroup 15, which is not targeted in either the 10- or 13-valent licensed PCV or a 15-valent PCV currently being developed, in causing IPD associated with antibiotic-resistant strains in the era of PCV immunization has also been reported in Canada.49

Other common nonvaccine serotypes in period 2, which were associated with a high proportion of IPD prior to infant PCV immunization in South Africa, were serotypes 6A and 19A. Although PCV7 has been associated with cross-protection against serotype 6A IPD,50 we did not identify any changes in the overall proportion of individuals colonized by serotype 6A between periods 1 and 2 among children or older age groups in our study. We also distinguished between serotype 6A and 6C, as cross-protection associated with 6B inclusion in PCV has been shown for 6A but not for 6C.50 Our findings on 6A corroborate that of The Gambian study, where the prevalence of serotype 6A remained unchanged in children and adults following PCV immunization of children.12 Decline in serotype 6A colonization among children has, however, been reported in Massachusetts, USA. This was, however, only identified 6 years after PCV7 introduction and was associated with concomitant increase in 6C colonization.51 Serotype 19A, which increased in the United States and other countries after PCV introduction,52 did not increase in our setting and is unlikely to increase because the immunization program had subsequently transitioned from PCV7 to PCV13 in 2011. Serotype 3 was the only serotype more common among adults than children and its prevalence did not change across periods. In South Africa, serotype 3 is an important cause of IPD46,53 and among HIV-infected patients in Uganda, serotype 3 was the most prevalent serotype identified from oropharyngeal swabs.54

Limitations of study include that we were dependent on self-reporting of HIV infection status. This was predicated by resource constraints in undertaking informed testing for all study participants, as well as attempting to minimize any stigma being associated with the study if perceived to be HIV related. Our study was not powered to detect changes in the prevalence of individual serotypes; nevertheless, significant decreases were observed in colonization by serotypes 6B, 18C, 19F and 23F among <2-year-old children. In addition, our study only spanned a 2-year period, which may underestimate the longer term effects of childhood PCV immunization on the epidemiology of pneumococcal colonization in the community. Furthermore, we do not have any data on invasive disease from the same community, so as to determine what effect the direct and indirect changes associated with vaccine and nonvaccine serotype colonization had on the incidence of IPD.

In conclusion, this study demonstrates indirect protection against vaccine serotype colonization among adolescents and adults in a community with high underlying HIV infection, which was induced by only modest levels of PCV immunization targeted solely at infants as part of a routine immunization program. Although our study was done within 2 years of implementation of the PCV7 immunization program, the findings are strongly suggestive that PCV7 immunization targeted at only infants reduces transmission of the targeted vaccine serotypes in high-risk, rural African populations such as ours.


1. Gray BM, Converse GM 3rd, Dillon HC Jr. Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis. 1980;142:923–933
2. Syrjänen RK, Auranen KJ, Leino TM, et al. Pneumococcal acute otitis media in relation to pneumococcal nasopharyngeal carriage. Pediatr Infect Dis J. 2005;24:801–806
3. Ghaffar F, Friedland IR, McCracken GH Jr. Dynamics of nasopharyngeal colonization by Streptococcus pneumoniae. Pediatr Infect Dis J. 1999;18:638–646
4. O’Brien KL, Dagan R, Makela HPSiber GR, Klugman KP, Makela PH. Nasopharyngeal carriage. Pneumococcal Vaccines. 20081st ed Washington, DC American Society for Microbiology Press
5. Dagan R, Givon-Lavi N, Zamir O, et al. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9-valent pneumococcal conjugate vaccine to toddlers attending day care centers. J Infect Dis. 2002;185:927–936
6. O’Brien KL, Millar EV, Zell ER, et al. Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial. J Infect Dis. 2007;196:1211–1220
7. . Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease—United States, 1998–2003 MMWR. September 16, 2005;54:893–897
8. Whitney CG, Farley MM, Hadler J, et al.Active Bacterial Core Surveillance of the Emerging Infections Program Network. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003;348:1737–1746
9. Pilishvili T, Lexau C, Farley MM, et al.Active Bacterial Core Surveillance/Emerging Infections Program Network. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis. 2010;201:32–41
10. Cohen AL, Harrison LH, Farley MM, et al.Active Bacterial Core Surveillance Team. Prevention of invasive pneumococcal disease among HIV-infected adults in the era of childhood pneumococcal immunization. AIDS. 2010;24:2253–2262
11. Flannery B, Heffernan RT, Harrison LH, et al. Changes in invasive Pneumococcal disease among HIV-infected adults living in the era of childhood pneumococcal immunization. Ann Intern Med. 2006;144:1–9
12. Roca A, Hill PC, Townend J, et al. Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in the Gambia: a cluster-randomized trial. PLoS Med. 2011;8:e1001107
13. Kahn K, Tollman SM, Collinson MA, et al. Research into health, population and social transitions in rural South Africa: data and methods of the Agincourt Health and Demographic Surveillance System. Scand J Public Health Suppl. 2007;69:8–20
14. Oladoyindbo OS, Slabbert M, Khosa MG, et al. HAART Programme retention/outcomes among cohort of patients initiated on ARV’s in a community primary health care setting in rural South Africa. 2011Paper presented at: 5th SA Aids Conference Durban
15. Millar EV, Watt JP, Bronsdon MA, et al. Indirect effect of 7-valent pneumococcal conjugate vaccine on pneumococcal colonization among unvaccinated household members. Clin Infect Dis. 2008;47:989–996
16. Gill CJ, Mwanakasale V, Fox MP, et al. Impact of human immunodeficiency virus infection on Streptococcus pneumoniae colonization and seroepidemiology among Zambian women. J Infect Dis. 2008;197:1000–1005
17. O’Brien KL, Nohynek HWorld Health Organization Pneumococcal Vaccine Trials Carriage Working Group. . Report from a WHO working group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae. Pediatr Infect Dis J. 2003;22:133–140
18. Carvalho Mda G, Tondella ML, McCaustland K, et al. Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA. J Clin Microbiol. 2007;45:2460–2466
19. Dagan R, Givon-Lavi N, Zamir O, et al. Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day-care centers. Pediatr Infect Dis J. 2003;22:532–540
20. Mbelle N, Huebner RE, Wasas AD, et al. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J Infect Dis. 1999;180:1171–1176
21. Millar EV, O’Brien KL, Watt JP, et al. Effect of community-wide conjugate pneumococcal vaccine use in infancy on nasopharyngeal carriage through 3 years of age: a cross-sectional study in a high-risk population. Clin Infect Dis. 2006;43:8–15
22. Obaro S, Adegbola R. The pneumococcus: carriage, disease and conjugate vaccines. J Med Microbiol. 2002;51:98–104
23. Cheung YB, Zaman SM, Nsekpong ED, et al. Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian children who participated in a 9-valent pneumococcal conjugate vaccine trial and in their younger siblings. Pediatr Infect Dis J. 2009;28:990–995
24. Givon-Lavi N, Fraser D, Dagan R. Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings. Pediatr Infect Dis J. 2003;22:524–532
25. Flasche S, Van Hoek AJ, Sheasby E, et al. Effect of pneumococcal conjugate vaccination on serotype-specific carriage and invasive disease in England: a cross-sectional study. PLoS Med. 2011;8:e1001017
26. Spijkerman J, van Gils EJ, Veenhoven RH, et al. Carriage of Streptococcus pneumoniae 3 years after start of vaccination program, the Netherlands. Emerg Infect Dis. 2011;17:584–591
27. Hammitt LL, Bruden DL, Butler JC, et al. Indirect effect of conjugate vaccine on adult carriage of Streptococcus pneumoniae: an explanation of trends in invasive pneumococcal disease. J Infect Dis. 2006;193:1487–1494
28. Scott JR, Millar EV, Lipsitch M, et al. Impact of more than a decade of pneumococcal conjugate vaccine use on carriage and invasive potential in Native American communities. J Infect Dis. 2012;205:280–288
29. Pelton SI, Loughlin AM, Marchant CD. Seven valent pneumococcal conjugate vaccine immunization in two Boston communities: changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates. Pediatr Infect Dis J. 2004;23:1015–1022
30. Mackenzie G, Carapetis J, Leach AJ, et al. Indirect effects of childhood pneumococcal vaccination on pneumococcal carriage among adults and older children in Australian Aboriginal communities. Vaccine. 2007;25:2428–2433
31. Hill PC, Akisanya A, Sankareh K, et al. Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian villagers. Clin Infect Dis. 2006;43:673–679
32. Madhi SA, Petersen K, Madhi A, et al. Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children. Pediatr Infect Dis J. 2000;19:1141–1147
33. Pelton SI, Weycker D, Klein JO, et al. 7-Valent pneumococcal conjugate vaccine and lower respiratory tract infections: effectiveness of a 2-dose versus 3-dose primary series. Vaccine. 2010;28:1575–1582
34. Abdullahi O, Karani A, Tigoi CC, et al. The prevalence and risk factors for pneumococcal colonization of the nasopharynx among children in Kilifi District, Kenya. PLoS One. 2012;7:e30787
35. Nunes MC, Shiri T, van Niekerk N, et al. Acquisition of Streptococcus pneumoniae in pneumococcal conjugate vaccine-naïve South African children and their mothers. Pediatr Infect Dis J. 2013;32:e192–e205
36. Cardoso VC, Cervi MC, Cintra OA, et al. Nasopharyngeal colonization with Streptococcus pneumoniae in children infected with human immunodeficiency virus. J Pediatr (Rio J). 2006;82:51–57
37. Polack FP, Flayhart DC, Zahurak ML, et al. Colonization by Streptococcus penumoniae in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2000;19:608–612
38. Kimani-Murage EW, Norris SA, Pettifor JM, et al. Nutritional status and HIV in rural South African children. BMC Pediatr. 2011;11:23
39. Nicoletti C, Brandileone MC, Guerra ML, et al. Prevalence, serotypes, and risk factors for pneumococcal carriage among HIV-infected adults. Diagn Microbiol Infect Dis. 2007;57:259–265
40. Gomez-Olive FX, Clark SJ, Houle B, et al. The prevalence of HIV among adults 15 and older in Rural South Africa. AIDS Care. 2013;25:1122–1128
41. Hendley JO, Sande MA, Stewart PM, et al. Spread of Streptococcus pneumoniae in families. I. Carriage rates and distribution of types. J Infect Dis. 1975;132:55–61
42. Regev-Yochay G, Raz M, Dagan R, et al. Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings. Clin Infect Dis. 2004;38:632–639
43. Obaro SK, Adegbola RA, Banya WA, et al. Carriage of pneumococci after pneumococcal vaccination. Lancet. 1996;348:271–272
44. Scott JA. The preventable burden of pneumococcal disease in the developing world. Vaccine. 2007;25:2398–2405
45. Huebner RE, Wasas AD, Klugman KP. Trends in antimicrobial resistance and serotype distribution of blood and cerebrospinal fluid isolates of Streptococcus pneumoniae in South Africa, 1991–1998. Int J Infectious Dis. 2000;4:214–218
46. Karstaedt AS, Khoosal M, Crewe-Brown HH. Pneumococcal bacteremia in adults in Soweto, South Africa, during the course of a decade. Clin Infect Dis. 2001;32:610–614
47. Silberbauer EJ, Ismail N, von Gotteberg A, et al. Serotype and antimicrobial profile distribution of invasive pneumococcal isolates in the pre-vaccine introduction era in Pretoria, South Africa, 2005 through 2009. Diagnostic Microbiology and Infectious Disease. 2011;71:309–311
48. Klugman KP, Madhi SA, Huebner RE, et al.Vaccine Trialists Group. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med. 2003;349:1341–1348
49. Wierbowski AK, Karlowsky JA, Laing N, et al.The Canadian Antimicrobial Resistance Alliance (CARA) UoMaHSC. Macrolide-resistant Streptococcus pneumoniae (Mac-R SPN) in Canada: 1998 to 2008 experience. 50th ICAAC. September 12–15, 2010 Boston, MA
50. Park IH, Moore MR, Treanor JJ, et al.Active Bacterial Core Surveillance Team. Differential effects of pneumococcal vaccines against serotypes 6A and 6C. J Infect Dis. 2008;198:1818–1822
51. Nahm MH, Lin J, Finkelstein JA, et al. Increase in the prevalence of the newly discovered pneumococcal serotype 6C in the nasopharynx after introduction of pneumococcal conjugate vaccine. J Infect Dis. 2009;199:320–325
52. Huang SS, Hinrichsen VL, Stevenson AE, et al. Continued impact of pneumococcal conjugate vaccine on carriage in young children. Pediatrics. 2009;124:e1–e11
53. Jones N, Huebner R, Khoosal M, et al. The impact of HIV on Streptococcus pneumoniae bacteraemia in a South African population. AIDS. 1998;12:2177–2184
54. Blossom DB, Namayanja-Kaye G, Nankya-Mutyoba J, et al. Oropharyngeal colonization by Streptococcus pneumoniae among HIV-infected adults in Uganda: assessing prevalence and antimicrobial susceptibility. Int J Infect Dis. 2006;10:458–464

pneumococcal vaccination; nasopharyngeal colonization; rural setting; high HIV prevalence

Supplemental Digital Content

© 2013 by Lippincott Williams & Wilkins, Inc.