A prospective cohort study was performed among children aged 2–35 months who were current patients at the Niños Primeros en Salud (NPS) program at the Centro de Salud Divina Providencia in Consuelo, DR. Consuelo is a rural municipality in southeastern DR, with a total population of about 30 000, more than 20% of whom are <9 years of age [14]. The NPS program represents a partnership with the Children’s Hospital of Philadelphia and serves children under age 5 years in 7 neighborhoods (barrios) in this community. Recruitment, enrollment, and data collection took place between November 2016 and July 2017.

Participants were recruited either at a clinic visit or during a home visit by an NPS doctor or nurse. Home visits are routinely conducted twice weekly as part of the NPS program. Patients with active signs of acute infection (fever) at the time of NP swab collection were excluded, as well as those children with craniofacial abnormalities that would limit NP sample collection. Only children aged 2–35 months in November 2016 were included, because this was the age group eligible for PCV13 vaccine receipt.

After informed consent and eligibility screening, study staff administered an enrollment questionnaire to the caretaker/parent, obtained an NP swab from the participating child, and conducted a chart review to confirm vaccination status and illness history. Charts at NPS included details for vaccines received at NPS, as well as data for those received at other government immunization sites (transcribed from the patient’s government-issued vaccine card). Four to 6 months after enrollment, all study participants received a second visit for completion of a follow-up questionnaire, collection of a second NP swab, and chart review to confirm any additional doses of PCV13 received and illness history since enrollment. Follow-up visits were either conducted on the NPS clinic premises or as a home visit. Both questionnaires included sociodemographic characteristics and clinical data known to be potential factors associated with pneumococcal colonization in prior studies [13, 15, 16]. The characteristics explored were child age, barrio (neighborhood) of residence, breastfeeding status, presence of other children in the home, presence of a wood- or coal-burning stove, smoker in the home, recent history of upper respiratory infection (URI) or hospitalization, recent antibiotic use (including name of antibiotic if known or documented), and history of chronic illness such as asthma. Recent URI was defined as cough or nasal congestion in the last 2 weeks, and recent hospitalization or antibiotic use was defined as occurring within the previous 8 weeks. The baseline questionnaire assessed additional parameters regarding vaccine knowledge and barriers, including caregiver’s previous receipt of vaccination counseling, awareness of the pneumococcal vaccine, experience of vaccine shortage, and barriers to vaccination.

Questionnaires were administered initially on paper and later transferred to a database on the Research Electronic Database Capture (REDCap) system [17].

This study among young children in a rural community found high rates (60%) of NP carriage of S. pneumoniae at both initial and follow-up sample collections. These rates, even 3 years after PCV13 introduction, were higher than the prevaccine colonization rate of 40% observed in Brazil among children aged 12–23 months, using the same laboratory methods [21].

Community NP carriage rates have not previously been reported in the DR, and this is 1 of only 2 studies to examine pneumococcal serotype distribution after PCV13 introduction [12]. Despite its inclusion in the national immunization program 3 years prior to this study, PCV13 coverage was low in this rural study population, with 52% and 57% UTD for age at initial and follow-up visits, respectively. This is consistent with 2016 findings among an urban pediatric population in Santo Domingo, where 44% of hospitalized children age-eligible to have received ≥1 dose of PCV13 vaccine were UTD for age [12]. Series completion rates were also low: When restricting to children aged ≥12 months, only half of eligible subjects had received all 3 doses at either sample (40/80 [50%] at sample 1 and 48/95 [51%] at sample 2). These low coverage rates stand in contrast to vaccination rates for other routine childhood immunizations in the DR, for example, 84% coverage for diphtheria, tetanus, and pertussis vaccine and 80% coverage for polio [22]. Lower rates of PCV13 vaccination are likely due to its relatively recent introduction (2013) into the extended immunization program compared to other vaccines, and its high implementation costs borne by the DR government, which provides all childhood vaccines [23]. Importantly, low coverage rates may limit the potential population-level impact of vaccination, contributing to the high carriage rates observed in this study.

The most prevalent VTs were 19F, 23F, 6B, and 19A, and the most common nonvaccine serotypes were 15B/C, 11A, and 34. Of the 13 serotypes included in PCV13, no samples were positive for serotype 1, 4, 5, 7F, or 9V. In 1 pre-PCV13 study of IPD in hospitalized Dominican children, the most common serotypes identified were 14, 1, 3, and 6A/6B [11]. Post-PCV13, a case-control study of IPD in the same Dominican hospital most frequently identified serotypes 6A/6B, 14, 3, and 19A [12]. Similar serotype patterns both pre- and post-PCV13 introduction likely reflect the low vaccination coverage of PCV13 in this pediatric community. As this study examined NP colonization in healthy children rather than isolates in subjects with IPD, the higher prevalence of serotypes with less invasive potential (such as 15B/C and 11A) is not surprising [10]. Additionally, serotype 19A carriage has been shown to persist in communities even >5 years after PCV13 introduction, which is consistent with this study’s findings [24].

Being UTD for age at sample 1 was also associated with lower odds of both overall and VT colonization. Receipt of all 3 recommended doses of PCV13 among children ≥12 months was associated with lower odds of VT colonization at sample 1, even after adjusting for antibiotic use in the prior 8 weeks. These associations were not found at sample 2. Partial vaccination did not have statistically significant association with VT colonization status, except for children aged ≥12 months who had received 2 doses at sample 1 (OR, 7.10; Fisher exact P < .01).

A higher prevalence of VT colonization was observed from sample 1 to sample 2 for both children UTD with vaccination (18% vs 27%) and fully vaccinated children (10% vs 25%). This was not observed for children who were not UTD (VT prevalence 37% at sample 1 vs 29% at sample 2) or were not fully vaccinated for age (45% vs 26%). The reasons for these differences are unclear. NP colonization in young children is dynamic and highly influenced by their household and community [13]. The majority of children (92 [78%]) did not change vaccination status between samples 1 and 2, so these differences in colonization likely reflect other factors outside of vaccination status, such as colonization prevalence within the subject’s family or surrounding social circle. Recent URI, reported by the majority of subjects (83% and 70% in samples 1 and 2, respectively) may also have influenced colonization rates, as the composition of existing microflora in the upper respiratory tract is known to influence the success of pneumococcal colonization [5].

The role played by the seasonality of pneumococci is also unclear. As observed in other countries, IPD peaks during the rainy season [25]. Sample 2 collection occurred during the months of May and July (months of heavier rainfall), whereas sample 1 collection occurred between November and January (typically drier months). Therefore, seasonality may have played a role in the differences in VT colonization that were observed, independent of vaccination status.

Emerging studies in low- and middle-income countries (LMICs) have documented high NP carriage rates of VT serotypes among vaccinated individuals, even years after PCV13 introduction [26]. All 4 fully vaccinated subjects colonized by VT at sample 1 retained carriage at sample 2. Though 3 of the 12 fully vaccinated subjects with VT carriage at sample 2 had received an interim dose of vaccine, 2 retained carriage by the same VT serotype. Studies in various settings have demonstrated that PCVs have a greater impact on colonization incidence (carriage acquisition) than on carriage clearance [9, 27]. More data are needed from LMICs like the DR, where colonization rates are high, to better understand the drivers of persistent colonization postvaccination.

The overall high rate of colonization by VT serotypes in sample 1 and sample 2 is concerning because it suggests ongoing transmission in the community. Inconsistent or heterogeneous vaccination can create “pockets of persistence” in pneumococcal colonization, similar to this study’s findings [13].

Multiple studies have shown that a booster dose given after 12 months of age is important for overall immunity and may actually be the most important dose of the pneumococcal vaccine series [28]. In the study population, the majority of subjects were >12 months of age (64% and 81% at samples 1 and 2, respectively) and therefore eligible for 3 doses, but half were missing the third dose of vaccine. Considering the clinical importance of the third dose on immunity, it is important to understand barriers to immunization and reasons for noncompletion of the series. One-third of mothers reported facing a lack of vaccine supply when they took their children to be immunized.

This study had several limitations. Specimens had to be transported not only from the rural site of collection to the capital city, but also from the DR to the US. Some pneumococcal colonies could have been missed in this process. Attempts to mitigate this risk were made by following laboratory standard protocols established by the CDC, as well as by reculturing a proportion of negative samples (20 samples [42%]) to assess for missed positives. All remained negative, indicating solid methodology and consistency across both laboratory sites.

The study was also limited by its rural setting, thus limiting generalizability. Risk factors may be different in this cohort compared with the rest of the Dominican population. More information is needed on serotype distribution across different community types in the DR. However, the low PCV13 coverage found in this study is similar to what was found in Santo Domingo and also similar to the World Health Organization/United Nations Children’s Fund coverage estimates [22].

Last, the study population was small and at times was not sufficiently powered to show statistically significant associations between clinical or sociodemographic factors and colonization. The small cohort size, coupled with existing low vaccination coverage in this population, may account for the inconsistent association between colonization and vaccination status noted from sample 1 to sample 2. This was intended to be a pilot study to provide baseline data for future larger-scale studies.

Future studies could inform continued vaccination efforts and monitor pneumococcal serotype distribution. Responding to the need for greater access to pneumococcal vaccines, the DR immunization program (Programa Ampliado de Inmunización) has taken steps to begin a catch-up campaign. This will provide all children 1–4 years of age with a booster dose of PCV13, regardless of previous vaccination status. Based on these findings, this campaign has the potential for great impact on VT pneumococcal NP carriage in Dominican children.

Supplementary materials are available at The Journal of Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.