Risk Factors for Pneumococcal Carriage in Day Care Centers

A Retrospective Study During a 10-year Period

Abstract

In this retrospective epidemiologic study, we present pneumococcal carriage data from 109 Swedish day care centers over a period of 10 years. Aspects of season, age, personnel and group size were studied. We found a significant seasonal variation in pneumococcal carriage. Group size was a significant risk factor for pneumococcal carriage. Pneumococcal carriage was 4.5 % in personnel.

Pediatric nasopharyngeal flora is considered the largest reservoir for Streptococcus pneumoniae and nasopharyngeal carriage is a prerequisite for infection.¹ The rate of acquisition depends on the age of the host but varies in relation to demographic factors such as geographic area, genetic background, smoking, socioeconomic conditions, family size (especially the number of siblings), income, recent antibiotic use and vaccination.¹ Day care centers (DCCs) provide an optimal environment for horizontal spread of pneumococci. Children cared for at home have significantly reduced carriage rate of pneumococci.²

Large epidemiologic studies on pneumococcal carriage in this environment are often related to pre- or postvaccination carriage or antimicrobial resistance. The South Swedish Pneumococcal Intervention Project (SSPIP) enabled us to study the prevalence of pneumococcal nasopharyngeal carriage in personnel and children attending DCCs and the impact of factors such as group size, age and season.

MATERIAL AND METHODS

Study Design

This retrospective epidemiologic study is based on pneumococcal carriage data from the SSPIP. The SSPIP was initiated in January 1995 to restrict dispersion of Penicillin nonsusceptible pneumococci (PNSP) with high MIC values and has been described in detail elsewhere.³ In short, when an individual attending a DCC was found to be nasopharyngeal carrier of a PNSP (index case) with a MIC of PcG ≥0.5 mg/L (PNSP_0.5), a screening for pneumococcal carriage was started at the DCC with an aim to find more cases of PNSP_0.5. The cutoff 0.5 mg/L was chosen to have a marginal to the resistant strain (>2.0 mg/L) where treatment failure with penicillin would be anticipated. PNSP_0.5 carriers were suspended and discovery of new contact cases often caused the DCC to close down temporarily. In parallel, a second screening was performed and the DCC did not open again for attendees until they could show a culture yielding no growth of PNSP_0.5. All the children were screened in a healthy state at the DCC. Children absent at the time of the screening were screened separately before returning to the DCC.

Screened children aged 0–7 years and personnel at DCCs in the cities of Malmö, Trelleborg and their surrounding areas with a total of 346,429 (2000) to 394,307 (2010) inhabitants were included. The study period was from June 2000 to December 2010. The following data were extracted from paper files at the Regional Department of Communicable Disease Control in Skåne County: age, gender, number of attendees at the DCC department, month and year for screening and culture result (growth of pneumococci or not, regardless of resistance).

Children and personnel in 112 DCC were screened. Three DCCs were excluded; 2 were screened by a private general practitioner whose results we could not access and 1 was excluded because the index case did not carry PNSP_0.5. In total, 6863 cultures (109 index cases) were included in the study of which 5558 were obtained from children and 1305 were from personnel.

Microbiology

Nasopharyngeal swabs were obtained and cultured according to Swedish standard methods, described in detail by Melander et al.³ The samples were grown on blood agar plates, and pneumococci were identified by colony morphology and susceptibility to optochin.

Statistics

Statistical analyses were performed using the software R, version 2.14.1 and SPSS 20. Dichotomous outcomes were analyzed using logistic regression; checks for linearity of continuous covariates were done using generalized additive model.

Ethical Approval

This study was approved by the Regional Ethical Review Board in Lund, Sweden (2011/65).

RESULTS

Forty-two percentage of the screened children were pneumococcal carriers and younger children were significantly more often carriers. Among the children, 49% (n = 2754) were girls and the median age was 44 (6–93) months. Of the cultured children, 42% (n = 2387) were carriers of pneumococci. The total number of cultures (children and personnel) and the carriage rate of pneumococci per year varied significantly during the study period (P < 0.001 and P < 0.001; see Figure, Supplemental Digital Content 1, https://links.lww.com/INF/B734, where sample and carriage rate in children and variation in carriage rate are presented by year). The proportion of pneumococcal carriage decreased significantly (P = 0.001) with age (see Figure, Supplemental Digital Content 2, https://links.lww.com/INF/B735, which demonstrates the carriage rate by age). The carriage rates were 57% the second year in life, 53% the third, 44% the fourth, 34% the fifth, 30 % the sixth and 27% the seventh year of life.

Significant Seasonal Variation of Pneumococcal Carriage

Among sampled children, a significant seasonal variation in pneumococcal carriage was noted (P < 0.001) with a deep dip in carriage rate in July and August (Fig. 1) and smaller dips in January and April. The number of children in the DCC group is a risk factor for pneumococcal carriage.

FIGURE 1: The log-odds ratios for different months from a multiple logistic regression adjusting for screening occasion, year, month, age of individual child and number of children per department. The relationship is statistically significant (P < 0.001, χ² = 73.8, df = 8.95) and 95% approximate CIs are plotted (dashed lines). School holidays are marked in the bottom of the figure: Christmas holidays are week 52 and 1, Easter holiday with 1 week off starting from 15 March to 15 April and summer vacations from the middle of June to the middle of August.

Group size was a significant risk factor for pneumococcal carriage (P = 0.001) when compensation for the other known risk factors such as age (P < 0.001), month of culture (P < 0.001) and screening occasion (first or second screening; P < 0.001) was executed. The relationship was not linear (see Figure, Supplemental Digital Content 3, https://links.lww.com/INF/B736).

Personnel were seldom colonized with pneumococci compared with children. During the study, 1305 personnel were cultured, 4.5 % (n = 59, 95% confidence interval: 3.7–6.2%) had a positive culture for pneumococci.

DISCUSSION

This retrospective study is made from a unique and large material of nasopharyngeal cultures taken during more than 10 years in Skåne County in a structured form as part of the SSPIP. A weakness in this study is the fact that there was a variation in the number of cultures taken every year. This variation can be explained by a higher incidence of index cases with PNSP_0.5 over a few years causing a more extended screening activity in the DCCs. The pneumococcal isolates were not saved making it impossible to perform serotyping or to make genetic analyses to study these factors. Vaccination with pneumococcal conjugate vaccine (PCV-7) was introduced in the child immunization program in January 2009 and after May 2010 PCV-10 was used. We found a significant variation in carriage rate over the study period. This may partly be due to the variation in yearly number of cultures taken. No decline was noted after PCV introduction. The impact of PCV on colonization rate during the study period was probably very small because a child has to be 1 year of age to attend a DCC in Sweden.

We found that group size is a significant risk factor for pneumococcal carriage even after compensating for confounding factors in a multivariate analyze. Theoretically, children in a large day care group are at risk to be more exposed to pneumococci and are more likely to be or become carriers. The relation was not linear; we speculate that this is due to the fact that larger groups often are divided into subgroups. In a study by Karlsson et al⁴ using a individual-based network model, the size of DCC group seems to possess a very important role in pneumococcal transmission dynamics, but clinical data supporting this model are scarce.

We found significant seasonal variation in pneumococcal carriage in the DCC. Earlier studies show divergent results in this aspect.^5,6 Studies proving a significant seasonal variation in pneumococcal disease^6,7 show that the carriage rate of pneumococci increase during virus and influenza season. However, in our study, the peak of the influenza season varied during the studied years and is therefore not a likely explanation for this finding. We noted a significant lower carriage rate after major holidays and leaves. Even though January is a month with a high incidence of viral infections, there was a dip in carriage rate. We believe that the seasonal variation mainly is due to absence from the DCC environment.

The pneumococcal carriage rate in children decreased significantly with age as shown in other studies.³ On the other hand, data on pneumococcal carriage in personnel at DCCs are scarce; the number of cultures is often few and collected over a short period. Auranen et al⁸ found a carriage rate of 22 % in DCC personnel in Denmark, but only 37 personnel were included. In our study, 4.5% of the 1305 personnel were colonized with pneumococci. This should be compared with carriage rates of only a few percent in the normal adult population in studies from Northern Europe.⁹

In summary, this study is made from an unique and large material of nasopharyngeal cultures from DCC personnel and children in a period of >10 years. DCC group size proved to be a risk factor for pneumococcal carriage. To the best of our knowledge, group size has not been proven to be a risk factor for pneumococcal carriage even though this has been believed on theoretical grounds. We also suggest that the seasonal variation in pneumococcal carriage is due to absence from the DCC. These findings support the thesis that crowding in the DCC should be avoided if dispersion of pneumococci should be restricted. Carriage rate in personnel was found to be higher compared with a normal population.

ACKNOWLEDGEMENTS

The authors thank Rosmarie Fält at the Regional Department of Communicable Disease Control in Skåne County for support with finding and interpreting the data from paper files. The authors also thank Fredrik Nilsson at the Region Skåne Competence Center for support with the statistical analysis.