Invasive Pneumococcal Disease in Refugee Children, Germany

Refugee children in Germany are not routinely given a pneumococcal conjugate vaccine. Cases of invasive pneumococcal disease (IPD) in 21 refugee children were compared with those in 405 Germany-born children for 3 pneumococcal seasons. Refugee children had significantly higher odds of vaccine-type IPD and multidrug-resistant IPD than did Germany-born children.


The Study
In this retrospective, unmatched case-control study, we considered all 514 isolates from children (<16 years of age) with IPD in the GNRCS collection isolated during July 1, 2014-June 30, 2017, for inclusion in the analysis. We defined a case of IPD as Streptococcus pneumoniae (identified by optochin sensitivity and bile solubility) isolated from a normally sterile site. For the analysis, case isolates were from refugee children with IPD, and control isolates were from Germany-born children with IPD. Refugee status was documented by GNRCS personnel in conjunction with determining vaccination status, as described elsewhere (9). Because identification of refugee status was tied to the determination of vaccination status, all children with an unknown vaccination status were excluded.
We determined serotype by using Neufeld's Quellung reaction and antimicrobial drug resistance by MIC testing, as previously described (10). Antimicrobial drug resistance was defined by the Clinical and Laboratory Standards Institute 2015 breakpoints (11).
We calculated odds ratios (ORs) and 95% CIs with R software version 3.4.0 (https://www.r-project.org/foundation) using Firth's bias-reduced logistic regression and adjusted for age and sex using the logistf package (12). We assigned statistical significance to ORs for which the 95% CI did not exceed 1. Variables considered in the analysis were age, sex, vaccination status, and refugee status of the patient, as well as the serotype and antimicrobial drug resistance profile of the isolate.

Conclusions
Refugee children in Germany are at greater risk of contracting vaccine-type IPD, antimicrobial drug-resistant IPD, and antibiotic-resistant vaccine-type IPD. As such, a PCV program for refugee children may be worth considering in Germany. Vaccination in newly arrived refugees presents an opportunity to cost-effectively, safely, and humanely protect a vulnerable population from negative health outcomes resulting from vaccine-preventable diseases (13). Given that children in Germany with insecure residence status are twice as likely to be incompletely vaccinated (2), a PCV program for refugee children in Germany might require additional follow-up measures to ensure consistency and provide sufficient protection, particularly because PCV dosing in Germany-born children with IPD has been lax (9). A PCV program could help reduce antimicrobial drugresistant pneumococcal infections, the carriage of resistant strains (14), overall antimicrobial drug use, and the prevalence of resistance genes within the pneumococcal population (15).
The IPD case numbers from refugees are low, but the proportion of vaccine-type isolates and antimicrobial drug-resistant isolates from refugee children are nevertheless much higher than those of Germany-born children. Children of unknown vaccination status (n = 109) were excluded from the analysis; because of the small sample sizes, if even 1 additional child with vaccine-type IPD per year was a refugee, the effects we describe would be magnified (online Technical Appendix Table 3).
The risk of vaccine-type IPD is low among fully vaccinated children in Germany. However, among unvaccinated and undervaccinated children, a reintroduction of vaccine-type pneumococci may result in increased risk of pneumococcal disease. Without intervention, refugee children may continue to constitute a special risk group for vaccine-type IPD and antimicrobial drug-resistant IPD in Germany. Fully immunizing these children against vaccine-type IPDs may help reduce the risk for IPD illness and death in Germany.

About the Author
Mrs. Perniciaro is a doctoral candidate at the German National Reference Center for Streptococci, University Hospital RWTH Aachen. Her interests include invasive pneumococcal disease epidemiology and pneumococcal conjugate vaccine effectiveness.