advanced search

<< Back To Home

NEW THIS SATURDAY: CARRIAGE OF M. PNEUMONIAE IN SYMPTOMATIC AND ASYMPTOMATIC CHILDREN

Wednesday, 29th of May 2013

·       CARRIAGE OF MYCOPLASMA PNEUMONIAE IN THE UPPER RESPIRATORY TRACT OF SYMPTOMATIC AND ASYMPTOMATIC CHILDREN: AN OBSERVATIONAL STUDY

Abstract below; full text, with graphics, is at

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001444

Background

Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods.

Methods and Findings

This study was conducted at the Erasmus MC–Sophia Childrens Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%–25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%–20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo.

Conclusions

Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection.

Editors Summary

Background

Pneumonia (a form of acute respiratory infection) is the single largest cause of death in children worldwide, killing an estimated 1.2 million children aged five and under every year, particularly in South Asia and sub-Saharan Africa. In these settings, bacterial infections with Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of bacterial pneumonia. However, in high-income settings, bacterial infection with Mycoplasma pneumoniae is a major cause of upper and lower respiratory tract infections in children: over one-third of childhood cases of community-acquired pneumonia that require admission to a hospital are caused by M. pneumoniae. Currently, diagnosis of M. pneumoniae infections relies on the detection of antibodies against M. pneumoniae in the blood or detection of bacterial DNA in samples from the upper respiratory tract through polymerase chain reaction (PCR) tests.

Why Was This Study Done?

Other bacteria, such as Streptococcus pneumoniae, are commonly present in children without causing infection, a situation known as asymptomatic carriage. However, to date, it is unknown whether M. pneumoniae is also commonly carried in the upper respiratory tract of children without causing symptoms or leading to infection. The possibility of asymptomatic carriage of M. pneumoniae could have major implications for the interpretation of the results of diagnostic tests and also for clinical management. So in this study conducted in The Netherlands, the researchers investigated whether asymptomatic carriage of M. pneumoniae exists and also whether symptomatic infection could be differentiated from asymptomatic carriage by current diagnostic methods.

What Did the Researchers Do and Find?

Between 2008 and 2011, the researchers recruited children aged between three months and 16 years attending a hospital in Rotterdam for an elective surgical procedure (asymptomatic group) or admitted with a respiratory tract infection (symptomatic group). All children had blood tests and respiratory samples (nasopharyngeal swab) taken on admission and were tested for other pathogens. The researchers invited children who tested positive for M. pneumoniae by PCR to attend for further follow-up and tested them monthly for the presence of M. pneumoniae DNA in the upper respiratory tract until the test was negative on two occasions. Using these methods, the researchers recruited 726 children over the study period—405 in the asymptomatic group and 321 in the symptomatic group. The researchers found that the prevalence of M. pneumoniae did not differ between the asymptomatic group and the symptomatic group, with prevalences of 21.2% and 16.2%, respectively (the prevalence of M. pneumoniae also did not differ significantly between those with lower versus upper respiratory infection). There were also no differences in prevalence in the asymptomatic and symptomatic groups when diagnosed using blood tests. The researchers found a high rate of multiple, coexisting bacterial and viral pathogens in both asymptomatic and symptomatic children: two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Furthermore, season and the year of enrollment affected the prevalence of M. pneumoniae in the asymptomatic group, ranging from 3% during the spring of 2009 to 58% during the summer of 2010. Finally, of the 21 children from the asymptomatic group who participated in the follow-up study, 15 (71%) tested negative within one month, and in the symptomatic group, 19 of 22 children (86%) tested negative after the first visit.

What Do These Findings Mean?

These findings show that M. pneumoniae is carried at high rates in the upper respiratory tracts of healthy children, and that this asymptomatic carriage cannot be differentiated from symptomatic respiratory tract infection by diagnostic tests (serology or PCR). As the prevalence of M. pneumoniae varied between year and season, carriage of M. pneumoniae may follow a cyclic epidemic pattern. This study is from a single study site in one city in The Netherlands, with a relatively small number of children, and so these findings may not be generalizable to other populations. However, as this study suggests that current diagnostic tests do not discriminate between carriage and infection, clinicians may need to reconsider the clinical significance of a positive test result. Future studies are needed to address this diagnostic challenge and also to investigate possible factors that may affect the progression of asymptomatic carriage of M. pneumoniae to symptomatic infection.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1​001444.

• MicrobeWiki has more information on M. pneumoniae
• Lab Tests Online explains current tests for M. pneumoniae

Citation: Spuesens EBM, Fraaij PLA, Visser EG, Hoogenboezem T, Hop WCJ, et al. (2013) Carriage of Mycoplasma pneumoniae in the Upper Respiratory Tract of Symptomatic and Asymptomatic Children: An Observational Study. PLoS Med 10(5): e1001444. doi:10.1371/journal.pmed.1001444

Academic Editor: Keith P. Klugman, Emory University, United States of America

Received: September 5, 2012; Accepted: April 4, 2013; Published: May 14, 2013

Copyright: © 2013 Spuesens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: “Stichting Vrienden van het Sophia,” Rotterdam, The Netherlands (www.vriendensophia.nl). AMR was supported for this study by an Erasmus MC Fellowship Award (http://www.erasmusmc.nl/research), a Clinical Fellowship Award of The Netherlands Organisation for Health Research and Development (http://www.zonmw.nl/en/), and a Fellowship Award of the European Society for Paediatric Infectious Diseases (http://www.espid.org/award_content.aspx?​Group=Awards&Page=Fellowship). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: At the time of the study, AB was a paid member on the Cepheid Scientific Advisory Board in which he is no longer taking part. After the study, AB joined bioMérieux, a company specializing in infectious disease diagnostics. ADO is Head of the department of Virology of the Erasmus MC. He is involved in or with many initiatives within the virology field. This involvement ranges from expert advice to various international organisations involved in the area of general human and veterinary health to advising spin-out companies of the Erasmus University Medical Center Rotterdam that are endeavouring to bridge the gap between scientific discovery/knowledge and putting these to practical use in society. For purposes of transparency and to avoid of possible conflicts of interest, Professor Osterhaus discloses all his interests in matters related, directly or indirectly, to his position as head of the Department of Virology of Erasmus MC. Professor Osterhaus has share certificates in Viroclinics Biosciences B.V. AMR received fees for speaking from Abbott. AMR has received grants from the NutsOhra Foundation, The Netherlands, and the Thrasher Fund, USA. All other authors have declared that no competing interests exist.

Abbreviations: RTD, respiratory tract disease; RTI, respiratory tract infection; URT, upper respiratory tract