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Volume 20, Number 2—February 2014

Nasopharyngeal Bacterial Interactions in Children

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To the Editor: Xu and colleagues (1) examined the nasopharyngeal bacterial colonization rates in children with acute otitis media (AOM) and in healthy children. They found that Haemophilus influenzae colonization was competitively associated with Streptococcus pneumoniae and Morexella catarrhalis colonization in children with AOM but was not associated with S. pneumoniae and M. catarrhalis colonization in healthy children. We have a serious concern regarding their analysis.

The authors calculated odds ratios (ORs) by considering a bacterial colonization as an outcome variable and another bacterial colonization as an exposure variable. They considered an OR >1 as the presence of synergistic associations between bacteria (i.e., co-colonization is more likely to occur than it would by chance) and OR <1 as the presence of competitive associations (i.e., co-colonization is less likely to occur than it would by chance). This inference may be justified in a population-based cross-sectional study. If 2 bacterial colonizations occur independently in a stationary population, the prevalence of co-colonization will be the product (multiplication) of each prevalence, and the OR between 2 bacterial colonizations in the population (ORpop) will be 1 (Technical Appendix).

However, the authors enrolled their case-patients according to clinical signs (i.e., AOM or healthy). Let us assume that case-patients are enrolled from a population of children during a time period of t. Let rc be the risk for enrollment (that is, of developing the disease) among colonized children and rn be the risk for enrollment among noncolonized children. The OR among the enrolled case-patients (ORcase-patient) becomes rn/rc, which is the reciprocal of the risk ratio (RR) of developing the disease (RR = rc/rn) (online Technical Appendix). Usually, RR is >1 for diseased children and <1 for healthy children. Therefore, even in this independent colonization scenario, ORcase-patient becomes <1 (“pseudo-competitive associations”) in diseased children, and ORcase-patient becomes >1 (“pseudo-synergistic associations”) in healthy children. This is probably what the authors have observed in the study.

We cannot infer an association of multiple bacterial colonizations in a population despite an observed association in the diseased (or healthy) children, and this association is widely misunderstood (24). The authors’ discussion regarding a potential emergence of H. influenzae, associated with AOM, after the introduction of pneumococcal conjugate vaccine is thus unjustifiable.


Motoi SuzukiComments to Author , Bhim Gopal Dhoubhadel, Lay Myint Yoshida, and Koya Ariyoshi
Author affiliations: Institute of Tropical Medicine, Nagasaki University, Japan



  1. Xu  Q, Almudervar  A, Casey  JR, Pichichero  ME. Nasopharyngeal bacterial interactions in children. Emerg Infect Dis. 2012;18:173845. DOIPubMedGoogle Scholar
  2. Regev-Yochay  G, Dagan  R, Raz  M, Carmeli  Y, Shainberg  B, Derazne  E, Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in children. JAMA. 2004;292:71620. DOIPubMedGoogle Scholar
  3. Pettigrew  MM, Gent  JF, Revai  K, Patel  JA, Chonmaitree  T. Microbial interactions during upper respiratory tract infections. Emerg Infect Dis. 2008;14:158491. DOIPubMedGoogle Scholar
  4. Brunstein  JD, Cline  CL, McKinney  S, Thomas  E. Evidence from multiplex molecular assays for complex multipathogen interactions in acute respiratory infections. J Clin Microbiol. 2008;46:97102. DOIPubMedGoogle Scholar


Cite This Article

DOI: 10.3201/eid2002.121724

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Table of Contents – Volume 20, Number 2—February 2014

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Please use the form below to submit correspondence to the authors or contact them at the following address:

Motoi Suzuki, Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, JapanMotoi Suzuki, Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan

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Page created: January 16, 2014
Page updated: January 16, 2014
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