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Journal of Clinical Microbiology, November 2002, p. 4357-4359, Vol. 40, No. 11
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.11.4357-4359.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

High Rate of Transmission of Penicillin-Resistant Streptococcus pneumoniae between Parents and Children

Kazuhiko Hoshino,1* Hiroshi Watanabe,1 Rinya Sugita,2 Norichika Asoh,1 Simon Angelo Ntabaguzi,1 Kiwao Watanabe,1 Kazunori Oishi,1 and Tsuyoshi Nagatake1

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki and,1 Sugita Otorhinolaryngologic Clinic, Chiba, Japan2

Received 23 May 2002/ Returned for modification 1 July 2002/ Accepted 5 August 2002


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ABSTRACT
 
Transmission of Streptococcus pneumoniae between children and their parents was evaluated in 29 pairs from 25 families. The serotypes of 35 pneumococcal isolates from 18 (62.1%) of 29 child-parent pairs were identical. Of the 35 isolates, 23 showed intermediate resistance and 10 were fully resistant to penicillin G. PCR indicated that all 35 strains had at least one alteration in penicillin-binding protein genes pbp1a, pbp2x, and pbp2b and 33 strains had macrolide resistance genes mef(A) and/or erm(B). As a result, the PCR patterns of 16 of 18 pairs were identical. Molecular typing by pulsed-field gel electrophoresis showed that 12 pairs were indistinguishable, 3 pairs were closely related, 2 pairs were possibly related, and only one pair was different. Our data indicate the presence of a high rate of transmission of penicillin-resistant S. pneumoniae between children and their parents.


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TEXT
 
Streptococcus pneumoniae, which can colonize the human nasopharynx, is a leading bacterial cause of pneumonia, as well as otitis media, sinusitis, septicemia, and meningitis (10). Especially, children are frequent carriers of pneumococci, which may lead to invasive pneumococcal disease (5, 6). Penicillin-resistant S. pneumoniae (PRSP) is widespread all over the world, and the resistance is broadening to include other antimicrobial agents (1, 9, 15). It has been reported that children could acquire PRSP at child care centers (13) or from their siblings (14). However, the problem of whether PRSP colonizing the upper respiratory tract can be transmitted between children and parents and cause invasive diseases is not clear. To address this issue, we conducted the following prospective study.

New patients with invasive infections (e.g., pneumonia, sinusitis, otitis media, etc.) caused by S. pneumoniae who visited Nagasaki University Hospital or the Sugita Otorhinolaryngologic Clinic from January 2000 to May 2001 were asked to bring their family as soon as possible for clinical examination and collection of biological specimens (e.g., sputum, nasopharynx, middle ear). To diagnose invasive disease caused by pneumococci, gram-stained smears and cultures of good-quality specimens, according to the criteria of Bartlett (2), that were obtained as recently as possible were performed by standard methods. Fifty-four S. pneumoniae isolates from 29 pairs of children (mean age, 1.7 years) and their parents (mean age, 31.5 years) in 25 families were evaluated. We collected two isolates from each of 21 families and three isolates from each of 4 families. Culture plates were incubated overnight in a 5% CO2 incubator. Optochin sensitivity and bile solubility tests were performed for confirmation of S. pneumoniae. The MICs of penicillin G (Meiji Seika Kaisha, Tokyo, Japan) for 54 S. pneumoniae isolates were determined by the broth microdilution method in accordance with the guidelines of the NCCLS (12). Pneumococci were serotyped on the basis of capsular swelling (Quellung reaction) observed microscopically after suspension in Pneumococcal Diagnostic Antiserum (Statens Seruminstitut, Copenhagen, Denmark). PCR was performed for the 35 pneumococcal isolates whose serotypes were identical in the children and parents to detect the alteration of penicillin-binding protein genes pbp1a, pbp2x, and pbp2b and macrolide resistance genes mef(A) and erm(B) as described previously (11). Pulsed-field gel electrophoresis (PFGE) after digestion with SmaI (Takara Shuzo Co., Shiga, Japan) was also performed for the 35 pneumococci as described previously (17), and the interpretation of PFGE patterns was based on the criteria described by Tenover et al. (16).

The serotypes of 35 strains of S. pneumoniae in 18 (62.1%) of 29 pairs from children and parents were identical. Those were classified into six different serotypes, and 19F, 23F, and 6A were predominant (Table 1). On the other hand, the serotypes of 19 strains of pneumococci that were not identical in children and their parents varied widely and those included three isolates each of serotypes 19F and 23A; two isolates each of serotypes 6A, 6B, and 23F; and one isolate each of serotypes 9V, 11A, 14, 18C, 28F, 29, and 34. Of the 35 isolates whose serotypes were identical in children and their parents, 23 (65.7%) showed intermediate resistance (MIC, 0.12 to 1.0 µg/ml) and 10 (28.6%) were fully resistant (MIC, >=2.0 µg/ml) to penicillin G and only 2 isolates were susceptible (Table 1). Of the remaining 19 isolates, 15 showed intermediate resistance and 4 were susceptible to penicillin G. Thirty (85.7%) of 35 pneumococcal isolates had alterations in pbp1a, -2x, and -2b; 3 (8.6%) had alterations in pbp2x and -b; and 2 (5.7%) had alterations in pbp2x. Thirty-three strains (94.3%) had macrolide resistance genes mef(A) and/or erm(B). As a result, the PCR patterns of 16 (88.9%) of 18 pairs were identical (Table 1). Of the 18 pairs, molecular typing by PFGE showed that 12 pairs (66.7%) were indistinguishable, 3 pairs (16.7%) were closely related, 2 pairs (11.1%) were possibly related, and only 1 pair (5.6%) was different (Table 1 and Fig. 1).


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  		TABLE 1. Epidemiological characteristics of pneumococcal isolates with identical serotypes from children and their parents



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  		FIG. 1. PFGE patterns of SmaI-digested DNA of pneumococcal isolates from children and parents from 10 families (A to J). The patterns of pneumococcal isolates from children and their parents are indistinguishable in families A, C, D, E, G, and I; closely related in families F and H; possibly related in one pair each (strains 3 and 4) from families B and J; and different in the other pair (strains 3 and 5) from family B. Lanes M contained molecular size markers.

Infants and young children tend to acquire S. pneumoniae in the upper respiratory tract because of their low immunity. This pneumococcal colonization can become a risk factor for invasive pneumococcal disease (5, 6), which is a major cause of morbidity and mortality in infants and young children worldwide (8). In our study, when patients with invasive infections caused by S. pneumoniae appeared, young children in the family were colonized by S. pneumoniae with and without infection and the high rate of correlation between colonizations of children and parents was confirmed by serotyping, PCR, and PFGE. Moreover, most (94.3%) of the colonizations were by PRSP (MIC, >0.1 µg/ml) when the serotypes of pneumococci were identical in the children and their parents. It has been reported that immunization with pneumococcal polysaccharide vaccine was associated with poor results in children under the age of 2 years (3). On the other hand, pneumococcal conjugate vaccine seems to be effective for not only prevention of invasive pneumococcal disease but also reduction of nasopharyngeal carriage of vaccine serotypes in young children (4, 8, 18). In our study, the serotype coverage of such vaccine against S. pneumoniae was 71.4% (25 of 35) when the serotypes of pneumococci from children and their parents were identical, although we should note that invasive-disease-causing serotype 6A and 34 strains are not included in such a vaccine. Therefore, pneumococcal conjugate vaccine interrupts the transmission of pneumococci, including PRSP, and thus decreases the burden of antibiotic resistance in immunized children and their contacts (7).

In conclusion, our results demonstrated a high rate of transmission of PRSP between children and their parents. Therefore, we should consider the introduction of highly effective vaccines in young children for prevention of invasive pneumococcal disease.


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ACKNOWLEDGMENTS
 
We thank Akihiro Wada (Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University), Chieko Shimauchi (Miyazaki Prefectural Nursing University), and Matsuhisa Inoue (Kitasato University School of Medicine) for help in the completion of PFGE studies. We also thank Yumiko Suzuki (Tokyo Clinical Research Center) for measuring MICs against S. pneumoniae and Mai Yanase (Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University) for help with the PCR analysis.


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FOOTNOTES
 
* Corresponding author. Mailing address: Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Phone: 81 (95) 849-7842. Fax: 81 (95) 849-7843. E-mail: khoshino{at}net.nagasaki-u.ac.jp. Back


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Journal of Clinical Microbiology, November 2002, p. 4357-4359, Vol. 40, No. 11
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.11.4357-4359.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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