In February 1995, single-dose azithromycin was given to children with trachoma and their household contacts who were children. For children with trachoma, rates of carriage of pneumococci immediately before treatment with azithromycin and 2-3 weeks, 2 months, and 6 months after treatment were 68% (54 of 79), 29% (11 of 38), 78% (29 of 37), and 87% (34 of 39), respectively. The proportion of carriage-positive children with azithromycin-resistant Streptococcus pneumoniae strains was 1 of 54 (1.9%) before treatment and then 6 of 11 (54.5%), 10 of 29 (34.5%), and 2 of 34 (5.9%) at follow-up visits. The profile of pneumococcal serotypes changed after azithromycin treatment. Azithromycin-resistant strains (serotypes 10F, 23A, and 45) were isolated from 1 (1.3%) of 79 pretreatment swab specimens, from 16 (21.3%) of 75 swab specimens collected up to 2 months after treatment, and from 2 (6%) of 32 obtained 6 months after treatment. Mathematical modeling showed a more rapid appearance of azithromycin-resistant pneumococcal strains in previously colonized children than in previously noncolonized children. Thus, it appears that the selective effect of azithromycin allowed the growth and transmission of preexisting azithromycin-resistant strains. More research is needed to clarify the clinical relevance and implications of azithromycin use.
SUMMARYRates of acquisition and mean duration of nasal carriage of different serotypes of Streptococcus pneumoniae have been estimated by fitting a stochastic model to longitudinal carriage data in children from Papua New Guinea. Immunogenicity and two indices of relative invasiveness were determined for each serotype. Immunogenic serotypes were less frequently acquired and were carried for shorter periods, but no relationship between immunogenicity and invasiveness was apparent using either index of invasiveness. Frequent invasion was associated with a high acquisition rate and high frequency and prolonged duration of carriage. Carriage studies can provide a broad indication of which serotypes cause invasive disease but not the proportion of disease due to individual serotypes; some serotypes which cause invasive disease (e.g. serotype 46) are not found even in extensive carriage studies. The antibiotic resistance of carriage organisms, however, does approximate the resistance patterns of invasive organisms and thus may be used to monitor changing patterns of antimicrobial susceptibility in the community.
These findings have implications for both standard treatment protocols and vaccine strategies. The high rate of coinfection may make it difficult to develop simple clinical predictors of bacterial infection. In the setting of a developed country with efficient patient evacuation services, management algorithms that focus on disease severity and need for hospital referral will be most useful to health staff in remote communities. Pneumococcal conjugate vaccines will be required to reduce the high attack rate of pneumococcal disease.
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