Villages associated with the Lesotho Highlands Development Agency were randomized with a bias in favour of larger villages, and children < 5 years of age from cluster-randomized households in these villages were chosen for the assessment of antibiotic resistance in pneumococci. Children of the same age group attending clinics in the capital, Maseru, were selected for comparison. Nasopharyngeal cultures of Streptococcus pneumoniae from both groups of children were examined for antibiotic resistance and a questionnaire was used to assess risk factors for the acquisition of resistant strains. Carriage of penicillin- and tetracycline-resistant pneumococci was significantly higher among 196 Maseru children compared with 324 rural children (P < 0.05 and P = 0.01, respectively). Maseru children tended to visit clinics at an earlier age compared with their rural counterparts. The rural children were less exposed to antibiotics (P < 0.01), were less frequently hospitalized (P < 0.001), and rarely attended day care centres (P < 0.001). The very low incidence of antibiotic resistance in rural Lesotho and the higher incidence in Maseru are in stark contrast with the much higher frequencies found in the Republic of South Africa, many European countries, and the USA
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