Household contacts of patients with pertussis are at increased risk of acquiring infection. Chemoprophylaxis has been recommended to decrease transmission, particularly to young infants who are at increased risk of severe disease. Although epidemiologic investigations of outbreaks have suggested a benefit, there have been no prospective studies evaluating the efficacy of chemoprophylaxis in preventing secondary cases of pertussis.
To determine whether erythromycin estolate chemoprophylaxis is effective in household contacts of children with culture-positive pertussis.
Randomized, double-blind, placebo-controlled study.
Community based.
All household contacts of 152 children with culture-positive pertussis who provided consent (n= 362). After withdrawals, there were 135 households with 310 contacts. Exclusions included pregnancy, age <6 months, already receiving an erythromycin-containing antibiotic, and erythromycin allergy.
Erythromycin estolate (40 mg/kg/day in 3 divided doses; maximum dose 1 g) or placebo for 10 days. Nasopharyngeal cultures, pertussis antibodies, and clinical symptoms were assessed before and after treatment.
Measure efficacy of erythromycin estolate chemoprophylaxis calculated by the proportion of households in each group with a member who developed a nasopharyngeal culture positive forBordetella pertussis.
There was no difference in the development of respiratory tract symptoms compatible with a case definition of pertussis in the erythromycin- and placebo-treated groups. There were 20 households with secondary culture-positive cases of pertussis; 4 households in the erythromycin-treated group and 15 in the placebo-treated group (efficacy of erythromycin chemoprophylaxis for bacterial eradication 67.5% [95% confidence interval: 7.6–88.7]). However, medication-associated adverse reactions were reported by 34.0% of erythromycin and 15.7% of placebo recipients.
Under the conditions of this study, erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis.
We thank Dr. Heininger for his comments about our study. We agree that the low secondary attack rate could have been due to either previous natural infection or immunization. The effect of immunization was assessed but was hampered by the lack of reliable immunization records for nearly half of the household contacts (mostly adults). Of those household members for whom immunization status was known, all bacteriological chemoprophylaxis failures in both the placebo and the erythromycin groups occurred in individuals who had received at least four doses of pertussis vaccine. There was no effect on the clinical efficacy according to immunization status. Although there was an effect of compliance with medication on bacteriological efficacy (as reported in the manuscript), there was no effect of patient compliance on the clinical efficacy presented in Table 4.
I would like to congratulate the authors on their interesting findings and share a few comments. The secondary attack rate in household members treated with placebo after exposure to children with pertussis was only 5.1%-6.6%. This suggests a high level of immunity, either by previous natural infection (as the authors discuss) but also possibly by immunization (what the authors do not mention). Information on the pertussis immunization status is missing in the paper but would have been of substantial interest. Could this be provided? Furthermore, the analysis of clinical efficacy of erythromycin prophylaxis presented in Table 4 does not take the patients' compliance into account. It would be interesting to see a separate analysis restricted to erythromycin recipients with what the authors considered "excellent compliance". This might demonstrate a possible effect of erythromycin more clearly. Best regards, Ulrich Heininger