Hem Jha

Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal.

Mass administration of azithromycin to eliminate blindness due to trachoma has raised concerns regarding the emergence of antimicrobial resistance. During 2000, we compared the antimicrobial resistance of nasopharyngeal pneumococcal isolates recovered from and the prevalence of impetigo, respiratory symptoms, and diarrhea among 458 children in Nepal before and after mass administration of azithromycin. No azithromycin-resistant pneumococci were isolated except from 4.3% of children who had received azithromycin during 2 previous mass treatments (P<.001). There were decreases in the prevalence of impetigo (from 14% to 6% of subjects; adjusted odds ratio [OR], 0.41; 95% confidence interval [CI], 0.21-0.80) and diarrhea (from 32% to 11%; adjusted OR, 0.26; 95% CI, 0.14-0.43) 10 days after azithromycin treatment. The absence of macrolide-resistant isolates after 1 mass treatment with azithromycin is encouraging, although the recovery of azithromycin-resistant isolates after 2 mass treatments suggests the need for resistance monitoring when multiple rounds of antimicrobial treatment are given.

Comparison of two azithromycin distribution strategies for controlling trachoma in Nepal

OBJECTIVE The study compares the effectiveness of two strategies for distributing azithromycin in an area with mild-to-moderate active trachoma in Nepal. METHODS The two strategies investigated were the use of azithromycin for 1) mass treatment of all children, or 2) targeted treatment of only those children who were found to be clinically active, as well as all members of their household. FINDINGS Mass treatment of children was slightly more effective in terms of decreasing the prevalence of clinically active trachoma (estimated by clinical examination) and of chlamydial infection (estimated by DNA amplification tests), although neither result was statistically significant. CONCLUSION Both strategies appeared to be effective in reducing the prevalence of clinically active trachoma and infection six months after the treatment. Antibiotic treatment reduced the prevalence of chlamydial infection more than it did the level of clinically active trachoma.

Topical ocular antibiotics induce bacterial resistance at extraocular sites

Aim: To compare the prevalence of antibiotic resistance found in nasopharyngeal Streptococcus pneumoniae between villages treated with topical tetracycline or systemic azithromycin as part of a trachoma control programme. Methods: All children aged 1–10 years were offered either single dose oral azithromycin treatment (20 mg/kg) or a course of topical 1% tetracycline ointment, depending on the area. Treatment was given annually for 3 years. Six months after the third annual treatment in each village, children were surveyed for nasopharyngeal carriage of S pneumoniae and resistance was determined using broth dilution MIC technique. Children in two additional villages, which had not yet been treated, were also surveyed. Results: Nasopharyngeal carriage of S pneumoniae was similar in the tetracycline treated, azithromycin treated, and untreated areas (p = 0.57). However, resistance to tetracycline and azithromycin was distributed differently between the three areas (p = 0.004). The village treated with topical tetracycline had a higher prevalence of tetracycline resistance than the other villages (p = 0.010), while the oral azithromycin treated village had a higher prevalence of macrolide resistance than the other villages (p = 0.014). Conclusions: Annual mass treatment with oral azithromycin may alter the prevalence of drug resistant S pneumoniae in a community. Surprisingly, topical tetracycline may also increase nasopharyngeal pneumococcal resistance. Topical antibiotics may have an effect on extraocular bacterial resistance.

Cost-effectiveness of trachoma control measures: comparing targeted household treatment and mass treatment of children

OBJECTIVE The present study compares the cost-effectiveness of targeted household treatment and mass treatment of children in the most westerly part of Nepal. METHODS Effectiveness was measured as the percentage point change in the prevalence of trachoma. Resource measures included personnel time required for treatment, transportation, the time that study subjects had to wait to receive treatment, and the quantity of azithromycin used. The costs of the programme were calculated from the perspectives of the public health programme sponsor, the study subjects, and the society as a whole. FINDINGS Previous studies have indicated no statistically significant differences in effectiveness, and the present work showed no significant differences in total personnel and transportation costs per child aged 1-10 years, the total time that adults spent waiting, or the quantity of azithromycin per child. However, the mass treatment of children was slightly more effective and used less of each resource per child aged 1-10 years than the targeted treatment of households. CONCLUSION From all perspectives, the mass treatment of children is at least as effective and no more expensive than targeted household treatment, notwithstanding the absence of statistically significant differences. Less expensive targeting methods are required in order to make targeted household treatment more cost-effective.

Pooling of Chlamydia laboratory tests to determine the prevalence of ocular Chlamydia trachomatis infection

With the Global Elimination of Trachoma by 2020 program underway, it has become increasingly important to identify the prevalence of ocular chlamydia infection in communities. DNA amplification tests are the gold standard, but are prohibitively expensive. In the present paper, we investigate whether pooling multiple specimens into a single test is feasible. The conjunctivae of 170 children in western Nepal were examined and swabbed. The prevalence of chlamydial infection was estimated in two ways using the ligase chain reaction: by testing all 170 specimens individually, and by testing 34 pools of 5 specimens each. We show that the confidence interval for 34 pooled specimens approaches that of doing all 170 specimens as the prevalence decreases. We also determine the optimal number of specimens to pool into a single test to minimize the confidence interval of the estimate. If the population prevalence is expected to be around 10%, then 14 specimens should be pooled per test. Even at 50% prevalence, costs can be reduced by pooling two samples per test.

Disappearance of Trachoma from Western Nepal

We assessed how much of the observed decline in the prevalence of trachoma in a district of Western Nepal was due to an antibiotic treatment program and how much to an underlying secular trend outside of the program. Although antibiotic treatments clearly have an effect at 6 months, we were unable to show that this effect persisted at 12 months; in fact, long-term gains may be due to a secular trend in the area.

Eliminating Trachoma in areas with limited disease

The common wisdom is that a trachoma program cannot eliminate ocular chlamydia from a community, just reduce infection to a level where there would be minimal blindness. We describe the success of multiple mass antibiotic treatments, demonstrating that complete elimination of infection may be an attainable goal in an area with modest disease.

Does clinical diagnosis indicate ocular chlamydial infection in areas with a low prevalence of trachoma

The WHO has initiated a global program to eliminate trachoma. This program includes mass antibiotic administrations to reduce the prevalence of Chlamydia trachomatis, the causative agent in trachoma. DNA amplification tests are the most sensitive methods to diagnose C. trachomatis infection, but are expensive and not typically performed in trachoma-endemic areas. Trachoma programs use clinical examination to determine which communities and which individuals within communities would benefit from antibiotic treatment, so understanding the relationship between clinical activity and chlamydial infection is important. In this study, we determine what percent of individuals with clinically active trachoma are infected with chlamydia in low prevalence communities of China and Nepal (with <10% clinical activity in children), and compare this against a high prevalence community of Nepal (with >30% clinical activity in children). In the low prevalence areas, only 8% clinically active cases had evidence of chlamydia. In the high prevalence community, 70% of clinically active cases harbored chlamydia. These results imply that clinical activity is less indicative of infection at a lower prevalence. In the context of a trachoma program, both clinically active cases and the community as a whole may stand to benefit less from antibiotic treatment in lower prevalence areas.

Community treatment with azithromycin for trachoma is not associated with antibiotic resistance in Streptococcus pneumoniae at 1 year.

Aims: To determine if macrolide resistant Streptococcus pneumoniae will be a major concern in areas that receive annual mass azithromycin distributions for trachoma. Methods: A cross sectional survey was conducted of nasopharyngeal S pneumoniae isolates for susceptibility to azithromycin 1 year after administering a single dose of azithromycin to treat trachoma in a village in Nepal. Results: S pneumoniae was isolated from 50 (86%) of 57 nasopharyngeal cultures and no resistance to azithromycin was detected. Conclusion: The authors were unable to demonstrate that mass azithromycin therapy for trachoma produced macrolide resistant S pneumoniae that persists until the next scheduled annual treatment.

Trachoma Decline and Widespread Use of Antimicrobial Drugs

Widespread use of antimicrobial drugs may be contributing to trachoma decline.