Ramesh C. Bhatta

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.

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.

Control of Trachoma from Achham District, Nepal: A Cross-Sectional Study from the Nepal National Trachoma Program

Background The WHO seeks to control trachoma as a public health problem in endemic areas. Achham District in western Nepal was found to have TF (trachoma follicular) above 20% in a 2006 government survey, triggering 3 annual mass drug administrations finishing in 2010. Here we assess the level of control that has been achieved using surveillance for clinical disease, ocular chlamydia trachomatis infection, and serology for antibodies against chlamydia trachomatis protein antigens. Methods We conducted a cross-sectional survey of children aged 1–9 years in communities in Achham District in early 2014 including clinical examination validated with photographs, conjunctival samples for Chlamydia trachomatis (Amplicor PCR), and serological testing for antibodies against chlamydia trachomatis protein antigens pgp3 and CT694 using the Luminex platform. Findings In 24 randomly selected communities, the prevalence of trachoma (TF and/or TI) in 1–9 year olds was 3/1124 (0.3%, 95% CI 0.1 to 0.8%), and the prevalence of ocular chlamydia trachomatis infection was 0/1124 (0%, 95% CI 0 to 0.3%). In 18 communities selected because they had the highest prevalence of trachoma in a previous survey, the prevalence of TF and/or TI was 7/716 (1.0%, 95% CI 0.4 to 2.0%) and the prevalence of ocular chlamydia trachomatis infection was 0/716 (0%, 95% CI 0 to 0.5%). In 3 communities selected for serological testing, the prevalence of trachoma was 0/68 (0%, 95% CI 0 to 5.3%), the prevalence of ocular chlamydia trachomatis infection was 0/68 (0%, 95% CI 0 to 0.5%), the prevalence of antibodies against chlamydia trachomatis protein antigen pgp3 was 1/68 (1.5%, 95% CI 0.04% to 7.9%), and the prevalence of antibodies against chlamydia trachomatis protein antigen CT694 was 0/68 (0%, 95% CI 0 to 5.3%). Conclusion/Significance This previously highly endemic district in Nepal has little evidence of recent clinical disease, chlamydia trachomatis infection, or serological evidence of trachoma, suggesting that epidemiological control has been achieved.