Effectiveness of Azithromycin Mass Drug Administration on Trachoma: A Systematic Review
Trachoma, caused by the bacterium Chlamydia trachomatis, remains a leading infectious cause of blindness worldwide, particularly in low-income and resource-limited settings. The World Health Organization (WHO) has endorsed the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvement) as a comprehensive approach to eliminate trachoma as a public health problem. A critical component of this strategy is mass drug administration (MDA) of azithromycin, an antibiotic that effectively targets the infection. This systematic review evaluates the effectiveness of azithromycin MDA in controlling trachoma, focusing on the relationship between baseline prevalence and treatment outcomes, the impact of different MDA strategies, and the challenges faced in hyperendemic regions.
Background and Context
Trachoma is a neglected tropical disease that disproportionately affects children and women in endemic regions, particularly in sub-Saharan Africa, the Middle East, and parts of Asia. The disease progresses through repeated infections, leading to conjunctival scarring, trichiasis, and ultimately blindness. WHO has set a global target to eliminate trachoma as a public health problem by reducing the prevalence of trachomatous inflammation-follicular (TF) to less than 5.0% in endemic districts. Azithromycin MDA has been a cornerstone of this effort, with over 900 million doses distributed worldwide.
The WHO recommends 3 to 5 years of annual azithromycin MDA in districts with a baseline TF prevalence of 10.0% or higher, with treatment coverage exceeding 80.0%. However, despite significant progress in many regions, trachoma remains endemic in over 40 countries, affecting approximately 136 million people. This systematic review aims to assess the effectiveness of azithromycin MDA across different epidemiological settings and explore strategies to enhance its impact, particularly in hyperendemic areas.
Methods
The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov up to February 2021. Studies reporting the effects of azithromycin MDA on trachoma were included, while mathematical modeling studies, animal studies, case reports, and reviews were excluded. The primary outcome was the reduction in TF prevalence to below 5.0%, the threshold for eliminating trachoma as a public health problem.
Two researchers independently screened studies, extracted data, and assessed the risk of bias. The Oxford Centre for Evidence-Based Medicine’s Levels of Evidence and Grades of Recommendation were used to evaluate the quality of evidence. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions for randomized controlled trials (RCTs) and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool for non-randomized studies.
Results
A total of 1543 studies were identified, of which 67 met the inclusion criteria. These included 13 cluster-randomized controlled trials and 54 non-randomized studies (23 longitudinal studies and 31 cross-sectional studies). The studies were predominantly conducted in Tanzania and Ethiopia, with baseline TF prevalence ranging from 5.0% to 90.0%. The duration of azithromycin MDA varied from a single distribution to more than 7 years of annual or biannual treatment.
Effectiveness of Azithromycin MDA by Baseline Prevalence
The effectiveness of azithromycin MDA was closely tied to the baseline TF prevalence in the target districts. In areas with a baseline TF prevalence between 5.0% and 9.9%, a single round of MDA was sufficient to reduce TF prevalence below 5.0% in four out of five studies. In districts with a baseline TF prevalence between 10.0% and 29.9%, 3 to 5 years of annual MDA achieved TF prevalence below 5.0% in some areas, while others reached levels close to the elimination threshold (5.0%–10.0%). However, in hyperendemic districts with a baseline TF prevalence exceeding 30.0%, particularly those with prevalence above 50.0%, annual MDA failed to reduce TF prevalence below 5.0% even after 5 to 7 years of treatment.
Single Dose of Azithromycin MDA
Twenty-three studies evaluated the impact of a single round of azithromycin MDA. In districts with baseline TF prevalence between 5.0% and 9.9%, four out of five studies reported TF prevalence below 5.0% after treatment. In districts with baseline TF prevalence between 10.0% and 29.9%, two out of eight studies achieved TF prevalence below 5.0%, while three others reduced TF prevalence to between 5.0% and 10.0%. However, in districts with baseline TF prevalence above 30.0%, none of the studies achieved TF prevalence below 5.0%.
Annual Azithromycin MDA for 2 Years
Nine studies assessed the impact of 2 years of annual azithromycin MDA. In districts with baseline TF prevalence below 20.0%, three studies reported TF prevalence below or close to 5.0%. However, in districts with baseline TF prevalence above 20.0%, six studies reported TF prevalence exceeding 10.0% after treatment.
Annual Azithromycin MDA for 3 to 5 Years
Twenty-five studies evaluated the impact of 3 to 5 years of annual azithromycin MDA. In districts with baseline TF prevalence below 40.0%, three studies achieved TF prevalence below 5.0%. In districts with baseline TF prevalence between 12.0% and 50.5%, nine studies reported TF prevalence between 5.0% and 10.0%. However, in districts with baseline TF prevalence above 30.0%, ten studies reported TF prevalence exceeding 10.0% after treatment.
Biannual Azithromycin MDA for 2 to 3 Years
Four studies assessed the impact of biannual azithromycin MDA. In districts with baseline TF prevalence between 20.0% and 30.0%, one study reduced TF prevalence to between 5.4% and 10.1%. However, in districts with baseline TF prevalence above 40.0%, three studies reported TF prevalence between 17.0% and 37.0% after treatment.
Quarterly Azithromycin MDA
Six cluster-randomized trials compared the effectiveness of different MDA frequencies (annual, biannual, and quarterly). Quarterly MDA was found to be more effective in reducing Chlamydia trachomatis infection than annual or biannual MDA. However, data on TF prevalence following quarterly MDA were limited.
Enhancing the Effectiveness of Azithromycin MDA
Several strategies were explored to enhance the effectiveness of azithromycin MDA. Increasing the frequency of MDA from annual to biannual or quarterly showed promise, particularly in hyperendemic districts. However, enhancing treatment coverage beyond 90.0% did not yield additional benefits compared to standard coverage (80.0%–90.0%). Targeting different populations, such as all residents versus households with children with TF, also showed no significant difference in effectiveness.
Discussion
The findings of this systematic review highlight the critical role of baseline TF prevalence in determining the effectiveness of azithromycin MDA. While the WHO’s recommendation of 3 to 5 years of annual MDA is effective in districts with moderate TF prevalence (10.0%–29.9%), it falls short in hyperendemic areas with TF prevalence exceeding 30.0%. In these regions, even 7 to 9 years of annual MDA failed to achieve the elimination threshold in most cases.
The review underscores the need for tailored MDA strategies based on local epidemiology. In low-prevalence districts (TF 5.0%–9.9%), a single round of MDA with adequate coverage (>80.0%) is sufficient to achieve TF prevalence below 5.0%. In moderate-prevalence districts (TF 10.0%–29.9%), 3 to 5 years of annual MDA can reduce TF prevalence to near or below the elimination threshold. However, in hyperendemic districts (TF >30.0%), annual MDA is inadequate, and more frequent treatment, such as quarterly MDA, may be necessary.
The review also highlights the limitations of current strategies. Despite the widespread distribution of azithromycin, progress has stalled in many hyperendemic regions. This may be due to factors such as high transmission rates, inadequate treatment coverage, or the presence of resistant strains of Chlamydia trachomatis. Further research is needed to explore the role of these factors and to develop innovative strategies to enhance the impact of MDA in these challenging settings.
Conclusions
Azithromycin MDA is a critical tool in the global effort to eliminate trachoma as a public health problem. However, its effectiveness is highly dependent on the baseline prevalence of TF in the target districts. While a single round of MDA is sufficient in low-prevalence areas, 3 to 5 years of annual MDA is required in moderate-prevalence districts. In hyperendemic regions, annual MDA is insufficient, and more frequent treatment, such as quarterly MDA, may be necessary to achieve the elimination threshold. These findings underscore the need for tailored MDA strategies based on local epidemiology and highlight the importance of ongoing surveillance and research to optimize trachoma control efforts.
doi.org/10.1097/CM9.0000000000001717
Was this helpful?
0 / 0