TITLE: Discontinuation of mass  azithromycin distribution for trachoma: a systematic review
AUTHORS: hamidah.mahmud , Catherine Oldenburg

[DESCRIPTION]
<div class = "text-blocks"><div class = "text-block"><span>The WHO recommends continuing azithromycin mass drug administration (MDA) for trachoma until endemic regions drop below 5% prevalence of active trachoma in children aged 1-9 years. Azithromycin targets the ocular strains of</span><span style = "font-style:italic;">Chlamydia trachomatis</span><span>that cause trachoma. Regions with low prevalence of active trachoma may have little if any ocular chlamydia, and thus may not benefit from azithromycin treatment. Understanding what happens to active trachoma and ocular chlamydia prevalence after mass distributions of azithromycin are discontinued may improve future treatment decisions. We systematically reviewed published evidence for community prevalence of both active trachoma and ocular chlamydia after cessation of azithromycin distribution. We included published studies from the peer-reviewed literature that included at least two post-discontinuation of mass azithromycin distribution surveys of ocular chlamydia and/or trachomatous inflammation—follicular (TF) prevalence. We assessed trends in the prevalence of both indicators over time after azithromycin discontinuation. We searched electronic databases for publications up through May 20, 2020. Of 140 identified studies, 21 met inclusion criteria and were used for qualitative synthesis. Although we found a gradual increase in ocular chlamydia infection prevalence over time post-discontinuation of azithromycin distribution, the TF prevalence generally gradually declined. Ocular chlamydia infection may return faster in communities compared to TF following discontinuation of treatment.</span></div></div>

[STEPS]
?. [Review questions ]
1. What is the prevalence of clinical trachoma (TF) and ocular chlamydia infection pre-MDA and post MDA?
?. [Review questions ]
2. Is there a correlation between pre-treatment trachoma prevalence and return of trachoma infection prevalence after discontinuing oral azithromycin treatment?
?. [Search strategy ]
Search Items: -Trachoma-Azithromycin
?. [Search strategy ]
Synonyms to be searched, if needed:- Azithromycin: Zithromax
?. [Search strategy ]
Search algorithm:("Trachoma"[Mesh] OR trachoma) AND ("Azithromycin"[Mesh] OR azithromycin OR zithromax)·
?. [Search strategy ]
Databases searched and search details:o   MEDLINESearch bar:("Trachoma"[Mesh] OR trachoma) AND ("Azithromycin"[Mesh] OR azithromycin OR zithromax)Full search details:("Trachoma"[Mesh] OR ("trachoma"[MeSH Terms] OR "trachoma"[All Fields])) AND ("Azithromycin"[Mesh] OR ("azithromycin"[MeSH Terms] OR "azithromycin"[All Fields]) OR ("azithromycin"[MeSH Terms] OR "azithromycin"[All Fields] OR "zithromax"[All Fields]))o   EMBASESearch bar:('trachoma'/exp OR trachoma) AND ('azithromycin'/exp OR azithromycin)o   Web of ScienceSearch bar (TOPIC):("Trachoma"[Mesh] OR trachoma) AND ("Azithromycin"[Mesh] OR azithromycin OR zithromax)o   Cochrane LibrarySearch bar (Title, Abstract, Keywords):Trachoma AND azithromycin
?. [Search strategy ]
Other sources:o   AbstractsAbstracts available online from the following conferences will be searched using the search terms outlined above:· American Society of Tropical Medicine and Hygiene (ASTMH)· Association for Research in Vision and Ophthalmology (ARVO)
?. [Article eligibility criteria]
Inclusion criteria:o   Primary, quantitative datao   Studies of community-wide oral azithromycin distribution for trachomao   Includes measurement of prevalence of ocular chlamydia and/or clinical trachoma before and after azithromycin distributiono   Studies must include one pre-treatment time point and at least two post-treatment time pointso   Dates of inclusion: All primary abstracts, reports, etc. published through May 2020
?. [Article eligibility criteria]
Exclusion criteria:o   Studies on mathematical modeling, surveillance reports, review articleso   Studies without sufficient information on number of individuals/ villages testedo   Studies without two distinct time points of pre- and post- azithromycin distributiono   Studies on the use of azithromycin for purposes other than treatment of trachomaWe will not exclude studies that concurrently use topical tetracycline for trachoma treatment
?. [Outcomes]
Primary outcomes of interest:o   Prevalence of clinical trachoma pre-MDA and post-MDAo   Prevalence of ocular chlamydia infection pre-MDA and post-MDA
?. [Outcomes]
Secondary outcomeso   Correlation between pre- and post-MDA prevalence of clinical trachoma if possibleo   Correlation between pre- and post-MDA prevalence of ocular chlamydia infection if possible
?. [Data Extraction]
Variables to extract:o   Titleo   Authorso   Journalo   Year of publicationo   Study designo   Geographic location of studyo   Sample size (numbers of communities, numbers of individuals)o   Pre-MDA trachoma prevalence (ocular chlamydia infection and/or clinical trachoma/TF)o   Post-MDA trachoma prevalence (ocular chlamydia infection and/or clinical trachoma/TF)o   Frequency of MDAo   Duration of MDA
?. [Analysis]
Strategy for data synthesis (qualitative, quantitative):o   A qualitative synthesis of individual studies will be performed to discuss individual findings per the variables extracted.o   For quantitative synthesis, a meta-analysis will be performed per the procedures outlined below
?. [Analysis]
Meta-analysis (if data is not too heterogenic to allow):o   Estimates of prevalence pre- and post-MDA will be pooled across studies using a DerSimonian and Laird random effects model for overall prevalence of each outcome (clinical trachoma and ocular chlamydia infection)-Pre-MDA prevalence is predicting post-MDA prevalenceo   The I² statistic will be calculated as a measure of heterogeneity across studies. Sources of heterogeneity, including pre-MDA trachoma prevalence, country of origin, and year, will be evaluated using a random effects meta-regression model.
?. [Analysis]
·      Quality Assessmento   Risk of bias will be assessed using the Cochrane risk of bias tool for randomized controlled trials and the ROBINS-I tool for non-randomized studies