Mycoplasma genitalium incidence, persistence, concordance between partners and progression: systematic review and meta-analysis

Background Mycoplasma genitalium is increasingly seen as an emerging sexually transmitted pathogen, and has been likened to Chlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determine M. genitalium incidence, persistence, concordance between sexual partners and the risk of pelvic inflammatory disease (PID). Methods We searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies. Results We screened 4634 records and included 18 studies; six (4201 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI 0.61 to 1.53, I2 0%). Median persistence of M. genitalium was estimated from one to three months in four studies but 15 months in one study. In 10 studies measuring M. genitalium infection status in couples, 39%–50% of male or female sexual partners of infected participants also had M. genitalium detected. In prospective studies, PID incidence was higher in women with M. genitalium than those without (risk ratio 1.73, 95% CI 0.92 to 3.28, I2 0%, two studies). Discussion Incidence of M. genitalium in very highly developed countries is similar to that for C. trachomatis, but concordance might be lower. Taken together with other evidence about age distribution and antimicrobial resistance in the two infections, M. genitalium is not the new chlamydia. Synthesised data about prevalence, incidence and persistence of M. genitalium infection are inconsistent. These findings can be used for mathematical modelling to investigate the dynamics of M. genitalium. Registration numbers CRD42015020420, CRD42015020405


Rationale
3 Describe the rationale for the review in the context of what is already known. 5 Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.
6 Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

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Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

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Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.
Supplementary material 2-4 (Text S1) Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).
Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

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Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. 7

Risk of bias in individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. for each meta-analysis.

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Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

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Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

Study selection
17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

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Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

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Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.