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Hiam Chemaitelly, Helen A Weiss, Alex Smolak, Elzahraa Majed, and Laith J Abu-Raddad

Abstract

Background

The epidemiology of sexually transmitted infections (STIs) and the role of commercial heterosexual sex networks in driving STI transmission in the Middle East and North Africa (MENA) region remain largely unknown.

Objective

To characterize the epidemiology of Treponema pallidum (syphilis), Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and herpes simplex virus type 2 (HSV-2) among female sex workers (FSWs) in MENA using an in-depth quantitative assessment.

Methods

A systematic review on ten international, regional, and country-level databases was conducted, and reported following PRISMA guidelines. Pooled prevalences of current and/or ever infection for each STI were estimated using random-effects meta-analyses. Sources of between-study heterogeneity were investigated through random-effects meta-regressions.

Results

One T. pallidum incidence study and 144 STI prevalence studies were identified for 45 812 FSWs in 13 MENA countries. The pooled prevalence of current infection was 12.7% (95% confidence interval (CI) = 8.5%-17.7%) for T. pallidum, 14.4% (95% CI = 8.2%-22.0%) for C. trachomatis, 5.7% (95% CI = 3.5%-8.4%) for N. gonorrhoeae, and 7.1% (95% CI = 4.3%-10.5%) for T. vaginalis. The pooled prevalence of ever infection (seropositivity using antibody testing) was 12.8% (95% CI = 9.4%-16.6%) for T. pallidum, 80.3% (95% CI = 53.2%-97.6%) for C. trachomatis, and 23.7% (95% CI = 10.2%-40.4%) for HSV-2. The multivariable meta-regression for T. pallidum infection demonstrated strong subregional differences, with the Horn of Africa and North Africa showing, respectively 6-fold (adjusted odds ratio (AOR): 6.4; 95% CI = 2.5-16.7) and 5-fold (AOR = 5.0; 95% CI = 2.5-10.6) higher odds of infection than Eastern MENA. There was also strong evidence for declining T. pallidum odds of infection at 7% per year (AOR = 0.93; 95% CI = 0.88-0.98). Study-specific factors including diagnostic method, sample size, sampling methodology, and response rate, were not associated with syphilis infection. The multivariable model explained 48.5% of the variation in T. pallidum prevalence.

Conclusions

STI infection levels among FSWs in MENA are considerable, supporting a key role for commercial heterosexual sex networks in transmission dynamics, and highlighting the health needs of this neglected and vulnerable population. Syphilis prevalence in FSWs appears to have been declining for at least three decades. Gaps in evidence persist for multiple countries.


The burden of sexually transmitted infections (STIs) and sequelae remains a major global health concern [1]. Nearly one million persons are infected with a curable STI every day [2], and about half a billion are living with herpes simplex virus type 2 (HSV-2) [3]. The largely asymptomatic nature of STIs, particularly for women, leaves most individuals unaware of their infection [1]. STIs have been associated with HIV acquisition [4-6], and poor reproductive health outcomes including pelvic inflammatory disease, ectopic pregnancy, infertility, and perinatal deaths [1,7].

Commercial heterosexual sex networks (CHSNs) are believed to play a critical role in STI transmission [8-10]. STIs have been demonstrated as proxy biomarkers of sexual risk behaviour [11,12], and as a powerful tool for understanding the structure of sexual networks and predicting HIV epidemic potential [11-13]. However, unlike HIV, STI epidemiology in CHSNs remains, globally, a neglected area of research [1]. Programmatically, STI surveillance among female sex workers (FSWs) continues to be weak and infection levels poorly quantified [1]. Sexual propagation of STIs along CHSNs is also poorly understood given the dearth or limited validity of self-reported sexual behaviour data [13-15].

To attend to the United Nations’ Sustainable Development Goals (SDGs) and targets [16], particularly SDG3 target of “ensuring universal access to sexual and reproductive health services” [16], and to reduce the global burden of disease attributed to STIs, the World Health Organization (WHO) has recently formulated the “Global Health Sector Strategy on STIs” [6]. The goal of this strategy is to eliminate STIs as a major public health concern by 2030 through an integrated approach for prevention and control [6]. Milestones for 2020 include achieving 70% coverage for comprehensive STI prevention services among key populations [6]. The strategy’s first strategic direction entails “understanding the STI epidemic as a basis for advocacy, political commitment, national planning, resource mobilization and allocation, implementation, and programme improvement” [6].

Despite remarkable progress in HIV research [17], and an understanding of the role of FSWs [18], people who inject drugs (PWID) [19], and men who have sex with men (MSM) [20], in the HIV epidemic in the Middle East and North Africa (MENA) region, the epidemiology of STIs and the role of CHSNs in driving STI transmission remain largely unknown [21]. The two global reviews of STI epidemiology in FSWs had no data for any of the 23 MENA countries [22,23]. A large volume of STI data in the region resides in databases that were never analyzed, or in country-level reports that were never published in the scientific literature [24,25].

Against this background, our study aimed to characterize the epidemiology of key STIs among FSWs in MENA by 1) systematically reviewing and synthesizing all available published and unpublished evidence for Treponema pallidum (henceforth referred to as syphilis), Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and HSV-2 incidence and/or prevalence, 2) estimating, for each STI, the pooled mean prevalence of current and/or ever (seropositivity using antibody testing) infection, and 3) identifying sources of between-study heterogeneity, and regional and temporal trends associated with STI prevalence.

METHODS

We conducted a systematic review and an in-depth quantitative assessment to characterize STI epidemiology among FSWs in MENA. Details of the study methodology (including specific statistical analyses) can be found in subsequent sections.

Search strategy and selection criteria

Evidence for syphilis, C. trachomatis, N. gonorrhaoeae, T. vaginalis, and HSV-2 immunoglobulin G (IgG) incidence and/or prevalence among FSWs in MENA was systematically reviewed, informed by Cochrane’s Collaboration guidelines [26]. Findings were reported following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines [27] (checklist in Table S1 in Online Supplementary Document). The MENA definition covers 23 countries—Afghanistan, Algeria, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, United Arab Emirates (UAE), and Yemen—based on convention in HIV research [19,20,24,25], and definitions of WHO, Joint United Nations Programme on HIV/AIDS (UNAIDS), and World Bank [24].

Systematic searches were performed up to September 20, 2018, on international databases (PubMed and Embase), regional and national databases (WHO Global Health Observatory data repository [28], WHO African Index Medicus database, WHO Index Medicus for the Eastern Mediterranean Region database, Iranian Scientific Information Database, Iraqi Academic Scientific Journals’ database, and Pakistan’s PakMediNet database), abstract archives of International AIDS Society Conferences [29], as well as published and unpublished country-level and international organizations’ reports available through the MENA HIV/AIDS Epidemiology Synthesis Project database [24,25]. Search strings were broad (MeSH/Emtree terms exploded to cover all subheadings and free text terms) with no language or year restrictions (Box S1 in Online Supplementary Document).

Duplicate citations were identified using a reference manager, Endnote. Titles and abstracts were then screened for relevance, with relevant/potentially relevant citations undergoing full-text screening. Any document reporting an incidence and/or prevalence measure in FSWs for an STI of interest, based on primary data, was eligible for inclusion. Case reports, case series, editorials, commentaries, and reviews were excluded. Hand searching was further performed on reference lists of all relevant articles.

The term ‘study’ is used here to refer to a specific STI incidence or prevalence measure in a specific FSW population. Accordingly, one document/report could contribute multiple studies and one study could be published in different reports. Duplicate study results were included only once using the more detailed/recent report.

Data extraction and synthesis

Extraction was performed by HC, and double extraction by AS (extraction list in Box S2 in Online Supplementary Document). Discrepancies were settled by consensus, or by contacting authors. Full-texts in languages other than English were extracted by native speakers. Data were stratified by infection type (current vs ever (seropositivity using antibody testing)), and summarized using medians, ranges, and interquartile ranges (IQR). Definitions of infection types and details of the classification of diagnostic methods’ results into current, recent, and ever infection can be found in Table S2 in Online Supplementary Document. It was assumed, for N. gonorrhoeae and T. vaginalis studies, whenever a diagnostic method was not explicitly specified, that the diagnostic method assessed current infection.

All STI studies were extracted and reported. However, studies applying the same assay to different biological specimens from the same person were included only once in analyses, for statistical independence. This was done based on a sequential order that prioritized infection detection in endocervical swabs, followed by vaginal, then urine samples. Studies assessing prevalence using different diagnostic methods, were also included only once in analyses, with studies using polymerase chain reaction prioritized over those using culture or other methods.

Quality assessment

The quality assessment for each STI prevalence study was informed by Cochrane Collaboration guidelines (criteria in Table S3 in Online Supplementary Document) [30]. Studies were classified as having “low” vs “high” risk of bias (ROB) on each of three quality domains assessing the 1) rigor of sampling methodology (probability-based; non-probability-based), 2) response rate (≥60% or ≥60% of target sample size reached for studies using respondent-driven or time-location sampling; <60%), and 3) STI ascertainment (biological assay explicitly indicated; otherwise). Studies with missing information for a specific domain were classified as having “unclear” ROB for that domain.

Given reported limitations in HSV-2 diagnostics [31,32], the quality of HSV-2 assays was determined by consulting with an expert advisor, Professor Rhoda Ashley-Morrow, University of Washington, Seattle. Studies where the validity of the diagnostic method could not be confirmed, were excluded from the systematic review.

Quality domains were included in meta-regression analyses (described below) to assess their impact on prevalence.

Meta-analyses

For each STI, the pooled mean prevalence of current and/or ever infection, along with the corresponding 95% confidence intervals (CIs), were estimated using meta-analysis. Overall prevalence measures were replaced by their strata where applicable. For each study, one final stratification was considered based on a pre-defined sequential order that prioritizes country of origin, followed by type of FSW, year, region, and age. Subregional and time-trend analyses were conducted as warranted by data. Variances were stabilized using Freeman-Tukey type arcsine square-root transformation [33,34]. Weights were applied using the inverse-variance method [34,35], before pooling measures using a Dersimonian-Laird random-effects model [36], thereby accounting for sampling variation and for true heterogeneity [37]. Missing sample sizes for measures or their strata (<4% of all studies) were imputed using the median sample size, as calculated from studies with available information.

Heterogeneity assessment used Cochran’s Q statistic to confirm existence of heterogeneity across studies, I2 to determine magnitude of between-study variation that is due to true differences in effect size (prevalence) rather than chance, and prediction intervals to estimate the 95% interval of the true effect sizes’ distribution [37,38].

Meta-analyses were implemented in R 3.4.2 (R core team, Vienna, Austria) [39].

Meta-regressions

Only syphilis had a considerable number of measures (>100) to warrant conduct of random-effects meta-regression analyses. Independent variables considered a priori were: country/subregion, year of data collection, infection type, diagnostic method, STI ascertainment, sample size, sampling methodology, and response rate. Details of subgrouping and justifications are in Table S4 in Online Supplementary Document. Meta-regression was conducted using the log-transformed odds of syphilis infection and corresponding variance. Factors associated with higher odds of infection at P ≤ 0.10 in univariable analyses were included in the multivariable analysis. Factors with P ≤ 0.05 in the multivariable model were considered as significant predictors of heterogeneity in syphilis prevalence.

Meta-regressions were implemented in Stata/SE 15.1 (StataCorp, College Station, TX, USA) [40].

RESULTS

Search results and scope of evidence

Figure 1 shows the study selection process based on PRISMA. The search identified a total of 11 832 citations: 240 through PubMed, 1949 through Embase, and 9643 through the rest of the databases. After removing duplicates and screening of titles and abstracts, 157 reports qualified for full-text screening, of which 31 were eligible for inclusion in the systematic review.

Figure 1.  Flowchart presenting the process of study selection following PRISMA guidelines [27].
jogh-09-020408-F1


Thirteen additional reports, two of which replaced eligible articles, and four additional STI measures, were further identified through the MENA HIV/AIDS Epidemiology Synthesis Project database. Fourteen additional syphilis prevalence measures were identified through the WHO Global Health Observatory data repository. Two studies were excluded based on consultation with Professor Rhoda Ashley-Morrow, an expert advisor in HSV-2 diagnostics, because the validity of the type-specific HSV-2 serology could not be confirmed [41,42].

In sum, 42 eligible reports and 18 additional STI measures were included in the systematic review. These yielded one syphilis incidence study, and 144 prevalence studies assessing the different STIs. The latter contributed 173 stratified measures for inclusion in meta-analyses and meta-regressions.

STI prevalence data were available for 45 812 FSWs from 13 of the 23 MENA countries. Nearly two-thirds (58.9%) of prevalence studies assessed syphilis (in 29 769 FSWs), 16.3% assessed C. trachomatis (in 5613 FSWs), 12.8% assessed N. gonorrhoeae (in 5230 FSWs), 8.5% assessed T. vaginalis (in 4258 FSWs), and 3.6% assessed HSV-2 IgG (in 942 FSWs). Most studies (80.8%) were conducted post-2000. Over half (51.1%) of studies reported on current infection, 30.5% on ever infection (seropositivity using antibody testing), and 1.4% on recent infection. Time of exposure was unclear for the rest of studies (17.0%).

Incidence studies

The only one identified incidence study assessed syphilis incidence in FSWs. The study was conducted in 1988 in Mogadishu, Somalia, and reported cumulative incidence at 12.5% after six months of follow-up [43].

Prevalence studies

Prevalence of current syphilis infection among FSWs ranged, across studies (n = 28), from 0%-50.8%, with a median of 9.4% (IQR = 3.0%-23.4%; Table 1). Meanwhile, seropositivity for syphilis (n = 33) antibodies ranged from 0%-69.0%, with a median of 4.2% (IQR = 1.9%-15.2%).

Table 1.  Prevalence of syphilis among FSWs in the Middle East and North Africa*
Country short citation Year(s) of data collection City/province Sampling Study site Assay type Tested (n) Prevalence (%)
CURRENT INFECTION
Afghanistan:
Todd, 2010 [44] 2006-08 Jalalabad, Kabul, Mazar-i-Sharif Conv NGO RPR+ & TPHA+ 520 0
Egypt:
MOH, 2000 [45] 1999-00 Greater Cairo Conv Community RPR+ & TPHA+ 52 5.8
Iran:
Kassaian, 2012 [46] 2009-10 Isfahan Conv Prison, drop-in center RPR+ 91 0
Navadeh, 2012 [42] 2010 Kerman RDS Community VDRL+ 139 7.2
Kazerooni, 2014 [41] 2010-11 Shiraz RDS Community VDRL+ & FTA-ABS+ 278 0
Jahanbakhsh, 2017 [47] 2012 Tehran Conv Homeless shelters RPR+ 14 0
Morocco:
MOH, 2008 [48] 2007 Agadir, Rabat-Sale, Tanger Conv Clinic VDRL+ & TPHA+ 141 13.5
MOH, 2012 [49] 2011-12 Agadir RDS Community VDRL+ & TPHA+ 362 21.4
MOH, 2012 [49] 2011-12 Fes RDS Community VDRL+ & TPHA+ 359 18.8
MOH, 2012 [49] 2011-12 Rabat RDS Community VDRL+ & TPHA+ 392 13.9
MOH, 2012 [49] 2011-12 Tanger RDS Community VDRL+ & TPHA+ 318 13.3
Pakistan:
Baqi, 1998 [50] 1993-94 Karachi Conv Red-light district VDRL+ & FTA-ABS+ 81† 5.0
Rehan, 2009 [51] & NACP, 2005 [52] 2004 Karachi Snowball Community RPR+ & TPHA+ 421 3.6
Rehan, 2009 [51] & NACP, 2005 [52] 2004 Lahore SyCS Red-light district RPR+ & TPHA+ 387 16.0
Shah, 2004 [53] 2004 Hyderabad Conv Community VDRL+ & TPHA+ 157 11.5
Hawkes, 2009 [54] 2007 Abbottabad RDS Community RPR+ & TPHA+ 107 2.8
Hawkes, 2009 [54] 2007 Rawalpindi RDS Community RPR+ & TPHA+ 426 1.2
Khan, 2011 [55] 2007 Lahore RDS Community RPR+ & TPHA+ 730 4.5
Somalia:
Jama, 1987 [56] 1985-86 Mogadishu Conv Community VDRL+ & TPHA+ 85 44.7
Jama Ahmed, 1991 [43] 1988-89 Mogadishu Conv Community VDRL/RPR+ & TPHA+ 155 47.7
Scott, 1991 [57] 1989 Kismayu, Merca Conv NR RPR+ & FTA-ABS+ 57 50.8
Corwin, 1991 [58] 1990 Chismayu, Merca, Mogadishu Conv NR RPR+ & FTA-ABS+ 302 35.4
Watts, 1994 [59] 1990 Chismayu, Merca, Mogadishu Conv NR RPR+ & FTA-ABS+ 236 30.9
IOM, 2017 [60] 2014 Hargeisa RDS Community RDT+ & RPR+ 96 2.4
Sudan:
MOH, 2016 [61] 2015-16 Juba, South Sudan RDS Community RDT+ & RPR+ 832 7.3
Tunisia:
Bchir, 1988 [62] 1987 Sousse Conv NR VDRL+ & TPHA+ 42 28.6
Ayachi, 1997 [63] 1992-94 Tunis Conv NR VDRL+ & TPHA+ 79 24.1
Yemen:
Stulhofer, 2008 [64] 2008 Aden RDS Community VDRL+ 244 4.9
EVER INFECTION‡
Afghanistan:
NACP, 2010 [65] 2009 Kabul RDS Community RDT+ 368 5.4
NACP, 2012 [66] 2012 Herat RDS Community RDT+ 344 0.9
NACP, 2012 [66] 2012 Kabul RDS Community RDT+ 333 0.0
NACP, 2012 [66] 2012 Mazar-i-Sharif RDS Community RDT+ 355 2.0
Algeria:
MOH, 2009 [67] 2004 National Conv Sentinel surveillance TPHA+ 185 11.9
MOH, 2009 [67] 2007 National Conv Sentinel surveillance TPHA+ 380 18.4
Iran:
Mirzazadeh, 2016 [68] 2015 National Conv Community, clinic RDT+ 1,337 0.4
Pakistan:
Hawkes, 2009 [54] 2007 Abbottabad RDS Community TPHA+ 107 2.8
Hawkes, 2009 [54] 2007 Rawalpindi RDS Community TPHA+ 426 1.6
Bibi, 2010 [69] 2003 Hyderabad Conv Red-light district TPHA+ 50 44.0
Raza, 2015 [70] 2014 Rawalpindi Conv Clinic RDT+ NR 20.0
Somalia:
Jama, 1987 [56] 1985-86 Mogadishu Conv Community TPHA+ 85 57.6
Jama Ahmed, 1991 [43] 1988-89 Mogadishu Conv Community TPHA+ 155 69.0
Burans, 1990 [71] NR Mogadishu Conv NR TPHA+ 89 28.1
IOM, 2017 [60] 2008 Hargeisa RDS Community RDT+ 237 3.4
Sudan:
Sudan NACP, 2012 [72] 2011 Alshamalia RDS Community RDT+ 305 1.5
Sudan NACP, 2012 [72] 2011 Blue Nile RDS Community RDT+ 279 3.4
Sudan NACP, 2012 [72] 2011 Gadarif RDS Community RDT+ 282 3.4
Sudan NACP, 2012 [72] 2011 Gezira RDS Community RDT+ 296 5.4
Sudan NACP, 2012 [72] 2011 Kassala RDS Community RDT+ 288 4.3
Sudan NACP, 2012 [72] 2011 Khartoum RDS Community RDT+ 287 1.7
Sudan NACP, 2012 [72] 2011 North Darfur RDS Community RDT+ 303 5.2
Sudan NACP, 2012 [72] 2011 North Kodofan RDS Community RDT+ 296 4.1
Sudan NACP, 2012 [72] 2011 Red Sea RDS Community RDT+ 293 8.9
Sudan NACP, 2012 [72] 2011 River Nile RDS Community RDT+ 291 1.9
Sudan NACP, 2012 [72] 2011 Sinnar RDS Community RDT+ 303 5.3
Sudan NACP, 2012 [72] 2011 South Darfur RDS Community RDT+ 299 1.8
Sudan NACP, 2012 [72] 2011 West Darfur RDS Community RDT+ 284 1.8
Sudan NACP, 2012 [72] 2011 White Nile RDS Community RDT+ 288 4.2
MOH, 2016 [61] 2015-16 Juba, South Sudan RDS Community RDT+ 832 12.0
Tunisia
Bchir, 1988 [62] 1987 Sousse Conv NR TPHA+ 42 38.1
Ayachi, 1997 [63] 1992-94 Tunis Conv NR TPHA+ 79 36.7
Znazen, 2010 [73] 2007 Gabes, Sousse, Tunis Conv Clinic TPHA+ 183 2.7
UNCLEAR
Afghanistan:
WHO, 2018 [28] 2010 NR NR NR NR NR 8.7
MENA HIV ESP, 2013 [74] 2012 Kabul NR NR NR 440 5.7
WHO, 2018 [28] 2017 NR NR NR NR 2,457 1.3
Algeria:
WHO, 2018 [28] 2013 Oran NR NR NR 27 7.4
WHO, 2018 [28] 2014 Saida NR NR NR 24 29.2
WHO, 2018 [28] 2016 NR Conv VCT NR 183 14.2
WHO, 2018 [28] 2017 NR Conv VCT NR 81 16.0
Djibouti:
WHO, 2015 [1] 2014 4 urban sites NR NR NR 361 5.0
Iran:
WHO, 2018 [28] 2008 NR NR NR NR NR 1.6
Moayedi-Nia, 2016 [75] 2012-13 Tehran RDS Community NR 161 0
Jordan:
WHO, 2015 [1] 2008 NR NR NR NR NR 6.7
Morocco:
Khattabi, 2005 [76] 2004 National Conv Prison NR 332 9.6
Khattabi, 2005 [76] 2004 National Conv Clinic NR 272 12.1
Khattabi, 2005 [76] 2004 Grand Casablanca Conv STI clinic NR 143 9.0
Bennani, 2006 [77] 2005 National Conv Prison NR 102 11.8
Bennani, 2006 [77] 2005 National Conv Clinic NR 143 13.3
WHO, 2018 [28] 2008 NR NR NR NR NR 16.9
Pakistan:
MENA HIV ESP, 2010 [24] 2007 NR NR NR NR NR 23.5
Somalia:
WHO, 2018 [28] 2017 Bossaso, Hargeisa, Mogadishu RDS Community NR 860 2.7
Sudan:
WHO, 2018 [28] 2016 National RDS Community NR 4,123 4.1
WHO, 2018 [28] 2017 South Sudan NR NR NR 1,244 14.4
Yemen:
WHO, 2018 [28] 2010 Hodeida RDS Community NR 301 0

Conv – convenience, FTA-ABS – fluoresceent treponemal antibody absorption test, IOM – International Organization for Migration, MENA HIV ESP – MENA HIV/AIDS Epidemiology Synthesis Project database, MOH – Ministry of Health, NACP – National AIDS Control Program, NGO – non-governmental organization, NR – not reported, RDS – respondent-driven sampling, RDT – rapid diagnostic test, RPR – rapid plasma regain, STI – sexually transmitted infection, SyCS – systematic cluster sampling, TPHA – Treponema pallidum haemagglutination assay, VCT – voluntary counseling and testing center, VDRL – venereal disease research laboratory

*The table is sorted, for each country, by data collection year(s) then city/province.

†Sample comprised of 77 FSWs and 4 transgender women.

‡Ever infection indicates seropositivity using antibody testing.



Current C. trachomatis infection prevalence (n = 14) ranged from 0.7%-72.9%, with a median of 7.7% (IQR = 1.7%-22.4%), while seropositivity prevalence using IgG (n = 5) ranged from 19.8%-100%, with a median of 85.8% (IQR = 46.8%-97.1%; Table 2). Two studies reported recent C. trachomatis infection (assessed using serological biomarkers) at 29.2% [79] and 95.0% [78].

Table 2.  Prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis among FSWs in the Middle East and North Africa*
Country short citation Year(s) of data collection City/province Sampling Study site Specimen Assay type Tested (n) Prevalence (%)
CURRENT INFECTION
Chlamydia trachomatis
Algeria:
Kadi, 1989 [78] NR NR Conv Clinic Endocervical IFAT 44 45.5
Egypt:
MOH, 2000 [45] 1999-00 Cairo Conv Community Urine NAAT 52 7.7
Iran:
Darougar, 1983 [79] NR Bandar Abbas, Tehran Conv Clinic Endocervical Culture 116 6.9
Kazerooni, 2014 [41] 2010-11 Shiraz RDS Community Vaginal NAAT 278 9.0
Mirzazadeh, 2016 [68] 2015 National Conv Clinic, community Vaginal NAAT 1337 6.0
Morocco:
MOH, 2008 [48] 2007 Agadir, Rabat Sale, Tanger Conv Clinic Endocervical & urine NAAT 141 22.7
MOH, 2012 [49] 2011-12 Agadir RDS Community Endocervical NAAT 368 22.4
Pakistan:
Rehan, 2009 [51] 2004 Karachi Snowball Community Vaginal NAAT 348 5.2
Rehan, 2009 [51] 2004 Lahore SyCS Red-light district Vaginal NAAT 283 11.0
Hawkes, 2009 [54] 2007 Abbottabad RDS Community Endocervical NAAT 107 0.9
Hawkes, 2009 [54] 2007 Rawalpindi RDS Community Endocervical NAAT 426 1.7
Khan, 2011 [55] 2007 Lahore RDS Community Endocervical NAAT 730 7.7
Somalia:
IOM, 2017 [60] 2014 Hargeisa RDS Community Urine NAAT 90 0.7
Tunisia:
Znazen, 2010 [73] 2007 Gabes, Sousse, Tunis Conv Clinic Endocervical NAAT 188 72.9
Neisseria gonorrhoeae
Egypt:
MOH, 2000 [45] 1999-00 Cairo Conv Community Urine NAAT 52 7.7
Iran:
Kazerooni, 2014 [41] 2010-11 Shiraz RDS Community Vaginal Culture 278 1.4
Navadeh, 2012 [42] & WHO, 2011 [80] 2010 Kerman RDS Community NR NR† 144 0
Nasirian, 2017 [81] 2013-14 Isfahan Conv Harm reduction Endocervical NAAT 99 9.1
Nasirian, 2017 [81] 2013-14 Isfahan Conv Harm reduction Urine NAAT 99 0‡
Taghizadeh, 2015 [82] 2014 Sari Conv Drop-in center NR NR† 117 1.0
Mirzazadeh, 2016 [68] 2015 National Conv Clinic, community Vaginal NAAT 1337 1.3
Morocco:
MOH, 2008 [48] 2007 Agadir, Rabat Sale, Tanger Conv Clinic Endocervical & urine NAAT 141 10.6
MENA HIV ESP, 2010 [24] NR NR NR NR NR NR† NR 3.5
MOH, 2012 [49] 2011-12 Agadir RDS Community Endocervical NAAT 368 11.7
Pakistan:
Rehan, 2009 [51] 2004 Karachi Snowball Community Vaginal NAAT 348 9.8
Rehan, 2009 [51] 2004 Lahore SyCS Red-light district Vaginal NAAT 383 12.3
Hawkes, 2009 [54] 2007 Abbottabad RDS Community Endocervical NAAT 107 1.9
Hawkes, 2009 [54] 2007 Rawalpindi RDS Community Endocervical NAAT 426 2.0
Khan, 2011 [55] 2007 Lahore RDS Community Endocervical NAAT 730 7.5
Somalia:
Burans, 1990 [71] NR Mogadishu Conv NR NR Culture 89 11.2
IOM, 2017 [60] 2014 Hargeisa RDS Community Urine NAAT 91 0.4
Tunisia:
NACP, 2005 [83] 2005 NR NR NR NR NR† NR 12.0-17.0§
Znazen, 2010 [73] 2007 Gabes, Sousse, Tunis Conv Clinic Endocervical Culture 188 3.7‖
Znazen, 2010 [73] 2007 Gabes, Sousse, Tunis Conv Clinic Endocervical NAAT 188 11.2
Trichomonas vaginalis
Egypt:
MOH, 2000 [45] 1999-00 Cairo Conv Community Urine NAAT 52 19.2
Iran:
Vafaei, 2015 [84] 2009-11 Shiraz Conv Clinic, drop-in center Endocervical Wet mount 85 8.2
Navadeh, 2012 [42] & WHO, 2011 [80] 2010 Kerman RDS Community NR NR† 144 1.4
Nasirian, 2017 [81] 2013-14 Isfahan Conv Harm reduction Endocervical NAAT 99 0.0
Nasirian, 2017 [81] 2013-14 Isfahan Conv Harm reduction Urine NAAT 99 0.0‡
Mirzazadeh, 2016 [68] 2015 National Conv Clinic, community Vaginal NAAT 1337 11.9
Morocco:
MOH, 2008 [48] 2007 Agadir, Rabat Sale, Tanger Conv Clinic Endocervical & vaginal Culture 141 14.9
MOH, 2012 [49] 2011-12 Agadir RDS Community Vaginal NAAT 367 11.8
Pakistan:
Rehan, 2009 [51] 2004 Karachi Snowball Community Vaginal Culture 386 5.2
Rehan, 2009 [51] 2004 Lahore SyCS Red-light district Vaginal Culture 384 19.3
Hawkes, 2009 [54] 2007 Abbottabad RDS Community Vaginal NAAT 107 5.7
Hawkes, 2009 [54] 2007 Rawalpindi RDS Community Vaginal NAAT 426 4.3
Khan, 2011 [55] 2007 Lahore RDS Community Vaginal Culture 730 5.1
RECENT INFECTION
Chlamydia trachomatis
Algeria:
Kadi, 1989 [78] NR NR Conv Clinic Serum MIF>1:64¶ 44 95.0
Iran:
Darougar, 1983 [79] NR Bandar Abbas, Tehran Conv Clinic Serum MIF-IgM 154 29.2
EVER INFECTION**
Chlamydia trachomatis
Algeria:
Kadi, 1989 [78] NR NR Conv Clinic Serum MIF-IgG 44 100
Iran:
Darougar, 1983 [79] NR Bandar Abbas, Tehran Conv Clinic Serum MIF-IgG 154 94.2
Kassaian, 2012 [46] 2009-10 Isfahan Conv Drop-in center Serum ELISA-IgG 91 19.8
Tunisia
Bchir, 1988 [62] 1987 Sousse Conv NR Serum MIF>1:16 42 73.8
Znazen, 2010 [73] 2007 Gabes, Sousse, Tunis Conv Clinic Serum MIF-IgG 183 85.8
UNCLEAR:
Chlamydia trachomatis
Iran:
Navadeh, 2012 [42] & WHO, 2011 [80] 2010 Kerman RDS Community NR NR 144 2.9
Morocco:
MENA HIV ESP, 2010 [24] NR NR NR NR NR NR NR 19.1

Conv – convenience, ELISA – enzyme-linked immunosorbent assay, IFAT – indirect immunofluorescence antibody test, IgG – immuneglobulin G, IgM - immunoglobulin M, IOM – International Organization for Migration, MENA HIV ESP – MENA HIV/AIDS Epidemiology Synthesis Project database, MIF – micro-immunofluorescence, MOH – Ministry of Health, NAAT – Nucleic acid amplification test, NR – not reported, RDS – respondent-driven sampling, SyCS – systematic cluster sampling, WHO – World Health Organization

*The table is sorted for each country by data collection year(s) then city/province.

†For Neisseria gonorrhoeae and Trichomonas vaginalis studies, whenever the diagnostic method was not explicitly specified, it was assumed that the diagnostic method assessed current infection.

‡Studies reported in the systematic review, but not included in analyses considering the priority order followed for selecting studies applying the same assay to different biological specimens.

§Range reported based on several studies whose abstracts or full-texts could not be retrieved (mid-point: 14.5%).

‖Studies reported in the systematic review, but not included in analyses as prevalence was also assessed using NAAT.

¶Reported in study as recent infection.

**Ever infection indicates seropositivity using antibody testing.



Current N. gonorrhoeae infection prevalence (n = 18) ranged from 0%-14.5%, with a median of 7.6% (IQR = 1.3%-11.1%; Table 2). Current T. vaginalis infection prevalence (n = 12) ranged from 0%-19.3%, with a median of 7.0% (IQR = 4.5%-14.2%; Table 2). HSV-2 seropositivity (using IgG; n = 5) ranged from 4.7%-55.5%, with a median of 20.0% (IQR = 6.4%-39.1%; Table 3).

Table 3.  Prevalence of herpes simplex virus type 2 (HSV-2) immunoglobulin G (IgG) sero-markers among FSWs in the Middle East and North Africa
Country short citation Year(s) of data collection City/province Sampling Study site Specimen Assay type Tested (n) Prevalence (%)
Pakistan:
Hawkes, 2009 [54] 2007 Abbottabad RDS Community Serum ELISA-IgG 107 4.7
Hawkes, 2009 [54] 2007 Rawalpindi RDS Community Serum ELISA-IgG 426 8.0
Syria:
Ibrahim, 2000 [85] 1995-98 Damascus Conv Cheap hotels & prison Serum MEIA-IgG 101 22.8
Ibrahim, 2000 [85] 1995-98 Damascus Conv Bars Serum MEIA-IgG 125 20.0
Tunisia:
Znazen, 2010 [73] 2007 Gabes, Sousse, Tunis Conv Clinic Serum ELISA-IgG 183 55.5

Conv – convenience, ELISA – enzyme-linked immunosorbent assay. MEIA – micro-enzyme immunoassay. RDS – respondent-driven sampling



Quality assessment

The summarized and study-specific ROB assessments of prevalence measures are in Tables S5 and S6 in Online Supplementary Document, respectively. Briefly, nearly half of studies (44.7%) used probability-based sampling. Most studies (78.7%) indicated explicitly the biological assay used for STI ascertainment. Response rate information was missing in over half of studies (51.8%).

Overall, studies were of reasonable quality. Close to 60% of studies had low ROB on at least two quality domains, and none had high ROB on two or more domains.

Pooled mean prevalence estimates

Table 4 shows the results of meta-analyses estimating the pooled mean prevalence of current and/or ever infection for each STI. The mean prevalence of current infection was estimated at 12.7% (95% CI = 8.5%-17.7%) for syphilis, 14.4% (95% CI = 8.2%-22.0%) for C. trachomatis, 5.7% (95% CI = 3.5%-8.4%) for N. gonorrhoeae, and 7.1% (95% CI = 4.3%-10.5%) for T. vaginalis.

Table 4.  Results of meta-analyses on prevalence studies for Treponema pallidum (syphilis), Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and herpes simplex virus type 2 (HSV-2) among FSWs in the Middle East and North Africa
Sexually transmitted infection* Studies Samples Reported prevalence Pooled mean prevalence Heterogeneity measures
N† Tested Positive Median‡ (%) Range‡
(%) Estimate (%) 95% CI Q§ (P) I2‖ (%; 95% CI) Prediction interval¶ (95%)
Current infection:
Treponema pallidum (syphilis) 34 7103 842 10.8 0-62.0 12.7 8.5-17.7 1045.3 (P < 0.0001) 96.8 (96.2-97.4) 0.0-48.8
Chlamydia trachomatis 16 4608 512 8.4 0.7-76.2 14.4 8.2-22.0 611.4 (P < 0.0001) 97.5 (96.9-98.1) 0.0-53.6
Neisseria gonorrhoeae 20 5230 301 7.9 0-17.5 5.7 3.5-8.4 248.2 (P < 0.0001) 92.3 (89.6-94.4) 0.0-21.6
Trichomonas vaginalis 13 4258 397 7.1 0-19.3 7.1 4.3-10.5 164.7 (P < 0.0001) 92.7 (89.3-95.0) 0.0-23.7
Recent infection:
Chlamydia trachomatis 2** 198 87 62.1 29.2-95.0
Ever infection:††
Treponema pallidum (syphilis) 50 9968 710 7.0 0-92.3 12.8 9.4-16.6 1261.0 (P < 0.0001) 96.1 (95.5-96.7) 0.0-45.2
Chlamydia trachomatis 6 514 395 84.7 19.8-100 80.3 53.2-97.6 213.0 (P < 0.0001) 97.7 (96.4-98.5) 0.0-100.0
Herpes simplex virus type 2 IgG 8 942 188 20.3 4.7-59.7 23.7 10.2-40.4 185.0 (P < 0.0001) 96.2 (94.3-97.5) 0.0-84.9
Unclear:
Treponema pallidum (syphilis) 22 12 698 771 8.9 0-29.2 7.7 5.1-10.7 591.3 (P < 0.0001) 96.4 (95.5-97.2) 0.0-25.7
Chlamydia trachomatis 2** 293 32 11.0 2.9-19.1

CI – confidence interval, FSWs – female sex workers, IgG – immunoglobulin G, P – P-value

*The same population may have contributed different measures for both current infection and ever (seropositivity using antibody testing) infection.

†Missing sample sizes for measures (or their strata) were imputed using the median sample size calculated from studies with available information (only two stratified measures for Neisseria gonorrhoeae, one stratified measure for Chlamydia trachomatis, one stratified measure for current syphilis infection, 5 stratified measures of unclear syphilis infection, had their sample size imputed, that is 5% of all data).

‡Medians and ranges were calculated based on the stratified prevalence measures.

§Q – the Cochran’s Q statistic is a measure assessing the existence of heterogeneity in effect size (here, prevalence) across studies.

‖I2 – a measure assessing the magnitude of between-study variation that is due to differences in effect size (here, prevalence) across studies rather than chance.

¶Prediction interval: a measure estimating the 95% interval of the distribution of true effect sizes (here, prevalence measures).

**Meta-analyses were performed if at least three studies were available.

††Ever infection indicates seropositivity using antibody testing.



The mean prevalence of ever infection was estimated at 12.8% (95% CI = 9.4%-16.6%) for syphilis, 80.3% (95% CI = 53.2%-97.6%) for C. trachomatis, and 23.7% (95% CI = 10.2%-40.4%) for HSV-2 IgG.

There was strong evidence for heterogeneity in effect size (here, prevalence). P for Cochran’s Q statistic was always <0.0001. I2 was >90% in all meta-analyses, indicating that most variability is due to true differences in effect size across studies, rather than being due to chance. Prediction intervals were also wide affirming high heterogeneity.

Additional meta-analyses at the subregional level indicated the mean prevalence of current syphilis infection at 3.0% (95% CI = 0.9%-9.2%) in Eastern MENA, 17.6% (95% CI = 14.2%-21.3%) in North Africa, and 27.8% (95% CI = 15.2%-42.4%) in the Horn of Africa (Table S7 in Online Supplementary Document). There was also a tendency for a decline in current infection prevalence post-2010 (Table S8 and Figure S1A in Online Supplementary Document). For the rest of the STIs, the number of studies was small and the CIs were wide and overlapping to warrant conclusive statement about the temporal trend (Table S8 in Online Supplementary Document).

Predictors of variability in syphilis infection

Country/subregion, year of data collection, diagnostic method, sample size, sampling methodology, and response rate were associated with higher odds of syphilis infection in the univariable meta-regression analyses. These were, therefore, included in the multivariable model (Table 5). About a third of the variability was explained by each of year of data collection and subregion (adjusted R-squared: 34.6% and 31.5%, respectively). Meanwhile, no evidence for an association with infection type (current infection; ever infection), or STI ascertainment (biological assay explicitly indicated; otherwise) was found.

Table 5.  Results of meta-regression analyses to identify associations and sources of between-study heterogeneity in syphilis prevalence in the Middle East and North Africa (MENA)
Factors Studies Samples Univariable analyses Multivariable analysis*
Total N Total n OR† (95% CI) P P‡ of LR test Variance explained R2 (%) AOR† (95% CI) P P§ of LR test
Country/subregion:‖
Eastern MENA Afghanistan, Iran, Pakistan 28 10 865 1.00 <0.001 31.52 1.00 <0.001
Egypt, Jordan, Yemen Egypt, Jordan, Yemen 4 881 0.89 (0.15-5.10) 0.893 0.66 (0.13-3.28) 0.609
North Africa Algeria, Morocco, Sudan, Tunisia 48 12 394 5.34 (2.45-11.61) <0.001 5.01 (2.37-10.61) <0.001
Horn of Africa Djibouti, Somalia, South Sudan 26 5629 21.63 (8.89-52.69) <0.001 6.40 (2.45-16.69) <0.001
Year of data collection 106 29 769 0.88 (0.85-0.91) <0.001 <0.001 34.61 0.93 (0.88-0.98) 0.005 0.005
Infection type Current 34 7103 1.00 0.515 0.00
Ever** 50 9968 1.25 (0.52-3.00) 0.622
Unclear 22 12 698 0.69 (0.23-2.04) 0.501
Diagnostic method RPR/VDRL & TPHA/FTA-ABS/RDT 29 6095 1.00 <0.001 22.44 1.00 0.444
RPR/VDRL 4 488 0.09 (0.01-0.61) 0.013 0.76 (0.15-4.00) 0.746
TPHA 28 1781 2.17 (0.86-5.45) 0.099 1.29 (0.54-3.07) 0.558
RDT 23 8707 0.17 (0.06-0.45) <0.001 0.46 (0.18-1.18) 0.104
Not specified 22 12 698 0.43 (0.16-1.16) 0.094 0.75 (0.24-2.33) 0.614
STI ascertainment Biological assay not reported 23 13 066 1.00 0.284 0.15
Biological assay explicitly indicated 83 16 703 1.66 (0.65-4.20) 0.284
Sample size <100 participants 42 1960 1.00 <0.001 20.02†† 1.00
≥100 participants 64 27 809 0.16 (0.08-0.32) <0.001 1.60 (0.62-4.15) 0.329 0.329
Sampling methodology Non-probability/unclear sampling 66 12 555 1.00 <0.001 18.73‡‡ 1.00
Probability-based sampling 40 17 214 0.16 (0.08-0.34) <0.001 0.63 (0.25-1.63) 0.339 0.339
Response rate <60%/unclear 69 18 400 1.00 <0.001 10.23§§ 1.00
≥60% 37 11 369 0.25 (0.12-0.54) 0.001 0.73 (0.29-1.84) 0.495 0.495

AOR – adjusted odds ratio, CI – confidence interval, FTA-ABS – fluorescent treponemal antibody absorption test, LR – likelihood ratio, OR – odds ratio, P – P-value, RDT – rapid diagnostic test, RPR – rapid plasma regain, STI – sexually transmitted infection TPHA – Treponema pallidum haemagglutination assay. VDRL – venereal disease research laboratory

*Adjusted R2 in the multivariable model: 48.46%.

†An increment of 0.1 was added to number of events when generating log odds of syphilis infection. This is because 8 stratified measures had zero events.

‡Factors with P ≤ 0.1 were eligible for inclusion in the multivariable analysis.

§Factors with P < 0.05 in the multivariable model were considered as significant predictors.

‖Countries were grouped based on geography and similarity in prevalence levels.

¶Missing values for year of data collection (only one stratified measure) were imputed using data for year of publication adjusted by the median difference between year of publication and median year of data collection for studies with complete information.

**Ever infection indicates seropositivity using antibody testing.

††The high R2 was investigated and found to be due to confounding with year of data collection. Most studies with sample size ≥100 were conducted in recent years.

‡‡The high R2 was investigated and found to be due to confounding with country and year of data collection. Studies with non-probability sampling were mostly from the Horn of Africa. These studies tended also to be conducted in earlier years.

§§The high R2 was investigated and found to be due to confounding with year of data collection. Most studies with response rate ≥60% were conducted in recent years.



The multivariable analysis showed strong evidence for subregional differences, with Horn of Africa and North Africa showing, respectively, 6-fold (adjusted odds ratio (AOR): 6.4; 95% CI = 2.5-16.7) and 5-fold (AOR = 5.0; 95% CI = 2.5-10.6), higher odds of syphilis infection than Eastern MENA.

There was also strong evidence for a temporal trend of decreasing odds of infection at 7% per year (AOR = 0.93; 95% CI = 0.88-0.98; linearity dictated by data (Figure S1 in Online Supplementary Document) over the last three decades. Although this trend was noted in all subregions, individual subregion meta-regressions were not always powered to detect statistical significance (not shown).

No evidence for an association with diagnostic method, sample size, sampling methodology, and response rate was identified in the multivariable model. The multivariable model explained 48.5% of variation in syphilis prevalence.

DISCUSSION

We provided, to our knowledge, the first detailed assessment of the epidemiology of key STIs in FSWs in MENA, a neglected key population. Our findings indicated substantial STI prevalence, several folds higher than that among the general population [2,13,24,86]. These findings suggest a major role for CHSNs in driving STI transmission in MENA. We further found large heterogeneity in syphilis infection levels by subregion within MENA, as well as a trend of decreasing odds of infection by ~ 7% per year – less than the 17% [86] annual decline needed to achieve the target of 90% reduction in syphilis incidence by 2030 [6].

Despite the significant infection burden, STI surveillance and response in MENA continue to be rudimentary [21], and far below the coverage targets of WHO Global Health Sector Strategy for STIs [6]. Infected individuals are often identified through routine case notifications with surveillance/testing being largely limited to HIV [21,24,87], and sexual health programs, where they exist, cater to general population women rather than women at high risk [24].

Although our expansive search identified considerable evidence at the regional-level, including data that will appear in the scientific literature for the first time, evidence varied by country. Over half of countries had no data on any of the STIs in this key population, less than a third had data on C. trachomatis, N. gonorrhoeae, or T. vaginalis, and only three countries had data on HSV-2 IgG (Table 1, Table 2 and Table 3). This outcome is of concern, given the considerable, yet preventable, STI infection burden among FSWs in the region (Table 4), and the major “core group” role that CHSNs play in STI transmission in any population [10]. Indeed, while the population proportion of FSWs (proportion of FSWs out of the total women population) varies across countries and may seem relatively small [18,88], the size of CHSNs is large suggesting a considerable number of women and men at risk of STI-related morbidity, either through engagement in high sexual risk behavior, or through onward infection transmission [89].

Availability of STI data stands in contrast to HIV data, for which the volume of evidence among FSWs was several fold higher and encompassed most countries [18]. Attending to WHO Global Health Sector Strategy on STIs [6] necessitates a major expansion of STI research and surveillance, as has been done for HIV [17,87,90]. Regrettably, integrated bio-behavioural surveillance surveys (IBBSS) among key populations continue to be focused on HIV, rarely incorporating STIs [91,92]. This presents an important, yet lost, opportunity for monitoring STI levels and trends in key populations, informing programming efforts, gaining an in-depth understanding of sexual networks’ structure, and advancing STI research in this region [13,91,93].

Subregion and time explained most variation in syphilis prevalence—each explained over a third of the variation, and both (remarkably) explained ~ 50% of the variation (Table 5). The strong subregional differences, with Horn of Africa showing the highest prevalence, followed by North Africa, and then Eastern MENA (Table 5 and Table S7 in Online Supplementary Document), appear to reflect variability in the risk environment, such as differences in structure of sexual networks [24], condom use [18], and access to care [24]. The same pattern has been seen in HIV epidemiology among FSWs [18].

There was strong evidence for a time trend of decreasing odds of infection at ~ 7% per year (Table 5, and Table S8 and Figure S1 in the OSD), consistent with, but smaller than, the decline reported for the general population in MENA in a recent global analysis [86], and the declines reported for the general populations in other regions [86]. Different factors may have contributed to this trend including safer sex following the HIV epidemic [94], increased condom use to prevent unwanted pregnancy [18], and HIV-related mortality which may have disproportionally affected populations at higher risk of STIs [95]. This may have been also a consequence of a shorter duration of active syphilis infection in FSWs or their sex partners [96,97], possibly because of improvements in syphilis diagnostics and treatment, or because of widespread use of antibiotics (including for non-STI infections, which sometimes may cure concurrent syphilis) [86].

This being said, recent surveillance data seems also to suggest an increase in syphilis incidence and/or prevalence in other sexual networks or in specific settings, such as among MSM [98-100], and even among reproductive-age women in few countries where congenital syphilis appears to be rising [101,102]. Contributors to these trends may include behavioral factors, such as more sexual partners and unprotected sex among MSM, as well as contextual factors, and possibly even biological factors [99,100,102-104].

Prevalence measures for syphilis and for C. trachomatis in FSWs in MENA were comparable to global levels [22,23], but prevalence measures for N. gonorrhoeae and T. vaginalis leaned towards the lower end of the global range [22,23]. Even though the risk environment among FSWs in MENA seems less conducive to STI transmission, as compared to other regions [18], STI prevalence levels are substantial, perhaps affected by poor access to health care and prevention interventions [21,24,105], as well as absence of enabling environments for this vulnerable population, in a context of criminality [106,107] and stigma [108-110].

While interventions aiming at promoting safer sex, such as condom use, and STI etiological diagnosis and treatment, in high risk populations are widely accepted and advocated for [6,111-114], STI syndromic case management and presumptive treatment have been increasingly subject to criticism amid growing concerns about their role in promoting pathogens’ antimicrobial resistance (AMR) [111,115-119]. Indeed, substantial AMR prevalence and multiple drug resistant strains have been found in gonococcal isolates from FSWs in sub-Saharan Africa [120,121] and elsewhere [122]. This suggests that despite the effectiveness of targeted STI treatment services in reducing STI incidence and prevalence, their appropriateness and sustainable implementation will need to be informed by surveillance and monitoring, notably for AMR, and thus may vary across settings [111,122]. This further supports WHO efforts towards building a global business case for accelerating development of STI vaccines as a fundamental solution to STI drug resistance [123-125].

This study is limited by the quantity and quality of available data. STI prevalence among FSWs remains unknown in over half of countries. While there was considerable evidence for syphilis, less evidence was found for C. trachomatis, N. gonorrhoeae, T. vaginalis, and HSV-2, limiting our ability to conduct advanced meta-analytics—meta-regressions were carried out only for syphilis. Though, for syphilis prevalence, the differences between current vs ever (seropositivity using antibody testing) infection, as well as the differences between diagnostics, were consistent with the findings of a large global analysis for the general population [86], the confidence intervals were wide owing to the smaller number of studies (Table 5). Several measures were based on routine data reporting, and did not include sufficient documentation of study methodology. There was also a wide array of diagnostics used for STI ascertainment, which may have affected observed prevalence.

Available studies may not be representative of the wider population of FSWs, or could be subject to biases, such as selection bias or detection bias. Of note, however, that there was no evidence that any of the assessed study-specific quality domains (Tables S5-S6 in Online Supplementary Document), including sampling methodology, response rate, and explicit indication of the assay used for infection ascertainment, had an effect on prevalence in the multivariable meta-regression (Table 5). Despite limitations, our study provided a detailed synthesis of STI epidemiology in FSWs in MENA, in a background of lack of evidence for this region [22,23]. A significant volume of published and unpublished data was identified and analyzed, and for the first time.

In conclusion, STI levels among FSWs are considerable, supporting a key role for CHSNs in STI transmission dynamics in MENA, and highlighting the public health needs of this neglected and vulnerable population. Despite the progress in our epidemiological understanding, major gaps persist, with no evidence being available for over half of MENA countries. With the limited STI surveillance [24,126], and the focus of programmatic response on case management and syndromic approach, rather than being evidence-informed and grounded on etiological studies [24,126], there is a critical need to expand STI surveillance and the broader STI research agenda. STI testing should be part of IBBSS studies, as well as part of voluntary counseling and testing services for HIV [91,93]. Interventions should factor research findings to ensure adequate and efficient resource allocation. Without such expansion of STI efforts, it will not be possible to monitor infection trends, or to inform a public health response that attends to the WHO Global Health Sector Strategy on STIs [6].

Additional material
Acknowledgements

The authors gratefully acknowledge Professor Rhoda Ashley-Morrow from the University of Washington, for her support in assessing the quality of herpes simplex virus type 2 diagnostic methods. The authors also gratefully acknowledge Ms. May Al-Kassar for her assistance with study diagnostics, and Ms. Adona Canlas for her assistance with locating full-texts of articles. The authors further gratefully acknowledge the Department of Reproductive Health and Research at the World Health Organization, for making syphilis routine data reporting available for public use, through the Global Health Observatory data repository. Ethics approval deemed as not required for this research by the Research Governance & Integrity Office at the London School of Hygiene and Tropical Medicine.

Notes

[1] Funding: This publication was made possible by NPRP grant number 9-040-3-008 from the Qatar National Research Fund (a member of Qatar Foundation). Infrastructure support was provided by the Biostatistics, Epidemiology, and Biomathematics Research Core at the Weill Cornell Medicine-Qatar. Salary for HAW was from the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement (K012126/1). The statements made herein are solely the responsibility of the authors.

[2] Authorship contributions: HC conceived and designed the study, conducted the systematic review of the literature, performed the data analyses, and wrote the first draft of the article. AS double extracted the data. EM contributed to the title and abstract screening of regional and country-level databases. HAW contributed to study design, data analyses, and drafting of the article. LJA contributed to study design, data analyses, and drafting of the article. All authors contributed to discussion and interpretation of the results and writing of the manuscript. All authors have read and approved the final manuscript.

[3] Competing interests: The authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no competing interests.

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