Do Peer Navigators Improve Initiation and Retention in HIV/VH/STI Treatment Programs for People From Key Populations? A Systematic Review of Effectiveness, Values and Preferences, and Cost.

BACKGROUND: Key populations are disproportionately affected by HIV, viral hepatitis (VH), and sexually transmitted infections (STIs) and face barriers to care. Peer navigation programs are widely used, but evidence supporting their use has not been synthesized. SETTING: Peer navigation programs for sex workers, men who have sex with men, people who inject drugs, prisoners, and trans and gender diverse people globally. METHODS: To inform World Health Organization guidelines, we conducted a systematic review of effectiveness, values and preferences, and cost studies published between January 2010 and May 2021. We searched CINAHL, PsycINFO, PubMed, and EMBASE; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials and comparative observational studies evaluating time to diagnosis or linkage to care, treatment initiation, treatment retention/completion, viral load, cure, or mortality. We assessed risk of bias and summarized findings in GRADE evidence profiles. Values and preferences and cost data were summarized descriptively. RESULTS: Four studies evaluated the effectiveness of peer navigators for key populations. All were focused on HIV; none were designed for VH or STIs. These studies showed mixed effects on linkage to care, treatment retention/completion, and viral load; no studies measured treatment initiation, cure, or mortality. Two values and preferences studies with community-based organization staff and health workers suggested peer navigators for key populations were acceptable and valued, although continued challenges remained. No cost studies were identified. CONCLUSIONS: Although limited, available studies provide moderate certainty evidence for benefits of HIV/VH/STI peer navigation programs for key populations. Further evaluations are needed.

Vaccine value profile for Neisseria gonorrhoeae.

Neisseria gonorrhoeae infection (gonorrhoea) is a global public health challenge, causing substantial sexual and reproductive health consequences, such as infertility, pregnancy complications and increased acquisition or transmission of HIV. There is an urgency to controlling gonorrhoea because of increasing antimicrobial resistance to ceftriaxone, the last remaining treatment option, and the potential for gonorrhoea to become untreatable. No licensed gonococcal vaccine is available. Mounting observational evidence suggests that N. meningitidis serogroup B outer membrane vesicle-based vaccines may induce cross-protection against N. gonorrhoeae (estimated 30%-40% effectiveness using the 4CMenB vaccine). Clinical trials to determine the efficacy of the 4CMenB vaccine against N. gonorrhoeae are underway, as are Phase 1/2 studies of a new gonococcal-specific vaccine candidate. Ultimately, a gonococcal vaccine must be accessible, affordable and equitably dispensed, given that those most affected by gonorrhoea are also those who may be most disadvantaged in our societies, and most cases are in less-resourced settings. This vaccine value profile (VVP) provides a high level, holistic assessment of the current data to inform the potential public health, economic and societal value of pipeline vaccines. This was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations. All contributors have extensive expertise on various elements of the N. gonorrhoeae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using published data obtained from peer-reviewed journals or reports.

The role of syphilis self-testing as an additional syphilis testing approach in key populations: a systematic review and meta-analysis.

BACKGROUND: Syphilis is causing epidemics in many countries. Syphilis self-testing (SST) has potential to increase testing and treatment coverage in the same manner as documented for self-testing of, for example, HIV, hepatitis C virus, and COVID-19. We aimed to synthesise current evidence on the utility of SST. METHODS: We conducted a systematic review and, where possible, meta-analysis. We searched MEDLINE, Embase, CINAHL, Scopus, and Web of Science for publications published from Jan 1, 2000, to Oct 13, 2022. We included publications with original data on any syphilis rapid tests, including dual HIV-syphilis tests. Study populations were not restricted. We used random-effects meta-analysis to calculate the pooled proportion of people offered SST who undertook the test. The systematic review was registered in PROSPERO (CRD42022302129). FINDINGS: In total, 40 499 citations were identified. 11 publications from seven studies from the USA, Zimbabwe, and China met eligibility criteria. Of those, four studies reported data from men who have sex with men and five studies used dual HIV-SST. Using data from one randomised controlled trial and three observational studies, the pooled proportion of people who received SST kits who undertook the test was 88% (95% CI 85-91). No studies provided data on the sensitivity or specificity of SST. Overall, user and provider preference for SST was high, with participants reporting convenience, privacy, rapid results, autonomy, trust in blood-based tests, decreased facility contact, and time savings, with individuals being able to correctly self-test. Publications from China reported that SST had lower costs per person tested than existing facility-based testing options. INTERPRETATION: Our review builds on the literature for self-testing across different disease areas and demonstrates that SST has the potential to reach underserved populations. As this review found that SST use was acceptable and feasible to implement, SST can be used as an additional syphilis testing approach. Since no data on the sensitivity and specificity of SST were found, further implementation research will be required to guide the best strategies for SST service delivery and future scale-up. FUNDING: WHO, Australian National Health and Medical Research Council, and Unitaid.

Missed opportunities for HIV testing among those who accessed sexually transmitted infection (STI) services, tested for STIs and diagnosed with STIs: a systematic review and meta-analysis.

INTRODUCTION: Of 37.7 million people living with HIV in 2020, 6.1 million still do not know their HIV status. We synthesize evidence on concurrent HIV testing among people who tested for other sexually transmitted infections (STIs). METHODS: We conducted a systematic review using five databases, HIV conferences and clinical trial registries. We included publications between 2010 and May 2021 that reported primary data on concurrent HIV/STI testing. We conducted a random-effects meta-analysis and meta-regression of the pooled proportion for concurrent HIV/STI testing. RESULTS: We identified 96 eligible studies. Among those, 49 studies had relevant data for a meta-analysis. The remaining studies provided data on the acceptability, feasibility, barriers, facilitators, economic evaluation and social harms of concurrent HIV/STI testing. The pooled proportion of people tested for HIV among those attending an STI service (n = 18 studies) was 71.0% (95% confidence intervals: 61.0-80.1, I2 = 99.9%), people tested for HIV among those who were tested for STIs (n = 15) was 61.3% (53.9-68.4, I2 = 99.9%), people tested for HIV among those who were diagnosed with an STI (n = 13) was 35.3% (27.1-43.9, I2 = 99.9%) and people tested for HIV among those presenting with STI symptoms (n = 3) was 27.1% (20.5-34.3, I2 = 92.0%). The meta-regression analysis found that heterogeneity was driven mainly by identity as a sexual and gender minority, the latest year of study, country-income level and region of the world. DISCUSSION: This review found poor concurrent HIV/STI testing among those already diagnosed with an STI (35.3%) or who had symptoms with STIs (27.1%). Additionally, concurrent HIV/STI testing among those tested for STIs varied significantly according to the testing location, country income level and region of the world. A few potential reasons for these observations include differences in national STI-related policies, lack of standard operation procedures, clinician-level factors, poor awareness and adherence to HIV indicator condition-guided HIV testing and stigma associated with HIV compared to other curable STIs. CONCLUSIONS: Not testing for HIV among people using STI services presents a significant missed opportunity, particularly among those diagnosed with an STI. Stronger integration of HIV and STI services is urgently needed to improve prevention, early diagnosis and linkage to care services.

The World Health Organization's work and recommendations for improving the health of trans and gender diverse people.

INTRODUCTION: The World Health Organization (WHO) is guided by its global programme of work and the goal that a billion more people have universal health coverage (UHC). To achieve UHC, access for those most vulnerable must be guaranteed and prioritized. WHO is committed to developing evidence-based guidance to work towards UHC for trans and gender diverse (TGD) people. This commentary describes WHO's work related to TGD people over the last decade. DISCUSSION: In 2011, WHO developed guidelines for the prevention and treatment of HIV and sexually transmitted infections (STIs) in men who have sex with men and TGD people. In 2013, the "HIV civil society reference group" called on WHO to provide specific guidance for TGD people. Values and preferences of TGD people were considered by WHO for the first time, which informed the development of the 2014 WHO Consolidated Guidelines on HIV Prevention, Diagnosis, Treatment and Care for Key Populations. The 2014 Guidelines included a comprehensive package of HIV-related health and enabling interventions with specific considerations for TGD people, as well as a specific policy brief in 2015. Regional WHO offices developed and/or supported the development of blueprints on transgender health and HIV in 2014 and 2016. A 2015 WHO report on sexual health, human rights and the law elucidated the harmful impacts of discriminatory laws on the basis of sexual orientation and gender identity. In 2019, the 11th edition of the international classification of diseases saw the removal of "transsexualism" as a mental and behavioural disorder. WHO's first guideline on self-care interventions, updated in 2021, included key considerations concerning TGD people. In 2022, WHO's updated key populations guidelines include a prioritized package of not just HIV, but also viral hepatitis and STI health interventions for TGD people. Still, a broader and more specific health approach and a greater focus on social issues are needed to better serve the health needs of TGD people. CONCLUSIONS: WHO's understanding and commitment to TGD people's health has evolved and improved over the past decade. Together with professional and community trans health organizations, WHO should now start developing evidence-informed global guidance on TGD health as part of its remit to support UHC to all.

Improved rapid diagnostic tests to detect syphilis and yaws: a systematic review and meta-analysis.

BACKGROUND: Current rapid tests for syphilis and yaws can detect treponemal and non-treponemal antibodies. We aimed to critically appraise the literature for rapid diagnostic tests (RDTs) which can better distinguish an active infection of syphilis or yaws. METHODS: We conducted a systematic review and meta-analysis, searching five databases between January 2010 and October 2021 (with an update in July 2022). A generalised linear mixed model was used to conduct a bivariate meta-analysis for the pooled sensitivity and specificity. Heterogeneity was assessed using the I2 statistic. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) to assess the risk of bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to evaluate the certainty of evidence. RESULTS: We included 17 studies for meta-analyses. For syphilis, the pooled sensitivity and specificity of the treponemal component were 0.93 (95% CI: 0.86 to 0.97) and 0.98 (95% CI: 0.96 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.90 (95% CI: 0.82 to 0.95) and 0.97 (95% CI: 0.92 to 0.99), respectively. For yaws, the pooled sensitivity and specificity of the treponemal component were 0.86 (95% CI: 0.66 to 0.95) and 0.97 (95% CI: 0.94 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.80 (95% CI: 0.55 to 0.93) and 0.96 (95% CI: 0.92 to 0.98), respectively. CONCLUSIONS: RDTs that can differentiate between active and previously treated infections could optimise management by providing same-day treatment and reducing unnecessary treatment. PROSPERO REGISTRATION NUMBER: CRD42021279587.

HIV prevalence ratio of international migrants compared to their native-born counterparts: A systematic review and meta-analysis.

Background: People on the move, including international migrants, may face health inequities that expose them to a higher risk for HIV than native-born populations. We conducted a systematic review to calculate the HIV prevalence ratio of international migrants compared with native-born populations. Methods: We searched five databases between January 2010 and March 2022. Using random-effects meta-analysis, we calculated the pooled HIV prevalence ratios (PR) by comparing the HIV prevalence of migrants with native-born populations. Our research protocol is registered in the International prospective register of systematic reviews (PROSPERO, CRD42021250867). Findings: In total, 5,121 studies were screened, and 38 were included in the final analysis: 7,121,699 migrants and more than 270 million natives were included in the analysis. The pooled PR for any foreign-born migrants was 1·70 (95% CI 1·11 - 2·61, I2 =99·67%, n = 33 studies), refugees was 2·37 (95% CI 0·33-16·99, I2 =99·5%, n = 5), undocumented people was 3·98 (95% CI 0·11-143·01, I2 =94·6%, n = 3), whilst asylum seekers was 54·79 (95% CI 17·23-174·23, I2 =90·2%, n = 2). Meta-regression revealed that population type (adjusted R-squared 11.5%), region of origin (11.3%) and migrant type (10.8%) accounted for heterogeneity more than country-income (2.4%) and study setting (2.3%). Interpretation: Although it was not possible to assess if HIV infection occurred in the country of origin or destination, the HIV prevalence ratio was higher among migrants than in native-born populations. Inclusive health policies and strategies for delivering HIV testing, prevention and treatment services for migrant populations tailored to their needs are urgently needed. Funding: J.J.O. and E.P.F.C. are supported by the Australian National Health and Medical Research Council (NHMRC) Emerging Leader Fellowship (GNT1193955 and GNT1172873, respectively).

A systematic review of the prevalence of selected sexually transmitted infections in young people in Latin America.

Objective: To estimate the burden of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and human papillomavirus (HPV) infections among people aged 10 to 25 in Latin America and the Caribbean. Methods: The MEDLINE, EMBASE, and LILACS databases were searched, as well as documents from regional organizations or national health Institutions. Population-based studies that reported prevalence or incidence of CT, NG, TP, and HPV detected through confirmatory tests in adolescents and young people were included. Two reviewers independently selected studies and extracted data. The quality of studies was assessed using the Newcastle-Ottawa Scale. Pooled estimators were calculated in cases where heterogeneity was <70%; when not feasible, prevalence ranges were reported. Results: Out of a total of 3 583 references, 15 prevalence studies complied with the inclusion criteria. Due to substantial heterogeneity (>70%), it was not possible to pool frequency estimators. Among the general population, the prevalence of CT infection ranged between 2.1% and 30.1% (9 studies, 5 670 participants); for NG, prevalence ranged between 0% and 2.9% (8 studies, 5 855 participants); for TP, prevalence varied between 0% and 0.7% (3 studies, 11 208 participants), and for HPV infection, prevalence ranged between 25.1% and 55.6% (8 studies, 3 831 participants). Conclusions: Reliable, population-based data on sexually transmitted infections (STIs) in adolescents and youth in Latin America and the Caribbean are limited. Additional studies are needed to better understand the burden of STIs in this population. However, given the substantial prevalence of STIs detected, countries need public health policies for prevention, early diagnosis, and treatment of STIs in young people.

Assessment of country implementation of the WHO global health sector strategy on sexually transmitted infections (2016-2021).

BACKGROUND: In 2016, WHO launched the Global Health Sector Strategy on STIs, 2016-2021 (GHSS) to provide guidance and benchmarks for country achievement by 2020 and four global targets for achievement by 2030. METHODS: A country survey jointly developed by experienced technical personnel at WHO Headquarters (HQ) and WHO regional offices was reviewed and distributed by WHO regional advisors to 194 WHO Member States in September-March 2020. The survey sought to assess implementation and prioritization of STI policy, surveillance, service delivery, commodity availability, and surveillance based on targets of the GHSS. RESULTS: A majority (58%, 112/194) of countries returned a completed survey reflecting current (2019) STI activities. The regions with the highest survey completion rates were South-East Asia Region (91%, 10/11), Region of the Americas (71%, 25/35) and Western Pacific Region (67%, 18/27). Having a national STI strategy was reported by 64% (72/112) and performing STI surveillance activities by 88% (97/110) of reporting countries. Availability of STI services within primary health clinics was reported by 88% of countries (99/112); within HIV clinics by 92% (103/112), and within reproductive health services by 85% (95/112). Existence of a national strategy to eliminate mother-to-child transmission of HIV and syphilis (EMTCT) was reported by 70% of countries (78/112). Antimicrobial resistance (AMR) monitoring for gonococcal infection (gonorrhoea) was reported by 64% (57/89) of reporting countries with this laboratory capacity. Inclusion of HPV vaccine for young women in the national immunization schedule was reported by 59% (65/110) and availability of cervical cancer screening was reported by 91% (95/104). Stockouts of STI medicines, primarily benzathine penicillin, within the prior four years were reported by 34% (37/110) of countries. CONCLUSIONS: Mechanisms to support improvements to STI service delivery through national-level policy, commitment, programming and surveillance are needed to operationalize, accelerate and monitor progress towards achievement of the 2030 global STI strategy targets.

The diagnostic accuracy of pooled testing from multiple individuals for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae: a systematic review.

OBJECTIVES: Molecular testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is costly. Therefore, we appraised the evidence regarding pooling samples from multiple individuals to test for CT/NG. METHODS: In this systematic review, we searched 5 databases (2000-2021). Studies were included if they contained primary data describing pooled testing. We calculated the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. RESULTS: We included 22 studies: most were conducted in high-income countries (81.8%, 18 of 22), among women (73.3%, 17 of 22), and pooled urine samples (63.6%, 14 of 22). Eighteen studies provided 25 estimates for the meta-analysis of diagnostic accuracy, with data from 6,913 pooled specimens. The pooled sensitivity for CT was 98.4% (95% confidence intervals [CI]: 96.8-99.2%, I2=77.5, p<0.001), and pooled specificity was 99.9% (95% CI: 99.6-100.0%, I2=62.6, p<0.001). Only 2 studies reported pooled testing for NG, and both reported similarly high sensitivity and specificity as for CT. Sixteen studies provided data on the cost of pooling, reporting cost-savings ranging from 39%-90%. CONCLUSIONS: Pooled testing from multiple individuals for CT is highly sensitive and specific compared with individual testing. This approach has the potential to reduce the cost of screening in populations for which single anatomic site screening is recommended.

A systematic review of the prevalence of selected sexually transmitted infections in young people in Latin America / Revisión sistemática de la prevalencia de determinadas infecciones de transmisión sexual en la población joven en América Latina / Revisão sistemática da prevalência de determinadas infecções sexualmente transmissíveis em jovens na América Latina

ABSTRACT Objective. To estimate the burden of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and human papillomavirus (HPV) infections among people aged 10 to 25 in Latin America and the Caribbean. Methods. The MEDLINE, EMBASE, and LILACS databases were searched, as well as documents from regional organizations or national health Institutions. Population-based studies that reported prevalence or incidence of CT, NG, TP, and HPV detected through confirmatory tests in adolescents and young people were included. Two reviewers independently selected studies and extracted data. The quality of studies was assessed using the Newcastle-Ottawa Scale. Pooled estimators were calculated in cases where heterogeneity was <70%; when not feasible, prevalence ranges were reported. Results. Out of a total of 3 583 references, 15 prevalence studies complied with the inclusion criteria. Due to substantial heterogeneity (>70%), it was not possible to pool frequency estimators. Among the general population, the prevalence of CT infection ranged between 2.1% and 30.1% (9 studies, 5 670 participants); for NG, prevalence ranged between 0% and 2.9% (8 studies, 5 855 participants); for TP, prevalence varied between 0% and 0.7% (3 studies, 11 208 participants), and for HPV infection, prevalence ranged between 25.1% and 55.6% (8 studies, 3 831 participants). Conclusions. Reliable, population-based data on sexually transmitted infections (STIs) in adolescents and youth in Latin America and the Caribbean are limited. Additional studies are needed to better understand the burden of STIs in this population. However, given the substantial prevalence of STIs detected, countries need public health policies for prevention, early diagnosis, and treatment of STIs in young people.

RESUMEN Objetivo. Calcular la carga de infecciones por Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (PT) y el virus del papiloma humano (VPH) en personas de edades comprendidas entre los 10 y los 25 años en América Latina y el Caribe. Métodos. Se realizaron búsquedas en las bases de datos MEDLINE, EMBASE y LILACS, así como en documentos de organizaciones regionales o instituciones nacionales de salud. Se incluyeron estudios poblacionales que notificaron la prevalencia o la incidencia de CT, NG, TP y VPH, detectados mediante pruebas confirmatorias en adolescentes y jóvenes. Dos revisores seleccionaron de forma independiente los estudios y extrajeron los datos. La calidad de los estudios se evaluó mediante la escala de Newcastle-Ottawa. Se hicieron estimaciones combinadas en los casos en que la heterogeneidad era <70 %; cuando no era posible, se presentaron los rangos de prevalencia. Resultados. De un total de 3 583 referencias, 15 estudios de prevalencia cumplieron los criterios de inclusión. Debido a una significativa heterogeneidad (>70%), no fue posible agrupar las estimaciones de frecuencia. En la población general, la prevalencia de infección por CT fluctuó entre 2,1 % y 30,1 % (9 estudios y 5 670 participantes); en el caso de NG, la prevalencia fluctuó entre 0 % y 2,9 % (8 estudios y 5 855 participantes); en el caso de PT, la prevalencia varió entre 0 % y 0,7 % (3 estudios y 11 208 participantes) y en el caso de infección por VPH, la prevalencia fluctuó entre 25,1 % y 55,6 % (8 estudios y 3 831 participantes). Conclusiones. Los datos poblacionales fiables sobre las infecciones de transmisión sexual (ITS) en adolescentes y jóvenes en América Latina y el Caribe son limitados. Es necesario hacer estudios adicionales para comprender mejor la carga de las ITS en este grupo poblacional. Sin embargo, dada la significativa prevalencia de ITS detectada, los países requieren políticas de salud pública para la prevención, el diagnóstico temprano y el tratamiento de las ITS en la población joven.

RESUMO Objetivo. Estimar a carga de infecção por Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP) e papilomavírus humano (HPV) na população entre 10 e 25 anos de idade na América Latina e no Caribe. Métodos. Foi realizada uma pesquisa nas bases de dados MEDLINE, EMBASE e LILACS, assim como da documentação de entidades regionais ou nacionais que atuam na área da saúde. Foram incluídos na revisão estudos populacionais que registraram a incidência ou a prevalência de infecção por CT, NG, TP e HPV, verificada por meio de exames confirmatórios realizados em adolescentes e jovens. Dois revisores trabalharam de modo independente na seleção dos estudos e extração dos dados. A qualidade dos estudos foi avaliada utilizando a Escala de Newcastle-Ottawa. Foi feito o cálculo dos estimadores combinados quando a heterogeneidade era <70% e apresentada a variação da prevalência nos outros casos quando essa estimativa não foi possível. Resultados. Das 3 583 referências levantadas, 15 eram estudos de prevalência que satisfizeram os critérios de inclusão. Devido à heterogeneidade considerável entre os estudos (>70%), não foi possível combinar os estimadores de frequência. Na população geral, a prevalência de infecção por CT variou entre 2,1% e 30,1% (9 estudos, 5 670 participantes); a de NG, entre 0 e 2,9% (8 estudos, 5 855 participantes); a de TP, entre 0 e 0,7% (3 estudos, 11 208 participantes); e a de infecção por HPV, entre 25,1% e 55,6% (8 estudos, 3 831 participantes). Conclusões. Faltam dados populacionais confiáveis relativos a infecções sexualmente transmissíveis (ISTs) em adolescentes e jovens na América Latina e no Caribe. Outros estudos devem ser realizados para um entendimento melhor da carga dessas infecções na população. Diante da elevada prevalência verificada, os países precisam dispor de políticas de saúde pública para prevenção, diagnóstico precoce e tratamento de ISTs na população jovem.'

Diagnostic accuracy of pooling urine, anorectal, and oropharyngeal specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae: a systematic review and meta-analysis.

BACKGROUND: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at genital and extragenital sites is needed for most key populations, but molecular diagnostic tests for CT/NG are costly. We aimed to determine the accuracy of pooled samples from multiple anatomic sites from one individual to detect CT/NG using the testing of a single sample from one anatomic site as the reference. METHODS: In this systematic review and meta-analysis, we searched five databases for articles published from January 1, 2000, to February 4, 2021. Studies were included if they contained original data describing the diagnostic accuracy of pooled testing compared with single samples, resource use, benefits and harms of pooling, acceptability, and impact on health equity. We present the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. The study protocol is registered in PROSPERO, an international database of prospectively registered systematic reviews (CRD42021240793). We used GRADE to evaluate the quality of evidence. RESULTS: Our search yielded 7814 studies, with 17 eligible studies included in our review. Most studies were conducted in high-income countries (82.6%, 14/17) and focused on men who have sex with men (70.6%, 12/17). Fourteen studies provided 15 estimates for the meta-analysis for CT with data from 5891 individuals. The pooled sensitivity for multisite pooling for CT was 93.1% [95% confidence intervals (CI) 90.5-95.0], I2=43.3, and pooled specificity was 99.4% [99.0-99.6], I2=52.9. Thirteen studies provided 14 estimates for the meta-analysis for NG with data from 6565 individuals. The pooled sensitivity for multisite pooling for NG was 94.1% [95% CI 90.9-96.3], I2=68.4, and pooled specificity was 99.6% [99.1-99.8], I2=83.6. Studies report significant cost savings (by two thirds to a third). CONCLUSION: Multisite pooled testing is a promising approach to improve testing coverage for CT/NG in resource-constrained settings with a small compromise in sensitivity but with a potential for significant cost savings.

High-risk human papillomavirus infection among women living with HIV in Latin America and the Caribbean: A systematic review and meta-analysis.

We carried out a systematic review to summarize available data regarding prevalence of high-risk human papillomavirus (HR-HPV) among women living with HIV (WLHIV) in Latin America and the Caribbean (LAC). A literature search in PubMed and LILACS was conducted and supplemented with cross-referencing and grey literature. The primary outcome was prevalence of HR-HPV by age as a major determinant of HPV infection. Pooled prevalence and weighted averages were obtained. A random effects meta-analysis conducted for HPV- and HIV-associated factors. In total, 6157 women from 19 cross-sectional studies were included. Weighted prevalence of HR-HPV in WLHIV was 51.0% (95% CI 42.8-59.1, I2 = 97.4%) with a bimodal trend by age. No association between antiretroviral therapy and HR-HPV prevalence was observed, but low CD4 cell count was associated (PR 1.64, 95% CI 1.07-2.52). Although not significant, a higher HR-HPV prevalence was observed with Hybrid Capture 2 versus PCR. The high prevalence of HR-HPV among WLHIV in LAC underlines the need for improved cervical cancer prevention and early detection in this vulnerable population. Moreover, the high prevalence across age groups, and particularly in young women, deserves careful consideration for defining target populations of HPV-based screening and HPV immunization programs.

Optimizing HIV retesting during pregnancy and postpartum in four countries: a cost-effectiveness analysis.

INTRODUCTION: HIV retesting during late pregnancy and breastfeeding can help detect new maternal infections and prevent mother-to-child HIV transmission (MTCT), but the optimal timing and cost-effectiveness of maternal retesting remain uncertain. METHODS: We constructed deterministic models to assess the health and economic impact of maternal HIV retesting on a hypothetical population of pregnant women, following initial testing in pregnancy, on MTCT in four countries: South Africa and Kenya (high/intermediate HIV prevalence), and Colombia and Ukraine (low HIV prevalence). We evaluated six scenarios with varying retesting frequencies from late in antenatal care (ANC) through nine months postpartum. We compared strategies using incremental cost-effectiveness ratios (ICERs) over a 20-year time horizon using country-specific thresholds. RESULTS: We found maternal retesting once in late ANC with catch-up testing through six weeks postpartum was cost-effective in Kenya (ICER = $166 per DALY averted) and South Africa (ICER=$289 per DALY averted). This strategy prevented 19% (Kenya) and 12% (South Africa) of infant HIV infections. Adding one or two additional retests postpartum provided smaller benefits (1 to 2 percentage point increase in infections averted versus one retest). Adding three retests during the postpartum period averted additional infections (1 to 3 percentage point increase in infections averted versus one retest) but ICERs ($7639 and in Kenya and $11 985 in South Africa) greatly exceeded the cost-effectiveness thresholds. In Colombia and Ukraine, all retesting strategies exceeded the cost-effectiveness threshold and prevented few infant infections (up to 31 and 5 infections, respectively). CONCLUSIONS: In high HIV burden settings with MTCT rates similar to those seen in Kenya and South Africa, HIV retesting once in late ANC, with subsequent intervention, is the most cost-effective strategy for preventing infant HIV infections. In these settings, two HIV retests postpartum marginally reduced MTCT and were less costly than adding three retests. Retesting in low-burden settings with MTCT rates similar to Colombia and Ukraine was not cost-effective at any time point due to very low HIV prevalence and limited breastfeeding.

Cost-effectiveness of dual maternal HIV and syphilis testing strategies in high and low HIV prevalence countries: a modelling study.

BACKGROUND: Dual HIV and syphilis testing might help to prevent mother-to-child transmission (MTCT) of HIV and syphilis through increased case detection and treatment. We aimed to model and assess the cost-effectiveness of dual testing during antenatal care in four countries with varying HIV and syphilis prevalence. METHODS: In this modelling study, we developed Markov models of HIV and syphilis in pregnant women to estimate costs and infant health outcomes of maternal testing at the first antenatal care visit with individual HIV and syphilis tests (base case) and at the first antenatal care visit with a dual rapid diagnostic test (scenario one). We additionally evaluated retesting during late antenatal care and at delivery with either individual tests (scenario two) or a dual rapid diagnosis test (scenario three). We modelled four countries: South Africa, Kenya, Colombia, and Ukraine. Strategies with an incremental cost-effectiveness ratio (ICER) less than the country-specific cost-effectiveness threshold (US$500 in Kenya, $750 in South Africa, $3000 in Colombia, and $1000 in Ukraine) per disability-adjusted life-year averted were considered cost-effective. FINDINGS: Routinely offering testing at the first antenatal care visit with a dual rapid diagnosis test was cost-saving compared with the base case in all four countries (ICER: -$26 in Kenya,-$559 in South Africa, -$844 in Colombia, and -$454 in Ukraine). Retesting during late antenatal care with a dual rapid diagnostic test (scenario three) was cost-effective compared with scenario one in all four countries (ICER: $270 in Kenya, $260 in South Africa, $2207 in Colombia, and $205 in Ukraine). INTERPRETATION: Incorporating dual rapid diagnostic tests in antenatal care can be cost-saving across countries with varying HIV prevalence. Countries should consider incorporating dual HIV and syphilis rapid diagnostic tests as the first test in antenatal care to support efforts to eliminate MTCT of HIV and syphilis. FUNDING: WHO, US Agency for International Development, and the Bill & Melinda Gates Foundation.

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

Syphilis management in pregnancy: a review of guideline recommendations from countries around the world.

Guidelines can help healthcare practitioners manage syphilis in pregnancy and prevent perinatal death or disability. We conducted systematic reviews to locate guidance documents describing management of syphilis in pregnancy, 2003-2017. We compared country and regional guidelines with current World Health Organization (WHO) guidelines. We found 64 guidelines with recommendations on management of syphilis in pregnancy representing 128 of the 195 WHO member countries, including the two WHO guidelines published in 2016 and 2017. Of the 62 guidelines, 16 were for countries in Africa, 21 for the Americas, two for Eastern Mediterranean, six for Europe and 17 for Asia or the Pacific. Fifty-seven (92%) guidelines recommended universal syphilis screening in pregnancy, of which 46 (81%) recommended testing at the first antenatal care visit. Also, 46 (81%) recommended repeat testing including 21 guidelines recommended this during the third pregnancy trimester and/or at delivery. Fifty-nine (95%) guidelines recommended benzathine penicillin G (BPG) as the first-line therapy for syphilis in pregnancy, consistent with WHO guidelines. Alternative regimens to BPG were listed in 42 (68%) guidelines, primarily from Africa and Asia; only 20 specified that non-penicillin regimens are not proven-effective in treating the fetus. We identified guidance recommending use of injectable penicillin in exposed infants for 112 countries. Most guidelines recommended universal syphilis testing for pregnant women, repeat testing for high-risk women and treatment of infected women with BPG; but several did not. Updating guidance on syphilis testing and treatment in pregnancy to reflect global norms could prevent congenital syphilis and save newborn lives.

Correction: Global burden of maternal and congenital syphilis and associated adverse birth outcomes-Estimates for 2016 and progress since 2012.

[This corrects the article DOI: 10.1371/journal.pone.0211720.].

Access to sexual and reproductive health services for women living with HIV in Latin America and the Caribbean: systematic review of the literature.

INTRODUCTION: Systematic reviews show that women living with HIV (WLHIV) have high unmet sexual and reproductive health (SRH) needs due to barriers to access sexual and reproductive health services (SRHS). In Latin America and the Caribbean (LAC), as of 2016, there were nearly one million WLHIV, but the existing evidence of their SRH needs comes from a few individual studies. This systematic review provides an overview of these women's needs to help define new and/or adapt existing public health strategies to the local context. This review synthesizes the evidence from the literature on the use of and access to SRHS related to family planning, antenatal care, abortion services and violence against WLHIV in LAC. METHODS: Using a systematic review of mixed studies, a search was performed in MEDLINE, EMBASE, LILACS, INASP, POPLINE, SCOPUS, for studies conducted in LAC, from 2004 to 2017, as well as contact with authors and hand search as needed. Two independent reviewers evaluated the quality of the studies using the Mixed Methods Appraisal Tool; inclusion was conducted according to the PRISMA flow diagram. An exploratory narrative synthesis followed by quantitative synthesis data was undertaken. Group analysis or meta-analysis was not considered appropriate given the level of heterogeneity of the studies. RESULTS: A total of 18 studies in 13 LAC countries for a population of 5672 WLHIV were included. Data from individual studies reported unmet family planning needs; higher, but inconsistent use of condom as the sole contraceptive method OR=1.46 [1.26 to 1.69]; lesser use of other non-permanent contraceptive methods OR=0.26 [0.22 to 0.31]; more unplanned pregnancies OR=1.30 [1.02 to 1.66]; more induced abortions OR=1.96 [1.60 to 2.39]; higher risk of immediate postpartum sterilization; and higher exposure to sexual and institutional violence by WLHIV when compared with women without HIV. CONCLUSIONS: This review presents evidence from LAC about the SRH unmet needs of WLHIV that must be addressed by decreasing institutional and structural barriers, facilitating services and reducing stigma, and discrimination among healthcare providers to improve access to SRHS based on human rights, so women independently of their HIV status can make their own reproductive decisions, free of violence and coercion.

Global burden of maternal and congenital syphilis and associated adverse birth outcomes-Estimates for 2016 and progress since 2012.

BACKGROUND: In 2007 the World Health Organization (WHO) launched the global initiative to eliminate mother-to-child transmission of syphilis (congenital syphilis, or CS). To assess progress towards the goal of <50 CS cases per 100,000 live births, we generated regional and global estimates of maternal and congenital syphilis for 2016 and updated the 2012 estimates. METHODS: Maternal syphilis estimates were generated using the Spectrum-STI model, fitted to sentinel surveys and routine testing of pregnant women during antenatal care (ANC) and other representative population data. Global and regional estimates of CS used the same approach as previous WHO estimates. RESULTS: The estimated global maternal syphilis prevalence in 2016 was 0.69% (95% confidence interval: 0.57-0.81%) resulting in a global CS rate of 473 (385-561) per 100,000 live births and 661,000 (538,000-784,000) total CS cases, including 355,000 (290,000-419,000) adverse birth outcomes (ABO) and 306,000 (249,000-363,000) non-clinical CS cases (infants without clinical signs born to un-treated mothers). The ABOs included 143,000 early fetal deaths and stillbirths, 61,000 neonatal deaths, 41,000 preterm or low-birth weight births, and 109,000 infants with clinical CS. Of these ABOs- 203,000 (57%) occurred in pregnant women attending ANC but not screened for syphilis; 74,000 (21%) in mothers not enrolled in ANC, 55,000 (16%) in mothers screened but not treated, and 23,000 (6%) in mothers enrolled, screened and treated. The revised 2012 estimates were 0.70% (95% CI: 0.63-0.77%) maternal prevalence, and 748,000 CS cases (539 per 100,000 live births) including 397,000 (361,000-432,000) ABOs. The estimated decrease in CS case rates between 2012 and 2016 reflected increased access to ANC and to syphilis screening and treatment. CONCLUSIONS: Congenital syphilis decreased worldwide between 2012 and 2016, although maternal prevalence was stable. Achieving global CS elimination, however, will require improving access to early syphilis screening and treatment in ANC, clinically monitoring all women diagnosed with syphilis and their infants, improving partner management, and reducing syphilis prevalence in the general population by expanding testing, treatment and partner referral beyond ANC.