Effect of antenatal Chlamydia trachomatis and Neisseria gonorrhoeae screening on postdelivery prevalence and vertical transmission in Gaborone, Botswana: findings from an exploratory study.

OBJECTIVES: Chlamydia trachomatis and Neisseria gonorrhoeae are common sexually transmitted infections (STIs). Untreated infection in pregnancy can result in adverse neonatal outcomes, including vertical transmission. Screening for these infections is not routine in low- and middle-income countries (LMICs). METHODS: The Maduo Study was a non-randomised cluster crossover trial in Botswana to provide preliminary data on the effect of antenatal C. trachomatis and N. gonorrhoeae screening and treatment on postdelivery prevalence and vertical transmission to infants. Pregnant women asymptomatic for STIs were enrolled at four clinics (seven clusters). The intervention arm received C. trachomatis and N. gonorrhoeae screening at first antenatal care, third trimester and postdelivery. The standard-of-care arm received postdelivery screening only. Infants of women with a positive test postdelivery in both arms were screened. A cluster-level analysis was performed to compare the risk of postdelivery infection between intervention and standard-of-care arms. RESULTS: The study enrolled 500 women; 206 (82.1%) and 187 (75.1%) were retained in the intervention and standard-of-care arms, respectively and screened ≤12 weeks postdelivery. C. trachomatis prevalence in the intervention arm reduced from 22.7% at first antenatal care to 1.0% postdelivery. N. gonorrhoeae prevalence reduced from 1.2% at first antenatal care to 0% postdelivery. The risk of C. trachomatis and/or N. gonorrhoeae was lower in the intervention arm postdelivery (0.6%) compared with the standard-of-care arm (15.7%); adjusted risk difference: -14.7% (95% CI -23.0%, -6.4%). Among 26 infants born to women with either infection postdelivery, 10 (38.5%) tested positive (C. trachomatis: 9; N. gonorrhoeae: 1). CONCLUSIONS: Postdelivery prevalence of C. trachomatis was significantly lower among pregnant women in Botswana who received diagnostic antenatal screening. Among women with C. trachomatis and/or N. gonorrhoeae postdelivery, more than one-third transmitted the infection to their infants. This exploratory study suggests antenatal STI screening has the potential to reduce infection in newborns in similar LMIC settings. TRIAL REGISTRATION NUMBER: NCT04955717.

Prevalence of sexually transmitted infection in pregnancy and their association with adverse birth outcomes: a case-control study at Queen Elizabeth Central Hospital, Blantyre, Malawi.

BACKGROUND: There are limited data on the epidemiology of sexually transmitted infections (STI) and their contribution to adverse birth outcomes (ABO) in sub-Saharan Africa (SSA). We performed a case-control study to assess the prevalence of STI and their association with ABO among women attending Queen Elizabeth Central Hospital, Blantyre, Malawi. METHODS: A composite case definition for ABO included stillborn, preterm and low birthweight infants and infants admitted to neonatal intensive care unit within 24 hours of birth. Following recruitment of an infant with an ABO, the next born healthy infant was recruited as a control. Multiplex PCR for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV) was performed on maternal vaginal swabs. HIV and syphilis status was determined on maternal and infant serum. For syphilis, we used combined treponemal/non-treponemal rapid point-of-care tests in parallel with rapid plasma reagin tests, PCR for Treponema pallidum and clinical parameters to diagnose and stage the infection. We compared STI positivity between cases and controls. RESULTS: We included 259 cases and 251 controls. Maternal prevalence of STI was 3.1%, 2.7% and 17.1% for NG, CT and TV, respectively. Maternal prevalence of untreated syphilis was 2.0% and 6.1% for early stage and late/unknown stage, respectively; prevalence of treated syphilis was 2.7%. The HIV prevalence was 16.5%. HIV infection significantly increased the odds for ABO (OR=3.31; 95% CI 1.10 to 9.91) as did NG positivity (OR=4.30; 95% CI 1.16 to 15.99). We observed higher rates of ABO among women with untreated maternal syphilis (early: OR=7.13; 95% CI 0.87 to 58.39, late/unknown stage: OR=1.43; 95% CI 0.65 to 3.15). Maternal TV and CT infections were not associated with ABO. CONCLUSION: STI prevalence among pregnant women in Malawi is comparable to other SSA countries. HIV, NG and untreated syphilis prevalence was higher among women with ABO compared with women with healthy infants.

Use of Expedited Partner Therapy for Pregnant Women Treated for Sexually Transmitted Infections in Gaborone, Botswana.

BACKGROUND: Partner notification and treatment for sexually transmitted infections are critical to prevent reinfection and reduce transmission. However, partner treatment rates are low globally. Expedited partner therapy (EPT), in which the patient delivers treatment directly to their partner, may result in more partners treated. We assessed partner notification and treatment outcomes among pregnant women in Gaborone, Botswana, including EPT intent, uptake, and effectiveness. METHODS: The Maduo study was a cluster-controlled trial evaluating the effect of antenatal Chlamydia trachomatis and Neisseria gonorrhoeae infection screening in pregnant women. The intervention arm received screening at first antenatal care (ANC), third-trimester, and postnatal care visits. The standard-of-care arm received screening postnatally. Participants screening positive were given options for partner treatment: contact slips, in-clinic treatment, or EPT. Self-reported partner notification and treatment outcomes were assessed at test-of-cure visit. RESULTS: Of 51 women who screened positive for C. trachomatis / N. gonorrhoeae at first ANC and returned for test of cure, 100% reported notifying their partner and 48 (94.1%) reported their partner received treatment. At third trimester 100% (n = 5), reported partners were treated. Before testing, EPT intent was lower than EPT uptake at all time points (first ANC: 17.9% vs. 80.4%; third-trimester: 57.1% vs. 71.4%; postnatal care: 0% vs. 80.0%). Partner treatment success was 100% among EPT users compared with 70% among nonusers ( P = 0.006). CONCLUSIONS: Partner notification and treatment success was high in this population. Despite low pretest intent to use EPT, uptake was high and associated with greater partner treatment success. Our findings suggest that EPT may be a successful partner treatment strategy to pursue in low- and middle-income countries.

Syphilis Prevalence Among People Living With and Without HIV in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Syphilis is a curable sexually transmitted infection that, untreated, is associated with significant morbidity and mortality. In people living with HIV (PLWH), syphilis carries greater risks of disease progression. We estimated syphilis prevalence among PLWH in the general population in sub-Saharan Africa and compared the prevalence among PLWH and without HIV. METHODS: We searched for studies published January 1, 2011, to March 28, 2022, reporting syphilis prevalence among PLWH in sub-Saharan Africa (PROSPERO No. CRD42020167328). We excluded studies in high-risk subpopulations. We estimated pooled syphilis prevalence among PLWH using random-effects modeling and compared the prevalence with people without HIV when included in the same study. We examined influences of region, study setting, and test type in subgroup analyses. RESULTS: We identified 926 studies; 53 were included in the meta-analysis. Pooled syphilis prevalence among PLWH was 7.3% (95% confidence interval [CI], 6.3%-8.5%). Prevalence differed by region: 3.1% (95% CI, 2.2%-4.0%) in Southern, 5.5% (95% CI, 2.3%-9.3%) in West/Central, and 10.5% (95% CI, 8.0%-13.1%) in Eastern Africa. Prevalence also differed by study setting: 13.8% (95% CI, 5.7%-23.0%) in sexual and reproductive health/sexually transmitted infection care, 8.7% (95% CI, 5.0%-12.8%) in HIV care, 7.1% (95% CI, 5.8%-8.5%) in antenatal care, and 3.8% (95% CI, 2.0%-5.8%) in household/community-based settings. Syphilis prevalence was higher among PLWH than without HIV (relative risk, 3.5; 95% CI, 2.8-4.5). CONCLUSIONS: Syphilis is highly prevalent among PLWH in sub-Saharan Africa and is more common among PLWH than without HIV. Integration of syphilis screening and management into HIV care may reduce complications of HIV-syphilis coinfection among PLWH in sub-Saharan Africa.

A Conference Designathon to Spark Innovation: Actionable Ideas to Enhance Sexually Transmitted Disease Control.

BACKGROUND: Designathons can be used to enhance public health training and spur innovation. A designathon is a 3-stage participatory activity that includes preparation, intensive collaboration, and follow-up activities. We organized a designathon focused on developing actionable sexually transmitted disease (STD) control strategies and examined the content of ideas resulting from an STD designathon. METHODS: For this designathon, we created four groups: early career researchers, silver group (people with >10 years of experience), travelers (people from low- and middle-income countries and those who received a conference scholarship) and a community group. Each group developed its own plan to consult members, iteratively develop ideas, and aggregate insights. Each group developed STD control strategies that were presented. Cross-cutting themes across these ideas were identified. RESULTS: Designathon participants included a subset of conference participants. Cross-cutting themes from final ideas included cocreating STD interventions with end-users, using sex-positive framing, enhancing open access digital STD resources, and reducing STD stigma. Early career researchers presented a call for community ideas focusing on ending STD epidemics by increasing accessibility to STD care services among all populations. The silver group proposed digital innovations, including an AI-powered tool for testing and treatment and a social game to promote sex positivity. The traveler group conceptualized an information hub to support implementation of STD programs. Community members underscored the importance of a more human-centered approach to STD control, which reduces stigma and normalizes sex and sexual pleasure. CONCLUSION: Sex positive campaigns and open access digital resources should be considered within STD programs. Implementation research studies are needed to evaluate these ideas.

Evaluating Chlamydia trachomatis and Neisseria gonorrhoeae screening and treatment among asymptomatic pregnant women to prevent preterm birth and low birthweight in Gaborone, Botswana: A secondary analysis from a non-randomised, cluster-controlled trial.

OBJECTIVE: To evaluate the impact of screening and treating asymptomatic pregnant women for Chlamydia (C.) trachomatis and Neisseria (N.) gonorrhoeae infections on the frequency of preterm birth or low birthweight infants in Botswana. DESIGN: Non-randomised, cluster-controlled trial. SETTING: Four antenatal care clinics in Gaborone, Botswana. POPULATION: Pregnant women aged ≥15 years, attending a first antenatal care visit, ≤27 weeks of gestation and without urogenital symptoms were eligible. METHODS: Participants in the intervention clinics received screening (GeneXpert®, Cepheid) during pregnancy and at the postnatal visit. Participants in the standard-of-care clinics received screening at the postnatal visit only. We used multivariable logistic regression and post-estimation predictive margins analysis. Post-hoc analysis was conducted among sub-samples stratified by parity. MAIN OUTCOME MEASURES: Preterm birth (<37 weeks of gestation) and low birthweight (<2500 g). RESULTS: After controlling for parity, hypertension, antenatal care visits and clinic site, the predicted prevalence of preterm birth or low birthweight was lower in the intervention arm (11%) compared with the standard-of-care arm (16%) (adjusted odds ratio [aOR] 0.59; 95% confidence interval [CI] 0.28-1.24). In post-hoc analysis, the intervention was more effective than the standard-of-care (aOR 0.20; 95% CI 0.07-0.64) among nulliparous participants. CONCLUSION: A C. trachomatis and N. gonorrhoeae infection screening and treatment intervention among asymptomatic pregnant women may have reduced preterm birth or low birthweight outcomes, but results were not statistically significant. Post-hoc analysis found that the intervention reduced adverse outcomes among nulliparous participants.

Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial.

BACKGROUND: Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods. METHODS: In this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant. The primary outcome was free testosterone at 6 months. RESULTS: We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p <  0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference - 22.98, p <  0.001). Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference - 50.04, p <  0.001 and than DMPA (mean percentage difference - 39.45, p <  0.001). Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001). CONCLUSIONS: This is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study. ECHO TRIAL REGISTRATION: ClinicalTrials.gov , number NCT02550067 15/09/2015. Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method. Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users' own circulating sex hormones, both the 'female' and the 'male' sex hormones (androgens). In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years. We measured the participants' androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods. This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.

The International Sexual Health And REproductive Health during COVID-19 (I-SHARE) Study: A Multicountry Analysis of Adults from 30 Countries Prior to and During the Initial Coronavirus Disease 2019 Wave.

BACKGROUND: There is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of coronavirus disease 2019 (COVID-19). To address this gap, our team organized a multicountry, cross-sectional online survey as part of a global consortium. METHODS: Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service use, and we compared 3 months prior to and during policy measures to mitigate COVID-19. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence. RESULTS: Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%), and 640 (14.1%) reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063 of 15 144, 7.0%) compared to before COVID-19 measures (1469 of 15 887, 9.3%). COVID-19 measures impeded access to condoms (933 of 10 790, 8.7%), contraceptives (610 of 8175, 7.5%), and human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing (750 of 1965, 30.7%). Pooled estimates from meta-analysis indicate that during COVID-19 measures, 32.3% (95% confidence interval [CI], 23.9%-42.1%) of people needing HIV/STI testing had hindered access, 4.4% (95% CI, 3.4%-5.4%) experienced partner violence, and 5.8% (95% CI, 5.4%-8.2%) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy. CONCLUSIONS: Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings.

Prolonged Cotrimoxazole Prophylaxis Has No Impact on Child Growth in the First Two Years of Life: Findings from a Randomized Controlled Trial in Botswana.

We investigated the impact of prolonged cotrimoxazole prophylaxis on growth in 2848 HIV-exposed uninfected children enrolled in the Mpepu study, a randomized, placebo-controlled trial in Botswana. No significant differences in mean weight-for-age, length-for-age, or weight-for-length z scores between placebo and cotrimoxazole arms were observed overall through 18 months.

Development of an international sexual and reproductive health survey instrument: results from a pilot WHO/HRP consultative Delphi process.

Population health surveys are rarely comprehensive in addressing sexual health, and population-representative surveys often lack standardised measures for collecting comparable data across countries. We present a sexual health survey instrument and implementation considerations for population-level sexual health research. The brief, comprehensive sexual health survey and consensus statement was developed via a multi-step process (an open call, a hackathon, and a modified Delphi process). The survey items, domains, entire instruments, and implementation considerations to develop a sexual health survey were solicited via a global crowdsourcing open call. The open call received 175 contributions from 49 countries. Following review of submissions from the open call, 18 finalists and eight facilitators with expertise in sexual health research, especially in low- and middle-income countries (LMICs), were invited to a 3-day hackathon to harmonise a survey instrument. Consensus was achieved through an iterative, modified Delphi process that included three rounds of online surveys. The entire process resulted in a 19-item consensus statement and a brief sexual health survey instrument. This is the first global consensus on a sexual and reproductive health survey instrument that can be used to generate cross-national comparative data in both high-income and LMICs. The inclusive process identified priority domains for improvement and can inform the design of sexual and reproductive health programs and contextually relevant data for comparable research across countries.

Bridging the Gap Between Pilot and Scale-Up: A Model of Antenatal Testing for Curable Sexually Transmitted Infections From Botswana.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are common sexually transmitted infections (STIs) associated with adverse outcomes, yet most countries do not test and conduct syndromic management, which lacks sensitivity and specificity. Innovations allow for expanded STI testing; however, cost is a barrier. METHODS: Using inputs from a pilot program in Botswana, we developed a model among a hypothetical population of 50,000 pregnant women to compare 1-year costs and outcomes associated with 3 antenatal STI testing strategies: (1) point-of-care, (2) centralized laboratory, and (3) a mixed approach (point of care at high-volume sites, and hubs elsewhere), and syndromic management. RESULTS: Syndromic management had the lowest delivery cost but was associated with the most infections at delivery, uninfected women treated, CT/NG-related low-birth-weight infants, disability-adjusted life years, and low birth weight hospitalization costs. Point-of-care CT/NG testing would treat and cure the most infections but had the highest delivery cost. Among the testing scenarios, the mixed scenario had the most favorable cost per woman treated and cured ($534/cure). Compared with syndromic management, the mixed approach resulted in a mean incremental cost-effectiveness ratio of $953 per disability-adjusted life years averted, which is cost-effective under World Health Organization's one-time per-capita gross domestic product willingness-to-pay threshold. CONCLUSIONS: As countries consider new technologies to strengthen health services, there is an opportunity to determine how to best deploy resources. Compared with point-of-care, centralized laboratory, and syndromic management, the mixed approach offered the lowest cost per infection averted and is cost-effective if policy makers' willingness to pay is informed by the World Health Organization's gross domestic product/capita threshold.

Evaluating the diagnosis and treatment of Chlamydia trachomatis and Neisseria gonorrhoeae in pregnant women to prevent adverse neonatal consequences in Gaborone, Botswana: protocol for the Maduo study.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are extremely common sexually transmitted infections (STIs) that are associated with adverse birth and neonatal outcomes, and the risk of vertical transmission of CT and NG during delivery is high. The majority of CT and NG infections are asymptomatic and missed by the standard of care in most countries (treatment based on symptoms). Thus, it is likely that missed maternal CT and NG infections contribute to preventable adverse health outcomes among women and children globally. This study aims to assess the effectiveness of CT and NG testing for asymptomatic pregnant women to prevent adverse neonatal outcomes, understand the inflammatory response linking CT and NG infections to adverse neonatal outcomes, and conduct an economic analysis of the CT and NG testing intervention. METHODS: The Maduo ("results" in Setswana) is a prospective, cluster-controlled trial in Gaborone, Botswana to compare a near point-of-care CT and NG testing and treatment intervention implemented in "study clinics" with standard antenatal care (World Health Organization-endorsed "syndromic management" strategy based on signs and symptoms without laboratory confirmation) implemented in "standard of care clinics" among asymptomatic pregnant women. The primary outcome is vertical transmission of CT/NG infection. Secondary outcomes include preterm birth (delivery < 37 completed weeks of gestation) and/or low birth weight (< 2500 g). The trial will also evaluate immunological and inflammatory markers of adverse neonatal outcomes, as well as the costs and cost-effectiveness of the intervention compared with standard care. DISCUSSION: The Maduo study will improve our understanding of the effectiveness and cost-effectiveness of CT and NG testing among asymptomatic pregnant women. It will also increase knowledge about the CT/NG-related immune responses that might drive adverse neonatal outcomes. Further, results from this study could encourage expansion of STI testing during antenatal care in low resource settings and improve maternal and neonatal health globally. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (Identifier NCT04955717, First posted: July 9, 2021)).

HPV prevalence among young adult women living with and without HIV in Botswana for future HPV vaccine impact monitoring.

INTRODUCTION: In 2015, Botswana introduced quadrivalent human papillomavirus (HPV) vaccine for girls aged 9-13 years. To establish a baseline HPV prevalence for future HPV vaccine impact monitoring, we evaluated HPV prevalences among the youngest unvaccinated women in Botswana and compared HPV prevalences among women living with HIV (WLHIV) and without HIV. METHODS: Women aged 18-22 years were recruited from the University of Botswana and HIV clinics in Gaborone from October 2019-January 2021. Demographic and behavioral characteristics were self-reported during structured interviews; HIV clinical characteristics were abstracted from medical charts. Self-collected vaginal swabs were tested for 28 HPV types using Seegene Anyplex II HPV28. We compared prevalence of any HPV, high risk (HR)-HPV, and quadrivalent HPV vaccine types (HPV6/11/16/18) among WLHIV and women without HIV and evaluated risk factors for prevalence of HR-HPV. RESULTS: A total of 306 WLHIV and 500 women without HIV were recruited. Compared to women without HIV, WLHIV were more likely to be sexually experienced (86.6% versus 74.4%) and have ≥ 3 lifetime sex partners (55.3% versus 27.8%). All HPV type prevalences were significantly higher among WLHIV compared to women without HIV, including prevalence of any HPV (82.7% versus 63.0%), HR-HPV (72.9% versus 53.8%), and quadrivalent vaccine HPV types (34.3% versus 21.0%). Among WLHIV, there were no differences between those perinatally and non-perinatally infected for HPV prevalences, number of HPV types detected, CD4 count, or viral load. CONCLUSIONS: Over one-third of WLHIV and nearly a quarter of those without HIV had vaccine-type HPV detected. This study supports need for the national HPV vaccination program in Botswana and provides important baseline data for future evaluation of impact of the program.

Pain management for medical abortion before 14 weeks' gestation.

BACKGROUND: Abortion is common worldwide and increasingly abortions are performed at less than 14 weeks' gestation using medical methods, specifically using a combination of mifepristone and misoprostol. Medical abortion is known to be a painful process, but the optimal method of pain management is unclear. We sought to identify and compare pain management regimens for medical abortion before 14 weeks' gestation.  OBJECTIVES: Primary objective To determine if there is evidence of superiority of any particular pain relief regimen in the management of combination medical abortion (mifepristone + misoprostol) under 14 weeks' gestation (i.e. up to 13 + 6 weeks or 97 days). Secondary objectives To compare the rate of gastrointestinal side effects resulting from different methods of analgesia To compare the rate of complete abortion resulting from different methods of analgesia during medical abortion To determine if the induction-to-abortion interval is associated with different methods of analgesia To determine if any method of analgesia is associated with unscheduled contact with the care provider in relation to pain. SEARCH METHODS: On 21 August 2019 we searched CENTRAL, MEDLINE, Embase, CINAHL, LILACs, PsycINFO, the World Health Organization International Clinical Trials Registry and ClinicalTrials.gov together with reference checking and handsearching of conference abstracts of relevant learned societies and professional organisations to identify further studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and observational studies (non-randomised studies of interventions (NRSIs)) of any pain relief intervention (pharmacological and non-pharmacological) for mifepristone-misoprostol combination medical abortion of pregnancies less than 14 weeks' gestation. DATA COLLECTION AND ANALYSIS: Two review authors (JRW and MA) independently assessed all identified papers for inclusion and risks of bias, resolving any discrepancies through discussion with a third and fourth author as required (CM and SC). Two review authors independently conducted data extraction, including calculations of pain relief scores, and checked for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included four RCTs and one NRSI. Due to the heterogeneity of study designs, interventions and outcome reporting, we were unable to perform meta-analysis for any of the primary or secondary outcomes in this review. Only one study found evidence of an effect between interventions on pain score: a prophylactic dose of ibuprofen 1600 mg likely reduces the pain score when compared to a dose of paracetamol 2000 mg (mean difference (MD) 2.26 out of 10 lower, 95% confidence interval (CI) 3.00 to 1.52 lower; 1 RCT 108 women; moderate-certainty evidence). There may be little to no difference in pain score when comparing pregabalin 300 mg with placebo (MD 0.5 out of 10 lower, 95% CI 1.41 lower to 0.41 higher; 1 RCT, 107 women; low-certainty evidence).  There may be little to no difference in pain score when comparing ibuprofen 800 mg with placebo (MD 1.4 out of 10 lower, 95% CI 3.33 lower to 0.53 higher; 1 RCT, 61 women; low-certainty evidence). Ambulation or non-ambulation during medical abortion treatment may have little to no effect on pain score, but the evidence is very uncertain (MD 0.1 out of 5 higher, 95% CI 0.26 lower to 0.46 higher; 1 NRSI, 130 women; very low-certainty evidence). There may be little to no difference in pain score when comparing therapeutic versus prophylactic administration of ibuprofen 800 mg (MD 0.2 out of 10 higher, 95% CI 0.41 lower to 0.81 higher; 1 RCT, 228 women; low-certainty evidence).   Other outcomes of interest were reported inconsistently across studies. Where these outcomes were reported, there was no evidence of difference in incidence of gastrointestinal side effects, complete abortion rate, interval between misoprostol administration to pregnancy expulsion, unscheduled contact with a care provider, patient satisfaction with analgesia regimen nor patient satisfaction with abortion experience overall. However, the certainty of evidence was very low to low. AUTHORS' CONCLUSIONS: The findings of this review provide some support for the use of ibuprofen as a single dose given with misoprostol prophylactically, or in response to pain as needed. The optimal dosing of ibuprofen is unclear, but a single dose of ibuprofen 1600 mg was shown to be effective, and it was less certain whether 800 mg was effective. Paracetamol 2000 mg does not improve pain scores as much as ibuprofen 1600 mg, however its use does not appear to cause greater frequency of side effects or reduce the success of the abortion. A single dose of pregabalin 300 mg does not affect pain scores during medical abortion, but like paracetamol, does not appear to cause harm. Ambulation or non-ambulation during the medical abortion procedure does not appear to affect pain scores, outcomes, or duration of treatment and so women can be advised to mobilise or not, as they wish. The majority of outcomes in this review had low- to very low-certainty evidence, primarily due to small sample sizes and two studies at high risk of bias. High-quality, large-scale RCT research is needed for pain management during medical abortion at gestations less than 14 weeks. Consistent recording of pain with a validated measure would be of value to the field going forward.

High risk of adverse birth outcomes among adolescents living with HIV in Botswana compared to adult women living with HIV and adolescents without HIV.

BACKGROUND: Adolescent girls are three times more likely to be living with HIV than boys of the same age. Prior studies have found associations between adolescent pregnancies and increased maternal morbidity and infant mortality, but few studies have assessed the impact of HIV infection on maternal and infant outcomes in adolescents. METHODS: The Tsepamo Study abstracts maternal and infant data from obstetric records in government maternity wards in Botswana. We assessed maternal complications and adverse birth outcomes for all singleton pregnancies from August 2014 to August 2020 at eighteen Tsepamo sites among adolescents (defined as 10-19 years of age) and adults (defined as 20-35 years of age), by HIV status. Univariate and multivariate logistic regression using a complete case analysis method were used to evaluate differences in outcomes. RESULTS: This analysis included 142,258 singleton births, 21,133 (14.9%) to adolescents and 121,125 (85.1%) to adults. The proportion of adults living with HIV (N = 22,114, 22.5%) was higher than adolescents (N = 1593, 7.6%). The proportion of most adverse birth outcomes was higher in adolescents. Among adolescents, those with HIV had increased likelihoods of anemia (aOR = 1.89, 95%CI 1.66, 2.15) and cesarean sections (aOR = 1.49, 95%CI 1.3,1.72), and infants with preterm birth (aOR = 1.15, 95%CI 1.0, 1.32), very preterm birth (aOR = 1.35, 95%CI 1.0,1.8), small for gestational age (aOR = 1.37, 95%CI 1.20,1.58), and very small for gestational age (aOR = 1.46, 95%CI 1.20, 1.79). CONCLUSIONS: Adolescent pregnancy and adolescent HIV infection remain high in Botswana. Adolescents have higher risk of adverse maternal and infant birth outcomes than adults, with the worst outcomes among adolescents living with HIV. Linking HIV prevention and family planning strategies for this age group may help minimize the number of infants with poor birth outcomes among this already vulnerable population.

Support for lowering cervical cancer screening age to 25 for women living with HIV: retrospective cross-sectional programmatic data from Botswana.

BACKGROUND: Women living with human immunodeficiency virus (HIV) tend to develop cervical cancer at a younger age than women without HIV. The World Health Organization's (WHO) 2021 guidelines for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention include a conditional recommendation for initiating screening at age 25 for women living with HIV (WLWH). This recommendation is based on low-certainty evidence, and WHO calls for additional data. We describe the association of age and HIV status with visual inspection with acetic acid (VIA) positivity and cervical intraepithelial neoplasia grade two or higher (CIN2+) in Botswana. METHODS: This was a retrospective cross-sectional study of 5714 participants aged 25 to 49 years who underwent VIA screening in a clinic mainly serving WLWH. VIA-positive women received cryotherapy if eligible or were referred for colposcopy and excisional treatment. Known cervical cancer risk factors, screening outcome, and histological results were extracted from the program database. We compared the proportions and association of VIA positivity and CIN2+ by age and HIV status. RESULTS: The median age was 35 years [IQR 31-39], and 18% of the women were aged 25-29. Ninety percent were WLWH; median CD4 count was 250 cells/µL [IQR 150-428], and 34.2% were on anti-retroviral treatment (ART). VIA-positivity was associated with younger age (OR 1.48, CI 1.28, 1.72 for 25-29 years vs. 30-49 years), and HIV-positivity (OR 1.85, CI 1.51, 2.28). CIN2+ was only associated with HIV-positivity (OR 6.12, CI 3.39, 11.10), and proportions of CIN2+ were similar for both age groups in WLWH (69.1% vs. 68.3%). CONCLUSIONS: Younger WLWH in Botswana had a significant burden of CIN2+. This finding further supports lowering the screening age for WLWH from 30 to 25.

Integrating Sexually Transmitted Infection Testing and Treatment With Routine HIV Care in Gaborone, Botswana.

BACKGROUND: Sexually transmitted infection (STI) testing is not routinely offered in many countries, and management is symptoms based. Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are associated with an increased risk of HIV transmission. We assess the feasibility and acceptability of integrating CT/NG testing into routine HIV care in Botswana, as well as the prevalence and correlates of CT/NG infections. METHOD: A prospective study was conducted at an HIV clinic in Gaborone between February and October 2019. Eligibility criteria included the following: ≥18 years, HIV infected, and not treated for CT/NG in the past month. Participants self-collected samples and responded to a questionnaire on sociodemographic and health characteristics. Samples were processed using the GeneXpert. Patients were offered same-day results in person or by telephone. Those who tested positive were treated. RESULTS: Of 806 patients informed of the study, 526 (65%) expressed interest and 451 (60%) were enrolled. The median age was 48 years, and 66% were women. All participants provided self-collected samples, were successfully tested, and received results. Almost all reported sample self-collection was easy. The prevalence of CT/NG was 5%. Most participants (73%) with a positive result were asymptomatic. Among infected, 20 (91%) received same-day results and all were treated. Younger age, female sex, and pain during sex were associated with having CT/NG. CONCLUSIONS: Integrating STI testing into routine HIV care was feasible, self-collecting specimens was highly acceptable, but uptake of testing was low. Where blanket screening to the entire clinic population may not be feasible because of resource limitation, one strategy could be to prioritize sexually active patients, younger patients, and women.

Experience of and factors associated with violence against sexual and gender minorities in nine African countries: a cross-sectional study.

OBJECTIVE: The objective of this research was to assess physical and sexual violence experienced by sexual and gender minorities in nine African countries, and to examine factors associated with violence. METHODS: We conducted an exploratory multi-country cross-sectional study among self-identifying sexual and gender minorities, using a survey tool available in paper and online. Participants were sampled through venue-based and web-based convenience sampling. We analysed data using descriptive statistics and logistic regression, with Stata15. FINDINGS: Of 3798 participants, 23% were gender minorities, 20% were living with HIV, and 18% had been coerced into marriage. Fifty-six per cent of all participants had experienced physical or sexual violence in their lifetime, and 29% in the past year. Gender minorities had experienced significantly higher levels of violence compared to cisgender (sexual minority) participants. The variable most strongly associated with having experienced violence was being coerced into marriage (AOR, 3.02), followed by people living nearby knowing about one's sexual orientation and/or gender identity (AOR, 1.90) and living with HIV (AOR, 1.47). CONCLUSION: Sexual and gender minorities in Eastern and Southern Africa experience high levels of violence. Sexual orientation and gender identity need to be recognised as risk factors for violence in national and regional law and policy frameworks. States should follow the African Commission Resolution 275 and provide protection against violence based on real or perceived sexual orientation or gender identity.

Relationship, partner factors and stigma are associated with safer conception information, motivation, and behavioral skills among women living with HIV in Botswana.

BACKGROUND: A significant proportion (20-59%) of people living with HIV in sub-Saharan Africa desire childbearing, are of reproductive age, and are in sero-different relationships (~50%). Thus it is plausible that some portion of new HIV transmissions are due to attempts to become pregnant. Safer conception (SC) methods that effectively reduce the risk of HIV transmission exist and can be made available in resource-constrained settings. Few studies in the region, and none in Botswana, have quantitatively examined the correlates of information, motivation, and behavioral skills for SC uptake. METHODS: We surveyed 356 women living with HIV from 6/2018 to 12/2018 at six public-sector health clinics in Gaborone, Botswana. Participants were 18-40 years old, not pregnant, and desired future children or were unsure about their childbearing plans. We examined correlates of SC information, motivation, and behavioral skills using nested linear regression models, adjusting for socio-demographic, interpersonal, and structural variables. RESULTS: Knowledge of SC methods varied widely. While some SC methods were well known (medical male circumcision by 83%, antiretroviral therapy for viral suppression by 64%), most other methods were known by less than 40% of participants. Our final models reveal that stigma as well as relationship and partner factors affect SC information, motivation, and behavioral skills. Both internalized childbearing stigma (ß=-0.50, 95%CI:-0.17, -0.02) and perceived community childbearing stigma were negatively associated with SC information (ß=-0.09, 95%CI:-0.80, -0.21). Anticipated (ß=-0.06, 95%CI:-0.12, -0.003) and internalized stigma (ß=-0.27, 95%CI:-0.44; -0.10) were associated with decreased SC motivation, while perceived community childbearing stigma was associated with increased SC motivation (ß=0.07, 95%CI:0.02, 0.11). Finally, internalized childbearing stigma was associated with decreased SC behavioral skills (ß=-0.80, 95%CI: -1.12, -0.47) while SC information (ß=0.24, 95%CI:0.12, 0.36), motivation (ß=0.36, 95%CI:0.15, 0.58), and perceived partner willingness to use SC (ß=0.47, 95%CI:0.36, 0.57) were positively associated with behavioral skills CONCLUSIONS: Low SC method-specific information levels are concerning since almost half (47%) of the study participants reported they were in sero-different relationships and desired more children. Findings highlight the importance of addressing HIV stigma and partner dynamics in interventions to improve SC information, motivation, and behavioral skills.

Perceptions matter: Narratives of contraceptive implant robbery in Cape Town, South Africa.

Uptake of contraceptive implants has declined in South Africa since their introduction in 2014, with side effects and inadequate health provider training cited as primary contributors underlying a poor community perception of implants. In this paper we explore a theme that emerged unexpectedly during analysis of our research in Cape Town that may be an additional factor in this decline: narratives of women being assaulted by robbers who physically remove the implants for smoking as drugs. Narratives were described consistently across interviews and focus groups with youth (aged 18-24 years) and in interviews with health providers, with six participants (two young people, four health providers) sharing personal experiences of robbery. While there was a range of perspectives on whether narratives are based on real experiences or are myths, there was strong consensus that narratives of implant robbery may be influencing women's decisions around implant use in Cape Town. This is a potent example of how perceptions of new products can affect uptake and offers important lessons for implementers to reflect on in planning for rollout of other health technologies.