Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Subvariant Neutralization Following a Primary Vaccine Series of NVX-CoV2373 and BNT162b2 Monovalent Booster Vaccine.

We evaluated the immunologic response to a novel vaccine regimen that included 2 doses of NVX-CoV2373 (Novavax) followed by 1 dose of BNT162b2 (Pfizer-BioNTech) monovalent booster vaccine. A durable neutralizing antibody response to Omicron BA.4/BA.5 and BA.1 variants was observed at month 6 after the booster, while immune escape was noted for the XBB.1.5 variant.

Prevalence and Predictors of Chlamydia trachomatis and Neisseria gonorrhoeae Among HIV-Negative Pregnant Women in Kenya.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in pregnancy contribute to adverse perinatal outcomes. We identified predictors of CT and/or NG infection among pregnant Kenyan women. METHODS: Women without HIV were enrolled at 2 antenatal clinics in Western Kenya. Both CT and NG were assessed using endocervical samples for nucleic acid amplification tests. Poisson regression models were used to evaluate potential CT/NG risk factors. Classification and regression trees were generated to evaluate the joint effects of predictors. RESULTS: Overall, 1276 women had both CT and NG assessments. Women enrolled at a median of 26 weeks' gestation (interquartile range, 22-31 weeks), median age was 22 years (interquartile range, 19-27 years), and 78% were married. In total, 98 (7.7%) tested positive for CT/NG: 70 (5.5%) for CT and 32 (2.5%) for NG, 4 of whom (0.3%) had coinfections. Two-thirds (66%) of CT/NG cases were asymptomatic and would have been missed with only syndromic management. Risk factors of CT/NG included age <22 years, crowded living conditions, being unmarried, being in partnerships for <1 year, abnormal vaginal discharge, sexually transmitted infection history, and Trichomonas vaginalis diagnosis ( P < 0.1). Classification and regression tree analyses identified unmarried women <22 years in relationships for <1 year as 6.1 times more likely to have CT/NG compared with women without these characteristics (26% vs. 6%, adjusted prevalence ratio = 6.1, 95% confidence interval = 3.55-10.39, P < 0.001). CONCLUSIONS: Chlamydia trachomatis / Neisseria gonorrhoeae was frequently asymptomatic and common among young unmarried women in newer partnerships in this cohort. Integrating CT/NG testing into routine antenatal care may be beneficial, especially for young women in Kenya.

Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results.

Cervical cancer burden is high where prophylactic vaccination and screening coverage are low. We demonstrated in a multicenter randomized, double-blind, controlled trial that single-dose human papillomavirus (HPV) vaccination had high vaccine efficacy (VE) against persistent infection at 18 months in Kenyan women. Here, we report findings of this trial through 3 years of follow-up. Overall, 2,275 healthy women aged 15-20 years were recruited and randomly assigned to receive bivalent (n = 760), nonavalent (n = 758) or control (n = 757) vaccine. The primary outcome was incident-persistent vaccine type-specific cervical HPV infection. The primary evaluation was superiority analysis in the modified intention-to-treat (mITT) HPV 16/18 and HPV 16/18/31/33/45/52/58 cohorts. The trial met its prespecified end points of vaccine type-specific persistent HPV infection. A total of 75 incident-persistent infections were detected in the HPV 16/18 mITT cohort: 2 in the bivalent group, 1 in the nonavalent group and 72 in the control group. Nonavalent VE was 98.8% (95% CI 91.3-99.8%, P < 0.0001) and bivalent VE was 97.5% (95% CI 90.0-99.4%, P < 0.0001). Overall, 89 persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: 5 in the nonavalent group and 84 in the control group; nonavalent VE was 95.5% (95% CI 89.0-98.2%, P < 0.0001). There were no vaccine-related severe adverse events. Three years after vaccination, single-dose HPV vaccination was highly efficacious, safe and conferred durable protection. ClinicalTrials.gov no. NCT03675256 .

Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women.

BACKGROUND: Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking. METHODS: We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Hair samples were collected quarterly for objective assessment of doxycycline use. RESULTS: A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae-positive isolates were resistant to doxycycline. CONCLUSIONS: Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.).

Results of a cluster randomized trial testing the Systems Analysis and Improvement Approach to increase cervical cancer screening in family planning clinics in Mombasa County, Kenya.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Kenyan women. Integrating cervical cancer screening into family planning (FP) clinics is a promising strategy to improve health for reproductive-aged women. The objective of this cluster randomized trial was to test the efficacy of an implementation strategy, the Systems Analysis and Improvement Approach (SAIA), as a tool to increase cervical cancer screening in FP clinics in Mombasa County, Kenya. METHODS: Twenty FP clinics in Mombasa County were randomized 1:1 to SAIA versus usual procedures. SAIA has five steps: (1) cascade analysis tool to understand the cascade and identify inefficiencies, (2) sequential process flow mapping to identify bottlenecks, (3) develop and implement workflow modifications (micro-interventions) to address identified bottlenecks, (4) assess the micro-intervention in the cascade analysis tool, and (5) repeat the cycle. Prevalence ratios were calculated using Poisson regression with robust standard errors to compare the proportion of visits where women were screened for cervical cancer in SAIA clinics compared to control clinics. RESULTS: In the primary intent-to-treat analysis in the last quarter of the trial, 2.5% (37/1507) of visits with eligible FP clients at intervention facilities included cervical cancer screening compared to 3.7% (66/1793) in control clinics (prevalence ratio [PR] 0.67, 95% CI 0.45-1.00). When adjusted for having at least one provider trained to perform cervical cancer screening at baseline, there was no significant difference between screening in intervention clinics compared to control clinics (adjusted PR 1.14, 95% CI 0.74-1.75). CONCLUSIONS: The primary analysis did not show an effect on cervical cancer screening. However, the COVID-19 pandemic and a healthcare worker strike likely impacted SAIA's implementation with significant disruptions in FP care delivery during the trial. While SAIA's data-informed decision-making and clinic-derived solutions are likely important, future work should directly study the mechanisms through which SAIA operates and the influence of contextual factors on implementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03514459. Registered on April 19, 2018.

HIV incidence among women engaging in sex work in sub-Saharan Africa: a systematic review and meta-analysis.

Introduction: HIV incidence among women in sub-Saharan Africa (SSA) has declined steadily, but it is unknown whether new infections among women who engage in sex work (WESW) have declined at a similar rate. We synthesised estimates of HIV incidence among WESW in SSA and compared these to the wider female population to understand levels and trends in incidence over time. Methods: We searched Medline, Embase, Global Health, Popline, Web of Science, and Google Scholar from January 1990 to October 2022, and grey literature for estimates of HIV incidence among WESW in SSA. We included studies reporting empirical estimates in any SSA country. We calculated incidence rate ratios (IRR) compared to age-district-year matched total female population incidence estimates. We conducted a meta-analysis of IRRs and used a continuous mixed-effects model to estimate changes in IRR over time. Results: From 32 studies between 1985 and 2020, 2,194 new HIV infections were observed in WESW over 51,000 person-years (py). Median HIV incidence was 4.3/100py (IQR 2.8-7.0/100py), declining from a median of 5.96/100py between 1985 and 1995 to a median of 3.2/100py between 2010 and 2020. Incidence among WESW was nine times higher than in matched total population women (RR 8.6, 95%CI: 5.7-12.9), and greater in Western and Central Africa (RR 22.4, 95%CI: 11.3-44.3) than in Eastern and Southern Africa (RR 5.3, 95%CI: 3.7-7.6). Annual changes in log IRRs were minimal (-0.1% 95%CI: -6.9 to +6.8%). Conclusions: Across SSA, HIV incidence among WESW remains disproportionately high compared to the total female population but showed similar rates of decline between 1990 and 2020. Improved surveillance and standardisation of approaches to obtain empirical estimates of sex worker incidence would enable a clearer understanding of whether we are on track to meet global targets for this population and better support data-driven HIV prevention programming.

A prospective preconception cohort study of the association between Mycoplasma genitalium and fecundability in Kenyan women trying to conceive.

STUDY QUESTION: Is Mycoplasma genitalium-infection associated with reduced fecundability? SUMMARY ANSWER: Preconception M. genitalium-infection was associated with 27% lower fecundability though confidence intervals were wide, and the association between M. genitalium and fecundability may be dependent on concurrent bacterial vaginosis (BV). WHAT IS KNOWN ALREADY: M. genitalium has been associated with cervicitis, pelvic inflammatory disease, infertility, and preterm birth, but the extent to which M. genitalium is causally related to adverse reproductive sequelae in women is debated. STUDY DESIGN, SIZE, DURATION: Kenyan women enrolled in a prospective preconception cohort provided vaginal fluid specimens and underwent monthly pregnancy testing. Stored samples from 407 women who had been trying to conceive for ≤6 months were tested for M. genitalium using a nucleic acid amplification test. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on first day of last menstrual period, sexual behavior, pregnancy status, and vaginal specimens were collected at monthly preconception visits. The association between M. genitalium detected at the visit prior to each pregnancy test and fecundability was estimated using discrete time proportional probabilities models. Secondary analyses explored the influence of concurrent BV on the association between M. genitalium and fecundability. MAIN RESULTS AND THE ROLE OF CHANCE: The 407 participants experienced 1220 menstrual cycles and 213 pregnancies. The prevalence of M. genitalium at enrollment was 7.7%. After adjustment for age, frequency of condomless sex in the last 4 weeks, and study site, M. genitalium was associated with a 27% lower fecundability, but confidence intervals were wide (adjusted fecundability ratio (aFR) 0.73, 95% CI 0.44, 1.23). In secondary analyses, when compared to cycles without M. genitalium or BV at the visit prior, women with both M. genitalium and BV at the visit prior had a 51% lower fecundability (aFR = 0.49, 95% CI 0.22, 1.09) whereas there was no association of M. genitalium alone (aFR = 0.98 (95% CI 0.54, 1.76)), and a smaller reduction in fecundability for women with BV only (aFR = 0.80 (95% CI 0.60, 1.07)). LIMITATIONS, REASONS FOR CAUTION: Results should be interpreted cautiously given the relatively low prevalence of M. genitalium and wide confidence intervals. WIDER IMPLICATIONS OF THE FINDINGS: In this cohort of Kenyan women trying to conceive, the association between M. genitalium and fecundability was influenced by concurrent BV status, suggesting there may be a synergistic effect of M. genitalium and BV on fecundability. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a National Institutes of Health grant (NICHD R01 HD087346-RSM). R.S.M. received additional support for mentoring (NICHD K24 HD88229). E.M.L. was supported by pre- and post-doctoral fellowships (NIAID T32 AI07140, NICHD F32 HD100202). Data collection and management were completed using REDCap electronic data capture tools hosted at the University of Washington's Institute of Translational Health Science supported by grants from NCATS/NIH (UL1 TR002319). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. R.S.M. receives research funding, paid to the University of Washington, from Hologic Corporation and consulting fees from Lupin Pharmaceuticals. L.E.M. receives research funding and material for research studies, paid to the University of Washington, from Hologic Corporation and Nabriva Therapeutics, travel support from Hologic, and consulting fees from Health Advances. E.M.L.'s contributions to this study primarily occurred while affiliated with the University of Washington; at the time of submission, E.M.L. was an employee of and holds stock or stock grants for AbbVie, Inc. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Characteristics of Kenyan women using HIV PrEP enrolled in a randomized trial on doxycycline postexposure prophylaxis for sexually transmitted infection prevention.

INTRODUCTION: The global incidence of sexually transmitted infections (STIs) has been rapidly increasing over the past decade, with more than one million curable STIs being acquired daily. Young women in sub-Saharan Africa have a high prevalence and incidence of both curable STIs and HIV. The use of doxycycline as a prophylaxis to prevent STIs is promising; however, clinical trials, to date, have only been conducted among men who have sex with men (MSM) in high-income settings. We describe the characteristics of participants enrolled in the first trial to determine the efficacy of doxycycline post-exposure prophylaxis (PEP) to reduce STI incidence among women taking daily, oral HIV pre-exposure prophylaxis (PrEP). METHODS: This is an open-label 1:1 randomized clinical trial on the efficacy of doxycycline PEP compared with standard of care (e.g., quarterly STI screening and treatment) to reduce incident bacterial STIs - Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum - among Kenyan women aged ≥18 and ≤30 years. All were also taking HIV pre-exposure prophylaxis (PrEP). We describe the baseline characteristics, STI prevalence, and STI risk perception of participants. RESULTS: Between February 2020 and November 2021, 449 women were enrolled. The median age was 24 years (IQR 21-27), the majority were never married (66.1%), 370 women (82.4%) reported having a primary sex partner, and 33% had sex with new partners in the three months prior to enrolment. Two-thirds (67.5%, 268 women) did not use condoms, 36.7% reported transactional sex, and 43.2% suspected their male partners of having sex with other women. Slightly less than half (45.9%, 206 women) were recently concerned about being exposed to an STI. The prevalence of STIs was 17.9%, with C. trachomatis accounting for the majority of infections. Perceived risk of STIs was not associated with the detection of an STI. CONCLUSION: Young cisgender women using HIV PrEP in Kenya and enrolled in a trial of doxycycline postexposure prophylaxis had a high prevalence of curable STIs and represent a target population for an STI prevention intervention.

Randomized controlled trial of a theory-informed mHealth intervention to support ART adherence and viral suppression among women with HIV in Mombasa, Kenya: preliminary efficacy and participant-level feasibility and acceptability.

BACKGROUND: Mobile Health ("mHealth") interventions have shown promise in improving HIV treatment outcomes for stigmatized populations. This paper presents the findings from a randomized controlled trial to assess the efficacy, participant-level feasibility and acceptability of a theory-informed mHealth intervention, Motivation Matters!, designed to improve viral suppression and ART adherence among HIV-seropositive women who engage in sex work in Mombasa, Kenya. METHODS: A total of 119 women were randomized between the intervention and standard of care control. The primary outcome examined viral suppression (≤ 30 copies/mL) six months following ART initiation. ART adherence was assessed monthly using a visual analogue scale. Participant-level feasibility was measured through response rates to study text messages. Acceptability was assessed through qualitative exit interviews. RESULTS: Six months following treatment initiation, 69% of intervention and 63% of control participants were virally suppressed (Risk Ratio [RR] = 1.09, 95% Confidence Interval [95% CI] (0.83, 1.44). Among women who were viremic at baseline and endorsed engagement in sex work, 74% of women in the intervention arm compared with 46% of women in the control arm achieved viral suppression at month six RR = 1.61, 95% CI (1.02, 2.55). Adherence was higher in intervention versus control participants every month. All participants responded to at least one message, and there was a 55% overall response rate to intervention text messages. Qualitative exit interviews suggested high acceptability and perceived impact of the intervention. CONCLUSION: The improvements in ART adherence and viral suppression, combined with encouraging data on feasibility and acceptability, provides preliminary evidence that Motivation Matters! could support ART adherence and viral suppression in women who engage in sex work. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02627365, 10/12/2015; http://clinicaltrials.gov ).

Changes in Vaginal Bacteria and Inflammatory Mediators From Periconception Through the Early Postpartum Period in a Cohort of Kenyan Women Without HIV.

BACKGROUND: Women's increased risk of HIV acquisition during pregnancy and postpartum may be mediated by changes in vaginal microbiota and/or cytokines. METHODS: A cohort of 80 Kenyan women who were HIV-1 seronegative contributed 409 vaginal samples at 6 pregnancy time points: periconception, positive pregnancy test result, first trimester, second trimester, third trimester, and postpartum. Concentrations of vaginal bacteria linked with HIV risk and Lactobacillus spp were measured using quantitative polymerase chain reaction. Cytokines were measured by immunoassay. RESULTS: Based on Tobit regression, later pregnancy time points were associated with lower concentrations of Sneathia spp (P = .01), Eggerthella sp type 1 (P = .002), and Parvimonas sp type 2 (P = .02) and higher concentrations of Lactobacillus iners (P < .001), Lactobacillus crispatus (P < .001), Lactobacillus vaginalis (P < .001), interleukin 6 (P < .001), TNF (P = .004), C-X-C motif chemokine ligand 10 (CXCL10; P < .001), C-C motif ligand 3 (P = .009), C-C motif ligand 4 (P < .001), C-C motif ligand 5 (P = .002), interleukin 1ß (P = .02), and interleukin 8 (P = .002). Most cervicovaginal cytokines and vaginal bacteria clustered separately in principal component analysis, except for CXCL10, which did not group with either cytokines or bacteria. The shift toward a Lactobacillus-dominated microbiota during pregnancy mediated the relationship between pregnancy time point and CXCL10. CONCLUSIONS: Increases in proinflammatory cytokines, but not vaginal bacterial taxa linked with higher HIV risk, could provide an explanation for increased HIV susceptibility during pregnancy and postpartum.

Impact of the COVID-19 pandemic on obstetrical care at a tertiary care facility in Mombasa, Kenya: Time-series analyses and staff perspectives.

The COVID-19 pandemic caused disruption in healthcare delivery due to reductions in both health facility capacity and care-seeking behavior. For women experiencing obstetric complications, access to comprehensive emergency obstetric care is critical for maternal and child health. In Kenya, pandemic-related restrictions began in March 2020 and were compounded by a healthcare worker strike in December 2020. We examined medical record data at Coast General Teaching and Referral Hospital, a large public hospital, and conducted staff interviews to understand how healthcare disruptions impacted care delivery and perinatal outcomes. Routinely collected data from all mother-baby dyads admitted to the Labor and Delivery Ward from January 2019 through March 2021 were included in interrupted time-series analyses. Outcomes included number of admissions and proportion of deliveries that resulted in caesarean sections and adverse birth outcomes. Interviews were conducted with nurses and medical officers to understand how the pandemic impacted clinical care. Pre-pandemic, the ward averaged 810 admissions/month, compared to 492 admissions/month post-pandemic (average monthly decrease: 24.9 admissions; 95% CI: -48.0, -1.8). The proportion of stillbirths increased 0.3% per month during the pandemic compared to the pre-pandemic period (95% CI: 0.1, 0.4). No significant differences were seen in the proportion of other adverse obstetrical outcomes. Interview results suggested that pandemic-related disruptions included reduced access to surgical theaters and protective equipment, and absence of COVID-19 guidelines. While these disruptions were perceived as impacting care for high-risk pregnancies, providers believed that overall quality of care did not diminish during the pandemic. However, they expressed concern about a likely increase in at-home births. In conclusion, while the pandemic had minimal adverse impact on hospital-based obstetrical outcomes, it reduced the number of patients able to access care. Emergency preparedness guidelines and public health messaging promoting timely obstetrical care are needed to ensure continuation of services during future healthcare disruptions.

Next generation sequencing to examine associations between vaginal washing and vaginal microbiota: A cohort study.

BACKGROUND: The association between vaginal washing and HIV risk may be mediated by vaginal washing-associated changes in vaginal microbiota. METHODS: Data from a cohort of HIV-negative US and Kenyan women enrolled in the Preventing Vaginal Infections trial were analyzed. Vaginal fluid samples and vaginal washing data were collected every 2 months for 12 months. Bacterial relative abundances were measured by broad-range 16S rRNA gene polymerase chain reaction with next generation sequencing. Generalized estimating equations were used to evaluate the association between vaginal washing and i) the Shannon Diversity Index (SDI); and ii) mean change in percent bacterial relative abundances, with application of a 10% false discovery rate (FDR). RESULTS: Participants (N = 111) contributed 93/630 (14.8%) vaginal washing visits. Mean SDI was 0.74 points higher (95% CI 0.35, 1.14; p < 0.001) at washing visits among US participants (N = 26). Vaginal washing was not associated with SDI in Kenyan participants (N = 85). There were no associations between vaginal washing and vaginal bacterial relative abundances after applying the FDR. CONCLUSIONS: The discordant results in Kenyan versus US women suggests the link between vaginal washing and sub-optimal vaginal microbiota may be context specific. Vaginal microbial shifts may not fully explain the association between vaginal washing and HIV acquisition.

Fertility Desire and Associations with Condomless Sex, Antiretroviral Adherence, and Transmission Potential in a Cohort of Kenyan Women Living with HIV in Sero-discordant Relationships: A Mixed Methods Study.

For women living with HIV (WLH) in serodiscordant partnerships, decisions about childbearing can challenge condom use and antiretroviral adherence. In a prospective cohort of 148 WLH in serodiscordant partnerships, 58 (39%) wanted more children in the future but were not currently trying to conceive (fertility desire), and 32 (22%) were currently trying to become pregnant (fertility intent). Detection of prostate specific antigen (PSA) in vaginal secretions, a marker for recent condomless sex, was lowest in women with fertility desire and highest in women with fertility intent. Detectable viral load followed a similar pattern. Risk of HIV transmission, when condomless sex and PSA detection occurred concurrently, was three to fourfold higher at visits with fertility intent compared to visits with fertility desire. Qualitative interviews underscored the importance women place on childbearing and suggested that they had limited information about the role of antiretroviral therapy in reducing sexual HIV transmission.

The Systems Analysis and Improvement Approach: specifying core components of an implementation strategy to optimize care cascades in public health.

BACKGROUND: Healthcare systems in low-resource settings need simple, low-cost interventions to improve services and address gaps in care. Though routine data provide opportunities to guide these efforts, frontline providers are rarely engaged in analyzing them for facility-level decision making. The Systems Analysis and Improvement Approach (SAIA) is an evidence-based, multi-component implementation strategy that engages providers in use of facility-level data to promote systems-level thinking and quality improvement (QI) efforts within multi-step care cascades. SAIA was originally developed to address HIV care in resource-limited settings but has since been adapted to a variety of clinical care systems including cervical cancer screening, mental health treatment, and hypertension management, among others; and across a variety of settings in sub-Saharan Africa and the USA. We aimed to extend the growing body of SAIA research by defining the core elements of SAIA using established specification approaches and thus improve reproducibility, guide future adaptations, and lay the groundwork to define its mechanisms of action. METHODS: Specification of the SAIA strategy was undertaken over 12 months by an expert panel of SAIA-researchers, implementing agents and stakeholders using a three-round, modified nominal group technique approach to match core SAIA components to the Expert Recommendations for Implementing Change (ERIC) list of distinct implementation strategies. Core implementation strategies were then specified according to Proctor's recommendations for specifying and reporting, followed by synthesis of data on related implementation outcomes linked to the SAIA strategy across projects. RESULTS: Based on this review and clarification of the operational definitions of the components of the SAIA, the four components of SAIA were mapped to 13 ERIC strategies. SAIA strategy meetings encompassed external facilitation, organization of provider implementation meetings, and provision of ongoing consultation. Cascade analysis mapped to three ERIC strategies: facilitating relay of clinical data to providers, use of audit and feedback of routine data with healthcare teams, and modeling and simulation of change. Process mapping matched to local needs assessment, local consensus discussions and assessment of readiness and identification of barriers and facilitators. Finally, continuous quality improvement encompassed tailoring strategies, developing a formal implementation blueprint, cyclical tests of change, and purposefully re-examining the implementation process. CONCLUSIONS: Specifying the components of SAIA provides improved conceptual clarity to enhance reproducibility for other researchers and practitioners interested in applying the SAIA across novel settings.

Predominance of High-Level Tetracycline-Resistant Neisseria gonorrhoeae in Kenya: Implications for Global Implementation of Doxycycline Postexposure Prophylaxis for Prevention of Sexually Transmitted Infections.

ABSTRACT: Using archived Neisseria gonorrhoeae samples from 2008 to 2012, the prevalence of tet (M) genemediating high-level tetracycline resistance in N. gonorrhoeae was 96% among 50 Kenyan women. Determining the local and national prevalence of gonococcal tetracycline resistance and surveillance of gonococcal antimicrobial resistance can inform the implementation of doxycycline postexposure prophylaxis for STI prevention.

The cost of implementing the Systems Analysis and Improvement Approach for a cluster randomized trial integrating HIV testing into family planning services in Mombasa County, Kenya.

BACKGROUND: Although HIV testing in family planning (FP) clinics is a promising approach for engaging women in HIV treatment and prevention services, HIV testing rates are low in FP clinics in Kenya. In 2018, a cluster randomized trial was implemented in Mombasa, Kenya applying the Systems Analysis and Improvement Approach (SAIA) to integrate HIV testing into FP services (1K24HD088229-01). We estimated the incremental costs and explored cost drivers of the FP HIV SAIA implementation in Mombasa, Kenya. METHODS: We conducted a costing evaluation from the payer perspective for the FP HIV SAIA randomized control trial. We identified relevant activities for the intervention including start-up, training, research and FP HIV SAIA. We estimated activity time burden using a time-and motion study. We derived unit costs through staff interviews and programmatic budgets. We present cost estimates for two different scenarios: as-implemented including research and projected costs for a Ministry of Health-supported intervention. All costs are reported in 2018 USD. RESULTS: For an annual program output of 36,086 HIV tests administered to new FP clients, we estimated the total annual program cost to be $91,994 with an average cost per new FP client served of $2.55. Personnel and HIV rapid testing kits comprised 55% and 21% of programmatic costs, respectively. Assuming no changes to program outputs and with efficiency gains under the MOH scenario, the estimated cost per new FP client served decreased to $1.30 with a programmatic cost reduction of 49%. CONCLUSION: FP HIV SAIA is a low-cost and flexible implementation strategy for facilitating integrated delivery of HIV testing alongside FP services. Although cost implications of the FP HIV SAIA intervention must continue to be evaluated over time, these findings provide context-specific cost data useful for budget planning and decision-making regarding intervention delivery and expansion. TRIAL REGISTRATION: The trial was registered on December 15, 2016, with clinicaltrials.gov (NCT02994355).

A cross-sectional study of the prevalence, barriers, and facilitators of cervical cancer screening in family planning clinics in Mombasa County, Kenya.

BACKGROUND: Cervical cancer is the most common cancer in sub-Saharan Africa. With appropriate screening and treatment, cervical cancer can be prevented. In Kenya, cervical cancer screening is recommended for all women of reproductive age who visit a health facility. In particular, the Kenyan Ministry of Health has tasked family planning clinics and HIV clinics with implementing cervical cancer screening as part of the overall cervical cancer screening strategy. A cross-sectional survey was conducted to understand cervical cancer screening practices and explore clinic-level barriers and facilitators to screening in family planning clinics (FP) in Mombasa County, Kenya. METHODS: Structured interviews were conducted with randomly sampled FP clinic managers to collect information about clinic size, location, type, management support, infrastructure, screening practices, and availability of screening commodities. Data were abstracted from FP registers for a 15-month period from October 1, 2017 until December 31, 2018 to understand cervical cancer screening prevalence. Generalized linear models were used to calculate prevalence ratios (PR) and identify clinic-level correlates of reporting any cervical cancer screening. RESULTS: A total of 70 clinics were sampled, 54% (38) were urban and 27% (19) were public facilities. The median number of staff in a clinic was 4 (interquartile range [IQR] 2-6) with a median of 1 provider trained to perform screening (IQR 0-3). Fifty-four percent (38/70) of clinic managers reported that their clinics performed cervical cancer screening. Of these, only 87% (33) and 71% (27) had dependable access to speculums and acetic acid, respectively. Being a public FP clinic was associated with higher prevalence of reported screening (14/38 [37%] vs 6/32 [16%]; prevalence rate ratio [PR] 1.57, 95%CI 1.05-2.33). Clinics that reported cervical cancer screening were much more likely to have at least one provider trained to perform cervical cancer screening (84%, 32/38) compared to clinics that did not report screening (28%, 9/32; PR 3.77, 95%CI 1.82-7.83). CONCLUSION: Integration of cervical cancer screening into FP clinics offers great potential to reach large numbers of reproductive-aged women. Increasing training of healthcare providers and ensuring adequate commodity supplies in FP clinics offer concrete solutions to increase screening in a largely unscreened population.

Assessing the sustainability of the Systems Analysis and Improvement Approach to increase HIV testing in family planning clinics in Mombasa, Kenya: results of a cluster randomized trial.

BACKGROUND: In Kenya, HIV incidence is highest among reproductive-age women. A key HIV mitigation strategy is the integration of HIV testing and counseling (HTC) into family planning services, but successful integration remains problematic. We conducted a cluster-randomized trial using the Systems Analysis and Improvement Approach (SAIA) to identify and address bottlenecks in HTC integration in family planning clinics in Mombasa County, Kenya. This trial (1) assessed the efficacy of this approach and (2) examined if SAIA could be sustainably incorporated into the Department of Health Services (DOHS) programmatic activities. In Stage 1, SAIA was effective at increasing HTC uptake. Here, we present Stage 2, which assessed if SAIA delivery would be sustained when implemented by the Mombasa County DOHS and if high HTC performance would continue to be observed. METHODS: Twenty-four family planning clinics in Mombasa County were randomized to either the SAIA implementation strategy or standard care. In Stage 1, the study staff conducted all study activities. In Stage 2, we transitioned SAIA implementation to DOHS staff and compared HTC in the intervention versus control clinics 1-year post-transition. Study staff provided training and minimal support to DOHS implementers and collected quarterly HTC outcome data. Interviews were conducted with family planning clinic staff to assess barriers and facilitators to sustaining HTC delivery. RESULTS: Only 39% (56/144) of planned SAIA visits were completed, largely due to the COVID-19 pandemic and a prolonged healthcare worker strike. In the final study quarter, 81.6% (160/196) of new clients at intervention facilities received HIV counseling, compared to 22.4% (55/245) in control facilities (prevalence rate ratio [PRR]=3.64, 95% confidence interval [CI]=2.68-4.94). HIV testing was conducted with 60.5% (118/195) of new family planning clients in intervention clinics, compared to 18.8% (45/240) in control clinics (PRR=3.23, 95% CI=2.29-4.55). Interviews with family planning clinic staff suggested institutionalization contributed to sustained HTC delivery, facilitated by low implementation strategy complexity and continued oversight. CONCLUSIONS: Intervention clinics demonstrated sustained improvement in HTC after SAIA was transitioned to DOHS leadership despite wide-scale healthcare disruptions and incomplete delivery of the implementation strategy. These findings suggest that system interventions may be sustained when integrated into DOHS programmatic activities. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02994355) registered on 16 December 2016.

Qualitative evaluation of the Systems Analysis and Improvement Approach as a strategy to increase HIV testing in family planning clinics using the Consolidated Framework for Implementation Research and the Implementation Outcomes Framework.

BACKGROUND: Significant gaps remain in HIV testing and counseling (HTC) in family planning (FP) clinics. To address these gaps, our group tested an implementation strategy called the Systems Analysis and Improvement Approach (SAIA), an evidenced-based multi-component implementation strategy focused on improving entire care cascades. In a cluster randomized trial of 24 FP clinics in Mombasa County, Kenya, SAIA led to a significant increase in HTC in intervention clinics compared to control clinics. The objective of this manuscript was to evaluate SAIA using the Consolidated Framework for Implementation Research (CFIR) and assess the Implementation Outcomes Framework outcomes of acceptability, appropriateness, and feasibility. METHODS: This qualitative assessment was nested within the cluster-randomized trial. Data collection included questionnaires to assess modifiable and non-modifiable health system factors related to HTC and in-depth interviews to query clinic norms, priorities, communication strategies, and readiness for change. The primary outcomes of interest were feasibility, appropriateness, and acceptability of SAIA. Data on inner setting and structural characteristics of FP clinics were collected to inform how context may impact outcomes. All interviews were recorded and analyzed using a rapid assessment approach. RESULTS: Of the 12 intervention clinics, 6 (50%) were public facilities. Availability of resources varied by clinic. Most clinics had a positive implementation climate, engaged leadership, and access to resources and information. While not all clinics identified HTC as a clinic priority, most reported a strong culture of embracing change and recognition of the importance of HIV testing within FP clinics. Interviews highlighted very high acceptability, appropriateness, and feasibility of SAIA. The implementation strategy was not complicated and fit well into existing clinic processes. In particular, staff appreciated that SAIA allowed clinic staff to generate contextually relevant solutions that they implemented. CONCLUSIONS: SAIA was implemented in FP clinics of varying sizes, capacity, and management support and was found to be acceptable, appropriate, and feasible. The agency that clinic staff felt in proposing and implementing their own solutions was likely part of SAIA's success. We anticipate this will continue to be a mechanism of SAIA's success when it is scaled up to more clinics in future trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02994355) registered 16 December 2016.