Tanah Papua, comprising Papua and West Papua (Papua Barat) , includes only 1.5% of Indonesia’s total population but accounts for over 15% of the country’s new human immunodeficiency virus (HIV) cases. Overall, adult HIV prevalence in Indonesia in 2018 was 0.26%; in Papua it was nearly ten times higher at 2.3%, and almost all new infections occurred through heterosexual transmission. Being a predominantly Muslim country, male circumcision (MC) is nearly universal in Indonesia except in Papua where MC is little practiced. The Indonesian government has turned attention to World Health Organization/UNAIDS 2007 recommendations to offer voluntary medical male circumcision (VMMC) in Tanah Papua as part of a comprehensive package of HIV services. Currently, there are no functioning VMMC programs designed specifically for Papua or with input by Papuans. Using a community-participatory approach, we developed and pilot-tested the Papua Indigenous Model (PIM) of VMMC for acceptability, feasibility, and safety as part of a comprehensive HIV prevention strategy to reduce HIV sexual transmission in Papua. The model of VMMC was developed based on numerous meetings with government officials, health providers, teachers, students, parents, and community leaders. In total, 88 adults and 31 adolescents provided input during focused group discussions. Thirty-two meetings were held with approximately 1050 community members. Staff at three community health facilities were trained in safe VMMC services according to WHO guidelines. While all males ages 15 and above were eligible for VMMC, recruitment by trained peer outreach workers focused especially on Papuan ethnic males ages 15–19 years. Based on other VMMC programs and our consultations with community members, we expected to screen 400 potential participants, but ultimately only 104 participants volunteered to be screened at the three facilities. Of the 104, 94 participants were eligible and accepted circumcision. The average pain score reported by participants was low: 3.4 at 30 min post-circumcision. Two participants (2.1%) experienced a moderate adverse event (AE); no severe AE occurred. Upon follow-up, 98% said that they were somewhat or very satisfied with the procedure; 98% agreed that “If I had a son , I would get him circumcised;” and all but three participants reported that if they had it to do again, they would get circumcised. Despite extensive consultation with local communities, VMMC uptake was lower than anticipated, while levels of satisfaction among those circumcised were high. Even with substantial community input into its promotion, achieving a successful scale-up of VMMC in Papua will be highly challenging, requiring significant support from local, national, and international stakeholders. Nevertheless, it should be made available, integrated with the numerous other evidence-based HIV prevention measures.

IntroductionMillions of women worldwide annually undergo manual vacuum aspiration (MVA) with no pain medication, which is a violation of their basic human dignity. We designed a novel device (Chloe SED®) to administer paracervical block (PCB) during MVA in countries where pain medication is not typically given due to the high cost of the necessary tools.MethodsWe conducted a single-blinded, randomized controlled non-inferiority trial including 61 patients at two hospitals in Kisumu, Kenya, to validate Chloe SED® for administration of PCB during MVA. PCB administered with Chloe SED® was compared to PCB administered with a standard spinal needle. Patients requiring MVA were block randomized in blocks of six, each provider completing six PCBs—three with the Chloe SED® and three with the standard spinal needle. The trial was registered with the Kenya Pharmacy and Poisons Board, ECCT/19/03/01 (https://ctr.pharmacyboardkenya.org/applications/index/protocol_no:RUNDVC8xOS8wMy8wMQ__/filter:/investigator:/sites:/pages:5/start_date:/end_date:/disease_condition:/users:/ercs:/stages). An intention-to-treat analysis was completed. The primary outcome was the non-inferiority of the pain score during uterine evacuation with a non-inferiority margin of 2 points on an 11-point numerical rating scale. Secondary outcomes included the non-inferiority of the pain score at four other time points and patient satisfaction.ResultsChloe SED® showed non-inferiority of the primary outcome with a mean pain score during evacuation of 3.8 [90% confidence interval (CI): 3.1–4.6] compared with the spinal needle at 4.1 (90% CI: 3.5–4.7). Non-inferiority of the pain score was shown at all time points. Most patients expressed a desire for the continued use of the device to administer PCB for MVA. No adverse events were noted.ConclusionIn summary, the Chloe SED® appears non-inferior to the spinal needle and desirable for the administration of PCB during MVA.

Elevated levels of anxiety in relation to chronic pain have been consistently associated with greater distress and disability. Thus, accurate measurement of pain-related anxiety is an important re-quirement in modern pain services. The Pain Anxiety Symptom Scale (PASS) was introduced over 30 years ago, with a shortened 20-item version introduced 10 years later. Both versions of the PASS were derived using Principal Components Analysis, an established method of measure development with roots in classical test theory. Item Response Theory (IRT) is a complementary approach to measure development that can reduce the number of items needed and maximize item utility with minimal loss of statistical and clinical information. The present study used IRT to shorten the 20-item PASS (PASS-20) in a large sample of people with chronic pain (N = 2,669). Two shortened versions were evaluated, 1 composed of the single best-performing item from each of its 4 subscales (PASS-4) and the other with the 2 best-performing items from each subscale (PASS-8). Several supplementary analyses were performed, in-cluding comparative item convergence evaluations based on sample characteristics (ie, female or male sex; clinical or online sample), factor invariance testing, and criterion validity evaluation of the 4, 8, and 20-item versions of the PASS in hierarchical regression models predicting pain-related distress and in-terference. Overall, both shortened PASS versions performed adequately across these supplemental tests, although the PASS-4 had more consistent item convergence between samples, stronger evidence for factor invariance, and accounted for 83% of the variance accounted for by the PASS-20% and 92% of the variance accounted for by the PASS-8 in criterion variables. Consequently, the PASS-4 is re-commended for use in situations where a briefer evaluation of pain-related anxiety is appropriate. Perspective: The Pain Anxiety Symptom Scale (PASS) is an established measure of pain-related fear. This study derived 4 and 8-item versions of the PASS using IRT. Both versions showed strong psychometric properties, stability of factor structure, and relation to important aspects of pain-related functioning.(R) 2023 The Author(s). Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Introduction:Little is known about the impact that the COVID-19 pandemic had on risk of HIV acquisition in sub-Saharan Africa. We assessed the impact of COVID-19-related clinic closures on HIV incidence in a cohort of gay, bisexual, and other men who have sex with men (MSM) and transgender women in Kenya.Methods:MSM and transgender women enrolled in a prospective, multicentre cohort study were followed quarterly for HIV testing, behaviour assessments, and risk. We estimated the HIV incidence rate and its 95% credible intervals (CrI) among participants who were HIV-negative before COVID-19-related clinic closure, comparing incidence rate and risk factors associated with HIV acquisition before vs. after clinic reopening, using a Bayesian Poisson model with weakly informative priors.Results:A total of 690 (87%) participants returned for follow-up after clinic reopening (total person-years 664.3 during clinic closure and 1013.3 after clinic reopening). HIV incidence rate declined from 2.05/100 person-years (95% CrI = 1.22-3.26, n = 14) during clinic closures to 0.96/100 person-years (95% CrI = 0.41-2.07, n = 10) after clinic reopening (IRR = 0.47, 95% CrI = 0.20-1.01). The proportion of participants reporting hazardous alcohol use and several sexual risk behaviours was higher during clinic closures than after clinic reopening. In multivariable analysis adjusting for study site and participant characteristics, HIV incidence was lower after clinic reopening (IRR 0.57, 95% CrI = 0.23-1.33). Independent risk factors for HIV acquisition included receptive anal intercourse (IRR 1.94, 95% CrI = 0.88-4.80) and perceived risk of HIV (IRR 3.03, 95% CRI = 1.40-6.24).Conclusion:HIV incidence during COVID-19-related clinic closures was moderately increased and reduced after COVID-19 restrictions were eased. Ensuring access to services for key populations is important during public health emergencies.

ABSTRACTBackgroundEvidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) by risk groups is limited in Africa. We assessed prevalence, trends, and transmission dynamics of pre-treatment HIVDR within-and-between men who have sex with men (MSM), people who inject drugs (PWID), female sex workers (FSW), heterosexuals (HET), and children infected perinatally in Kenya.MethodsHIV-1 partialpolsequences from antiretroviral-naïve samples collected between 1986-2020 were used. Pre-treatment RTI, PI and INSTI mutations were assessed using the Stanford HIVDR database. Phylogenetics methods were used to determine and date transmission clusters.ResultsOf 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSW (15.1%) and HET (13.9%). No INSTI resistance mutations were detected. Among HET, pre-treatment HIVDR increased from 6.6% in 1986-2005 to 20.2% in 2011-2015 but dropped to 6.5% in 2016-2020. Overall, 22 clusters with shared pre-treatment HIVDR mutations were identified. The largest was a K103N mutation cluster involving 16 MSM sequences sampled between 2010-2017, with an estimated tMRCA of 2005 (HPD, 2000-2008). This lineage had a growth rate=0.1/year and R0=1.1, indicating propagation over 12 years among ART-naïve MSM in Kenya.ConclusionsCompared to HET, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2016 may have reversed the increase in pre-treatment RTI mutations in Kenya. Continued surveillance of HIVDR, with a particular focus on children and key populations, is warranted to inform treatment strategies in Kenya.SummaryCompared to the heterosexual population, key populations had higher levels of pre-treatment HIV-1 drug resistance (HIVDR). Propagation of HIVDR was risk-group exclusive. Introduction of integrase inhibitors abrogated propagation of reverse transcriptase inhibitors mutations among the heterosexual, but not key populations.

The use of face masks has been widely promoted and at times mandated to prevent coronavirus disease 2019 (COVID-19). The 2023 publication of an updated Cochrane review on mask effectiveness for respiratory viruses as well as the unfolding epidemiology of COVID-19 underscore the need for an unbiased assessment of the current scientific evidence. It appears that the widespread promotion, adoption, and mandating of masking for COVID-19 were based not primarily on the strength of evidence for effectiveness but more on the imperative of decision-makers to act in the face of a novel public health emergency, with seemingly few good alternatives. Randomized clinical trials of masking for prevention of COVID-19 and other respiratory viruses have so far shown no evidence of benefit (with the possible exception of continuous use of N95 respirators by hospital workers). Observational studies provide lower-quality evidence and do not convincingly demonstrate benefit from masking or mask mandates. Unless robust new evidence emerges showing the effectiveness of masks in reducing infection or transmission risks in either trials or real-world conditions, mandates are not warranted for future epidemics of respiratory viral infections.

Worldwide, sexual and gender minority individuals have disproportionate burden of HIV. There are limited quantitative data from sub-Saharan Africa on the intersection of risks experienced by transgender women (TGW) in comparison to cis-men who have sex with men (MSM). This analysis addresses this gap by comparing reported stigma, psychosocial measures of health, and sexual risk practices between TGW and cis-MSM in Kenya. We analyzed data from the baseline visit of an ongoing prospective cohort study taking place in three diverse metropolitan areas. Eligible participants were HIV-negative, assigned male at birth, ages 18–29 years, and reported anal intercourse in the past 3 months with a man or TGW. Data collected by audio computer assisted self-interview included sociodemographic measures, and sexual practices occurring in the past 3 months. Multivariable regressions assessed differences between TGW and cis-MSM in selected sexual practices, depressive symptoms, alcohol and drug use, and stigma. From September, 2019, through May, 2021, 838 participants were enrolled: 108 (12.9

Underfunded healthcare infrastructures in low-resource settings in sub-Saharan Africa have resulted in a lack of medical devices crucial to provide healthcare for all. A representative example of this scenario is medical devices to administer paracervical blocks during gynaecological procedures. Devices needed for this procedure are usually unavailable or expensive. Without these devices, providing paracervical blocks for women in need is impossible resulting in compromising the quality of care for women requiring gynaecological procedures such as loop electrosurgical excision, treatment of miscarriage, or incomplete abortion. In that perspective, interventions that can be integrated into the healthcare system in low-resource settings to provide women needing paracervical blocks remain urgent. Based on a context-specific approach while leveraging circular economy design principles, this research catalogues the development of a new medical device called Chloe SED® that can be used to support the provision of paracervical blocks. Chloe SED®, priced at US$ 1.5 per device when produced in polypropylene, US$ 10 in polyetheretherketone, and US$ 15 in aluminium, is attached to any 10-cc syringe in low-resource settings to provide paracervical blocks. The device is designed for durability, repairability, maintainability, upgradeability, and recyclability to address environmental sustainability issues in the healthcare domain. Achieving the design of Chloe SED® from a context-specific and circular economy approach revealed correlations between the material choice to manufacture the device, the device's initial cost, product durability and reuse cycle, reprocessing method and cost, and environmental impact. These correlations can be seen as interconnected conflicting or divergent trade-offs that need to be continually assessed to deliver a medical device that provides healthcare for all with limited environmental impact. The study findings are intended to be seen as efforts to make available medical devices to support women's access to reproductive health services.

Abstract Background Tuberculosis (TB) is an infectious disease that induces a complex response from the host immune system. Most carriers of the bacteria experience the asymptomatic, non-infectious phase, latent tuberculosis infection (LTBI), but have the potential to reactivate to active, contagious TB infection. Current diagnostics for TB are not sufficient for LTBI and are focused on using one biomarker, interferon-gamma (IFN-g). To build better diagnostics for the complex disease, multi-biomarker approaches to profile the immune system, coupled with machine learning algorithms, are necessary to diagnose LTBI and determine patients' risks of reactivation to active TB. We aim to use a multiplexed silicon photonic microring resonator sensing platform to profile thirteen biomarkers in patients with LTBI infection and use machine learning data analysis to identify biomarkers relevant for diagnosing LTBI and predicting reactivation risk. Methods We employed microring resonators coupled with a sandwich-style detection format to simultaneously detect thirteen cytokines and chemokines in plasma in under 40 minutes. Chip-integrated silicon photonic microrings are small in size and easily multiplexed with up to sixteen different capture agents. Biomolecular binding events are measured by monitoring the resonant wavelength within the sensing cavity, which shifts as binding events occur. Quantitation of each biomarker is possible with calibration curves that correlate standard protein concentrations to wavelength shifts. The multiplexed assay has been optimized for each individual biomarker, tested for cross-reactivity, and calibrated in the plasma matrix of interest. The LODs vary, depending on biomarker and matrix dilution, but range from 4.9 pg/mL to 691 pg/mL. The patient plasma samples are left over from the TB screening IFN-g release assay, QuantiFERON-TB Gold Plus (QFT), putting this method within the current clinical workflow. We use precision normalization approaches from the four QFT stimulations to account for immunologic differences among the subjects. The biomarker concentrations are evaluated using a random forest machine learning model to identify which biomarkers are important for identifying patients with LTBI and predicting their reactivation risk. Results We used this sensor method to profile 42 patients, 24 LTBI negative controls and 18 LTBI positive controls, with 13 being considered at high risk of reactivation. Using a precision normalization approach, a combination of nine normalized conditions using five of the thirteen biomarkers (CCL4, CCL8, IP-10, IL-2, IL-17) discriminated between LTBI positive and negative subjects with a ROC AUC of 0.90. Additionally, eight normalized conditions using four of the same biomarkers discriminated between high and low-risk subjects with an AUC of 0.83. Currently, we have expanded the sample cohort to include an additional 72 subjects, 25 LTBI positive and 47 LTBI negative. Preliminary analysis shows CCL8, IL-2, and IP-10 alone are able to distinguish between LTBI status (P values <0.01) using raw target concentrations prior to precision normalization. Conclusion Overall, we show the importance of multi-biomarker approaches to develop diagnostic and prognostic tools for a complex disease, such as TB. Further work to use the initial machine learning algorithm with the expanded cohort to validate biomarker importance is underway.

Introduction: Little is known about the impact that the COVID-19 pandemic had on risk of HIV acquisition in sub-Saharan Africa. We assessed the impact of COVID-19-related clinic closures on HIV incidence in a cohort of gay, bisexual, and other men who have sex with men (MSM) and transgender women in Kenya. Methods: MSM and transgender women enrolled in a prospective, multicentre cohort study were followed quarterly for HIV testing, behaviour assessments, and risk. We estimated the HIV incidence rate and its 95% credible intervals (CrI) among participants who were HIV-negative before COVID-19-related clinic closure, comparing incidence rate and risk factors associated with HIV acquisition before vs. after clinic reopening, using a Bayesian Poisson model with weakly informative priors. Results: A total of 690 (87%) participants returned for follow-up after clinic reopening (total person-years 664.3 during clinic closure and 1013.3 after clinic reopening). HIV incidence rate declined from 2.05/100 person-years (95% CrI = 1.22–3.26, n = 14) during clinic closures to 0.96/100 person-years (95% CrI = 0.41–2.07, n = 10) after clinic reopening (IRR = 0.47, 95% CrI = 0.20–1.01). The proportion of participants reporting hazardous alcohol use and several sexual risk behaviours was higher during clinic closures than after clinic reopening. In multivariable analysis adjusting for study site and participant characteristics, HIV incidence was lower after clinic reopening (IRR 0.57, 95% CrI = 0.23–1.33). Independent risk factors for HIV acquisition included receptive anal intercourse (IRR 1.94, 95% CrI = 0.88–4.80) and perceived risk of HIV (IRR 3.03, 95% CRI = 1.40–6.24). Conclusion: HIV incidence during COVID-19-related clinic closures was moderately increased and reduced after COVID-19 restrictions were eased. Ensuring access to services for key populations is important during public health emergencies.

Male circumcision is an evidence-based intervention with numerous health benefits, including a decreased risk for men acquiring HIV through sex with women, and is recommended by WHO in generalised HIV-epidemic settings.1WHOGuidelines: preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics: recommendations and key considerations. World Health Organization, Geneva2020Google Scholar National voluntary medical male circumcision (VMMC) programmes in sub-Saharan African countries provided nearly 30 million preventive circumcisions between 2007 and 2020,2UNAIDSWHOUneven progress on voluntary medical male circumcision: programme across 15 eastern and southern African countries in the face of the COVID-19 pandemic.https://www.malecircumcision.org/resource/uneven-progress-vmmc-unaids-and-who-progress-brief-april-2022-2007%E2%80%932020Date: April, 2022Date accessed: August 12, 2022Google Scholar which are estimated to avert 1·6 million HIV infections by 2030. Consequently, VMMC is positioned as a pillar of regional strategy for controlling the HIV epidemic. Most of these circumcisions were done in individuals aged 10 years or older, who could begin reaping the benefits of HIV prevention either immediately or soon after the procedure (eg, at sexual debut), which is expected to decrease transmission rates over the next decade. The appropriate role of early infant male circumcision (EIMC) in these settings, particularly in the longer term, is a more complex question. EIMC remains attractive to many implementers and national health leaders for several reasons, including greater procedural simplicity than VMMC and expectations of lower cost. However, the small scale-up of EIMC to date stems largely from concerns about its current risk–benefit balance, as well as historical unfamiliarity with the procedure in communities across east and southern Africa. Leaving aside questions around the ethics of removing living tissue from individuals who are unable to provide informed consent, early experiences with rare severe and lethal EIMC adverse events (AEs) in these settings,3Bailey RC Adera F Makesey-Amiti ME et al.Prospective comparison of two models of integrating early infant male circumcision with maternal child health services in Kenya: the Mtoto Msafi Mbili study.PLoS One. 2017; 12e0184170Google Scholar, 4Lucas TJ Toledo C Davis SM et al.Case series of glans injuries during voluntary medical male circumcision for HIV prevention—eastern and southern Africa, 2015–2018.BMC Urol. 2020; 20: 45Google Scholar as well as the long delay until most benefits are observed in an unknown context of future epidemics, and the success of standard VMMC programmes, have discouraged donor funding, leaving EIMC programmes largely to the national budgets of interested countries. The current VMMC endorsement by WHO does not include infants for similar reasons.1WHOGuidelines: preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics: recommendations and key considerations. World Health Organization, Geneva2020Google Scholar Thus, safety advances, particularly devices eliminating serious AEs (eg, glans injury, severe bleeding, and urethral fistula), might affect the risk–benefit balance. In The Lancet Global Health, Spyridon Basourakos and colleagues5Basourakos SP Nang QG Ballman KV et al.ShangRing versus Mogen clamp for early infant male circumcision in eastern sub-Saharan Africa: a multicentre, non-inferiority, adaptive, randomised controlled trial.Lancet Glob Health. 2022; 10: e1514-e1577Google Scholar report the findings of a non-inferiority randomised controlled trial comparing the safety and efficacy of the ShangRing, a surgical assist device new to the infant age group, with that of the Mogen clamp, an established device popular in both resource-rich and resource-limited settings, for EIMC. The authors established non-inferiority in the risk of moderate or severe AEs (29 [4·2%] in the ShangRing group vs 30 [4·4%] in the Mogen clamp group; difference –0·1%; one-sided 95% CI upper limit of 1·7%; p=0·89). Excluding moderate or severe AEs related to pain, there were nine (1·3%) moderate or severe AEs in the ShangRing group and seven (1·0%) in the Mogen clamp group. Pain was controlled with topical anaesthetic, oral sucrose, and rectal acetaminophen, instead of the more common practice of injected anaesthetic use. The researchers conclude that the ShangRing is a safe option for EIMC. Safety remains the primary consideration when evaluating EIMC methods. In sub-Saharan Africa, the ShangRing enters a field occupied by legacy devices—eg, the reusable Mogen clamp, the Gomco clamp, and the single-use Plastibell device—and the newer AccuCirc device. Both the ShangRing and AccuCirc device are single-use, eliminating device wear as a cause of AEs, and, importantly, are engineered to protect the glans and urethra. Nevertheless, neither device has yet been used programmatically in sufficient volume to show very rare severe AEs. In the Article by Basourakos and colleagues,5Basourakos SP Nang QG Ballman KV et al.ShangRing versus Mogen clamp for early infant male circumcision in eastern sub-Saharan Africa: a multicentre, non-inferiority, adaptive, randomised controlled trial.Lancet Glob Health. 2022; 10: e1514-e1577Google Scholar the moderate or severe AEs unrelated to pain and reasonably attributable to the ShangRing were one case each of excessive foreskin removal, insufficient foreskin removal, infection, wound edge adhesion, and fever. One death per group occurred, although both were deemed to be unrelated to the procedure. The case of excessive foreskin removal was managed conservatively and the case of insufficient foreskin removal was treated with procedural circumcision, both of which are feasible procedures in resource-limited settings. No moderate or severe bleeding was noted in the ShangRing group. Thus, EIMC by ShangRing appears to be as safe as existing options, and might prove to be superior if bleeding that requires intervention is not observed among larger study populations. Because the ShangRing remains in place for 1–2 weeks, the possibility of detachment and proximal migration causing rare serious complications from compression, as seen with the Plastibell device,6Bode CO Ikhisemojie S Ademuyiwa AO Penile injuries from proximal migration of the Plastibell circumcision ring.J Pediatr Urol. 2010; 6: 23-27Google Scholar should be addressed in size selection training, safety monitoring, and parental instructions. As the authors note, topical anaesthetic safety is separate, and requires the inclusion of methaemoglobinaemia risk in training and monitoring.7WHOJhpiegoManual for early infant male circumcision under local anaesthesia. World Health Organization, Geneva2010Google Scholar Furthermore, topical anaesthetic alone might be less effective than injected anaesthetic;8Rossi S Buonocore G Bellieni CV Management of pain in newborn circumcision: a systematic review.Eur J Pediatr. 2021; 180: 13-20Google Scholar direct comparison using the authors’ multimodal approach could be needed. EIMC, with an understandable lack of WHO endorsement and new device guidance, makes for difficult programmatic decisions. Programmes including EIMC will need exceptionally strong safety standards and monitoring. The reduced costs cited in resource-rich settings might not transfer to resource-limited settings, especially when training for new provider cadres, social marketing for a novel intervention, and complex supply chains for single-use devices (eg, multiple infant sizes with the ShangRing) are considered. Perhaps the greatest challenge is the uncertainty of the future context of the HIV epidemic, when current infants reach the age of sexual debut. Unknown factors include future HIV incidence and, thus, what absolute risk reduction circumcision will confer, and what other prevention methods will exist. In this difficult context, a new, possibly safer device—and the price competition it could bring—could broaden the options available to programmes allocating scarce resources to control the HIV epidemic. We declare no competing interests. ShangRing versus Mogen clamp for early infant male circumcision in eastern sub-Saharan Africa: a multicentre, non-inferiority, adaptive, randomised controlled trialUse of the ShangRing device for EIMC showed safety, achieved high caregiver satisfaction, and did not differ from the Mogen clamp in other key measures. The ShangRing could be used by health systems and international organisations to further scale up EIMC across sub-Saharan Africa. 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BackgroundPenile microbiome composition has been associated with HSV-2 and HIV in men and with bacterial vaginosis (BV) and HSV-2 in female sex partners. This study sought to 1) characterize penile microbiome composition over a 1-year period and 2) identify factors associated with penile microbiome composition over time.MethodsThis prospective study of community-recruited heterosexual couples in Kenya measured penile and vaginal microbiomes via 16S ribosomal RNA gene amplicon sequencing at 4 time points over 1 year (1, 6, and 12 months after baseline). We used longitudinal mixed-effects modeling to assess associated demographic, behavioral, and disease factors and changes in community type, meatal taxa with the highest mean relative abundance, and alpha and beta diversity measures. We estimated group-based trajectories to elucidate compositional trends.ResultsAmong 218 men with 740 observations, men had a median age of 26 years, 11.6% were living with HIV, and 46.1% were HSV-2 seropositive. We identified 7 penile community types that varied with circumcision status, female partner vaginal microbiome community state type (CST), condom use, and penile washing. Across varying analytic approaches, 50%–60% of men had stable penile microbiome compositions. Alpha diversity measures were lower for circumcised men and those who reported condom use; they were stable over time but higher if female partners had diverse CSTs or BV. BV was positively associated with the relative abundance of numerous individual penile taxa. The decreased Bray–Curtis similarity was more common for men with HSV-2, and HSV-2 was also associated with a lower relative abundance of Corynebacterium and Staphylococcus.ConclusionsOver a 1-year period, penile microbiome composition was stable for a substantial proportion of men and was influenced by men’s circumcision status, sexual practices, female partner’s vaginal CST and BV status, and men’s HSV-2 status. In the female genital tract, a diverse CST is often associated with poorer health outcomes. Our results contribute toward understanding whether this framework extends to the penile microbiome and whether diversity and the associated penile microbiome compositions influence susceptibility or resilience to poorer health outcomes in men. Focusing on understanding how these factors influence the penile microbiome may lead to therapeutic avenues for reduced HSV-2 and BV infections in men and their female sex partners.

In Kenya, HIV-1 key populations including men having sex with men (MSM), people who inject drugs (PWID) and female sex workers (FSW) are thought to significantly contribute to HIV-1 transmission in the wider, mostly heterosexual (HET) HIV-1 transmission network. However, clear data on HIV-1 transmission dynamics within and between these groups are limited. We aimed to empirically quantify rates of HIV-1 flow between key populations and the HET population, as well as between different geographic regions to determine HIV-1 'hotspots' and their contribution to HIV-1 transmission in Kenya. We used maximum-likelihood phylogenetic and Bayesian inference to analyse 4058 HIV-1 pol sequences (representing 0.3 per cent of the epidemic in Kenya) sampled 1986-2019 from individuals of different risk groups and regions in Kenya. We found 89 per cent within-risk group transmission and 11 per cent mixing between risk groups, cyclic HIV-1 exchange between adjoining geographic provinces and strong evidence of HIV-1 dissemination from (i) West-to-East (i.e. higher-to-lower HIV-1 prevalence regions), and (ii) heterosexual-to-key populations. Low HIV-1 prevalence regions and key populations are sinks rather than major sources of HIV-1 transmission in Kenya. Targeting key populations in Kenya needs to occur concurrently with strengthening interventions in the general epidemic.

Abstract Background We determined how the vaginal and penile microbiomes contribute to herpes simplex virus type 2 (HSV-2) serostatus within sexual partnerships. Methods Microbiomes were characterized in cervicovaginal lavage and penile meatal swab specimens through high-throughput 16s ribosomal RNA gene amplicon sequencing. HSV-2 antibody was detected in serum specimens. We modeled vaginal and penile taxa and covariates contributing to HSV-2 status in women and men using bivariate probit analysis. Results Among 231 couples, HSV-2 was detected in both partners in 78 couples (33.8%), in the woman only in 52 (22.5%),in the man only in 27 (11.7%), and in neither in 74 (32.0%). Among the women (median age, 22 years) 10.9% had human immunodeficiency virus (HIV), and 21.4% had Bacterial vaginosis. Among men (median age, 26 years), 11.8% had HIV, and 55.0% circumcised. In an analysis with adjustment for sociodemographics and Bacterial vaginosis, enrichment of vaginal Gardnerella vaginalis and Lactobacillus iners was associated with increased likelihood of HSV-2 in both partners. Penile taxa (including Ureaplasma and Aerococcus) were associated with HSV-2 in women. Conclusions We demonstrate that penile taxa are associated with HSV-2 in female partners, and vaginal taxa are associated with HSV-2 in male partners. Our findings suggest that couples-level joint consideration of genital microbiome and sexually transmitted infection or related outcomes could lead to new avenues for prevention.

Data on challenges with pre-exposure prophylaxis (PrEP) uptake and adherence among Kenyan gay, bisexual, and other men who have sex with men (GBMSM) are limited. In this mixed-methods sequential explanatory design study, our quantitative phase followed 157 at-risk, HIV-negative GBMSM who accepted PrEP and enrolled in a cohort with 12-month follow-up. Stored dried blood spots collected at two intervals were batch tested for tenofovir diphosphate (TFV-DP) concentrations at study end. Despite high self-reported adherence, only 14.6% of individuals had protective TFV-DP levels at any visit. Protective TFV-DP levels were positively associated with injection drug use and a self-assessed moderate risk of acquiring HIV, and negatively associated with time since enrolment. In our subsequent qualitative phase, an intensive workshop was conducted with the GBMSM community to identify barriers and facilitators to PrEP uptake and adherence. These data revealed numerous challenges with traditional PrEP programs that must be addressed through community collaborations.

HIV-1 transmission dynamics involving men who have sex with men (MSM) in Africa are not well understood. We investigated the rates of HIV-1 transmission between MSM across three regions in Kenya: Coast, Nairobi, and Nyanza. We analyzed 372 HIV-1 partial pol sequences sampled during 2006–2019 from MSM in Coast ( N = 178, 47.9%), Nairobi ( N = 137, 36.8%), and Nyanza ( N = 57, 15.3%) provinces in Kenya. Maximum-likelihood (ML) phylogenetics and Bayesian inference were used to determine HIV-1 clusters, evolutionary dynamics, and virus migration rates between geographic regions. HIV-1 sub-subtype A1 (72.0%) was most common followed by subtype D (11.0%), unique recombinant forms (8.9%), subtype C (5.9%), CRF 21A2D (0.8%), subtype G (0.8%), CRF 16A2D (0.3%), and subtype B (0.3%). Forty-six clusters (size range 2–20 sequences) were found—half (50.0%) of which had evidence of extensive HIV-1 mixing among different provinces. Data revealed an exponential increase in infections among MSM during the early-to-mid 2000s and stable or decreasing transmission dynamics in recent years (2017–2019). Phylogeographic inference showed significant (Bayes factor, BF > 3) HIV-1 dissemination from Coast to Nairobi and Nyanza provinces, and from Nairobi to Nyanza province. Strengthening HIV-1 prevention programs to MSM in geographic locations with higher HIV-1 prevalence among MSM (such as Coast and Nairobi) may reduce HIV-1 incidence among MSM in Kenya.

HIV prevention method preferences were evaluated among Kenyan men who have sex with men (MSM) and transgender women (TW) from three sites: Kisumu, Nairobi and the Coast. Information sessions detailing the attributes, duration of protection, route of administration and probable visibility were attended by 464 HIV negative participants, of whom 423 (median age: 24 years) agreed to be interviewed. Across pairwise comparisons daily PrEP was by far the least preferred (1%); quarterly injections (26%) and monthly pills (23%) were most preferred, followed by yearly implant (19%) and condoms (12%). When participants were "forced" to choose their most preferred PrEP option, only 10 (2.4%) chose the daily pill; more (37.1%) chose the quarterly injection than the monthly pill (34.8%) and the yearly implant (25.8%). TW preferred the yearly implant over the quarterly injection. To achieve the rates of PrEP uptake and adherence necessary for protecting large proportions of vulnerable MSM and TW, a variety of long-acting products should be developed and made accessible to appeal to a diversity of preferences.

The differential spread and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing Coronavirus Disease 2019 (COVID-19), across regions is a major focus for researchers and policy makers. Africa has attracted tremendous attention, due to predictions of catastrophic impacts that have not yet materialized. Early in the pandemic, the seemingly low African case count was largely attributed to low testing and case reporting. However, there is reason to consider that many African countries attenuated the spread and impacts early on. Factors explaining low spread include early government community-wide actions, population distribution, social contacts, and ecology of human habitation. While recent data from seroprevalence studies posit more extensive circulation of the virus, continuing low COVID-19 burden may be explained by the demographic pyramid, prevalence of pre-existing conditions, trained immunity, genetics, and broader sociocultural dynamics. Though all these prongs contribute to the observed profile of COVID-19 in Africa, some provide stronger evidence than others. This review is important to expand what is known about the differential impacts of pandemics, enhancing scientific understanding and gearing appropriate public health responses. Furthermore, it highlights potential lessons to draw from Africa for global health on assumptions regarding deadly viral pandemics, given its long experience with infectious diseases.

Background: Strategies to control coronavirus 2019 disease (COVID-19) have often been based on preliminary and limited data and have tended to be slow to evolve as new evidence emerges. Yet knowledge about COVID-19 has grown exponentially, and the expanding rollout of vaccines presents further opportunity to reassess the response to the pandemic more broadly.Main text: We review the latest evidence concerning 10 key COVID-19 policy and strategic areas, specifically addressing: 1) the expansion of equitable vaccine distribution, 2) the need to ease restrictions as hospitalization and mortality rates eventually fall, 3) the advantages of emphasizing educational and harm reduction approaches over coercive and punitive measures, 4) the need to encourage outdoor activities, 5) the imperative to reopen schools, 6) the far-reaching and long-term economic and psychosocial consequences of sustained lockdowns, 7) the excessive focus on surface disinfection and other ineffective measures, 8) the importance of reassessing testing policies and practices, 9) the need for increasing access to outpatient therapies and prophylactics, and 10) the necessity to better prepare for future pandemics.Conclusions: While remarkably effective vaccines have engendered great hope, some widely held assumptions underlying current policy approaches call for an evidence-based reassessment. COVID-19 will require ongoing mitigation for the foreseeable future as it transforms from a pandemic into an endemic infection, but maintaining a constant state of emergency is not viable. A more realistic public health approach is to adjust current mitigation goals to be more data-driven and to minimize unintended harms associated with unfocused or ineffective control efforts. Based on the latest evidence, we therefore present recommendations for refining 10 key policy areas, and for applying lessons learned from COVID-19 to prevent and prepare for future pandemics.