Estimation of country-specific and global prevalence of male circumcision.

BACKGROUND: Male circumcision (MC) status and genital infection risk are interlinked and MC is now part of HIV prevention programs worldwide. Current MC prevalence is not known for all countries globally. Our aim was to provide estimates for country-specific and global MC prevalence. METHODS: MC prevalence data were obtained by searches in PubMed, Demographic and Health Surveys, AIDS Indicator Surveys, and Behavioural Surveillance Surveys. Male age was ≥15 years in most surveys. Where no data were available, the population proportion whose religious faith or culture requires MC was used. The total number of circumcised males in each country and territory was calculated using figures for total males from (i) 2015 US Central Intelligence Agency (CIA) data for sex ratio and total population in all 237 countries and territories globally and (ii) 2015 United Nations (UN) figures for males aged 15-64 years. RESULTS: The estimated percentage of circumcised males in each country and territory varies considerably. Based on (i) and (ii) above, global MC prevalence was 38.7 % (95 % confidence interval [CI]: 33.4, 43.9) and 36.7 % (95 % CI: 31.4, 42.0). Approximately half of circumcisions were for religious and cultural reasons. For countries lacking data we assumed 99.9 % of Muslims and Jews were circumcised. If actual prevalence in religious groups was lower, then MC prevalence in those countries would be lower. On the other hand, we assumed a minimum prevalence of 0.1 % related to MC for medical reasons. This may be too low, thereby underestimating MC prevalence in some countries. CONCLUSIONS: The present study provides the most accurate estimate to date of MC prevalence in each country and territory in the world. We estimate that 37-39 % of men globally are circumcised. Considering the health benefits of MC, these data may help guide efforts aimed at the use of voluntary, safe medical MC in disease prevention programs in various countries

Use of injectable hormonal contraception and women’s risk of herpes simplex virus type 2 acquisition: a prospective study of couples in Rakai, Uganda

Background The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been associated with increased risk of HIV acquisition, but fi ndings are inconsistent. Whether DMPA increases the risk of other sexually transmitted viral infections is unknown. We assessed the association between DMPA use and incident herpes simplex virus type 2 (HSV2) infection in women. Methods In this prospective study, we enrolled HIV-negative and HSV2-negative women aged 15–49 years whose HIV-negative male partners were concurrently enrolled in a randomised trial of male circumcision in Rakai, Uganda. We excluded women if either they or their male partners HIV seroconverted. The primary outcome was HSV2 seroconversion, assessed annually. The male circumcision trial was registered with ClinicalTrials.gov, number NCT00425984. Findings Between Aug 11, 2003, and July 6, 2006, we enrolled 682 women in this study. We noted HSV2 seroconversions in 70 (10%) women. Incidence was 13·5 per 100 person-years in women consistently using DMPA (nine incident infections per 66·5 person-years), 4·3 per 100 person-years in pregnant women who were not using hormonal contraception (18 incident infections per 423·5 person-years), and 6·6 per 100 person-years in women who were neither pregnant nor using hormonal contraception (35 incident infections per 529·5 person-years). Women consistently using DMPA had an adjusted hazard ratio for HSV2 seroconversion of 2·26 (95% CI 1·09–4·69; p=0·029) compared with women who were neither pregnant nor using hormonal contraception. Of 132 women with HSV2-seropositive partners, seroconversion was 36·4 per 100 person-years in consistent DMPA users (four incident infections per 11 person-years) and 10·7 per 100 person-years in women who were neither pregnant nor using hormonal contraception (11 incident infections per 103 person-years; adjusted hazard ratio 6·23, 95% CI 1·49–26·3; p=0·012). Interpretation Consistent DMPA use might increase risk of HSV2 seroconversion; however, study power was low. These fi ndings should be assessed in larger populations with more frequent follow-up than in this study, and other contraceptive methods should also be assessed. Access to a wide range of highly eff ective contraceptive methods is needed for women, particularly in sub-Saharan Africa

Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. IMPORTANCE The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable

Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention: Analyses from the Rakai Trials

Ron Gray and colleagues analyze data from two circumcision trials in Uganda to assess how HSV-2 status and genital ulcer disease affect the procedure's ability to reduce HIV infection

Antibody attributes that predict the neutralization and effector function of polyclonal responses to SARS-CoV-2

BACKGROUND: While antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. METHODS: We employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. RESULTS: To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. CONCLUSIONS: Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions

Malaria parasitemia among blood donors in Uganda

Background: Malaria remains a leading transfusion associated infectious risk in endemic areas. However, the prevalence of malaria parasitemia has not been well characterized in blood donor populations. This study sought to determine the prevalence of Plasmodium in red blood cell (RBC) and whole blood (WB) units after the rainy season in Uganda. Methods and materials: Between May and July 2018, blood was collected from the sample diversion pouch of 1000 WB donors in Kampala and Jinja, Uganda. The RBC pellet from ethylenediamine tetraacetic acid (EDTA) anticoagulated blood was stored at -80°C until testing. DNA was extracted and nested PCR was used to screen samples at the genus level for Plasmodium, with positive samples further tested for species identification. Results: Malaria parasitemia among asymptomatic, eligible blood donors in two regions of Uganda was 15.4%; 87.7% (135/154) of infections were with P. falciparum, while P. malariae and P. ovale were also detected. There were 4.3% of blood donors who had mixed infection with multiple species. Older donors (>30 years vs. 17-19 years; aPR = 0.31 [95% CI = 0.17-0.58]), females (aPR = 0.60 [95% CI = 0.42-0.87]), repeat donors (aPR = 0.44 [95% CI = 0.27-0.72]) and those donating near the capital city of Kampala versus rural Jinja region (aPR = 0.49 [95% CI = 0.34-0.69]) had a lower prevalence of malaria parasitemia. Conclusions: A high proportion of asymptomatic blood donors residing in a malaria endemic region demonstrate evidence of parasitemia at time of donation. Further research is needed to quantify the risk and associated burden of transfusion-transmitted malaria (TTM) in order to inform strategies to prevent TTM

COVID-19 Convalescent Plasma Therapy Decreases Inflammatory Cytokines: A Randomized Controlled Trial

This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity

HIV epidemiologic trends among occupational groups in Rakai, Uganda: A population-based longitudinal study, 1999–2016

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23–0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18–0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming

Dynamics of Inflammatory Responses After SARS-CoV-2 Infection by Vaccination Status in the USA: A Prospective Cohort Study

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). FINDINGS: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log INTERPRETATION: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. FUNDING: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation

A 'snip' in time: what is the best age to circumcise?

<p>Abstract</p> <p>Background</p> <p>Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also pediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves.</p> <p>Discussion</p> <p>We show here that infancy is an optimal time for clinical circumcision because an infant's low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used.</p> <p>Summary</p> <p>Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision.</p