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

Community-based wound management in a rural setting of Côte d'Ivoire

BACKGROUND: Wounds are a neglected health problem in rural communities of low-income countries, mostly caused by trauma and ulcerative skin diseases including Neglected Tropical Diseases (NTDs) and associated with systemic complications and disability. Rural communities have limited access to high quality health services-based wound care. METHODS: We conducted a prospective observational study on wound management at three levels-community (C), health centre (HC), district hospital (DH)-in a rural community of Cote d'Ivoire. Patients with skin wounds actively identified in a house-to-house survey and passively in the health services in a defined area of the Taabo Health and Demographic Surveillance System were asked to participate and followed-up longitudinally. Endpoints were proportion of wounds closed, time to wound closure, wound size over time, frequency of secondary bacterial infection, need for recapturing after follow-up interruption, and duration of treatment stratified by health service level and wound aetiology. RESULTS: We enrolled 561 patients with 923 wounds between May 2019 and March 2020. The observation period ended in March 2021. Median age was 10 years (IQR 7-15), 63.0% of patients were male. Almost all (99.5%, 870/874) wounds closed within the observation period, 5.3% (49/923) were lost to follow-up. Wounds primarily treated in C, HC and DH closed within a median time of 10, 16 and 170 days, respectively. Median time to acute wound and chronic wound closure was 13 and 72 days, respectively. Wounds treated in C, HC and DH presented with secondary bacterial infections in 10.3% (36/350), 31.0% (133/429) and 100% (5/5) of cases, respectively. Recapturing was required in 68.3% (630/923) of wounds with participants reporting wound closure as the main reason for not attending follow-up. CONCLUSIONS: We describe a wound management model based on national and WHO recommendations focusing on early identification and treatment in the community with potential for broad implementation in low-income countries. TRIAL REGISTRATION: Registration at ClinicalTrials.gov (NCT03957447)

Skin wounds in a rural setting of Côte d'Ivoire: population-based assessment of the burden and clinical epidemiology

BACKGROUND: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. METHODS: We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Cote d'Ivoire. Patients identified with wounds received free care and were invited to participate in the wound management study simultaneously carried out in the survey area. The data were analysed for wound prevalence, stratified by wound and patient characteristics. RESULTS: 3842 HDSS-registered persons were surveyed. Overall wound prevalence derived from combined active and passive case finding was 13.0%. 74.1% (403/544) of patients were below the age of 15 years. Most frequent aetiologies were mechanical trauma (85.3%), furuncles (5.1%), burns (2.9%) and Buruli ulcer (2.2%). Most wounds were acute and smaller than 5 cm2 in size. 22.0% (176/799) of wounds showed evidence of secondary bacterial infection. 35.5% (22/62) of chronic wounds had persisted entirely neglected for years. Buruli ulcer prevalence was 2.3 per 1000 individuals and considerably higher than expected from an annual incidence of 0.01 per 1000 individuals as reported by WHO for Cote d'Ivoire at the time of the study. CONCLUSIONS: Skin wounds are highly prevalent in rural West Africa, where they represent a widely neglected problem. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. TRIAL REGISTRATION: Registration at ClinicalTrials.gov NCT03957447

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

Male Circumcision in the General Population of Kisumu, Kenya: Beliefs about Protection, Risk Behaviors, HIV, and STIs

Using a population-based survey we examined the behaviors, beliefs, and HIV/HSV-2 serostatus of men and women in the traditionally non-circumcising community of Kisumu, Kenya prior to establishment of voluntary medical male circumcision services. A total of 749 men and 906 women participated. Circumcision status was not associated with HIV/HSV-2 infection nor increased high risk sexual behaviors. In males, preference for being or becoming circumcised was associated with inconsistent condom use and increased lifetime number of sexual partners. Preference for circumcision was increased with understanding that circumcised men are less likely to become infected with HIV

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

Worldwide Genetic Variability of the Duffy Binding Protein: Insights into Plasmodium vivax Vaccine Development

The dependence of Plasmodium vivax on invasion mediated by Duffy binding protein (DBP) makes this protein a prime candidate for development of a vaccine. However, the development of a DBP-based vaccine might be hampered by the high variability of the protein ligand (DBPII), known to bias the immune response toward a specific DBP variant. Here, the hypothesis being investigated is that the analysis of the worldwide DBPII sequences will allow us to determine the minimum number of haplotypes (MNH) to be included in a DBP-based vaccine of broad coverage. For that, all DBPII sequences available were compiled and MNH was based on the most frequent nonsynonymous single nucleotide polymorphisms, the majority mapped on B and T cell epitopes. A preliminary analysis of DBPII genetic diversity from eight malaria-endemic countries estimated that a number between two to six DBP haplotypes (17 in total) would target at least 50% of parasite population circulating in each endemic region. Aiming to avoid region-specific haplotypes, we next analyzed the MNH that broadly cover worldwide parasite population. The results demonstrated that seven haplotypes would be required to cover around 60% of DBPII sequences available. Trying to validate these selected haplotypes per country, we found that five out of the eight countries will be covered by the MNH (67% of parasite populations, range 48–84%). In addition, to identify related subgroups of DBPII sequences we used a Bayesian clustering algorithm. The algorithm grouped all DBPII sequences in six populations that were independent of geographic origin, with ancestral populations present in different proportions in each country. In conclusion, in this first attempt to undertake a global analysis about DBPII variability, the results suggest that the development of DBP-based vaccine should consider multi-haplotype strategies; otherwise a putative P. vivax vaccine may not target some parasite populations

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