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Nikita Naicker,1 Hylton Rodel,2 Rubeshan Perumal,1 Yashica Ganga,2 Mallory Bernstein,2 Ntombi Benede,2 Salim Abdool Karim,1,3 Nesri Padayacthi,1,3 Alex Sigal,2,4,5 Kogieleum Naidoo1,3 1Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; 2Africa Health Research Institute, Durban, South Africa; 3MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute; University of KwaZulu-Natal, Durban, South Africa; 4School of Laboratory Medicine and Medical Sciences; University of KwaZulu-Natal, Durban, South Africa; 5Max Planck Institute for Infection Biology, Berlin, GermanyCorrespondence: Nikita Naicker, Doris Duke Medical Research Institute, 2nd Floor, 719 Umbilo Road, Durban, 4041, South Africa, Tel +27843011636, Email nikita.naicker@caprisa.orgIntroduction: Current TB treatment regimens are pathogen-directed and can be severely compromised by the development of drug resistance. Metformin has been proposed as an adjunctive therapy for TB, however relatively little is known about how metformin modulates the cellular interaction between Mtb and macrophages. We aimed to characterize how metformin modulates Mtb growth within macrophages.Methods: We utilized live cell tracking through time-lapse microscopy to better understand the biological effect of metformin in response to Mtb infection. Furthermore, the potent first-line anti-TB drug, isoniazid, was used as a comparator and as a companion drug.Results: Metformin caused a 14.2-fold decrease in Mtb growth compared to the untreated control. Metformin combined with isoniazid controlled Mtb growth is slightly better than isoniazid alone. Metformin demonstrated the ability to regulate the cytokine and chemokine response over a 72 hour period, better than isoniazid only.Conclusion: We provide novel evidence that metformin controls mycobacterial growth by increasing host cell viability, and a direct and independent pro-inflammatory response to Mtb. Understanding the impact of metformin on Mtb growth within macrophages will advance our current knowledge on metformin as an adjunctive therapy, providing a new host-directed approach to TB treatment.Keywords: metformin, tuberculosis, host-directed therapy, INH, adjunctive therapy

Background: Vaccine adjuvants are detected by the innate immune system and influence adaptive immune responses. The modestly efficacious RV144 Thai trial used alum to adjuvant the gp120 protein boost, whereas the non-efficacious HVTN 702 South African trial used MF59. Volunteers enrolled in HVTN 107 (NCT03284710) were administered these adjuvants with a subtype C pox-protein vaccine, affording a unique opportunity to contrast systemic innate immune responses and potentially inform the results of HVTN 702. Methods: Eighteen volunteers were enrolled per group. T1, T2 and T4 received 2 doses of ALVAC-HIV followed by 3 doses of ALVAC-HIV plus subtype C gp120 administered with MF59 (T1), alum (T2), or un-adjuvanted (T4). T3 received 4 doses of ALVAC-HIV with MF59-adjuvanted gp120. Innate immune responses were measured pre-vaccination and at days 1, 3 and 7 after the first (T3) or third (T1,T2, T4) vaccinations. Alterations in circulating leukocytes were assessed by CBC. Thirty-one serum immunomodulatory mediators were quantitated. Results: Neutrophil concentrations increased on day 1 in all groups (FDR-p's < 0.02) and monocyte concentrations increased in T2,T3 and T4 (FDR-p's < 0.12); lymphocyte concentrations significantly decreased at day 1 only in T1 (FDR-p = 0.03). Serum cytokines were also significantly altered post-vaccination in all groups (FDR-p's < 0.2). On Day 1, nine cytokines were induced in T1, including pro-inflammatory IFN-g, CXCL10, TNF-a, IL-6, as well as CCL4 and IL-2, with many factors remaining elevated at Day 3 and returning to baseline on Day 7. In contrast, only IL-2 and IL-6 were induced in T2 on Day 1 and twelve factors were repressed on Day 7 relative to pre-vaccination, including IFN-g and monocyte-chemotactic factors CCL8, CCL13, and CCL22. Responses in the MF59 groups differed when co-administered at the first vaccination (T3) relative to the third vaccination (T1) with 12 cytokines repressed on Day 1 in T3. Conclusions: Alum-adjuvanted protein administered in a prime/boost regimen including ALVAC-HIV reduced early systemic serum cytokine and chemokine responses to the vaccine, in stark contrast to MF59, where induction of a diverse immunomodulatory cytokine profile was observed in Southern African volunteers. Work on elucidating the differential effect of these two adjuvants on the types of innate immune cell responses in humans continues., OA18.03 E. Andersen-Nissen (1); V. Voillet (2); A. Naidoo (2); J. Kee (1); A. Fiore-Gartland (1); O. Dintwe (2); N. Grunenberg (1); L. Polakowski (3); L. Fleurs (4); I. Jani [...]

Background: The partially efficacious RV144 HIV-1 vaccine trial utilized a gp120 protein boost adjuvanted with alum, whereas the non-efficacious HVTN 702 preventive HIV vaccine utilized a gp120 protein boost adjuvanted with MF59. We compared Env-specific IgG and IgA responses in HVTN 107, a phase 1/2a partially double-blinded clinica trial, utilizing a Clade C ALVAC-HIV prime and 100 mcg gp120 protein boost adjuvanted with alum or MF59 vs. a protein-only boost. Methods: We randomized 132 participants into 4 groups and analyzed Env-specific IgG and IgA binding antibodies at Months 6.5 and 12 (NCT03284710). Results: Robust IgG (96.3% to 100%) and IgA (92% to 93%) responses were seen for all trial arms at the month 6.5 timepoint to gp120 Env proteins contained in the vaccine regimen (ZM96, TV1.C and 1086.C). Compared to all other trial arms, T3 (MF59-adjuvanted co-administration) exhibited significantly greater response rates and magnitudes to vaccine-matched Env proteins at the month 12 time-point. Comparable IgG response rates and magnitudes to vaccine-matched Env proteins were observed between the alum and MF59 prime-boost trial arms. Compared to other groups, T3 exhibited significantly higher IgG response rates to V1V2 panel antigens gp70_B.CaseA_V1V2 (83% vs. 18%-48%, p Conclusions: Env-specific antibody response rates between Alum and MF59-adjuvanted vaccine regimens were similar, including V1V2 IgG response rates that correlated with decreased HIV risk in RV144. On the other hand, co-administration of ALVAC-HIV with gp120 in MF59 induced the highest antibody response rates and magnitudes. Additional studies of vaccine-elicited antibody specificity and function will inform adjuvant-specific induction of potentially protective humoral immune responses., OA18.02 P. Goepfert (1); K. Mngadi (2); Z. Moodie (3); N. Grunenberg (3); J.J. Kee (3); K. Seaton (4); G. Tomaras (4); E. Andersen-Nissen (5); O. Dintwe (5); F. Laher [...]

Background. Proper handwashing can reduce the burden of diseases related to hand hygiene (HH) and so contribute reducing under-5 mortality. Preschoolers can benefit from HH interventions by the burden of disease and absenteeism being reduced. Objective. To perform a scoping review of literature to assess the types and effectiveness of HH interventions at preschools, with a view to providing a guideline for appropriate interventions for South African facilities. Methods. A literature search was conducted through the PubMed database to identify relevant studies. An iterative screening process to focus the review allowed for information on the type and effectiveness of interventions to be collated. An updated PubMed search was conducted to determine whether any interventions related to COVID-19 at preschools could be included. Results. No additional studies relating to COVID-19 were found. Of the 305 studies identified during the initial search, only 12 fitted the specific search criteria. Of these, 10 studies showed improvements in HH-related indicators following the interventions. Only two studies used health education as an intervention, whereas the others included the supply of HH products (to varying extents) as part of the intervention. Conclusion. HH interventions appear successful in reducing diseases spread by poor HH, improving general HH practices and reducing absenteeism among preschoolers. Studies using innovative, entertaining methods of educating children have shown to be successful in improving handwashing techniques and decreasing microbial growth on children's hands. HH interventions are suggested as an effective measure to improve HH during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The experience of violent crime can have a significant impact on the physical and psychological well-being of victims and their families. This paper looks at household experience of violence in five impoverished sites in the city of Johannesburg, South Africa. Five sites were purposefully selected to reflect the prevailing housing profiles in settings of relative impoverishment in Johannesburg. A structured questionnaire was used to obtain information on demographic profiles, socioeconomic data, environmental conditions and health status. Bivariate analyses were conducted to assess the relationship between household experience of violence, and potential risk factors and health/social outcomes. Overall, members of 28% of households had been a victim of violence in the year preceding the study. Across sites, experience of violence within households ranged from 21% to 36%. Perceptions of drug abuse (p=0.01) and drug peddling (p=0.03) as being major problems in the neighbourhood, and living in a house of poor quality (p=0.01), were significantly associated with household experience of crime. In households with experience of violence, fear of crime (p=0.03) and depression (p<0.001) were elevated, and levels of exercise in men were decreased (p=0.05). This paper highlights the high prevalence of violence in impoverished urban areas in South Africa, and contributes to existing evidence regarding the associations between experience of violent crime and psychological ill health in affected communities. The high prevalence of violent crime, and the resultant health and social effects, demand a cross-sectoral intervention to reduce violence, with the health and social sectors playing key roles. [ABSTRACT FROM AUTHOR]

BACKGROUND A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cel-lular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections ofALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gpl20-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month followup, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P=0.84). CONCLUSIONS The ALVAC-gpl20 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence ofimmunogenicity. (HVTN 702 ClinicalTrials .gov number, NCT02968849.). [ABSTRACT FROM AUTHOR]

Limited studies have been conducted on the safety and effectiveness of heterologous COVID-19 vaccine boosting in lower income settings, especially those with high-HIV prevalence., The Sisonke Heterologous mRNA-1273 boost after prime with Ad26.COV2.S (SHERPA) trial evaluated a mRNA-1273 boost after Ad26.COV2.S priming in South Africa. SHERPA was a single-arm, open-label, phase 3 study nested in the Sisonke implementation trial of 500000 healthcare workers (HCWs). Sisonke participants were offered mRNA-1273 boosters between May and November 2022, when Omicron sub-lineages were circulating. Adverse events (AE) were self-reported, and co-primary endpoints (SARS-CoV-2 infections and COVID-19 hospitalizations or deaths) were collected through national databases. We used Cox regression models with booster status as a time-varying covariate to determine the relative vaccine effectiveness (rVE) of the mRNA-1273 booster among SHERPA versus unboosted Sisonke participants. Of 11248 SHERPA participants in the rVE analysis cohort (79.3% female, median age 41), 45.4% had received one and 54.6% two Ad26.COV2.S doses. Self-reported comorbidities included HIV (18.7%), hypertension (12.9%) and diabetes (4.6%). In multivariable analysis including 413161 unboosted Sisonke participants, rVE of the booster was 59% (95%CI 29-76%) against SARS-CoV-2 infection: 77% (95%CI 9-94%) in the one-Ad26.COV2.S dose group and 52% (95%CI 13-73%) in the two-dose group. Severe COVID-19 was identified in 148 unboosted Sisonke participants, and only one SHERPA participant with severe HIV-related immunosuppression. Of 11798 participants in the safety analysis, 228 (1.9%) participants reported 575 reactogenicity events within 7 days of the booster (most commonly injection site pain, malaise, myalgia, swelling, induration and fever). More reactogenicity events were reported among those with prior SARS-CoV-2 infections (adjusted odds ratio [aOR] 2.03, 95%CI 1.59-2.59) and less among people living with HIV (PLWH) (aOR 0.49, 95%CI 0.34-0.69). There were 115 unsolicited adverse events (AEs) within 28 days of vaccination. No related serious AEs were reported. In an immunogenicity sub-study, mRNA-1273 increased binding and neutralizing antibody titres and spike-specific T-cell responses 4 weeks after boosting regardless of the number of prior Ad26.COV2.S doses, or HIV status, and generated Omicron spike-specific cross-reactive responses. mRNA-1273 boosters after one or two Ad26.COV2.S doses were well-tolerated, safe and effective against Omicron SARS-CoV-2 infections among HCWs and PLWH. Trial registration: The SHERPA study is registered in the Pan African Clinical Trials Registry (PACTR): PACTR202310615330649 and the South African National Clinical Trial Registry (SANCTR): DOH-27-052022-5778., Competing Interests: KA and BL are employees of Moderna, Inc. and may hold stock/stock options in the company. The other authors declare no conflict of interests., (Copyright: © 2024 Garrett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Human papillomavirus (HPV) can cause cervical cancer, a leading cause of female cancer mortality in South Africa and worldwide. We assessed the burden of, and factors associated with, HPV infection using a molecular assay and cervical cytology among women living with HIV (WLHIV) in South Africa., Methods: In this cross-sectional analysis, WLHIV initiating antiretroviral therapy (ART) underwent cervical Xpert HPV testing and liquid-based cytology. The Xpert test detects 14 high-risk (hr) HPV types reported in a pooled qualitative result. We evaluated clinical and sociodemographic variables and proportions between women testing positive and negative for hr-HPV, compared cytology with hr-HPV results and assessed associations with HPV positivity., Results: We enrolled 260 WLHIV, median age 31.0 (IQR 26.0-38.0) years. Overall, 91.3% of women were never screened for cervical cancer previously and none received HPV vaccination. In total, 67.3% (175/260) of women tested positive for any hr-HPV type, of which HPV16 and HPV18/45 were detected in 17.3% (45/260) and 22.7% (59/260) of women, respectively, and 56.5% (147/260) tested positive for 11 other hr-types. Of 258 WLHIV, 33.3% (86/258) had abnormal cytology: high-grade squamous intraepithelial lesion (SIL) 7.8% (20/258), low-grade SIL 24.0% (62/258) and atypical squamous cells of undetermined significance 1.6% (4/258). Of these, 93.0% (80/86) tested positive for hr-HPV: 30.0% (24/80) for HPV16, 31.3% (25/80) for HPV18/45 and 92.5% (74/80) for other hr-HPV types. Having a CD4 count<200 cells/µL was associated with hr-HPV infection (adjusted prevalence ratio 2.24; 95% CI 1.69 to 2.99 (p<0.001))., Conclusions: hr-HPV infection and cervical abnormalities are common among WLHIV starting ART, especially those with low CD4 counts, highlighting that early HIV testing and treatment initiation must be prioritised together with cervical cancer screening. The diversity of hr-HPV types suggests a need for vaccines with expanded HPV type coverage in this setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Occupational injuries are a growing public health problem. Approximately 1,000 workers die daily from occupational injuries globally. Artisans working in the informal sector of the construction industry in many low/middle income countries like Nigeria have a higher injury predisposition. This study will assess the determinants of occupational injuries and design a safety intervention for informal sector artisans in the Nigerian construction industry., Methods: A sequential mixed-methods design will be employed to study 840 bricklayers and carpenters (420 per artisan group) in Osun State, Nigeria. Quantitative data will be collected first while qualitative data will be collected thereafter. Thirdly, a modified Delphi-technique will be employed to co-design a safety education intervention. For the quantitative study, artisans will be recruited via multi-stage sampling and a semi-structured questionnaire will be administered to obtain information on artisans' socio-demographics, work-patterns and occupational injuries. A multivariable regression model will be used to determine the association between injury occurrence and independent variables. Twelve to sixteen focus group discussion (FGD) sessions will be conducted for artisans to obtain group perspectives about injuries and preferred safety training topics. From the FGD and quantitative study findings, a list of items for the safety training module will be compiled for the modified-Delphi process. Thereafter, the content validation index (CVI) will be derived and items with CVI of ≥0.80 will be included in the final safety training module., Conclusion: This paper describes the process required to assess the determinants of occupational injuries among artisans in the informal sector of the construction industry in Nigeria and further proposes the design of a context-relevant safety training intervention. The information from this study will be essential in promoting safe working environments for construction artisans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ojo, Onayade and Naicker.)

Purpose: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888)., Methods: Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review (BICR), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pembrolizumab 200 mg intravenously once every 3 weeks for ≤35 cycles and carboplatin AUC 5 mg/mL/min intravenously once every 3 weeks for ≤6 cycles and investigator's choice of paclitaxel 100 mg/m 2 on days 1 and 8 or 175 mg/m 2 on day 1, intravenously once every 3 weeks. The primary end point was objective response rate per RECIST v1.1 by BICR., Results: Between October 27, 2020, and April 29, 2022, 149 patients were screened and 101 received treatment. As of February 20, 2023, the median follow-up was 18.9 months (range, 9.1-27.0). At this final analysis, 49 (49%) of 101 patients had an objective response (95% CI, 38.4 to 58.7), including seven patients (7%) with a confirmed complete response. Of the 101 treated patients, grade 3-5 and serious treatment-related adverse events occurred in 76 (75%) and 27 (27%), respectively. There were no new safety signals., Conclusion: Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC, suggesting this combination may be an alternative option for this patient population.

Background: Reactogenicity informs vaccine safety, and may influence vaccine uptake. We evaluated factors associated with reactogenicity in HVTN 702, a typical HIV vaccine efficacy trial with multiple doses and products., Methods: HVTN 702, a phase 2b/3 double-blind placebo-controlled trial, randomized 5404 African participants aged 18-35 years without HIV to placebo, or ALVAC-HIV (vCP2438) at months 0, 1 and ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 at months 3, 6, 12 and 18. Using multivariate logistic regression, we evaluated associations between reactogenicity with clinical, sociodemographic and laboratory variables., Results: More vaccine than placebo-recipients reported local symptoms (all p < 0.001), arthralgia (p = 0.008), chills (p = 0.012) and myalgia (p < 0.001). Reactogenicity was associated with female sex at birth (OR v  = 2.50, OR p  = 1.81, both p < 0.001) and geographic region. Amongst vaccine-recipients, each year of age was associated with 3 % increase in reactogenicity (OR = 1.03, p = 0.002)., Conclusion: Vaccine receipt, female sex at birth, older age, and region may affect reactogenicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration)., Methods and Findings: Between June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses., Conclusions: Although MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen., Trial Registration: HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710)., Competing Interests: MK and OVDM are employed by GSK and hold shares in the company. MK reports grants from Bill & Melinda Gates Foundation and grants from NIH during the conduct of the study. NKT was an employee of GSK Biologicals and Novartis Vaccines & Diagnostics during the time of the trial. All other authors have nothing to declare., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: For women living with HIV (WLHIV), co-infection with herpes simplex virus type 2 (HSV-2) causes severe genital ulcers and presents additional challenges for their HIV care. To inform preventive strategies, we aimed to determine the incidence and risk factors of HSV-2 positivity in a prospective cohort of South African women., Methods: The CAPRISA 002 study enrolled women at acute HIV infection between 2004 and 2020. HSV-2 testing was conducted by multiplex polymerase chain reaction (PCR) assay on collected vaginal swabs up to twice annually during follow-up. We calculated incidence as the number of new cases per 100 person-years (PYs) and used Cox-proportional-hazard regression to identify factors associated with time-to-HSV-2 PCR positivity., Results: At enrolment, the median age of 171 women was 24 years, interquartile range (IQR 21-28), and the estimated median days since HIV infection was 42 (IQR 22-65). Of participants tested at enrolment, HSV-2 antibody prevalence was 81.4% (105/129), and 10.6% (12/113) were positive by PCR. Among 147 women with a prior negative HSV-2 PCR diagnosis, we observed 47 new HSV-2 PCR positive cases over 424.4 PYs of follow-up, yielding an incidence rate of 11.1 cases per-100-PYs. HSV-2 PCR positivity incidence was higher among younger women (<25 years: adjusted Hazard Ratio [aHR] = 5.91, 95%CI 3.02-11.6), those with bacterial vaginosis (BV) (Nugent score 7-10: aHR = 2.17, 95%CI 1.15-4.10) and lower CD4 counts (<500 cells/μl: aHR = 2.04, 95%CI 1.08-3.87)., Conclusion: After acute HIV infection in women, the incidence of HSV-2 PCR positivity was associated with younger age, BV diagnosis and lower CD4 count., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Human papillomavirus (HPV) infection is a leading cause of cervical cancer. Although this relies on infection and persistence of HPV in epithelial cells, often occurring in the context of other sexually transmitted infections (STIs) and bacterial vaginosis (BV), data on the relationships between these and their relative effects on epithelial barrier integrity in women remain sparse. This study describes the epidemiology of HPV combined with STI and/or BV prevalence and the relative impact on matrix metalloproteinases (MMPs) among South African women., Methods: Roche Linear Array was used for HPV genotyping in menstrual cup pellets of 243 HIV-negative women participating in the CAPRISA 083 cohort study. Vulvovaginal swabs were tested for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis using Xpert® CT/NG assay and lateral flow assay, and Gram staining was performed to diagnose BV using Nugent scoring criteria. Concentrations of 5 MMPs were measured in menstrual cup supernatants by multiplexed ELISA. Fisher's exact tests, Mann-Whitney U tests, and multivariable regression models determined associations between HPV infection, STI and/or BV, and MMP concentrations., Results: HPV was prevalent in 34% of women (83/243; median 23 years, interquartile range (IQR) 21-27 years). Low-risk (lr) (71%, 59/83) and high-risk (hr)-HPV infections (54.2%, 45/83) were common. Hr-HPV was frequently detected in STI and/or BV-positive women compared to women without STIs or BV (p = 0.029). In multivariable analysis, BV was associated with increased odds of hr-HPV detection (OR: 2.64, 95%CI: 1.02-6.87, p = 0.046). Furthermore, Gardasil®9 vaccine-type strains were more frequently detected in women diagnosed with STI and/or BV (55.2%, 32/58 vs 24%, 6/25; p = 0.009). Among STI and/or BV-positive women, HPV detection was significantly associated with increased MMP-10 concentrations (b = 0.55, 95% CI 0.79-1.01; p = 0.022)., Conclusion: Most women with hr-HPV had another STI and/or BV, emphasizing an urgent need for STI and BV screening and intensive scale-up of cervical cancer screening and HPV vaccination programmes. Furthermore, the study highlights the need for more extensive research to confirm and understand the relationship between HPV infection and barrier integrity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Qulu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Antimicrobial resistance (AMR) is a global challenge that has raised concern globally, owing to its detrimental effects on the health and economy of countries. The ever-growing threat of AMR and sources of AMR are still being investigated. Wastewater plays an important role as a habitat for bacteria and an environment conducive to gene transfer. The primary aim of this review was to highlight the contribution of wastewater to AMR., Methods: Evidence of AMR in wastewater was drawn from literature published in the last 10 years, from 2012 to 2022., Results: Wastewater from agricultural practices, pharmaceutical manufacturing plants, and hospital effluents was established to promote AMR. Furthermore, stress factors such as the presence of antibiotics, heavy metals, pH, and temperature initiate and propagate AMR in bacteria living in wastewater. AMR in bacteria from wastewater was established to be either natural or acquired. Wastewater treatment techniques such as membrane filtration, coagulation, adsorption, and advanced oxidation processes have been used to remove resistant bacteria with varying success levels., Conclusion: Wastewater is a major contributor to AMR, and an understanding of its role in AMR is necessary to find a lasting solution. In this regard, the spread of AMR in wastewater should be considered a threat that requires a strategy to stop further damage., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)