The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs.

This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted to the Vaccines Special Issue on the "Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs". To tackle the SARS-CoV-2 pandemic, an acceleration of vaccine development across different technology platforms resulted in the emergency use authorization of multiple vaccines in less than a year. Despite this record speed, many limitations surfaced including unequal access to products and technologies, regulatory hurdles, restrictions on the flow of intellectual property needed to develop and manufacture vaccines, clinical trials challenges, development of vaccines that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, and the distorted allocation of funding to favour dominant companies in affluent countries. Key to future epidemic and pandemic responses will be sustainable, global-public-health-driven vaccine development and manufacturing based on equitable access to platform technologies, decentralised and localised innovation, and multiple developers and manufacturers, especially in low- and middle-income countries (LMICs). There is talk of flexible, modular pandemic preparedness, of technology access pools based on non-exclusive global licensing agreements in exchange for fair compensation, of WHO-supported vaccine technology transfer hubs and spokes, and of the creation of vaccine prototypes ready for phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped by current commercial incentives, the unwillingness of pharmaceutical companies and governments to share intellectual property and know-how, the precariousness of building capacity based solely on COVID-19 vaccines, the focus on large-scale manufacturing capacity rather than small-scale rapid-response innovation to stop outbreaks when and where they occur, and the inability of many resource-limited countries to afford next-generation vaccines for their national vaccine programmes. Once the current high subsidies are gone and interest has waned, sustaining vaccine innovation and manufacturing capability in interpandemic periods will require equitable access to vaccine innovation and manufacturing capabilities in all regions of the world based on many vaccines, not just "pandemic vaccines". Public and philanthropic investments will need to leverage enforceable commitments to share vaccines and critical technology so that countries everywhere can establish and scale up vaccine development and manufacturing capability. This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first.

Gender, Power, and Health: Measuring and Assessing Sexual Relationship Power Equity Among Young Sub-Saharan African Women and Men, a Systematic Review.

Gender inequity, including low sexual relationship power (SRP), is an important determinant of intimate partner violence (IPV) and negative sexual, reproductive, and mental health. Different versions of the Sexual Relationship Power Scale (SRPS) are commonly used within youth studies to examine how gender inequities, including controlling behaviors, in heterosexual relationships impact the lives of young people in sub-Saharan Africa. This review aims to (1) describe definitions and measures of SRP within sub-Saharan African youth studies and (2) review and summarize associations between SRP equity, IPV, and sexual, reproductive, and mental health. After searching Pubmed, Ovid Med, Psych info, Web of Science, Google Scholar, and relevant research forums, 304 papers were identified, of which 29 papers based on 15 distinct studies (published 2004-2019) met our criteria for being youth-specific, conducted in sub-Saharan Africa, and including a quantitative measure of SRP. Details of each SRPS are described, including any adaptations and psychometric properties, as well as associations with IPV, sexual, reproductive, and mental health behaviors and outcomes. Results indicate that there are variations to the SRPS, and a paucity of evidence has detailed the psychometric properties of such measures within sub-Saharan African youth studies. Measures of SRP equity are associated with experiences (among women) and perpetration of (among men) IPV as numerous pathways to HIV risk; however, the evidence remains mixed. In order to address overlapping epidemics of violence against women and HIV, efforts are needed to ensure that measures, including the SRPS, are valid and reliable among highly affected populations.

Creating equity in health research to drive more and better evidence.

Health research is rapidly changing with evidence being gathered through new agile methods. This evolution is critical but must be globally equitable so the poorest nations do not lose out. We must harness this change to better tackle the daily burden of diseases that affect the most impoverished populations and bring research capabilities to every corner of the world so that rapid and fair responses to new pathogen are possible; anywhere they appear. We must seize this opportunity to make research easier, better and more equitable. Currently too many nations are unable to generate the evidence or translate it to directly change health outcomes in their own communities. It is essential to act and harness this emerging change in how research data can be generated and shared, so that all nations sustainably gain from this development. There are positive examples to draw on from COVID-19, but we now need to act. Here we present an initiative to develop a new framework that can guide researchers in the design and execution of their studies. This highly agile system will work by adapting to risk and complexity in any given study, whilst generating quality, safe and ethical data.

Intimate Partner Violence, Depression, and Anxiety Are Associated With Higher Perceived Stress Among Both Young Men and Women in Soweto and Durban, South Africa.

Objectives: Psychological stress is an important determinant of health, including for mental well-being and sexual health. However, little is known about the prevalence and psychosocial and sexual health correlates of perceived stress among young people in South Africa, where elevated life-stressors are an important driver of health inequities. This study examines the association between intimate partner violence (IPV), psychosocial and sexual health, and perceived stress, by gender, among South African adolescents and young adults. Methods: Using baseline survey data from AYAZAZI, a cohort study enrolling youth (16-24 years) from Durban and Soweto, we used the 10-item Perceived Stress Scale (PSS-10) to measure the degree to which an individual perceives their life situations as unpredictable, uncontrollable, and overloaded. Possible scores range between 0 and 40; higher scores indicating higher perceived stress. Crude and adjusted gender-stratified linear regression models examined associations between sexual health factors, experiences (young women) and perpetration (young men) of IPV, anxiety (APA 3-item Scale, ≥2 = probable anxiety), and depression (10-item CES-D Scale, ≥10 = probable depression) and perceived stress. Multivariable models adjusted for age, income, sexual orientation, and financial dependents. Results: Of the 425 AYAZAZI participants, 60% were young women. At baseline, 71.5% were students//learners and 77.2% earned ≤ ZAR1600 per month (~$100 USD). The PSS-10 had moderate reliability (α = 0.70 for young women, 0.64 for young men). Young women reported significantly higher mean PSS scores than young men [18.3 (6.3) vs. 16.4 (6.0)]. In adjusted linear regression models, among young women experiences of IPV (ß = 4.33; 95% CI: 1.9, 6.8), probable depression (ß = 6.63; 95% CI: 5.2, 8.1), and probable anxiety (ß = 5.2; 95% CI: 3.6, 6.8) were significantly associated with higher PSS scores. Among young men, ever perpetrating IPV (ß = 2.95; 95% CI: 0.3, 5.6), probable depression (ß = 6; 95% CI: 4.3, 7.6), and probable anxiety (ß = 3.9; 95% CI: 2.1, 5.8) were significantly associated with higher perceived stress. Conclusion: We found that probable depression, anxiety, perpetration of IPV among young men, and experiences of IPV among young women, were associated with higher perceived stress. Critical efforts are needed to address the gendered stressors of young men and women and implement services to address mental health within violence prevention efforts.

A mixed methods investigation of implementation barriers and facilitators to a daily mobile phone sexual risk assessment for young women in Soweto, South Africa.

BACKGROUND: The HIV epidemiology in South Africa reveals stark age and gender disparities, with young women being the most vulnerable to HIV acquisition in 2017. Evaluation of HIV exposure is a challenge in HIV prevention research. Intermittent in-clinic interviewer-administered risk behaviour assessments are utilised but may be limited by social desirability and recall biases. We piloted a mobile phone application for daily self-report of sexual risk behaviour in fifty 18-25 year old women at risk of HIV infection enrolled in HIV Vaccine Trials Network 915 (HVTN 915) in Soweto, South Africa. Through a mixed-methods investigation, we explored barriers and facilitators to completing daily mobile phone surveys among HVTN 915 study participants and staff. METHODS: We analysed quantitative data on barriers and facilitators to mobile phone study completion collected during the larger HVTN 915 study as well as two post-study focus group discussions (FGDs) with fifteen former participants with a median age of 24 years (IQR 23-25) and six individual in-depth interviews (IDIs) with HVTN 915 staff. FGDs and IDIs utilised semi-structured interview guides, were audio-recorded, transcribed verbatim and translated to English. After coding, thematic analysis was performed. RESULTS: The main facilitator for daily mobile phone survey completion assessed across 336 follow-up visits for 49 participants was the daily short message system (SMS) reminders (93%, 312/336). Across 336 visits, 31/49 (63%) retained participants reported barriers to completion of daily mobile phone surveys: forgetting (20%, 12/49), being too busy (19%, 11/49) and the survey being an inconvenience (15%, 9/49). Five main themes were identified during the coding of IDIs and FGDs: (1) facilitators of mobile phone survey completion, such as daily SMS reminders and follow up calls for non-completers; (2) barriers to mobile phone survey completion, including partner, time-related and technical barriers; (3) power of incentives; (4) response bias in providing sensitive information, and (5) recommendations for future mobile phone based interventions. CONCLUSION: Despite our enthusiasm to use innovation to optimise sexual risk assessments, technical and practical solutions are required to improve implementation. We recommend further engagement with participants to optimise this approach and to further understand social desirability bias and study incentives in sexual risk reporting.

Demographics and health profile on precursors of non-communicable diseases in adults testing for HIV in Soweto, South Africa: a cross-sectional study.

OBJECTIVES: This cross-sectional study investigated the burden of HIV-non-communicable disease (NCD) precursor comorbidity by age and sex. Policies stress integrated HIV-NCD screenings; however, NCD screening is poorly implemented in South African HIV testing services (HTS). SETTING: Walk-in HTS Centre in Soweto, South Africa. PARTICIPANTS: 325 voluntary adults, aged 18+ years, who provided written or verbal informed consent (with impartial witness) for screening procedures were enrolled. PRIMARY AND SECONDARY OUTCOMES: Data on sociodemographics, tuberculosis and sexually transmitted infection symptoms, blood pressure (BP) (≥140/90=elevated) and body mass index (<18.5 underweight; 18.5-25.0 normal; >25 overweight/obese) were stratified by age-group, sex and HIV status. RESULTS: Of the 325 participants, the largest proportions were female (51.1%; n=166/325), single (71.5%; n=231/323) and 25-34 years (33.8%; n=110/325). Overall, 20.9% (n=68/325) were HIV infected, 27.5% (n=89/324) had high BP and 33.5% (n=109/325) were overweight/obese. Among HIV-infected participants, 20.6% (14/68) had high BP and 30.9% (21/68) were overweight/obese, as compared with 29.3% (75/256) and 12.1% (31/256) of the HIV-uninfected participants, respectively. Females were more likely HIV-infected compared with males (26.5% (44/166) vs 15.1% (24/159); p=0.012). In both HIV-infected and uninfected groups, high BP was most prevalent in those aged 35-44 years (25% (6/24) vs 36% (25/70); p=0.3353) and >44 years (29% (4/14) vs 48% (26/54); p=0.1886). Males had higher BP than females (32.9% (52/158) vs 22.3% (37/166); p=0.0323); more females were overweight/obese relative to males (45.8% (76/166) vs 20.8% (33/159); p<0.0001). Females were more likely to be HIV infected and overweight/obese. CONCLUSION: Among HTS clients, NCD precursors rates and co-morbidities were high. Elevated BP occurred more in older participants. Targeted integrated interventions for HIV-infected females and HIV-infected people aged 18-24 and 35-44 years could improve HIV public health outcomes. Additional studies on whether integrated HTS will improve the uptake of NCD treatment and improve health outcomes are required.

Measuring sexual relationship power equity among young women and young men South Africa: Implications for gender-transformative programming.

INTRODUCTION: Measures used to assess equitable relationship dynamics, including the sexual relationship power scale (SRPS) have previously been associated with lower HIV-risk among young women, and reduced perpetration of intimate partner violence among men. However, few studies describe how the SRPS has been adapted and validated for use within global youth sexual health studies. We examined gender-specific psychometric properties, reliability, and validity of a SRPS used within a South African youth-engaged cohort study. METHODS: Young men and women (16-24 years) enrolled in community-based cohorts in Durban and Soweto (2014-2016) reporting a primary partner at 6-month follow-up completed a 13-item (strongly agree/agree/disagree/strongly disagree) South African adaptation of Pulerwitz's SRPS (range 13-52, higher scores indicating greater sexual relationship power [SRP] equity). SRPS modifications were made using gender-specific exploratory factor analyses (EFAs), removing items with factor loadings <0.3. Cronbach alphas were conducted for full and modified scales by gender. Using modified scales, unadjusted and adjusted regression models examined associations between 1. relevant socio-demographic and relationship determinants and SRP equity, and 2. SRP equity and sexual relationship related outcomes. All models adjusted for education, age, site, and current employment. RESULTS: 235 sexually-active youth (66% women, median age = 20) were included. Mean scores across all 13 scale items were 2.71 (SD 0.30) for women and 2.70 (SD 0.4) for men. Scale Cronbach's alphas were 0.63 for women and 0.64 for men. EFAs resulted in two gender-specific single-factor SRPS. Modified SRPS Cronbach alphas increased to 0.67 for women (8-items) and 0.70 for men (9-items). After adjusting for age, site and current employment, higher education remained associated with SRP equity across genders. In adjusted models, correlates of SRP equity included primary partnerships that were age-similar (<5 years older) and <2 years in length for women and living in Soweto and younger age for men. Greater SRP equity among women was also independently associated with no recent partner violence. CONCLUSIONS: Results highlight important gender differences in SRP equity measures and associations, highlighting the critically need for future research to examine gendered constructions of SRP equity in order to accurately develop, validate and use appropriate measures within quantitative surveys.

Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa.

BACKGROUND: RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective. METHODS: Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions. RESULTS: Our analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750). CONCLUSIONS: While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.

Universal health coverage and intersectoral action for health: key messages from Disease Control Priorities, 3rd edition.

The World Bank is publishing nine volumes of Disease Control Priorities, 3rd edition (DCP3) between 2015 and 2018. Volume 9, Improving Health and Reducing Poverty, summarises the main messages from all the volumes and contains cross-cutting analyses. This Review draws on all nine volumes to convey conclusions. The analysis in DCP3 is built around 21 essential packages that were developed in the nine volumes. Each essential package addresses the concerns of a major professional community (eg, child health or surgery) and contains a mix of intersectoral policies and health-sector interventions. 71 intersectoral prevention policies were identified in total, 29 of which are priorities for early introduction. Interventions within the health sector were grouped onto five platforms (population based, community level, health centre, first-level hospital, and referral hospital). DCP3 defines a model concept of essential universal health coverage (EUHC) with 218 interventions that provides a starting point for country-specific analysis of priorities. Assuming steady-state implementation by 2030, EUHC in lower-middle-income countries would reduce premature deaths by an estimated 4·2 million per year. Estimated total costs prove substantial: about 9·1% of (current) gross national income (GNI) in low-income countries and 5·2% of GNI in lower-middle-income countries. Financing provision of continuing intervention against chronic conditions accounts for about half of estimated incremental costs. For lower-middle-income countries, the mortality reduction from implementing the EUHC can only reach about half the mortality reduction in non-communicable diseases called for by the Sustainable Development Goals. Full achievement will require increased investment or sustained intersectoral action, and actions by finance ministries to tax smoking and polluting emissions and to reduce or eliminate (often large) subsidies on fossil fuels appear of central importance. DCP3 is intended to be a model starting point for analyses at the country level, but country-specific cost structures, epidemiological needs, and national priorities will generally lead to definitions of EUHC that differ from country to country and from the model in this Review. DCP3 is particularly relevant as achievement of EUHC relies increasingly on greater domestic finance, with global developmental assistance in health focusing more on global public goods. In addition to assessing effects on mortality, DCP3 looked at outcomes of EUHC not encompassed by the disability-adjusted life-year metric and related cost-effectiveness analyses. The other objectives included financial protection (potentially better provided upstream by keeping people out of the hospital rather than downstream by paying their hospital bills for them), stillbirths averted, palliative care, contraception, and child physical and intellectual growth. The first 1000 days after conception are highly important for child development, but the next 7000 days are likewise important and often neglected.

Projected economic evaluation of the national implementation of a hypothetical HIV vaccination program among adolescents in South Africa, 2012.

BACKGROUND: Adolescents in South Africa are at high risk of acquiring HIV. The HIV vaccination of adolescents could reduce HIV incidence and mortality. The potential impact and cost-effectiveness of a national school-based HIV vaccination program among adolescents was determined. METHOD: The national HIV disease and cost burden was compared with (intervention) and without HIV vaccination (comparator) given to school-going adolescents using a semi-Markov model. Life table analysis was conducted to determine the impact of the intervention on life expectancy. Model inputs included measures of disease and cost burden and hypothetical assumptions of vaccine characteristics. The base-case HIV vaccine modelled cost at US$ 12 per dose; vaccine efficacy of 50 %; duration of protection of 10 years achieved at a coverage rate of 60 % and required annual boosters. Incremental cost-effectiveness ratios (ICER) were calculated using life years gained (LYG) serving as the outcome measure. Sensitivity analyses were conducted on the vaccine characteristics to assess parameter uncertainty. RESULTS: The HIV vaccination model yielded an ICER of US$ 5 per LYG (95 % CI ZAR 2.77-11.61) compared with the comparator, which is considerably less than the national willingness-to-pay threshold of cost-effectiveness. This translated to an 11 % increase in per capita costs from US$ 80 to US$ 89. National implementation of this intervention could potentially result in an estimated cumulative gain of 23.6 million years of life (95 % CI 8.48-34.3 million years) among adolescents age 10-19 years that were vaccinated. The 10 year absolute risk reduction projected by vaccine implementation was 0.42 % for HIV incidence and 0.41 % for HIV mortality, with an increase in life expectancy noted across all age groups. The ICER was sensitive to the vaccine efficacy, coverage and vaccine pricing in the sensitivity analysis. CONCLUSIONS: A national HIV vaccination program would be cost-effective and would avert new HIV infections and decrease the mortality and morbidity associated with HIV disease. Decision makers would have to discern how these findings, derived from local data and reflective of the South African epidemic, can be integrated into the national long term health planning should a HIV vaccine become available.

Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention: A Randomized Trial.

BACKGROUND: A prophylactic HIV-1 vaccine is a global health priority. OBJECTIVE: To assess a novel vaccine platform as a prophylactic HIV-1 regimen. DESIGN: Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149). SETTING: United States, East Africa, and South Africa. PATIENTS: Healthy adults without HIV infection. INTERVENTION: 2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations. MEASUREMENTS: Safety and immunogenicity and the effect of baseline vector immunity. RESULTS: 217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States. LIMITATIONS: Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown. CONCLUSION: Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response. PRIMARY FUNDING SOURCE: International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.

The Case for Adolescent HIV Vaccination in South Africa: A Cost-Effectiveness Analysis.

Despite comprising 0.7% of the world population, South Africa is home to 18% of the global human immunodeficiency virus (HIV) prevalence. Unyielding HIV subepidemics among adolescents threaten national attempts to curtail the disease burden. Should an HIV vaccine become available, establishing its point of entry into the health system becomes a priority. This study assesses the impact of school-based HIV vaccination and explores how variations in vaccine characteristics affect cost-effectiveness. The cost per quality adjusted life year (QALY) gained associated with school-based adolescent HIV vaccination services was assessed using Markov modeling that simulated annual cycles based on national costing data. The estimation was based on a life expectancy of 70 years and employs the health care provider perspective. The simultaneous implementation of HIV vaccination services with current HIV management programs would be cost-effective, even at relatively higher vaccine cost. At base vaccine cost of US$ 12, the incremental cost effectiveness ratio (ICER) was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to duration of vaccine mediated protection and variations in vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values. School-based HIV vaccine services of adolescents, in addition to current HIV prevention and treatment health services delivered, would be cost-effective.

The Price of Prevention: Cost Effectiveness of Biomedical HIV Prevention Strategies in South Africa.

BACKGROUND: South Africa has the highest global burden of human immunodefciency virus [HIV]. The study compared the cost-effectiveness of individual and combination HIV preventive strategies against the current rollout of ART and possible ART scale-up. METHODS: Adolescents attending South African schools in 2012 were included in the semi-Markov running annual cycles. The ART and HIV counseling and testing program [comparator] was weighed against the interventions [viz. HIV vaccine, a dual vaccine strategy [HIV and HPV vaccines], oral pre-exposure prophylaxis [PrEP] and voluntary medical male circumcision [VMMC]; and various combinations thereof. Quality-adjusted life years [QALY] determined changes in HIV associated mortality and infections averted. One-way and probabilistic sensitivity analysis determined parameter uncertainty. Discount rates of 3% with a lifetime horizon [70 years] were applied. RESULTS: Dual vaccination was highly cost-effective strategy [US$ 7 per QALY gained] and averted 29% of new HIV infections. VMMC [US$ 30 per QALY gained] proved more cost-effective than HIV vaccination alone [US$ 93 per QALY gained], though VMMC averted 6% more new infections than the HIV vaccine when considered among male participants. PrEP interventions were the least cost-effective with pharmaceutical and human resource spending driving the costs. Combined dual vaccination and VMMC strategies were a dominant intervention. Strategies involving PrEP were the least cost-effective. CONCLUSION: VMMC, HIV vaccination and dual vaccination strategies were more cost-effective than any PrEP strategies. A multi-intervention biomedical approach could avert considerable new HIV infections and present a cost-effective use of resources; particularly where large scale multi-interventional randomized controlled trials are absent.

Precision of the Kalon Herpes Simplex Virus Type 2 IgG ELISA: an international inter-laboratory assessment.

BACKGROUND: The commercial Kalon HSV-2 IgG ELISA is currently recommended for research use in sub-Saharan Africa because of its superior accuracy compared to other serologic assays. However, there are no data on key precision parameters of Kalon such as inter-operator variation, repeatability, and reproducibility, thus contributing to a barrier for its acceptance and use in clinical trials in sub-Saharan Africa. We evaluated the analytical and field precision of the Kalon HSV-2 IgG ELISA. METHODS: A total of 600 HIV-infected and uninfected serum samples from South Africa and Zambia, previously tested by the gold standard University of Washington HSV western blot (UW-WB), were tested using Kalon by two technologists in an United States reference laboratory. Aliquots of 183 samples were retested using Kalon by an on-site technologist in a South African laboratory and a Zambian laboratory. RESULTS: Intra-assay variation was below 10 %. Intra-assay, intra-laboratory, and inter-laboratory correlation and agreement were significantly high (p < 0.01). In comparison to the UW-WB, accurate performance of Kalon was reproducible by each operator and laboratory. Receiver operating characteristic curve analysis indicated high selectivity of Kalon in the overall study population (area under the curve = 0.95, 95%CI = 0.92-0.97). DISCUSSION: Kalon is a robust assay with high precision and reproducibility. Accordingly, operator errorlikely does not contribute to the variability observed in Kalon's specificity throughout sera from sub-Saharan Africa. CONCLUSIONS: In populations with optimal diagnostic accuracy, Kalon is a reliable stand-alone method for on-site HSV-2 IgG antibody detection.

Exposure to and experiences of violence among adolescents in lower socio-economic groups in Johannesburg, South Africa.

BACKGROUND: We explored exposure to and experiences of violence and their risk factors amongst ethnically diverse adolescents from lower socio economic groups in Johannesburg. METHODS: This cross-sectional study recruited a stratified sample of 16-18 year old adolescents from four low socio-economic suburbs in Johannesburg to reflect ethnic group clustering. We collected socio-demographic, sexual behaviour, alcohol and drug use and trauma events data. Proportions and risk factors were assessed by chi-square and logistic regression. RESULTS: Of 822 adolescents, 57% (n = 469) were female. Approximately 62% (n = 506) were Black, 13% (n = 107) Coloured, 13% (n = 106) Indian and 13% (n = 103) White. Approximately 67% (n = 552) witnessed violence to a non-family member, 28% (n = 228) experienced violence by a non-family member, and 10% (n = 83) reported sexual abuse. Multivariate analysis determined that witnessing violence in the community was associated with being Black (OR: 4.6, 95%CI: 2.7-7.9), Coloured (OR: 3.9, 95%CI: 2.0-7.4) or White (OR: 8.0, 95%CI:4.0-16.2), repeating a grade (OR: 1.5, 95%CI: 1.01-2.1), having more than one sexual partner (OR: 1.7, 95%CI: 1.1-2.5) and ever taking alcohol (OR: 2.1, 95%CI: 1.5-2.9). Witnessing violence in the family was associated with being female (OR: 1.8, 95%CI: 1.3-2.6), being Black (OR: 2.2, 95%CI: 1.1-4.1), or White (OR: 3.0, 95%CI: 1.4-6.4), repeating a grade (OR: 1.6, 95%CI: 1.1-2.2) and ever taking alcohol (OR: 2.9, 95%CI: 2.0-4.3). CONCLUSIONS: In low socio-economic areas in Johannesburg, Black, White and Coloured adolescents experience a high burden of violence. Interventions to mitigate the effects of violence are urgently required.