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In 2007 the World Health Organization (WHO) launched the global initiative to eliminate mother-to-child transmission of syphilis (congenital syphilis, or CS). To assess progress towards the goal of <50 CS cases per 100,000 live births, we generated regional and global estimates of maternal and congenital syphilis for 2016 and updated the 2012 estimates. Maternal syphilis estimates were generated using the Spectrum-STI model, fitted to sentinel surveys and routine testing of pregnant women during antenatal care (ANC) and other representative population data. Global and regional estimates of CS used the same approach as previous WHO estimates. The estimated global maternal syphilis prevalence in 2016 was 0.69% (95% confidence interval: 0.57-0.81%) resulting in a global CS rate of 473 (385-561) per 100,000 live births and 661,000 (538,000-784,000) total CS cases, including 355,000 (290,000-419,000) adverse birth outcomes (ABO) and 306,000 (249,000-363,000) non-clinical CS cases (infants without clinical signs born to un-treated mothers). The ABOs included 143,000 early fetal deaths and stillbirths, 61,000 neonatal deaths, 41,000 preterm or low-birth weight births, and 109,000 infants with clinical CS. Of these ABOs- 203,000 (57%) occurred in pregnant women attending ANC but not screened for syphilis; 74,000 (21%) in mothers not enrolled in ANC, 55,000 (16%) in mothers screened but not treated, and 23,000 (6%) in mothers enrolled, screened and treated. The revised 2012 estimates were 0.70% (95% CI: 0.63-0.77%) maternal prevalence, and 748,000 CS cases (539 per 100,000 live births) including 397,000 (361,000-432,000) ABOs. The estimated decrease in CS case rates between 2012 and 2016 reflected increased access to ANC and to syphilis screening and treatment. Congenital syphilis decreased worldwide between 2012 and 2016, although maternal prevalence was stable. Achieving global CS elimination, however, will require improving access to early syphilis screening and treatment in ANC, clinically monitoring all women diagnosed with syphilis and their infants, improving partner management, and reducing syphilis prevalence in the general population by expanding testing, treatment and partner referral beyond ANC.

To estimate trends in prevalence and incidence of syphilis, gonorrhea and chlamydia in adult men and women in South Africa. The Spectrum-STI tool estimated trends in prevalence and incidence of active syphilis, gonorrhea and chlamydia, fitting South African prevalence data. Results were used, alongside programmatic surveillance data, to estimate trends in incident gonorrhea cases resistant to first-line treatment, and the reporting gap of symptomatic male gonorrhea and chlamydia cases treated but not reported as cases of urethritis syndrome. In 2017 adult (15-49 years) the estimated female and male prevalences for syphilis were 0.50% (95% CI: 0.32-0.80%) and 0.97% (0.19-2.28%), for gonorrhea 6.6% (3.8-10.8%) and 3.5% (1.7-6.1%), and for chlamydia 14.7% (9.9-21%) and 6.0% (3.8-10.4%), respectively. Between 1990 and 2017 the estimated prevalence of syphilis declined steadily in women and men, probably in part reflecting improved treatment coverage. For gonorrhea and chlamydia, estimated prevalence and incidence showed no consistent time trend in either women or men. Despite growing annual numbers of gonorrhea cases - reflecting population growth - the estimated number of first line treatment-resistant gonorrhea cases did not increase between 2008 and 2017, owing to changes in first-line antimicrobial treatment regimens for gonorrhea in 2008 and 2014/5. Case reporting completeness among treated male urethritis syndrome episodes was estimated at 10-28% in 2017. South Africa continues to suffer a high STI burden. Improvements in access and quality of maternal, STI and HIV health care services likely contributed to the decline in syphilis prevalence. The lack of any decline in gonorrhea and chlamydia prevalence highlights the need to enhance STI services beyond clinic-based syndromic case management, to reinvigorate primary STI and HIV prevention and, especially for women, to screen for asymptomatic infections.

In 2016 the World Health Assembly adopted the global strategy on Sexually Transmitted Infections (STI) 2016-2021 aiming to reduce curable STIs by 90% by 2030. We costed scaling-up priority interventions to coverage targets. Strategy-targeted declines in Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum and Trichomonas vaginalis were applied to WHO-estimated regional burdens at 2012. Syndromic case management was costed for these curable STIs, symptomatic Herpes Simplex Virus 2 (HSV-2), and non-STI vaginal syndromes, with incrementally expanding etiologic diagnosis. Service unit costs were multiplied with clinic attendances and people targeted for screening or prevention, by income tier. Human papilloma virus (HPV) vaccination and screening were costed for coverage increasing to 60% of 10-year-old girls for vaccination, and 60% of women 30-49 years for twice-lifetime screening (including clinical follow-up for positive screens), by 2021. Strategy implementation will cost an estimated US$ 18.1 billion over 2016-2021 in 117 low- and middle-income countries. Cost drivers are HPV vaccination ($3.26 billion) and screening ($3.69 billion), adolescent chlamydia screening ($2.54 billion), and antenatal syphilis screening ($1.4 billion). Clinical management-of 18 million genital ulcers, 29-39 million urethral discharges and 42-53 million vaginal discharges annually-will cost $3.0 billion, including $818 million for service delivery and $1.4 billion for gonorrhea and chlamydia testing. Global costs increase from $2.6 billion to $ 4.0 billion over 2016-2021, driven by HPV services scale-up, despite vaccine price reduction. Sub-Saharan Africa, bearing 40% of curable STI burdens, covers 44% of global service needs and 30% of cost, the Western Pacific 15% of burden/need and 26% of cost, South-East Asia 20% of burden/need and 18% of cost. Costs of global STI control depend on price trends for HPV vaccines and chlamydia tests. Middle-income and especially low-income countries need increased investment, innovative financing, and synergizing with other health programs.

Mozambique continues to face a severe HIV epidemic and high cost for its control, largely born by international donors. We assessed feasible targets, likely impact and costs for the 2015-2019 national strategic HIV/AIDS plan (NSP). The HIV epidemic and response was modelled in the Spectrum/Goals/Resource Needs dynamical simulation model, separately for North/Center/South regions, fitted to antenatal clinic surveillance data, household and key risk group surveys, program statistics, and financial records. Intervention targets were defined in collaboration with the National AIDS Council, Ministry of Health, technical partners and implementing NGOs, considering existing commitments. Implementing the NSP to meet existing coverage targets would reduce annual new infections among all ages from 105,000 in 2014 to 78,000 in 2019, and reduce annual HIV/AIDS-related deaths from 80,000 to 56,000. Additional scale-up of prevention interventions targeting high-risk groups, with improved patient retention on ART, could further reduce burden to 65,000 new infections and 51,000 HIV-related deaths in 2019. Program cost would increase from US$ 273 million in 2014, to US$ 433 million in 2019 for 'Current targets', or US$ 495 million in 2019 for 'Accelerated scale-up'. The 'Accelerated scale-up' would lower cost per infection averted, due to an enhanced focus on behavioural prevention for high-risk groups. Cost and mortality impact are driven by ART, which accounts for 53% of resource needs in 2019. Infections averted are driven by scale-up of interventions targeting sex work (North, rising epidemic) and voluntary male circumcision (Center & South, generalized epidemics). The NSP could aim to reduce annual new HIV infections and deaths by 2019 by 30% and 40%, respectively, from 2014 levels. Achieving incidence and mortality reductions corresponding to UNAIDS' 'Fast track' targets will require increased ART coverage and additional behavioural prevention targeting key risk groups.

When used correctly and consistently, the male condom offers triple protection from unintended pregnancy and the transmission of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). However, with health funding levels stagnant or falling, it is important to understand the cost and health impact associated with prevention technologies. This study is one of the first to attempt to quantify the cost and combined health impact of condom use, as a means to prevent unwanted pregnancy and to prevent transmission of STIs including HIV. This paper describes the analysis to make the case for investment in the male condom, including the cost, impact and cost-effectiveness by three scenarios (low in which 2015 condom use levels are maintained; medium in which condom use trends are used to predict condom use from 2016-2030; and high in which condom use is scaled up, as part of a package of contraceptives, to meet all unmet need for family planning by 2030 and to 90% for HIV and STI prevention by 2016) for 81 countries from 2015-2030. An annual gap between current and desired use of 10.9 billion condoms was identified (4.6 billion for family planning and 6.3 billion for HIV and STIs). Under a high scenario that completely reduces that gap between current and desired use of 10.9 billion condoms, we found that by 2030 countries could avert 240 million DALYs. The additional cost in the 81 countries through 2030 under the medium scenario is $1.9 billion, and $27.5 billion under the high scenario. Through 2030, the cost-effectiveness ratios are $304 per DALY averted for the medium and $115 per DALY averted for the high scenario. Under the three scenarios described above, our analysis demonstrates the cost-effectiveness of the male condom in preventing unintended pregnancy and HIV and STI new infections. Policy makers should increase budgets for condom programming to increase the health return on investment of scarce resources.

We estimated national-level trends in the prevalence of probable active syphilis in adult women using the Spectrum Sexually Transmitted Infections (STI) model to inform program planning, target-setting, and progress evaluation in STI control. The model fitted smoothed-splines polynomial regressions to data from antenatal clinic surveys and screening and representative household surveys, adjusted for diagnostic test performance and weighted by national coverage. Eligible countries had ≥1 data point from 2010 or later and ≥3 from 2000 or later from adult populations considered representative of the general female population (pregnant women or community-based studies). Between 2012 and 2016, the prevalence of probable active syphilis in women decreased in 54 (41%) of 132 eligible countries; this decrease was substantive (≥10% proportionally, ≥0.10% percentage-point absolute difference and non-overlapping 95% confidence intervals in 2012 and 2016) in 5 countries. Restricting eligible data to prevalence measurements of dual treponemal and non-treponemal testing limited estimates to 85 countries; of these, 45 countries (53%) showed a decrease. These standardized trend estimates highlight the need for increased investment in national syphilis surveillance and control efforts if the World Health Organization target of a 90% reduction in the incidence of syphilis between 2018 and 2030 is to be met.

Antiretroviral therapy (ART) reduces mortality in patients with active tuberculosis (TB), but the population-level relationship between ART coverage and TB mortality is untested. We estimated the reduction in population-level TB mortality that can be attributed to increasing ART coverage across 41 high HIV-TB burden countries. We compiled TB mortality trends between 1996 and 2011 from two sources: (1) national program-reported TB death notifications, adjusted for annual TB case detection rates, and (2) WHO TB mortality estimates. National coverage with ART, as proportion of HIV-infected people in need, was obtained from UNAIDS. We applied panel linear regressions controlling for HIV prevalence (5-year lagged), coverage of TB interventions (estimated by WHO and UNAIDS), gross domestic product per capita, health spending from domestic sources, urbanization, and country fixed effects. Models suggest that that increasing ART coverage was followed by reduced TB mortality, across multiple specifications. For death notifications at 2 to 5 years following a given ART scale-up, a 1% increase in ART coverage predicted 0.95% faster mortality rate decline (p = 0.002); resulting in 27% fewer TB deaths in 2011 alone than would have occurred without ART. Based on WHO death estimates, a 1% increase in ART predicted a 1.0% reduced TB death rate (p<0.001), and 31% fewer deaths in 2011. TB mortality was higher at higher HIV prevalence (p<0.001), but not related to coverage of isoniazid preventive therapy, cotrimoxazole preventive therapy, or other covariates. This econometric analysis supports a substantial impact of ART on population-level TB mortality realized already within the first decade of ART scale-up, that is apparent despite variable-quality mortality data.

Background Syphilis is a sexually transmitted infection causing significant global morbidity and mortality. To inform policymaking and economic evaluation studies for syphilis, we summarised utility and disability weights for health states associated with syphilis. Methods We conducted a systematic review, searching six databases for economic evaluations and primary valuation studies related to syphilis from January 2000 to February 2022. We extracted health state utility values or disability weights, including identification of how these were derived. The study was registered in the international prospective register of systematic reviews (PROSPERO, CRD42021230035). Findings Of 3401 studies screened, 22 economic evaluations, two primary studies providing condition-specific measures, and 13 burden of disease studies were included. Fifteen economic evaluations reported outcomes as disability-adjusted life years (DALYs) and seven reported quality-adjusted life years (QALYs). Fourteen of 15 economic evaluations that used DALYS based their values on the original Global Burden of Disease (GBD) study from 1990 (published in 1996). For the seven QALY-related economic evaluations, the methodology varied between studies, with some studies using assumptions and others creating utility weights or converting them from disability weights. Interpretation We found a limited evidence base for the valuation of health states for syphilis, a lack of transparency for the development of existing health state utility values, and inconsistencies in the application of these values to estimate DALYs and QALYs. Further research is required to expand the evidence base so that policymakers can access accurate and well-informed economic evaluations to allocate resources to address syphilis and implement syphilis programs that are cost-effective.

Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa. We model a best case scenario of 90% annual HIV testing coverage in adults 15-49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm(3) (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011-2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses. Expanding ART to CD4 count <350 cells/mm(3) prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9-194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%. Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated.

Introduction Identifying strategies to further reduce AIDS‐related mortality requires accurate estimates of the extent to which mortality among people living with HIV (PLHIV) is due to AIDS‐related or non‐AIDS‐related causes. Existing approaches to estimating AIDS‐related mortality have quantified AIDS‐related mortality as total mortality among PLHIV in excess of age‐ and sex‐matched mortality in populations without HIV. However, recent evidence suggests that, with high antiretroviral therapy (ART) coverage, a growing proportion of excess mortality among PLHIV is non‐AIDS‐related. Methods We searched Embase on 22/09/2023 for English language studies that contained data on AIDS‐related mortality rates among adult PLHIV and age‐matched comparator all‐cause mortality rates among people without HIV. We extracted data on the number and rates of all‐cause and AIDS‐related deaths, demographics, ART use and AIDS‐related mortality definitions. We calculated the proportion of excess mortality among PLHIV that is AIDS‐related. The proportion of excess mortality due to AIDS was pooled using random‐effects meta‐analysis. Results Of 4485 studies identified by the initial search, eight were eligible, all from high‐income settings: five from Europe, one from Canada, one from Japan and one from South Korea. No studies reported on mortality among only untreated PLHIV. One study included only PLHIV on ART. In all studies, most PLHIV were on ART by the end of follow‐up. Overall, 1,331,742 person‐years and 17,471 deaths were included from PLHIV, a mortality rate of 13.1 per 1000 person‐years. Of these deaths, 7721 (44%) were AIDS‐related, an overall AIDS‐related mortality rate of 5.8 per 1000 person‐years. The mean overall mortality rate among the general population was 2.8 (95% CI: 1.8–4.0) per 1000 person‐years. The meta‐analysed percentage of excess mortality that was AIDS‐related was 53% (95% CI: 45–61%); 52% (43–60%) in Western and Central Europe and North America, and 71% (69–74%) in the Asia‐Pacific region. Discussion Although we searched all regions, we only found eligible studies from high‐income countries, mostly European, so, the generalizability of these results to other regions and epidemic settings is unknown. Conclusions Around half of the excess mortality among PLHIV in high‐income regions was non‐AIDS‐related. An emphasis on preventing and treating comorbidities linked to non‐AIDS mortality among PLHIV is required.