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.
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.
Papua New Guinea (PNG) has among the highest rates of sexually transmitted infections (STIs) globally and is committed to reducing their incidence. The Syphilis Interventions Towards Elimination ...(SITE) model was used to explore the expected impact and cost of alternative syphilis intervention scale-up scenarios.
SITE is a dynamical model of syphilis transmission among adults 15–49 years. Individuals are divided into nine groups based on sexual behaviour and into six stages of infection. The model was calibrated to PNG using data from routine surveillance, bio-behavioural surveys, research studies and program records. Inputs included syphilis prevalence, risk behaviours, intervention coverage and service delivery unit costs. Scenarios compared different interventions (clinical treatment, contact tracing, syphilis screening, and condom promotion) for incidence and cost per infection averted over 2021–2030.
Increasing treatment coverage of symptomatic primary/secondary-stage syphilis cases from 25–35% in 2020 to 60% from 2023 onwards reduced estimated incidence over 2021–2030 by 55%, compared to a scenario assuming constant coverage at 2019–2020 levels. The introduction of contact tracing in 2020, assuming 0.4 contacts per symptomatic person treated, reduced incidence over 2021–2030 by 10%. Increasing screening coverage by 20–30 percentage points from the 2019–2020 level reduced incidence over 2021–2030 by 3–16% depending on the target population. Scaling-up clinical, symptom-driven treatment and contact tracing had the lowest cost per infection averted, followed by condom promotion and periodic screening of female sex workers and men who have sex with men.
PNG could considerably reduce its syphilis burden by scaling-up clinical treatment and contact tracing alongside targeted behavioural risk reduction interventions. SITE is a useful tool countries can apply to inform national STI programming and resource allocation.
To study the interactions between two sexually transmitted diseases without remission of the infections, we propose to use Markovian models. One model allows the estimation of the per-partnership ...female-to-male transmission probabilities for each infection, and the other the per-sex-act transmission probabilities. These models take into account the essential factors for the propagation of both infections, including the variability according to age of the rates of prevalence in the population of female partners for the male individuals constituting our sample. We estimate transmission probabilities and relative risks (for circumcision, usage of condoms and the effect of one infection on the infectivity of the other) by using the maximum likelihood method. Bootstrap procedures are used to provide confidence intervals for the parameters. We illustrate the new procedures with the study of the interactions between herpes simplex virus type 2 and human immunodeficiency virus by using data from the male circumcision trial that was conducted in Orange Farm (South Africa). The study shows that the probability that a susceptible male individual acquires one of the viruses is significantly higher when he is already infected with the other. Using the Akaike information criterion, we show that the per-partnership model fits the data better than the per-sex-act model.
Randomized controlled trials have shown that voluntary medical male circumcision (VMMC) reduces HIV infection by 50% to 60% in sub-Saharan African populations; however, little is known about the ...population-level effect of adult male circumcision (MC) as an HIV prevention method. We assessed the effectiveness of VMMC roll-out on the levels of HIV in the South African township of Orange Farm where the first randomized controlled trial (RCT) to test the effect of VMMC on HIV acquisition was conducted in 2002-2005.
The Bophelo Pele project is a community-based campaign against HIV, which includes the roll-out of free VMMC. A baseline cross-sectional biomedical survey was conducted in 2007-2008 among a random sample of 1,998 men aged 15 to 49 (survey response rate 80.7%). In 2010-2011, we conducted a follow-up random survey among 3,338 men aged 15 to 49 (survey response rate 79.6%) to evaluate the project. Participants were interviewed, blood samples were collected and tested for HIV and recent HIV infection (using the BED HIV incidence assay), and MC status was assessed through a clinical examination. Data were analyzed using multivariate and propensity statistical methods. Owing to the VMMCs performed in the context of the RCT and the Bophelo Pele project, the prevalence rate of adult MC increased from 0.12 (95% CI 0.10-0.14) to 0.53 (95% CI 0.51-0.55). Without these VMMCs, the HIV prevalence rate in 2010-2011 would have been 19% (95% CI 12%-26%) higher (0.147 instead of 0.123). When comparing circumcised and uncircumcised men, no association of MC status with sexual behavior was detected. Among circumcised and uncircumcised men, the proportion consistently using condoms with non-spousal partners in the past 12 months was 44.0% (95% CI 41.7%-46.5%) versus 45.4% (95% CI 42.2%-48.6%) with weighted prevalence rate ratio (wPRR) = 0.94 (95% CI 0.85-1.03). The proportion having two or more non-spousal partners was 50.4% (95% CI 47.9%-52.9%) versus 44.2% (95% CI 41.3%-46.9%) with wPRR = 1.03 (95% CI 0.95-1.10). We found a reduction of BED-estimated HIV incidence rate ranging from 57% (95% CI 29%-76%) to 61% (95% CI 14%-83%) among circumcised men in comparison with uncircumcised men.
Findings suggest that the roll-out of VMMC in Orange Farm is associated with a significant reduction of HIV levels in the community. The main limitation of the study is that it was not randomized and cannot prove a causal association. The roll-out of VMMC among adults in sub-Saharan Africa should be an international priority and needs to be accelerated to effectively combat the spread of HIV. Please see later in the article for the Editors' Summary.
This paper presents two approaches to smoothing time trends in prevalence and estimating the underlying incidence of remissible infections. In the first approach, we use second order segmented ...polynomials to smooth a curve in a bounded domain. In the second, incidence is modeled instead and the prevalence is reconstructed using the recovery rate which is assumed to be known. In both approaches, the number of knots and their positions are estimated, resulting in non-linear regressions. Akaike Information Criterion is used for model selection. The method is illustrated with Syphilis and Gonorrhea prevalence smoothing and incidence trend estimation in Guinea-Bissau and South Africa, respectively.
Introduction
Model‐based estimates of key HIV indicators depend on past epidemic trends that are derived based on assumptions about HIV disease progression and mortality in the absence of ...antiretroviral treatment (ART). Population‐based HIV Impact Assessment (PHIA) household surveys conducted between 2015 and 2018 found substantial numbers of respondents living with untreated HIV infection. CD4 cell counts measured in these individuals provide novel information to estimate HIV disease progression and mortality rates off ART.
Methods
We used Bayesian multi‐parameter evidence synthesis to combine data on (1) cross‐sectional CD4 cell counts among untreated adults living with HIV from 10 PHIA surveys, (2) survival after HIV seroconversion in East African seroconverter cohorts, (3) post‐seroconversion CD4 counts and (4) mortality rates by CD4 count predominantly from European, North American and Australian seroconverter cohorts. We used incremental mixture importance sampling to estimate HIV natural history and ART uptake parameters used in the Spectrum software. We validated modelled trends in CD4 count at ART initiation against ART initiator cohorts in sub‐Saharan Africa.
Results
Median untreated HIV survival decreased with increasing age at seroconversion, from 12.5 years 95% credible interval (CrI): 12.1–12.7 at ages 15–24 to 7.2 years (95% CrI: 7.1–7.7) at ages 45–54. Older age was associated with lower initial CD4 counts, faster CD4 count decline and higher HIV‐related mortality rates. Our estimates suggested a weaker association between ART uptake and HIV‐related mortality rates than previously assumed in Spectrum. Modelled CD4 counts in untreated people living with HIV matched recent household survey data well, though some intercountry variation in frequencies of CD4 counts above 500 cells/mm3 was not explained. Trends in CD4 counts at ART initiation were comparable to data from ART initiator cohorts. An alternate model that stratified progression and mortality rates by sex did not improve model fit appreciably.
Conclusions
Synthesis of multiple data sources results in similar overall survival as previous Spectrum parameter assumptions but implies more rapid progression and longer survival in lower CD4 categories. New natural history parameter values improve consistency of model estimates with recent cross‐sectional CD4 data and trends in CD4 counts at ART initiation.
The COVID-19 pandemic could lead to disruptions to provision of HIV services for people living with HIV and those at risk of acquiring HIV in sub-Saharan Africa, where UNAIDS estimated that more than ...two-thirds of the approximately 38 million people living with HIV resided in 2018. We aimed to predict the potential effects of such disruptions on HIV-related deaths and new infections in sub-Saharan Africa.
In this modelling study, we used five well described models of HIV epidemics (Goals, Optima HIV, HIV Synthesis, an Imperial College London model, and Epidemiological MODeling software EMOD) to estimate the effect of various potential disruptions to HIV prevention, testing, and treatment services on HIV-related deaths and new infections in sub-Saharan Africa lasting 6 months over 1 year from April 1, 2020. We considered scenarios in which disruptions affected 20%, 50%, and 100% of the population.
A 6-month interruption of supply of antiretroviral therapy (ART) drugs across 50% of the population of people living with HIV who are on treatment would be expected to lead to a 1·63 times (median across models; range 1·39–1·87) increase in HIV-related deaths over a 1-year period compared with no disruption. In sub-Saharan Africa, this increase amounts to a median excess of HIV deaths, across all model estimates, of 296 000 (range 229 023–420 000) if such a high level of disruption occurred. Interruption of ART would increase mother-to-child transmission of HIV by approximately 1·6 times. Although an interruption in the supply of ART drugs would have the largest impact of any potential disruptions, effects of poorer clinical care due to overstretched health facilities, interruptions of supply of other drugs such as co-trimoxazole, and suspension of HIV testing would all have a substantial effect on population-level mortality (up to a 1·06 times increase in HIV-related deaths over a 1-year period due to disruptions affecting 50% of the population compared with no disruption). Interruption to condom supplies and peer education would make populations more susceptible to increases in HIV incidence, although physical distancing measures could lead to reductions in risky sexual behaviour (up to 1·19 times increase in new HIV infections over a 1-year period if 50% of people are affected).
During the COVID-19 pandemic, the primary priority for governments, donors, suppliers, and communities should focus on maintaining uninterrupted supply of ART drugs for people with HIV to avoid additional HIV-related deaths. The provision of other HIV prevention measures is also important to prevent any increase in HIV incidence.
Bill & Melinda Gates Foundation.
The objectives of this study were to determine the capacity of BED incidence testing to a) estimate the effect of a HIV prevention intervention and b) provide adequate statistical power, when used ...among young people from sub-Saharan African settings with high HIV incidence rates.
Firstly, after having elaborated plausible scenarios based on empirical data and the characteristics of the BED HIV-1 Capture EIA (BED) assay, we conducted statistical calculations to determine the BED theoretical power and HIV incidence rate ratio (IRR) associated with an intervention when using BED incidence testing. Secondly, we simulated a cross-sectional study conducted in a population among whom an HIV intervention was rolled out. Simulated data were analyzed using a log-linear Poisson model to recalculate the IRR and its confidence interval, and estimate the BED practical power. Calculations were conducted with and without corrections for misclassifications.
Calculations showed that BED incidence testing can yield a BED theoretical power of 75% or more of the power that can be obtained in a classical cohort study conducted over a duration equal to the BED window period. Statistical analyses using simulated populations showed that the effect of a prevention intervention can be estimated with precision using classical statistical analysis of BED incidence testing data, even with an imprecise knowledge of the characteristics of the BED assay. The BED practical power was lower but of the same magnitude as the BED theoretical power.
BED incidence testing can be applied to reasonably small samples to achieve good statistical power when used among young people to estimate IRR.
PDF
