As antiretroviral treatment (ART) coverage for people living with HIV (PLHIV) increases, HIV programmes require up-to-date information about evolving HIV risk behaviour and transmission risk, including those with low-level viremia (LLV; >50 to ≤1000 copies/mL), to guide prevention priorities. We aimed to assess differences in sexual risk behaviours, distribution of viral load (VL) and proportion of transmission across PLHIV subgroups. We analysed data from Population-based HIV Impact Assessment surveys in 14 sub-Saharan African countries during 2015-2019. We estimated adjusted prevalence ratios (aPR) of self-reported HIV high-risk behaviour (multiple partners and condomless sex) across cascade stages via generalised estimation equations. We modelled the proportions of transmission from each subgroup using relative self-reported sexual risk, a Hill function for transmission rate by VL, and proportions within cascade stages from surveys and UNAIDS country estimates for 2010-2020. Compared to PLHIV with undetectable VL (≤50 copies/mL), undiagnosed PLHIV (aPR women: 1.28 [95% CI: 1.08-1.52]; men: 1.61 [1.33-1.95]) and men diagnosed but untreated (2.06 [1.52-2.78]) were more likely to self-report high-risk sex. High-risk behaviour was not significantly associated with LLV. Mean VL was similar among undiagnosed, diagnosed but untreated, and on ART but non-suppressed sub-groups. Across surveys, undiagnosed and diagnosed but untreated contributed most to transmission (40-91% and 1-41%, respectively), with less than 1% from those with LLV. Between 2010 and 2020, the proportion of transmission from individuals on ART but non-suppressed increased. In settings with high ART coverage, effective HIV testing, ART linkage, and retention remain priorities to reduce HIV transmission. Persons with LLV are an increasing share of PLHIV but their contribution to HIV transmission was small. Improving suppression among PLHIV on ART with VL ≥1000 copies/mL will become increasingly important.

BACKGROUND: Voluntary medical male circumcision (VMMC) reduces the risk of male HIV acquisition by 60%. Programmes to provide VMMCs for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Traditional circumcision is also a long-standing male coming-of-age ritual, but practices vary considerably across populations. Accurate estimates of circumcision coverage by age, type, and time at subnational levels are required for planning and delivering VMMCs to meet targets and evaluating their impacts on HIV incidence. METHODS: We developed a Bayesian competing risks time-to-event model to produce region-age-time-type specific probabilities and coverage of male circumcision with probabilistic uncertainty. The model jointly synthesises data from household surveys and health system data on the number of VMMCs conducted. We demonstrated the model using data from five household surveys and VMMC programme data to produce estimates of circumcision coverage for 52 districts in South Africa between 2008 and 2019. RESULTS: Nationally, in 2008, 24.1% (95% CI: 23.4-24.8%) of men aged 15-49 were traditionally circumcised and 19.4% (18.9-20.0%) were medically circumcised. Between 2010 and 2019, 4.25 million VMMCs were conducted. Circumcision coverage among men aged 15-49 increased to 64.0% (63.2-64.9%) and medical circumcision coverage to 42% (41.3-43.0%). Circumcision coverage varied widely across districts, ranging from 13.4 to 86.3%. The average age of traditional circumcision ranged between 13 and 19 years, depending on local cultural practices. CONCLUSION: South Africa has made substantial, but heterogeneous, progress towards increasing medical circumcision coverage. Detailed subnational information on coverage and practices can guide programmes to identify unmet need to achieve national and international targets. | Voluntary medical male circumcision reduces the risk of male HIV acquisition. Programmes to provide circumcisions for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Estimates of circumcision coverage are needed for planning and delivering circumcisions to meet targets and evaluate their impacts on HIV incidence. We developed a model to integrate date from both household surveys and health systems on the number of circumcisions conducted, and applied it to understand how the practices and coverage of circumcision are changing in South Africa. National circumcision coverage increased considerably between 2008 and 2019, however, there remains a substantial subnational variation across districts and age groups. Further progress is needed to reach national and international targets. | eng

BACKGROUND: Quantifying subnational need for antiretroviral therapy (ART) for HIV is challenging because people living with HIV (PLHIV) access health facilities in areas that may differ from their residence. We defined and demonstrated new indicators for PLHIV treatment needed to guide health system target setting and resource allocation. SETTING: Botswana. METHODS: We extended Naomi, a Bayesian small-area model for estimating district-level HIV indicators from national household survey and HIV service delivery data. We used model outputs for ART seeking probabilities in neighboring districts to define the "PLHIV (attending)" indicator representing the estimated number of PLHIV who would seek treatment at health facilities in a district, and "Untreated PLHIV attending" representing gaps in ART service provision. Botswana 2021 district HIV estimates were used to demonstrate new outputs and assess the sensitivity to uncertainty in district population sizes. RESULTS: Across districts of Botswana, estimated adult ART coverage in December 2021 ranged 90%-96%. In the capital city Gaborone, there were 50,400 resident PLHIV and 64,200 receiving ART, of whom 24% (95% CI: 20 to 32) were estimated to reside in neighboring districts. Applying ART attendance probabilities gave a "PLHIV attending" denominator of 68,300 and unmet treatment need of 4100 adults (95% CI: 3000 to 5500) for Gaborone health facilities. The facility-based "PLHIV attending" denominator was less-sensitive to fluctuations in district population size assumptions. CONCLUSIONS: New indicators provided more consistent targets for HIV service provision, but are limited by ART data quality. This challenge will increase as treatment coverage reaches high levels and treatment gaps are smaller.

BACKGROUND: Routine health system data are central to monitoring HIV trends. In Mozambique, the reported number of women receiving antenatal care (ANC) and antiretroviral therapy for prevention of mother-to-child transmission (PMTCT) has exceeded the Spectrum-estimated number of pregnant women since 2017. In some provinces, reported HIV prevalence in pregnant women has declined faster than epidemiologically plausible. We hypothesized that these issues are linked and caused by programmatic overenumeration of HIV-negative pregnant women at ANC. METHODS: We triangulated program-reported ANC client numbers with survey-based fertility estimates and facility birth data adjusted for the proportion of facility births. We used survey-reported ANC attendance to produce adjusted time series of HIV prevalence in pregnant women, adjusted for hypothesized program double counting. We calibrated the Spectrum HIV estimation models to adjusted HIV prevalence data to produce adjusted adult and pediatric HIV estimates. RESULTS: ANC client numbers were not consistent with facility birth data or modeled population estimates indicating ANC data quality issues in all provinces. Adjusted provincial ANC HIV prevalence in 2021 was median 45% [interquartile range 35%-52% or 2.3 percentage points (interquartile range 2.5-3.5)] higher than reported HIV prevalence. In 2021, calibrating to adjusted antenatal HIV prevalence lowered PMTCT coverage to less than 100% in most provinces and increased the modeled number of new child infections by 35%. The adjusted results better reconciled adult and pediatric antiretroviral treatment coverage and antenatal HIV prevalence with regional fertility estimates. CONCLUSIONS: Adjusting HIV prevalence in pregnant women using nationally representative household survey data on ANC attendance produced estimates more consistent with surveillance data. The number of children living with HIV in Mozambique has been substantially underestimated because of biased routine ANC prevalence. Renewed focus on HIV surveillance among pregnant women would improve PMTCT coverage and pediatric HIV estimates.

BACKGROUND: Key population HIV programmes in sub-Saharan Africa require epidemiological information to ensure equitable and universal access to effective services. We aimed to consolidate and harmonise survey data among female sex workers, men who have sex with men, people who inject drugs, and transgender people to estimate key population size, HIV prevalence, and antiretroviral therapy (ART) coverage for countries in mainland sub-Saharan Africa. METHODS: Key population size estimates, HIV prevalence, and ART coverage data from 39 sub-Saharan Africa countries between 2010 and 2023 were collated from existing databases and verified against source documents. We used Bayesian mixed-effects spatial regression to model urban key population size estimates as a proportion of the gender-matched, year-matched, and area-matched population aged 15-49 years. We modelled subnational key population HIV prevalence and ART coverage with age-matched, gender-matched, year-matched, and province-matched total population estimates as predictors. FINDINGS: We extracted 2065 key population size data points, 1183 HIV prevalence data points, and 259 ART coverage data points. Across national urban populations, a median of 1·65% (IQR 1·35-1·91) of adult cisgender women were female sex workers, 0·89% (0·77-0·95) were men who have sex with men, 0·32% (0·31-0·34) were men who injected drugs, and 0·10% (0·06-0·12) were women who were transgender. HIV prevalence among key populations was, on average, four to six times higher than matched total population prevalence, and ART coverage was correlated with, but lower than, the total population ART coverage with wide heterogeneity in relative ART coverage across studies. Across sub-Saharan Africa, key populations were estimated as comprising 1·2% (95% credible interval 0·9-1·6) of the total population aged 15-49 years but 6·1% (4·5-8·2) of people living with HIV. INTERPRETATION: Key populations in sub-Saharan Africa experience higher HIV prevalence and lower ART coverage, underscoring the need for focused prevention and treatment services. In 2024, limited data availability and heterogeneity constrain precise estimates for programming and monitoring trends. Strengthening key population surveys and routine data within national HIV strategic information systems would support more precise estimates. FUNDING: UNAIDS, Bill & Melinda Gates Foundation, and US National Institutes of Health.

2020 saw the continuation of the second largest outbreak of Ebola virus disease (EVD) in history. Determining epidemiological links between cases is a key part of outbreak control. However, due to the large quantity of data and subsequent data entry errors, inconsistencies in potential epidemiological links are difficult to identify. We present chainchecker, an online and offline shiny application which visualises, curates and verifies transmission chain data. The application includes the calculation of exposure windows for individual cases of EVD based on user defined incubation periods and user specified symptom profiles. It has an upload function for viral hemorrhagic fever data and utility for additional entries. This data may then be visualised as a transmission tree with inconsistent links highlighted. Finally, there is utility for cluster analysis and the ability to highlight nosocomial transmission. chainchecker is a R shiny application which has an offline version for use with VHF (viral hemorrhagic fever) databases or linelists. The software is available at https://shiny.dide.imperial.ac.uk/chainchecker which is a web-based application that links to the desktop application available for download and the github repository, https://github.com/imperialebola2018/chainchecker.

We report key epidemiologic parameter estimates for coronavirus disease identified in peer-reviewed publications, preprint articles, and online reports. Range estimates for incubation period were 1.8-6.9 days, serial interval 4.0-7.5 days, and doubling time 2.3-7.4 days. The effective reproductive number varied widely, with reductions attributable to interventions. Case burden and infection fatality ratios increased with patient age. Implementation of combined interventions could reduce cases and delay epidemic peak up to 1 month. These parameters for transmission, disease severity, and intervention effectiveness are critical for guiding policy decisions. Estimates will likely change as new information becomes available.

Health planners from global to local levels must anticipate year-to-year and week-to-week variation in seasonal influenza activity when planning for and responding to epidemics to mitigate their impact. To help with this, countries routinely collect incidence of mild and severe respiratory illness and virologic data on circulating subtypes and use these data for situational awareness, burden of disease estimates and severity assessments. Advanced analytics and modelling are increasingly used to aid planning and response activities by describing key features of influenza activity for a given location and generating forecasts that can be translated to useful actions such as enhanced risk communications, and informing clinical supply chains. Here, we describe the formation of the Influenza Incidence Analytics Group (IIAG), a coordinated global effort to apply advanced analytics and modelling to public influenza data, both epidemiological and virologic, in real-time and thus provide additional insights to countries who provide routine surveillance data to WHO. Our objectives are to systematically increase the value of data to health planners by applying advanced analytics and forecasting and for results to be immediately reproducible and deployable using an open repository of data and code. We expect the resources we develop and the associated community to provide an attractive option for the open analysis of key epidemiological data during seasonal epidemics and the early stages of an influenza pandemic.

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014-2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.

Although the severe acute respiratory illness (SARI) case definition is increasingly used for inpatient influenza surveillance, pneumonia is a more familiar term to clinicians and policymakers. We evaluated WHO case definitions for severe acute respiratory illness (SARI) and pneumonia (Integrated Management of Childhood Illnesses (IMCI) for children aged <5 years and Integrated Management of Adolescent and Adult Illnesses (IMAI) for patients aged ≥13 years) for detecting laboratory-confirmed influenza among hospitalized ARI patients. Sensitivities were 84% for SARI and 69% for IMCI pneumonia in children aged <5 years and 60% for SARI and 57% for IMAI pneumonia in patients aged ≥13 years. Clinical pneumonia case definitions may be a useful complement to SARI for inpatient influenza surveillance.

BACKGROUND: The cost-effectiveness of screening for type 2 diabetes mellitus (DM2) in developing countries remains unknown. The Brazilian government conducted a nationwide population screening program for type 2 diabetes mellitus (BNDSP) in which 22 million capillary glucose tests were performed in individuals aged 40 years and older. The objective of this study was to evaluate the life-time cost-effectiveness of a national population-based screening program for DM2 conducted in Brazil. METHODS: We used a Markov-based cost-effectiveness model to simulate the long-term costs and benefits of screening for DM2, compared to no screening program. The analysis was conducted from a public health care system perspective. Sensitivity analyses were conducted to examine the robustness of results to key model parameters. RESULTS: Brazilian National diabetes screening program will yield a large health benefit and higher costs. Compared with no screening, screen detection of undiagnosed diabetes resulted in US$ 31,147 per QALY gained. Results from sensitivity analyses found that screening targeted at hypertensive individuals would cost US$ 22,695/QALY. When benefits from early glycemic control on cardiovascular outcomes were considered, the cost per QALY gained would reduce significantly. CONCLUSIONS: In the base case analysis, not considering the intangible benefit of transferring diabetes management to primary care nor the benefit of using statin to treat eligible diabetic patients, CE ratios were not cost-effective considering thresholds proposed by the World Health Organization. However, significant uncertainty was demonstrated in sensitivity analysis. Our results indicate that policy-makers should carefully balance the benefit and cost of the program while considering using a population-based approach to screen for diabetes.

Chronic kidney disease is now recognized to be a worldwide problem associated with significant morbidity and mortality and there is a steep increase in the number of patients reaching end-stage renal disease. In many parts of the world, the disease affects younger people without diabetes or hypertension. The costs to family and society can be enormous. Early recognition of CKD may help prevent disease progression and the subsequent decline in health and longevity. Surveillance programs for early CKD detection are beginning to be implemented in a few countries. In this article, we will focus on the challenges and successes of these programs with the hope that their eventual and widespread use will reduce the complications, deaths, disabilities, and economic burdens associated with CKD worldwide.

More than half of persons living with HIV infection in the United States (U.S.) will be ≥50 years of age by 2020, including postmenopausal women. We conducted a systematic literature review about the effects of (1) HIV infection on age at menopause and (2) menopause on antiretroviral therapy (ART) response, in order to inform optimal treatment strategies for menopausal women living with HIV infection. We used the Ovid Medline database from 1980 to 2012. We included studies that focused on HIV-infected persons, included postmenopausal women, and reported outcome data for either age at menopause or response to ART across menopause. We identified six original research articles for age at menopause and five for response to ART across menopause. Our review revealed that current data were conflicting and inconclusive; more rigorous studies are needed. Disentangling the effects of menopause requires well-designed studies with adequate numbers of HIV-infected and HIV-uninfected women, especially disproportionately affected women of color. Future studies should follow women from premenopause through menopause, use both surveys and laboratory measurements for menopause diagnoses, and control for confounders related to normal aging processes, in order to inform optimal clinical management for menopausal women living with HIV.

BACKGROUND: A cost-effectiveness model that accurately represents disease progression, outcomes, and associated costs is necessary to evaluate the cost-effectiveness of interventions for chronic kidney disease (CKD). STUDY DESIGN: We developed a microsimulation model of the incidence, progression, and treatment of CKD. The model was validated by comparing its predictions with survey and epidemiologic data sources. SETTING & POPULATION: US patients. MODEL, PERSPECTIVE, & TIMEFRAME: The model follows up disease progression in a cohort of simulated patients aged 30 until age 90 years or death. The model consists of 7 mutually exclusive states representing no CKD, 5 stages of CKD, and death. Progression through the stages is governed by a person's glomerular filtration rate and albuminuria status. Diabetes, hypertension, and other risk factors influence CKD and the development of CKD complications in the model. Costs are evaluated from the health care system perspective. INTERVENTION: Usual care, including incidental screening for persons with diabetes or hypertension. OUTCOMES: Progression to CKD stages, complications, and mortality. RESULTS: The model provides reasonably accurate estimates of CKD prevalence by stage. The model predicts that 47.1% of 30-year-olds will develop CKD during their lifetime, with 1.7%, 6.9%, 27.3%, 6.9%, and 4.4% ending at stages 1-5, respectively. Approximately 11% of persons who reach stage 3 will eventually progress to stage 5. The model also predicts that 3.7% of persons will develop end-stage renal disease compared with an estimate of 3.0% based on current end-stage renal disease lifetime incidence. LIMITATIONS: The model synthesizes data from multiple sources rather than a single source and relies on explicit assumptions about progression. The model does not include acute kidney failure. CONCLUSION: The model is well validated and can be used to evaluate the cost-effectiveness of CKD interventions. The model also can be updated as better data for CKD progression become available.

BACKGROUND: Microalbuminuria screening may detect chronic kidney disease in its early stages, allowing for treatment that delays or prevents disease progression. The cost-effectiveness of microalbuminuria screening has not been determined. STUDY DESIGN: A cost-effectiveness model simulating disease progression and costs. SETTING & POPULATION: US patients. MODEL, PERSPECTIVE, AND TIMEFRAME: The microsimulation model follows up disease progression and costs in a cohort of simulated patients from age 50 to 90 years or death. Costs are evaluated from the health care system perspective. INTERVENTION: Microalbuminuria screening at 1-, 2-, 5-, or 10-year intervals followed by treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. We considered universal screening, as well as screening targeted at persons with diabetes, persons with hypertension but no diabetes, and persons with neither diabetes nor hypertension. OUTCOMES: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS: For the full model population, universal screening increases costs and increases QALYs. Universal annual screening starting at age 50 years has a cost-effectiveness ratio of $73,000/QALY relative to no screening and $145,000/QALY relative to usual care. Cost-effectiveness ratios improved with longer screening intervals. Relative to no screening, targeted annual screening has cost-effectiveness ratios of $21,000/QALY, $55,000/QALY, and $155,000/QALY for persons with diabetes, those with hypertension, and those with neither current diabetes nor current hypertension, respectively. LIMITATIONS: Results necessarily are based on a microsimulation model because of the long time horizon appropriate for chronic kidney disease. The model includes only health care costs. CONCLUSIONS: Microalbuminuria screening is cost-effective for patients with diabetes or hypertension, but is not cost-effective for patients with neither diabetes nor hypertension unless screening is conducted at longer intervals or as part of existing physician visits.