Characterizing HIV epidemiology among female sex workers and their clients in the Middle East and North Africa.

OBJECTIVES: This thesis aims to address the evidence gap in understanding HIV epidemiology among female sex workers (FSWs) in the Middle East and North Africa (MENA) region by 1) conducting the first comprehensive assessment of HIV epidemic status among FSWs and their clients, and of other key sexually transmitted infections (STIs) among FSWs, 2) investigating the utility of herpes simplex virus type 2 (HSV-2) prevalence in predicting HIV epidemic potential in FSWs, and 3) estimating HIV incidence in heterosexual sex work networks (HSWNs) and assessing the impact of interventions on epidemiological measures of relevance to HIV response. METHODS: Methodologies include systematic reviews, meta-analyses and meta-regressions of HIV/STI prevalence data, ecological analysis of global HSV-2/HIV prevalence data among FSWs, and an individual-based mathematical model simulating HIV transmission dynamics in HSWNs. RESULTS: The median proportion of reproductive-age women reporting current/recent sex work was 0.6% (range: 0.2-2.4%), and of men reporting currently/recently buying sex was 5.7% (range: 0.3-13.8%). Risk behaviors varied widely within and across countries. The HIV epidemic was concentrated in Djibouti and South Sudan (prevalence ~20%), of intermediate intensity in North Africa and Somalia (1-5%), and limited in other countries (<1%). There was steady growth in odds of HIV prevalence since 2003 at ~15% per year (95% CI: 9-21%). STI prevalence among FSWs was substantial (relative to general population women), supporting a key role for HSWNs in STI transmission dynamics. Pooled prevalence of current infection was 12.7% (95% CI: 8.5-17.7%) for T. pallidum (syphilis), 14.4% (95% CI: 8.2-22.0%) for C. trachomatis, 5.7% (95% CI: 3.5-8.4%) for N. gonorrhoeae, and 7.1% (95% CI: 4.3-10.5%) for T. vaginalis, while that of lifetime infection was 23.7% (95% CI: 10.2-40.4%) for HSV-2. Syphilis prevalence varied by MENA subregion and has been declining by 7% per year for three decades. Analysis of 231 global paired HSV-2/HIV measures identified a strong positive association among FSWs after adjusting for confounders such as region, temporal trend, and condom use. HIV prevalence was negligible where HSV-2 prevalence was ≤20%, but HIV infection odds doubled with each 25% increase in HSV-2 prevalence indicating a threshold effect and utility of HSV-2 in predicting HIV epidemic potential. The individual-based model was developed, calibrated, tested, and applied to 12 MENA countries with sufficient input data. The estimated number of new infections in 2020 in these countries was 3,471 (range: 1,295-10,308) among FSWs, 6,416 (range: 3,144-14,223) among clients, and 4,717 (range: 3,490-7,288) among client spouses. These infections accounted for 25.1% of total HIV incidence in MENA. Incidence was distributed equally among FSWs, clients, and client spouses. The contribution of incidence in HSWNs to total incidence ranged from 3.3% in Pakistan where injecting drug use is prevalent to 71.8% in South Sudan and 72.7% in Djibouti where sex is the dominant mode of transmission. Scale-up of interventions such as antiretroviral therapy, condom use, and pre-exposure prophylaxis substantially reduced incidence among FSWs, clients, and client spouses either directly or indirectly by reducing onward transmission. CONCLUSIONS: HIV epidemics among FSWs in MENA are emerging, and some are already established. The epidemic has been growing steadily in recent years, but with strong regionalization and heterogeneity. Integrating testing for HSV-2 in HIV surveillance can be useful in predicting HIV epidemic potential particularly in countries where HIV among FSWs is still limited but has potential to grow. Substantial HIV incidence occurs in HSWNs, suggesting the need for rapidly scaling up comprehensive treatment and prevention services at least for FSWs

Characterizing the transitioning epidemiology of herpes simplex virus type 1 in the USA: Model-based predictions

Background: Herpes simplex virus type 1 (HSV-1) is a prevalent lifelong infection that appears to be undergoing an epidemiologic transition in the United States (US). Using an analytical approach, this study aimed to characterize HSV-1 transitioning epidemiology and estimate its epidemiologic indicators, past, present, and future. Methods: An age-structured mathematical model was developed to describe HSV-1 transmission through oral and sexual modes of transmission. The model was fitted to the National Health and Nutrition Examination Surveys, 1976-2016 data series. Results: HSV-1 seroprevalence was projected to decline from 61.5% in 1970 to 54.8% in 2018, 48.5% in 2050, and 42.0% in 2100. In 30% for those aged 0-19 years, but 60. Meanwhile, the number of new infections per year (oral and genital) was persistent at 2,762,000 in 1970, 2,941,000 in 2018, 2,933,000 in 2050, and 2,960,000 in 2100. Of this total, genital acquisitions contributed 252,000 infections in 1970, 410,000 in 2018, 478,000 in 2050, and 440,000 in 2100 - a quarter of which are symptomatic with clinical manifestations. For those aged 15-49 years, nearly 25% of incident infections are genital. Most genital acquisitions (> 85%) were due to oral-to-genital transmission through oral sex, as opposed to genital-to-genital transmission through sexual intercourse. Conclusion: HSV-1 epidemiology is undergoing a remarkable transition in the US, with less exposure in childhood and more in adulthood, and less oral but more genital acquisition. HSV-1 will persist as a widely prevalent infection, with ever-increasing genital disease burden.This publication was made possible by NPRP grant number 9-040-3-008 from the Qatar National Research Fund (a member of Qatar Foundation). The findings achieved herein are solely the responsibility of the authors. The authors are also grateful for pilot funding provided by the Biomedical Research Program and infrastructure support provided by the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine in Qatar

Characterizing HIV epidemiology in stable couples in Cambodia, the Dominican Republic, Haiti, and India.

Using a set of statistical methods and HIV mathematical models applied on nationally representative Demographic and Health Survey data, we characterized HIV serodiscordancy patterns and HIV transmission dynamics in stable couples (SCs) in four countries: Cambodia, the Dominican Republic, Haiti, and India. The majority of SCs affected by HIV were serodiscordant, and about a third of HIV-infected persons had uninfected partners. Overall, nearly two-thirds of HIV infections occurred in individuals in SCs, but only about half of these infections were due to transmissions within serodiscordant couples. The majority of HIV incidence in the population occurred through extra-partner encounters in SCs. There is similarity in HIV epidemiology in SCs between these countries and countries in sub-Saharan Africa, despite the difference in scale of epidemics. It appears that HIV epidemiology in SCs may share similar patterns globally, possibly because it is a natural 'spillover' effect of HIV dynamics in high-risk populations

Characterizing the transitioning epidemiology of herpes simplex virus type 1 in the USA: model-based predictions.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) is a prevalent lifelong infection that appears to be undergoing an epidemiologic transition in the United States (US). Using an analytical approach, this study aimed to characterize HSV-1 transitioning epidemiology and estimate its epidemiologic indicators, past, present, and future. METHODS: An age-structured mathematical model was developed to describe HSV-1 transmission through oral and sexual modes of transmission. The model was fitted to the National Health and Nutrition Examination Surveys, 1976-2016 data series. RESULTS: HSV-1 seroprevalence was projected to decline from 61.5% in 1970 to 54.8% in 2018, 48.5% in 2050, and 42.0% in 2100. In  30% for those aged 0-19 years, but  60. Meanwhile, the number of new infections per year (oral and genital) was persistent at 2,762,000 in 1970, 2,941,000 in 2018, 2,933,000 in 2050, and 2,960,000 in 2100. Of this total, genital acquisitions contributed 252,000 infections in 1970, 410,000 in 2018, 478,000 in 2050, and 440,000 in 2100-a quarter of which are symptomatic with clinical manifestations. For those aged 15-49 years, nearly 25% of incident infections are genital. Most genital acquisitions (> 85%) were due to oral-to-genital transmission through oral sex, as opposed to genital-to-genital transmission through sexual intercourse. CONCLUSION: HSV-1 epidemiology is undergoing a remarkable transition in the US, with less exposure in childhood and more in adulthood, and less oral but more genital acquisition. HSV-1 will persist as a widely prevalent infection, with ever-increasing genital disease burden

Epidemiological Impact of Novel Preventive and Therapeutic HSV-2 Vaccination in the United States: Mathematical Modeling Analyses.

This study aims to inform herpes simplex virus type 2 (HSV-2) vaccine development, licensure, and implementation by delineating the population-level impact of vaccination. Mathematical models were constructed to describe the transmission dynamics in presence of prophylactic or therapeutic vaccines assuming 50% efficacy, with application to the United States. Catch-up prophylactic vaccination will reduce, by 2050, annual number of new infections by 58%, incidence rate by 60%, seroprevalence by 21%, and avert yearly as much as 350,000 infections. Number of vaccinations needed to avert one infection was only 50 by 2050, 34 by prioritizing those aged 15-19 years, 4 by prioritizing the highest sexual risk group, 43 by prioritizing women, and 47 by prioritizing men. Therapeutic vaccination of infected adults with symptomatic disease will reduce, by 2050, annual number of new infections by 12%, incidence rate by 13%, seroprevalence by 4%, and avert yearly as much as 76,000 infections. Number of vaccinations needed to avert one infection was eight by 2050, two by prioritizing those aged 15-19 years, three by prioritizing the highest sexual risk group, seven by prioritizing men, and ten by prioritizing women. HSV-2 vaccination offers an impactful and cost-effective intervention to prevent genital herpes medical and psychosexual disease burden

Hepatitis C virus infection spontaneous clearance: Has it been underestimated?

OBJECTIVES: Hepatitis C virus (HCV) clearance rate (fclearance) is defined as the proportion of infected persons who will spontaneously clear their infection after acute infection. We aimed to estimate fclearance using a novel approach that avoids limitations in existing estimates, and to clarify the link between fclearance and HCV viremic rate-the latter being the proportion of RNA positivity among those antibody positive. METHODS: A mathematical model was developed to describe HCV transmission. fclearance was estimated by fitting the model to probability-based and nationally representative population-based data for Egypt (Egypt 2008 and Egypt 2015) and USA (NHANES A and NHANES B). Uncertainty and sensitivity analyses were conducted. RESULTS: fclearance was estimated at 39.9% (95% uncertainty interval (UI): 34.3%-46.4%) and 33.5% (95% UI: 29.2%-38.3%) for Egypt 2008 and Egypt 2015 data, respectively; and at 29.6% (23.0%-37.1%) and 39.9% (31.2%-51.0%) for NHANES A and NHANES B data, respectively. fclearance was found related to HCV viremic rate through (approximately) the formula fclearance=1.16 (1-HCV viremic rate). HCV viremic rate was higher with higher risk of HCV exposure. Robustness of results was demonstrated in uncertainty and sensitivity analyses. CONCLUSION: One-third of HCV-infected persons clear their infection spontaneously, higher than earlier estimates-the immune-system capacity to clear HCV infection may have been underestimated

Characterizing the historical role of parenteral antischistosomal therapy in hepatitis C virus transmission in Egypt.

BACKGROUND: Egypt is the nation most affected by hepatitis C virus (HCV) infection, following an epidemic of historic proportions. We aimed to characterize the epidemic's historical evolution and to delineate the role of parenteral antischistosomal therapy (PAT) campaigns in transmission. METHODS: A mathematical model was constructed and analysed in order to understand HCV-transmission dynamics. The model was fitted to Egypt's Demographic and Health Survey data and to a systematic database of HCV-prevalence data. RESULTS: The incidence rate peaked in 1966 at 15.7 infections per 1000 person-years-a period of time that coincides with the PAT campaigns-and rapidly declined thereafter, beginning the mid-1990s. The annual number of new infections peaked in 1993 at 581 200 (with rapid demographic growth), leading to a high-incidence-cohort effect, and declined to 67 800 by 2018. The number of individuals ever infected (1950-2018) was 16.4 million, with HCV prevalence peaking in 1979. The number of individuals ever exposed to PAT was 8.3 million; however, of these individuals, 7.3 million were alive in 1980 and only 3.5 million alive in 2018. The number of individuals ever infected due to PAT exposure was 963 900, with 850 200 individuals alive in 1980 and only 389 800 alive in 2018. The proportion of PAT-attributed prevalent infections peaked at 19.9% in 1972, declining to 5.5% by 2018. CONCLUSIONS: PAT campaigns played an important role in HCV transmission, yet explain only 6% of infections-they appear to be a manifestation, rather than a cause, of the epidemic. A possible driver of the epidemic could be the mass expansion of inadequate-quality healthcare during PAT campaigns and subsequent decades. Despite a historic toll, the epidemic has been rapidly diminishing since the mid-1990s

Treatment as prevention for hepatitis C virus in the Middle East and North Africa: a modeling study

Background: Direct-acting antivirals opened an opportunity for eliminating hepatitis C virus (HCV) infection in the Middle East and North Africa (MENA), the region most affected by HCV infection. Impact of HCV treatment as prevention (HCV-TasP) was investigated in 19 MENA countries. Methods: An age-structured mathematical model was used to assess program impact using epidemiologic and programming measures. The model was fitted to a database of systematically gathered HCV antibody prevalence data. Two main scenarios were investigated for the treatment roll-out to achieve (i) 80% reduction in HCV incidence by 2030, and (ii) incidence rate < 1 per 100,000 person-years by 2030. Results: In the target-80%-incidence-reduction scenario, number of treatments administrated by 2030 ranged from 2,610 in Lebanon to 180,416 in Sudan with a median of 53,079, and treatment coverage ranged between 40.2 and 78.4% with a median of 60.4%. By 2030, prevalence of chronic infection ranged between 0.0 and 0.3% with a median of 0.1%, and incidence rate, per 100,000 person-years, ranged between 0.9 and 16.3 with a median of 3.2. Program-attributed reduction in incidence rate ranged between 47.8 and 81.9% with a median of 68.5%, and number of averted infections ranged between 401 and 68,499 with a median of 8,703. Number of treatments needed to prevent one new infection ranged from 1.7 in Oman to 25.9 in Tunisia with a median of 6.5. In the target incidence rate < 1 per 100,000 person-years scenario, number of treatments administrated by 2030 ranged from 3,470 in Lebanon to 211,912 in Sudan with a median of 54,479, and treatment coverage ranged between 55.5 and 95.9% with a median of 87.5%. By 2030, prevalence of chronic infection was less than 0.1%, and incidence rate, per 100,000 person-years, reached less than 1. Program-attributed reduction in incidence rate ranged between 61.0 and 97.5% with a median of 90.7%, and number of averted infections ranged between 559 and 104,315 with a median of 12,158. Number of treatments needed to prevent one new infection ranged from 1.3 in Oman to 25.9 in Tunisia with a median of 5.5. Conclusion: HCV-TasP is an effective and indispensable prevention intervention to control MENA's HCV epidemic and to achieve elimination by 2030.This publication was made possible by NPRP grant number 12S-0216-190094 from the Qatar National Research Fund (a member of Qatar Foundation; https://www.qnrf.org ). HHA acknowledges the support of Qatar University QUCG-CAS-23/24-114. The statements made herein are solely the responsibility of the authors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the views, decisions, or policies of World Health Organization. The authors are also grateful for infrastructure support provided by the Biostatistics, Epidemiology, and Biomathematics Research Core at Weill Cornell Medicine-Qatar.Scopu

Epidemiological Differences in the Impact of COVID-19 Vaccination in the United States and China.

This study forecasts Coronavirus Disease 2019 (COVID-19) vaccination impact in two countries at different epidemic phases, the United States (US) and China. We assessed the impact of both a vaccine that prevents infection (VES of 95%) and a vaccine that prevents only disease (VEP of 95%) through mathematical modeling. For VES of 95% and gradual easing of restrictions, vaccination in the US reduced the peak incidence of infection, disease, and death by >55% and cumulative incidence by >32% and in China by >77% and >65%, respectively. Nearly three vaccinations were needed to avert one infection in the US, but only one was needed in China. For VEP of 95%, vaccination benefits were half those for VES of 95%. In both countries, impact of vaccination was substantially enhanced with rapid scale-up, vaccine coverage >50%, and slower or no easing of restrictions, particularly in the US. COVID-19 vaccination can flatten, delay, and/or prevent future epidemic waves. However, vaccine impact is destined to be heterogeneous across countries because of an underlying "epidemiologic inequity" that reduces benefits for countries already at high incidence, such as the US. Despite 95% efficacy, actual vaccine impact could be meager in such countries if vaccine scale-up is slow, acceptance is poor, or restrictions are eased prematurely

Modeling the population-level impact of treatment on COVID-19 disease and SARS-CoV-2 transmission

Different COVID-19 treatment candidates are under development, and some are becoming available including two promising drugs from Merck and Pfizer. This study provides conceptual frameworks for the effects of three types of treatments, both therapeutic and prophylactic, and to investigate their population-level impact, to inform drug development, licensure, decision-making, and implementation. Different drug efficacies were assessed using an age-structured mathematical model describing SARS-CoV-2 transmission and disease progression, with application to the United States as an illustrative example. Severe and critical infection treatment reduces progression to COVID-19 severe and critical disease and death with small number of treatments needed to avert one disease or death. Post-exposure prophylaxis treatment had a large impact on flattening the epidemic curve, with large reductions in infection, disease, and death, but the impact was strongly age dependent. Pre-exposure prophylaxis treatment had the best impact and effectiveness, with immense reductions in infection, disease, and death, driven by the robust control of infection transmission. Effectiveness of both pre-exposure and post-exposure prophylaxis treatments was disproportionally larger when a larger segment of the population was targeted than a specific age group. Additional downstream potential effects of treatment, beyond the primary outcome, enhance the population-level impact of both treatments. COVID-19 treatments are an important modality in controlling SARS-CoV-2 disease burden. Different types of treatment act synergistically for a larger impact, for these treatments and vaccination.The authors are grateful for support provided by the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar. This publication was made possible by extension of models developed through the National Priorities Research Program (NPRP), Qatar, grant number 9–040-3–008 (Principal investigator: LJA) and NPRP grant number 12S-0216–190094 (Principal investigator: LJA) from the Qatar National Research Fund (a member of Qatar Foundation; https://www.qnrf.org). The statements made herein are solely the responsibility of the authors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript