Assessing the impact of COVID-19 on HIV care cascade for people living with HIV in Ethiopia: a retrospective longitudinal study.

OBJECTIVE: The study aimed to investigate the impact of COVID-19 on the cascade of HIV care for people living with HIV (PLHIV) in Ethiopia. DESIGN: A retrospective longitudinal study. SETTING: The study was conducted in North Showa Zone, Ethiopia, from pre-COVID-19 (January 2018-December 2019) and during COVID-19 (January 2020-December 2021). PARTICIPANTS: We identified 61901 records from 3925 PLHIV, of which 23 848 were recorded during the pandemic. MAIN OUTCOME MEASURE: We investigated indicators from four stages of the HIV care cascade, including HIV screening and diagnosis, HIV care, HIV treatment and HIV disease progression, according to a WHO framework. The indicator changes were assessed with incidence rate ratios (IRRs). RESULTS: For HIV screening and diagnosis, the monthly number of HIV tests experienced a 46% decline from 2520 to 1361 since the pandemic (IRR 0.553; 95% CI 0.546 to 0.561). For HIV care, the monthly number of consultations was reduced by 49.6% (from 1582 to 798) since the pandemic (IRR 0.591; 95% CI 0.581 to 0.601). Similarly, the monthly number of viral load tests was reduced by 42.8% (IRR 0.614; 95% CI 0.581 to 0.650). For HIV treatment, the number of antiretroviral therapy (ART) initiations was reduced by 27.8% and the number of ART adherence by 52.5% since the pandemic. For HIV disease progression, the monthly number of PLHIV achieving viral suppression was reduced by 61.6%, while HIV-related deaths doubled during the pandemic. CONCLUSION: The study highlights pandemic-induced disruptions in the cascade of care for PLHIV. Targeted interventions are necessary to protect PLHIV in public health emergencies.

Hepatitis B virus infection and vaccination among people who use drugs in Xi'an, China.

BACKGROUND: While hepatitis B virus (HBV) infection in children has declined dramatically in China due to the vaccination strategy for newborns, HBV infection in high-risk adults is receiving an increasing attention. The number of people who use drugs (PWUD) in China is huge, but their status of HBV infection and vaccination is less reported, especially from large samples. The related knowledge can help decision makers develop the further strategy of HBV prevention and control. METHODS: A seroepidemiological survey was conducted in all four compulsory isolated detoxification centers (CIDCs) and all eight methadone maintenance treatment (MMT) clinics located in Xi'an, China. All PWUD who were undergoing detoxification or treatment in these settings were included. A questionnaire was designed to obtain the information of HBV vaccination history of participants, and sociodemographic and behavioral data of participants were obtained from the registration records of their respective CIDCs or MMT clinics. RESULTS: A total of 4705 PWUD participated in the survey. Positive rates of HBsAg (current infection) and HBsAg or anti-HBc (current/past infection) were 5.50% and 58.02%, notably higher than those reported for the general adult population in the same province during the same period. As age increased, the anti-HBc positive rate increased with statistically significant trend. The all-negative for HBsAg, anti-HBc, and anti-HBs accounted for 28.82%. Only 18.49% were identified by the questionnaire as having received HBV vaccine. The logistic regression found that compared with identified vaccinated PWUD, those unsure if having been vaccinated and those identified non-vaccinated had a significantly higher HBV current/past infection rate, with an increasing trend. CONCLUSION: PWUD are a high-risk adult group of HBV infection in China. Of them, more than half have not received HBV vaccine, and a significant portion are susceptible to HBV. Catch-up vaccination is need for this population to prevent and control HBV transmission.

Blueprint to hepatitis B elimination in China: A modelling analysis of clinical strategies.

Background & Aims: Globally, one-third of individuals infected with HBV live in China. Eliminating HBV in China would therefore be paramount in achieving the World Health Organization's (WHO's) targets of viral hepatitis elimination as a worldwide public health threat. Methods: We constructed a dynamic HBV transmission model in China, structured by age and sex. We calibrated the model by HBsAg prevalence, acute HBV incidence, and nationally reported HBV-related cancer mortality. We investigated seven intervention scenarios (A-G) based on assumptions in diagnostic, linkage-to-care, and treatment coverages in achieving the WHO's HBV elimination goals. Results: With the status quo, HBsAg prevalence among children 1-4 years would reduce to 0.09% (95% CI 0.09-0.10%) by 2025; acute HBV incidence would drop to <2/100,000 person-years by 2024, achieving the elimination target of 90% incidence reduction. Nonetheless, China would not achieve a 65% reduction target in HBV-related mortality until 2059 with 9.98 (95% CI 9.27-10.70) million HBV-related deaths occurred by 2100. If China achieves 90% diagnostic and 80% treatment coverages (scenario E), HBV elimination would be achieved 8 years earlier, potentially saving 1.98 (95% CI 1.83-2.12) million lives. With more effective therapies for HBV control in preventing cirrhosis and hepatocellular carcinoma, elimination targets could be achieved in 2048 (scenario F) and 2038 (scenario G), additionally saving 3.59 (95% CI 3.37-3.82) and 5.19 (95% CI 4.83-5.55) million lives, respectively. Conclusions: Eliminating HBV will require interventional strategies to improve diagnostic, linkage-to-care, and treatment coverages. Developing novel therapies will be crucial in further reducing HBV-related mortality and removing HBV as a public health threat. Impact and Implications: This study explores the key developments and optimal intervention strategies needed to achieve WHO hepatitis B elimination targets by 2030 in China. It highlights that China can realise the HBV elimination targets in the incidence by 2025, and by upscaling diagnostic, linkage-to-care, and treatment coverages, up to 2 million lives could potentially be saved from HBV-related deaths.

Shared-care models are highly effective and cost-effective for managing chronic hepatitis B in China: reinterpreting the primary care and specialty divide.

Background: We evaluate the impact and cost-effectiveness of shared primary-specialty chronic hepatitis B (CHB) care models in China. Methods: We constructed a decision-tree Markov model to simulate hepatitis B virus (HBV) disease progression in a cohort of 100,000 CHB individuals aged ≥18 years over their lifetime (aged 80). We evaluated the population impacts and cost-effectiveness in three scenarios: (1) status quo; (2) shared-care model with HBV testing and routine CHB follow-ups in primary care and antiviral treatment initiation in specialty care; and (3) shared-care model with HBV testing, treatment initiation and routine CHB follow-up in primary care and treatment for predetermined conditions in specialty care. We evaluated from a healthcare provider's perspective with 3% discounting rate and a willingness-to-pay (WTP) threshold of 1-time China's GDP. Findings: Compared with status quo, scenario 2 would result in an incremental cost of US$5.79-132.43m but a net gain of 328-16,993 quality-adjusted life years (QALYs) and prevention of 39-1935 HBV-related deaths over cohort's lifetime. Scenario 2 was not cost-effective with a WTP of 1-time GDP per capita, but became cost-effective when treatment initiation rate increased to 70%. In contrast, compared with status quo, secnario 3 would save US$144.59-192.93m in investment and achieve a net gain of 23,814-30,476 QALYs and prevention of 3074-3802 HBV-related deaths. Improving HBV antiviral treatment initiation among eligible CHB individuals substantially improved the cost-effectiveness of the shared-care models. Interpretation: Shared-care models with HBV testing, follow up and referring of predetermined conditions to specialty care at an appropriate time, especially antiviral treatment initiation in primary care, are highly effective and cost-effective in China. Funding: National Natural Science Foundation of China.

Cost-effectiveness of artificial intelligence-assisted liquid-based cytology testing for cervical cancer screening in China.

Background: The 2021 World Health Organization (WHO) guidelines for cervical cancer screening recommend human papillomavirus (HPV) DNA or mRNA testing. Artificial intelligence (AI)-assisted liquid-based cytology (LBC) systems also have the potential to facilitate rapid scale-up of cervical cancer screening. We aimed to evaluate the cost-effectiveness of AI-assisted LBC testing, compared with the manual LBC and HPV-DNA testing, for primary cervical cancer screening in China. Methods: We developed a Markov model for a cohort of 100,000 women aged 30 years over a lifetime to simulate the natural history of cervical cancer progression. We evaluated the incremental cost-effectiveness ratios (ICER) of 18 screening strategies (a combination of the three screening methods with six screening frequencies) from a healthcare provider's perspective. The willingness-to-pay threshold (US$30,828) was chosen as three times the Chinese per-capita gross domestic product in 2019. Univariate and probabilistic sensitivity analyses were performed to examine the robustness of the results. Findings: Compared with no screening, all 18 screening strategies were cost-effective, with an ICER of $622-24,482 per quality-adjusted life-year (QALY) gained. If HPV testing after scaling up to population level screening costs $10.80 or more, screening once every 5 years using AI-assisted LBC would be the most cost-effective strategy with an ICER of $8790/QALY gained compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. Its probability of being cost-effective was higher (55.4%) than other strategies. Sensitivity analyses showed that the most cost-effective strategy would become AI-assisted LBC testing once every 3 years if the sensitivity (74.1%) and specificity (95.6%) of this method were both reduced by ≥10%. The most cost-effective strategy would become HPV-DNA testing once every 5 years if the cost of AI-assisted LBC was more expensive than manual LBC or if the HPV-DNA test cost is slightly reduced (from $10.8 to <$9.4). Interpretation: AI-assisted LBC screening once every 5 years could be more cost-effective than manually-read LBC. Using AI-assisted LBC could have comparable cost-effectiveness to HPV DNA screening, but the relative pricing of HPV DNA testing is critical in this result. Funding: National Natural Science Foundation of China, National Key R&D Program of China.

Vaccinating women previously treated for human papillomavirus-related cervical precancerous lesions is highly cost-effective in China.

Background: The 2021 Chinese Expert Consensus on the Clinical Application of the Human Papillomavirus (HPV) Vaccine recommended vaccination for women who previously received ablative or excisional treatment for high-grade squamous intraepithelial lesion (HSIL). This study evaluates the cost-effectiveness of HPV vaccination in women previously treated for cervical precancerous lesions. Methods: We used a Markov model to simulate the disease progression of both low- and high-risk HPV subtypes. We followed a cohort of 100,000 women aged 18-45 years who received treatment for cervical precancerous lesions for a lifetime (80 years). We used the Incremental Cost-Effectiveness Ratios (ICER) with a 5% discount rate to measure the cost-effectiveness of nine vaccination strategies, including a combination of HPV bivalent (HPV-2), quadrivalent (HPV-4) and nonavalent vaccine (HPV-9), each with three vaccination doses (one-, two- and three-dose). We conducted one-way sensitivity analysis and probabilistic sensitivity analysis. We followed the CHEERS 2022 guidelines. Results: Compared to the status quo, the nine vaccination strategies would result in $3.057-33.124 million incremental cost and 94-1,211 incremental quality-adjusted life-years (QALYs) in 100,000 women previously treated for cervical precancerous lesions. Three vaccination strategies were identified on the cost-effectiveness frontier. In particular, ICER for one-dose HPV-4 vaccination was US$10,025/QALY compared to the status quo (no vaccination); ICER for two-dose HPV-4 vaccination was US$17,641//QALY gained compared to one-dose HPV-4 vaccination; ICER for three-dose HPV-4 vaccination was US$27,785/QALY gained compared with two-dose HPV-4 vaccination. With a willingness-to-pay of three times gross domestic product per capita (US$37655), three-dose HPV-4 vaccination was the most cost-effective vaccination strategy compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. A probabilistic sensitivity analysis confirmed a 99.1% probability of being cost-effective. If the cost of the HPV-9 is reduced to 50% of the current price, three-dose HPV-9 vaccination would become the most cost-effective strategy. Discussion: Three-dose HPV-4 vaccination is the most cost-effective vaccination strategy for women treated for precancerous cervical lesions in the Chinese setting.

mRNA-based COVID-19 booster vaccination is highly effective and cost-effective in Australia.

BACKGROUND: Australia implemented an mRNA-based booster vaccination strategy against the COVID-19 Omicron variant in November 2021. We aimed to evaluate the effectiveness and cost-effectiveness of the booster strategy over 180 days. METHODS: We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy (administered 3 months after 2nd dose) in those aged ≥ 16 years, from a healthcare system perspective. The willingness-to-pay threshold was chosen as A$ 50,000. RESULTS: Compared with 2-doses of COVID-19 vaccines without a booster, Australia's booster strategy would incur an additional cost of A$0.88 billion but save A$1.28 billion in direct medical cost and gain 670 quality-adjusted life years (QALYs) in 180 days of its implementation. This suggested the booster strategy is cost-saving, corresponding to a benefit-cost ratio of 1.45 and a net monetary benefit of A$0.43 billion. The strategy would prevent 1.32 million new infections, 65,170 hospitalisations, 6,927 ICU admissions and 1,348 deaths from COVID-19 in 180 days. Further, a universal booster strategy of having all individuals vaccinated with the booster shot immediately once their eligibility is met would have resulted in a gain of 1,599 QALYs, a net monetary benefit of A$1.46 billion and a benefit-cost ratio of 1.95 in 180 days. CONCLUSION: The COVID-19 booster strategy implemented in Australia is likely to be effective and cost-effective for the Omicron epidemic. Universal booster vaccination would have further improved its effectiveness and cost-effectiveness.

Global Diabetes Prevalence in COVID-19 Patients and Contribution to COVID-19- Related Severity and Mortality: A Systematic Review and Meta-analysis.

BACKGROUND: COVID-19 and diabetes both contribute to large global disease burdens. PURPOSE: To quantify the prevalence of diabetes in various COVID-19 disease stages and calculate the population attributable fraction (PAF) of diabetes to COVID-19-related severity and mortality. DATA SOURCES: Systematic review identified 729 studies with 29,874,938 COVID-19 patients. STUDY SELECTION: Studies detailed the prevalence of diabetes in subjects with known COVID-19 diagnosis and severity. DATA EXTRACTION: Study information, COVID-19 disease stages, and diabetes prevalence were extracted. DATA SYNTHESIS: The pooled prevalence of diabetes in stratified COVID-19 groups was 14.7% (95% CI 12.5-16.9) among confirmed cases, 10.4% (7.6-13.6) among nonhospitalized cases, 21.4% (20.4-22.5) among hospitalized cases, 11.9% (10.2-13.7) among nonsevere cases, 28.9% (27.0-30.8) among severe cases, and 34.6% (32.8-36.5) among deceased individuals, respectively. Multivariate metaregression analysis explained 53-83% heterogeneity of the pooled prevalence. Based on a modified version of the comparative risk assessment model, we estimated that the overall PAF of diabetes was 9.5% (7.3-11.7) for the presence of severe disease in COVID-19-infected individuals and 16.8% (14.8-18.8) for COVID-19-related deaths. Subgroup analyses demonstrated that countries with high income levels, high health care access and quality index, and low diabetes disease burden had lower PAF of diabetes contributing to COVID-19 severity and death. LIMITATIONS: Most studies had a high risk of bias. CONCLUSIONS: The prevalence of diabetes increases with COVID-19 severity, and diabetes accounts for 9.5% of severe COVID-19 cases and 16.8% of deaths, with disparities according to country income, health care access and quality index, and diabetes disease burden.

Modelling the prevalence of hepatitis B towards eliminating it as a major public health threat in China.

BACKGROUND: The World Health Organization (WHO) requires reduction in the prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) in children to 0.1% by 2030, a key indicator for eliminating viral hepatitis as a major public health threat. Whether and how China can achieve this target remains unknown, although great achievements have been made. We aimed to predict the decline of HBsAg prevalence in China and identify key developments needed to achieve the target. METHODS: An age- and time-dependent dynamic compartmental model was constructed based on the natural history of HBV infection and the national history and current status of hepatitis B control. The model was run from 2006 to 2040 to predict the decline of HBsAg prevalence under three scenarios including maintaining current interventions (status quo), status quo + peripartum antiviral prophylaxis (PAP, recommended by WHO in 2020), and scaling up current interventions + PAP. RESULTS: Under the status quo, HBsAg prevalence would decrease steadily in all age groups, but the WHO's target of 0.1% prevalence in children aged < 5 years would not be achieved until 2037. The results are robust according to sensitivity analyses. Under the status quo + PAP, the HBsAg prevalence of children aged < 5 years would significantly decrease with the introduction of PAP, and the higher the successful interruption coverage is achieved by PAP, the more significant the decline. However, even if the successful interruption coverage reaches 90% by 2030, the 0.1% prevalence target would not be met until 2031. Under the scaling up current interventions + PAP, combined with scale-up of current interventions, the WHO's 0.1% target would be achieved on time or one year in advance if PAP is introduced and the successful interruption coverage is scaled up to 80% or 90% by 2030, respectively. CONCLUSIONS: It is difficult for China to achieve the WHO's target of 0.1% HBsAg prevalence in children by 2030 by maintaining current interventions. PAP may play an important role to shorten the time to achieve the target. A comprehensive scale-up of available interventions including PAP will ensure that China achieves the target on schedule.

Effect of Direct Bilirubin Level on Clinical Outcome and Prognoses in Severely/Critically Ill Patients With COVID-19.

Objectives: We aimed to investigate how changes in direct bilirubin (DBiL) levels in severely/critically ill the coronavirus disease (COVID-19) patients during their first week of hospital admission affect their subsequent prognoses and mortality. Methods: We retrospectively enrolled 337 severely/critically ill COVID-19 patients with two consecutive blood tests at hospital admission and about 7 days after. Based on the trend of the two consecutive tests, we categorized patients into the normal direct bilirubin (DBiL) group (224), declined DBiL group (44) and elevated DBiL group (79). Results: The elevated DBiL group had a significantly larger proportion of critically ill patients (χ2-test, p < 0.001), a higher risk of ICU admission, respiratory failure, and shock at hospital admission (χ2-test, all p < 0.001). During hospitalization, the elevated DBiL group had significantly higher risks of shock, acute respiratory distress syndrome (ARDS), and respiratory failure (χ2-test, all p < 0.001). The same findings were observed for heart damage (χ2-test, p = 0.002) and acute renal injury (χ2-test, p = 0.009). Cox regression analysis showed the risk of mortality in the elevated DBiL group was 2.27 (95% CI: 1.50-3.43, p < 0.001) times higher than that in the normal DBiL group after adjusted age, initial symptom, and laboratory markers. The Receiver Operating Characteristic curve (ROC) analysis demonstrated that the second test of DBiL was consistently a better indicator of the occurrence of complications (except shock) and mortality than the first test in severely/critically ill COVID-19 patients. The area under the ROC curve (AUC) combined with two consecutive DBiL levels for respiratory failure and death was the largest. Conclusion: Elevated DBiL levels are an independent indicator for complication and mortality in COVID-19 patients. Compared with the DBiL levels at admission, DBiL levels on days 7 days of hospitalization are more advantageous in predicting the prognoses of COVID-19 in severely/critically ill patients.

Cost-effectiveness analysis of BNT162b2 COVID-19 booster vaccination in the United States.

OBJECTIVES: To evaluate the cost-effectiveness of a booster strategy in the United States. METHODS: We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy of the Pfizer-BioNTech BNT162b2 (administered 6 months after the second dose) among older adults from a healthcare system perspective. RESULTS: Compared with 2 doses of BNT162b2 without a booster, the booster strategy in a 100,000 cohort of older adults would incur an additional cost of $3.4 million in vaccination cost but save $6.7 million in direct medical cost and gain 3.7 quality-adjusted life-years in 180 days. This corresponds to a benefit-cost ratio of 1.95 and a net monetary benefit of $3.4 million. Probabilistic sensitivity analysis indicates that a booster strategy has a high chance (67%) of being cost-effective. Notably, the cost-effectiveness of the booster strategy is highly sensitive to the population incidence of COVID-19, with a cost-effectiveness threshold of 8.1/100,000 person-day. If vaccine efficacies reduce by 10%, 30%, and 50%, this threshold will increase to 9.7/100,000, 13.9/100,000, and 21.9/100,000 person-day, respectively. CONCLUSION: Offering the BNT162b2 booster to older adults aged ≥65 years in the United States is likely to be cost-effective. Less efficacious vaccines and boosters may still be cost-effective in settings of high SARS-CoV-2 transmission.

Cost-effectiveness of universal screening for chronic hepatitis B virus infection in China: an economic evaluation.

BACKGROUND: China has the highest prevalence of hepatitis B virus (HBV) infection worldwide. Universal HBV screening might enable China to reach the WHO 2030 target of 90% diagnostics, 80% treatment, and 65% HBV-related death reduction, and eventually elimination of viral hepatitis. We evaluated the cost-effectiveness of implementing universal HBV screening in China and identified optimal screening strategies. METHODS: We used a Markov cohort model, inputting parameters based on data from previous studies and public databases, to assess the cost-effectiveness of four HBV serological screening strategies in China in different screening scenarios. We simulated universal screening scenarios in 15 adult age groups between 18 and 70 years, with different years of screening implementation (2021, 2026, and 2031) and compared to the status quo (ie, no universal screening); in total, we investigated 180 different screening scenarios. We calculated the incremental cost-effectiveness ratio (ICER) between the different screening strategies and the status quo (current screening strategy). We performed probabilistic and one-way deterministic sensitivity analyses to assess the robustness of our findings. FINDINGS: With a willingness-to-pay level of three times the Chinese gross domestic product (GDP) per capita (US$30 828), all universal screening scenarios in 2021 were cost-effective compared with the status quo. The serum HBsAg/HBsAb/HBeAg/HBeAb/HBcAb (five-test) screening strategy in people aged 18-70 years was the most cost-effective strategy in 2021 (ICER $18 295/quality-adjusted life-years [QALY] gained). This strategy remained the most cost-effective, when the willingness-to-pay threshold was reduced to 2 times GDP per capita. The two-test strategy for people aged 18-70 years became more cost-effective at lower willingness-to-pay levels. The five-test strategy could prevent 3·46 million liver-related deaths in China over the lifetime of the cohort. It remained the most cost-effective strategy when implementation was delayed until 2026 (ICER $20 183/QALY) and 2031 (ICER $23 123/QALY). Screening young people (18-30 years) will no longer be cost-effective in delayed scenarios. INTERPRETATION: The five-test universal screening strategy in people aged 18-70 years, implemented within the next 10 years, is the optimal HBV screening strategy for China. Other screening strategies could be cost-effective alternatives, if budget is limited in rural areas. Delaying strategy implementation reduces overall cost-effectiveness. Early screening initiation will aid global efforts in achieving viral hepatitis elimination. FUNDING: National Natural Science Foundation of China.

Critical timing and extent of public health interventions to control outbreaks dominated by SARS-CoV-2 variants in Australia: a mathematical modelling study.

OBJECTIVES: The exact characteristics of a coronavirus disease 2019 (COVID-19) outbreak that trigger public health interventions are poorly defined. The aim of this study was to assess the critical timing and extent of public health interventions to contain COVID-19 outbreaks in Australia. METHODS: A practical model was developed using existing epidemic data in Australia. The effective combinations of public health interventions and the critical number of daily cases for intervention commencement under various scenarios of changes in transmissibility of new variants and vaccination coverage were quantified. RESULTS: In the past COVID-19 outbreaks in four Australian states, the number of reported cases on the day that interventions commenced strongly predicted the size and duration of the outbreaks. In the early phase of an outbreak, containing a wildtype-dominant epidemic to a low level (≤10 cases/day) would require effective combinations of social distancing and face mask use interventions to be commenced before the number of daily reported cases reaches six. Containing an Alpha-dominant epidemic would require more stringent interventions that commence earlier. For the Delta variant, public health interventions alone would not contain the epidemic unless the vaccination coverage was ≥70%. CONCLUSIONS: This study highlights the importance of early and decisive action in the initial phase of an outbreak. Vaccination is essential for containing variants.

Potential effect of antiseptic mouthwash on the incidence of Neisseria gonorrhoeae among men who have sex with men: a mathematical modelling study.

OBJECTIVES: The incidence of Neisseria gonorrhoeae and its antimicrobial resistance is increasing in many countries. Antibacterial mouthwash may reduce gonorrhoea transmission without using antibiotics. We modelled the effect that antiseptic mouthwash may have on the incidence of gonorrhoea. DESIGN: We developed a mathematical model of the transmission of gonorrhoea between each anatomical site (oropharynx, urethra and anorectum) in men who have sex with men (MSM). We constructed four scenarios: (1) mouthwash had no effect; (2) mouthwash increased the susceptibility of the oropharynx; (3) mouthwash reduced the transmissibility from the oropharynx; (4) the combined effect of mouthwash from scenarios 2 and 3. SETTING: We used data at three anatomical sites from 4873 MSM attending Melbourne Sexual Health Centre in 2018 and 2019 to calibrate our models and data from the USA, Netherlands and Thailand for sensitivity analyses. PARTICIPANTS: Published available data on MSM with multisite infections of gonorrhoea. PRIMARY AND SECONDARY OUTCOME MEASURES: Incidence of gonorrhoea. RESULTS: The overall incidence of gonorrhoea was 44 (95% CI 37 to 50)/100 person-years (PY) in scenario 1. Under scenario 2 (20%-80% mouthwash coverage), the total incidence increased (47-60/100 PY) and at all three anatomical sites by between 7.4% (5.9%-60.8%) and 136.6% (108.1%-177.5%). Under scenario 3, with the same coverage, the total incidence decreased (20-39/100 PY) and at all anatomical sites by between 11.6% (10.2%-13.5%) and 99.8% (99.2%-100%). Under scenario 4, changes in the incidence depended on the efficacy of mouthwash on the susceptibility or transmissibility. The effect on the total incidence varied (22-55/100 PY), and at all anatomical sites, there were increases of nearly 130% and large declines of almost 100%. CONCLUSIONS: The effect of mouthwash on gonorrhoea incidence is largely predictable depending on whether it increases susceptibility to or reduces the transmissibility of gonorrhoea.

Evaluating the Impact of SARS-CoV-2 Variants on the COVID-19 Epidemic and Social Restoration in the United States: A Mathematical Modelling Study.

Background: Multiple SARS-CoV-2 variants are still rampant across the United States (US). We aimed to evaluate the impact of vaccination scale-up and potential reduction in the vaccination effectiveness on the COVID-19 epidemic and social restoration in the US. Methods: We extended a published compartmental model and calibrated the model to the latest US COVID-19 data. We estimated the vaccine effectiveness against the variant and evaluated the impact of a potential reduction in vaccine effectiveness on the epidemics. We explored the epidemic trends under different levels of social restoration. Results: We estimated the overall existing vaccine effectiveness against the variant as 88.5% (95% CI: 87.4-89.5%) with the vaccination coverage of 70% by the end of August, 2021. With this vaccine effectiveness and coverage, there would be 498,972 (109,998-885,947) cumulative infections and 15,443 (3,828-27,057) deaths nationwide over the next 12 months, of which 95.0% infections and 93.3% deaths were caused by the variant. Complete social restoration at 60, 65, 70% vaccination coverage would increase cumulative infections to 1.6 (0.2-2.9) million 0.7 (0.1-1.2) million, and 511,159 (110,578-911,740), respectively. At same time it would increase cumulative deaths to 39,040 (5,509-72,570), 19,562 (3,873-35,250), 15,739 (3,841-27,638), respectively. However, if the vaccine effectiveness were reduced to 75%, 50% or 25% due to new SARS-CoV-2 variants, there would be 667,075 (130,682-1,203,468), 1.7 (0.2-3.2) million, 19.0 (5.3-32.7) million new infections and 19,249 (4,281-34,217), 42,265 (5,081-79,448), 426,860 (117,229-736,490) cumulative deaths to occur over the next 12 months. Further, social restoration at a lower vaccination coverage would lead to even greater secondary outbreaks. Conclusion: Current COVID-19 vaccines remain effective against the SARS-CoV-2 variant, and 70% vaccination coverage would be sufficient to restore social activities to a pre-pandemic level. Further reduction in vaccine effectiveness against SARS-CoV-2 variants would result in a potential surge of the epidemic. Multiple measures, including public health interventions, vaccination scale-up and development of a new vaccine booster, should be integrated to counter the new challenges of new SARS-CoV-2 variants.

Modeling the epidemiological impact and cost-effectiveness of a combined schoolgirl HPV vaccination and cervical cancer screening program among Chinese women.

Human papillomavirus (HPV) infection is common in women and also the main cause of cervical cancer. Based on a dynamic compartmental model, we aimed to evaluate the population impact and cost-effectiveness of strategies that combined cervical cancer screening and HPV schoolgirl vaccination for Chinese women. The effectiveness of interventions was assessed by comparing modeled scenarios to the status quo, where a 3-y cervical cancer screening program remained at a 20% coverage and without a universal HPV vaccination program. Our study demonstrated that increasing screening coverage from 20% to 50% would reduce the high-risk HPV (HR-HPV) prevalence to 5.4%, whereas a universal schoolgirl vaccination program using the quadrivalent vaccine (qHPV) with a coverage of 50% would reduce the prevalence to 2.9% by 2069. Scaling-up the cervical screening coverage to 50% will prevent 16,012 (95% CI: 8,791 to 25,913) Disability-Adjusted Life-Years (DALYs) per year, with an incremental cost-effectiveness ratio (ICER) of US$ 10,958 (95% CI: $169 to $26,973)/DALY prevented. At the current qHPV price, vaccinating 50% of school girls will prevent 13,854 (95% CI: 8,355 to 20,776) DALYs/year, but the corresponding incremental cost-effectiveness ratio (ICER, US$ 83,043, 95% CI: $52,234 to $138,025) exceeds cost-effectiveness threshold (i.e., 3 times GDP per-capita of China: $30,792). The qHPV vaccine requires at least a 50% price reduction to be cost-effective. Vaccinating schoolgirls will result in a large population health benefit in the long term, but such a universal HPV vaccination program can only be cost-effective with a substantial price reduction.

Chlamydia trachomatis transmission between the oropharynx, urethra and anorectum in men who have sex with men: a mathematical model.

BACKGROUND: It has been presumed that Chlamydia trachomatis is transmitted between men only through anal or oral sex, but no mathematical models have tested this presumption. METHODS: To test this presumption, we created 20 compartmental mathematical models of different sexual practices that included both oral and anal sex and calibrated these models to the observed rates of Chlamydia trachomatis infection at three anatomical sites from 4888 men who have sex with men (MSM) in Melbourne Sexual Health Centre during 2018-2019. RESULTS: A model that included only oral and anal sex could replicate the observed rates of single-site infection at the oropharynx, urethra and rectum alone, but could not replicate infection at more than one of these sites (multisite). However, if we included transmission from sexual practices that followed one another in the same sexual episode (e.g. saliva contamination of the penis from oral sex transmitting chlamydia to the rectum by anal sex), we significantly improved the calibration of multisite infection rates substantially. CONCLUSIONS: Our modelling study suggests that transmission routes other than just oral and anal sex are necessary to explain the high rate of Chlamydia trachomatis infection at more than one site.

Domestic HPV vaccine price and economic returns for cervical cancer prevention in China: a cost-effectiveness analysis.

BACKGROUND: Coinciding with the release of the first Chinese domestic human papillomavirus (HPV) vaccine Cecolin in 2019, and the substantial advancements in cervical cancer screening technology, we aimed to evaluate the cost-effectiveness of the combined strategies of cervical cancer screening programmes and universal vaccination of girls (aged 9-14 years) with Cecolin in China. METHODS: We did a cost-effectiveness analysis in China, in which we developed a Markov model of cervical cancer to evaluate the incremental cost-effectiveness ratios of 61 intervention strategies, including a combination of various screening methods at different frequencies with and without vaccination, and also vaccination alone, from a health-care system perspective. We did univariate and probabilistic sensitivity analyses to assess the robustness of the model's findings. FINDINGS: Compared with no intervention, various combined screening and vaccination strategies would incur an additional cost of US$6 157 000-22 146 000 and result in 691-970 quality-adjusted life-years (QALYs) gained in a designated cohort of 100 000 girls aged 9-14 years over a lifetime. With a willingness-to-pay threshold of three times the Chinese per-capita gross domestic product (GDP), careHPV screening (a rapid HPV test) once every 5 years with vaccination would be the most cost-effective strategy with an incremental cost-effectiveness ratio of $21 799 per QALY compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier, and the probability of it being cost-effective (44%) outperformed other strategies. Strategies that combined screening and vaccination would be more cost-effective than screening alone strategies when the vaccination cost was less than $50 for two doses, even with a lower willingness-to-pay of one times the per-capita GDP. INTERPRETATION: careHPV screening once every 5 years with vaccination is the most cost-effective strategy for cervical cancer prevention in China. A reduction in the domestic HPV vaccine price is necessary to ascertain a good economic return for the future vaccination programme. The findings provide important evidence that informs health policies for cervical cancer prevention in China. FUNDING: National Natural Science Foundation of China.

What Is Required to Prevent a Second Major Outbreak of SARS-CoV-2 upon Lifting Quarantine in Wuhan City, China.

BACKGROUND: The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted. METHODS: We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic. RESULTS: We projected a declining trend of the COVID-19 epidemic if the current quarantine strategy continues, and Wuhan would record the last new confirmed cases in late April 2020. At the end of the epidemic, 65,733 (45,722-99,015) individuals would be infected by the virus, among which 16,166 (11,238-24,603, 24.6%) were through public contacts, 45,996 (31,892-69,565, 69.7%) through household contact, and 3,571 (2,521-5,879, 5.5%) through hospital contacts (including 778 (553-1,154) non-COVID-19 patients and 2,786 (1,969-4,791) medical staff). A total of 2,821 (1,634-6,361) would die of COVID-19 related pneumonia in Wuhan. Early quarantine lifting on 21st March is viable only if Wuhan residents sustain a high facial mask usage of ≥85% and a pre-quarantine level public contact rate. Delaying city resumption to mid/late April would relax the requirement of facial mask usage to ≥75% at the same contact rate. CONCLUSIONS: The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.