Challenges of COVID-19 Case Forecasting in the US, 2020-2021.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

Enhanced cholera surveillance to improve vaccination campaign efficiency.

Systematic testing for Vibrio cholerae O1 is rare, which means that the world's limited supply of oral cholera vaccines (OCVs) may not be delivered to areas with the highest true cholera burden. Here we used a phenomenological model with subnational geographic targeting and fine-scale vaccine effects to model how expanding V. cholerae testing affected impact and cost-effectiveness for preventive vaccination campaigns across different bacteriological confirmation and vaccine targeting assumptions in 35 African countries. Systematic testing followed by OCV targeting based on confirmed cholera yielded higher efficiency and cost-effectiveness and slightly fewer averted cases than status quo scenarios targeting suspected cholera. Targeting vaccine to populations with an annual incidence rate greater than 10 per 10,000, the testing scenario averted 10.8 (95% prediction interval (PI) 9.4-12.6) cases per 1,000 fully vaccinated persons while the status quo scenario averted 6.9 (95% PI 6.0-7.8) cases per 1,000 fully vaccinated persons. In the testing scenario, testing costs increased by US$31 (95% PI 25-39) while vaccination costs reduced by US$248 (95% PI 176-326) per averted case compared to the status quo. Introduction of systematic testing into cholera surveillance could improve efficiency and reach of global OCV supply for preventive vaccination.

Cholera Deaths During Outbreaks in Uvira, Eastern Democratic Republic of the Congo, 10-35 Months After Mass Vaccination.

Our understanding of the burden and drivers of cholera mortality is hampered by limited surveillance and confirmation capacity. Leveraging enhanced clinical and laboratory surveillance in the cholera-endemic community of Uvira, eastern Democratic Republic of Congo, we describe cholera deaths across 3 epidemics between September 2021 and September 2023 following mass vaccination.

Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination.

In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-19 Scenario Modeling Hub, an ensemble of nine mechanistic models produced 6-month scenario projections for July-December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July-December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July-December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, although may have had even greater impacts, considering the underestimated resurgence magnitude from the model.

Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: The highly transmissible SARS-CoV-2 Delta variant has begun to cause increases in cases, hospitalizations, and deaths in parts of the United States. With slowed vaccination uptake, this novel variant is expected to increase the risk of pandemic resurgence in the US in July-December 2021. WHAT IS ADDED BY THIS REPORT?: Data from nine mechanistic models project substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant. These resurgences, which have now been observed in most states, were projected to occur across most of the US, coinciding with school and business reopening. Reaching higher vaccine coverage in July-December 2021 reduces the size and duration of the projected resurgence substantially. The expected impact of the outbreak is largely concentrated in a subset of states with lower vaccination coverage. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Renewed efforts to increase vaccination uptake are critical to limiting transmission and disease, particularly in states with lower current vaccination coverage. Reaching higher vaccination goals in the coming months can potentially avert 1.5 million cases and 21,000 deaths and improve the ability to safely resume social contacts, and educational and business activities. Continued or renewed non-pharmaceutical interventions, including masking, can also help limit transmission, particularly as schools and businesses reopen.

Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios - United States, April-September 2021.

After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months.

Modelling impact and cost-effectiveness of oral pre-exposure prophylaxis in 13 low-resource countries.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) provision is a priority intervention for high HIV prevalence settings and populations at substantial risk of HIV acquisition. This mathematical modelling analysis estimated the impact, cost and cost-effectiveness of scaling up oral PrEP in 13 countries. METHODS: We projected the impact and cost-effectiveness of oral PrEP between 2018 and 2030 using a combination of the Incidence Patterns Model and the Goals model. We created four PrEP rollout scenarios involving three priority populations-female sex workers (FSWs), serodiscordant couples (SDCs) and adolescent girls and young women (AGYW)-both with and without geographic prioritization. We applied the model to 13 countries (Eswatini, Ethiopia, Haiti, Kenya, Lesotho, Mozambique, Namibia, Nigeria, Tanzania, Uganda, Zambia and Zimbabwe). The base case assumed achievement of the Joint United Nations Programme on HIV/AIDS 90-90-90 antiretroviral therapy targets, 90% male circumcision coverage by 2020 and 90% efficacy and adherence levels for oral PrEP. RESULTS: In the scenarios we examined, oral PrEP averted 3% to 8% of HIV infections across the 13 countries between 2018 and 2030. For all but three countries, more than 50% of the HIV infections averted by oral PrEP in the scenarios we examined could be obtained by rollout to FSWs and SDCs alone. For several countries, expanding oral PrEP to include medium-risk AGYW in all regions greatly increased the impact. The efficiency and impact benefits of geographic prioritization of rollout to AGYW varied across countries. Variations in cost-effectiveness across countries reflected differences in HIV incidence and expected variations in unit cost. For most countries, rolling out oral PrEP to FSWs, SDCs and geographically prioritized AGYW was not projected to have a substantial impact on the supply chain for antiretroviral drugs. CONCLUSIONS: These modelling results can inform prioritization, target-setting and other decisions related to oral PrEP scale-up within combination prevention programmes. We caution against extensive use given limitations in cost data and implementation approaches. This analysis highlights some of the immediate challenges facing countries-for example, trade-offs between overall impact and cost-effectiveness-and emphasizes the need to improve data availability and risk assessment tools to help countries make informed decisions.

Age targeting and scale-up of voluntary medical male circumcision in Mozambique.

BACKGROUND: The voluntary medical male circumcision (VMMC) program in Mozambique aimed to increase male circumcision (MC) coverage to 80 percent among males ages 10 to 49 by 2018. Given the difficulty in attracting adult men over age 20 for circumcision, Mozambique became interested in assessing its age-targeting strategy and progress at the provincial level to inform program planning. METHODS: We examined the impact and cost-effectiveness of circumcising different age groups of men using the Decision Makers' Program Planning Toolkit, Version 2.1 (DMPPT 2). We also applied the model to assess the scale-up efforts through the end of September 2017 and project their impact on HIV incidence through 2030. The DMPPT 2 is a compartmental Excel-based model that analyzes the effects of age at circumcision on program impact and cost-effectiveness. The model tracks changes in age-specific MC coverage due to VMMC program circumcisions. Baseline MC prevalence was based on data from the 2011 Demographic and Health Survey. The DMPPT 2 was populated with HIV incidence projections from Spectrum/Goals under an assumption that Mozambique would reach its national targets for HIV treatment and prevention by 2022. RESULTS: We estimate the VMMC program increased MC coverage among males ages 10 to 49 from 27 percent in 2009 to 48 percent by end of September 2017. Coverage increased primarily in males ages 10 to 29. VMMCs conducted in the national program through the end of September 2017 are projected to avert 67,076 HIV infections from 2010 to 2030. Scaling up circumcisions in males ages 20 to 29 will have the most immediate impact on HIV incidence, while the greatest impact over a 15-year period is obtained by circumcising males ages 15 to 24 in the majority of priority provinces. Circumcising 80 percent of males ages 10 to 29 can achieve 77 percent of the impact through 2030 compared with circumcising 80 percent of males ages 10 to 49. CONCLUSION: The VMMC program in Mozambique has made great strides in increasing MC coverage, particularly for males ages 10 to 29. Scaling up and maintaining MC coverage in this age group offers an attainable and cost-effective target for VMMC in Mozambique.

Age targeting and scale-up of voluntary medical male circumcision in Mozambique

Background: The voluntary medical male circumcision (VMMC) program in Mozambique aimed to increase male circumcision (MC) coverage to 80 percent among males ages 10 to 49 by 2018. Given the difficulty in attracting adult men over age 20 for circumcision, Mozambique became interested in assessing its age-targeting strategy and progress at the provincial level to inform program planning. Methods: We examined the impact and cost-effectiveness of circumcising different age groups of men using the Decision Makers' Program Planning Toolkit, Version 2.1 (DMPPT 2). We also applied the model to assess the scale-up efforts through the end of September 2017 and project their impact on HIV incidence through 2030. The DMPPT 2 is a compartmental Excel-based model that analyzes the effects of age at circumcision on program impact and cost-effectiveness. The model tracks changes in age-specific MC coverage due to VMMC program circumcisions. Baseline MC prevalence was based on data from the 2011 Demographic and Health Survey. The DMPPT 2 was populated with HIV incidence projections from Spectrum/Goals under an assumption that Mozambique would reach its national targets for HIV treatment and prevention by 2022. Results: We estimate the VMMC program increased MC coverage among males ages 10 to 49 from 27 percent in 2009 to 48 percent by end of September 2017. Coverage increased primarily in males ages 10 to 29. VMMCs conducted in the national program through the end of September 2017 are projected to avert 67,076 HIV infections from 2010 to 2030. Scaling up circumcisions in males ages 20 to 29 will have the most immediate impact on HIV incidence, while the greatest impact over a 15-year period is obtained by circumcising males ages 15 to 24 in the majority of priority provinces. Circumcising 80 percent of males ages 10 to 29 can achieve 77 percent of the impact through 2030 compared with circumcising 80 percent of males ages 10 to 49. Conclusion: The VMMC program in Mozambique has made great strides in increasing MC coverage, particularly for males ages 10 to 29. Scaling up and maintaining MC coverage in this age group offers an attainable and cost-effective target for VMMC in Mozambique.

Changing hearts and minds: Results from a multi-country gender and sexual diversity training.

Engaging key populations, including gender and sexual minorities, is essential to meeting global targets for reducing new HIV infections and improving the HIV continuum of care. Negative attitudes toward gender and sexual minorities serve as a barrier to political will and effective programming for HIV health services. The President's Emergency Plan for AIDS Relief (PEPFAR), established in 2003, provided Gender and Sexual Diversity Trainings for 2,825 participants including PEPFAR staff and program implementers, U.S. government staff, and local stakeholders in 38 countries. The outcomes of these one-day trainings were evaluated among a subset of participants using a mixed methods pre- and post-training study design. Findings suggest that sustainable decreases in negative attitudes toward gender and sexual minorities are achievable with a one-day training.