By April 2, 2020, >1 million persons worldwide were infected with severe acute respiratory syndrome coronavirus 2. We used a mathematical model to investigate the effectiveness of social distancing ...interventions in a mid-sized city. Interventions reduced contacts of adults >60 years of age, adults 20-59 years of age, and children <19 years of age for 6 weeks. Our results suggest interventions started earlier in the epidemic delay the epidemic curve and interventions started later flatten the epidemic curve. We noted that, while social distancing interventions were in place, most new cases, hospitalizations, and deaths were averted, even with modest reductions in contact among adults. However, when interventions ended, the epidemic rebounded. Our models suggest that social distancing can provide crucial time to increase healthcare capacity but must occur in conjunction with testing and contact tracing of all suspected cases to mitigate virus transmission.
Vaccines, when available, will likely become our best tool to control the COVID-19 pandemic. Even in the most optimistic scenarios, vaccine shortages will likely occur. Using an age-stratified ...mathematical model paired with optimization algorithms, we determined optimal vaccine allocation for four different metrics (deaths, symptomatic infections, and maximum non-ICU and ICU hospitalizations) under many scenarios. We find that a vaccine with effectiveness ≥50% would be enough to substantially mitigate the ongoing pandemic, provided that a high percentage of the population is optimally vaccinated. When minimizing deaths, we find that for low vaccine effectiveness, irrespective of vaccination coverage, it is optimal to allocate vaccine to high-risk (older) age groups first. In contrast, for higher vaccine effectiveness, there is a switch to allocate vaccine to high-transmission (younger) age groups first for high vaccination coverage. While there are other societal and ethical considerations, this work can provide an evidence-based rationale for vaccine prioritization.
Cholera is an acute, diarrheal disease caused by Vibrio cholerae O1 or 139 that is associated with a high global burden.
We analyzed the estimated duration of immunity following cholera infection ...from available published studies. We searched PubMed and Web of Science for studies of the long-term immunity following cholera infection. We identified 22 eligible studies and categorized them as either observational, challenge, or serological.
We found strong evidence of protection at 3 years after infection in observational and challenge studies. However, serological studies show that elevated humoral markers of potential correlates of protection returned to baseline within 1 year. Additionally, a subclinical cholera infection may confer lower protection than a clinical one, as suggested by 3 studies that found that, albeit with small sample sizes, most participants with a subclinical infection from an initial challenge with cholera had a symptomatic infection when rechallenged with a homologous biotype.
This review underscores the need to elucidate potential differences in the protection provided by clinical and subclinical cholera infections. Further, more studies are warranted to bridge the gap between the correlates of protection and cholera immunity. Understanding the duration of natural immunity to cholera can help guide control strategies and policy.
Most COVID-19 vaccines require two doses, however with limited vaccine supply, policymakers are considering single-dose vaccination as an alternative strategy. Using a mathematical model combined ...with optimization algorithms, we determined optimal allocation strategies with one and two doses of vaccine under various degrees of viral transmission. Under low transmission, we show that the optimal allocation of vaccine vitally depends on the single-dose efficacy. With high single-dose efficacy, single-dose vaccination is optimal, preventing up to 22% more deaths than a strategy prioritizing two-dose vaccination for older adults. With low or moderate single-dose efficacy, mixed vaccination campaigns with complete coverage of older adults are optimal. However, with modest or high transmission, vaccinating older adults first with two doses is best, preventing up to 41% more deaths than a single-dose vaccination given across all adult populations. Our work suggests that it is imperative to determine the efficacy and durability of single-dose vaccines, as mixed or single-dose vaccination campaigns may have the potential to contain the pandemic much more quickly.
A global stockpile of oral cholera vaccine (OCV) was established in 2013 for use in outbreak response and are licensed as two-dose regimens. Vaccine availability, however, remains limited. Previous ...studies have found that a single dose of OCV may provide substantial protection against cholera.
Using a mathematical model with two age groups paired with optimization algorithms, we determine the optimal vaccination strategy with one and two doses of vaccine to minimize cumulative overall infections, symptomatic infections, and deaths. We explore counterfactual vaccination scenarios in three distinct settings: Maela, the largest refugee camp in Thailand, with high in- and out-migration; N'Djamena, Chad, a densely populated region; and Haiti, where departments are connected by rivers and roads.
Over the short term under limited vaccine supply, the optimal strategies for all objectives prioritize one dose to the older age group (over five years old), irrespective of setting and level of vaccination coverage. As more vaccine becomes available, it is optimal to administer a second dose for long-term protection. With enough vaccine to cover the whole population with one dose, the optimal strategies can avert up to 30% to 90% of deaths and 36% to 92% of symptomatic infections across the three settings over one year. The one-dose optimal strategies can avert 1.2 to 1.8 times as many cases and deaths compared to the standard two-dose strategy.
In an outbreak setting, speedy vaccination campaigns with a single dose of OCV is likely to avert more cases and deaths than a two-dose pro-rata campaign under a limited vaccine supply.
Trial results for two COVID-19 vaccines suggest at least 90% efficacy against symptomatic disease (VE
). It remains unknown whether this efficacy is mediated by lowering SARS-CoV-2 infection ...susceptibility (VE
) or development of symptoms after infection (VE
). We aim to assess and compare the population impact of vaccines with different efficacy profiles (VE
and VE
) satisfying licensure criteria. We developed a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington. Rollout scenarios starting December 2020 were simulated with combinations of VE
and VE
resulting in up to 100% VE
. We assumed no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported. Rollouts of 1 M vaccinations (5000 daily) using vaccines with 50% VE
are projected to prevent 23-46% of infections and 31-46% of deaths over 1 year. In comparison, vaccines with 90% VE
are projected to prevent 37-64% of infections and 46-64% of deaths over 1 year. In both cases, there is a greater reduction if VE
is mediated mostly by VE
. The use of a "symptom reducing" vaccine will require twice as many people vaccinated than a "susceptibility reducing" vaccine with the same 90% VE
to prevent 50% of the infections and death over 1 year. Delaying the start of the vaccination by 3 months decreases the expected population impact by more than 50%. Vaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.
Pandemic influenza A (H1N1) 2009 (pandemic H1N1) is spreading throughout the planet. It has become the dominant strain in the Southern Hemisphere, where the influenza season has now ended. Here, on ...the basis of reported case clusters in the United States, we estimated the household secondary attack rate for pandemic H1N1 to be 27.3% 95% confidence interval (CI) from 12.2% to 50.5%. From a school outbreak, we estimated that a typical schoolchild infects 2.4 (95% CI from 1.8 to 3.2) other children within the school. We estimated the basic reproductive number, R₀, to range from 1.3 to 1.7 and the generation interval to range from 2.6 to 3.2 days. We used a simulation model to evaluate the effectiveness of vaccination strategies in the United States for fall 2009. If a vaccine were available soon enough, vaccination of children, followed by adults, reaching 70% overall coverage, in addition to high-risk and essential workforce groups, could mitigate a severe epidemic.
Despite the development of safe and effective vaccines, effective treatments for COVID-19 disease are still urgently needed. Several antiviral drugs have shown to be effective in reducing progression ...of COVID-19 disease.
In the present work, we use an agent-based mathematical model to assess the potential population impact of the use of antiviral treatments in four countries with different demographic structure and current levels of vaccination coverage: Kenya, Mexico, United States (US) and Belgium. We analyzed antiviral effects on reducing hospitalization and death, and potential antiviral effects on reducing transmission. For each country, we varied daily treatment initiation rate (DTIR) and antiviral effect in reducing transmission (AVT).
Irrespective of location and AVT, widespread antiviral treatment of symptomatic adult infections (20% DTIR) prevented the majority of COVID-19 deaths, and recruiting 6% of all adult symptomatic infections daily reduced mortality by over 20% in all countries. Furthermore, our model projected that targeting antiviral treatment to the oldest age group (65 years old and older, DTIR of 20%) can prevent over 30% of deaths. Our results suggest that early antiviral treatment (as soon as possible after inception of infection) is needed to mitigate transmission, preventing 50% more infections compared to late treatment (started 3 to 5 days after symptoms onset). Our results highlight the synergistic effect of vaccination and antiviral treatment: as the vaccination rate increases, antivirals have a larger relative impact on population transmission. Finally, our model projects that even in highly vaccinated populations, adding antiviral treatment can be extremely helpful to mitigate COVID-19 deaths.
These results suggest that antiviral treatments can become a strategic tool that, in combination with vaccination, can significantly reduce COVID-19 hospitalizations and deaths and can help control SARS-CoV-2 transmission.
Pandemic influenza A(H1N1) 2009 began spreading around the globe in April of 2009 and vaccination started in October of 2009. In most countries, by the time vaccination started, the second wave of ...pandemic H1N1 2009 was already under way. With limited supplies of vaccine, we are left to question whether it may be a good strategy to vaccinate the high-transmission groups earlier in the epidemic, but it might be a better use of resources to protect instead the high-risk groups later in the epidemic. To answer this question, we develop a deterministic epidemic model with two age-groups (children and adults) and further subdivide each age group in low and high risk.
We COMPARE optimal vaccination strategies started at various points in time in two different.
a population in a developed country where children account for 24% of the population, and a population in a less developed country where children make up the majority of the population, 55%. For each of these populations, we minimize mortality or hospitalizations and we find an optimal vaccination strategy that gives the best vaccine allocation given a starting vaccination time and vaccine coverage level. We find that population structure is an important factor in determining the optimal vaccine distribution. Moreover, the optimal policy is dynamic as there is a switch in the optimal vaccination strategy at some time point just before the peak of the epidemic. For instance, with 25% vaccine coverage, it is better to protect the high-transmission groups before this point, but it is optimal to protect the most vulnerable groups afterward.
Choosing the optimal strategy before or early in the epidemic makes an important difference in minimizing the number of influenza infections, and consequently the number of influenza deaths or hospitalizations, but the optimal strategy makes little difference after the peak.
There are many COVID-19 vaccines currently available, however, Low- and middle-income countries (LMIC) still have large proportions of their populations unvaccinated. Decision-makers must decide how ...to effectively allocate available vaccines (e.g. boosters or primary series vaccination, which age groups to target) but LMIC often lack the resources to undergo quantitative analyses of vaccine allocation, resulting in ad-hoc policies. We developed Covid19Vaxplorer (https://covid19vaxplorer.fredhutch.org/), a free, user-friendly online tool that simulates region-specific COVID-19 epidemics in conjunction with vaccination with the purpose of providing public health officials worldwide with a tool for vaccine allocation planning and comparison. We developed an age-structured mathematical model of SARS-CoV-2 transmission and COVID-19 vaccination. The model considers vaccination with up to three different vaccine products, primary series and boosters. We simulated partial immunity derived from waning of natural infection and vaccination. The model is embedded in an online tool, Covid19Vaxplorer that was optimized for its ease of use. By prompting users to fill information through several windows to input local parameters (e.g. cumulative and current prevalence), epidemiological parameters (e.g basic reproduction number, current social distancing interventions), vaccine parameters (e.g. vaccine efficacy, duration of immunity) and vaccine allocation (both by age groups and by vaccination status). Covid19Vaxplorer connects the user to the mathematical model and simulates, in real time, region-specific epidemics. The tool then produces key outcomes including expected numbers of deaths, hospitalizations and cases, with the possibility of simulating several scenarios of vaccine allocation at once for a side-by-side comparison. We provide two usage examples of Covid19Vaxplorer for vaccine allocation in Haiti and Afghanistan, which had as of Spring 2023, 2% and 33% of their populations vaccinated, and show that for these particular examples, using available vaccine as primary series vaccinations prevents more deaths than using them as boosters.
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