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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, coronavirus disease 2019 (COVID-19), has caused a devastating pandemic worldwide. Here, we explain basic concepts underlying the transition from an epidemic to an endemic state, where a pathogen is stably maintained in a population. We discuss how the number of infections and the severity of disease change in the transition from the epidemic to the endemic phase and consider the implications of this transition in the context of COVID-19.

Purpose The aim of this study was to measure the effect of a multicomponent human papillomavirus (HPV) vaccine promotion campaign on adolescent HPV vaccine uptake at school-based health centers (SBHCs) in Seattle, WA. Methods Youth-led HPV vaccine promotion campaigns were introduced in 2016 in 13 schools with SBHCs in Seattle. Five other schools with SBHCs served as controls. Vaccination records for students were obtained from the Washington Immunization Information System from September 2012 to August 2018. We compared increase in HPV vaccine uptake in SBHCs between 1) intervention and control schools, and 2) pre- and post-intervention periods in intervention schools using generalized estimating equations. Results HPV vaccine uptake was high at baseline among students that use SBHCs for vaccines and has steadily increased between 2012 and 2018. Implementing the promotion campaign resulted in 14% higher (95% Confidence Interval (CI): 1%, 30%) HPV vaccine uptake in intervention SBHCs compared to control SBHCs, adjusting for time and confounders. Comparing pre-and post-intervention periods in intervention SBHCs, HPV vaccine uptake was 14% higher (95% CI: −4%, 35%) in the post-intervention period. SBHCs that received more active intervention activities saw 9% higher (95% CI: 1%, 21%) vaccine uptake compared to those that received passive intervention. Conclusion The vaccination promotion program implemented in a school-based setting resulted in higher HPV vaccine uptake in the post-intervention period compared to pre-intervention period, but this increase was not statistically significant. Even so, schools that received more intervention activities for longer periods of time had higher HPV vaccine uptake.

The current pediatric vaccination program in England and Wales administers Live-Attenuated Influenza Vaccine (LAIV) to children ages 2-16 years old. Annual administration of LAIV to this age group is costly and poses substantial logistical issues. This study aims to evaluate the cost-effectiveness of prioritizing vaccination to age groups within the 2-16 year old age range to mitigate the operational and resource challenges of the current strategy. We performed economic evaluations comparing the influenza vaccination program from 1995-2013 to seven alternative strategies targeted at low risk individuals along the school age divisions Preschool (2-4 years old), Primary school (5-11 years old), and Secondary school (12-16 years old). These extensions are evaluated incrementally on the status quo scenario (vaccinating subgroups at high risk of influenza-related complications and individuals 65+ years old). Impact of vaccination was assessed using a transmission model from a previously published study and updated with new data. At all levels of coverage, all strategies had a 100% probability of being cost-effective at the current National Health Service threshold, £20,000/QALY gained. The incremental analysis demonstrated vaccinating Primary School children was the most cost-efficient strategy compared incrementally against others with an Incremental Cost-Effectiveness Ratio of £639 spent per QALY gained (Net Benefit: 404 M£ [155, 795]). When coverage was varied between 30%, 55%, and 70% strategies which included Primary school children had a higher probability of being cost-effective at lower willingness-to-pay levels. Although children were the vaccine target the majority of QALY gains occurred in the 25-44 years old and 65+ age groups. Influenza strain A/H3N2 incurred the greatest costs and QALYs lost regardless of which strategy was used. Improvement could be made to the current LAIV pediatric vaccination strategy by eliminating vaccination of 2-4 year olds and focusing on school-based delivery to Primary and Secondary school children in tandem.

Influenza A virus subtype H5N1 has been a public health concern for almost 20years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: (1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and (2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48-0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32-0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15mcg had the highest estimated theoretical vaccine efficacy: Dose (1) 45% (95% CI: 36-57%), 53% (95% CI: 42-63%) and 55% (95% CI: 44-64%), respectively and Dose (2) 93% (95% CI: 89-96%), 97% (95% CI: 95-98%) and 97% (95% CI: 96-100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect individuals against a potential avian influenza pandemic.

Avian influenza A (H7N9), emerged in China in April 2013, sparking fears of a new, highly pathogenic, influenza pandemic. In addition, avian influenza A (H5N1) continues to circulate and remains a threat. Currently, influenza H7N9 vaccines are being tested to be stockpiled along with H5N1 vaccines. These vaccines require two doses, 21 days apart, for maximal protection. We developed a mathematical model to evaluate two possible strategies for allocating limited vaccine supplies: a one-dose strategy, where a larger number of people are vaccinated with a single dose, or a two-dose strategy, where half as many people are vaccinated with two doses. We prove that there is a threshold in the level of protection obtained after the first dose, below which vaccinating with two doses results in a lower illness attack rate than with the one-dose strategy; but above the threshold, the one-dose strategy would be better. For reactive vaccination, we show that the optimal use of vaccine depends on several parameters, with the most important one being the level of protection obtained after the first dose. We describe how these vaccine dosing strategies can be integrated into effective pandemic control plans.

Recent advances in typhoid vaccine, and consideration of support from Gavi, the Vaccine Alliance, raise the possibility that some endemic countries will introduce typhoid vaccine into public immunization programs. This decision, however, is limited by lack of definitive information on disease burden. We propose use of a vaccine probe study approach. This approach would more clearly assess the total burden of typhoid across different syndromic groups and account for lack of access to care, poor diagnostics, incomplete laboratory testing, lack of mortality and intestinal perforation surveillance, and increasing antibiotic resistance. We propose a cluster randomized trial design using a mass immunization campaign among all age groups, with monitoring over a 4-year period of a variety of outcomes. The primary outcome would be the vaccine preventable disease incidence of prolonged fever hospitalization. Sample size calculations suggest that such a study would be feasible over a reasonable set of assumptions.

Summary Background The 2014 epidemic of Ebola virus disease in parts of west Africa defines an unprecedented health threat. We developed a model of Ebola virus transmission that integrates detailed geographical and demographic data from Liberia to overcome the limitations of non-spatial approaches in projecting the disease dynamics and assessing non-pharmaceutical control interventions. Methods We modelled the movements of individuals, including patients not infected with Ebola virus, seeking assistance in health-care facilities, the movements of individuals taking care of patients infected with Ebola virus not admitted to hospital, and the attendance of funerals. Individuals were grouped into randomly assigned households (size based on Demographic Health Survey data) that were geographically placed to match population density estimates on a grid of 3157 cells covering the country. The spatial agent-based model was calibrated with a Markov chain Monte Carlo approach. The model was used to estimate Ebola virus transmission parameters and investigate the effectiveness of interventions such as availability of Ebola treatment units, safe burials procedures, and household protection kits. Findings Up to Aug 16, 2014, we estimated that 38·3% of infections (95% CI 17·4–76·4) were acquired in hospitals, 30·7% (14·1–46·4) in households, and 8·6% (3·2–11·8) while participating in funerals. We noted that the movement and mixing, in hospitals at the early stage of the epidemic, of patients infected with Ebola virus and those not infected was a sufficient driver of the reported pattern of spatial spread. The subsequent decrease of incidence at country and county level is attributable to the increasing availability of Ebola treatment units (which in turn contributed to drastically decreased hospital transmission), safe burials, and distribution of household protection kits. Interpretation The model allows assessment of intervention options and the understanding of their role in the decrease in incidence reported since Sept 7, 2014. High-quality data (eg, to estimate household secondary attack rate, contact patterns within hospitals, and effects of ongoing interventions) are needed to reduce uncertainty in model estimates. Funding US Defense Threat Reduction Agency, US National Institutes of Health.

Objectives: To project the potential economic impact of pandemic influenza mitigation strategies from a societal perspective in the United States. Methods: We use a stochastic agent-based model to simulate pandemic influenza in the community. We compare 17 strategies: targeted antiviral prophylaxis (TAP) alone and in combination with school closure as well as prevaccination. Results: In the absence of intervention, we predict a 50% attack rate with an economic impact of $187 per capita as loss to society. Full TAP (FTAP) is the most effective single strategy, reducing number of cases by 54% at the lowest cost to society ($127 per capita). Prevaccination reduces number of cases by 48% and is the second least costly alternative ($140 per capita). Adding school closure to FTAP or prevaccination further improves health outcomes but increases total cost to society by approximately $2700 per capita. Conclusion: FTAP is an effective and cost-saving measure for mitigating pandemic influenza.

Summary Background A bioterrorist release of smallpox is a constant threat to the population of the USA and other countries. Design A stochastic simulation model of the spread of smallpox due to a large bioterrorist attack in a structured population was constructed. Disease natural history parameter estimates, time lines of behavioral activities, and control scenarios were based on the literature and on the consensus opinion of a panel of smallpox experts. Results The authors found that surveillance and containment, i.e., isolation of known cases and vaccination of their close contacts, would be sufficient to effectively contain a large intentional smallpox release. Given that surveillance and containment measures are in place, preemptive vaccination of hospital workers would further reduce the number of smallpox cases and deaths but would require large numbers of prevaccinations. High levels of reactive mass vaccination after the outbreak begins would further reduce smallpox cases and deaths to a minimum, but would require even larger numbers of vaccinations. Reactive closure of schools would have a minimal effect. Conclusion A rapid and well-organized response to a bioterrorist attack would be necessary for effective surveillance and containment to control spread. Preemptive vaccination of hospital workers and reactive vaccination of the target population would further limit spread, but at a cost of many more vaccinated. This cost in resources and potential harm due to vaccination will have to be weighed against the potential benefits should an attack occur. Prevaccination of the general population is not necessary.

In the event of pandemic influenza, only limited supplies of vaccine may be available. We use stochastic epidemic simulations, genetic algorithms (GA), and random mutation hill climbing (RMHC) to find optimal vaccine distributions to minimize the number of illnesses or deaths in the population, given limited quantities of vaccine. Due to the non-linearity, complexity and stochasticity of the epidemic process, it is not possible to solve for optimal vaccine distributions mathematically. However, we use GA and RMHC to find near optimal vaccine distributions. We model an influenza pandemic that has age-specific illness attack rates similar to the Asian pandemic in 1957-1958 caused by influenza A(H2N2), as well as a distribution similar to the Hong Kong pandemic in 1968-1969 caused by influenza A(H3N2). We find the optimal vaccine distributions given that the number of doses is limited over the range of 10-90% of the population. While GA and RMHC work well in finding optimal vaccine distributions, GA is significantly more efficient than RMHC. We show that the optimal vaccine distribution found by GA and RMHC is up to 84% more effective than random mass vaccination in the mid range of vaccine availability. GA is generalizable to the optimization of stochastic model parameters for other infectious diseases and population structures.

Using a stochastic simulation model of influenza transmission, clinical illness, and economic costs, we estimated the population-wide benefits of routinely vaccinating US children (ages 6 months to 18 years) against influenza. Disease burden was projected to decline as a result of both reduced susceptibility to infection among vaccinees and reductions in disease transmission to others in the community. Vaccination of 20% of children would reduce the total number of influenza cases in the US by 46%; 80% coverage would reduce the total number of cases by 91%. Similar reductions were estimated to occur in influenza-related mortality and economic costs.

We estimated the effect of pertussis vaccination on reducing transmission from vaccinated breakthrough cases from a comprehensive follow-up of a community of 30,000 residents in Niakhar, Senegal. Using a wide spectrum of case definitions, vaccine efficacy was estimated as 1 - the ratio of secondary attack rates (SAR) in all households with cases during the calendar year 1993, a pertussis epidemic year. Vaccine efficacy for infectiousness (VEi) was 85% (95% confidence interval (CI), 46-95%) for children vaccinated with three doses of a whole-cell (WC; 94%) or an acellullar (6%) pertussis vaccine, with pertussis defined as a cough >/=21 days with paroxysms confirmed by culture, serology, or contact with a culture-confirmed person. It was high for all case definitions. Partial vaccination reduced infectiousness. Pertussis vaccination is highly effective in reducing transmission from vaccinated breakthrough cases.

The authors provide an analysis of data from a two-year (1996-1998), multicenter (ten US cities), double-blinded, placebo-controlled influenza vaccine trial in children. The vaccine was the trivalent cold-adapted influenza vaccine. Estimates are made of the vaccine efficacy for susceptibility to culture-confirmed influenza (VE(S)) while taking inter-center variability in the risk of infection into account. Our overall estimate of VE(S) against influenza is 0.92 (95% confidence interval (CI) 0.89-0.94). In addition, for the second year, although the vaccine contained antigen for A/Wuhan-like (H3N2), the estimated VE(S) for epidemic variant A/Sydney-like (H3N2) was 0.89 (95% CI 0.81-0.94). Thus, the vaccine showed a high degree of protection against a variant not closely matched to the vaccine antigen. With regard to natural immunity, an influenza A infection in the first year reduces the estimated risk of an influenza A infection in the second year by a factor of 0.88 (95% CI 0.21-0.98). When comparing year 1 to year 2, there is a negative correlation of -0.50 in the center-specific attack rates in the placebo groups. This is consistent with the theory that natural immunity provides overall community protection to children. The authors argue that mass vaccination of 70% of the children with the cold-adapted influenza vaccine could provide substantial protection to the community at large.

Experimental and theoretical progress in HIV research includes an improved resolution of the spatial heterogeneity and the dynamics (time course and turnover rates) of virus and CD4 + cells. Some of these advances have resulted from the joint work of experimental and theoretecal groups, demonstrating that interdisciplinary research can be fruitful.