Schistosoma mansoni miracidia: revisiting motility and survival parameters for improved computational modelling.

Schistosoma mansoni is the main causative agent of intestinal schistosomiasis which affects millions of people worldwide. At the larval stage, miracidia are released into bodies of water where they utilize their motility to successfully infect their intermediate host, snails. Here, we revisit the motility and survival of S. mansoni miracidia throughout its life span. Briefly, miracidia motility was monitored at 30-min and 60-min intervals under the presence/absence of natural/artificial light. Based on a subjective evaluation of activity, body shape and transparency, 6 categories of miracidia activity were established from its fully active stage to its immobile larva stage. The estimated life span of miracidia was 5.8 and 3.5 h in the experiments with 60-min and 30-min observation intervals, respectively. Death was defined by an absence of cilia and body movement. When mobility was used as a proxy for infectivity, infective miracidia were detected at 2.5 and 4.5 h, respectively. The present miracidia motility and survival re-evaluation supports parameters optimization for computational modelling of schistosomiasis transmission dynamics. Target control interventions, especially at late stages next to transmission interruption, may greatly benefit from improved modelling studies.

Impact of nonpharmaceutical strategies on trends of COVID-19 in São Paulo State.

Interrupted time series analyses were conducted to measure the impact of social distancing policies (instituted on March 22, 2020) and of subsequent mandatory masking in the community (instituted on May 4, 2020) on the incidence and effective reproductive number of COVID-19 in São Paulo State, Brazil. Overall, the impact of social distancing both on incidence and Rt was greater than the incremental effect of mandatory masking. Those findings may reflect either a small impact of face masking or the loosening of social distancing after mandatory use of masks.

Assessing the effects of diagnostic sensitivity on schistosomiasis dynamics.

Schistosomiasis is a parasite infection that affects millions of people around the world. It is endemic in 13 different states in Brazil and responsible for increasing morbidity in the population. One of its main characteristics is a heterogeneous distribution of worm burden in the human population, which makes the diagnosis difficult. We aimed to investigate how the sensitivity of the diagnostic method may contribute to successful control interventions against infections in a population. In order to do that, we present an ordinary differential equations model that considers three levels of worm burden in the human population, a snail population, and a miracidium reservoir. Through a steady-state analysis and its local stability, we show how this worm-burden heterogeneity can be responsible for the persistence of infection, especially due to reinfection in the highest level of worm burden. The analysis highlights sensitive diagnosis, besides treatment and sanitary improvements, as a key factor for schistosomiasis transmission control.

Projecting the impact of a two-dose COVID-19 vaccination campaign in Ontario, Canada.

BACKGROUND: A number of highly effective COVID-19 vaccines have been developed and approved for mass vaccination. We evaluated the impact of vaccination on COVID-19 outbreak and disease outcomes in Ontario, Canada. METHODS: We used an agent-based transmission model and parameterized it with COVID-19 characteristics, demographics of Ontario, and age-specific clinical outcomes. We implemented a two-dose vaccination program according to tested schedules in clinical trials for Pfizer-BioNTech and Moderna vaccines, prioritizing healthcare workers, individuals with comorbidities, and those aged 65 and older. Daily vaccination rate was parameterized based on vaccine administration data. Using estimates of vaccine efficacy, we projected the impact of vaccination on the overall attack rate, hospitalizations, and deaths. We further investigated the effect of increased daily contacts at different stages during vaccination campaigns on outbreak control. RESULTS: Maintaining non-pharmaceutical interventions (NPIs) with an average of 74% reduction in daily contacts, vaccination with Pfizer-BioNTech and Moderna vaccines was projected to reduce hospitalizations by 27.3% (95% CrI: 22.3% - 32.4%) and 27.0% (95% CrI: 21.9% - 32.6%), respectively, over a one-year time horizon. The largest benefits of vaccination were observed in preventing deaths with reductions of 31.5% (95% CrI: 22.5% - 39.7%) and 31.9% (95% CrI: 22.0% - 41.4%) for Pfizer-BioNTech and Moderna vaccines, respectively, compared to no vaccination. We found that an increase of only 10% in daily contacts at the end of lockdown, when vaccination coverage with only one dose was 6%, would trigger a surge in the outbreak. Early relaxation of population-wide measures could lead to a substantial increase in the number of infections, potentially reaching levels observed during the peak of the second wave in Ontario. CONCLUSIONS: Vaccination can substantially mitigate ongoing COVID-19 outbreaks. Sustaining population-wide NPIs, to allow for a sufficient increase in population-level immunity through vaccination, is essential to prevent future outbreaks.

The use of health geography modeling to understand early dispersion of COVID-19 in São Paulo, Brazil.

Public health policies to contain the spread of COVID-19 rely mainly on non-pharmacological measures. Those measures, especially social distancing, are a challenge for developing countries, such as Brazil. In São Paulo, the most populous state in Brazil (45 million inhabitants), most COVID-19 cases up to April 18th were reported in the Capital and metropolitan area. However, the inner municipalities, where 20 million people live, are also at risk. As governmental authorities discuss the loosening of measures for restricting population mobility, it is urgent to analyze the routes of dispersion of COVID-19 in São Paulo territory. We hypothesize that urban hierarchy is the main responsible for the disease spreading, and we identify the hotspots and the main routes of virus movement from the metropolis to the inner state. In this ecological study, we use geographic models of population mobility to check for patterns for the spread of SARS-CoV-2 infection. We identify two patterns based on surveillance data: one by contiguous diffusion from the capital metropolitan area, and the other hierarchical with long-distance spread through major highways that connects São Paulo city with cities of regional relevance. This knowledge can provide real-time responses to support public health strategies, optimizing the use of resources in order to minimize disease impact on population and economy.

Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada.

The novel coronavirus disease 2019 (COVID-19) has caused severe outbreaks in Canadian long-term care facilities (LTCFs). In Canada, over 80% of COVID-19 deaths during the first pandemic wave occurred in LTCFs. We sought to evaluate the effect of mitigation measures in LTCFs including frequent testing of staff, and vaccination of staff and residents. We developed an agent-based transmission model and parameterized it with disease-specific estimates, temporal sensitivity of nasopharyngeal and saliva testing, results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada. Characteristics of staff and residents, including contact patterns, were integrated into the model with age-dependent risk of hospitalization and death. Estimates of infection and outcomes were obtained and 95% credible intervals were generated using a bias-corrected and accelerated bootstrap method. Weekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 25.9% (95% CrI: 23.3% - 28.3%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2-4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 95.9% (95% CrI: 95.4% - 96.3%) and 95.8% (95% CrI: 95.5% - 96.1%), respectively, over 200 days from the start of vaccination. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.

Impact of nonpharmaceutical strategies on trends of COVID-19 in São Paulo State

ABSTRACT Interrupted time series analyses were conducted to measure the impact of social distancing policies (instituted on March 22, 2020) and of subsequent mandatory masking in the community (instituted on May 4, 2020) on the incidence and effective reproductive number of COVID-19 in São Paulo State, Brazil. Overall, the impact of social distancing both on incidence and Rt was greater than the incremental effect of mandatory masking. Those findings may reflect either a small impact of face masking or the loosening of social distancing after mandatory use of masks.

Two hundred days of COVID-19 in São Paulo State, Brazil.

Two hundred days after the first confirmed case of COVID-19 in Brazil, the epidemic has rapidly spread in metropolitan areas and advanced throughout the countryside. We followed the temporal epidemic pattern at São Paulo State, the most populous of the country, the first to have a confirmed case of COVID-19, and the one with the most significant number of cases until now. We analysed the number of new cases per day in each regional health department and calculated the effective reproduction number (Rt) over time. Social distance measures, along with improvement in testing and isolating positive cases, general population mask-wearing and standard health security protocols for essential and non-essential activities, were adopted and impacted on slowing down epidemic velocity but were insufficient to stop transmission.

Projecting influenza vaccine effectiveness: A simulation study.

The impact of influenza vaccination is largely measured by estimating vaccine effectiveness (VE), which vary in different seasons. Strain mutations and waning immunity present two key mechanisms affecting VE. We sought to quantify the relative effect of these mechanisms by projecting VE and the reduction of illness due to vaccination. We developed a stochastic age-structured agent-based simulation model of influenza transmission dynamics to encapsulate intraseason waning of immunity post-vaccination, and mutation-induced antigenic distance between circulating strains and vaccine strains. Parameterizing the model with published estimates, we projected the temporal and overall VE during an epidemic season, and estimated the reduction of infection for high (70%) and low (30%) vaccine efficacies to reflect the levels of vaccine-induced protection in randomized control trials. Both temporal and overall VE decreased as the attack rate increased, with lower median values for epidemics starting with strains that were antigenically more distant from vaccine strains. We observed a higher rate of temporal decline with considerably lower median values of the overall VE in the presence of intraseason waning of immunity compared with only the antigenic distance effect. The highest benefit of vaccination in preventing influenza infection was achieved at moderate attack rates in the range of 6%-15%. The results show that even when VE is relatively low in the population and almost negligible for older age groups (i.e., 50+ years), vaccination can still prevent significant illness in high-risk individuals; thereby reducing healthcare resource utilization and economic burden. Our study indicates that early vaccination remains an important strategy for alleviating the burden of seasonal influenza. Policy discussions on optimal timing of vaccination to reduce the effect of intraseason waning of immunity should be considered in the context of strain mutations within the epidemic course.

Risk of influenza infection with low vaccine effectiveness: the role of avoidance behaviour.

Low vaccine-effectiveness has been recognised as a key factor undermining efforts to improve strategies and uptake of seasonal influenza vaccination. Aiming to prevent disease transmission, vaccination may influence the perceived risk-of-infection and, therefore, alter the individual-level behavioural responses, such as the avoidance of contact with infectious cases. We asked how the avoidance behaviour of vaccinated individuals changes disease dynamics, and specifically the epidemic size, in the context of imperfect vaccination. For this purpose, we developed an agent-based simulation model, and parameterised it with published estimates and relevant databases for population demographics and agent characteristics. Encapsulating an age-stratified structure, we evaluated the per-contact risk-of-infection and estimated the epidemic size. Our results show that vaccination could lead to a larger epidemic size if the level of avoidance behaviour in vaccinated individuals reduces below that of susceptible individuals. Furthermore, the risk-of-infection in vaccinated individuals, which follows the pattern of age-dependent frailty index of the population, increases for older age groups, and may reach, or even exceed, the risk-of-infection in susceptible individuals. Our findings indicate that low engagement in avoidance behaviour can potentially offset the benefits of vaccination even for vaccines with high effectiveness. While highlighting the protective effects of vaccination, seasonal influenza immunisation programmes should enhance strategies to promote avoidance behaviour despite being vaccinated.

Cost-effectiveness of a potential Zika vaccine candidate: a case study for Colombia.

BACKGROUND: A number of Zika vaccine platforms are currently being investigated, some of which have entered clinical trials. We sought to evaluate the cost-effectiveness of a potential Zika vaccine candidate under the WHO Vaccine Target Product Profile for outbreak response, prioritizing women of reproductive age to prevent microcephaly and other neurological disorders. METHODS: Using an agent-based simulation model of ZIKV transmission dynamics in a Colombian population setting, we conducted cost-effectiveness analysis with and without pre-existing herd immunity. The model was parameterized with estimates associated with ZIKV infection, risks of microcephaly in different trimesters, direct medical costs, and vaccination costs. We assumed that a single dose of vaccine provides a protection efficacy in the range 60% to 90% against infection. Cost-effectiveness analysis was conducted from a government perspective. RESULTS: Under a favorable scenario when the reproduction number is relatively low (R0 = 2.2) and the relative transmissibility of asymptomatic infection is 10% compared with symptomatic infection, a vaccine is cost-saving (with negative incremental cost-effective ratio; ICER) for vaccination costs up to US$6 per individual without herd immunity, and up to US$4 per individual with 8% herd immunity. For positive ICER values, vaccination is highly cost-effective for vaccination costs up to US$10 (US$7) in the respective scenarios with the willingness-to-pay of US$6610 per disability-adjusted life-year, corresponding to the average per capita GDP of Colombia between 2013 and 2017. Our results indicate that the effect of other control measures targeted to reduce ZIKV transmission decreases the range of vaccination costs for cost-effectiveness due to reduced returns of vaccine-induced herd immunity. In all scenarios investigated, the median reduction of microcephaly exceeded 64% with vaccination. CONCLUSIONS: Our study suggests that a Zika vaccine with protection efficacy as low as 60% could significantly reduce the incidence of microcephaly. From a government perspective, Zika vaccination is highly cost-effective, and even cost-saving in Colombia if vaccination costs per individual is sufficiently low. Efficacy data from clinical trials and number of vaccine doses will be important requirements in future studies to refine our estimates, and conduct similar studies in other at-risk populations.