Epidemic dynamics of respiratory syncytial virus in current and future climates.

A key question for infectious disease dynamics is the impact of the climate on future burden. Here, we evaluate the climate drivers of respiratory syncytial virus (RSV), an important determinant of disease in young children. We combine a dataset of county-level observations from the US with state-level observations from Mexico, spanning much of the global range of climatological conditions. Using a combination of nonlinear epidemic models with statistical techniques, we find consistent patterns of climate drivers at a continental scale explaining latitudinal differences in the dynamics and timing of local epidemics. Strikingly, estimated effects of precipitation and humidity on transmission mirror prior results for influenza. We couple our model with projections for future climate, to show that temperature-driven increases to humidity may lead to a northward shift in the dynamic patterns observed and that the likelihood of severe outbreaks of RSV hinges on projections for extreme rainfall

Mortality in Puerto Rico after Hurricane Maria

BACKGROUND Quantifying the effect of natural disasters on society is critical for recovery of public health services and infrastructure. The death toll can be difficult to assess in the aftermath of a major disaster. In September 2017, Hurricane Maria caused massive infrastructural damage to Puerto Rico, but its effect on mortality remains contentious. The official death count is 64. METHODS Using a representative, stratified sample, we surveyed 3299 randomly chosen households across Puerto Rico to produce an independent estimate of all-cause mortality after the hurricane. Respondents were asked about displacement, infrastructure loss, and causes of death. We calculated excess deaths by comparing our estimated post-hurricane mortality rate with official rates for the same period in 2016. RESULTS From the survey data, we estimated a mortality rate of 14.3 deaths (95% confidence interval [CI], 9.8 to 18.9) per 1000 persons from September 20 through December 31, 2017. This rate yielded a total of 4645 excess deaths during this period (95% CI, 793 to 8498), equivalent to a 62% increase in the mortality rate as compared with the same period in 2016. However, this number is likely to be an underestimate because of survivor bias. The mortality rate remained high through the end of December 2017, and one third of the deaths were attributed to delayed or interrupted health care. Hurricane-related migration was substantial. CONCLUSIONS This household-based survey suggests that the number of excess deaths related to Hurricane Maria in Puerto Rico is more than 70 times the official estimate. (Funded by the Harvard T.H. Chan School of Public Health and others.

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A map for all seasons: Tracking transmission dynamics and mortality of childhood infections through the year

Among infectious diseases, the dynamics of directly-transmitted, immunizing childhood infections are arguably the best understood. Yet, there are key gaps in our understanding of the complex interactions between disease dynamics, demography, socioeconomic factors, and the environment. This dissertation addresses some of these gaps. In the first chapter, I study six common childhood infections in Mexico, and show that the aggregation of children in schools is a key determinant of the population-level dynamics of these infections. In addition, for some pathogens, I find evidence for the role of socioeconomic and environmental drivers. My findings from Mexico add to a body of research that has shown that childhood infection dynamics are influenced by age-dependency in contact rates. This first analysis was grounded in the oft-used Time-series Susceptible-Infected-Recovered (TSIR) model, which assumes mass-action or homogeneous mixing, yet is able to accurately predict dynamics of childhood infections through forward simulation in many contexts. This is remarkable, considering that childhood infection dynamics are inherently age-structured. In the second chapter, I show, theoretically and using simulations, that the success of the TSIR lies in the fact that age structure can be collapsed to a simple mass-action mixing model, by allowing the transmission rates to vary over time. Finally, in the last chapter, I turn to the mortality burden of measles, a major cause of childhood morbidity and mortality in many parts of the world. I use historical mortality data from Matlab, Bangladesh, and a mechanistic model of measles transmission, to quantify changes in the case-fatality rate - an important component of disease burden - in a population that experienced war and famine. My results suggest that the period of turmoil during and after the war, and the sustained effects of the famine, is likely to have contributed to the high fatality burden of the 1976 measles outbreak in Matlab. Overall, the findings of this dissertation strengthen our ability to model and accurately predict the dynamics of directly-transmitted, immunizing, childhood infections, and to design effective control strategies. This work also opens up a number of intriguing directions for further work, including in disentangling climatic drivers of transmission

Quantifying population contact patterns in the United States during the COVID-19 pandemic.

SARS-CoV-2 is transmitted primarily through close, person-to-person interactions. Physical distancing policies can control the spread of SARS-CoV-2 by reducing the amount of these interactions in a population. Here, we report results from four waves of contact surveys designed to quantify the impact of these policies during the COVID-19 pandemic in the United States. We surveyed 9,743 respondents between March 22 and September 26, 2020. We find that interpersonal contact has been dramatically reduced in the US, with an 82% (95%CI: 80%-83%) reduction in the average number of daily contacts observed during the first wave compared to pre-pandemic levels. However, we find increases in contact rates over the subsequent waves. We also find that certain demographic groups, including people under 45 and males, have significantly higher contact rates than the rest of the population. Tracking these changes can provide rapid assessments of the impact of physical distancing policies and help to identify at-risk populations

Quantifying population contact patterns in the United States during the COVID-19 pandemic.

SARS-CoV-2 is transmitted primarily through close, person-to-person interactions. Physical distancing policies can control the spread of SARS-CoV-2 by reducing the amount of these interactions in a population. Here, we report results from four waves of contact surveys designed to quantify the impact of these policies during the COVID-19 pandemic in the United States. We surveyed 9,743 respondents between March 22 and September 26, 2020. We find that interpersonal contact has been dramatically reduced in the US, with an 82% (95%CI: 80%-83%) reduction in the average number of daily contacts observed during the first wave compared to pre-pandemic levels. However, we find increases in contact rates over the subsequent waves. We also find that certain demographic groups, including people under 45 and males, have significantly higher contact rates than the rest of the population. Tracking these changes can provide rapid assessments of the impact of physical distancing policies and help to identify at-risk populations

Evaluating primary and booster vaccination prioritization strategies for COVID-19 by age and high-contact employment status using data from contact surveys

The debate around vaccine prioritization for COVID-19 has revolved around balancing the benefits from: (1) the direct protection conferred by the vaccine amongst those at highest risk of severe disease outcomes, and (2) the indirect protection through vaccinating those that are at highest risk of being infected and of transmitting the virus. While adults aged 65+ are at highest risk for severe disease and death from COVID-19, essential service and other in-person workers with greater rates of contact may be at higher risk of acquiring and transmitting SARS-CoV-2. Unfortunately, there have been relatively little data available to understand heterogeneity in contact rates and risk across these demographic groups. Here, we retrospectively analyze and evaluate vaccination prioritization strategies by age and worker status. We use a mathematical model of SARS-CoV-2 transmission and uniquely detailed contact data collected as part of the Berkeley Interpersonal Contact Survey to evaluate five vaccination prioritization strategies: (1) prioritizing only adults over age 65, (2) prioritizing only high-contact workers, (3) splitting prioritization between adults 65+ and high-contact workers, (4) tiered prioritization of adults over age 65 followed by high-contact workers, and (5) tiered prioritization of high-contact workers followed by adults 65+. We find that for the primary two-dose vaccination schedule, assuming 70% uptake, a tiered roll-out that first prioritizes adults 65+ averts the most deaths (31% fewer deaths compared to a no-vaccination scenario) while a tiered roll-out that prioritizes high contact workers averts the most number of clinical infections (14% fewer clinical infections compared to a no-vaccination scenario). We also consider prioritization strategies for booster doses during a subsequent outbreak of a hypothetical new SARS-CoV-2 variant. We find that a tiered roll-out that prioritizes adults 65+ for booster doses consistently averts the most deaths, and it may also avert the most number of clinical cases depending on the epidemiology of the SARS-CoV-2 variant and the vaccine efficacy