Quantifying heterogeneities in arbovirus transmission: Description of the rationale and methodology for a prospective longitudinal study of dengue and Zika virus transmission in Iquitos, Peru (2014-2019).

Current knowledge of dengue virus (DENV) transmission provides only a partial understanding of a complex and dynamic system yielding a public health track record that has more failures than successes. An important part of the problem is that the foundation for contemporary interventions includes a series of longstanding, but untested, assumptions based on a relatively small portion of the human population; i.e., people who are convenient to study because they manifest clinically apparent disease. Approaching dengue from the perspective of people with overt illness has produced an extensive body of useful literature. It has not, however, fully embraced heterogeneities in virus transmission dynamics that are increasingly recognized as key information still missing in the struggle to control the most important insect-transmitted viral infection of humans. Only in the last 20 years have there been significant efforts to carry out comprehensive longitudinal dengue studies. This manuscript provides the rationale and comprehensive, integrated description of the methodology for a five-year longitudinal cohort study based in the tropical city of Iquitos, in the heart of the Peruvian Amazon. Primary data collection for this study was completed in 2019. Although some manuscripts have been published to date, our principal objective here is to support subsequent publications by describing in detail the structure, methodology, and significance of a specific research program. Our project was designed to study people across the entire continuum of disease, with the ultimate goal of quantifying heterogeneities in human variables that affect DENV transmission dynamics and prevention. Because our study design is applicable to other Aedes transmitted viruses, we used it to gain insights into Zika virus (ZIKV) transmission when during the project period ZIKV was introduced and circulated in Iquitos. Our prospective contact cluster investigation design was initiated by detecttion of a person with a symptomatic DENV infection and then followed that person's immediate contacts. This allowed us to monitor individuals at high risk of DENV infection, including people with clinically inapparent and mild infections that are otherwise difficult to detect. We aimed to fill knowledge gaps by defining the contribution to DENV transmission dynamics of (1) the understudied majority of DENV-infected people with inapparent and mild infections and (2) epidemiological, entomological, and socio-behavioral sources of heterogeneity. By accounting for factors underlying variation in each person's contribution to transmission we sought to better determine the type and extent of effort needed to better prevent virus transmission and disease.

Representativeness, Vaccination Uptake, and COVID-19 Clinical Outcomes 2020-2021 in the UK Oxford-Royal College of General Practitioners Research and Surveillance Network: Cohort Profile Summary.

BACKGROUND: The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) is one of Europe's oldest sentinel systems, working with the UK Health Security Agency (UKHSA) and its predecessor bodies for 55 years. Its surveillance report now runs twice weekly, supplemented by online observatories. In addition to conducting sentinel surveillance from a nationally representative group of practices, the RSC is now also providing data for syndromic surveillance. OBJECTIVE: The aim of this study was to describe the cohort profile at the start of the 2021-2022 surveillance season and recent changes to our surveillance practice. METHODS: The RSC's pseudonymized primary care data, linked to hospital and other data, are held in the Oxford-RCGP Clinical Informatics Digital Hub, a Trusted Research Environment. We describe the RSC's cohort profile as of September 2021, divided into a Primary Care Sentinel Cohort (PCSC)-collecting virological and serological specimens-and a larger group of syndromic surveillance general practices (SSGPs). We report changes to our sampling strategy that brings the RSC into alignment with European Centre for Disease Control guidance and then compare our cohort's sociodemographic characteristics with Office for National Statistics data. We further describe influenza and COVID-19 vaccine coverage for the 2020-2021 season (week 40 of 2020 to week 39 of 2021), with the latter differentiated by vaccine brand. Finally, we report COVID-19-related outcomes in terms of hospitalization, intensive care unit (ICU) admission, and death. RESULTS: As a response to COVID-19, the RSC grew from just over 500 PCSC practices in 2019 to 1879 practices in 2021 (PCSC, n=938; SSGP, n=1203). This represents 28.6% of English general practices and 30.59% (17,299,780/56,550,136) of the population. In the reporting period, the PCSC collected >8000 virology and >23,000 serology samples. The RSC population was broadly representative of the national population in terms of age, gender, ethnicity, National Health Service Region, socioeconomic status, obesity, and smoking habit. The RSC captured vaccine coverage data for influenza (n=5.4 million) and COVID-19, reporting dose one (n=11.9 million), two (n=11 million), and three (n=0.4 million) for the latter as well as brand-specific uptake data (AstraZeneca vaccine, n=11.6 million; Pfizer, n=10.8 million; and Moderna, n=0.7 million). The median (IQR) number of COVID-19 hospitalizations and ICU admissions was 1181 (559-1559) and 115 (50-174) per week, respectively. CONCLUSIONS: The RSC is broadly representative of the national population; its PCSC is geographically representative and its SSGPs are newly supporting UKHSA syndromic surveillance efforts. The network captures vaccine coverage and has expanded from reporting primary care attendances to providing data on onward hospital outcomes and deaths. The challenge remains to increase virological and serological sampling to monitor the effectiveness and waning of all vaccines available in a timely manner.