Etiology of Acute Febrile Illness in the Peruvian Amazon as determined by modular formatted quantitative PCR: A Protocol for RIVERA, a Health Facility-Based Case-Control Study (preprint)

Background: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity.  We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. Methods: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. Discussion: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 hours and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific, prevalent pathogens as a cause of acute illness. Study Registration: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Effects of hydrometeorological and other factors on SARS-CoV-2 reproduction number in three contiguous countries of Tropical Andean South America: a spatiotemporally disaggregated time series analysis. (preprint)

Background: The COVID-19 pandemic has caused societal disruption globally and South America has been hit harder than other lower-income regions. This study modeled effects of 6 weather variables on district-level SARS-CoV-2 reproduction numbers (Rt) in three contiguous countries of Tropical Andean South America (Colombia, Ecuador, and Peru), adjusting for environmental, policy, healthcare infrastructural and other factors. Methods: Daily time-series data on SARS-CoV-2 infections were sourced from health authorities of the three countries at the smallest available administrative level. Rt values were calculated and merged by date and unit ID with variables from a Unified COVID-19 dataset and other publicly available sources for May - December 2020. Generalized additive mixed effects models were fitted. Findings: Relative humidity and solar radiation were inversely associated with SARS-CoV-2 Rt. Days with radiation above 1,000 KJ/m2 saw a 1.3%, and those with humidity above 50%, a 1.0% reduction in Rt. Transmission was highest in densely populated districts, and lowest in districts with poor healthcare access and on days with least population mobility. Temperature, region, aggregate government policy response and population age structure had little impact. The fully adjusted model explained 3.9% of Rt variance. Interpretation: Dry atmospheric conditions of low humidity increase, and higher solar radiation decrease district-level SARS-CoV-2 reproduction numbers, effects that are comparable in magnitude to population factors like lockdown compliance. Weather monitoring could be incorporated into disease surveillance and early warning systems in conjunction with more established risk indicators and surveillance measures.