Pooled Cohort Profile: ReCoDID Consortium's Harmonized Acute Febrile Illness Arbovirus Meta-Cohort.

Infectious disease (ID) cohorts are key to advancing public health surveillance, public policies, and pandemic responses. Unfortunately, ID cohorts often lack funding to store and share clinical-epidemiological (CE) data and high-dimensional laboratory (HDL) data long term, which is evident when the link between these data elements is not kept up to date. This becomes particularly apparent when smaller cohorts fail to successfully address the initial scientific objectives due to limited case numbers, which also limits the potential to pool these studies to monitor long-term cross-disease interactions within and across populations. CE data from 9 arbovirus (arthropod-borne viruses) cohorts in Latin America were retrospectively harmonized using the Maelstrom Research methodology and standardized to Clinical Data Interchange Standards Consortium (CDISC). We created a harmonized and standardized meta-cohort that contains CE and HDL data from 9 arbovirus studies from Latin America. To facilitate advancements in cross-population inference and reuse of cohort data, the Reconciliation of Cohort Data for Infectious Diseases (ReCoDID) Consortium harmonized and standardized CE and HDL from 9 arbovirus cohorts into 1 meta-cohort. Interested parties will be able to access data dictionaries that include information on variables across the data sets via Bio Studies. After consultation with each cohort, linked harmonized and curated human cohort data (CE and HDL) will be made accessible through the European Genome-phenome Archive platform to data users after their requests are evaluated by the ReCoDID Data Access Committee. This meta-cohort can facilitate various joint research projects (eg, on immunological interactions between sequential flavivirus infections and for the evaluation of potential biomarkers for severe arboviral disease).

Correction: Pooled Cohort Profile: ReCoDID Consortium's Harmonized Acute Febrile Illness Arbovirus Meta-Cohort.

[This corrects the article DOI: 10.2196/54281.].

Assessing vulnerability for future Zika virus outbreaks using seroprevalence data and environmental suitability maps.

The 2015-17 Zika virus (ZIKV) epidemic in the Americas subsided faster than expected and evolving population immunity was postulated to be the main reason. Herd immunization is suggested to occur around 60-70% seroprevalence, depending on demographic density and climate suitability. However, herd immunity was only documented for a few cities in South America, meaning a substantial portion of the population might still be vulnerable to a future Zika virus outbreak. The aim of our study was to determine the vulnerability of populations to ZIKV by comparing the environmental suitability of ZIKV transmission to the observed seroprevalence, based on published studies. Using a systematic search, we collected seroprevalence and geospatial data for 119 unique locations from 37 studies. Extracting the environmental suitability at each location and converting to a hypothetical expected seroprevalence, we were able to determine the discrepancy between observed and expected. This discrepancy is an indicator of vulnerability and divided into three categories: high risk, low risk, and very low risk. The vulnerability was used to evaluate the level of risk that each location still has for a ZIKV outbreak to occur. Of the 119 unique locations, 69 locations (58%) fell within the high risk category, 47 locations (39%) fell within the low risk category, and 3 locations (3%) fell within the very low risk category. The considerable heterogeneity between environmental suitability and seroprevalence potentially leaves a large population vulnerable to future infection. Vulnerability seems to be especially pronounced at the fringes of the environmental suitability for ZIKV (e.g. Sao Paulo, Brazil). The discrepancies between observed and expected seroprevalence raise the question: "why did the ZIKV epidemic stop with large populations unaffected?". This lack of understanding also highlights that future ZIKV outbreaks currently cannot be predicted with confidence.

Dietary Patterns and Anti-Flavivirus IgG Seroconversion in Colombian Children.

The burden of flaviviral infections, especially dengue and Zika, is high in the Americas. Malnutrition affects the risk and response to infections, but the role of diet on flaviviral infection risk is uncertain. The objective of this study was to investigate the relations between dietary patterns adherence and anti-flavivirus IgG seroconversion in children during a Zika epidemic in a dengue-endemic area of Colombia. In 2015-2016, we followed 424 anti-flavivirus IgG seronegative children aged 2 to 12 years for 1 year. Baseline data included children's sociodemographic, anthropometric, and dietary information collected through a 38-item food frequency questionnaire (FFQ). IgG testing was repeated at the end of follow-up. The primary exposure was adherence to each of four dietary patterns (animal foods, traditional, ultraprocessed foods, and prudent) that were identified from the FFQ through principal component analysis. Secondary exposures were intake frequencies of foods contributing to relevant patterns. We estimated risk of seroconversion by quartiles of adherence scores and compared them using relative risks (RR) and 95% CI from Poisson regression adjusted for sex, age, and socioeconomic status indicators. Seroconversion risk was 32.1%. Adherence to the traditional pattern was positively related to seroconversion. RR comparing fourth versus first quartiles of adherence was 1.52 (95% CI: 1.04-2.21; P trend = 0.02). Of the most representative foods in this pattern, potato and sugarcane water intake frequencies were related to increased seroconversion risk. In conclusion, adherence to a traditional foods pattern, including potatoes and sugarcane water, was positively associated with anti-flavivirus IgG seroconversion.

Validation of RT-qPCR test for SARS-CoV-2 in saliva specimens.

BACKGROUND: Saliva samples may be an easier, faster, safer, and cost-saving alternative to NPS samples, and can be self-collected by the patient. Whether SARS-CoV-2 RT-qPCR in saliva is more accurate than in nasopharyngeal swaps (NPS) is uncertain. We evaluated the accuracy of the RT-qPCR in both types of samples, assuming both approaches were imperfect. METHODS: We assessed the limit of detection (LoD) of RT-qPCR in each type of sample. We collected paired NPS and saliva samples and tested them using the Berlin Protocol to detect SARS-CoV-2 envelope protein (E). We used a Bayesian latent class analysis (BLCA) to estimate the sensitivity and specificity of each test, while accounting for their conditional dependence. RESULTS: The LoD were 10 copies/mL in saliva and 100 copies/mL in NPS. Paired samples of saliva and NPS were collected in 412 participants. Out of 68 infected cases, 14 were positive only in saliva. RT-qPCR sensitivity ranged from 82.7 % (95 % CrI: 54.8, 94.8) in NPS to 84.5 % (50.9, 96.5) in saliva. Corresponding specificities were 99.1 % (95 % CrI: 95.3, 99.8) and 98.4 %(95 % CrI: 92.8, 99.7). CONCLUSIONS: SARS-CoV-2 RT-qPCR test in saliva specimens has a similar or better accuracy than RT-qPCR test in NPS. Saliva specimens may be ideal for surveillance in general population, particularly in children, and in healthcare or other personnel in need of serial testing.

Heterogeneity of dengue transmission in an endemic area of Colombia.

Population based serological surveys are the gold-standard to quantify dengue (DENV) transmission. The purpose of this study was to estimate the age-specific seroprevalence and the force of infection of DENV in an endemic area of Colombia. Between July and October 2014, we conducted a household based cross-sectional survey among 1.037 individuals aged 2 to 40 years living in 40 randomly selected locations in urban Piedecuesta, Santander, Colombia. In addition, we also enrolled 246 indviduals living in rural "veredas". Participants were asked to answer a questionnaire that included demographic, socioeconomic and environmental questions and to provide a 5 ml blood sample. Sera were tested using the IgG indirect ELISA (Panbio) kit to determine past DENV infection. The overall DENV seroprevalence was 70% (95% CI = 67%-71%), but was significantly higher in urban (81%, 95% CI = 78%-83%) as compared to rural (21%, 95% CI = 17%-27%) locations. Age was a major predictor of seropositivity, consistent with endemic circulation of the virus. Using catalytic models we estimated that on average, 12% (95%CI = 11%-13%) of susceptible individuals living in the city are infected by DENV each year. Beyond age, the only predictor of seropositivity in urban locations was prior history of dengue diagnosed by a physician (aPR 1.15, 95% CI = 0.98-1.35). Among participants living in rural settings, those that reported traveling outside of their vereda were more likely to be seropositive (aPR 3.60, 95%CI = 1.54-8.42) as well as those who were born outside of Santander department (aPR = 2.77, 95%CI = 1.20-6.37). These results are consistent with long term endemic circulation of DENV in Piedecuesta, with large heterogeneities between urban and rural areas located just a few kilometers apart. Design of DENV control interventions, including vaccination, will need to consider this fine scale spatial heterogeneity.

Burden of dengue among febrile patients at the time of chikungunya introduction in Piedecuesta, Colombia.

OBJECTIVE: To estimate the age-specific incidence of symptomatic dengue and chikungunya in Colombia. METHOD: A passive facility-based fever surveillance study was conducted among individuals with undifferentiated fever. Confirmatory diagnostics included serological and molecular tests in paired samples, and surveillance's underreporting was assessed using capture-recapture methods. RESULTS: Of 839 febrile participants 686 completed the study. There were 33.2% (295/839) dengue infections (51% primary infections), and 35.9% (191/532) of negative dengue cases there were chikungunya cases. On average, dengue cases were younger (median = 18 years) than chikungunya cases (median = 25 years). Thrombocytopaenia and abdominal pain were the main dengue predictors, while presence of rash was the main predictor for chikungunya diagnosis. Underreporting of dengue was 31%; the estimated expansion factors indicate an underreporting rate of dengue cases of threefold for all cases and of almost sixfold for inpatients. CONCLUSIONS: These findings highlight the ongoing coexistence of both arboviruses, a distinct clinical profile of each condition in the study area that could be used by clinicians to generate a differential diagnosis, and the presence of underreporting, mostly among hospitalised cases.

Serum fatty acids and progression from dengue fever to dengue haemorrhagic fever/dengue shock syndrome.

PUFA might modulate inflammatory responses involved in the development of severe dengue. We aimed to examine whether serum PUFA concentrations in patients diagnosed with dengue fever (DF) were related to the risk of progression to dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). A secondary aim was to assess correlations between fatty acids (FA) and inflammatory biomarkers in patients with DF. We conducted a prospective case-control study nested within a cohort of patients who were diagnosed with DF and followed during the acute episode. We compared the distribution of individual FA (% of total FA) at onset of fever between 109 cases who progressed to DHF/DSS and 235 DF non-progressing controls using unconditional logistic regression. We estimated correlations between baseline FA and cytokine concentrations and compared FA concentrations between the acute episode and >1 year post-convalescence in a subgroup. DHA was positively related to progression to DHF/DSS (multivariable adjusted OR (AOR) for DHA in quintile 5 v. 1=5·34, 95 % CI 2·03, 14·1; P trend=0·007). Dihomo-γ-linolenic acid (DGLA) was inversely associated with progression (AOR for quintile 5 v. 1=0·30, 95 % CI 0·13, 0·69; P trend=0·007). Pentadecanoic acid concentrations were inversely related to DHF/DSS. Correlations of PUFA with cytokines at baseline were low. PUFA were lower during the acute episode than in a disease-free period. In conclusion, serum DHA in patients with DF predicts higher odds of progression to DHF/DSS whereas DGLA and pentadecanoic acid predict lower odds.

Alteraciones bioquímicas como marcadores predictores de gravedad en pacientes con fiebre por dengue / Biochemical alterations as prediction markers for the severity of illness in dengue fever patients

Introducción. El dengue es la infección transmitida por mosquitos más importante en el mundo. Existe información de que las alteraciones bioquímicas pueden utilizarse como herramientas predictoras de gravedad del dengue. Objetivo. Evaluar las alteraciones bioquímicas como posibles marcadores predictores de gravedad del dengue. Materiales y métodos. Se llevó a cabo un estudio de casos y controles anidado en una cohorte. Se seleccionaron al azar 125 casos con dengue grave y 120 controles con dengue no grave para evaluar los niveles séricos de lactato-deshidrogenasa (LDH), creatina cinasa (CK), proteína C reactiva (PCR) y albúmina, en sueros obtenidos en las primeras horas de la enfermedad. Para evaluar el valor diagnóstico de cada biomarcador, se establecieron puntos de corte con una sensibilidad del 90 % en la detección de casos graves. Resultados. Se observó una asociación entre los niveles de PCR por debajo de 9,8 mg/l (OR=0,04; IC 95% =0,02-0,08 ; p=0,000), de LDH inferiores a 400 U/L (OR=0,49; IC 95% =0,24-1,02; p=0,053) y de albúmina menor de 4 mg/dl (OR=3,46; IC 95% =1,96-6,12; p=0,000), con la gravedad del dengue. En contraste, los niveles de la CK no mostraron asociación con la gravedad de la enfermedad. Conclusiones. Los hallazgos de nuestro estudio sugieren una asociación de los niveles de PCR, LDH y albúmina con la gravedad del dengue. Estas pruebas bioquímicas podrían ser utilizadas como herramientas predictoras del curso clínico de la infección.

Introduction: Dengue is the most important mosquito-borne infection in the world. There is evidence supporting the use of biochemical alterations as prediction tools for severity of illness in dengue. Objective: To evaluate biochemical alterations as potential prediction markers for severity in dengue. Materials and methods: This was a case-control study nested in a cohort. We randomly selected 125 severe dengue cases and 120 controls with non-severe dengue for measuring LDH, CK, CRP and albumin serum levels using acute phase sera. To evaluate the predictive value for each biomarker, we established cut-off points with 90% sensitivity in detecting severe cases. Results: There was association among the CRP levels < 9.8 mg/L (OR=0.04; 95%CI=0.02-0.08; p=0.000), <400 U/L LDH levels (OR=0.49; 95%CI=0.24-1.02; p=0.053) and <4 mg/dl albumin levels (OR=3.46; 95%CI=1.96-6.12; p=0.000) with the severity of dengue. In contrast, the CK levels showed no association with the severity of the disease. Conclusions: Our findings suggest an association of CRP, LDH and albumin levels with the severity of dengue. These biochemical tests could be used as predictive tools in the clinical course of the infection.

[Biochemical alterations as prediction markers for the severity of illness in dengue fever patients]. / Alteraciones bioquímicas como marcadores predictores de gravedad en pacientes con fiebre por dengue.

INTRODUCTION: Dengue is the most important mosquito-borne infection in the world. There is evidence supporting the use of biochemical alterations as prediction tools for severity of illness in dengue. OBJECTIVE: To evaluate biochemical alterations as potential prediction markers for severity in dengue. MATERIALS AND METHODS: This was a case-control study nested in a cohort. We randomly selected 125 severe dengue cases and 120 controls with non-severe dengue for measuring LDH, CK, CRP and albumin serum levels using acute phase sera. To evaluate the predictive value for each biomarker, we established cut-off points with 90% sensitivity in detecting severe cases. RESULTS: There was association among the CRP levels < 9.8 mg/L (OR=0.04; 95%CI=0.02-0.08; p=0.000), <400 U/L LDH levels (OR=0.49; 95%CI=0.24-1.02; p=0.053) and <4 mg/dl albumin levels (OR=3.46; 95%CI=1.96-6.12; p=0.000) with the severity of dengue. In contrast, the CK levels showed no association with the severity of the disease. CONCLUSIONS: Our findings suggest an association of CRP, LDH and albumin levels with the severity of dengue. These biochemical tests could be used as predictive tools in the clinical course of the infection.