Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Sensitivity and efficiency of RNA sample pooling for real-time quantitative polymerase chain reaction testing for SARS-CoV-2

DigitalBackground: In spite of the worth of pool testing in public health, data on the sensitivity and efficiency of real-time quantitative polymerase chain reaction (RT-qPCR) pool testing for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in middle and low-income countries are limited. Methods: We mixed single specimens of extracted RNA positive for the SARS-CoV-2 envelope (E) gene by RT-qPCR with negative specimens, in pools of 4 (n=89), 8 (n=92), 16 (n=102), and 32 (n=105) specimens each. We estimated the average change in cycle threshold (Ct) for each pool size and added it to the Ct values of the first 1,350 tests in our lab, to obtain dilution-corrected Ct values. We estimated pool sensitivity as the proportion of samples with dilution-corrected Ct >40, and used it in simulations of the efficiency (tests used/true case detected) of binary split pool testing. Results: We tested 388 pools. Average Ct changes were 2.21, 2.51, 3.27, and 3.94 cycles, for pools of 4, 8, 16, and 32 specimens, respectively. Corresponding pool tests sensitivities were 91.1%, 89.6%, 85.8% and 82.5%. Pool testing was substantially more efficient than individual testing. For prevalence of 0.5% to 2.0%, the efficiency of pools of ≥8 specimens was 30% to 280% higher, and the number of people tested was 4.4 to 13.9 times higher than those of individual testing. Conclusions: Binary split pool testing substantially increases the number of people tested and the number of true cases detected per test used. This strategy is key to curtail the transmission of SARS-CoV-2, by increasing efficiency in the identification and isolation of symptomatic and asymptomatic infected individuals.Ciencias Médicas y de la Salu

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

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

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)

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. Discussion: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV