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Multiplex-based serological surveillance is a valuable but underutilized tool to understand gaps in population-level exposure, susceptibility, and immunity to infectious diseases. Assays for which blood samples can be tested for antibodies against several pathogens simultaneously, such as multiplex bead immunoassays, can more efficiently integrate public health surveillance in low- and middle-income countries. On March 7-8, 2023 a group of experts representing research institutions, multilateral organizations, private industry, and country partners met to discuss experiences, identify challenges and solutions, and create a community of practice for integrated, multi-pathogen serosurveillance using multiplex bead assay technologies. Participants were divided into six working groups: 1) supply chain; 2) laboratory assays; 3) seroepidemiology; 4) data analytics; 5) sustainable implementation; and 6) use case scenarios. These working groups discussed experiences, challenges, solutions, and research needs to facilitate integrated, multi-pathogen serosurveillance for public health. Several solutions were proposed to address challenges that cut across working groups.

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)., (©Gustavo Gómez, Heather Hufstedler, Carlos Montenegro Morales, Yannik Roell, Anyela Lozano-Parra, Adriana Tami, Tereza Magalhaes, Ernesto T A Marques, Angel Balmaseda, Guilherme Calvet, Eva Harris, Patricia Brasil, Victor Herrera, Luis Villar, Lauren Maxwell, Thomas Jaenisch, ReCoDID Arbovirus harmonization study group. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 23.07.2024.)

Background: Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and its effects on subsequent platelet count, severe dengue, and plasma leakage., Methods: We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models., Results: Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5-6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes., Conclusions: This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials., Funding: Wellcome Trust and European Union Seventh Framework Programme., Competing Interests: NV, NQ, NT, KD, HD, PL, DT, TV, CS, RG No competing interests declared, TJ reports receiving personal fees as members of the Roche Pharmaceuticals Advisory Board on Severe Dengue, outside the submitted work, SY reports receiving personal honorarium for attending the Novartis dengue drug ad board meeting and Takeda dengue education symposium, outside the submitted work, BW reports receiving personal fees (a) as a member of the Roche Advisory Board on Severe Dengue and (b) as a member of the Data Monitoring and Adjudication Committees for the Takeda dengue vaccine trials, both outside the remit of the submitted work, (© 2024, Vuong et al.)

Background: It is necessary to harmonize and standardize data variables used in case report forms (CRFs) of clinical studies to facilitate the merging and sharing of the collected patient data across several clinical studies. This is particularly true for clinical studies that focus on infectious diseases. Public health may be highly dependent on the findings of such studies. Hence, there is an elevated urgency to generate meaningful, reliable insights, ideally based on a high sample number and quality data. The implementation of core data elements and the incorporation of interoperability standards can facilitate the creation of harmonized clinical data sets., Objective: This study's objective was to compare, harmonize, and standardize variables focused on diagnostic tests used as part of CRFs in 6 international clinical studies of infectious diseases in order to, ultimately, then make available the panstudy common data elements (CDEs) for ongoing and future studies to foster interoperability and comparability of collected data across trials., Methods: We reviewed and compared the metadata that comprised the CRFs used for data collection in and across all 6 infectious disease studies under consideration in order to identify CDEs. We examined the availability of international semantic standard codes within the Systemized Nomenclature of Medicine - Clinical Terms, the National Cancer Institute Thesaurus, and the Logical Observation Identifiers Names and Codes system for the unambiguous representation of diagnostic testing information that makes up the CDEs. We then proposed 2 data models that incorporate semantic and syntactic standards for the identified CDEs., Results: Of 216 variables that were considered in the scope of the analysis, we identified 11 CDEs to describe diagnostic tests (in particular, serology and sequencing) for infectious diseases: viral lineage/clade; test date, type, performer, and manufacturer; target gene; quantitative and qualitative results; and specimen identifier, type, and collection date., Conclusions: The identification of CDEs for infectious diseases is the first step in facilitating the exchange and possible merging of a subset of data across clinical studies (and with that, large research projects) for possible shared analysis to increase the power of findings. The path to harmonization and standardization of clinical study data in the interest of interoperability can be paved in 2 ways. First, a map to standard terminologies ensures that each data element's (variable's) definition is unambiguous and that it has a single, unique interpretation across studies. Second, the exchange of these data is assisted by "wrapping" them in a standard exchange format, such as Fast Health care Interoperability Resources or the Clinical Data Interchange Standards Consortium's Clinical Data Acquisition Standards Harmonization Model., (©Caroline Stellmach, Sina Marie Hopff, Thomas Jaenisch, Susana Marina Nunes de Miranda, Eugenia Rinaldi, The NAPKON, LEOSS, ORCHESTRA, and ReCoDID Working Groups. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 10.06.2024.)

Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) conducted with non-randomized exposures, published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis. Unfortunately, we found that causal methodologies were rarely implemented, and reporting was generally poor across studies. Specifically, only three of the 29 articles used quasi-experimental methods, and no study used G-methods to adjust for time-varying confounding. To address these issues, we propose stronger collaborations between physicians and methodologists to ensure that causal methodologies are properly implemented in IPD-MAs. In addition, we put forward a suggested checklist of reporting guidelines for IPD-MAs that utilize causal methods. This checklist could improve reporting thereby potentially enhancing the quality and trustworthiness of IPD-MAs, which can be considered one of the most valuable sources of evidence for health policy., (© 2024. The Author(s).)

Competing Interests: Disclosure of Interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: Clair Blacketer is an employee of Johnson & Johnson and hold stock and stock options. Andreas Kremer is on the Board of Directors of i2b2 tranSMART, holds a position on ELIXIT’s Industry Advisory Committee, and holds stock and stock options with ITTM S.A..At the time of the data standards meeting, both Kit Howard and Bess LeRoy were employees of CDISC.

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Roell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This short communication is an effort to describe and elucidate the trajectory of the modern historical concept of "One Health." It is dedicated to the many integrated approaches of health closely related to One Health, while also recognizing the contribution and origination of One Health perspectives/notions from those that have led the way and spearheaded this movement while considering Indigenous cultures across the world. The effects of synergies of those involved in building these integrative approaches are potentially bigger and better lasting than the sum of the individual players. It is only through collaboration, cooperation and diplomacy that we can achieve impactful transformation to benefit health. In this commentary, we aim to appropriately and accurately describe how the current use of "One Health" came to be and who were the main players., Competing Interests: There are no conflicts of interest to disclose., (Published by Elsevier B.V.)

We present a framework for a federated, virtual biorepository system (VBS) with locally collected and managed specimens, as a 'global public good' model based on principles of equitable access and benefit sharing. The VBS is intended to facilitate timely access to biological specimens and associated data for outbreak-prone infectious diseases to accelerate the development and evaluation of diagnostics, assess vaccine efficacy, and to support surveillance and research needs. The VBS is aimed to be aligned with the WHO BioHub and other specimen sharing efforts as a force multiplier to meet the needs of strengthening global tools for countering epidemics. The purpose of our initial research is to lay the basis of the collaboration, management and principles of equitable sharing focused on low- and middle-income country partners. Here we report on surveys and interviews undertaken with biorepository-interested parties to better understand needs and barriers for specimen access and share examples from the ZIKAlliance partnership on the governance and operations of locally organized biorepositories., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Giri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The four Dengue viruses (DENV) serotypes were re-introduced in Brazil's Northeast region in a couple of decades, between 1980's and 2010's, where the DENV1 was the first detected serotype and DENV4 the latest. Zika (ZIKV) and Chikungunya (CHIKV) viruses were introduced in Recife around 2014 and led to large outbreaks in 2015 and 2016, respectively. However, the true extent of the ZIKV and CHIKV outbreaks, as well as the risk factors associated with exposure to these viruses remain vague., Methods: We conducted a stratified multistage household serosurvey among residents aged between 5 and 65 years in the city of Recife, Northeast Brazil, from August 2018 to February 2019. The city neighborhoods were stratified and divided into high, intermediate, and low socioeconomic strata (SES). Previous ZIKV, DENV and CHIKV infections were detected by IgG-based enzyme linked immunosorbent assays (ELISA). Recent ZIKV and CHIKV infections were assessed through IgG3 and IgM ELISA, respectively. Design-adjusted seroprevalence were estimated by age group, sex, and SES. The ZIKV seroprevalence was adjusted to account for the cross-reactivity with dengue. Individual and household-related risk factors were analyzed through regression models to calculate the force of infection. Odds Ratio (OR) were estimated as measure of effect., Principal Findings: A total of 2,070 residents' samples were collected and analyzed. The force of viral infection for high SES were lower as compared to low and intermediate SES. DENV seroprevalence was 88.7% (CI95%:87.0-90.4), and ranged from 81.2% (CI95%:76.9-85.6) in the high SES to 90.7% (CI95%:88.3-93.2) in the low SES. The overall adjusted ZIKV seroprevalence was 34.6% (CI95%:20.0-50.9), and ranged from 47.4% (CI95%:31.8-61.5) in the low SES to 23.4% (CI95%:12.2-33.8) in the high SES. The overall CHIKV seroprevalence was 35.7% (CI95%:32.6-38.9), and ranged from 38.6% (CI95%:33.6-43.6) in the low SES to 22.3% (CI95%:15.8-28.8) in the high SES. Surprisingly, ZIKV seroprevalence rapidly increased with age in the low and intermediate SES, while exhibited only a small increase with age in high SES. CHIKV seroprevalence according to age was stable in all SES. The prevalence of serological markers of ZIKV and CHIKV recent infections were 1.5% (CI95%:0.1-3.7) and 3.5% (CI95%:2.7-4.2), respectively., Conclusions: Our results confirmed continued DENV transmission and intense ZIKV and CHIKV transmission during the 2015/2016 epidemics followed by ongoing low-level transmission. The study also highlights that a significant proportion of the population is still susceptible to be infected by ZIKV and CHIKV. The reasons underlying a ceasing of the ZIKV epidemic in 2017/18 and the impact of antibody decay in susceptibility to future DENV and ZIKV infections may be related to the interplay between disease transmission mechanism and actual exposure in the different SES., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Braga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management., Methods: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values., Findings: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only., Interpretation: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook., Funding: EU's Seventh Framework Programme., Translations: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests TJ reports personal fees from the Roche Severe Dengue Advisory Board, Takeda Pharmaceutical Company, Merck Pharmaceuticals, and Emergent Biosolutions, as a member of advisory boards, outside the submitted work. BAW reports personal fees from Takeda Pharmaceutical Company and from the Roche Severe Dengue Advisory Board, outside the submitted work. SY reports personal fees from Roche, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

A common problem in the analysis of multiple data sources, including individual participant data meta-analysis (IPD-MA), is the misclassification of binary variables. Misclassification may lead to biased estimators of model parameters, even when the misclassification is entirely random. We aimed to develop statistical methods that facilitate unbiased estimation of adjusted and unadjusted exposure-outcome associations and between-study heterogeneity in IPD-MA, where the extent and nature of exposure misclassification may vary across studies. We present Bayesian methods that allow misclassification of binary exposure variables to depend on study- and participant-level characteristics. In an example of the differential diagnosis of dengue using two variables, where the gold standard measurement for the exposure variable was unavailable for some studies which only measured a surrogate prone to misclassification, our methods yielded more accurate estimates than analyses naive with regard to misclassification or based on gold standard measurements alone. In a simulation study, the evaluated misclassification model yielded valid estimates of the exposure-outcome association, and was more accurate than analyses restricted to gold standard measurements. Our proposed framework can appropriately account for the presence of binary exposure misclassification in IPD-MA. It requires that some studies supply IPD for the surrogate and gold standard exposure, and allows misclassification to follow a random effects distribution across studies conditional on observed covariates (and outcome). The proposed methods are most beneficial when few large studies that measured the gold standard are available, and when misclassification is frequent., (© 2022 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)

Background: There has been a large influx of COVID-19 seroprevalence studies, but comparability between the seroprevalence estimates has been an issue because of heterogeneities in testing platforms and study methodology. One potential source of heterogeneity is the response or participation rate., Methods: We conducted a review of participation rates (PR) in SARS-CoV-2 seroprevalence studies collected by SeroTracker and examined their effect on the validity of study conclusions. PR was calculated as the count of participants for whom the investigators had collected a valid sample, divided by the number of people invited to participate in the study. A multivariable beta generalized linear model with logit link was fitted to determine if the PR of international household and community-based seroprevalence studies was associated with the factors of interest, from 1 December 2019 to 10 March 2021., Results: We identified 90 papers based on screening and were able to calculate the PR for 35 out of 90 papers (39%), with a median PR of 70% and an interquartile range of 40.92; 61% of the studies did not report PR., Conclusions: Many SARS-CoV-2 seroprevalence studies do not report PR. It is unclear what the median PR rate would be had a larger portion not had limitations in reporting. Low participation rates indicate limited representativeness of results. Non-probabilistic sampling frames were associated with higher participation rates but may be less representative. Standardized definitions of participation rate and data reporting necessary for the PR calculations are essential for understanding the representativeness of seroprevalence estimates in the population of interest., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by 3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected.

Background: Young children in Sub-Saharan Africa (SSA), particularly those from resource-limited settings, are heavily burdened by anemia and malaria. While malaria infected children frequently become anemic (hemoglobin < 110 g/L), anemia is a strongly multifactorial disease with many other risk factors than malaria. Due to the complex and often overlapping contributors to anemia, it remains challenging to isolate the true impact of malaria on population level hemoglobin concentrations., Methods: We quantified the malaria-induced effect on hemoglobin levels in children under 5 years of age, leveraging data from 7,384 twins and other multiples, aged 6 to 59 months, from 57 nationally representative Demographic and Health Surveys (DHSs) from 23 SSA countries from 2006 to 2019. The quasi-experimental twin fixed-effect design let us minimize the impact of potential confounders that do not vary between twins., Results: Our analyses of twins revealed a malaria-induced hemoglobin decrease in infected twins of 9 g/L (95% CI -10; -7, p <0.001). The relative risk of severe anemia was higher (RR = 3.01, 95% CI 1.79; 5.1, p <0.001) among malaria positive children, compared to malaria negative children. Conversely, malaria positive children are only half as likely to be non-anemic (RR = 0.51, 95% CI 0.43; 0.61, p <0.001)., Conclusion: Even after rigorous control for confounding through a twin fixed-effects study design, malaria substantially decreased hemoglobin levels among SSA twins, rendering them much more susceptible to severe anemia. This effect reflects the population-level effect of malaria on anemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Starck, Dambach, Rouamba, Tinto, Osier, Oldenburg, Adam, Bärnighausen, Jaenisch and Bulstra.)

The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens., (© 2022 New York Academy of Sciences.)

Background: Many serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested. Methods: We conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between 1 January 2020, and 19 November 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment. Results: Among 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [−0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence. Conclusions: The Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays., Competing Interests: R.K.A. reports consulting fees from the Bill and Melinda Gates Foundation Strategic Investment Fund, past employment with Health Canada, and equity in Alethea Medical, all outside the submitted work. D.A.C. reports consulting fees from Sensyne Health, Oxford University Innovation, and BioBeats, each outside the submitted work. L.S. is employed by WHO. No others at WHO and no other funders, had any role in the design of this study, its execution, analyses, interpretation of the data, or decision to submit results. This manuscript does not necessarily reflect the views of the World Health Organization or any other funder.

Introduction: This study aims to measure how transmission of SARS-CoV-2 occurs in communities and to identify conditions that lend to increased transmission focusing on congregate situations. We will measure SARS-CoV-2 in exhaled breath of asymptomatic and symptomatic persons using face mask sampling-a non-invasive method for SARS-CoV-2 detection in exhaled air. We aim to detect transmission clusters and identify risk factors for SARS-CoV-2 transmission in presymptomatic, asymptomatic and symptomatic individuals., Methods and Analysis: In this observational prospective study with daily follow-up, index cases and their respective contacts are identified at each participating institution. Contact definitions are based on Centers for Disease Control and Prevention and local health department guidelines. Participants will wear masks with polyvinyl alcohol test strips adhered to the inside for 2 hours daily. The strips are applied to all masks used over at least 7 days. In addition, self-administered nasal swabs and (optional) finger prick blood samples are performed by participants. Samples are tested by standard PCR protocols and by novel antigen tests., Ethics and Dissemination: This study was approved by the Colorado Multiple Institutional Review Board and the WHO Ethics Review Committee. From the data generated, we will analyse transmission clusters and risk factors for transmission of SARS-CoV-2 in congregate settings. The kinetics of asymptomatic transmission and the evaluation of non-invasive tools for detection of transmissibility are of crucial importance for the development of more targeted control interventions-and ultimately to assist with keeping congregate settings open that are essential for our social fabric., Trial Registration Number: ClinicalTrials.gov (#NCT05145803)., Competing Interests: Competing interests: TJ, MML, WW, BA, GE and MC report grant support from WHO for this study for salaries or equipment/reagents. SB, OP, AB, CH, JR, JKovacs and MZ report grant/salary support for unrelated research without conflict of interest. EG, MH, CC, DO, SH, JKovarik, LCB, JTvS, SJ, JSS and LG report no conflict of interest. MZ reports speaker honoraria at academic institutions. BM reports industry support from Regeneron and Eli Lilly Foundation (as investigator, to the institution), MB reports support from the UK National Core Study on Transmission, and PF reports stock in Darwin Biosciences and support (equipment and reagents) from Ceres Nanosciences., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Dengue is not included explicitly in the WHO Integrated Management of Childhood Illness (IMCI) algorithm. However, the assessment, classification and management of dengue has been incorporated into several IMCI country adaptations. We aimed to evaluate the dengue algorithms incorporated into IMCI guidelines and discuss the need for harmonization, including an extension of the age range for IMCI., Methods: This study included three steps. First, we investigated dengue algorithms incorporated into five Southeast-Asian (Myanmar, Philippines, Vietnam, Indonesia, Cambodia) country IMCI guidelines through a desk-based analysis. Second, we conducted an expert survey to elicit opinions regarding the integration of dengue and extension of the age range in IMCI. Third, we compared our findings with data from a large multicentric prospective study on acute febrile illness., Results: We found considerable heterogeneity between the country specific IMCI guidelines in the dengue algorithms as well as classification schemes. Most guidelines did not differentiate between diagnostic algorithms for the detection of dengue versus other febrile illness, and warning signs for progression to severe dengue. Our expert survey resulted in a consensus to further integrate dengue in IMCI and extend the age range for IMCI guidelines beyond 5 years of age. Most of the interviewees responded that their country had a stand-alone clinical guideline for dengue, which was not integrated into the IMCI approach and considered laboratory testing for dengue necessary on day three of consecutive fever. Using data from a large multicentric study of children 5-15 years of age, we could confirm that the likelihood of dengue increased with consecutive fever days. However, a significant proportion of children (36%) would be missed if laboratory testing was only offered on the third consecutive day of fever., Conclusions: This study supports the extension of the IMCI age range beyond 5 years of age as well as the inclusion of dengue relevant content in the algorithm. Because of the challenge of distinguishing dengue from other febrile illnesses, simple laboratory testing (e.g., full blood count) should be offered at an early stage during the course of the illness. Testing only children with consecutive fever over 3 days may lead to an underdiagnosis of dengue among those with acute febrile illness in children 5-15 years of age. In addition, specific laboratory testing for dengue should be made available to peripheral health facilities., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: MWW is a WHO staff member.

The COVID-19 pandemic saw a massive investment into collaborative research projects with a focus on producing data to support public health decisions. We relay our direct experience of four projects funded under the Horizon2020 programme, namely ReCoDID, ORCHESTRA, unCoVer and SYNCHROS. The projects provide insight into the complexities of sharing patient level data from observational cohorts. We focus on compliance with the General Data Protection Regulation (GDPR) and ethics approvals when sharing data across national borders. We discuss procedures for data mapping; submission of new international codes to standards organisation; federated approach; and centralised data curation. Finally, we put forward recommendations for the development of guidelines for the application of GDPR in case of major public health threats; mandatory standards for data collection in funding frameworks; training and capacity building for data owners; cataloguing of international use of metadata standards; and dedicated funding for identified critical areas., Competing Interests: MB reports grants to UMCU from Janssen Vaccines, Novartis and CureVac, consulting fees from Astra Zeneca, Pfizer, Janssen Vaccines, Novartis,Takeda,Janssen Vaccines and payments from Sanofi for Participation on a Data Safety Monitoring Board or Advisory Board. ET, EC and RJD report H2020 funding for ORCHESTRA. JH reports H2020 funding for ORCHESTRA, funding from the German Research Council for the SEPAN Project, funding from German Ministry of Education and Research for the EMUNE and the INSIDe Project and funding from Volkswagen Stiftung for the E2 project. AS and EV report H2020 funding for SYNCHROS. TJ reports H2020 funding for ReCoDID. All other authors declare no competing interests., (© 2022 The Authors.)

Background: SARS-CoV-2 emerged in 2019 and resulted in a pandemic causing millions of infections worldwide. Gold-standard for SARS-CoV-2 detection uses quantitative RT-qPCR on respiratory secretions to detect viral RNA (vRNA). Acquiring these samples is invasive, can be painful for those with xerostomia and other health conditions, and sample quality can vary greatly. Frequently only symptomatic individuals are tested even though asymptomatic individuals can have comparable viral loads and efficiently transmit virus., Methods: We utilized a non-invasive approach to detect SARS-CoV-2 in individuals, using polyvinyl alcohol (PVA) strips embedded in KN95 masks. PVA strips were tested for SARS-CoV-2 vRNA via qRT-PCR and infectious virus., Results: We show efficient recovery of vRNA and infectious virus from virus-spiked PVA with detection limits comparable to nasal swab samples. In infected individuals, we detect both human and SARS-CoV-2 RNA on PVA strips, however, these levels are not correlated with length of time mask was worn, number of times coughed or sneezed, or level of virus in nasal swab samples. We successfully cultured and deep-sequenced PVA-associated virus., Conclusions: These results demonstrate the feasibility of using PVA-embedded masks as a non-invasive platform for detecting SARS-CoV-2 in exhaled air in COVID-positive individuals regardless of symptom status., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To determine the incidence and risk of adverse obstetric and neonatal outcomes according to SARS-CoV-2 infection severity in pregnant women., Method: Open prospective study of pregnant women tested for SARS-CoV-2 by serological and molecular assays during pregnancy or delivery in two hospitals in Sao Paulo, Brazil from April 12, 2020, to February 28, 2021. Five groups were considered for analysis: C0, negative COVID-19 results and no COVID-19 symptoms; C1, positive COVID-19 results, and no symptoms; C2, positive COVID-19 results with mild symptoms; C3, positive COVID-19 results with moderate symptoms; and C4, positive COVID-19 results with severe symptoms. The association between obstetric and neonatal outcomes and COVID-19 severity was determined using multivariate analysis., Results: 734 eligible pregnant women were enrolled as follows: C0 (n = 357), C1 (n = 127), C2 (n = 174), C3 (n = 37), and C4 (n = 39). The following pregnancy and neonatal outcomes were associated with severe COVID-19: oligohydramnios (adjusted Odds Ratio [aOR] = 6.18; 95% CI 1.87‒20.39), fetal distress (aOR = 4.01; 95% Confidence Interval [CI] 1.84‒8.75), preterm birth (aOR = 5.51; 95% CI 1.47‒20.61), longer hospital stay (aOR = 1.66; 95% CI 1.36‒2.02), and admission to the neonatal intensive care unit (aOR = 19.36; 95% CI, 5.86‒63.99). All maternal (n = 6, 15.4%, p < 0.001) and neonatal (n = 5, 12.5%, p < 0.001) deaths and most fetal deaths (n = 4, 9.8%, p < 0.001) occurred in C4 group. Moderate COVID-19 was associated with oligohydramnios (aOR = 6.23; 95% CI 1.93‒20.13) and preterm birth (aOR = 3.60; 95% CI 1.45‒9.27). Mild COVID-19 was associated with oligohydramnios (aOR = 3.77; 95% CI 1.56‒9.07)., Conclusion: Adverse pregnancy and neonatal outcomes were associated with maternal symptomatic COVID-19 status, and risk increased with disease severity., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

It is currently not clear whether humoral immunity to Zika virus (ZIKV) elicited upon natural ZIKV infection is long-lasting. In addition, cross-reactivity of anti-ZIKV antibodies with antigenically related dengue viruses (DENV) may have biological implications in nonnaive individuals who subsequently acquire a heterotypic infection. Cross-reactive humoral immunity between ZIKV and DENV also complicates the interpretation of serological tests to evaluate previous exposure to either virus. Here, we have measured the 2-year decay of ZIKV neutralizing antibodies in people living in a ZIKV/DENV endemic area in Brazil who were identified as having an acute infection (group 1) or past (but recent) infection (group 2) with ZIKV in 2015-16. The titers of neutralizing antibodies to ZIKV decreased 9.1 and 2.3 times in groups 1 and 2, respectively. We also show that the plaque reduction neutralization assay (PRNT) is a reliable method to measure past exposure to ZIKV in coendemic areas.

Objectives: Among ID studies seeking to make causal inferences and pooling individual-level longitudinal data from multiple infectious disease cohorts, we sought to assess what methods are being used, how those methods are being reported, and whether these factors have changed over time., Study Design and Setting: Systematic review of longitudinal observational infectious disease studies pooling individual-level patient data from 2+ studies published in English in 2009, 2014, or 2019. This systematic review protocol is registered with PROSPERO (CRD42020204104)., Results: Our search yielded 1,462 unique articles. Of these, 16 were included in the final review. Our analysis showed a lack of causal inference methods and of clear reporting on methods and the required assumptions., Conclusion: There are many approaches to causal inference which may help facilitate accurate inference in the presence of unmeasured and time-varying confounding. In observational ID studies leveraging pooled, longitudinal IPD, the absence of these causal inference methods and gaps in the reporting of key methodological considerations suggests there is ample opportunity to enhance the rigor and reporting of research in this field. Interdisciplinary collaborations between substantive and methodological experts would strengthen future work., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Although dengue virus (DENV) affects almost half of the world's population there are neither preventive treatments nor any long-lasting and protective vaccines available at this time. The complexity of the protective immune response to DENV is still not fully understood. The most advanced vaccine candidates focus specifically on humoral immune responses and the production of virus-neutralizing antibodies. However, results from several recent studies have revealed the protective role of T cells in the immune response to DENV. Hence, in this study, we generated a novel and potent DENV vaccine candidate based on an Orf virus (ORFV, genus Parapoxvirus ) vector platform engineered to encode five highly conserved or cross-reactive DENV human leukocyte antigen (HLA)-A*02- or HLA-B*07-restricted epitopes as minigenes (ORFV-DENV). We showed that ORFV-DENV facilitates the in vitro priming of CD8 + T cells from healthy blood donors based on responses to each of the encoded immunogenic peptides. Moreover, we demonstrated that peripheral blood mononuclear cells isolated from clinically confirmed DENV-positive donors stimulated with ORFV-DENV generate cytotoxic T cell responses to at least three of the expressed DENV peptides. Finally, we showed that ORFV-DENV could activate CD8 + T cells isolated from donors who had recovered from Zika virus (ZIKV) infection. ZIKV belongs to the same virus family ( Flaviviridae ) and has epitope sequences that are homologous to those of DENV. We found that highly conserved HLA-B*07-restricted ZIKV and DENV epitopes induced functional CD8 + T cell responses in PBMCs isolated from confirmed ZIKV-positive donors. In summary, this proof-of-concept study characterizes a promising new ORFV D1701-VrV-based DENV vaccine candidate that induces broad and functional epitope-specific CD8 + T cell responses.

In 2017, a major outbreak of Zika virus (ZIKV) infection took place in Chincha Province, Peru, where arboviral circulation had never been reported before. We conducted a cross-sectional survey (March-May 2019) in two districts of Chincha Province: Pueblo Nuevo and Chincha Baja. We included residents who were 20 to 40 years old and who had lived in these districts for at least 1 year. Serological testing combined screening with a commercial NS1 protein-based Zika IgG ELISA, and confirmation by a cytopathic effect-based virus neutralization test (VNT). Prevalence ratios (PRs) were calculated using Poisson regression with robust error variance. Four hundred participants, divided equally among districts, were enrolled. Anti-ZIKV IgG ELISA was positive for 42 participants (10.5%) and borderline for 12 (3%). Fifty-two of these 54 samples were confirmed positive by ZIKV VNT (13% of the total population). The Pueblo Nuevo district exhibited a greater ZIKV seroprevalence based on VNT results than the Chincha Baja district (23.5% versus 2.5%), with participants from the Pueblo Nuevo district being 9.4 times more likely to have a positive ZIKV VNT result. Average monthly income greater than the minimum wage and adequate water storage were found to be protective factors (PR, 0.29 and 0.24, respectively). In multivariate analysis, living in the Pueblo Nuevo district and a personal history of fever and rash were strong predictors of ZIKV positivity by VNT. The low ZIKV seroprevalence should prompt health authorities to stimulate interventions to prevent potential future outbreaks. In the Pueblo Nuevo district, the seroprevalence was greater but presumably not sufficient to ensure protective herd immunity.