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To conduct a systematic review to estimate the prevalence of asymptomatic Zika virus infection in the general population and in specific population groups. We searched PubMed®, Embase® and LILACS online databases from inception to 26 January 2018. We included observational epidemiological studies where laboratory testing was used to confirm positive exposure of participants to Zika virus and in which Zika virus symptom status was also recorded. We excluded studies in which having symptoms of Zika virus was a criterion for inclusion. The main outcome assessed was percentage of all Zika virus-positive participants who were asymptomatic. We used a quality-effects approach and the double arcsine transformation for the meta-analysis. We assessed 753 studies for inclusion, of which 23 were included in the meta-analysis, totalling 11 305 Zika virus-positive participants. The high degree of heterogeneity in the studies (  = 99%) suggests that the pooled prevalence of asymptomatic Zika virus-positive participants was probably not a robust estimate. Analysis based on subgroups of the population (general population, returned travellers, blood donors, adults with Guillain-Barré syndrome, pregnant women and babies with microcephaly) was not able to explain the heterogeneity. Funnel and Doi plots showed major asymmetry, suggesting selection bias or true heterogeneity. Better-quality research is needed, using standardized methods, to determine the true prevalence of asymptomatic Zika virus and whether it varies between populations or over time.

Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs. A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings. The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity), we found that more than half the relevant studies supported a causal association with Zika virus infection. For GBS, we included 36 items, of which more than half the relevant studies supported a causal association in seven of ten dimensions (all except dose-response relationship, specificity, and animal experimental evidence). Articles identified nonsystematically from May 30 to July 29, 2016 strengthened the review findings. The expert panel concluded that (a) the most likely explanation of available evidence from outbreaks of Zika virus infection and clusters of microcephaly is that Zika virus infection during pregnancy is a cause of congenital brain abnormalities including microcephaly, and (b) the most likely explanation of available evidence from outbreaks of Zika virus infection and GBS is that Zika virus infection is a trigger of GBS. The expert panel recognised that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or GBS but agreed that the evidence was sufficient to recommend increased public health measures. Weaknesses are the limited assessment of the role of dengue virus and other possible cofactors, the small number of comparative epidemiological studies, and the difficulty in keeping the review up to date with the pace of publication of new research. Rapid and systematic reviews with frequent updating and open dissemination are now needed both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge. This systematic review found sufficient evidence to say that Zika virus is a cause of congenital abnormalities and is a trigger of GBS.

An additional challenge - exacerbated by COVID-19 especially for low-to-middle income countries (LMICs) - comes from underdeveloped or weak health research systems and resources allocated to this work along with poor health services, economic inequity, unemployment and hunger, lower income and conflict-affected states including lack of access to effective interventions [10]. In this commentary, we present how COVID-END works and what became a joint mission of these working groups; consolidated resources to facilitate trustworthy, rapid and equitable evidence synthesis, health technology assessments and guidelines for public health and clinical practice. The goal of this resource is to support more robust evidence generation, reduce unnecessary duplication and increase efficiency of processes.1.2 Examples of global responses for evidence synthesis and guidance The pandemic and the subsequent infodemic have risked overwhelming the traditional system of evidence synthesis and guideline production, especially as producers of evidence and recommendations follow different processes and standards leading to divergent, and sometimes opposing, recommendations without adequate reason. The pandemic has however, afforded the opportunity for organizations doing evidence synthesis and guidelines as well as academic groups to collaborate, share evidence and reduce research waste and unnecessary duplication, and increase evidence generation efficiency.1.3 COVID-END resources for evidence synthesis and guideline development Our aim was to create resources that assist those already supporting decision-making to find and use the best available evidence and resources (i.e., to support the evidence-demand side) and reduce duplication and avoid redundancy to better centralize and coordinate the evidence syntheses, HTAs and guidelines being produced (i.e., the support the evidence supply side) – by compiling existing resources in one place to streamline access and enhance use.

This paper examines the characteristics of implementation research (IR) efforts in low-income and middle-income countries (LMICs) by describing how key IR principles and concepts have been used in published health research in LMICs between 1998 and 2016, with focus on how to better apply these principles and concepts to support large-scale impact of health interventions in LMICs. There is a stark discrepancy between principles of IR and what has been published. Most IR studies have been conducted under conditions where the researchers have considerable influence over implementation and with extra resources, rather than in ‘real world’ conditions. IR researchers tend to focus on research questions that test a proof of concept, such as whether a new intervention is feasible or can improve implementation. They also tend to use traditional fixed research designs, yet the usual conditions for managing programmes demand continuous learning and change. More IR in LMICs should be conducted under usual management conditions, employ pragmatic research paradigm and address critical implementation issues such as scale-up and sustainability of evidence-informed interventions. This paper describes some positive examples that address these concerns and identifies how better reporting of IR studies in LMICs would include more complete descriptions of strategies, contexts, concepts, methods and outcomes of IR activities. This will help practitioners, policy-makers and other researchers to better learn how to implement large-scale change in their own settings.

Background Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses. Methods Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle–Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables. Results In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals. Conclusion Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.

Background Progress towards universal health coverage requires health policies and systems that are informed by contextualised and actionable research. Many challenges impede the uptake of evidence to enhance health policy implementation and the coverage, quality, efficiency and equity of health systems. To address this need, we developed an innovative model of implementation research embedded in real-world policy and programme cycles and led directly by policy-makers and health systems decision-makers. The approach was tested in ten settings in Latin America and the Caribbean, supported under a common funding and capacity strengthening initiative. The present study aims to analyse ten embedded implementation research projects in order to identify barriers and facilitators to embedding research into policy and practice as well as to assess the programme, policy and systems improvements and the cross-cutting lessons in conducting research embedded in real-world policy and systems decision-making. Methods The multi-country analysis is based on the triangulation of data collected via three methods, namely (1) document review, (2) an electronic questionnaire and (3) in-depth interviews with decision-makers. Data from the document review was charted and narratively synthesised. Data from the questionnaire was used to assess three characteristics of the decision-maker’s participation in embedded research, namely (1) level of engagement in different stages of research; (2) extent to which their capacities to conduct and use research were developed; and (3) the level of confidence in undertaking implementation research activities. Interview data was analysed using a thematic approach. Results The main barriers to effective delivery or scale-up of health interventions identified in the research projects were inadequate financing, fragmentation of healthcare services and information systems, limited capacity of health system stakeholders, insufficient time, cultural factors, and a lack of information. Decision-makers’ experience in embedded research showed strong engagement in protocol development, moderate engagement in data collection and low engagement in data analysis. The in-depth interviews identified 17 facilitators and 8 barriers to embedding research into policy and systems. The principal facilitating factors were actionability of findings, relevance of research and engagement of decision-makers, whereas the main barriers were time and political processes. In Argentina, the research led to the development of new monitoring indicators to improve the implementation of the perinatal health policy, while in Chile, empirical findings supported the establishment of a training programme on reproductive rights, targeted to municipal health facilities. Conclusions This multi-country analysis contributes to the evidence base for the embedded research approach to support health policy and systems decisions-making. Embedding research into policy and practice stimulates the relevance and applicability of research, while promoting decision-makers’ engagement and likelihood to use research evidence in policy-making and health systems strengthening.

Background The national science and technology agendas (NSTAs) of Latin America and the Caribbean (LAC) are crucial for formulating and implementing public policies by providing a strategic framework that guides state actions and priorities. The objective of this scoping review is to examine health-related targets from the national science and technology agendas (NSTA) of Latin America and the Caribbean (LAC), in accordance with the United Nations’ third Sustainable Development Goal (SDG-3), as well as within the frameworks of innovation and risk management and emergencies. Methods A scoping review was conducted, including policy documents issued between 2013 and 2023 by governmental science and technology authorities. The search strategy included government and international organization websites. A total of 108 documents were identified. Results Sixteen NSTAs were selected. Health-related targets aligned with SDG-3 were highlighted, particularly in areas such as communicable diseases and drug and vaccine development, but there was limited representation in public health and health systems. Innovations in health science and technology included diagnostic technologies, health products and artificial intelligence. Risk management for health emergencies and disasters was present in a minority of the agendas, with a focus on natural disasters and the COVID-19 pandemic. Conclusions This analysis provides a comprehensive view of the representation of health in NSTAs in LACs, highlighting common objectives among countries to foster collaboration, optimize research and innovation, and identify gaps in components necessary to enhance population health, such as disaster management, public health, and health systems. Registration This scoping review was not registered.

Chikungunya virus infection (CHIKV) is caused by a mosquito-borne alphavirus. CHIKV causes high fever and painful rheumatic disorders that may persist for years. Because little is known about interventions for treating CHIKV-related illness, we conducted a systematic review. We used Cochrane methods. We searched PubMed, EMBASE, Cochrane Library, LILACS and other sources from the earliest records to March 2016. We had no language restrictions. We included randomized controlled trials assessing any intervention for treating acute or chronic CHIKV-related illness. Our primary outcomes were pain relief, global health status (GHS) or health related quality of life (HRQL), and serious adverse events (SAEs). We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality. We screened 2,229 records and found five small trials with a total of 402 participants. Patients receiving chloroquine (CHQ) had better chronic pain relief than those receiving placebo (relative risk [RR] 2.67, 95% confidence interval [CI] 1.23 to 5.77, N = 54), but acute pain relief was marginally not different between groups (mean difference [MD] 1.46, 95% CI 0.00 to 2.92, N = 54). SAEs were similar (RR = 15.00, 95% CI 0.90 to 250.24, N = 54). Comparing CHQ with paracetamol (PCM), CHQ patients had better pain relief (RR = 1.52, 95% CI 1.20 to 1.93, N = 86). Compared with hydroxychloroquine (HCHQ), disease-modifying anti-rheumatic drugs (DMARDs) reduced pain (MD = -14.80, 95% CI -19.12 to -10.48, N = 72). DMARDs patients had less disability (MD = -0.74, 95% CI -0.92 to -0.56, N = 72) and less disease activity (MD = -1.35; 95% CI -1.70 to -1.00; N = 72). SAEs were similar between DMARDs and HCHQ groups (RR = 2.84, 95% CI 0.12 to 67.53, N = 72). Comparing meloxicam (MXM) with CHQ, there was no difference in pain relief (MD = 0.24, 95% CI = -0.81 to 1.29; p = 0.65, N = 70), GHS or HRQL (MD = -0.31, 95% CI -2.06 to 1.44, N = 70) or SAEs (RR = 0.85, 95% CI 0.30 to 2.42, N = 70). Finally, a four-arm trial (N = 120) compared aceclofenac (ACF) monotherapy to ACF+HCHQ, ACF+ prednisolone (PRD), or ACF+HCHQ+PRD. Investigators found reduced pain (p<0.001) and better HRQL (p<0.001) in the two patient groups receiving PRD, compared to those receiving ACF monotherapy or ACF+HCHQ. Trials were at high risk of bias. GRADE evidence quality for all outcomes was very low. Results from these small trials provide insufficient evidence to draw conclusions about the efficacy or safety of CHIKV interventions. Physicians should be cautious in prescribing and policy-makers should be cautious in recommending any intervention reviewed here. Rigorous trials with sufficient statistical power are urgently needed, with results stratified by disease stage and symptomology.

To synthesize existing knowledge on the features of, and approaches to, health intelligence, including definitions, key concepts, frameworks, methods and tools, types of evidence used, and research gaps. We applied a critical interpretive synthesis methodology, combining systematic searching, purposive sampling, and inductive analysis to explore the topic. We conducted electronic and supplementary searches to identify records (papers, books, websites) based on their potential relevance to health intelligence. The key themes identified in the literature were combined under each of the compass subquestions and circulated among the research team for discussion and interpretation. Of the 290 records screened, 40 were included in the synthesis. There is no clear definition of health intelligence in the literature. Some records describe it in similar terms as public health surveillance. Some focus on the use of artificial intelligence, while others refer to health intelligence in a military or security sense. And some authors have suggested a broader definition of health intelligence that explicitly includes the concepts of synthesis of research evidence for informed decision making. Rather than developing a new or all-encompassing definition, we suggest incorporating the concept and scope of health intelligence within the evidence ecosystem.