Clinical Manifestations and Health Outcomes Associated with Zika Virus Infections in Adults: A Systematic Review

Background Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. Methods This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. Findings We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Most subjects reported recovery from peak of neurological complications, though a small proportion endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. Conclusions The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.

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Postnatal symptomatic Zika virus infections in children and adolescents: A systematic review

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008612 ◽

2020 ◽

Vol 14 (10) ◽

pp. e0008612

Author(s):

Anna Ramond ◽

Ludmila Lobkowicz ◽

Nuria Sanchez Clemente ◽

Aisling Vaughan ◽

Marília Dalva Turchi ◽

...

Keyword(s):

Systematic Review ◽

Children And Adolescents ◽

Zika Virus ◽

Virus Infections

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Health outcomes associated with Zika virus infection in humans: a systematic review of systematic reviews

BMJ Open ◽

10.1136/bmjopen-2019-032275 ◽

2019 ◽

Vol 9 (11) ◽

pp. e032275 ◽

Cited By ~ 4

Author(s):

Raphael Ximenes ◽

Lauren C Ramsay ◽

Rafael Neves Miranda ◽

Shaun K Morris ◽

Kellie Murphy ◽

...

Keyword(s):

Systematic Review ◽

Health Outcomes ◽

Systematic Reviews ◽

Zika Virus ◽

Policy Decision ◽

Measurement Tool ◽

Registration Number ◽

New Research ◽

Meta Analyses

ObjectiveWith the emergence of Zika virus (ZIKV) disease in Central and South America in the mid-2010s and recognition of the teratogenic effects of congenital exposure to ZIKV, there has been a substantial increase in new research published on ZIKV. Our objective is to synthesise the literature on health outcomes associated with ZIKV infection in humans.MethodsWe conducted a systematic review (SR) of SRs following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE, Embase, Cochrane and LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde) databases from inception to 22 July 2019, and included SRs that reported ZIKV-associated health outcomes. Three independent reviewers selected eligible studies, extracted data and assessed the quality of included SRs using the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews 2) tool. Conflicts were resolved by consensus or consultation with a third reviewer.ResultsThe search yielded 1382 unique articles, of which 21 SRs met our inclusion criteria. The 21 SRs ranged from descriptive to quantitative data synthesis, including four meta-analyses. The most commonly reported ZIKV-associated manifestations and health outcomes were microcephaly, congenital abnormalities, brain abnormalities, neonatal death and Guillain-Barré syndrome. The included reviews were highly heterogeneous. The overall quality of the SRs was critically low with all studies having more than one critical weakness.ConclusionThe evolving nature of the literature on ZIKV-associated health outcomes, together with the critically low quality of existing SRs, demonstrates the need for high-quality SRs to guide patient care and inform policy decision making.PROSPERO registration numberCRD42018091087.

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Health Outcomes in Post-natally Acquired Pediatric Zika Virus Infection: A Systematic Review

Anais Online do "Health Technology Research in Brazil: Challenges for the New Decade" ◽

10.17648/htbr-2021-125084 ◽

2021 ◽

Author(s):

Laura K Erdman ◽

Lauren Ramsay ◽

Rafael Miranda ◽

Carsten Krueger ◽

Raphael Ximenes ◽

...

Keyword(s):

Systematic Review ◽

Virus Infection ◽

Health Outcomes ◽

Zika Virus ◽

Zika Virus Infection

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Differential Pattern of Soluble Immune Markers in Asymptomatic Dengue, West Nile and Zika Virus Infections

Scientific Reports ◽

10.1038/s41598-019-53645-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Rafaelle Fares-Gusmao ◽

Bruno Coelho Rocha ◽

Emilia Sippert ◽

Marion C. Lanteri ◽

Germán Áñez ◽

...

Keyword(s):

Zika Virus ◽

Viral Infections ◽

Severe Disease ◽

Clinical Manifestations ◽

Virus Infections ◽

Immune Markers ◽

West Nile ◽

Differential Pattern ◽

Asymptomatic Stage ◽

Asymptomatic Phase

AbstractInfections with dengue virus (DENV), West Nile virus (WNV) and Zika virus (ZIKV) usually present similar mild symptoms at early stages, and most infections (~80%) are asymptomatic. However, these infections may progress to severe disease with different clinical manifestations. In this study we attempted to identify unique characteristics for each infection at the presymptomatic/asymptomatic stage of infection and compared levels of soluble immune markers that have been shown to be altered during clinical course of these viral infections. Levels of soluble markers were determined by Luminex-based assays or by ELISA in plasma samples from asymptomatic blood donors who were reactive for RNA from DENV (n = 71), WNV (n = 52) or ZIKV (n = 44), and a control or non-infected (NI) group (n = 22). Results showed that even in the absence of symptoms, increased interleukin (IL) levels of IL-12, IL-17, IL-10, IL-5, CXCL9, E-Selectin and ST2/IL-1R4; and decreased levels of IL-13 and CD40 were found in all flavivirus group samples, compared to those from NI donors. DENV-infected donors demonstrated variation in expression of IL-1ra and IL-2; WNV-infected donors demonstrated variation in expression of IL-1ra, P-Selectin, IL-4 and IL-5; ZIKV-infected donors demonstrated variation in expression of IL-1ra, P-Selectin, IL-4, RANK-L, CD40L and C3a. The findings suggest that, even in the presymptomatic/asymptomatic phase of the infection, different immunomodulation profiles were associated with DENV, WNV and ZIKV infections.

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The trends of Zika virus-related research from 2014 to 2018: a systematic review and meta-analysis

10.21203/rs.3.rs-47737/v2 ◽

2021 ◽

Author(s):

Yong-Dae Gwon ◽

Magnus Evander

Keyword(s):

Systematic Review ◽

Zika Virus ◽

Research Collaboration ◽

Meta Analysis ◽

Antiviral Treatment ◽

Clinical Manifestations ◽

Research Area ◽

Research Field ◽

Diagnostic Methods ◽

Scientific Database

Abstract Background Zika virus (ZIKV) is a mosquito-borne disease discovered in 1947, but with no reports of serious disease for almost 60 years. The first large ZIKV outbreak was reported from Yap island in 2007, then in 2015, the emergence of ZIKV in the Americas highlighted clinical manifestations such as microcephaly and Guillain‐Barré syndrome. On February 1, 2016, WHO declared a Public Health Emergency of International Concern due to the magnitude of the outbreak, which then officially ended in November 2016. Methods Ever since the Brazilian authority released the first report of autochthonous transmission of ZIKV in 2015, it became the object of interdisciplinary investigation and global research collaboration. To follow and understand the trend of ZIKV research, we performed a systematic review and meta-analysis of ZIKV publications during 2014-2018, by using the scientific database Scopus.Results We found that the number of ZIKV related publications increased in 2016, 2017, and 2018 (39.2, 56.5, and 58.5 times, respectively) compared to an average number of publications (23.5) in 2014-2015. During the five years, there was not only an increment of publication numbers but also the area of research was expanded. In 2014-2015, the majority in the research area was epidemiological research with the aims to report the consequence of the ZIKV outbreak, and the trend was shifted to the development of diagnostic methods, antiviral treatment, and vaccine in the following three years. In addition, the number of countries involved in ZIKV research increased from 11 and 13 in 2014-2015 to 59, 67, and 66 in 2016-2018, showing that ZIKV research was changed from a low-level stage to active and globalized in the coming five years.Conclusions Our results highlight the importance of gathering public interest when the world is facing the phase of global health alert, and how it can drive the research field from inactive to active. However, despite this enormous progress in ongoing ZIKV research, many questions are yet to be answered and should be addressed to accelerate the development of effective ZIKV countermeasures. Nevertheless, our systematic review and meta-analysis emphasized the importance of a worldwide multidisciplinary effort to combat outbreaks or unknown infectious disease threats in the future.

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The frequency and clinical presentation of Zika virus coinfections: a systematic review

BMJ Global Health ◽

10.1136/bmjgh-2020-002350 ◽

2020 ◽

Vol 5 (5) ◽

pp. e002350

Author(s):

Ludmila Lobkowicz ◽

Anna Ramond ◽

Nuria Sanchez Clemente ◽

Ricardo Arraes de Alencar Ximenes ◽

Demócrito de Barros Miranda-Filho ◽

...

Keyword(s):

Systematic Review ◽

Case Report ◽

Zika Virus ◽

Clinical Presentation ◽

Clinical Signs ◽

Clinical Manifestations ◽

Case Series ◽

Signs And Symptoms ◽

Cross Sectional ◽

Epstein Barr

BackgroundThere is limited knowledge on the influence of concurrent coinfections on the clinical presentation of Zika virus (ZIKV) disease.MethodsTo better understand the types, frequencies and clinical manifestations of ZIKV coinfections, we did a systematic review of four databases (PubMed, Embase, Web of Science, LILACS) without restrictions for studies on ZIKV coinfections confirmed by nucleic acid (quantitative real-time-PCR) testing of ZIKV and coinfecting pathogens. The review aimed to identify cohort, cross-sectional, case series and case report studies that described frequencies and/or clinical signs and symptoms of ZIKV coinfections. Conference abstracts, reviews, commentaries and studies with imprecise pathogen diagnoses and/or no clinical evaluations were excluded.ResultsThe search identified 34 articles from 10 countries, comprising 2 cohort, 10 cross-sectional, 8 case series and 14 case report studies. Coinfections were most frequently reported to have occurred with other arthropod-borne viruses (arboviruses); out of the 213 coinfections described, ZIKV infections co-occurred with chikungunya in 115 cases, with dengue in 68 cases and with both viruses in 19 cases. Other coinfecting agents included human immunodeficiency, Epstein-Barr, human herpes and Mayaro viruses, Leptospira spp, Toxoplasma gondii and Schistosoma mansoni. ZIKV-coinfected cases primarily presented with mild clinical features, typical of ZIKV monoinfection; however, 9% of cases in cohort and cross-sectional studies were reported to experience complications.ConclusionBased on the evidence collated in this review, coinfections do not appear to strongly influence the clinical manifestations of uncomplicated ZIKV infections. Further research is needed to confirm whether risk of severe complications is altered when ZIKV infection co-occurs with other infections.PROSPERO registration numberCRD42018111023.

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Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: a systematic review

Bulletin of the World Health Organization ◽

10.2471/blt.16.176677 ◽

2016 ◽

Cited By ~ 2

Author(s):

Susannah Colt ◽

Maria N Garcia-Casal ◽

Juan Pablo Peña-Rosas ◽

Julia L. Finkelstein ◽

Pura Rayco-Solon ◽

...

Keyword(s):

Systematic Review ◽

Breast Milk ◽

Zika Virus ◽

Bodily Fluids

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How Does Mindfulness Affect Cognition? A Reflection on Confounding Issues Surrounding Mindfulness-based Intervention Research Targeting Cognitive Outcomes

10.31231/osf.io/86hrv ◽

2018 ◽

Author(s):

David R Vago ◽

Resh Gupta ◽

Sara Lazar

Keyword(s):

Systematic Review ◽

Health Outcomes ◽

Cognitive Functioning ◽

Cognitive Processes ◽

Methodological Quality ◽

Cognitive Outcomes ◽

Controlled Trials ◽

Randomized Controlled ◽

Existing Data

One potential pathway by which mindfulness-based meditation improves health outcomes is through changes in cognitive functioning. A systematic review of randomized controlled trials of mindfulness-based interventions (MBIs) was conducted with a focus on assessing the state of the evidence for effects on cognitive processes and associated assays. Here, we comment on confounding issues surrounding the reporting of these and related findings, including 1) criteria that appropriately define an MBI; 2) limitations of assays used to measure cognition; and 3) methodological quality of MBI trials and reporting of findings. Because these issues contribute to potentially distorted interpretations of existing data, we offer constructive means for interpretation and recommendations for moving the field of mindfulness research forward regarding the effects on cognition.

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