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PLoS Neglected Tropical Diseases Feb 2022Chikungunya virus (CHIKV) causes febrile illnesses and has always been misdiagnosed as other viral infections, such as dengue and Zika; thus, a laboratory test is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chikungunya virus (CHIKV) causes febrile illnesses and has always been misdiagnosed as other viral infections, such as dengue and Zika; thus, a laboratory test is needed. Serological tests are commonly used to diagnose CHIKV infection, but their accuracy is questionable due to varying degrees of reported sensitivities and specificities. Herein, we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of serological tests currently available for CHIKV.
METHODOLOGY AND PRINCIPAL FINDINGS
A literature search was performed in PubMed, CINAHL Complete, and Scopus databases from the 1st December 2020 until 22nd April 2021. Studies reporting sensitivity and specificity of serological tests against CHIKV that used whole blood, serum, or plasma were included. QUADAS-2 tool was used to assess the risk of bias and applicability, while R software was used for statistical analyses. Thirty-five studies were included in this meta-analysis; 72 index test data were extracted and analysed. Rapid and ELISA-based antigen tests had a pooled sensitivity of 85.8% and 82.2%, respectively, and a pooled specificity of 96.1% and 96.0%, respectively. According to our meta-analysis, antigen detection tests serve as a good diagnostic test for acute-phase samples. The IgM detection tests had more than 90% diagnostic accuracy for ELISA-based tests, immunofluorescence assays, in-house developed tests, and samples collected after seven days of symptom onset. Conversely, low sensitivity was found for the IgM rapid test (42.3%), commercial test (78.6%), and for samples collected less than seven of symptom onset (26.2%). Although IgM antibodies start to develop on day 2 of CHIKV infection, our meta-analysis revealed that the IgM detection test is not recommended for acute-phase samples. The diagnostic performance of the IgG detection tests was more than 93% regardless of the test formats and whether the test was commercially available or developed in-house. The use of samples collected after seven days of symptom onset for the IgG detection test suggests that IgG antibodies can be detected in the convalescent-phase samples. Additionally, we evaluated commercial IgM and IgG tests for CHIKV and found that ELISA-based and IFA commercial tests manufactured by Euroimmun (Lübeck, Germany), Abcam (Cambridge, UK), and Inbios (Seattle, WA) had diagnostic accuracy of above 90%, which was similar to the manufacturers' claim.
CONCLUSION
Based on our meta-analysis, antigen or antibody-based serological tests can be used to diagnose CHIKV reliably, depending on the time of sample collection. The antigen detection tests serve as a good diagnostic test for samples collected during the acute phase (≤7 days post symptom onset) of CHIKV infection. Likewise, IgM and IgG detection tests can be used for samples collected in the convalescent phase (>7 days post symptom onset). In correlation to the clinical presentation of the patients, the combination of the IgM and IgG tests can differentiate recent and past infections.
Topics: Antigens, Viral; Chikungunya Fever; Chikungunya virus; Humans; Immunoglobulin G; Immunoglobulin M; Sensitivity and Specificity; Serologic Tests
PubMed: 35120141
DOI: 10.1371/journal.pntd.0010152 -
PLoS Neglected Tropical Diseases Jun 2024Chikungunya is a viral disease caused by a mosquito-borne alphavirus. The acute phase of the disease includes symptoms such as fever and arthralgia and lasts 7-10 days.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chikungunya is a viral disease caused by a mosquito-borne alphavirus. The acute phase of the disease includes symptoms such as fever and arthralgia and lasts 7-10 days. However, debilitating symptoms can persist for months or years. Despite the substantial impact of this disease, a comprehensive assessment of its clinical picture is currently lacking.
METHODS
We conducted a systematic literature review on the clinical manifestations of chikungunya, their prevalence and duration, and related hospitalization. Embase and MEDLINE were searched with no time restrictions. Subsequently, meta-analyses were conducted to quantify pooled estimates on clinical outcomes, the symptomatic rate, the mortality rate, and the hospitalization rate. The pooling of effects was conducted using the inverse-variance weighting methods and generalized linear mixed effects models, with measures of heterogeneity reported.
RESULTS
The systematic literature review identified 316 articles. Out of the 28 outcomes of interest, we were able to conduct 11 meta-analyses. The most prevalent symptoms during the acute phase included arthralgia in 90% of cases (95% CI: 83-94%), and fever in 88% of cases (95% CI: 85-90%). Upon employing broader inclusion criteria, the overall symptomatic rate was 75% (95% CI: 63-84%), the chronicity rate was 44% (95% CI: 31-57%), and the mortality rate was 0.3% (95% CI: 0.1-0.7%). The heterogeneity between subpopulations was more than 92% for most outcomes. We were not able to estimate all predefined outcomes, highlighting the existing data gap.
CONCLUSION
Chikungunya is an emerging public health concern. Consequently, a thorough understanding of the clinical burden of this disease is necessary. Our study highlighted the substantial clinical burden of chikungunya in the acute phase and a potentially long-lasting chronic phase. Understanding this enables health authorities and healthcare professionals to effectively recognize and address the associated symptoms and raise awareness in society.
Topics: Chikungunya Fever; Humans; Chikungunya virus; Arthralgia; Hospitalization; Fever; Prevalence
PubMed: 38848443
DOI: 10.1371/journal.pntd.0012254 -
PLoS Neglected Tropical Diseases Jan 2022Chikungunya fever is an acute febrile illness that is often associated with severe polyarthralgia in humans. The disease is caused by chikungunya virus (CHIKV), a...
Chikungunya fever is an acute febrile illness that is often associated with severe polyarthralgia in humans. The disease is caused by chikungunya virus (CHIKV), a mosquito-borne alphavirus. Since its reemergence in 2004, the virus has spread throughout the tropical world and several subtropical areas affecting millions of people to become a global public health issue. Given the significant disease burden, there is a need for medical countermeasures and several vaccine candidates are in clinical development. To characterize the global epidemiology of chikungunya and inform vaccine development, we undertook a systematic literature review in MEDLINE and additional public domain sources published up to June 13, 2020 and assessed epidemiological trends from 1999 to 2020. Observational studies addressing CHIKV epidemiology were included and studies not reporting primary data were excluded. Only descriptive analyses were conducted. Of 3,883 relevant sources identified, 371 were eligible for inclusion. 46% of the included studies were published after 2016. Ninety-seven outbreak reports from 45 countries and 50 seroprevalence studies from 31 countries were retrieved, including from Africa, Asia, Oceania, the Americas, and Europe. Several countries reported multiple outbreaks, but these were sporadic and unpredictable. Substantial gaps in epidemiological knowledge were identified, specifically granular data on disease incidence and age-specific infection rates. The retrieved studies revealed a diversity of methodologies and study designs, reflecting a lack of standardized procedures used to characterize this disease. Nevertheless, available epidemiological data emphasized the challenges to conduct vaccine efficacy trials due to disease unpredictability. A better understanding of chikungunya disease dynamics with appropriate granularity and better insights into the duration of long-term population immunity is critical to assist in the planning and success of vaccine development efforts pre and post licensure.
Topics: Aedes; Animals; Chikungunya Fever; Chikungunya virus; Disease Outbreaks; Humans; Mosquito Vectors; Neglected Diseases; Seroepidemiologic Studies; Vaccine Development; Viral Vaccines
PubMed: 35020717
DOI: 10.1371/journal.pntd.0010069 -
PloS One 2017Chikungunya virus infection (CHIKV) is caused by a mosquito-borne alphavirus. CHIKV causes high fever and painful rheumatic disorders that may persist for years. Because... (Review)
Review
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Topics: Antirheumatic Agents; Chikungunya Fever; Chikungunya virus; Chloroquine; Humans; Hydroxychloroquine; Musculoskeletal Diseases; Quality of Life; Randomized Controlled Trials as Topic; Rheumatic Diseases
PubMed: 28609439
DOI: 10.1371/journal.pone.0179028 -
Revista Da Associacao Medica Brasileira... Jan 2018Chikungunya (CHIK) is a tropical arbovirus, transmitted by the female mosquito Aedes aegypti and Aedes albopictus. In Brazil, there have been cases reported since 2014.... (Review)
Review
INTRODUCTION
Chikungunya (CHIK) is a tropical arbovirus, transmitted by the female mosquito Aedes aegypti and Aedes albopictus. In Brazil, there have been cases reported since 2014. The initial manifestations of this virus are sudden onset high fever, headache, chills, rashes, myalgia and intense joint pain. Usually, CHIK presents the acute and chronic phases, the latter characterized by bilateral polyarthralgia, which can last for months or even years. During this period, autoimmune diseases can be triggered, making the picture even more complicated.
METHOD
A systematic review was performed on the PubMed and Scielo databases in January 2017. Clinical trials, cohorts, case-control and case reports were included in the study. Expert opinions, societal consensuses and literary reviews were exclusion criteria. Studies were conducted in English, Spanish and Portuguese. The studies were descriptively analyzed and the data was grouped according to methodological similarity.
RESULTS
Twenty-four (24) articles were selected and, in compliance with the inclusion and exclusion criteria, 18 were eliminated, with six studies remaining in the present review: five clinical trials and one case report.
CONCLUSION
When the manifestations of CHIK become chronic and, the longer they last, more complications arise. Polyarthralgia can be immaterial, distancing individuals from their daily-life activities. Anti-inflammatory drugs (either steroid or not), in addition to immunosuppressants, homeopathy and physiotherapy are measures of treatment that, according to the literature, have been successful in relieving or extinguishing symptoms. However, it is fundamental that studies of CHIK treatment be further developed.
Topics: Animals; Arthritis; Arthritis, Infectious; Chikungunya Fever; Chikungunya virus; Humans
PubMed: 29561944
DOI: 10.1590/1806-9282.64.01.63 -
Journal of Medical Entomology Feb 2020Here we conducted a systematic review and meta-analysis to reach a consensus on whether infected and uninfected mosquitoes respond differently to repellents. After... (Meta-Analysis)
Meta-Analysis
Here we conducted a systematic review and meta-analysis to reach a consensus on whether infected and uninfected mosquitoes respond differently to repellents. After screening 2,316 published studies, theses, and conference abstracts, we identified 18 studies that tested whether infection status modulated the effectiveness of repellents. Thirteen of these studies had outcomes available for meta-analysis, and overall, seven repellents were tested (typically DEET with 62% of outcomes), six mosquito species had repellence behaviors measured (typically Aedes aegypti (L.) (Diptera: Culicidae) mosquitoes with 71% of outcomes), and a broad diversity of infections were tested including Sindbis virus (Togaviridae: Alphavirus) (33% of outcomes), Dengue (Flaviviridae: Flavivirus) (31%), malaria (Plasmodium berghei Vincke & Lips (Haemospororida: Plasmodiidae) or P. falciparum Welch (Haemospororida: Plasmodiidae); 25%), Zika (Flaviviridae: Flavivirus) (7%), and microsporidia (4%). Pooling all outcomes with meta-analysis, we found that repellents were less effective against infected mosquitoes-marking an average 62% reduction in protective efficacy relative to uninfected mosquitoes (pooled odds ratio = 0.38, 95% confidence interval = 0.22-0.66; k = 96). Older infected mosquitoes were also more likely to show altered responses and loss of sensitivity to repellents, emphasizing the challenge of distinguishing between age or incubation period effects. Plasmodium- or Dengue-infected mosquitoes also did not show altered responses to repellents; however, Dengue-mosquito systems used inoculation practices that can introduce variability in repellency responses. Given our findings that repellents offer less protection against infected mosquitoes and that these vectors are the most dangerous in terms of disease transmission, then trials on repellent effectiveness should incorporate infected mosquitoes to improve predictability in blocking vector-human contact.
Topics: Aedes; Animals; Anopheles; Culex; Insect Repellents; Mosquito Control; Mosquito Vectors
PubMed: 31755530
DOI: 10.1093/jme/tjz209 -
PLoS Neglected Tropical Diseases Jan 2022Neglected tropical diseases (NTDs) primarily affect the poorest populations, often living in remote, rural areas, urban slums or conflict zones. Arboviruses are a...
BACKGROUND
Neglected tropical diseases (NTDs) primarily affect the poorest populations, often living in remote, rural areas, urban slums or conflict zones. Arboviruses are a significant NTD category spread by mosquitoes. Dengue, Chikungunya, and Zika are three arboviruses that affect a large proportion of the population in Latin and South America. The clinical diagnosis of these arboviral diseases is a difficult task due to the concurrent circulation of several arboviruses which present similar symptoms, inaccurate serologic tests resulting from cross-reaction and co-infection with other arboviruses.
OBJECTIVE
The goal of this paper is to present evidence on the state of the art of studies investigating the automatic classification of arboviral diseases to support clinical diagnosis based on Machine Learning (ML) and Deep Learning (DL) models.
METHOD
We carried out a Systematic Literature Review (SLR) in which Google Scholar was searched to identify key papers on the topic. From an initial 963 records (956 from string-based search and seven from a single backward snowballing procedure), only 15 relevant papers were identified.
RESULTS
Results show that current research is focused on the binary classification of Dengue, primarily using tree-based ML algorithms. Only one paper was identified using DL. Five papers presented solutions for multi-class problems, covering Dengue (and its variants) and Chikungunya. No papers were identified that investigated models to differentiate between Dengue, Chikungunya, and Zika.
CONCLUSIONS
The use of an efficient clinical decision support system for arboviral diseases can improve the quality of the entire clinical process, thus increasing the accuracy of the diagnosis and the associated treatment. It should help physicians in their decision-making process and, consequently, improve the use of resources and the patient's quality of life.
Topics: Aedes; Animals; Arbovirus Infections; Chikungunya Fever; Chikungunya virus; Decision Support Systems, Clinical; Deep Learning; Dengue; Dengue Virus; Humans; Mosquito Vectors; Neglected Diseases; South America; Zika Virus; Zika Virus Infection
PubMed: 35025860
DOI: 10.1371/journal.pntd.0010061 -
Reviews in Medical Virology May 2018We performed a systematic review on the neurological complications of chikungunya virus. Such complications are being reported increasingly, owing primarily to the scale... (Review)
Review
We performed a systematic review on the neurological complications of chikungunya virus. Such complications are being reported increasingly, owing primarily to the scale of recent epidemics but also to a growing understanding of the virus' neurovirulence. We performed a thorough literature search using PubMed and Scopus databases, summating the data on all published reports of neurological disease associated with chikungunya virus. We appraised the data for each major condition in adults, children, and neonates, as well as evaluating the latest evidence on disease pathogenesis and management strategies. The review provides a comprehensive summary for clinicians, public health officials, and researchers tackling the challenges associated with this important emerging pathogen.
Topics: Biomarkers; Chikungunya Fever; Chikungunya virus; Disease Management; Geography; Global Health; Humans; Nervous System Diseases; Symptom Assessment
PubMed: 29671914
DOI: 10.1002/rmv.1978 -
Joint Bone Spine Dec 2018To estimate the incidence of chronic articular symptoms after chikungunya virus infection of patients from the American continent. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the incidence of chronic articular symptoms after chikungunya virus infection of patients from the American continent.
METHODS
We performed a systematic review of the literature using the MEDLINE, Web of Science and Scopus databases. We included only cohort studies conducted in the American continent reporting the incidence of chronic articular symptoms after chikungunya virus acute infection. The quality of the selected studies was evaluated through the Newcastle-Ottawa Scale for non-randomized studies and relevant data were extracted. The pooled incidence of post-chikungunya chronic symptoms was estimated using a random-effect model meta-analysis. Heterogeneity was assessed by Q of Cochrane and its P-value, Tau and I. Subgroup analysis was performed, and studies were stratified by quality, sample size, region, country, period of follow-up and study design.
RESULTS
Up to February 24, 2018, a total of 1115 potentially relevant studies were identified through our search strategy. After exclusion of 226 duplicates and 845 irrelevant studies, we retrieved 41 articles for full-text appreciation, from which 18 studies met our inclusion criteria and were included in this systematic review. Our meta-analysis suggests that 52% of the patients infected with the chikungunya virus will present chronic articular symptoms, although a high heterogeneity between studies was also found (I = 94%).
CONCLUSION
Fifty-two percent of chikungunya infected patients in the American continent are expected to develop the chronic stage of the disease. Chikungunya fever needs to be dealt as a major world health problem.
Topics: Arthralgia; Arthritis; Chikungunya Fever; Chikungunya virus; Global Health; Humans; Incidence
PubMed: 30053609
DOI: 10.1016/j.jbspin.2018.03.019 -
The American Journal of Tropical... May 2014Mosquito-borne viruses are a major public health threat, but their incubation periods are typically uncited, non-specific, and not based on data. We systematically... (Review)
Review
Mosquito-borne viruses are a major public health threat, but their incubation periods are typically uncited, non-specific, and not based on data. We systematically review the published literature on six mosquito-borne viruses selected for their public health importance: chikungunya, dengue, Japanese encephalitis, Rift Valley fever, West Nile, and yellow fever viruses. For each, we identify the literature's consensus on the incubation period, evaluate the evidence for this consensus, and provide detailed estimates of the incubation period and distribution based on published experimental and observational data. We abstract original data as doubly interval-censored observations. Assuming a log-normal distribution, we estimate the median incubation period, dispersion, 25th and 75th percentiles by maximum likelihood. We include bootstrapped 95% confidence intervals for each estimate. For West Nile and yellow fever viruses, we also estimate the 5th and 95th percentiles of their incubation periods.
Topics: Alphavirus Infections; Animals; Chikungunya Fever; Chikungunya virus; Culicidae; Dengue; Dengue Virus; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Infectious Disease Incubation Period; Public Health; Rift Valley Fever; Rift Valley fever virus; West Nile Fever; West Nile virus; Yellow Fever; Yellow fever virus
PubMed: 24639305
DOI: 10.4269/ajtmh.13-0403