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Clinical Microbiology and Infection :... Sep 2021Appropriate laboratory diagnostics for emerging arboviruses are key for patient management, surveillance and intervention, including molecular tests and serological...
BACKGROUND
Appropriate laboratory diagnostics for emerging arboviruses are key for patient management, surveillance and intervention, including molecular tests and serological tests detecting viral antigen or virus-specific antibodies.
OBJECTIVES
We provide an overview of the challenges towards serological testing for the most important emerging arboviruses, including Zika, dengue and chikungunya viruses.
SOURCES
We retrieved a data set on performance of commercially available antibody- and antigen-detecting tests from 89 peer-reviewed articles conducting a systematic literature research in PubMed.
CONTENT
We identified commonly used antibody- and antigen-detecting tests and analysed their overall performance. We discuss how timing of serological testing and the use of paired samples from acute and convalescent phases of infection are crucial to optimize diagnostic sensitivity and specificity. We then exemplify how serological diagnostics are challenged by the patient's infection history through the 'original antigenic sin' and cross-reactive antibodies in the context of global co-circulation of antigenically related viruses. We highlight how individual infection histories with different arboviruses and with other pathogens such as herpes viruses and Plasmodia can produce inaccurate test results. We show that rapid tests for antibody and antigen detection in point-of-care settings have a significantly lower sensitivity compared with laboratory-based tests such as ELISA. We show that the performance of antibody- and antigen-detecting tests varies greatly between tropical regions of endemic transmission and non-endemic regions. Finally, we highlight that test sensitivity and specificity have to be equilibrated carefully and frequently either of them must be prioritized over the other, depending on disease prevalence and intended use of tests.
IMPLICATIONS
For reliable serological diagnostics, it is essential to be aware of inherent test limitations. Although multiplexed testing and testing of convalescence samples can improve diagnostic performance, global spread of (re-)emerging viruses requires careful implementation and evaluation of serological testing and unambiguous results may not always be achievable.
Topics: Antibodies, Viral; Antigens, Viral; Arbovirus Infections; Arboviruses; Humans; Sensitivity and Specificity; Serologic Tests
PubMed: 34111589
DOI: 10.1016/j.cmi.2021.05.047 -
Revista Da Sociedade Brasileira de... 2021Cerebrospinal fluid analysis contributes to the diagnosis and neuropathogenesis of neuroinvasive arboviruses. Neurological complications caused by dengue, Zika, and...
INTRODUCTION
Cerebrospinal fluid analysis contributes to the diagnosis and neuropathogenesis of neuroinvasive arboviruses. Neurological complications caused by dengue, Zika, and chikungunya infections have high clinical relevance because of their high potential to cause death or neurological deficits. We aimed to evaluate the use of cerebrospinal fluid assays for diagnostic support in neurological disorders associated with dengue, chikungunya, and Zika infections.
METHODS
A systematic review was carried out by searching the electronic databases LILACS, PubMed, Scopus, and Embase for articles written in English, Portuguese, or Spanish in the last 19 years. Published studies were reviewed using the terms "dengue," "Zika", "chikungunya", alone or in combination with "cerebrospinal fluid" in the period from 2000 to 2019.
RESULTS
A total of 98,060 studies were identified; of these, 1.1% (1,041 studies, 58,478 cases) used cerebrospinal fluid assays for neurological investigations. The most frequent neurological disorders included encephalitis (41.4%), congenital syndromes (17%), and microcephaly associated with Zika virus infections (8.9%). Neuroinvasive disorders were confirmed in 8.03% of 58,478 cases by specific cerebrospinal fluid analyses. The main methods used were IgM-specific antibodies (66%) and reverse transcription-polymerase chain reaction (10%). The largest number of scientific papers (29%) originated from Brazil, followed by India (18.4%) and the United States (14.4%).
CONCLUSIONS
Although cerebrospinal fluid analysis is of great importance for increasing neurological diagnostic accuracy and contributes to the early diagnosis of neuroinvasive dengue, chikungunya, and Zika infections, it is underused in routine laboratory investigations worldwide.
Topics: Brazil; Chikungunya Fever; Chikungunya virus; Dengue; Dengue Virus; Humans; Zika Virus; Zika Virus Infection
PubMed: 33950132
DOI: 10.1590/0037-8682-0891-2020 -
International Journal of Environmental... Apr 2021This review provided a systematic overview of the questionnaire-related dengue studies conducted in Malaysia and evaluated their reliability and validity used in the... (Meta-Analysis)
Meta-Analysis Review
This review provided a systematic overview of the questionnaire-related dengue studies conducted in Malaysia and evaluated their reliability and validity used in the questionnaires. An extensive literature search was conducted using various electronic databases, including PubMed, EMBASE, Medline, and ScienceDirect. Systematic reviews and meta-analysis (PRISMA) were selected as the preferred item reporting method. Out of 88 identified dengue-related, 57 published from 2000 to April 2020 met the inclusion criteria and were included. Based on the meta-analysis, a poor mean score was obtained for knowledge (49%), attitude (44%), and preventive practice (55%). The study showed that the level of knowledge on cardinal signs and modes of transmission for dengue virus were highest among health care workers, followed by students (international and local) and lastly community residents. In treatment-seeking behaviours, only half of the respondents (50.8%) would send their child to the nearest health clinics or hospitals when a child became restless or lethargic. The acceptance rate for dengue vaccine, bacteria (Wolbachia), as a vector for dengue control and self-test diagnostic kit for dengue showed considerably high (88.4%, 70%, and 44.8%, respectively). Health belief model (HBM) constructs, such as perceived barriers, perceived severity, perceived susceptibility, self-efficacy, and perceived benefit influence prevention practices. Lastly, only 23 articles (40.3%) had piloted or pretested the questionnaire before surveying, in which three reported Cronbach's alpha coefficient (0.70-0.90). A need for active participation of communities and healthcare personnel, promotion of awareness, and safe complementary medicines, as well as assessment of psychometric properties of questionnaire use in dengue surveys in Malaysia, in order for assessing dengue reliably and valid.
Topics: Child; Dengue; Health Knowledge, Attitudes, Practice; Humans; Malaysia; Reproducibility of Results; Surveys and Questionnaires
PubMed: 33922427
DOI: 10.3390/ijerph18094474 -
PLoS Neglected Tropical Diseases Apr 2021As the three major arthropod-borne viruses, dengue virus (DENV), chikungunya virus (CHIKV), and zika virus (ZIKV) are posing a growing threat to global public health and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As the three major arthropod-borne viruses, dengue virus (DENV), chikungunya virus (CHIKV), and zika virus (ZIKV) are posing a growing threat to global public health and socioeconomic development. Our study aimed to systematically review the global seroprevalences of these arboviruses from existing publications.
METHODS
Articles published between Jan 01, 2000 and Dec 31, 2019 in the databases of Embase, Pubmed and Web of Science were searched and collected. Countries or areas with known local presence of Aedes vector mosquitoes were included. Random effects model was utilized to estimate the pooled seroprevalences and the proportion of inapparent infection.
RESULTS
Out of 1375, a total of 133 articles involving 176,001 subjects were included for our analysis. The pooled seroprevalences of DENV, CHIKV and ZIKV were 38%, 25% and 18%, respectively; and their corresponding proportions of inapparent infections were 80%, 40% and 50%. The South-East Asia Region had the highest seroprevalences of DENV and CHIKV, while the Region of the Americas had the highest seroprevalence of ZIKV. The seroprevalences of DENV and CHIKV were similar when comparing developed and developing countries, urban and rural areas, or among different populations. In addition, we observed a decreased global seroprevalences in the new decade (2010-2019) comparing to the decade before (2000-2009) for CHIKV. For ZIKV, the positive rates tested with the nucleic acid detection method were lower than those tested with the antibody detection method. Lastly, numerous cases of dual seropositivity for CHIKV and DENV were reported.
CONCLUSIONS
Our results revealed a varied prevalence of arbovirus infections in different geographical regions and countries, and the inapparent infection accounted an unneglected portion of infections that requires more attention. This study will shed lights on our understanding of the true burden of arbovirus infections and promote appropriate vaccination in the future.
Topics: Aedes; Animals; Chikungunya Fever; Chikungunya virus; Dengue; Dengue Virus; Global Health; Humans; Mosquito Vectors; Seroepidemiologic Studies; Zika Virus; Zika Virus Infection
PubMed: 33909610
DOI: 10.1371/journal.pntd.0009337 -
PLoS Neglected Tropical Diseases Apr 2021Dengue is the world's most common mosquito-borne virus but remains diagnostically challenging due to its nonspecific presentation. Access to laboratory confirmation is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dengue is the world's most common mosquito-borne virus but remains diagnostically challenging due to its nonspecific presentation. Access to laboratory confirmation is limited and thus most reported figures are based on clinical diagnosis alone, the accuracy of which is uncertain. This systematic review assesses the diagnostic accuracy of the traditional (1997) and revised (2009) WHO clinical case definitions for dengue fever, the basis for most national guidelines.
METHODOLOGY/PRINCIPAL FINDINGS
PubMed, EMBASE, Scopus, OpenGrey, and the annual Dengue Bulletin were searched for studies assessing the diagnostic accuracy of the unmodified clinical criteria. Two reviewers (NR/SL) independently assessed eligibility, extracted data, and evaluated risk of bias using a modified QUADAS-2. Additional records were found by citation network analysis. A meta-analysis was done using a bivariate mixed-effects regression model. Studies that modified criteria were analysed separately. This systematic review protocol was registered on PROSPERO (CRD42020165998). We identified 11 and 12 datasets assessing the 1997 and 2009 definition, respectively, and 6 using modified criteria. Sensitivity was 93% (95% CI: 77-98) and 93% (95% CI: 86-96) for the 1997 and 2009 definitions, respectively. Specificity was 29% (95% CI: 8-65) and 31% (95% CI: 18-48) for the 1997 and 2009 definitions, respectively. Diagnostic performance suffered at the extremes of age. No modification significantly improved accuracy.
CONCLUSIONS/SIGNIFICANCE
Diagnostic accuracy of clinical criteria is poor, with significant implications for surveillance and public health responses for dengue control. As the basis for most reported figures, this has relevance to policymakers planning resource allocation and researchers modelling transmission, particularly during COVID-19.
Topics: COVID-19; Databases, Factual; Dengue; Diagnosis, Differential; Humans; SARS-CoV-2; Sensitivity and Specificity; World Health Organization
PubMed: 33901191
DOI: 10.1371/journal.pntd.0009359 -
Revista Brasileira de Epidemiologia =... 2021To describe the entry of Dengue virus (DENV) serotypes in Brazil and its federative units.
OBJECTIVE
To describe the entry of Dengue virus (DENV) serotypes in Brazil and its federative units.
METHODS
A systematic review of studies published between 1980 and 2018 in databases and in the gray literature was performed using descriptors related to the years of entry of the DENV serotypes. Additionally, experts and official sources of information (Brazilian Ministry of Health) were consulted.
RESULTS
From 100 publications selected for the systematic review, 26 addressed the entry of DENV serotypes in the North region of the country, 33 in the Northeast, 24 in the Southeast, 14 in the Central-West, and five in the South. DENV-1 and DENV-4 were introduced in the North region in 1981. DENV-2 was introduced in the Southeast in 1990. DENV-3 was introduced in the North in 1999.
CONCLUSION
The rapid expansion of dengue throughout the Brazilian territory was verified from the second half of the 1980s, with the gradual entry of the four serotypes, which resulted in the emergence of epidemics of arbovirus, which are currently verified in the country. Considering the epidemiology of the disease, more information should be disseminated and published in the wide-ranging scientific literature for a better understanding of the spread and circulation of DENV serotypes.
Topics: Brazil; Dengue; Dengue Virus; Geography; Humans; Serogroup
PubMed: 33825776
DOI: 10.1590/1980-549720210020 -
Dengue Virus Infection and Associated Risk Factors in Africa: A Systematic Review and Meta-Analysis.Viruses Mar 2021Dengue contributes a significant burden on global public health and economies. In Africa, the burden of dengue virus (DENV) infection is not well described. This review... (Meta-Analysis)
Meta-Analysis
Dengue contributes a significant burden on global public health and economies. In Africa, the burden of dengue virus (DENV) infection is not well described. This review was undertaken to determine the prevalence of dengue and associated risk factors. A literature search was done on PubMed/MEDLINE, Scopus, Embase, and Google Scholar databases to identify articles published between 1960 and 2020. Meta-analysis was performed using a random-effect model at a 95% confidence interval, followed by subgroup meta-analysis to determine the overall prevalence. Between 1960 and 2020, 45 outbreaks were identified, of which 17 and 16 occurred in East and West Africa, respectively. Dengue virus serotype 1 (DENV-1) and DENV-2 were the dominant serotypes contributing to 60% of the epidemics. Of 2211 cases reported between 2009 and 2020; 1954 (88.4%) were reported during outbreaks. Overall, the prevalence of dengue was 29% (95% CI: 20-39%) and 3% (95% CI: 1-5%) during the outbreak and non-outbreak periods, respectively. Old age (6/21 studies), lack of mosquito control (6/21), urban residence (4/21), climate change (3/21), and recent history of travel (3/21) were the leading risk factors. This review reports a high burden of dengue and increased risk of severe disease in Africa. Our findings provide useful information for clinical practice and health policy decisions to implement effective interventions.
Topics: Africa; Age Factors; Cost of Illness; Dengue; Dengue Virus; Disease Outbreaks; Humans; Mosquito Control; Prevalence; Risk Factors; Serogroup; Severe Dengue; Urban Population
PubMed: 33804839
DOI: 10.3390/v13040536 -
Reviews in Medical Virology Nov 2021Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)...
Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non-SARS-CoV2 infection supported the use of these agents in the present SARS-CoV2 outbreak. PubMed, EMBASE, Scopus and Web of Science (PROSPERO CRD42020183429) were searched from inception through 2 April 2020 without language restrictions. Of 1766 retrieved reports, 18 studies met our inclusion criteria, including 17 prospective controlled studies and one retrospective study. CQ or HCQ were compared to control for the treatment of infectious mononucleosis (EBV, n = 4), warts (human papillomavirus, n = 2), chronic HIV infection (n = 6), acute chikungunya infection (n = 1), acute dengue virus infection (n = 2), chronic HCV (n = 2), and as preventive measures for influenza infection (n = 1). Survival was not evaluated in any study. For HIV, the virus that was most investigated, while two early studies suggested HCQ reduced viral levels, four subsequent ones did not, and in two of these CQ or HCQ increased viral levels and reduced CD4 counts. Overall, three studies concluded CQ or HCQ were effective; four concluded further research was needed to assess the treatments' effectiveness; and 11 concluded that treatment was ineffective or potentially harmful. Prior controlled clinical trials with CQ and HCQ for non-SARS-CoV2 viral infections do not support these agents' use for the SARS-CoV2 outbreak.
Topics: Alphapapillomavirus; Antiviral Agents; COVID-19; Chikungunya Fever; Chikungunya virus; Chloroquine; Dengue Virus; HIV; HIV Infections; Hepacivirus; Hepatitis C, Chronic; Herpesvirus 4, Human; Humans; Hydroxychloroquine; Infectious Mononucleosis; SARS-CoV-2; Severe Dengue; Treatment Outcome; Warts; COVID-19 Drug Treatment
PubMed: 33694220
DOI: 10.1002/rmv.2228 -
The Lancet. Infectious Diseases Jul 2021The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and meta-analyses have found significant heterogeneity in predictors of severe disease due to large variation in these factors during the time course of the illness. We aimed to identify factors associated with progression to severe dengue disease that are detectable specifically in the febrile phase.
METHODS
We did a systematic review and meta-analysis to identify predictors identifiable during the febrile phase associated with progression to severe disease defined according to WHO criteria. Eight medical databases were searched for studies published from Jan 1, 1997, to Jan 31, 2020. Original clinical studies in English assessing the association of factors detected during the febrile phase with progression to severe dengue were selected and assessed by three reviewers, with discrepancies resolved by consensus. Meta-analyses were done using random-effects models to estimate pooled effect sizes. Only predictors reported in at least four studies were included in the meta-analyses. Heterogeneity was assessed using the Cochrane Q and I statistics, and publication bias was assessed by Egger's test. We did subgroup analyses of studies with children and adults. The study is registered with PROSPERO, CRD42018093363.
FINDINGS
Of 6643 studies identified, 150 articles were included in the systematic review, and 122 articles comprising 25 potential predictors were included in the meta-analyses. Female patients had a higher risk of severe dengue than male patients in the main analysis (2674 [16·2%] of 16 481 vs 3052 [10·5%] of 29 142; odds ratio [OR] 1·13 [95% CI 1·01-1·26) but not in the subgroup analysis of studies with children. Pre-existing comorbidities associated with severe disease were diabetes (135 [31·3%] of 431 with vs 868 [16·0%] of 5421 without; crude OR 4·38 [2·58-7·43]), hypertension (240 [35·0%] of 685 vs 763 [20·6%] of 3695; 2·19 [1·36-3·53]), renal disease (44 [45·8%] of 96 vs 271 [16·0%] of 1690; 4·67 [2·21-9·88]), and cardiovascular disease (nine [23·1%] of 39 vs 155 [8·6%] of 1793; 2·79 [1·04-7·50]). Clinical features during the febrile phase associated with progression to severe disease were vomiting (329 [13·5%] of 2432 with vs 258 [6·8%] of 3797 without; 2·25 [1·87-2·71]), abdominal pain and tenderness (321 [17·7%] of 1814 vs 435 [8·1%] of 5357; 1·92 [1·35-2·74]), spontaneous or mucosal bleeding (147 [17·9%] of 822 vs 676 [10·8%] of 6235; 1·57 [1·13-2·19]), and the presence of clinical fluid accumulation (40 [42·1%] of 95 vs 212 [14·9%] of 1425; 4·61 [2·29-9·26]). During the first 4 days of illness, platelet count was lower (standardised mean difference -0·34 [95% CI -0·54 to -0·15]), serum albumin was lower (-0·5 [-0·86 to -0·15]), and aminotransferase concentrations were higher (aspartate aminotransferase [AST] 1·06 [0·54 to 1·57] and alanine aminotransferase [ALT] 0·73 [0·36 to 1·09]) among individuals who progressed to severe disease. Dengue virus serotype 2 was associated with severe disease in children. Secondary infections (vs primary infections) were also associated with severe disease (1682 [11·8%] of 14 252 with vs 507 [5·2%] of 9660 without; OR 2·26 [95% CI 1·65-3·09]). Although the included studies had a moderate to high risk of bias in terms of study confounding, the risk of bias was low to moderate in other domains. Heterogeneity of the pooled results varied from low to high on different factors.
INTERPRETATION
This analysis supports monitoring of the warning signs described in the 2009 WHO guidelines on dengue. In addition, testing for infecting serotype and monitoring platelet count and serum albumin, AST, and ALT concentrations during the febrile phase of illness could improve the early prediction of severe dengue.
FUNDING
Wellcome Trust, National Institute for Health Research, Collaborative Project to Increase Production of Rural Doctors, and Royal Thai Government.
Topics: Abdominal Pain; Coinfection; Comorbidity; Disease Progression; Fever; Humans; Platelet Count; Risk Factors; Serum Albumin; Severe Dengue; Sex Factors; Vomiting
PubMed: 33640077
DOI: 10.1016/S1473-3099(20)30601-0 -
One Health (Amsterdam, Netherlands) Jun 2021Dengue is a rapidly spreading mosquito-borne flavivirus infection that is prevalent in tropical and sub-tropical regions. Humans are known to be the main reservoir host... (Review)
Review
Dengue is a rapidly spreading mosquito-borne flavivirus infection that is prevalent in tropical and sub-tropical regions. Humans are known to be the main reservoir host maintaining the epidemic cycles of dengue but it is unclear if dengue virus is also maintained in a similar enzootic cycle. The systematic review was conducted in accordance to Cochrane's PRISMA recommendations. A search was done on PubMed, EMBASE, Scopus and Cochrane Library. Key data on animal dengue positivity was extracted and classified according to animal type and diagnostic modes. Of the 3818 articles identified, 56 articles were used in this review. A total of 16,333 animals were tested, 1817 of which were positive for dengue virus by RT-PCR or serology. Dengue positivity was detected in bats (10.1%), non-human primates (27.3%), birds (11%), bovid (4.1%), dogs (1.6%), horses (5.1%), pigs (34.1%), rodents (3.5%), marsupials (13%) and other small animals (7.3%). While majority of dengue positivity via serology suggests potential enzootic transmission, but regular dengue virus spillback cannot be excluded. With the exception of bats, acute infection among animals is limited. Further investigation on animals is critically required to better understand their role as potential reservoir in dengue transmission.
PubMed: 33598525
DOI: 10.1016/j.onehlt.2021.100216