METHODS: In-depth individual interviews with thematic saturation were conducted between May and July 2018. The data was analyzed using thematic analysis.
RESULTS: Based on expert opinion, diagnosis of severe dengue is challenging as it depends on astute clinical interpretation of non-dengue-specific clinical and laboratory findings. A specific test that detects impending manifestation of severe dengue could 1) overcome failure in identifying severe disease for referral or admission, 2) facilitate timely and appropriate management of plasma leakage and bleeding, 3) overcome the lack of clinical expertise and laboratory diagnosis in rural health settings. The most important feature of any diagnostics for severe dengue is the point-of-care (POC) format where it can be performed at or near the bedside.
CONCLUSION: The development of diagnostics to detect impending severe dengue is warranted to reduce the morbidity and mortality rates of dengue infection and it should be prioritized.
METHODOLOGY AND PRINCIPAL FINDINGS: A total of 120 retrospective dengue serum specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR, sequencing and phylogenetic analysis. Subsequently, the dengue serotype and genotype data were statistically analyzed for 101 of 120 corresponding patients' clinical manifestations to generate a descriptive relation between the genetic components and clinical outcomes of dengue infected patients. During the study period, predominant dengue serotype and genotype were found to be DENV 1 genotype I. Additionally, non-severe clinical manifestations were commonly observed in patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2 infection showed significant warning signs and developed severe dengue (p = 0.007). Cases infected with DENV 2 were also commonly presented with persistent vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific clinical manifestations showed that DENV 2 Cosmopolitan was significantly common among severe dengue patients. An association was also found between genotype I of DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly common among patients with arthralgia.
CONCLUSION: The current data contended that different dengue serotype and genotype had caused distinct clinical characteristics in infected patients.
METHODS: Data related to the number of cases involving dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue infections caused by different serotypes of dengue virus were obtained by using the SCOPUS, the PUBMED and the OVID search engines with the keywords "(dengue* OR dengue virus*) AND (severe dengue* OR severity of illness index* OR severity* OR DF* OR DHF* OR DSS*) AND (serotypes* OR serogroup*)", according to the MESH terms suggested by PUBMED and OVID.
RESULTS: Approximately 31 studies encompassing 15,741 cases reporting on the dengue serotypes together with their severity were obtained, and meta-analysis was carried out to analyze the data. This study found that DENV-3 from the Southeast Asia (SEA) region displayed the greatest percentage of severe cases in primary infection (95% confidence interval (CI), 31.22-53.67, 9 studies, n = 598, I2 = 71.53%), whereas DENV-2, DENV-3, and DENV-4 from the SEA region, as well as DENV-2 and DENV-3 from non-SEA regions, exhibited the greatest percentage of severe cases in secondary infection (95% CI, 11.64-80.89, 4-14 studies, n = 668-3,149, I2 = 14.77-96.20%). Moreover, DENV-2 and DENV-4 from the SEA region had been found to be more highly associated with dengue shock syndrome (DSS) (95% CI, 10.47-40.24, 5-8 studies, n = 642-2,530, I2 = 76.93-97.70%), while DENV-3 and DENV-4 from the SEA region were found to be more highly associated with dengue hemorrhagic fever (DHF) (95% CI, 31.86-54.58, 9 studies, n = 674-2,278, I2 = 55.74-88.47%), according to the 1997 WHO dengue classification. Finally, DENV-2 and DENV-4 from the SEA region were discovered to be more highly associated with secondary infection compared to other serotypes (95% CI, 72.01-96.32, 9-12 studies, n = 671-2,863, I2 = 25.01-96.75%).
CONCLUSION: This study provides evidence that the presence of certain serotypes, including primary infection with DENV-3 from the SEA region and secondary infection with DENV-2, DENV-3, and DENV-4 also from the SEA region, as well as DENV-2 and DENV-3 from non SEA regions, increased the risk of severe dengue infections. Thus, these serotypes are worthy of special consideration when making clinical predictions upon the severity of the infection.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026093 (http://www.crd.york.ac.uk/PROSPERO).
METHODS: To determine Zika virus (ZIKV) seroprevalence in Kuala Lumpur, Malaysia, 1085 serum samples from 2012, 2014-2015 and 2017 were screened for anti-ZIKV antibodies using a ZIKV NS1 blockade-of-binding assay. Reactive samples were confirmed using neutralization assays against ZIKV and the four dengue virus (DENV) serotypes. A sample was possible ZIKV seropositive with a ZIKV 50% neutralization (NT50) titre ≥20. A sample was probable ZIKV seropositive if, in addition, all DENV NT50 titres were <20 or the ZIKV NT50 titre was >4-fold greater than the highest DENV NT50 titre.
RESULTS: We found low rates of possible ZIKV seropositivity (3.3% [95% confidence interval {CI} 2.4 to 4.6]) and probable ZIKV seropositivity (0.6% [95% CI 0.3 to 1.4]). Possible ZIKV seropositivity was independently associated with increasing age (odds ratio [OR] 1.04 [95% CI 1.02 to 1.06], p<0.0001) and male gender (OR 3.5 [95% CI 1.5 to 8.6], p=0.005).
CONCLUSIONS: The low ZIKV seroprevalence rate, a proxy for population immunity, does not explain the low incidence of Zika in dengue-hyperendemic Kuala Lumpur. Other factors, such as the possible protective effects of pre-existing flavivirus antibodies or reduced transmission by local mosquito vectors, should be explored. Kuala Lumpur is at high risk of a large-scale Zika epidemic.