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Fulltext Review of Dengue hemorrhagic fever fatal cases seen among adults: a retrospective study

Sam SS, Omar SF, Teoh BT, Abd-Jamil J, AbuBakar S

PLoS Negl Trop Dis, 2013;7(5):e2194.
PMID: 23658849 DOI: 10.1371/journal.pntd.0002194

Dengue is a mosquito-borne viral disease endemic in many countries in the tropics and sub-tropics. The disease affects mainly children, but in recent years it is becoming more of an adult disease. Malaysia experienced a large dengue outbreak in 2006 to 2007, involving mostly adults, with a high number of deaths.

Matched MeSH terms: Severe Dengue/mortality*
Dengue-induced Acute Kidney Injury (DAKI): A Neglected and Fatal Complication of Dengue Viral Infection--A Systematic Review

Mallhi TH, Sarriff A, Adnan AS, Khan YH, Hamzah AA, Jummaat F, et al.

J Coll Physicians Surg Pak, 2015 Nov;25(11):828-34.
PMID: 26577971 DOI: 11.2015/JCPSP.828834

Dengue Viral Infection (DVI) imperils an estimated 2.5 billion people living in tropical and subtropical regions. World Health Organization (2011) guidelines also classified dengue as 'Expanded Dengue Syndrome' to incorporate wide spectrum of unusual manifestations of dengue infection affecting various organ systems - including liver, kidney, heart and brain. Renal involvements are least appreciated area of dengue infection, therefore, we systematically reviewed studies describing renal disorders in dengue infection, with emphasis on Acute Kidney Injury (AKI). The purpose of current review is to underscore clinicians’attention to this neglected intricacy of DVI. It suggests that dengue induced renal involvements vary from glomerulonephritis, nephrotic range proteinuria and AKI. We observed great disparity in incidence of AKI among dengue patients, based upon criteria used to define AKI. AKI among dengue patients was found to be associated with significant morbidity, mortality and longer hospitalization, adding financial burden to patients and healthcare system. Additionally, we identified several predictors of AKI in dengue patients including old age, obesity, severe dengue infection and concurrent bacterial or viral infection. Direct viral injury and deposition of antigen-antibody complex in glomerulus were found to be possible causes of renal disorders in dengue infection. Prior knowledge of clinico-laboratory characteristics and risk factors with early detection of AKI by using appropriate criteria would not only reduce morbidity and mortality but also decrease burden to patients and healthcare system.

Matched MeSH terms: Severe Dengue/mortality*
Fulltext Prediction of mortality in severe dengue cases

Md-Sani SS, Md-Noor J, Han WH, Gan SP, Rani NS, Tan HL, et al.

BMC Infect Dis, 2018 05 21;18(1):232.
PMID: 29783955 DOI: 10.1186/s12879-018-3141-6

BACKGROUND: Increasing incidence of dengue cases in Malaysia over the last few years has been paralleled by increased deaths. Mortality prediction models will therefore be useful in clinical management. The aim of this study is to identify factors at diagnosis of severe dengue that predicts mortality and assess predictive models based on these identified factors.
METHOD: This is a retrospective cohort study of confirmed severe dengue patients that were admitted in 2014 to Hospital Kuala Lumpur. Data on baseline characteristics, clinical parameters, and laboratory findings at diagnosis of severe dengue were collected. The outcome of interest is death among patients diagnosed with severe dengue.
RESULTS: There were 199 patients with severe dengue included in the study. Multivariate analysis found lethargy, OR 3.84 (95% CI 1.23-12.03); bleeding, OR 8.88 (95% CI 2.91-27.15); pulse rate, OR 1.04 (95% CI 1.01-1.07); serum bicarbonate, OR 0.79 (95% CI 0.70-0.89) and serum lactate OR 1.27 (95% CI 1.09-1.47), to be statistically significant predictors of death. The regression equation to our model with the highest AUROC, 83.5 (95% CI 72.4-94.6), is: Log odds of death amongst severe dengue cases = - 1.021 - 0.220(Serum bicarbonate) + 0.001(ALT) + 0.067(Age) - 0.190(Gender).
CONCLUSION: This study showed that a large proportion of severe dengue occurred early, whilst patients were still febrile. The best prediction model to predict death at recognition of severe dengue is a model that incorporates serum bicarbonate and ALT levels.

Matched MeSH terms: Severe Dengue/mortality*
Fulltext A two-year review on epidemiology and clinical characteristics of dengue deaths in Malaysia, 2013-2014

Woon YL, Hor CP, Hussin N, Zakaria A, Goh PP, Cheah WK

PLoS Negl Trop Dis, 2016 05;10(5):e0004575.
PMID: 27203726 DOI: 10.1371/journal.pntd.0004575

BACKGROUND: Dengue infection is the fastest spreading mosquito-borne viral disease, which affects people living in the tropical and subtropical countries. Malaysia had large dengue outbreaks in recent years. We aimed to study the demographics and clinical characteristics associated with dengue deaths in Malaysia.

METHODS: We conducted a retrospective review on all dengue deaths that occurred nationwide between 1st January 2013 and 31st December 2014. Relevant data were extracted from mortality review reports and investigational forms. These cases were categorized into children (<15 years), adults (15-59 years) and elderly (≥60 years) to compare their clinical characteristics.

RESULTS: A total of 322 dengue deaths were reviewed. Their mean age was 40.7±19.30 years, half were females and 72.5% were adults. The median durations of first medical contact, and hospitalization were 1 and 3 days, respectively. Diabetes and hypertension were common co-morbidities among adults and elderly. The most common warning signs reported were lethargy and vomiting, with lethargy (p = 0.038) being more common in children, while abdominal pain was observed more often in the adults (p = 0.040). But 22.4% did not have any warning signs. Only 34% were suspected of dengue illness at their initial presentation. More adults developed severe plasma leakage (p = 0.018). More than half (54%) suffered from multi-organ involvement, and 20.2% were free from any organ involvement. Dengue deaths occurred at the median of 3 days post-admission. Dengue shock syndrome (DSS) contributed to more than 70% of dengue deaths, followed by severe organ involvement (69%) and severe bleeding (29.7%).

CONCLUSION: In Malaysia, dengue deaths occurred primarily in adult patients. DSS was the leading cause of death, regardless of age groups. The atypical presentation and dynamic progression of severe dengue in this cohort prompts early recognition and aggressive intervention to prevent deaths.

TRIAL REGISTRATION: National Medical Research Registry (NMRR, NMRR-14-1374-23352).

Matched MeSH terms: Severe Dengue/mortality*
Fulltext Determinants of mortality and prolonged hospital stay among dengue patients attending tertiary care hospital: a cross-sectional retrospective analysis

Mallhi TH, Khan AH, Sarriff A, Adnan AS, Khan YH

BMJ Open, 2017 Jul 10;7(7):e016805.
PMID: 28698348 DOI: 10.1136/bmjopen-2017-016805

OBJECTIVES: Dengue imposes substantial economic, societal and personal burden in terms of hospital stay, morbidity and mortality. Early identification of dengue cases with high propensity of increased hospital stay and death could be of value in isolating patients in need of early interventions. The current study was aimed to determine the significant factors associated with dengue-related prolonged hospitalisation and death.

DESIGN: Cross-sectional retrospective study.

SETTING: Tertiary care teaching hospital.

PARTICIPANTS: Patients with confirmed dengue diagnosis were stratified into two categories on the basis of prolonged hospitalisation (≤3 days and >3 days) and mortality (fatal cases and non-fatal cases). Clinico-laboratory characteristics between these categories were compared by using appropriate statistical methods.

RESULTS: Of 667 patients enrolled, 328 (49.2%) had prolonged hospitalisation. The mean hospital stay was 4.88±2.74 days. Multivariate analysis showed that dengue haemorrhagic fever (OR 2.3), elevated alkaline phosphatase (ALP) (OR 2.3), prolonged prothrombin time (PT) (OR 1.7), activated partial thromboplastin time (aPTT) (OR 1.9) and multiple-organ dysfunctions (OR 2.1) were independently associated with prolonged hospitalisation. Overall case fatality rate was 1.1%. Factors associated with dengue mortality were age >40 years (p=0.004), secondary infection (p=0.040), comorbidities (p<0.05), acute kidney injury (p<0.001), prolonged PT (p=0.022), multiple-organ dysfunctions (p<0.001), haematocrit >20% (p=0.001), rhabdomyolosis (p<0.001) and respiratory failure (p=0.007). Approximately half of the fatal cases in our study had prolonged hospital stay of greater than three days.

CONCLUSIONS: The results underscore the high proportion of dengue patients with prolonged hospital stay. Early identification of factors relating to prolonged hospitalisation and death will have obvious advantages in terms of appropriate decisions about treatment and management in high dependency units.

Study site: Hospital Universiti Sains Malaysia (HUSM), Kelantan

Matched MeSH terms: Severe Dengue/mortality*
Unusual, neurological and severe dengue manifestations during the outbreak in Sri Lanka, 2017

Ngwe Tun MM, Muthugala R, Nabeshima T, Rajamanthri L, Jayawardana D, Attanayake S, et al.

J Clin Virol, 2020 04;125:104304.
PMID: 32145478 DOI: 10.1016/j.jcv.2020.104304

BACKGROUND: Sri Lanka experienced its largest dengue outbreak in 2017 with more than 185,000 dengue cases including at least 250 fatalities.
OBJECTIVES: Our study aimed to characterize the clinical, immunological and virological features of confirmed dengue patients in Sri Lanka during the outbreak in 2017 when unusual manifestations of severe dengue were observed.
STUDY DESIGN: Sera from 295 patients who were admitted to Teaching Hospital Kandy, Kandy, Sri Lanka between March 2017- January 2018 were subjected to NS1 antigen, IgM and IgG ELISAs, virus isolation, conventional and real time RT-PCR and next generation sequencing.
RESULTS: Primary and secondary infections were detected in 48.5 % and 51.5 % of the study population, respectively. Two hundred twenty five DENV strains were isolated (219 DENV-2, one DENV-3, two DENV-4, two mixed infections of DENV-2 and -3 and one mixed infection of DENV-2 and -4). Unusual and severe manifestations such as encephalitis, encephalopathy, liver failure, kidney failure, myocarditis, Guillain-Barré syndrome and multi-organ failure were noted in 44 dengue patients with 11 deaths. The viraemia levels in patients with primary infection and unusual manifestations were significantly higher compared to those in patients with secondary infection. A new clade of DENV-2 Cosmopolitan genotype strains was observed with the strains closely related to those from China, Malaysia, Indonesia, Singapore and Taiwan.
CONCLUSIONS: The new clade of DENV-2 cosmopolitan genotype observed in Sri Lanka in 2017 caused an unprecedented, severe dengue outbreak. The emergence of DENV-3 and DENV-4 in the 2017 outbreak might cause future outbreaks in Sri Lanka.

Matched MeSH terms: Severe Dengue/mortality