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  1. Wartel TA, Prayitno A, Hadinegoro SR, Capeding MR, Thisyakorn U, Tran NH, et al.
    Asia Pac J Public Health, 2017 Jan;29(1):7-16.
    PMID: 28198645 DOI: 10.1177/1010539516675701
    We described and quantified epidemiologic trends in dengue disease burden in 5 Asian countries (Indonesia, Thailand, Malaysia, Philippines, and Vietnam) and identified and estimated outbreaks impact over the last 3 decades. Dengue surveillance data from 1980 to 2010 were retrieved from DengueNet and from World Health Organization sources. Trends in incidence, mortality, and case fatality rate (CFR) were systematically analyzed using annual average percent change (AAPC), and the contribution of epidemic years identified over the observation period was quantified. Over the 30-year period, incidence increased in all countries (AAPC 1980-2010: 6.7% in Thailand, 10.4% in Vietnam, 12.0% in Indonesia, 18.1% in Malaysia, 24.4% in Philippines). Mortality also increased in Indonesia, Malaysia, and Philippines (AAPC: 6.8%, 7.0%, and 29.2%, respectively), but slightly decreased in Thailand and Vietnam (AAPC: -1.3% and -2.5%), and CFR decreased in all countries (AAPC: -4.2% to -8.3%). Epidemic years, despite representing less than a third of the observation period, contributed from 1 to 3 times more cases versus nonepidemic years. Implementation of more sensitive surveillance methods over the study period may have contributed to a reporting or ascertainment bias in some countries. Nonetheless, these data support the urgent need for novel, integrated, or otherwise effective dengue prevention and control tools and approaches.
    Matched MeSH terms: Dengue/mortality
  2. Mia MS, Begum RA, Er AC, Abidin RD, Pereira JJ
    Asian Pac J Trop Med, 2013 Jun;6(6):462-6.
    PMID: 23711707 DOI: 10.1016/S1995-7645(13)60075-9
    OBJECTIVE: To analyze trends of dengue incidences and deaths in Malaysia from 2000 to 2010 as well as the predominant dengue virus serotypes during the last decade.

    METHODS: We used the national data on annual reported cases, deaths, incidence rate, mortality rate, and case fatality rate of dengue fever (DF) and dengue hemorrhagic fever (DHF) as well as dengue virus serotypes prevalent in Malaysia during the last decade. Trend/ regression lines were fitted to investigate the trend of dengue incidences and deaths due to the disease for a 11-year period (2000-2010). For the distribution of national incidence rate, mortality rate, and case fatality rate of DF and DHF, descriptive statistics using mean and 95% confidence intervals (CI 39) for means, and range were applied.

    RESULTS: The number of dengue cases and number of deaths have increased, on average, by 14% and 8% per year respectively. The average annual incidence rate of DF per 100 000 populations was higher as compared to that of DHF. Conversely, the yearly mean mortality rate of DHF per 100 000 populations was greater than that of DF. The simultaneous circulation of all four dengue serotypes has been found in Malaysia. But a particular dengue virus serotype predominates for at least two years before it becomes replaced by another serotype.

    CONCLUSIONS: The dengue situation in Malaysia has worsened with an increasing number of reported cases and deaths during the last decade. The increasing trend of dengue highlights the need for a more systematic surveillance and reporting of the disease.

    Matched MeSH terms: Dengue/mortality
  3. Lim TW, Wallace HG, Rudnick A, Cheong WH, Knudsen AB, Chew V
    PMID: 4432105
    Matched MeSH terms: Dengue/mortality
  4. Shepard DS, Undurraga EA, Halasa YA
    PLoS Negl Trop Dis, 2013;7(2):e2055.
    PMID: 23437406 DOI: 10.1371/journal.pntd.0002055
    BACKGROUND: Dengue poses a substantial economic and disease burden in Southeast Asia (SEA). Quantifying this burden is critical to set policy priorities and disease-control strategies.

    METHODS AND FINDINGS: We estimated the economic and disease burden of dengue in 12 countries in SEA: Bhutan, Brunei, Cambodia, East-Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Viet Nam. We obtained reported cases from multiple sources--surveillance data, World Health Organization (WHO), and published studies--and adjusted for underreporting using expansion factors from previous literature. We obtained unit costs per episode through a systematic literature review, and completed missing data using linear regressions. We excluded costs such as prevention and vector control, and long-term sequelae of dengue. Over the decade of 2001-2010, we obtained an annual average of 2.9 million (m) dengue episodes and 5,906 deaths. The annual economic burden (with 95% certainty levels) was US$950m (US$610m-US$1,384m) or about US$1.65 (US$1.06-US$2.41) per capita. The annual number of disability-adjusted life years (DALYs), based on the original 1994 definition, was 214,000 (120,000-299,000), which is equivalent to 372 (210-520) DALYs per million inhabitants.

    CONCLUSION: Dengue poses a substantial economic and disease burden in SEA with a DALY burden per million inhabitants in the region. This burden is higher than that of 17 other conditions, including Japanese encephalitis, upper respiratory infections, and hepatitis B.

    Matched MeSH terms: Dengue/mortality
  5. 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: Dengue/mortality*; Severe Dengue/mortality*
  6. 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*
  7. 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*
  8. Wkly. Epidemiol. Rec., 1994 Aug 12;69(32):237-9.
    PMID: 7917888
    Matched MeSH terms: Dengue/mortality
  9. George R, Duraisamy G
    Acta Trop, 1981 Mar;38(1):71-8.
    PMID: 6111919
    Analysis of the bleeding manifestations of 130 cases of dengue haemorrhagic fever admitted into the Children's ward of the General Hospital, Kuala Lumpur from May 1973 to September 1978 has been done. Petechial skin rash, epistaxis and gum bleeding were seen most commonly in mild and moderately severe cases. However, blood stained gastric aspirates, and severe haematemesis were seen in severe or very severe cases. Though with better vector control and preventive measures, a marked reduction in the incidence of the cases has been noted, severe cases were seen with symptoms of shock and gastrointestinal bleeding. These symptoms carried a bad prognosis. Among 15 children that died 10 had gastrointestinal bleeding and 2 had a disseminated intravascular coagulation defect. Lymphocytosis with atypical lymphocytes, low platelet count, low reticulocyte count and raised packed cell volume were the main haematological features seen in all these cases. All these features reverted to normal within a week. Mild evidence of disseminated intravascular coagulation was seen in a number of cases, but severe features were seen only in four. Two cases improved as a result of heparin therapy.
    Matched MeSH terms: Dengue/mortality
  10. Shekhar KC, Huat OL
    Asia Pac J Public Health, 1992;6(2):15-25.
    PMID: 1308765 DOI: 10.1177/101053959300600203
    Dengue hemorrhagic fever (DHF), though endemic in the sixties, emerged as a major public health problem in Malaysia from 1973 onwards. The incidence rate of DHF which was 10.1 per 100,000 in 1973 has fallen down to 1.9 per 100,000 in 1987 with a mean case fatality rate of 6.4 per 100 persons. The Chinese appear to be more prone to DHF with the highest mean morbidity rate of 5.5 per 100,000 and case fatality rate of 6.1%. The incidence of DHF is higher in the males with a higher case fatality rate in females. Male Chinese appear to be mainly affected. The overall age-specific incidence rate is highest in two age groups, viz. 5-9 years and 10-19 years of age with a mean morbidity rate of 4.9 cases per 100,000. The mean age-specific case fatality rate was highest in the 0-4 years age group. Dengue hemorrhagic fever is predominantly an urban disease in Malaysia with a mean incidence rate of 5.3 cases per 100,000 as opposed to 1.2 cases per 100,000 being reported from rural areas. The mean overall incidence of deaths in the urban area is 0.5 compared to 0.1 per 100,000 for rural areas. There is a marked seasonal correlation between DHF cases and rainfall, with a peak in August. While all four serotypes of dengue viruses are found in Malaysia, Den 2 appears to be isolated with greater frequency during all the epidemics.
    Publication year=1992-1993
    Matched MeSH terms: Dengue/mortality
  11. 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*
  12. Mallhi TH, Khan AH, Adnan AS, Sarriff A, Khan YH, Jummaat F
    PLoS One, 2015;10(9):e0138465.
    PMID: 26421839 DOI: 10.1371/journal.pone.0138465
    BACKGROUND: Dengue induced acute kidney injury (AKI) imposes heavy burden of illness in terms of morbidity and mortality. A retrospective study was conducted to investigate incidence, characteristics, risk factors and clinical outcomes of AKI among dengue patients.

    METHODOLOGY: A total 667 dengue patients (2008-2013) were retrospectively evaluated and were stratified into AKI and non-AKI groups by using AKIN criteria. Two groups were compared by using appropriate statistical methods.

    RESULTS: There were 95 patients (14.2%) who had AKI, with AKIN-I, AKIN-II and AKIN-III in 76.8%, 16.8% and 6.4% patients, respectively. Significant differences (P<0.05) in demographics and clinico-laboratory characteristics were observed between patients with and without AKI. Presence of dengue hemorrhagic fever [OR (95% CI): 8.0 (3.64–17.59), P<0.001],rhabdomyolysis [OR (95% CI): 7.9 (3.04–20.49)], multiple organ dysfunction OR (95% CI):17.9 (9.14–35.12), P<0.001], diabetes mellitus [OR (95% CI): 4.7 (1.12–19.86), P = 0.034], late hospitalization [OR (95% CI): 2.1 (1.12–19.86), P = 0.033] and use of nephrotoxic drugs [OR(95% CI): 2.9 (1.12–19.86), P = 0.006] were associated with AKI. Longer hospital stay (>3days) was also observed among AKI patients (OR = 1.3, P = 0.044) [corrected].Additionally, 48.4% AKI patients had renal insufficiencies at discharge that were signicantly associated with severe dengue, secondary infection and diabetes mellitus. Overall mortality was 1.2% and all fatal cases had AKI.

    CONCLUSIONS: The incidence of AKI is high at 14.2% among dengue patients, and those with AKI portended significant morbidity, mortality, longer hospital stay and poor renal outcomes. Our findings suggest that AKI in dengue is likely to increase healthcare burden that underscores the need of clinicians' alertness to this highly morbid and potentially fatal complication for optimal prevention and management.

    Matched MeSH terms: Dengue/mortality*
  13. Liew SM, Khoo EM, Ho BK, Lee YK, Omar M, Ayadurai V, et al.
    PLoS One, 2016;11(6):e0157631.
    PMID: 27336440 DOI: 10.1371/journal.pone.0157631
    BACKGROUND: The increasing incidence and geographical distribution of dengue has had significant impact on global healthcare services and resources. This study aimed to determine the factors associated with dengue-related mortality in a cohort of Malaysian patients.

    METHODS: This was a retrospective cohort study of patients in the Malaysian National Dengue Registry of 2013. The outcome measure was dengue-related mortality. Associations between sociodemographic and clinical variables with the outcome were analysed using multivariate analysis.

    RESULTS: There were 43 347 cases of which 13081 were serologically confirmed. The mean age was 30.0 years (SD 15.7); 60.2% were male. The incidence of dengue increased towards the later part of the calendar year. There were 92 probable dengue mortalities, of which 41 were serologically confirmed. Multivariate analysis in those with positive serology showed that increasing age (OR 1.03; CI:1.01-1.05), persistent vomiting (OR 13.34; CI: 1.92-92.95), bleeding (OR 5.84; CI 2.17-15.70) and severe plasma leakage (OR 66.68; CI: 9.13-487.23) were associated with mortality. Factors associated with probable dengue mortality were increasing age (OR 1.04; CI:1.03-1.06), female gender (OR 1.53; CI:1.01-2.33), nausea and/or vomiting (OR 1.80; CI:1.17-2.77), bleeding (OR 3.01; CI:1.29-7.04), lethargy and/or restlessness (OR 5.97; CI:2.26-15.78), severe plasma leakage (OR 14.72; CI:1.54-140.70), and shock (OR 1805.37; CI:125.44-25982.98), in the overall study population.

    CONCLUSIONS: Older persons and those with persistent vomiting, bleeding or severe plasma leakage, which were associated with mortality, at notification should be monitored closely and referred early if indicated. Doctors and primary care practitioners need to detect patients with dengue early before they develop these severe signs and symptoms.

    Matched MeSH terms: Dengue/mortality
  14. 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: Dengue/mortality; Severe Dengue/mortality
  15. Murphy A, Rajahram GS, Jilip J, Maluda M, William T, Hu W, et al.
    PLoS Negl Trop Dis, 2020 05;14(5):e0007504.
    PMID: 32392222 DOI: 10.1371/journal.pntd.0007504
    In South East Asia, dengue epidemics have increased in size and geographical distribution in recent years. We examined the spatiotemporal distribution and epidemiological characteristics of reported dengue cases in the predominantly rural state of Sabah, in Malaysian Borneo-an area where sylvatic and urban circulation of pathogens are known to intersect. Using a public health data set of routinely notified dengue cases in Sabah between 2010 and 2016, we described demographic and entomological risk factors, both before and after a 2014 change in the clinical case definition for the disease. Annual dengue incidence rates were spatially variable over the 7-year study period from 2010-2016 (state-wide mean annual incidence of 21 cases/100,000 people; range 5-42/100,000), but were highest in rural localities in the western districts of the state (Kuala Penyu, Nabawan, Tenom and Kota Marudu). Eastern districts exhibited lower overall dengue rates, although a high proportion of severe (haemorrhagic) dengue cases (44%) were focused in Sandakan and Tawau. Dengue incidence was highest for those aged between 10 and 29 years (24/100,000), and was slightly higher for males compared to females. Available vector surveillance data indicated that during large outbreaks in 2015 and 2016 the mosquito Aedes albopictus was more prevalent in both urban and rural households (House Index of 64%) than Ae. aegypti (15%). Demographic patterns remained unchanged both before and after the dengue case definition was changed; however, in the years following the change, reported case numbers increased substantially. Overall, these findings suggest that dengue outbreaks in Sabah are increasing in both urban and rural settings. Future studies to better understand the drivers of risk in specific age groups, genders and geographic locations, and to test the potential role of Ae. albopictus in transmission, may help target dengue prevention and control efforts.
    Matched MeSH terms: Dengue/mortality
  16. Low GK, Ogston SA, Yong MH, Gan SC, Chee HY
    Acta Trop, 2018 Jun;182:237-245.
    PMID: 29545158 DOI: 10.1016/j.actatropica.2018.03.014
    BACKGROUND: Since the introduction of 2009 WHO dengue case classification, no literature was found regarding its effect on dengue death. This study was to evaluate the effect of 2009 WHO dengue case classification towards dengue case fatality rate.

    METHODS: Various databases were used to search relevant articles since 1995. Studies included were cohort and cross-sectional studies, all patients with dengue infection and must report the number of death or case fatality rate. The Joanna Briggs Institute appraisal checklist was used to evaluate the risk of bias of the full-texts. The studies were grouped according to the classification adopted: WHO 1997 and WHO 2009. Meta-regression was employed using a logistic transformation (log-odds) of the case fatality rate. The result of the meta-regression was the adjusted case fatality rate and odds ratio on the explanatory variables.

    RESULTS: A total of 77 studies were included in the meta-regression analysis. The case fatality rate for all studies combined was 1.14% with 95% confidence interval (CI) of 0.82-1.58%. The combined (unadjusted) case fatality rate for 69 studies which adopted WHO 1997 dengue case classification was 1.09% with 95% CI of 0.77-1.55%; and for eight studies with WHO 2009 was 1.62% with 95% CI of 0.64-4.02%. The unadjusted and adjusted odds ratio of case fatality using WHO 2009 dengue case classification was 1.49 (95% CI: 0.52, 4.24) and 0.83 (95% CI: 0.26, 2.63) respectively, compared to WHO 1997 dengue case classification. There was an apparent increase in trend of case fatality rate from the year 1992-2016. Neither was statistically significant.

    CONCLUSIONS: The WHO 2009 dengue case classification might have no effect towards the case fatality rate although the adjusted results indicated a lower case fatality rate. Future studies are required for an update in the meta-regression analysis to confirm the findings.

    Matched MeSH terms: Dengue/mortality*
  17. 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*
  18. Rothan HA, Bahrani H, Mohamed Z, Abd Rahman N, Yusof R
    PLoS One, 2014;9(4):e94561.
    PMID: 24722532 DOI: 10.1371/journal.pone.0094561
    Dengue virus (DENV) broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1) and plectasin (PLSN) were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN) as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro) with half-maximal inhibitory concentration (IC50) 0.5±0.1 μM. The real-time proliferation assay (RTCA) and the end-point proliferation assay (MTT assay) showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities.
    Matched MeSH terms: Dengue/mortality
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