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Risk Factors for Fatality among Confirmed Adult Dengue Inpatients in Singapore: A Matched Case-Control Study  [PDF]
Tun-Linn Thein, Yee-Sin Leo, Dale A. Fisher, Jenny G. Low, Helen M. L. Oh, Victor C. Gan, Joshua G. X. Wong, David C. Lye
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081060
Abstract: Objectives To identify demographic, clinical and laboratory risk factors for death due to dengue fever in adult patients in Singapore. Methods Multi-center retrospective study of hospitalized adult patients with confirmed dengue fever in Singapore between 1 January 2004 and 31 December 2008. Non-fatal controls were selected by matching age and year of infection with fatal cases. World Health Organization 1997, 2009 criteria were applied to define dengue hemorrhagic fever (DHF), warning signs and severe dengue. Statistical significance was assessed by conditional logistic regression modeling. Results Significantly more fatal cases than matched controls had pre-existing co-morbid conditions, and presented with abdominal pain/tenderness. Median pulse rates were significantly higher while myalgia was significantly less frequent in cases. . Fatal cases also had higher leucocyte counts, platelet counts, serum sodium, potassium, urea, creatine and bilirubin levels on admission compared to controls. There was no statistical significant difference between the prevalence of DHF and hematocrit level among cases and controls. Multivariate analysis showed myalgia and leucocyte count at presentation were independent predictors of fatality (adjusted odds ratios 0.09 and 2.94 respectively). None of the controls was admitted to intensive care unit (ICU) or given blood transfusion, while 71.4% and 28.6% of fatal cases received ICU admission and blood transfusion. Conclusions Absence of myalgia and leucocytosis on admission were independently associated with fatality in our matched case-control study. Fatalities were also commonly associated with co-morbidities and clinicians should be alarmed if dengue patients fulfilled severe dengue case definition on admission.
Review of Dengue Hemorrhagic Fever Fatal Cases Seen Among Adults: A Retrospective Study  [PDF]
Sing-Sin Sam,Sharifah Faridah Syed Omar,Boon-Teong Teoh,Juraina Abd-Jamil,Sazaly AbuBakar
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002194
Abstract: Background 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. Methodology/Principal Findings We undertook a retrospective study to examine dengue death cases in our hospital from June 2006 to October 2007 with a view to determine if there have been changes in the presentation of severe to fatal dengue. Nine of ten fatal cases involved adult females with a median age of 32 years. All had secondary dengue infection. The mean duration of illness prior to hospitalization was 4.7 days and deaths occurred at an average of 2.4 days post-admission. Gastrointestinal pain, vomiting, diarrhea, intravascular leakages and bleeding occurred in the majority of cases. DSS complicated with severe bleeding, multi-organ failure and coagulopathy were the primary causes of deaths. Seven patients presented with thrombocytopenia and hypoalbuminemia, five of which had hemoconcentration and increased ALT and AST indicative of liver damage. Co-morbidities particularly diabetes mellitus was common in our cohort. Prominent unusual presentations included acute renal failure, acute respiratory distress syndrome, myocarditis with pericarditis, and hemorrhages over the brain and heart. Conclusions In our cohort, dengue fatalities are seen primarily in adult females with secondary dengue infection. The majority of the patients presented with common clinical and laboratory warning signs of severe dengue. Underlying co-morbidities may contribute to the rapid clinical deterioration in severe dengue. The uncommon presentations of dengue are likely a reflection of the changing demographics where adults are now more likely to contract dengue in dengue endemic regions.
Implications of Discordance in World Health Organization 1997 and 2009 Dengue Classifications in Adult Dengue  [PDF]
Victor C. Gan, David C. Lye, Tun L. Thein, Frederico Dimatatac, Adriana S. Tan, Yee-Sin Leo
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060946
Abstract: Background Revised dengue guidelines were published by the World Health Organization (WHO) in 2009 addressing severe dengue cases not classified by dengue hemorrhagic fever (DHF) and shock syndrome (DSS). Methods and Principal Findings We conducted a retrospective cohort study to compare WHO 2009 and 1997 classifications using 1278 adult dengue cases confirmed by polymerase chain reaction assay from Singapore epidemics in 2004 and 2007 (predominantly serotype 1 and 2 respectively).DHF occurred in 14.3%, DSS 2.7% and severe dengue 16.0%. The two WHO dengue classifications were discordant in defining severe disease (p<0.001). Five DSS patients (15%) were classified as non-severe dengue without warning signs. Of severe dengue patients, 107 did not fulfil DHF criteria. Of these, 14.9% had self-resolving isolated elevated aminotransferases, 18.7% gastrointestinal bleeding without hemodynamic compromise and 56.1% plasma leakage with isolated tachycardia. We compared both guidelines against requirement for intensive care including the single death in this series: all six had severe dengue; only four had DHF as two lacked bleeding manifestations but had plasma leakage. Increasing length of hospitalization was noted among severe cases with both classifications but the trend was only statistically significant for WHO 2009. Length of hospitalization was significantly longer for severe plasma leakage compared with severe bleeding or organ impairment. Requirement for hospitalization increased using WHO 2009 from 17.0% to 51.3%. Conclusions While the WHO 2009 dengue classification is clinically useful, we propose retaining criteria for plasma leakage and hemodynamic compromise from WHO 1997, and refining definitions of severe bleeding and organ impairment to improve clinical relevance having found that differences in these accounted for the discordance between classifications. Findings from our retrospective study may be limited by the study site - a tertiary referral center in a hyperendemic country - and should be evaluated in a wider range of geographic settings.
Diabetes with Hypertension as Risk Factors for Adult Dengue Hemorrhagic Fever in a Predominantly Dengue Serotype 2 Epidemic: A Case Control Study  [PDF]
Junxiong Pang ,Agus Salim,Vernon J. Lee,Martin L. Hibberd,Kee Seng Chia,Yee Sin Leo,David C. Lye
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001641
Abstract: Background Dengue hemorrhagic fever (DHF) is a severe form of dengue, characterized by bleeding and plasma leakage. A number of DHF risk factors had been suggested. However, these risk factors may not be generalized to all populations and epidemics for screening and clinical management of patients at risk of developing DHF. This study explored demographic and comorbidity risk factors for DHF in adult dengue epidemics in Singapore in year 2006 (predominantly serotype 1) and in year 2007–2008 (predominantly serotype 2). Methods A retrospective case-control study was conducted with 149 DHF and 326 dengue fever (DF) patients from year 2006, and 669 DHF and 1,141 DF patients from year 2007–2008. Demographic and reported comorbidity data were collected from patients previously. We performed multivariate logistic regression to assess the association between DHF and demographic and co-morbidities for year 2006 and year 2007–2008, respectively. Results Only Chinese (adjusted odds ratio [AOR] = 1.90; 95% confidence interval [CI]: 1.01–3.56) was independently associated with DHF in year 2006. In contrast, age groups of 30–39 years (AOR = 1.41; 95% CI:1.09–1.81), 40–49 years (AOR = 1.34; 95% CI:1.09–1.81), female (AOR = 1.57; 95% CI:1.28–1.94), Chinese (AOR = 1.67; 95% CI:1.24–2.24), diabetes (AOR = 1.78; 95% CI:1.06–2.97), and diabetes with hypertension (AOR = 2.16; 95%CI:1.18–3.96) were independently associated with DHF in year 2007–2008. Hypertension was proposed to have effect modification on the risk of DHF outcome in dengue patients with diabetes. Chinese who had diabetes with hypertension had 2.1 (95% CI:1.07–4.12) times higher risk of DHF compared with Chinese who had no diabetes and no hypertension. Conclusions Adult dengue patients in Singapore who were 30–49 years, Chinese, female, had diabetes or diabetes with hypertension were at greater risk of developing DHF during epidemic of predominantly serotype 2. These risk factors can be used to guide triaging of patients who require closer clinical monitoring and early hospitalization in Singapore, when confirmed in more studies.
Predictive Tools for Severe Dengue Conforming to World Health Organization 2009 Criteria  [PDF]
Luis R. Carrasco,Yee Sin Leo ,Alex R. Cook,Vernon J. Lee,Tun L. Thein,Chi Jong Go,David C. Lye
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002972
Abstract: Background Dengue causes 50 million infections per year, posing a large disease and economic burden in tropical and subtropical regions. Only a proportion of dengue cases require hospitalization, and predictive tools to triage dengue patients at greater risk of complications may optimize usage of limited healthcare resources. For severe dengue (SD), proposed by the World Health Organization (WHO) 2009 dengue guidelines, predictive tools are lacking. Methods We undertook a retrospective study of adult dengue patients in Tan Tock Seng Hospital, Singapore, from 2006 to 2008. Demographic, clinical and laboratory variables at presentation from dengue polymerase chain reaction-positive and serology-positive patients were used to predict the development of SD after hospitalization using generalized linear models (GLMs). Principal findings Predictive tools compatible with well-resourced and resource-limited settings – not requiring laboratory measurements – performed acceptably with optimism-corrected specificities of 29% and 27% respectively for 90% sensitivity. Higher risk of severe dengue (SD) was associated with female gender, lower than normal hematocrit level, abdominal distension, vomiting and fever on admission. Lower risk of SD was associated with more years of age (in a cohort with an interquartile range of 27–47 years of age), leucopenia and fever duration on admission. Among the warning signs proposed by WHO 2009, we found support for abdominal pain or tenderness and vomiting as predictors of combined forms of SD. Conclusions The application of these predictive tools in the clinical setting may reduce unnecessary admissions by 19% allowing the allocation of scarce public health resources to patients according to the severity of outcomes.
Epidemiological characteristics of the 2005 and 2007 dengue epidemics in Singapore - similarities and distinctions  [cached]
Teck Siang Ler,Li Wei Ang,Grace Siew Lian Yap,Lee Ching Ng
Western Pacific Surveillance and Response , 2011,
Abstract: Introduction: We investigated the epidemiological features of the 2007 dengue outbreak to determine the factors that could have triggered it two years after the previous large outbreak in 2005.Methods: All laboratory-confirmed cases of dengue reported during the year, as well as entomological and virological data, were analysed.Results: A total of 8826 cases including 24 deaths were reported in 2007, giving an incidence of 192.3 cases per 100 000 residents and a case-fatality rate of 0.27%. The median age of the cases was 37 years (interquartile range 25 to 50), with an age range from two days to 101 years, which was higher than the median age of 31 years (interquartile range 20 to 42), with a range from four days to 98 years, in 2005. The overall Aedes premises index in 2007 was 0.68%, lower than the 1.15% observed in 2005. The predominant dengue serotype in 2007 was dengue virus DENV-2 which re-emerged with a clade replacement in early 2007, and overtook the predominant serotype (DENV-1) of 2005. Seroprevalence studies conducted in the three largest outbreak clusters revealed that 73.2% of residents with recent infection were asymptomatic.Discussion: With the exception of an increase in the median age of the cases, and a change in the predominant dengue serotype, the epidemiological features of the 2007 epidemic were largely similar to those of 2005. Singapore remains vulnerable to major outbreaks of dengue, despite sustained vector control measures to maintain a consistently low Aedes premises index.
Statistical Modeling Reveals the Effect of Absolute Humidity on Dengue in Singapore  [PDF]
Hai-Yan Xu,Xiuju Fu ,Lionel Kim Hock Lee,Stefan Ma,Kee Tai Goh,Jiancheng Wong,Mohamed Salahuddin Habibullah,Gary Kee Khoon Lee,Tian Kuay Lim,Paul Anantharajah Tambyah,Chin Leong Lim,Lee Ching Ng
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002805
Abstract: Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM) was used to evaluate and compare the impact of weekly Absolute Humidity (AH) and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed) on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT) also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing factors into consideration in order to make meaningful public policy recommendations.
Economic Impact of Dengue Illness and the Cost-Effectiveness of Future Vaccination Programs in Singapore  [PDF]
Luis R. Carrasco,Linda K. Lee,Vernon J. Lee,Eng Eong Ooi,Donald S. Shepard,Tun L. Thein,Victor Gan,Alex R. Cook ,David Lye,Lee Ching Ng,Yee Sin Leo
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001426
Abstract: Background Dengue illness causes 50–100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact of dengue in higher resourced countries or the cost-effectiveness of potential dengue vaccines in such settings. Methods and Findings We estimate the direct and indirect costs of dengue from hospitalized and ambulatory cases in Singapore. We consider inter alia the impacts of dengue on the economy using the human-capital and the friction cost methods. Disease burden was estimated using disability-adjusted life years (DALYs) and the cost-effectiveness of a potential vaccine program was evaluated. The average economic impact of dengue illness in Singapore from 2000 to 2009 in constant 2010 US$ ranged between $0.85 billion and $1.15 billion, of which control costs constitute 42%–59%. Using empirically derived disability weights, we estimated an annual average disease burden of 9–14 DALYs per 100 000 habitants, making it comparable to diseases such as hepatitis B or syphilis. The proportion of symptomatic dengue cases detected by the national surveillance system was estimated to be low, and to decrease with age. Under population projections by the United Nations, the price per dose threshold for which vaccines stop being more cost-effective than the current vector control program ranged from $50 for mass vaccination requiring 3 doses and only conferring 10 years of immunity to $300 for vaccination requiring 2 doses and conferring lifetime immunity. The thresholds for these vaccine programs to not be cost-effective for Singapore were $100 and $500 per dose respectively. Conclusions Dengue illness presents a serious economic and disease burden in Singapore. Dengue vaccines are expected to be cost-effective if reasonably low prices are adopted and will help to reduce the economic and disease burden of dengue in Singapore substantially.
Pediatric Influenza-Associated Deaths in New York State: Death Certificate Coding and Comparison to Laboratory-Confirmed Deaths  [PDF]
Dina Hoefer,Bryan Cherry,Marilyn Kacica,Kristi McClamroch,Kimberly Kilby
Influenza Research and Treatment , 2012, DOI: 10.1155/2012/397890
Abstract: Introduction. Surveillance for laboratory-confirmed influenza-associated deaths in children is used to monitor the severity of influenza at the population level and to inform influenza prevention and control policies. The goal of this study was to better estimate pediatric influenza mortality in New York state (NYS). Methods. Death certificate data were requested for all passively reported deaths and any pneumonia and influenza (P&I) coded pediatric deaths occurring between October 2004 and April 2010, excluding New York City (NYC) residents. A matching algorithm and capture-recapture analysis were used to estimate the total number of influenza-associated deaths among NYS children. Results. Thirty-four laboratory-confirmed influenza-associated pediatric deaths were reported and 67 death certificates had a P&I coded death; 16 deaths matched. No laboratory-confirmed influenza-associated death had a pneumonia code and no pneumonia coded deaths had laboratory evidence of influenza infection in their medical record. The capture-recapture analysis estimated between 38 and 126 influenza-associated pediatric deaths occurred in NYS during the study period. Conclusion. Passive surveillance for influenza-associated deaths continues to be the gold standard methodology for characterizing influenza mortality in children. Review of death certificates can complement but not replace passive reporting, by providing better estimates and detecting any missed laboratory-confirmed deaths. 1. Introduction It has long been recognized that influenza is associated with substantial mortality during both epidemics and pandemics. Death due to influenza virus infection can result from a variety of causes, such as pneumonia or exacerbations of existing cardiopulmonary or other chronic conditions. Influenza-associated death among children in particular is rare, but when it occurs, it is often rapidly fatal and may affect children with no predisposing risk factor [1, 2]. Bacterial coinfections, especially methicillin-resistant Staphylococcus aureus (MRSA), are also increasingly being documented among influenza-associated pediatric deaths [1]. These were important factors in the Advisory Committee on Immunization Practices (ACIP) expanding influenza vaccine recommendations in 2008 to include all children aged 6 months through 18 years [3] when in years prior influenza vaccine was only recommended for children less than five years of age. Due to increased reports of deaths in children associated with influenza in the 2003-04 season [4, 5], in October 2004 laboratory-confirmed
Retrospective Study on Dengue in Fortaleza, State of Ceará, Brazil
Cunha, RV da;Miagostovich, MP;Petrola, Z;Araújo, ESM de;Cortez, D;Pombo, V;Souza, RV de;Nogueira, RMR;Schatzmayr, HG;
Memórias do Instituto Oswaldo Cruz , 1998, DOI: 10.1590/S0074-02761998000200003
Abstract: a retrospective serologic study was carried out in fortaleza, state of ceará, brazil, in order to detect the dengue virus activity before recognizing the epidemic of 1994. mac-elisa was performed by using a mixture of specific den-1 and den-2 antigens on serum samples from the emilio ribas laboratory collection. samples were obtained from 1,224 patients with exanthematic febrile disease and negative serological results for rubella. all specimens were taken during november 1993 to may 1994. the results confirmed dengue infections in fortaleza by november 1993, approximately six months before the beginning of the epidemic, proving how misleading diagnosis of dengue infection are still troublesome, in spite of the strong dengue activity in ceará. the authors stress the urgent necessity to implement the active surveillance system in order to prevent another extensive dengue fever epidemics in the state. epidemiological background of the dengue activity in the state of ceará is also described.
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