Dengue Deaths Research Articles

Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements.

BackgroundThere are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication.Methodology/Principal FindingsSeventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.Conclusions/SignificanceThe method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps cellular proteins for efficient amplification.

A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014.

BackgroundDengue 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.MethodsWe 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.ResultsA 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%).ConclusionIn 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 RegistrationNational Medical Research Registry (NMRR, NMRR-14-1374-23352)

Dengue mortality in Colombia, 1985-2012.

Dengue in Colombia is an important public health problem due to the huge economic and social costs it has caused, especially during the disease outbreaks. To describe the behavior of dengue mortality in Colombia between 1985 and 2012. We conducted a descriptive study. Information was obtained from mortality and population projection databases provided by the Departamento Administrativo Nacional de Estadística (DANE) for the 1985-2012 period. Mortality rates, rate ratios, and case fatality rates were estimated. A total of 1,990 dengue deaths were registered during this period in Colombia. Dengue mortality rates presented an increasing trend with statistical significance between 1985 and 1998. Higher mortality rates were reported in men both younger than 5 years and older than 65 years. Between 1995 and 2012, category 1 to 4 municipalities reported the highest mortality rates. Case fatality rates varied during the period between 0.01% and 0.39%. Dengue is an avoidable disease that should disappear from mortality statistics as a cause of death. The event is avoidable if the proposed activities from the Estrategia de Gestión Integrada (EGI)-Dengue are implemented and evaluated. We recommend encouraging the development of an informational culture to contribute to decision making and prioritizing resource allocation.

The global burden of dengue: an analysis from the Global Burden of Disease Study 2013

Dengue is the most common arbovirus infection globally, but its burden is poorly quantified. We estimated dengue mortality, incidence, and burden for the Global Burden of Disease Study 2013. We modelled mortality from vital registration, verbal autopsy, and surveillance data using the Cause of Death Ensemble Modelling tool. We modelled incidence from officially reported cases, and adjusted our raw estimates for under-reporting based on published estimates of expansion factors. In total, we had 1780 country-years of mortality data from 130 countries, 1636 country-years of dengue case reports from 76 countries, and expansion factor estimates for 14 countries. We estimated an average of 9221 dengue deaths per year between 1990 and 2013, increasing from a low of 8277 (95% uncertainty estimate 5353-10 649) in 1992, to a peak of 11 302 (6790-13 722) in 2010. This yielded a total of 576 900 (330 000-701 200) years of life lost to premature mortality attributable to dengue in 2013. The incidence of dengue increased greatly between 1990 and 2013, with the number of cases more than doubling every decade, from 8·3 million (3·3 million-17·2 million) apparent cases in 1990, to 58·4 million (23·6 million-121·9 million) apparent cases in 2013. When accounting for disability from moderate and severe acute dengue, and post-dengue chronic fatigue, 566 000 (186 000-1 415 000) years lived with disability were attributable to dengue in 2013. Considering fatal and non-fatal outcomes together, dengue was responsible for 1·14 million (0·73 million-1·98 million) disability-adjusted life-years in 2013. Although lower than other estimates, our results offer more evidence that the true symptomatic incidence of dengue probably falls within the commonly cited range of 50 million to 100 million cases per year. Our mortality estimates are lower than those presented elsewhere and should be considered in light of the totality of evidence suggesting that dengue mortality might, in fact, be substantially higher. Bill & Melinda Gates Foundation.

Dengue Deaths: Associated Factors and Length of Hospital Stay.

Background. Dengue continues to pose a public health problem globally. Objective. To review factors associated with patients who died from dengue in Trinidad. Methods. A retrospective case note review of hospitalized patients who died during 2001 to 2010. Results. A total of 23 cases were identified: 13 males, 10 females—12 East Indians, 9 Africans, and 2 unknown. More than half (n = 17) were over 40 years of age with 10 being over 60 years of age; three were children. A falling platelet count was observed in 16 while 18 patients had a low normal haematocrit. There was a significant association of ethnicity, hypertension, and diabetes with length of hospital stay. Conclusions. The study sample included 10 patients over 60 years of age. Patients with diabetes and hypertension and patients of East Indian origin appeared to have a shorter hospital stay prior to death.

Dengue Death Review: A Tool to Adjudge the Cause of Dengue Mortality and Use of the Tool for Prevention of Dengue Deaths

Dengue Death Review: A Tool to Adjudge the Cause of Dengue Mortality and Use of the Tool for Prevention of Dengue Deaths

Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

IntroductionHPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized.Case descriptionA 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow.Discussion and evaluationIt is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient’s bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection.ConclusionsThe findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

Trends and factors associated with dengue mortality and fatality in Brazil.

Studies that generate information that may reduce the dengue death risk are essential. This study analyzed time trends and risk factors for dengue mortality and fatality in Brazil from 2001 to 2011. Time trends for dengue mortality and fatality rates were analyzed using simple linear regression. Associations between the dengue mortality and the case fatality rates and socioeconomic, demographic, and health care indicators at the municipality level were analyzed using negative binomial regression. The dengue hemorrhagic fever case fatality rate increased in Brazil from 2001 to 2011 (β=0.67; p=0.036), in patients aged 0-14 years (β=0.48; p=0.030) and in those aged ≥15 years (β=1.1; p<0.01). Factors associated with the dengue case fatality rate were the average income per capita (MRR=0.99; p=0.038) and the number of basic health units per population (MRR=0.89; p<0.001). Mortality rates increased from 2001 to 2011 (β=0.350; p=0.002).Factors associated with mortality were inequality (RR=1.02; p=0.001) high income per capita (MRR=0.99; p=0.005), and higher proportions of populations living in urban areas (MRR=1.01; p<0.001). The increases in the dengue mortality and case fatality rates and the associated socioeconomic and health care factors, suggest the need for structural and intersectoral investments to improve living conditions and to sustainably reduce these outcomes.

Why are people with dengue dying? A scoping review of determinants for dengue mortality.

BackgroundDengue is a viral disease whose clinical spectrum ranges from unapparent to severe forms and fatal outcomes. Although dengue death is 99 % avoidable, every year around 20,000 deaths are estimated to occur in more than 100 countries. We consider that, along with biological factors, social determinants of health (SDHs) are related to dengue deaths as well.MethodsA scoping review was conducted to explore what has been written about the role of SDHs in dengue mortality. The inclusion criteria were that documents (grey or peer-reviewed) had to include information about dengue fatal cases in humans and be published between 1997 and 2013 and written in English, Spanish, Portuguese or French. The search was conducted using a set of key words related to dengue mortality in several electronic databases: PubMed, LILACS, COCHRANE, Scielo, Science Direct, WHOLIS, OpenGrey, OpenSingle and Google Scholar. Information on SDHs was categorized under individual, social and environmental, and health systems dimensions. A summative content analysis using QDA Miner was conducted to assess the frequency of information on SDHs and its contextual meaning in the reviewed literature. The role of each SDH in dengue mortality was assessed using content analysis results.ResultsFrom a total of 971 documents retrieved, 78 met the criteria. Those documents were published in the Americas region (50.0 %), Asia (38.4 %), Europe (9.0 %) and Africa (2.6 %). The described SDHs related to dengue deaths included, in the individual dimension: age, ethnicity, education, type of infection and immunological status; and in the social dimension: poverty and care-seeking behavior. The health systems dimension included access, opportunity, and quality of care, as well as health staff knowledge. Ethnicity was considered a determinant that depends on cultural and socioeconomic conditions.ConclusionsAlong with biological factors, there are several SDHs related to dengue mortality. However, only a few of these have been systematically analyzed, suggesting the need for more studies on this subject to inform the design and implementation of sustainable interventions to decrease dengue mortality. These findings nevertheless provide a better understanding of the non-biological factors involved in dengue mortality.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1058-x) contains supplementary material, which is available to authorized users.

Does immunoglobulin therapy have a role in treating Dengue virus infection with induced systemic capillary leak syndrome?

The report of severe cardiovascular changes in the eight children with secondary dengue infection and dengue shock syndrome (DSS) by Kositseth et al. [1] was consistent with systemic capillary leak syndrome (SCLS). It is thought to be distinct from classical dengue fever (DF). However, clinicians working in endemic areas need to be aware that such textbook presentations may not be applicable in this age when extremes of climate and increase in air travel have complicated the infection demographics in clinical medicine. A report published in March 2012, showed the high prevalence of SCLS among travelers, a third of which were primary dengue cases and 85% also had classical DF [2]. It is interesting to hypothesize that patients co-infected with two serotypes of dengue virus (DENV) may develop multiple organ failure and DSS, but no specific reports on these complications are available from Asia (DENV-2/-3 and DENV-3/-4), or the Americas (DENV-2/-3 and DENV-3/-4). Whether complications from multiple organ failure and DSS was the case in the recent epidemic of dengue virus related deaths in children and adults from Eastern India during the rainy season/autumn 2012 remains to be proven [3]. As with most infectious pathogens, homologous DENV genetic recombination events have been widely reported [4,5], but fortunately, there have not been any reports of heterologous DENV-serotype recombination events. Such events would result in new chimeric strains and the immunological hypothesis of antibodyenhanced disease and multi-organ failure would be the most likely explanation [6]. Does high-dose intravenous immunoglobulin (hdIVIG) sourced from the local donor population, rather than imported, offer a viable treatment option in DENV-related SCLS? A publication from the European Registry of patients with idiopathic SCLS showed improvement after treatment with hdIVIG [7]. Treatment with hdIVIG certainly remains a feasible option with viral-related autoimmune manifestations such as Kawasaki disease, but will this treatment prove effective against the dreaded thrombocytopenia and SCLS in DENV infection? [8,9] Only a multi-center clinical trial can answer this question. In the interim time, civic and health authorities must work together with entomology and virology centers to prevent unnecessary deaths from this vector-borne disease.

Epidemiological update on the dengue situation in the Western Pacific Region, 2012.

Dengue has caused a substantial public health burden in the Western Pacific Region. To assess this burden and regional trends, data were collated and summarized from indicator-based surveillance systems on dengue cases and deaths from countries and areas in the Western Pacific Region. In 2012, dengue notifications continued to increase with 356,838 dengue cases reported in the Region (relative to 244,855 cases reported in 2011) of which 1248 died. In the Asia subregion, the notification rate was highest in Cambodia, the Philippines and the Lao People's Democratic Republic (316.2, 198.9 and 162.4 per 100,000 population, respectively), and in the Pacific island countries and areas, the notification rate was highest in Niue, the Marshall Islands and the Federated States of Micronesia (8556.0, 337.0 and 265.1 per 100,000 population, respectively). All four serotypes were circulating in the Region in 2012 with considerable variabilitiy in distribution. Regional surveillance provides important information to enhance situational awareness, conduct risk assessments and improve preparedness activities.

Factors associated with death from dengue in the state of Minas Gerais, Brazil: historical cohort study.

To analyse the clinical and epidemiological profiles of dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS) and complicated dengue cases and deaths from 2008 to 2010 that occurred in the state of Minas Gerais, south-eastern Brazil, and to identify factors associated with death from dengue. Historical cohort study using data from the Brazilian Information System for Notifiable Diseases. A descriptive analysis of the DHF, DSS and complicated dengue cases and deaths was performed; the incidence, mortality and case-fatality rates were estimated. Logistic regression analysis was used to identify factors associated with death from dengue. Comorbidities were not included in the analysis because the information system does not contain such data. During the study period, 2214 DHF, DSS and complicated dengue cases were reported, including 156 deaths. The annual case-fatality rates for DHF/DSS and complicated dengue cases in the period of 2008-2010 were 7.3%, 4.8% and 7.9%, respectively. The factors associated with death from dengue included residence in a municipality with a population of fewer than 100,000 inhabitants [odds ratio (OR) 2.46; 95% confidence interval (CI) 1.71-3.55], age over 65 years (OR 3.05; 95% CI 1.99-4.68) and plasma leakage (OR 1.69; 95% CI 1.16-2.46). The results support the importance of plasma leakage as a warning sign associated with death from dengue as well as the signs and symptoms that allow the diagnosis of DHF. Moreover, our findings suggest that increased attention is necessary for individuals over 65 years of age and in municipalities with populations under 100,000 inhabitants to ensure a better quality of care during the management of severe patients of dengue in these locations. Differences in the interpretation of the DHF definition have hindered the comparison of data from different countries; it can improve from the WHO 2009 dengue classification.

A retrospective analysis of dengue fever case management and frequency of co-morbidities associated with deaths

BackgroundDengue epidemic in Lahore (2011) resulted in hundreds of deaths and affected thousands. As most of the studies were focused on its diagnosis and treatment, scanty data is available on associated diseases/co-morbidities in these patients that could have contributed to a higher mortality. There were no local guidelines available on recording, reporting and management of these co-morbidities. The objective of this study was to analyze the initial presentations of dengue cases and to estimate the frequency of co-morbidities in dengue patients.MethodsData of 556 dengue cases was retrieved from 2 major public sector tertiary-care hospitals for patients who were admitted during 2011 epidemic and a case record analysis was done. Data was retrieved from patient’s information reports which included demography, signs and symptoms and the laboratory investigations. In addition verbal autopsy of deceased cases was also done from their relatives using standardized WHO verbal autopsy form after making modifications as per needed.ResultsOf 556 cases studied, 390 (70%) were males. The mean age was 36 years and 30% of the cases were between 20-29 years. Average duration of the hospital stay was 6 days. Out of the total, 435 (78%) were dengue fever (DF) cases followed by dengue hemorrhagic fever (DHF) in 95 (17%) and dengue shock syndrome (DSS) in 26 (4%) cases. A total of 40 cases died and among them 17 were diagnosed with DSS, 13 DF and 10 DHF. Further the verbal autopsy from relatives of deceased cases showed 29 (60%) deceased had co-morbid diseases which included hypertension, diabetes etc. DSS was common in patients who had hypertension (27) either alone or associated with other illnesses.ConclusionsCo-morbidities with dengue infection were seen in 60% deceased cases indicating the reasons for high dengue related complications and death.

Laboratory diagnosis and incidence of Dengue virus infection: a hospital based study, Perambalur

Background: Tamil Nadu recorded more than one fourth of all dengue cases and deaths in the country the state recorded 9,249 dengue cases and 60 deaths in 2012. There is a need for specific, inexpensive dengue diagnostic tests that can be used for clinical management, surveillance and outbreak investigations and would permit early intervention to treat patients and prevent or control epidemics. Material and methods: This cross sectional study was done by using MAC capture ELISA for IgM, IgG capture ELISA and NS1 antigen detection by sandwich ELISA during 2013 to 2014 for one year. Results: Out of 151 suspected cases of dengue 60 were found to positive by using dengue ELISA kit. The incidence of dengue viral infection was 39.74%, whereas during 2012 to 2013 out of 162 samples 27 (incidence 16.66%) were positive in our hospital based on statistics as mentioned above. Conclusion: The laboratory diagnosis of dengue virus infection by three ELISA methods along with clinical correlation with proper case definition had improved case detection as well as proper treatment in our hospital. Based on this study we can conclude that September, October, November, and December are the months of higher incidence of dengue virus infection.

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Introduction: There are an estimated 390 million dengue virus infections worldwide, 96 million manifesting clinically, resulting in substantial morbidity and mortality in tropical and sub-tropical regions. Infected patients are at risk for dengue hemorrhagic fever and death from plasma leakage, decreased intravascular volume, and shock. Early recognition and proper intravascular volume resuscitation improve morbidity and mortality. The purpose of this study was to evaluate a noninvasive method which could potentially provide a real-time assessment of the risk for shock. Methods: Dengue patients admitted to Queen Sirikit National Institute for Child Health in Bangkok were enrolled in the study. Hematocrits (Hct) were determined at least once daily and the time of maximum Hct was noted. A blood sample was also taken 4–5 days after hospital discharge to assess baseline Hct and determine the maximum percent increase in Hct for each patient. An increase in Hct greater than 20% indicated plasma leakage and an enhanced risk for shock. A noninvasive SmO2 sensor was placed on the upper arm or thigh of the patient and SmO2 data were recorded intermittently during their 2–4 day hospital stay. SmO2 nearest the time of maximum Hct was extracted from the recorded data; only patients who had SmO2 values within 8 hours of the blood measurement were included. SmO2 at the time of maximum Hct was compared between patients with and without significant hemoconcentration using a t-test. Results: There were 11 patients with Hct increase >20% and 17 patients with Hct increase ≤20%. SmO2 was 53 ± 11% for patients with hemoconcentration and 62 ± 10% for those patients without; p=0.03. Conclusions: SmO2 was significantly lower for patients with substantial hemoconcentration in agreement with previous work that showed SmO2 to be a sensitive indicator of hypovolemia. Further work is required to determine if real-time assessment of SmO2 can help direct therapy to minimize the risk for shock in dengue patients.

Trends of dengue infections in Malaysia, 2000-2010

ObjectiveTo 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. MethodsWe 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. ResultsThe 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. ConclusionsThe 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.

Epidemiologic update on the dengue situation in the Western Pacific Region, 2011

Dengue is an emerging vectorborne infectious disease that is a major public health concern in the Asia and the Pacific. Official dengue surveillance data for 2011 provided by ministries of health were summarized as part of routine activities of the World Health Organization Regional Office for the Western Pacific. Based on officially reported surveillance data, dengue continued to show sustained activity in the Western Pacific Region. In 2011, Member States reported a total of 244,855 cases of which 839 died for a case fatality rate of 0.34%. More than 1000 cases were reported each from Cambodia, the Federated States of Micronesia, the Lao People's Democratic Republic, Malaysia, the Philippines, the Marshall Islands, Singapore and Viet Nam. Cambodia, the Federated States of Micronesia and the Marshall Islands reported higher activity relative to 2010. There continues to be great variability among the dengue-endemic countries and areas in the Region in the number of cases and serotype distribution. The continued high notification rate and complex dengue epidemiology in the Region highlight the need for information-sharing on a routine and timely basis.

Review of Dengue Hemorrhagic Fever Fatal Cases Seen Among Adults: A Retrospective Study

BackgroundDengue 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 FindingsWe 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.ConclusionsIn 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.

Virus-Specific Differences in Rates of Disease during the 2010 Dengue Epidemic in Puerto Rico

BackgroundDengue is a potentially fatal acute febrile illness (AFI) caused by four mosquito-transmitted dengue viruses (DENV-1–4) that are endemic in Puerto Rico. In January 2010, the number of suspected dengue cases reported to the passive dengue surveillance system exceeded the epidemic threshold and an epidemic was declared soon after.Methodology/Principal FindingsTo characterize the epidemic, surveillance and laboratory diagnostic data were compiled. A suspected case was a dengue-like AFI in a person reported by a health care provider with or without a specimen submitted for diagnostic testing. Laboratory-positive cases had: (i) DENV nucleic acid detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in an acute serum specimen; (ii) anti-DENV IgM antibody detected by ELISA in any serum specimen; or (iii) DENV antigen or nucleic acid detected in an autopsy-tissue specimen. In 2010, a total of 26,766 suspected dengue cases (7.2 per 1,000 residents) were identified, of which 46.6% were laboratory-positive. Of 7,426 RT-PCR-positive specimens, DENV-1 (69.0%) and DENV-4 (23.6%) were detected more frequently than DENV-2 (7.3%) and DENV-3 (<0.1%). Nearly half (47.1%) of all laboratory-positive cases were adults, 49.7% had dengue with warning signs, 11.1% had severe dengue, and 40 died. Approximately 21% of cases were primary DENV infections, and 1–4 year olds were the only age group for which primary infection was more common than secondary. Individuals infected with DENV-1 were 4.2 (95% confidence interval [CI]: 1.7–9.8) and 4.0 (95% CI: 2.4–6.5) times more likely to have primary infection than those infected with DENV-2 or -4, respectively.Conclusions/SignificanceThis epidemic was long in duration and yielded the highest incidence of reported dengue cases and deaths since surveillance began in Puerto Rico in the late 1960's. This epidemic re-emphasizes the need for more effective primary prevention interventions to reduce the morbidity and mortality of dengue.

Safety and cost savings of reducing adult dengue hospitalization in a tertiary care hospital in Singapore

BackgroundPreviously, most dengue cases in Singapore were hospitalized despite low incidence of dengue hemorrhagic fever (DHF) or death. To minimize hospitalization, the Communicable Disease Centre at Tan Tock Seng Hospital (TTSH) in Singapore implemented new admission criteria which included clinical, laboratory, and DHF predictive parameters in 2007.MethodAll laboratory-confirmed dengue patients seen at TTSH during 2006–2008 were retrospectively reviewed for clinical data. Disease outcome and clinical parameters were compared over the 3 years.ResultsThere was a 33.0% mean decrease in inpatients after the new criteria were implemented compared with the period before (p < 0.001). The proportion of inpatients with DHF increased significantly from 31.7% in 2006 to 34.4% in 2008 (p = 0.008); 68 DHF cases were managed safely on an outpatient basis after compared with none before implementation. DHF inpatients had more serious signs such as clinical fluid accumulation (15.5% vs 2.9% of outpatients), while most DHF outpatients had hypoproteinemia (92.7% vs 81.3% of inpatients). The eight intensive care unit admissions and five deaths during this time period all occurred among inpatients. The new criteria resulted in a median cost saving of US$1.4 million to patients in 2008.ConclusionThe new dengue admission criteria were effective in sustainably reducing length of hospitalization, yielding considerable cost savings. A minority of DHF patients with mild symptoms recovered uneventfully through outpatient management.