Laboratory-confirmed Dengue Patients Research Articles

Presence of dengue virus RNA in urine and oral fluid of laboratory-confirmed dengue patients: Implications for wastewater surveillance

IntroductionDengue cases in the Americas in 2024 have reached record highs, especially in Brazil. However, surveillance remains suboptimal and new methods are needed to monitor Dengue Virus (DENV) spread. To assess whether wastewater-based epidemiology would be a useful tool, we investigated the presence of DENV RNA in dengue patients’ urine and oral fluid from an endemic area to inform how shedding in these fluids occurs and provide insight for wastewater surveillance. MethodsWe examined how often DENV RNA is detected in urine and oral fluid from dengue patients confirmed by serum RT-qPCR, NS1 ELISA or IgM seroconversion in Salvador, Brazil. ResultsOf 88 confirmed cases, 9.1 % were positive for DENV RNA in urine (7/88) or oral fluid (1/88). Of 53 serum RT-qPCR-positive patients, 6 (11.3 %) showed detectable DENV RNA in acute- or convalescent-phase urine. Patients with RT-qPCR-positive urine had a lower frequency of DENV IgG in acute-phase serum (a proxy for secondary infection) (57 % vs. 74 %) and a lower median serum RT-qPCR cycle threshold than those with negative urine (21.8 vs. 23.9). ConclusionThe low presence of DENV RNA in urine suggests that additional research is needed to evaluate whether using wastewater-based epidemiology to monitor DENV transmission is possible.

Impact of pre-existing cross-reactive antibodies on cyclic dengue outbreaks in the hyperendemic region of Bali, Indonesia

The four serotypes of the dengue virus (DENV) cause a range of diseases ranging from mild fever to severe conditions. Understanding the immunological interactions among the four serotypes is crucial in comprehending the dynamics of serotype shifting during outbreaks in areas where all four serotypes co-circulate. Hence, we evaluated the neutralizing antibody and antibody-dependent enhancement responses against the four DENV serotypes using acute-phase plasma samples collected from 48 laboratory-confirmed dengue patients during a dengue outbreak in Bali, Indonesia in 2022. Employing single-round infectious particles to exclusively investigate immunogenicity to the structural surface proteins of DENV, which are the targets of antibodies, we found that individuals with a probable prior history of DENV-1 infection exhibited increased susceptibility to secondary DENV-3 infection, attributed to cross-reactive antibodies with limited neutralizing activity against DENV-3 (geometric mean 50 % neutralization titer (GMNT50) = 47.6 ± 11.5). This susceptibility was evident in vitro, with a mean fold enhancement of 28.4 ± 33.9. Neutralization titers against DENV-3 were significantly lower compared to other serotypes (DENV-1 GMNT50 = 678.1 ± 9.0; DENV-2 GMNT50 = 210.5 ± 8.7; DENV-4 GMNT50 = 95.14 ± 7.0). We demonstrate that prior immunity to one serotype provides limited cross-protection against the other serotypes, influencing the dominant serotype in subsequent outbreaks. These findings underscore the complexity of dengue immunity and its implications for vaccine design and transmission dynamics in hyperendemic regions.

Re-examination of the risk of dementia after dengue virus infection: A population-based cohort study.

Dengue infection can affect the central nervous system and cause various neurological complications. Previous studies also suggest dengue was associated with a significantly increased long-term risk of dementia. A population-based cohort study was conducted using national health databases in Taiwan and included 37,928 laboratory-confirmed dengue patients aged ≥ 45 years between 2002 and 2015, along with 151,712 matched nondengue individuals. Subdistribution hazard regression models showed a slightly increased risk of Alzheimer's disease, and unspecified dementia, non-vascular dementia, and overall dementia in dengue patients than the nondengue group, adjusted for age, sex, area of residence, urbanization level, income, comorbidities, and all-cause clinical visits within one year before the index date. After considering multiple comparisons using Bonferroni correction, only overall dementia and non-vascular dementia remained statistically significant (adjusted SHR 1.13, 95% CI 1.05-1.21, p = 0.0009; E-value 1.51, 95% CI 1.28-NA). Sensitivity analyses in which dementia cases occurring in the first three or five years after the index dates were excluded revealed no association between dengue and dementia. In conclusion, this study found dengue patients had a slightly increased risk of non-vascular dementia and total dementia than those without dengue. However, the small corresponding E-values and sensitivity analyses suggest the association between dengue and dementia may not be causal.

Myocarditis manifestations in dengue cases: A systematic review and meta-analysis

BackgroundDengue fever is a zoonotic viral infection that raises a global alarm in the tropics and subtropics, with the potentially escalating into newer geographical regions. Severe dengue may be associated with fatal complications such as myocarditis. There is a paucity of available data on the prevalence of dengue-associated myocarditis. The objective of this systematic review and meta-analysis was to estimate the global prevalence of dengue-associated myocarditis. MethodsA systematic search was conducted utilizing the Cochrane library, PubMed, Scopus, ProQuest, Web of Science, and Preprint servers such as arXiv, medRxiv, bioRxiv, BioRN, ChiRN, ChiRxiv, and SSRN as of November 25, 2022. All primary studies (case series, cross-sectional, retrospective, and prospective) that reported confirmed cases of dengue myocarditis were included. The I2 statistic test assessed the heterogenic characteristics and publication bias was evaluated using Doi plot and Egger regression tests. ResultsA total of 12 studies conducted between 2007 and 2022 with 2795 laboratory-confirmed dengue patients were included. Of the included cases, 502 were positive for myocarditis, with a prevalence of 2.4–78%. The pooled prevalence of dengue-induced myocarditis in the studied population was 21.0% (95% CI, 9 – 38%). The prediction interval was estimated to be 0.00 - 0.81. ConclusionMyocarditis in dengue patients is a significant and understudied complication in many aspects. To prevent dengue-associated myocarditis, appropriate measures such as early detection of cases and signs, symptoms-based diagnosis via electrocardiography and echocardiography, as well as relevant vector control policies must be implemented.

Self-care practices and health-seeking behaviours in patients with dengue fever: A qualitative study from patients’ and physicians’ perspectives

Outpatient management for dengue fever is the mainstay of treatment for most dengue cases. However, severe dengue can develop rapidly while patients are at home. Understanding the self-care practices and healthcare-seeking behaviours among dengue patients managed as outpatients will help improve the delivery of care to these patients. This study aimed to explore the self-care practices, health-seeking behaviour and outpatient management of dengue fever from the perspectives of patients and primary care physicians. This qualitative study used in-depth interviews and focus group discussions to obtain information from laboratory-confirmed dengue patients who received outpatient care and primary care physicians who cared for them. Patients and physicians shared their experiences and perceptions of self-care practices, decisions to seek urgent care, and outpatient management procedures and visit frequency. Data were coded and analysed using thematic analysis. 13 patients and 11 physicians participated. We discovered that the use of traditional remedies was common with patients perceiving no harm from it, whereas physicians did not see a benefit. Dengue patients' knowledge of warning signs was inadequate despite the information being provided by physicians during clinical follow-up visits. Regarding the decision to seek urgent medical care, physicians assumed patients would seek help immediately once they experienced warning signs. However, for the patients, other factors influenced their health-seeking behaviour, such as their personal perceptions of symptom severity and often more importantly, their social circumstances (e.g., availability of childcare). Patients also described regular outpatient follow-up for dengue as inconvenient. There was variation in the prescribed outpatient follow-up interval recommended by participating physicians who complained about the lack of clear guidelines. Perceptions around self-care practices, health-seeking behaviour and outpatient management of dengue often differed between physicians and patients, especially on comprehension of dengue warning signs. Addressing these gaps between patient and physician perceptions and recognition of patient drivers of health-seeking behaviour are needed to improve the safety and delivery of outpatient care for dengue patients.

Short-term, medium-term, and long-term risks of nonvariceal upper gastrointestinal bleeding after dengue virus infection.

Dengue patients have an increased risk of acute gastrointestinal (GI) bleeding. However, whether dengue virus (DENV) infection can cause an increased long-term risk of GI bleeding remains unknown, especially among elderly individuals who commonly take antithrombotic drugs. A retrospective population-based cohort study was conducted by analyzing the National Health Insurance Research Databases. Laboratory-confirmed dengue patients from 2002 to 2012 and four matched nondengue controls were identified. Multivariate Cox proportional hazard regression was used to evaluate the acute (<30 days), medium-term (31–365 days), and long-term (>365 days) risks of nonvariceal upper GI bleeding after DENV infection. Stratified analyses by age group (≤50, 51–64, ≥65 years old) were also performed. In total, 13267 confirmed dengue patients and 53068 nondengue matched controls were included. After adjusting for sex, age, area of residence, comorbidities, and medications, dengue patients had a significantly increased risk of nonvariceal upper GI bleeding within 30 days of disease onset (adjusted HR 55.40; 95% CI: 32.17–95.42). However, DENV infection was not associated with increased medium-term and long-term risks of upper GI bleeding overall or in each age group. Even dengue patients who developed acute GI bleeding did not have increased medium-term (adjusted HR; 0.55, 95% CI 0.05–6.18) and long-term risks of upper GI bleeding (adjusted HR; 1.78, 95% CI 0.89–3.55). DENV infection was associated with a significantly increased risk of nonvariceal upper GI bleeding within 30 days but not thereafter. Recovered dengue patients with acute GI bleeding can resume antithrombotic treatments to minimize the risk of thrombosis.

An Outbreak of Dengue Virus Serotype 2 Cosmopolitan Genotype in Nepal, 2017.

Dengue virus (DENV) is one of the most prevalent neglected tropical diseases, with half of the world’s population at risk of infection. In Nepal, DENV was first reported in 2004, and its prevalence is increasing every year. The present study aimed to obtain and characterize the full-length genome sequence of DENV from the 2017 outbreak. Hospital-based surveillance was conducted in two provinces of Nepal during the outbreak. Acute-phase serum samples were collected from 141 clinically suspected dengue patients after the rainy season. By serological and molecular techniques, 37 (26.9%) and 49 (34.8%), respectively, were confirmed as dengue patients. The cosmopolitan genotype of DENV-2 was isolated from 27 laboratory-confirmed dengue patients. Genomic analysis showed many amino acid substitutions distributed mainly among the E, NS3, and NS5 genes. Phylogenetic analyses of the whole genome sequence revealed two clades (Asian and Indian) among DENV-2 isolates from Nepal. The DENV isolates from hilly and Terai areas were similar to Asian and Indian strains, respectively. Further genomic study on different DENV serotypes is warranted to understand DENV epidemics in Nepal, where there are limited scientific resources and infrastructure.

Is there any association between body mass index and severity of dengue infection?

Dengue, an acute infectious disease caused by a flavivirus, is a threat to global health. There is sparse evidence exploring obesity and the development of more severe dengue cases in adults. With increasing prevalence of obesity in areas with a high risk of dengue infection, obesity may increase the burden and mortality related to dengue infection. Our study aimed to determine the association between obesity and the development of more severe dengue infection in primary healthcare settings and whether these associations were modified by dengue fever phase. A cohort study was conducted among laboratory-confirmed dengue patients aged >18 y in the central region of Peninsular Malaysia from May 2016 to November 2017. We collected demographic, clinical history, physical examination and laboratory examination information using a standardized form. Dengue severity (DS) was defined as either dengue with warning signs or severe dengue. Participants underwent daily follow-up, during which we recorded their vital signs, warning signs and full blood count results. Incidence of DS was modeled using mixed-effects logistic regression. Changes in platelet count and hematocrit were modeled using mixed-effects linear regression. The final multivariable models were adjusted for age, gender, ethnicity and previous dengue infection. A total of 173 patients were enrolled and followed up. The mean body mass index (BMI) was 37.4±13.75 kg/m2. The majority of patients were Malay (65.9%), followed by Chinese (17.3%), Indian (12.7%) and other ethnic groups (4.1%). A total of 90 patients (52.0%) were male while 36 patients (20.8%) had a previous history of dengue infection. BMI was significantly associated with DS (adjusted OR=1.17; 95% CI 1.04 to 1.34) and hematocrit (%) (aβ=0.09; 95% CI 0.01 to 0.16), but not with platelet count (x103/µL) (aβ=-0.01; 95% CI -0.84 to 0.81). In the dose response analysis, we found that as BMI increases, the odds of DS, hematocrit levels and platelet levels increase during the first phase of dengue fever. Higher BMI and higher hematocrit levels were associated with higher odds of DS. Among those with high BMI, the development of DS was observed during phase one of dengue fever instead of during phase two. These novel results could be used by clinicians to help them risk-stratify dengue patients for closer monitoring and subsequent prevention of severe dengue complications.

Risk of gastrointestinal bleeding after acute dengue virus infection

Background: Dengue fever is an important emerging infectious disease. Its incidence has dramatically increased worldwide over the past few decades with substantial geographical expansion to new countries and regions. Dengue has been considered as an acute illness; however, a few studies have reported that persistent dengue symptoms lasting for months or even years after acute infection do occur. Gastrointestinal bleeding is a common complication in acute dengue virus infection. However, whether people with previous dengue virus infection have a higher long-term risk of gastrointestinal bleeding has seldom been explored. Methods and materials: A retrospective population-based cohort study was conducted by analyzing data from the National Health Insurance Research Databases and the Notifiable Disease Dataset of Confirm Cases in Taiwan. Laboratory-confirmed dengue patients between 2002 and 2012 were identified from the latter database. Four non-dengue controls were randomly selected for each dengue patient by matching on age, sex, calendar year, and area of residence. All participants were followed up from the index dates to the diagnosis of gastrointestinal (GI) bleeding, death, or December 31, 2015. Multivariate Cox proportional hazard regression models were used to evaluate the risk of GI bleeding in different follow-up periods after dengue virus infection (<2 months, 3–12 months, >12 months), adjusting for matching factors and bleeding-related comorbidities and medications. Results: We identified 13269 newly diagnosed dengue patients and 53076 non-dengue matched controls. The overall incidence rate of GI bleeding was 699.01 per 100,000 person-years in the dengue cohort and 412.76 per 100,000 person-years in the controls. Stratified analyses by different follow-up periods showed that dengue patients had a higher risk of GI bleeding within two months after infection (adjusted HR 23.04, 95% CI 17.29–30.69), but there was no significant association between dengue and GI bleeding between 3–12 months (adjusted HR 0.87, 95% CI 0.59–1.30) or >12 months (adjusted HR 0.90, 95% CI 0.81–1.01) after infection. Conclusion: Dengue virus infection was associated with the risk of developing GI bleeding only within 2 months after disease onset. It seems that dengue virus infection does not increase the long-term risk of GI bleeding among infected people.

Burden of Dengue with Related Entomological and Climatic Characteristics in Surat City, Gujarat, India, 2011-2016: An Analysis of Surveillance Data.

We estimated the incidence of laboratory-confirmed dengue patients for Surat city, India, using surveillance data from 2011 to 2016 and described the related entomological indices and climatic factors. There was a rise in incidence from 1.5 to 17.6 per 100,000 population, as the numbers of notified cases have increased because of better surveillance system. The case notification was 1.3 times higher for the public sector than the private sector. The larval indices were below the transmission level (House index, Breteau index < 1%). The median age of dengue patients was 20 years (IQR: 14-28), with a male to female ratio of 1.6:1. Five peripheral vector control units contributed to 1,013 (41.4%) confirmed cases with rising incidence in other units also. The number of dengue patients peaked during post-monsoon. Spearman's correlation of vector density with humidity (r s = 0.556), rainfall (r s = 0.644), and number of cases (r s = 0.708) suggested climate favorable for vector breeding. There is a good system of public-private coordination for dengue surveillance. However, there is a need to reassess the vector indices threshold for transmission in the city.

Persistence of symptoms in dengue patients: a clinical cohort study.

Dengue is commonly considered an acute illness and follows three phases: febrile, critical in some cases and recovery. However, a number of studies have described a continuation of dengue symptoms for weeks or months, extending the recovery phase. Here we evaluate this persistence of dengue symptoms during convalescence. Our clinical cohort study included patients who sought medical services 48 to 144h from the onset of fever at seven hospitals or ambulatory centers in Morelos, Mexico. Seventy-nine laboratory-confirmed dengue patients were followed up regularly using clinic and/or home visits and telephone calls for as long as symptoms persisted or up to 6mo. In total, 55.7% of patients had dengue-related symptoms 1 mo after the onset of fever; pain and dermatological manifestations were the most common persistent symptoms. Prognostic factors for symptom persistence were: ≥4d of fever (RR1.72; 95% CI 1.35 to 2.19), platelet count ≤100 000/mm3 (RR1.20; 95% CI 1.20 to 2.20), petechiae/bruises (RR1.97; 95% CI 1.56 to 2.48) and abdominal pain/hepatomegaly (RR1.79; 95% CI 1.41 to 2.28). Persistence of dengue symptoms were common in laboratory-confirmed dengue patients. Manifestations related to tissue damage were associated with persistence after 30d; host characteristics, such as age and health status before infection, were associated with prolonged persistence (>60d). The burden of dengue may be higher than previously estimated.

Risk of Leukemia after Dengue Virus Infection: A Population-Based Cohort Study.

Infections account for about 15% of human cancers globally. Although abnormal hematologic profiles and bone marrow suppression are common in patients with dengue, whether dengue is associated with a higher risk of leukemia has not been investigated. We conducted a nationwide population-based cohort study by analyzing the National Health Insurance Research Databases in Taiwan. Laboratory-confirmed dengue patients between 2002 and 2011 were identified; five matched non-dengue controls were randomly selected for each patient. Follow-up ended on December 31, 2015. Multivariate Cox proportional hazard regression models were used to evaluate the effect of dengue virus infection on the risk of leukemia. Cancers other than leukemia were used as falsification endpoints to evaluate the validity of this study. We identified 12,573 patients with dengue and 62,865 non-dengue controls. Patients with dengue had a higher risk of leukemia [adjusted HR, 2.03; 95% confidence interval (CI), 1.16-3.53]. Stratified analyses by different follow-up periods showed that dengue virus infection was significantly associated with a higher risk of leukemia only between 3 and 6 years after infection (adjusted HR, 3.22; 95% CI, 1.25-8.32). There was no significant association between dengue and the risk of other cancers. This study provides the first epidemiologic evidence for the association between dengue virus infection and leukemia. Considering the rapidly increasing global incidence of dengue and the burden of leukemia, further studies are required to verify this association and to unravel the potential mechanisms of pathogenesis.

Investigation of laboratory confirmed Dengue outbreak in North-eastern Kenya, 2011.

The first laboratory confirmed dengue outbreak in Kenya was reported in coastal towns of Malindi and Kilifi in 1982. Since then, no other outbreak had been confirmed in Kenya. Dengue outbreak was confirmed among African Mission soldiers in Somalia (AMISOM) between May to October 2011. From September 2011, an upsurge of febrile patients who were negative for malaria on microscopy were reported in several health facilities in Mandera town, an adjacent area to Somalia in northern Kenya. We investigated a suspected dengue outbreak in Mandera town from 26th September 2011 to 5th October 2011. A suspected case was defined as acute onset of fever with two or more of the following: headache, arthralgia, myalgia, rash and hemorrhages and negative malaria microscopy results in a person presenting to a health facility in Mandera town from 1st August to 2nd October 2011. We prospectively identified new cases meeting the suspect case definition from 2nd October to 5th October 2011 and we collected blood samples from consenting patients. Blood was collected into plastic vacutainers and stored in dry shipper at -80oc to laboratory for dengue virus testing using real time reverse transcriptase polymerase chain reaction (rRT-PCR). We administered a standardized form to obtain clinical information. We calculated descriptive statistics to describe the outbreak. A total of 1,332 patients had been line listed by the district surveillance team, of which 381 (29%) met our suspect case definition of dengue. Cases peaked between 10th September and 1st October 2011 and thereafter declined. We prospectively identified 33 cases meeting the suspect case definition, of whom 30 (91%) were positive for dengue virus serotype 3 by PCR. Among the 30 laboratory confirmed patients, 20 (67%) required hospitalization (Median hospitalization period, two days with a range: 1–4 days)). And of these, 26 (86%) patients reported aches and pain, 16 (53%) reported vomiting, and four (13%) gingival bleeding. Twenty-three (77%) received anti-malarial therapy. Among laboratory-confirmed dengue patients, seven (23%) had malaria co-infection. This was the second confirmed Dengue outbreak in Kenya, and highlighted the need for improved surveillance to better define disease burden and continuous education to medical personnel to improve detection and clinical management. We also recommended enhanced community education for disease prevention.

Clinical and Laboratory Factors Associated with Severe Dengue: A Case-Control Study of Hospitalized Children.

More than half of the hospitalizations because of dengue in Brazil occurred in children <15 years of age in 2007 and 2008, an unexpected change in the epidemiological pattern. We sought to determine clinical and laboratory parameters associated with severity. A case-control study was conducted in three pediatric hospitals in Rio de Janeiro, Brazil; 233 laboratory-confirmed dengue patients were included: 69 cases and 164 controls. Specific clinical and laboratory factors were assessed using univariate and multivariate logistic regression models. Lethargy [adjusted odds ratio (ORa): 9.15, 95% confidence interval (CI): 3.08-27.12], dyspnea (ORa: 8.24, 95% CI: 3.27-20.72) and abdominal pain (ORa: 6.78, 95% CI: 1.44-31.84) were independently associated with severe dengue in children. Lethargy and dyspnea presented as early as 72 and 48 h, respectively, before shock. Abdominal pain and lethargy confirmed their role as warning signs, which along with dyspnea might be helpful in identifying cases progressing to severe dengue.

Age-associated differences in clinical manifestations and laboratory parameters during a dengue virus type 4 outbreak in Argentina.

Infection by any of the four dengue virus (DENV) serotypes produces a wide spectrum of clinical illness in humans. Differences in clinical manifestation and severity have been associated with secondary heterologous infection, patient age, and virus serotype. In this context, this retrospective study sought to analyze the presentation of dengue in patients during the 2014 DENV-4 outbreak affecting the City of Orán, Salta Province, Argentina. Demographic data, clinical manifestations, and laboratory abnormalities of laboratory-confirmed dengue patients were compared between age groups and between patients with and without warning signs. Of 301 patients with laboratory-confirmed dengue, 37.9% presented dengue with warning signs. Although nearly half of all patients had secondary DENV infections, no severe dengue cases, or deaths were reported. Furthermore, no association was found between incidence of warning signs and pre-existing immunity to DENV. Pediatric patients were least likely to present warning signs and showed significantly decreased risk of fever, retro-orbital pain, arthalgia, diarrhea and thrombocytopenia, and higher risk of rash compared to older patients. Female patients of all ages were also at higher risk of developing several symptoms. The characterization of DENV-4 infection in humans, a DENV serotype recently reported in Argentina, revealed differences in clinical manifestations, laboratory parameters and the presence/absence of warning signs based on age group. Further investigation of these age-related differences should contribute to better assessment of dengue disease in at risk populations.

Genetic variants of MICB and PLCE1 and associations with the laboratory features of dengue

BackgroundA previous genome-wide association study identified 2 susceptibility loci for severe dengue at MICB rs3132468 and PLCE1 rs3740360 and further work showed these mutations to be also associated with less severe clinical presentations. The aim of this study was to determine if these specific loci were associated with laboratory features of dengue that correlate with clinical severity with the aim of elucidating the functional basis of these genetic variants.MethodsThis was a case-only analysis of laboratory-confirmed dengue patients obtained from 2 prospective cohort studies and 1 randomised clinical trial in Vietnam (Trial registration: ISRCTN ISRCTN03147572. Registered 24th July 2012). 2742 dengue cases were successfully genotyped at MICB rs3132468 and PLCE1 rs3740360. Laboratory variables were compared between genotypes and stratified by DENV serotype.ResultsThe analysis showed no association between MICB and PLCE1 genotype and early viraemia level, platelet nadir, white cell count nadir, or maximum haematocrit in both overall analysis and in analysis stratified by serotype.DiscussionThe lack of an association between genotype and viremia level may reflect the sampling procedures within the included studies. The study findings mean that the functional basis of these mutations remains unclear.Trial registrationISRCTN ISRCTN03147572. Registered 24th July 2012.

Development of a Simple Clinical Risk Score for Early Prediction of Severe Dengue in Adult Patients.

We aimed to develop and validate a risk score to aid in the early identification of laboratory-confirmed dengue patients at high risk of severe dengue (SD) (i.e. severe plasma leakage with shock or respiratory distress, or severe bleeding or organ impairment). We retrospectively analyzed data of 1184 non-SD patients at hospital presentation and 69 SD patients before SD onset. We fit a logistic regression model using 85% of the population and converted the model coefficients to a numeric risk score. Subsequently, we validated the score using the remaining 15% of patients. Using the derivation cohort, two scoring algorithms for predicting SD were developed: models 1 (dengue illness ≤4 days) and 2 (dengue illness >4 days). In model 1, we identified four variables: age ≥65 years, minor gastrointestinal bleeding, leukocytosis, and platelet count ≥100×109 cells/L. Model 1 (ranging from −2 to +6 points) showed good discrimination between SD and non-SD, with an area under the receiver operating characteristic curve (AUC) of 0.848 (95% confidence interval [CI], 0.771–0.924). The optimal cutoff value for model 1 was 1 point, with a sensitivity and specificity for predicting SD of 70.3% and 90.6%, respectively. In model 2 (ranging from 0 to +3 points), significant predictors were age ≥65 years and leukocytosis. Model 2 showed an AUC of 0.859 (95% CI, 0.756–0.963), with an optimal cutoff value of 1 point (sensitivity, 80.3%; specificity, 85.8%). The median interval from hospital presentation to SD was 1 day. This finding underscores the importance of close monitoring, timely resuscitation of shock including intravenous fluid adjustment and early correction of dengue-related complications to prevent the progressive dengue severity. In the validation data, AUCs of 0.904 (95% CI, 0.825–0.983) and 0.917 (95% CI, 0.833–1.0) in models 1 and 2, respectively, were achieved. The observed SD rates (in both cohorts) were <3% for patients with a score <1 point, but >50% for those with a score of ≥2 points, irrespective of the day of illness onset, suggesting that our simple risk score can be easily implemented in resource-limited countries for early prediction of dengue patients at risk of SD provided that they have rapid dengue confirmed tests. For patients with other acute febrile illnesses or bacterial infections usually have SD risk score of >1. Thus, these scoring algorithms cannot totally replace good clinical judgement of the physician, and most importantly, early differentiating dengue from other febrile illnesses is critical for appropriate monitoring and management.

Clinical Profiles and Factors Associated with Death in Adults with Dengue Admitted to Intensive Care Units, Minas Gerais, Brazil

The purpose of our study was to describe the clinical profile of dengue-infected patients admitted to Brazilian intensive care units (ICU) and evaluate factors associated with death. A longitudinal, multicenter case series study was conducted with laboratory-confirmed dengue patients admitted to nine Brazilian ICUs situated in Minas Gerais state, southeastern Brazil from January 1, 2008, to December 31, 2013. Demographic, clinical and laboratory data; disease severity scores; and mortality were evaluated. A total of 97 patients were studied. The in-ICU and in-hospital mortality rates were 18.6% and 19.6%, respectively. Patients classified as having severe dengue according to current World Health Organization classifications showed an increased risk of death in a univariate analysis. Nonsurvivors were older, exhibited lower serum albumin concentrations and higher total leukocyte counts and serum creatinine levels. Other risk factors (vomiting, lethargy/restlessness, dyspnea/respiratory distress) were also associated with death in a univariate analysis. Multivariate analysis indicated that in-hospital mortality was significantly associated with Acute Physiology and Chronic Health Evaluation II and the Sequential Organ Failure Assessment score. The ICU and in-hospital mortality observed in this study were higher than values reported in similar studies. An increased frequency of ICU admission due to severe organ dysfunction, higher severity indices and scarcity of ICU beds may partially explain the higher mortality.

Direct costs of dengue hospitalization in Brazil: public and private health care systems and use of WHO guidelines.

BackgroundDengue, an arboviral disease, is a public health problem in tropical and subtropical regions worldwide. In Brazil, epidemics have become increasingly important, with increases in the number of hospitalizations and the costs associated with the disease. This study aimed to describe the direct costs of hospitalized dengue cases, the financial impact of admissions and the use of blood products where current protocols for disease management were not followed.Methods and ResultsTo analyze the direct costs of dengue illness and platelet transfusion in Brazil based on the World Health Organization (WHO) guidelines, we conducted a retrospective cross-sectional census study on hospitalized dengue patients in the public and private Brazilian health systems in Dourados City, Mato Grosso do Sul State, Brazil. The analysis involved cases that occurred from January through December during the 2010 outbreak. In total, we examined 8,226 mandatorily reported suspected dengue cases involving 507 hospitalized patients. The final sample comprised 288 laboratory-confirmed dengue patients, who accounted for 56.8% of all hospitalized cases. The overall cost of the hospitalized dengue cases was US $210,084.30, in 2010, which corresponded to 2.5% of the gross domestic product per capita in Dourados that year. In 35.2% of cases, blood products were used in patients who did not meet the blood transfusion criteria. The overall median hospitalization cost was higher (p = 0.002) in the group that received blood products (US $1,622.40) compared with the group that did not receive blood products (US $550.20).ConclusionThe comparative costs between the public and the private health systems show that both the hospitalization of and platelet transfusion in patients who do not meet the WHO and Brazilian dengue guidelines increase the direct costs, but not the quality, of health care.

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.