Dengue Illness Research Articles

Dengue fever-like illnesses: How different are they from each other?

In tropical countries and possibly elsewhere, dengue fever can be confused with other common tropical infections like enteric fever, leptospirosis, typhus fever, malaria, etc. Many of these illnesses can present in significant numbers after rains, and because of similar early presentations, can cause confusion in decision-making. With global warming, these diseases can assume significant proportions even in non-endemic areas. Identifying these illnesses in a non-immune returning traveller is equally challenging. Recognition of these diseases is important to diagnose them and treat them early, in order to avoid potentially fatal complications. This review is an attempt to highlight important clinical and laboratory differences among dengue fever-like illnesses.

Spontaneous splenic rupture in dengue fever with non-fatal outcome in an adult

A 26-year-old male presented with fever for five days and abdominal pain for 24 hours. System examination identified a soft abdomen with diffuse tenderness. CT-abdomen findings were consistent with splenic rupture with intra and peri-splenic hematoma. Laboratory investigations showed a platelet count of 40,000 per mm(3). In due course he developed hypotension and underwent splenectomy. Non-structural protein 1 (NS1) dengue antigen was positive in the admission sample and IgM dengue antibodies were detected in the follow-up sample. Histopathology of the spleen showed normal architecture with no evidence of hyperplasia, cellular infiltrates or haematological malignancy. Splenic rupture is a rare, but potentially fatal complication of dengue fever and severe dengue which should be suspected when a patient presents with abdominal pain and hypotension. Our case highlights the occurrence of splenic rupture in the viremic phase of dengue illness before the development of IgM antibodies.

Platelet Apoptosis and Apoptotic Platelet Clearance by Macrophages in Secondary Dengue Virus Infections

The mechanisms of thrombocytopenia and platelet phagocytosis in dengue illness are not fully understood. A prospective hospital-based study was conducted to examine the relationships between platelet counts, serum thrombopoietin (TPO) levels, and platelet apoptosis and phagocytosis in 81 patients with secondary dengue virus (DV) infections and 38 healthy volunteers. The apoptosis and phagocytosis of cultured platelets after exposure to DV were also examined. Platelet apoptosis, platelet phagocytosis, and serum TPO levels were increased significantly in patients during the acute and early convalescence phases compared with levels observed in patients during the convalescence phase and in healthy volunteers. A significant correlation between platelet apoptosis and platelet phagocytosis was also observed in these patients. Platelet phagocytosis was inhibited significantly by the D89E mutant, which carries a point mutation in the RGD motif of milk fat globule-epidermal growth factor 8, a phosphatidylserine-recognizing bridge molecule. DV-induced platelet apoptosis and increased phagocytosis of DV-induced apoptotic platelets was confirmed using in vitro assays. Our data suggest an increased phagocytosis of DV-induced apoptotic platelets by macrophages via a phosphatidylserine-recognizing pathway in secondary DV infection. Accelerated platelet clearance, however, was overcome by TPO-induced enhanced thrombopoiesis in these patients. UMIN000004835.

Re : Dengue Haemorrhagic Fever presenting as Acute Abdomen = رد على : البطن الحادة كعرض لحمى الدنك النزفية

Sir, I read the recent on acute abdomen in dengue with great interest.1 I would like to share with your readers experience on this specific issue of dengue. Indeed, the classical manifestation of dengue is high fever with haemorrhagic diathesis. The common laboratory triad of testing for thrombocytopenia and haemoconcentration and atypical lymphocytosis can be helpful in presumptive diagnosis;2 however, sometimes unusual clinical manifestations can be seen.3 Gastrointestinal manifestations of dengue are not a rare manifestation, and cannot be overlooked. In a recent report from Mexico, Ramos-De La Medina et al. noted that “close to 67% of patients with dengue fever have abdominal and gastrointestinal symptoms.”3 This rate is very high. Any organs in the gastrointestinal tract can be involved in the infection. There are various gastrointestinal manifestations in dengue. Bleeding in the gastrointestinal tract can also be seen although it is not common.4 Thrombocytopenia is the main predisposing factor for gastrointestinal bleeding in dengue.5 If we now focus on hepatic involvement, hepatitis due to dengue is also a possibility and abnormal liver function tests are not uncommon.3 Based on the author’s experience, about one-third of dengue cases have hepatitis and 8% of these cases can end up with severe complications such as hepatic encephalopathy.6 Abdominal pain can also be the manifestation in dengue and this is classified as an atypical manifestation.7 Indeed, abdominal pain is not uncommon and is accepted as an important warning sign in dengue.8,9 The severity of dengue is strongly relating to the presence of abdominal pain.10 In a recent article from India, it was reported as being seen in up to 70% of the paediatric cases.8 Conclusively, acute abdomen can be a first presentation of dengue and conservative management can be used similar to general dengue cases. However, it should be noted that co-morbidity of the disorder that needs surgical management is possible. Abdominal pain is an important warning sign that can be seen in either dengue or other acute febrile illness.11 Nevertheless, Mustafa et al. reported that abdominal pain is a more common presentation in dengue compared to other tropical acute febrile illness.12 In a recent report by Shamim, many conditions can co-present with dengue. Some co-morbidities can be serious and require surgical management. These include, for example, acute cholecystitis and acute appendicitis.13 It is suggested that dengue must be the differential diagnosis of any cases from the endemic area, South and Southeast Asia, which present with unexplained high fever.2 Also, abdominal pain might be the main complaint and, if vital sign monitoring is not done adequately to detect the fever, the case of dengue can be missed. Furthermore, although dengue infection can be confirmed in the case with acute abdomen, it is still necessary to rule out any possible co-morbidity. The use of abdominal ultrasonography can help determine the intrabdominal abnormalities in dengue and rule out other causes of abdominal pain.14

Limited cross-reactivity of mouse monoclonal antibodies against Dengue virus capsid protein among four serotypes

BackgroundDengue illness is one of the important mosquito-borne viral diseases in tropical and subtropical regions. Four serotypes of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4) are classified in the Flavivirus genus of the family Flaviviridae. We prepared monoclonal antibodies against DENV capsid protein from mice immunized with DENV-2 and determined the cross-reactivity with each serotype of DENV and Japanese encephalitis virus.Methods and resultsTo clarify the relationship between the cross-reactivity of monoclonal antibodies and the diversity of these viruses, we examined the situations of flaviviruses by analyses of phylogenetic trees. Among a total of 60 prepared monoclonal antibodies specific for DENV, five monoclonal antibodies stained the nuclei of infected cells and were found to be specific to the capsid protein. Three were specific to DENV-2, while the other two were cross-reactive with DENV-2 and DENV-4. No monoclonal antibodies were cross-reactive with all four serotypes. Phylogenetic analysis of DENV amino acid sequences of the capsid protein revealed that DENV-2 and DENV-4 were clustered in the same branch, while DENV-1 and DENV-3 were clustered in the other branch. However, these classifications of the capsid protein were different from those of the envelope and nonstructural 1 proteins. Phylogenetic distances between the four serotypes of DENV were as different as those of other flaviviruses, such as Japanese encephalitis virus and West Nile virus. Large variations in the DENV serotypes were comparable with the differences between species of flavivirus. Furthermore, the diversity of flavivirus capsid protein was much greater than that of envelope and nonstructural 1 proteins.ConclusionIn this study, we produced specific monoclonal antibodies that can be used to detect DENV-2 capsid protein, but not a cross-reactive one with all serotypes of DENV capsid protein. The high diversity of the DENV capsid protein sequence by phylogenetic analysis supported the low cross-reactivity of monoclonal antibodies against DENV capsid protein.

Unsuspected dengue and acute febrile illness in rural and semi-urban southern Sri Lanka

Unsuspected dengue and acute febrile illness in rural and semi-urban southern Sri Lanka

Economic Impact of Dengue Illness and the Cost-Effectiveness of Future Vaccination Programs in Singapore

BackgroundDengue 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 FindingsWe 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.ConclusionsDengue 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.

Dengue: a newly emerging viral infection in Andaman and Nicobar Islands, India

Prior to 2009 dengue fever had not been reported in the Andaman and Nicobar archipelago. In 2009, a few patients with dengue fever-like illness were reported, some of whom tested positive for dengue antibodies. In 2010, 516 suspected cases were reported, including some with dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS); 80 (15·5%) were positive for dengue antibodies. DENV RNA was detected in five patients and PCR-based typing showed that three of these belonged to serotype 1 and two to serotype 2. This was confirmed by sequence typing. Two clones of dengue virus, one belonging to serotype 1 and the other to serotype 2 appeared to be circulating in Andaman. Emergence of severe diseases such as DHF and DSS might be due to recent introduction of a more virulent strain or because of the enhancing effect of sub-neutralizing levels of antibodies developed due to prior infections. There is a need to revise the vector-borne disease surveillance system in the islands.

Preexisting Japanese Encephalitis Virus Neutralizing Antibodies and Increased Symptomatic Dengue Illness in a School-Based Cohort in Thailand

BackgroundDengue viruses (DENVs) and Japanese encephalitis virus (JEV) have significant cross-reactivity in serological assays; the clinical implications of this remain undefined. An improved understanding of whether and how JEV immunity modulates the clinical outcome of DENV infection is important as large-scale DENV vaccine trials will commence in areas where JEV is co-endemic and/or JEV immunization is routine.Methods and FindingsThe association between preexisting JEV neutralizing antibodies (NAbs) and the clinical severity of DENV infection was evaluated in a prospective school-based cohort in Thailand that captured asymptomatic, non-hospitalized, and hospitalized DENV infections. Covariates considered included age, baseline DENV antibody status, school of attendance, epidemic year, and infecting DENV serotype. 942 children experienced at least one DENV infection between 1998 and 2002, out of 3,687 children who were enrolled for at least one full year. In crude analysis, the presence of JEV NAbs was associated with an increased occurrence of symptomatic versus asymptomatic infection (odds ratio [OR] = 1.55, 95% CI: 1.08–2.23) but not hospitalized illness or dengue hemorrhagic fever (DHF). The association was strongest in children with negative DENV serology (DENV-naive) (OR = 2.75, 95% CI: 1.12–6.72), for whom the presence of JEV NAbs was also associated with a symptomatic illness of longer duration (5.4 days for JEV NAb+ versus 2.6 days for JEV NAb-, p = 0.048). JEV NAbs were associated with increased DHF in younger children with multitypic DENV NAb profiles (OR = 4.05, 95% CI: 1.18 to 13.87). Among those with JEV NAbs, the association with symptomatic illness did not vary by antibody titer.InterpretationThe prior existence of JEV NAbs was associated with an increased probability of symptomatic as compared to asymptomatic DENV illness. These findings are in contrast to previous studies suggesting an attenuating effect of heterologous flavivirus immunity on DENV disease severity.

Co-existence of major and minor viral populations from two different origins in patients secondarily infected with dengue virus serotype 2 in Bangkok

Generally, RNA viruses exhibit significant genetic diversity that sometimes effect viral fitness in infected hosts and probably also pathogenesis. Dengue viruses (DENVs) consist of four antigenically distinct serotypes. All the serotypes of DENV can cause mild to severe dengue illnesses. In this study, we examined the sequence variation of DENV in plasma obtained from four patients living in Bangkok who had been secondarily infected with serotype 2 (DENV-2) in 2010. The plasma-derived RNA was directly subjected to reverse transcriptase (RT)–polymerase chain reaction (PCR) at a region including most of domain III of the envelope (E) protein gene, and the PCR products obtained were subjected to clonal sequencing. Using 19–20 clones sequenced from each patient (78 total) plus 601 corresponding sequences from a public database, phylogenetic analysis revealed that the nucleic acid sequences fell into two clusters with clearly different origins. Interestingly, all patients gave sequences indicating that they carried viral populations containing 2, 3 or 5 genetic variants that consisted of one major variant plus one or more minor variants. Three patients showed a major variant from one cluster plus one or more minor components from the other while one showed major and minor variants from a single cluster. Thus, it can be concluded that DENV belonging to two different genetic lineages were co-circulated in Bangkok in 2010. For these two genotype clusters there was also a clear difference in H or Y at the deduced amino acid position 346 (i.e. H346Y) that was consistent for our sequences and 601 sequences from the public database. Thus, one among the mixed viral genotypes introduced into human individuals seems to be variably selected as the predominant component of the carried viral population, and it is possible that the dynamics of this process could influence virus evolution and disease severity.

A human challenge model for dengue infection reveals a possible protective role for sustained interferon gamma levels during the acute phase of illness

Dengue has recently been defined by the World Health Organization as a major international public health concern. Although several vaccine candidates are in various stages of development, there is no licensed vaccine available to assist in controlling the further spread of this mosquito borne disease. The need for a reliable animal model for dengue disease increases the risk to vaccine developers as they move their vaccine candidates into large-scale phase III testing. In this paper we describe the cellular immune responses observed in a human challenge model for dengue infection; a model that has the potential to provide efficacy data for potential vaccine candidates in a controlled setting. Serum levels of sIL-2Rα and sTNF-RII were increased in volunteers who developed illness. Supernatants from in vitro stimulated PBMC were tested for cytokines associated with a T H1 or T H2 T-cell response (IL-2, TNF-α, IFN-γ, IL-4, IL-10, IL-5) and only IFN-γ was associated with protection against fever and/or viremia. Interestingly, IFN-γ levels drop to 0 pg/mL for volunteers who develop illness after challenge suggesting that some mechanism of immunosuppression may play a role in dengue illness. The human challenge model provides an opportunity to test potential vaccine candidates for efficacy prior to large-scale phase III testing, and hints at a possible mechanism for immune suppression by dengue.

Determinants of Inapparent and Symptomatic Dengue Infection in a Prospective Study of Primary School Children in Kamphaeng Phet, Thailand

BackgroundDengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Inapparent dengue is an important component of the overall burden of dengue infection. It provides a source of infection for mosquito transmission during the course of an epidemic, yet by definition is undetected by health care providers. Previous studies of inapparent or subclinical infection have reported varying ratios of symptomatic to inapparent dengue infection.Methodology/Principal FindingsIn a prospective study of school children in Northern Thailand, we describe the spatial and temporal variation of the symptomatic to inapparent (S:I) dengue illness ratio. Our findings indicate that there is a wide fluctuation in this ratio between and among schools in a given year and within schools over several dengue seasons. The most important determinants of this S:I ratio for a given school were the incidence of dengue infection in a given year and the incidence of infection in the preceding year. We found no association between the S:I ratio and age in our population.Conclusions/SignificanceOur findings point to an important aspect of virus-host interactions at either a population or individual level possibly due to an effect of heterotypic cross-reactive immunity to reduce dengue disease severity. These findings have important implications for future dengue vaccines.

Molecular Mimicry of Human Endothelial Cell Antigen by Autoantibodies to Nonstructural Protein 1 of Dengue Virus

The pathogenesis of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), both serious complications of dengue virus (DV) infection, remains unclear. In this study, we found that anti-DV NS1 (nonstructural protein 1) polyclonal antibodies cross-reacted with human umbilical vein endothelial cells (HUVECs). We further identified a complex-specific mAb, DB16-1, which could recognize DV NS1 and cross-react with HUVECs and human blood vessels. The target protein of DB16-1 was further purified by immunoaffinity chromatography. LC-MS/MS analysis and co-immunoprecipitation revealed that the target protein of DB16-1 was human LYRIC (lysine-rich CEACAM1 co-isolated). Our newly generated anti-LYRIC mAbs bound to HUVECs in a pattern similar to that of DB16-1. The B-cell epitope of DB16-1 displayed a consensus motif, Lys-X-Trp-Gly (KXWG), which corresponded to amino acid residues 116-119 of DV NS1 and mimicked amino acid residues 334-337 in LYRIC. Moreover, the binding activity of DB16-1 in NS1 of DV-2 and in LYRIC disappeared after the KXWG epitope was deleted in each. In conclusion, DB16-1 targeted the same epitope in DV NS1 and LYRIC protein on human endothelial cells, suggesting that it might play a role in the pathogenesis of DHF/DSS. Future studies on the role of the anti-NS1 antibody in causing vascular permeability will undoubtedly be performed on sera collected from individuals before, during, and after the endothelial cell malfunction phase of a dengue illness.

Economic impact of dengue illness in the Americas.

The growing burden of dengue in endemic countries and outbreaks in previously unaffected countries stress the need to assess the economic impact of this disease. This paper synthesizes existing studies to calculate the economic burden of dengue illness in the Americas from a societal perspective. Major data sources include national case reporting data from 2000 to 2007, prospective cost of illness studies, and analyses quantifying underreporting in national routine surveillance systems. Dengue illness in the Americas was estimated to cost $2.1 billion per year on average (in 2010 US dollars), with a range of $1–4 billion in sensitivity analyses and substantial year to year variation. The results highlight the substantial economic burden from dengue in the Americas. The burden for dengue exceeds that from other viral illnesses, such as human papillomavirus (HPV) or rotavirus. Because this study does not include some components (e.g., vector control), it may still underestimate total economic consequences of dengue.

Neuralgic amyotrophy associated with dengue fever

Dengue is an acute mosquito borne viral infection caused by one of the four distinct serotype of dengue viruses (type 1-4), belonging to flavivirus family. Dengue fever, an arboviral infection is known to cause various neurological complications. Commonly reported neurological manifestations associated with dengue infection are encephalopathy, myelopathy, stroke, Guillain-Barre syndrome and hypokalemic paralysis. Brachial amyotrophy associated with dengue infection were not described previously. Here, we describe three patients presenting with brachial neuritis associated with dengue infection. Dengue infection should be considered in the etiological list of brachial neuritis in dengue endemic areas, especially if preceded by history of febrile illness compatible with dengue illness.

Neurological complications of dengue fever: Experience from a tertiary center of north India

Introduction:Dengue, an acute viral disease transmitted by Aedes mosquitoes, is highly endemic in many tropical and subtropical areas of the world. Neurological complications of dengue infection have been observed more frequently in the recent past and some studies highlighted varied neurological complications arising in the course of dengue illness. In this retrospective study, we report various neurological complications observed during the last 2 years in patients of dengue fever.Materials and Methods:The patients presenting with neurological complications with positive serology (IgM antibody) for dengue infection were consecutively recruited from the Department of Neurology/Medicine from a tertiary center of Lucknow, India. These patients were subjected to a detailed clinical evaluation, laboratory assessment including blood count, hematocrit, coagulation parameters, biochemical assays, serology for dengue fever, enzyme-linked immunosorbent assay for human immunodeficiency virus and other relevant investigations.Results:Twenty-six patients with neurological complications associated with confirmed dengue infection were observed during the last 2 years. Eighteen of these patients were male. Of the 26 patients, 10 patients were suffering from brachial neuritis, four patients had encephalopathy, three patients were consistent with the diagnosis of Guillain Barre syndrome, three patients had hypokalemic paralysis associated with dengue fever and two patients had acute viral myositis. Opsoclonus-myoclonus syndrome was diagnosed in two patients, myelitis in one patient and acute disseminated encephalo-myelitis also in one patient.Conclusion:Dengue fever was associated with widespread neurological complications. Brachial neuritis and opsoclonus-myoclonus syndrome were observed for the first time in this study.

Classification of Dengue Illness Based on Readily Available Laboratory Data

The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The sensitivity of the models ranged from 89.2% (dengue versus OFI) to 79.6% (DHF versus DF). The models showed high sensitivity in the validation dataset. These models could be used to calculate a probability and classify patients based on readily available clinical laboratory data, and they will need to be validated in other dengue-endemic regions.

Clinico-Epidemiological Profile of Children Hospitalized with Dengue

To study the clinico-epidemiological profile of children hospitalized with dengue illness. Prospective study of children hospitalized with the diagnosis of dengue illness during from September through November 2006 at a tertiary care centre in Jaipur. A total of 948 children including 671 (70.8%) boys and 277 (29.2%) girls were diagnosed to have dengue illness during the outbreak. Two third of children were from urban areas while 6-12 years was the most commonly affected age group (45.8%). 58.3% cases had dengue fever (DF) while 41.7% had DHF (dengue hemorrhagic fever). Dengue fever with bleed (DFB) accounted for 32% of cases. Common constitutional symptoms were vomiting (35.2%), pain abdomen (22.1%) and myalgia (10.1%). Bleeding manifestations were observed in 44.5% of cases.. Positive tourniquet test was the most common manifestation which was seen in 300 cases (31.6%) while in 9.2% cases bleeding was the only manifestation. Epistaxis (25%) was the most common spontaneous bleeding manifestation. Thrombocytopenia was documented in 84% of total cases and bleeding occurred more often in patients with severe thrombocytopenia. Ten children expired with a case fatality rate of 1.1%. Children between 6 and 12 yrs were most affected by dengue with larger number of cases from urban areas. DFB cases accounted for almost one third cases of dengue. Epistaxis was the most common spontaneous bleeding manifestation. Bleeding occurs more often in patients with severe thrombocytopenia.

Acute myocarditis in dengue hemorrhagic fever: a case report and review of cardiac complications in dengue-affected patients

We report a case of dengue hemorrhagic fever (DHF) complicated by acute myocarditis and review the literature. A 65-year-old woman experienced DHF due to dengue virus serotype 3, complicated with acute myocarditis and acute pulmonary edema. Clinically this masqueraded as acute myocardial infarction, with an electrocardiographically depressed ST segment in precordial leads and elevated serum cardiac-specific troponin I level. Under supportive management, the patient recovered 3 days later. A total of 18 pertinent articles involving 339 dengue-affected patients with cardiac complications were found by PubMed search. Clinical manifestations of cardiac complications varied considerably, from self-limiting tachy-brady arrhythmia to severe myocardial damage, leading to hypotension and pulmonary edema. Although rare, a fatal outcome was reported in some cases of dengue with cardiac complications. To avoid otherwise preventable morbidity and mortality, physicians should have a high index of suspicion for cardiac complications in patients with dengue illness and should manage this accordingly.

Prediction of Dengue Disease Severity among Pediatric Thai Patients Using Early Clinical Laboratory Indicators

BackgroundDengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries.Methods and FindingsWe compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different categories of dengue disease severity to distinguish between patients at elevated risk of developing a severe dengue illness and those at low risk. A diagnostic algorithm using WBC count, percent monocytes, platelet count, and hematocrit achieved 97% sensitivity to identify patients who went on to develop DSS while correctly excluding 48% of non-severe cases. Addition of an indicator of severe plasma leakage to the WHO definition led to 99% sensitivity using WBC count, percent neutrophils, AST, platelet count, and age.ConclusionsThis study identified two easily applicable diagnostic algorithms using early clinical indicators obtained within the first 72 hours of illness onset. The algorithms have high sensitivity to distinguish patients at elevated risk of developing severe dengue illness from patients at low risk, which included patients with mild dengue and other non-dengue febrile illnesses. Although these algorithms need to be validated in other populations, this study highlights the potential usefulness of specific clinical indicators early in illness.