The year under review has seen a remarkable proliferation of papers on dengue. Four prospective studies have been carried out across the dengue belt, many groups have been pushing at the question of pathogenesis of dengue haemorrhagic fever, and a breakthrough has been achieved in the development of a mouse model for human dengue haemorrhagic fever.
Over the past 20 years, dengue haemorrhagic fever (DHF) has been the subject of intensive epidemiological, clinical, virological and immunological investigations. Considerable debate and controversy have surrounded its causation and the probable role of immunological mechanisms in its pathogenesis. The exact cause of DHF is still uncertain and this article reviews current thinking about the problem.
Matched MeSH terms: Severe Dengue/physiopathology*
Dengue fever (DF) is an acute febrile viral disease frequently presented with headache, bone or joint and muscular pains, and rash. A significant percentage of DF patients develop a more severe form of disease, known as dengue haemorrhagic fever (DHF). DHF is the complication of DF. The main pathophysiology of DHF is the development of plasma leakage from the capillary, resulting in haemoconcentration, ascites, and pleural effusion that may lead to shock following defervescence of fever. Therefore, accurate prediction of the day of defervescence of fever is critical for clinician to decide on patient management strategy. To date, no known literature describes of any attempt to predict the day of defervescence of fever in DF patients. This paper describes a non-invasive prediction system for predicting the day of defervescence of fever in dengue patients using artificial neural network. The developed system bases its prediction solely on the clinical symptoms and signs and uses the multilayer feed-forward neural networks (MFNN). The results show that the proposed system is able to predict the day of defervescence in dengue patients with 90% prediction accuracy.
Matched MeSH terms: Dengue/physiopathology*; Severe Dengue/physiopathology*
Real-time monitoring and precise diagnosis of the severity of Dengue infection is needed for better decisions in disease management. The aim of this study is to use the Bioimpedance Vector Analysis (BIVA) method to differentiate between healthy subjects and severe and non-severe Dengue-infected patients. Bioimpedance was measured using a 50 KHz single-frequency bioimpedance analyzer. Data from 299 healthy subjects (124 males and 175 females) and 205 serologically confirmed Dengue patients (123 males and 82 females) were analyzed in this study. The obtained results show that the BIVA method was able to assess and classify the body fluid and cell mass condition between the healthy subjects and the Dengue-infected patients. The bioimpedance mean vectors (95% confidence ellipse) for healthy subjects, severe and non-severe Dengue-infected patients were illustrated. The vector is significantly shortened from healthy subjects to Dengue patients; for both genders the p-value is less than 0.0001. The mean vector of severe Dengue patients is significantly shortened compare to non-severe patients with a p-value of 0.0037 and 0.0023 for males and females, respectively. This study confirms that the BIVA method is a valid method in differentiating the healthy, severe and non-severe Dengue-infected subjects. All tests performed had a significance level with a p-value less than 0.05.
Dengue is the most common and widespread arthropod borne arboviral infection in the world today. It is estimated that there are at least 100 million cases of dengue fever (DF) annually and 500,000 cases of dengue hemorrhagic fever (DHF) which require hospitalization. In Malaysia, it has become a major public health problem. Malaysia recorded 19,544 dengue cases in 1997, the highest recorded since the disease was made notifiable in the country. Of 19,544 cases, 806 were DHF with 50 deaths. The objectives of this analysis were to describe the incidence of dengue fever and dengue hemorrhagic fever in Kota Bharu, Kelantan, Malaysia for the years 1998-2003 and to explore the characteristics of dengue fever and dengue hemorrhagic fever in Kota Bharu, Kelantan, Malaysia for years 1998-2003. A total of 4,716 dengue cases were notified involving 4,476 (94.9%) DF and 240 (5.1%) DHF cases, which increased though the years. The highest incidence was in January (701 or 14.9%), while the lowest was in May (188 or 4.0%). Forty percent of cases (n=1,890) were in the 15-29 year old group. The Majority were Malays (4,062 or 86.1%) and 2,602 or 55.2% were male. A total of 4,477 cases (95%) were local cases and 4,289 or 91% came from the urban area. For priority areas, 3,772 (80%) were from priority 1. More than half the cases had positive serology results. All symptoms occurred in more than 96% of cases and fever was the commonest (99.7%). The mean values for age, temperature, systolic and diastolic blood pressure (BP) were 27.8 +/- 15.4 years, 37.9 +/- 0.90 degrees C, 115 +/- 15.2 mmHg and 73 +/- 11.1 mmHg, respectively. The mean value for the time interval between the onset of symptoms and diagnosis, onset of symptoms and notification and time of diagnosis to notification were 5.1 +/- 2.3, 5.9 +/- 2.5 and 0.8 +/- 1.1 days, respectively. There were associations between the types of dengue and classification, area and priority area. Among the symptoms, the association was only seen in joint pain. The mean significant differences between DF and DHF were found in age and systolic blood pressure. The incidence of dengue in Kota Bharu is comparable to that in Malaysia. The increase in the number of cases needs to be addressed promptly with effective surveillance, prevention and control programs.
A consecutive series of 24 patients with clinical features of primary dengue infection and 22 controls (14 patients with viral fever of unknown origin and 8 healthy subjects) were assayed for serum levels of tumour necrosis factor (TNF). The acute sera of the 24 patients with clinical dengue infection were positive for dengue virus-specific IgM antibody. Clinically, 8 had dengue fever (DF), 14 dengue haemorrhagic fever (DHF) and 2 dengue shock syndrome (DSS). All 16 patients with DHF/DSS had significantly elevated serum TNF levels but the 8 DF patients had TNF levels equivalent to that in the 22 controls. A case is made for augmented TNF production having a role for the pathophysiological changes observed in DHF/DSS and mediator modulation as a possible therapeutic approach to treatment.
Dengue fever, Dengue hemorrhagic fever and Dengue shock syndrome within the dengue complex is a sinister disease of great public health importance and continues to ravage children, young adults and the aged in Malaysia. The history of the disease is traced for over the years and the changing pattern of clinical presentation are noted. Various hospital based studies have been compared and the pathognomonic features of the disease in Malaysia are highlighted.
BACKGROUND: Difficulties in the classification of dengue infection have been documented. Such difficulties could be due to the low awareness of the World Health Organization diagnostic guidelines among clinicians.
OBJECTIVE: To study the diagnostic practices of clinicians in classifying patients as dengue fever (DF) or dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS) at the time of discharge during an outbreak.
METHODS: A prospective descriptive study of clinical features and disease classification in adult and pediatric dengue patients in the University of Malaya Medical Centre.
RESULTS: Five hundred and twenty adult and 191 pediatric patients were enrolled. Thrombocytopenia and evidence of plasma leakage were present in 8% of adult and 19% of pediatric patients. Of these, 93% and 49%, respectively, were given the discharge diagnoses of DF instead of DHF/DSS. Hemoconcentration, serous effusion and thrombocytopenia were not recognized in clinicians' discharge diagnosis of DHF/DSS for adult patients. The receiver operating characteristic (ROC) curve suggested a lack of consistency in the use of WHO guidelines in establishing DHF/DSS in adult patients, while implying otherwise for pediatric patients.
CONCLUSION: DHF/DSS is an under-recognized condition by clinicians managing these patients. This can affect the case fatality rate of DHF/DSS and the economic burden of the disease. The lack of awareness in disease manifestations especially plasma leakage, can lead to delayed recognition of DHF/DSS.
Study site: Outpatient department and inpatients, adult medical and pediatric wards, University Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia
Matched MeSH terms: Dengue/physiopathology; Severe Dengue/physiopathology
The impact of dengue on liver function was studied on fifty serologically confirmed dengue cases admitted to Hospital Universiti Kebangsaan Malaysia (HUKM). Twenty-five of these patients had classic dengue fever (DF) and 25 had grade 1 or 2 dengue hemorrhagic fever (DHF). There were more (60%) DHF patients with hepatomegaly compared to DF (40%) but the difference was not statistically significant. Analysis of the liver profile showed that liver dysfunction was commoner in DHF compared to DF, indicating that the degree of liver impairment may be related to the severity of DHF. Hyperbilirubinemia was noted in 3 (12%) DHF and 2 (8%) DF patients. The mean (range) serum bilirubin was higher in DHF [14.2(5-50) micromol/l] compared to DF [10.9(5-30) micromol/l)] (p > 0.05). Elevated levels of serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were observed more frequently in DHF (20 and 12 patients respectively) compared to DF (16 and 8 patients respectively). Nine (36%) DHF and 6 (24%) DF patients had concomitant elevation of ALT and ALP levels. The mean (range) serum ALT levels were 109.3(23-325) U/l in DHF and 90.8(13-352) U/l in DF (p > 0.05). The mean (range) serum ALP levels were 102.2(15-319) U/l in DHF and 93.3(34-258) U/l in DF (p > 0.05). The ALT and ALP levels were significantly higher in DHF patients with spontaneous bleeding than those without bleeding (p < 0.05) None of the patients developed fulminant hepatitis. The immunoregulatory cells, which include the T (CD3), B (CD 19), CD4, CD8, CD5 and natural killer (NK) cells were significantly lower in DHF compared to DF patients (p < 0.05). However, the reduction in these cell counts did not correlate with the liver dysfunction seen in DHF patients. In conclusion, hepatomegaly and liver dysfunction were commoner in DHF compared to DF.
Matched MeSH terms: Dengue/physiopathology*; Severe Dengue/physiopathology*
In dengue shock syndrome, an acute increase in capillary permeability results in leakage of plasma into the interstitial space. Pleural effusion is commonly seen in dengue shock syndrome. We report three cases of dengue-associated adult respiratory distress syndrome (ARDS) in children, in all of whom dengue haemorrhagic fever, presenting with grade 3 or grade 4 dengue shock syndrome with disseminated intravascular coagulopathy, was confirmed. The criteria for the diagnosis of ARDS were based on the expanded definition of ARDS by Murray et al. Treatment consisted of fluid resuscitation, correction of coagulopathy and mechanical ventilation. All three children had multi-organ impairment, but it was more severe in the two who died. The one survivor was well at discharge.
Four recent cases of dengue fever with severe, unusual clinical manifestations are described. Two of these cases had features of fulminant hepatitis and encephalopathy; one of these cases was fatal. The two remaining cases showed hepatitis with renal impairment. The significance and importance of these unusual manifestations of dengue disease are discussed.
Although the disease burden of dengue is increasing, the impact on the quality of life (QoL) has not been investigated. A study to determine the QoL of confirmed dengue patients using the EuroQol visual thermometer scale was carried out at the University Malaya Medical Center. Of the 207 participants, 40% were ambulatory and 60% were hospitalized. Of eight health domains, 6.2 and 5.0 domains were affected in the hospitalized and ambulatory cohorts, respectively (P < 0.001), with cognition and interpersonal activities affected most. All patients experienced a drastic decrease in their QoL from the onset of symptoms. The QoL deteriorated to the lowest point (40% of healthy status) between the third and seventh days of illness. The duration of impaired QoL (9 days for ambulatory or 13 days for hospitalized patients) was longer than the duration of fever (5 and 7 days, respectively). Symptomatic dengue has major effects on patients' health.
Study site: e outpatient or inpatient care at the University Malaya Medical
Center.
Prospective evaluation of repeated standard tourniquet testing as a diagnostic indicator of dengue infection was done. Included were patients admitted to a children's hospital in Kuala Lumpur on a clinical suspicion of dengue infection based on the World Health Organization (WHO) criteria. A standard method of tourniquet was performed on 79 patients on a daily basis following admission. subjects and negative in the remaining 14 subjects. Fifty-eight subjects were serologically confirmed cases, 4 indeterminate and the remaining 17 subjects had negative serology. For diagnostic classification, 13 had dengue fever, 49 with dengue haemmorhagic fever (DHF) while 17 had non-dengue infection. The sensitivity and specificity of the tourniquet test was 82.8% and 23.5% respectively. The positive predictive value (PPV) was 78.7% while the negative predictive value (NPV) was 28.6%. In addition, the tourniquet test aided in the diagnosis of one-fifth of patients with DHF, who presented with a positive tourniquet test as the only bleeding manifestation. It seems that in a hospital setting, the tourniquet test adds little to the diagnosis of dengue infection/DHF. A positive tourniquet test, repeatedly performed, was found clinically useful as a preliminary screening test in dengue infection as recommended by WHO. However, it was not very specific and had a high false positive rate.
Background: There is an escalation of frequency and magnitude of dengue epidemics in Malaysia, with a concomitant increase in patient hospitalization. Prolonged hospitalization (PH) due to dengue virus (DENV) infections causes considerable socioeconomic burden. Early identification of patients needing PH could optimize resource consumption and reduce health care costs. This study aims to identify clinicopathological factors present on admission that are associated with PH among patients with DENV infections. Methods: This study was conducted in a tertiary referral hospital in Southern Malaysia. Relevant clinical and laboratory data upon admission were retrieved from medical records of 253 consecutive DENV nonstructural protein 1 (NS1) antigen and PCR-positive hospitalized patients. The DENV serotype present in each patient was determined. Patients were stratified based on duration of hospital stay (<4 vs. ≥4 days). Data were analyzed using IBM® SPSS® 25.0. Multivariate logistic regression was performed to examine the association between PH and admission parameters. Results: Of 253 DENV hospitalized patients, 95 (37.5%) had PH (≥4 days). The mean duration of hospital stay was 3.43 ± 2.085 days (median = 3 days, interquartile range = 7 days). Diabetes mellitus (adjusted odds ratio [AOR] = 6.261, 95% confidence interval [CI] = 2.130-18.406, p = 0.001), DENV-2 serotype (AOR = 2.581, 95% CI = 1.179-5.650, p = 0.018), duration of fever ≤4 days (AOR = 2.423, 95% CI = 0.872-6.734, p = 0.09), and a shorter preadmission fever duration (AOR = 0.679, 95% CI = 0.481-0.957, p = 0.027) were independently associated with PH. However, PH was not found to be associated with symptoms on admission, secondary DENV infections or platelet count, hematocrit, or liver enzyme levels on admission. Conclusions: Early identification of these factors at presentation may alert clinicians to anticipate and recognize challenges in treating such patients, leading to more focused management plans that may shorten the duration of hospitalization.