Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants

To establish the role of maternal dengue-specific antibodies in the development of dengue hemorrhagic fever and dengue shock syndrome caused by dengue 2 virus in infants, we examined sera from mothers of infants and toddlers with dengue hemorrhagic fever or dengue shock syndrome and mothers of infants with pyrexia of unknown origin. The mean titers of hemagglutination inhibition, neutralization, and infection-enhancing activities against dengue 2 virus were not statistically different among the three groups. However, among infants who developed dengue hemorrhagic fever/dengue shock syndrome there was a strong correlation between the mothers' dengue 2 neutralizing titers and infant age at the time of onset of severe illness, where no such correlation was found among the other two groups. Furthermore, the actual age at which dengue hemorrhagic fever/dengue shock syndrome occurred in each infant correlated with the age at which maximum enhancing activity for dengue 2 infection in mononuclear phagocytes was predicted. This critical time for the occurrence of dengue hemorrhagic fever/dengue shock syndrome was observed to be approximately 2 months after the time calculated for maternal dengue 2 neutralizing antibodies to degrade below a protective level. In addition, sera of mothers of infants with dengue hemorrhagic fever/dengue shock syndrome enhanced dengue 2 virus infection to a slightly greater degree than did sera from mothers of infants with pyrexia of unknown origin and toddlers with dengue hemorrhagic fever/dengue shock syndrome. These data are consistent with the hypothesis that maternal dengue antibodies play a dual role by first protecting and later increasing the risk of development of dengue hemorrhagic fever/dengue shock syndrome in infants who become infected by dengue 2 virus.     

Unilateral massive hemothorax in Dengue hemorrhagic fever: a unique presentation

Dengue hemorrhagic fever is a more serious form of disease characterised by plasma leakage syndrome, thrombocytopenia and disseminated intravascular coagulation. We present a 51 year old male who presented with fever, petechiae and acute onset of breathlessness. Emergency chest rhoentogram showed a massive right sided pleural effusion. On insertion of intercostal drain, there was a sudden gush of blood tinged fluid suggestive of hemothorax. There was no history of trauma or bleeding tendencies. Laboratory investigations revealed a raised hematocrit and severe thrombocytopenia. Dengue IgM was surprisingly positive. After aggressive supportive management the patient gradually improved and was discharged. While bilateral pleural effusion is a known occurrence in dengue hemorrhagic fever, massive hemothorax is unheard of. We report the first case in literature of dengue hemorrhagic fever presenting as unilateral massive hemothorax. A suspicion of dengue must also be borne in mind in cases of non-traumatic hemothorax especially in endemic areas.     

Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever

Serum specimens collected during a prospective study of dengue infections among schoolchildren in Bangkok were tested for their ability to enhance dengue 2 (DEN-2) virus growth in human monocytes in vitro. Two groups of dengue-immune sera were compared: 32 dengue antibody positive serum specimens from children who subsequently developed asymptomatic secondary dengue infections; and 9 dengue antibody positive serum specimens from children who subsequently developed severe symptomatic secondary dengue infections, 8 of which were clinically diagnosed as dengue hemorrhagic fever. Antibody-dependent enhancement of virus growth was quantitated by measurement of virus yields in supernatant fluids of normal human monocyte cultures that were infected with DEN-2 virus in the presence of undiluted test serum. Only 4 of 32 (12%) preinfection sera from asymptomatic children, but 6 of 9 (67%) preinfection sera from symptomatic children, had significant enhancing activity (P less than 0.001). High serum DEN-2 antibody dependent enhancing activity is a significant (relative risk = 6.2) risk factor for severe illness among children in a dengue hemorrhagic fever endemic region. Dengue antibodies can be neutralizing and therefore protective, or they can be enhancing and increase the risk of dengue hemorrhagic fever.     

Case report: Dengue hemorrhagic fever with encephalopathy in an adult

Encephalopathy in dengue hemorrhagic fever is a very rare condition and usually occurrs in the febrile stage. We report a 29-year-old woman, who presented with acute fever, thrombocytopenia and positive IgM antibodies for dengue virus. On the fourth hospital day, the fever subsided and she developed a confusional stage. CT scan and MRI of the brain were within normal limits. Electroencephalography (EEG) revealed generalized theta waves. Cerebrospinal fluid was normal. She was treated with supportive treatment. Five days later, she was fully recovered without any neurological deficits. This is a first case of encephalopathy in dengue hemorrhagic fever that developed after the fever subsided.     

Association between Nutritional Status and Severity of Dengue Infection in Children in El Salvador

Clinical observations and some studies suggest that dengue virus infection is more severe among children with better nutritional status. We examined the nutritional status of children in El Salvador and its relationship between this and the severity of dengue infection. Z-scores for weight-for-age, height-for-age, and body mass index (BMI)-for-age of children with dengue fever (66), dengue hemorrhagic fever (62), and healthy controls (74) were compared. There were no differences in weight-for-age or BMI-for-age Z-scores between the three groups. Children with dengue fever had a greater height-for-age than healthy controls but no significant differences in rates of stunting. There was no difference in height between children with dengue fever and dengue hemorrhagic fever. Excess nutrition does not appear to be a risk factor for severe forms of dengue infection in El Salvador, nor does malnutrition appear to be predictive of good outcomes.     

A prospective study of dengue infections in Bangkok

Dengue infections were prospectively studied among 4- to 16-year-old students at a Bangkok school. Blood samples were obtained from 1,757 students in June 1980, before the dengue season, and in January 1981, after the season, and tested for dengue antibodies by the hemagglutination inhibition method. Classrooms were monitored daily for school absences. Fifty percent of the children had antibodies to, and were presumably immune to, at least 1 dengue serotype by the age of 7 years. Most (90/103, 87%) students who became infected by dengue viruses during the study period were either asymptomatic or minimally symptomatic (absent only 1 day). Most (7/13, 53%) of the symptomatic dengue infections (absent with fever for greater than or equal to 2 days) were clinically recognized as cases of dengue hemorrhagic fever which required hospitalization. None of 47 primary dengue infections required hospitalization, whereas 7 of 56 secondary infections did (P = 0.012). Preexistent dengue immunity, as detected by conventional serologic techniques, was a significant (odds ratio greater than or equal to 6.5) risk factor for development of dengue hemorrhagic fever.     

Parturient and perinatal dengue hemorrhagic fever

A Thai woman in the shock stage of dengue hemorrhagic fever delivered a healthy infant by normal delivery. She had high, prolonged fever for five days, hepatomegaly, thrombocytopenia and a right pleural effusion. The serology performed later established a diagnosis of secondary dengue infection. She had no serious complications except for postpartum anemia. The newborn became febrile at the 48th hour of life. He had fever for 2 days, hepatomegaly, thrombocytopenia and a right pleural effusion. Dengue virus type 1 was detected from his serum by polymerase chain reaction (PCR). Although he developed prolonged, marked thrombocytopenia (12 days), his illness was uncomplicated. He recovered uneventfully and was discharged with his mother. This report was one of dengue vertical transmission with dengue hemorrhagic fever in humans.     

Dengue fever: a harmful disease in patients with thrombocytopenia?

We describe 2 patients with autoimmune thrombocytopenic disease who developed classic dengue fever associated with serious bleeding and extremely low platelet counts (1000 cells/mm(3) and 3000 cells/mm(3), respectively). Such patients should be properly advised as to the possibility that common dengue fever may substantially enhance their risk for hemorrhagic complications.     

Capillary leakage in travelers with dengue infection: implications for pathogenesis

Dengue hemorrhagic fever is characterized by the presence of a capillary leak syndrome. Its pathogenesis is presumed to differ from that of classical dengue fever (DF) and to be associated with secondary dengue infection. Returning travelers given a diagnosis of DF were evaluated for capillary leakage with abdominal sonography. Data were compared between travelers with primary/secondary infection defined by epidemiologic and serologic parameters. A total of 12 (34.3%) of 35 patients had sonographic signs of capillary leakage. Most (85%) patients with capillary leakage had classical DF. Capillary leak was diagnosed in 32% of primary dengue cases and in 40% of secondary dengue cases (P = 0.69). The two patients given a diagnosis of dengue hemorrhagic fever had primary infections. The high prevalence of capillary leakage among travelers, most of them with primary exposure to dengue, calls into question the importance of secondary infection in causing capillary leakage in dengue infection.     

Dengue hemorrhagic fever presenting with acute pancreatitis

Acute pancreatitis is an uncommon manifestation of dengue fever. Here we present a 47 year old male with dengue hemorrhagic fever who presented with acute pancreatitis and associated hyperglycemia. To our knowledge, this is the first reported case of dengue complicated with acute pancreatitis from South Asia.     

Clinical profile of dengue hemorrhagic fever cases in Mexico

OBJECTIVE: Dengue hemorrhagic fever is a public health problem in Mexico since 1994.With four serotypes circulating the risk of epidemic dengue hemorrhagic fever is increasing. MATERIAL AND METHODS: We describe the clinical features of confirmed cases in the social security health system (IMSS) from 1995 to 2003. Clinical picture and epidemiological features were compared and a multivariate model was fitted to evaluate associations. RESULTS: Cases were divided into two groups: 438 patients with dengue fever, including 109 cases with hemorrhagic manifestations without thrombocytopenia, and 977 cases with dengue hemorrhagic fever, including 79 deaths. The main risk factors associated with mortality were hematemesis (RR 2.6; CI 95% 1.4-4.6) and melena (RR 2.2; Cl 95% 1.2-3.7). CONCLUSIONS: Our results characterize the clinical profile of dengue hemorrhagic fever cases in Mexico and identify prognostic factors to alert clinician for the prevention of a fatal evolution.     

Cytokine Factors Present in Dengue Patient Sera Induces Alterations of Junctional Proteins in Human Endothelial Cells

Plasma leakage in severe dengue has been postulated to be associated with skewed cytokine immune responses. In this study, the association of cytokines with vascular permeability in dengue patients was investigated. Human serum samples collected from 48 persons (13 with dengue fever, 29 with dengue hemorrhagic fever, and 6 healthy) were subjected to cytokines analysis by using Luminex Multiplex Technology. Selected serum samples from patients with dengue hemorrhagic fever sera and recombinant human cytokines were then tested for roles on inducing vascular permeability by treatment of human umbilical vein endothelial cells. Confocal immunofluorescence staining indicated morphologic alteration of human umbilical vein endothelial cells treated with serum samples from patients with dengue hemorrhagic fever compared with serum samples from healthy persons. The findings suggest that cytokines produced during dengue hemorrhagic infections could induce alterations in the vascular endothelium, which may play a fundamental role in the pathophysiology of dengue.     

Dengue myocarditis

We report a 13-year-old boy who developed bradycardia and hypotension a day after recovery from dengue hemorrhagic fever. His electrocardiogram, during the bradycardia, showed a junctional rhythm with a rate of 50 beats/minute. This is the first reported case of sinus node dysfunction following dengue infection.     

Fatal dengue hemorrhagic fever imported into Germany

Dengue virus (DENV) is an arthropod-borne virus (family Flaviviridae) causing dengue fever or dengue hemorrhagic fever. Here, we report the first fatal DENV infection imported into Germany. A female traveler was hospitalized with fever and abdominal pain after returning from Ecuador. Due to a suspected acute acalculous cholecystitis, cholecystectomy was performed. After cholecystectomy, severe spontaneous bleeding from the abdominal wound occurred and the patient died. Postmortem analysis of transudate and tissue demonstrated a DENV secondary infection of the patient and a gallbladder wall thickening (GBWT) due to an extensive edema.     

重症登革热的研究进展

登革热是流行于全球尤其是热带亚热带地区的急性传染病,其中有重症表现的登革热是引起登革热患者死亡的主要原因,但是由于目前WHO关于登革热分类的缺陷,使得重症登革热发生率被低估,已经有越来越多的中外学者对WHO定义的登革热分类提出质疑,提出了重症登革热的概念并得到认可。文章主要对重症登革热的临床表现、流行情况、危险人群、危险指标等最新研究进展进行综述,以提高人们对重症登革热的认识,为制定新的登革热诊断标准和治疗方案提供理论基础。     

Dengue and hepatic failure

Dengue hemorrhagic fever/dengue shock syndrome is a serious manifestation of dengue fever, which is observed predominantly in the tropical regions of the West Pacific and in Southeast Asia and is associated with secondary infections, mainly in children under age 15. A concomitant microangiopathic coagulopathy has been described; moreover, encephalopathy and even Reye's syndrome have been rarely reported. This report describes a 51-year-old man with secondary dengue infection who presented with clinical evidence of severe hepatitis, encephalopathy, cranial nerve palsy, and microangiopathic coagulopathy and who had a favorable outcome. A careful surveillance for the occurrence of secondary dengue in the Western Hemisphere is proposed, and dengue is suggested as a diagnostic possibility in obscure febrile illnesses presenting as either hepatitis, encephalopathy, or coagulopathy in places in which the mosquito vector, Aedes aegypti, is present.     

Dengue hemorrhagic fever complicated by pancreatitis

Acute pancreatitis is an atypical complication of dengue fever and is rarely described. We are reporting a case of dengue hemorrhagic fever complicated by acute pancreatitis in a patient with history of diabetes mellitus type 1 and end stage renal disease on hemodialysis.     

Dengue fever with hemorrhagic manifestations in travellers returning to Quebec from Asia

Two cases of dengue fever with hemorrhagic manifestations were observed in 1990 and 1992 among travellers returning from Asia, while a third presented with classical dengue fever after the patient's first trip to an endemic region. All experienced rash, thrombocytopenia and coagulation disorders and had flavivirus serology consistent with exposure to dengue virus.     

Dengue hemorrhagic shock and disseminated candidiasis

Dengue fever, one of the common endemic viral fevers, often presents with fever, rash, and mild liver dysfunction. However, plasma leakage induced by dengue virus infection can lead to dengue hemorrhagic fever and dengue shock syndrome, and it can cause severe complications including liver failure and encephalopathy. Infection of dengue virus with other pathogens is an unusual but serious complication. We report a case of dengue shock syndrome with liver failure and impaired consciousness. The patient developed a disseminated Candida tropicalis infection, which may have been due to translocation of the fungus from the intestine damaged by the dengue virus.     

Dual infection: dengue hemorrhagic fever with unusual manifestations and mycoplasma pneumonia in a child

We report a case of pneumonia caused by Mycoplasma pneumoniae in an 8-year-old Thai girl. She had a dual infection with dengue hemorrhagic fever with unusual manifestations; liver failure. The diagnoses were based on relevant clinical findings and laboratory confirmations of both infections.