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.     

A case of disseminated gonococcal infection without typical skin rash

Few case reports have been published on disseminated gonococcal infection in Japan. We report such a non-HIV case without typical skin rash. A 49-year-old Japanese man living in Thailand on business was seen for fever and multiple arthralgia after returning to Japan. Given the travel history, differential diagnoses included endemic viral infection such as human immunodeficiency virus (HIV), dengue fever, and chikungunya. Diagnosis was based on right-knee arthrocentesis, and synovial fluid culture followed by Neisseria gonorrhoeae polymerase chain reaction (PCR). The isolated strain was sensitive to penicillin. The man was treated with intravenous ceftriaxone and oral levofloxacin. Disseminated gonococcal infection should thus be considered when examining those with classical polyarthralgia symptoms even without a typical skin rash.     

Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity

Viremia titers in serial plasma samples from 168 children with acute dengue virus infection who were enrolled in a prospective study at 2 hospitals in Thailand were examined to determine the role of virus load in the pathogenesis of dengue hemorrhagic fever (DHF). The infecting virus serotype was identified for 165 patients (DEN-1, 46 patients; DEN-2, 47 patients; DEN-3, 47 patients, DEN-4, 25 patients). Patients with DEN-2 infections experienced more severe disease than those infected with other serotypes. Eighty-one percent of patients experienced a secondary dengue virus infection that was associated with more severe disease. Viremia titers were determined for 41 DEN-1 and 46 DEN-2 patients. Higher peak titers were associated with increased disease severity for the 31 patients with a peak titer identified (mean titer of 107.6 for those with dengue fever vs. 108.5 for patients with DHF, P=.01). Increased dengue disease severity correlated with high viremia titer, secondary dengue virus infection, and DEN-2 virus type.     

Clinical features of 62 imported cases of dengue fever in Japan

To describe the clinical features of dengue cases in Japan, a retrospective study was conducted on 62 laboratory-confirmed Japanese dengue cases presented to Tokyo Metropolitan Komagome Hospital between 1985 and 2000. Age distribution was from 18 to 62 years old (mean, 31.5 years). All cases were imported from abroad and diagnosed as dengue fever. Clinical manifestations included fever (100%), headache (90%), and skin rash (82%). Laboratory examinations revealed leukocytopenia (71%), thrombocytopenia (57%), elevated levels of serum aspartate aminotransferase (78%), and lactate dehydrogenase (71%). Antibody responses were consistent with that of secondary flavivirus infection in 60% of cases. Severity of symptoms in patients with primary dengue antibody response and those with secondary flavivirus antibody responses didn't show statistical significance. Dengue virus infection should be taken into consideration in the differential diagnosis of febrile patients who recently entered Japan from tropical or subtropical countries.     

Isolation and partial characterization of dengue virus type 2 and 4 strains from dengue fever and dengue haemorrhagic fever patients from Mindanao, Republic of the Philippines

OBJECTIVE: Isolation of dengue virus from dengue fever and dengue haemorrhagic fever cases from Mindanao, Republic of the Philippines. METHODS: 12 patients with clinically suspected dengue fever (DF) or dengue haemorrhagic fever (DHF) presenting in four regional hospitals between August and September 1995 on Minadano were enrolled in the study. Dengue virus was isolated by inoculation of Vero/E6 or C6/36 cells with patient serum. IgM antibodies were measured using a commercial test system. Up to 454 bp of the capsid region and 240 bp of the E/NS1 gene junction of different viral isolates were sequenced and phylogenetically analyzed. RESULTS: Virus could be isolated from seven patients, five isolates were typed as dengue virus type 2 and two as dengue virus type 4 by immunostaining with monoclonal antibodies or by RT/PCR. Phylogenetic analysis confirmed a close relationship of the dengue virus type 2 isolates with viruses isolated in the Philippines in 1983 and 1988. CONCLUSION: As observed in studies from other parts of South East Asia, dengue virus type 2 was readily isolated from dengue haemorrhagic fever cases. Dengue virus type 2 and 4 circulate in Mindanao, Philippines, with dengue type 2 being responsible for most of our severe DF or DHF cases.     

Dengue fever in travellers: A challenge for European physicians

Dengue fever (DF) is one of the world's emerging infectious diseases. The steady increase in European tourists, as well as soldiers serving on peacekeeping duties, in endemic areas, coupled with the present resurgence of dengue, raises the risk of exposure for a large number of European travellers. Significant numbers of travellers have, in fact, developed DF. There is a risk of dengue haemorrhagic fever (DHF) in travellers who revisit the same place, and they have the potential not only to acquire, but also to spread, the dengue viral infection. Of concern is the potential for a dengue outbreak in a previously dengue-free country through imported cases. Another major concern is the potential area of dengue transmission, due to spread of its vectors through sizeable parts of southern Europe. In addition to the risk of haemorrhagic fever in returning tourists, the introduction of DF by returning travellers, whether they have symptoms or are unaffected by signs and symptoms of the disease, poses a threat to health systems in Europe.     

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.     

Clinical significance of skin rash in dengue fever:A focus on discomfort,complications,and disease outcome

Objective:To assess whether the cutaneous features in patients with dengue fever are associated with abnormal blood biochemistry,complications,and poor disease outcome.Methods:Forty five patients with dengue fever were identified at a medical center in Kaohsiung,Taiwan,from September to November 2014.All cases were exclusively caused by type 1 dengue virus.Patients were classified into two groups,based on the presence or absence of skin rash,and their rash was subclassified into maculopapular,morbilliform,and petechial types.Clinical symptoms,laboratory data,disease outcome,and complications were compared between the two groups.Results:Thirty two patients with dengue fever developed skin rash(SP group,n=32) while the rest of 13 did not(SN group,n=13).The patient numbers in the maculopapular,morbilliform,and petechial group were 4,21,and 7,respectively.The SP group was younger(P=0.001),experienced more pruritus(P=0.008) and more swollen palms/soles(P=0.015) than the SN group.However,the SN group had greater genital mucosa involvement(P=0.008),higher platelet transfusion rate(P=0.003),and lower hemoglobin and hematocrit levels(P=0.030) than the SP group.Patients with morbilliform lesions had a higher incidence of palm/sole swelling,less genital mucosal involvement,and a lower platelet transfusion rate than did patients with maculopapular or petechial lesions.Conclusions:Cutaneous manifestations provide an important clue to dengue fever.In patients with dengue fever,those with skin rash tend to have itching and swelling of the palms/soles,however,those without skin rash tend to have more complications and poor disease outcomes.     

Causes of fever in children with first febrile seizures: how common are human herpesvirus-6 and dengue virus infections?

This study was conducted to evaluate the etiologies of pyrexia in children with first febrile seizures using a prospectively recorded medical protocol, bacterial culture, and serologic tests for human herpesvirus-6 (HHV-6), dengue virus and Japanese B encephalitis (JE) virus. Of 82 children with first febrile seizures, who were between 3 months and 3 years old and had been admitted to Bhumibol Adulyadej Hospital between January 1997 and December 1998, 41 were boys and 41 were girls, with a mean age of 14.7 months. The average maximal body temperature was 39.7 degrees C. Approximately 70% of the children developed seizures on the first day of fever and the duration of the seizures varied from 1 to 30 minutes. In addition to fever and seizure, common symptoms and signs included coryza, diarrhea, vomiting, inflamed tympanic membranes and rash. The causes of fever documented upon discharge were, in order of frequency, upper respiratory tract infection, nonspecific febrile illness, diarrhea, urinary tract infection, viral infection, pneumonia, herpangina, measles, pneumococcal bacteremia and dengue fever. Serologic tests for HHV-6 IgM were positive in seven children (8.5%), and serologic tests for dengue and JE viruses were negative in all cases.     

Dengue virus infection in travellers returning to Berlin, Germany: clinical, laboratory, and diagnostic aspects

BACKGROUND: Dengue is a mosquito-borne viral infection endemic throughout the tropics and subtropics. The global prevalence of dengue has grown dramatically in recent years and it has been recognized as a potential hazard to tourists. OBJECTIVE: In this study, we analyzed the epidemiology, clinical manifestations, laboratory features and serological/virological results in a series of German travellers returning to Berlin with acute dengue virus infection. STUDY DESIGN: Laboratory-confirmed dengue virus infections among German travellers returning to Berlin were studied retrospectively during the period of 1993-2001. Seventy-one patients tested positive for dengue fever and were included in this study. RESULTS: The majority of patients (77.5%) contracted the disease in South Central and South East Asia. The most important clinical characteristics were fever and prostration (100%), headache, predominantly frontal or retroorbital (86%), arthralgia (79%), morbilliform rash (66%) and myalgia (48%). The most meaningful laboratory results were: marked leucopenia (72%), thrombocytopenia (70-89%), hyponatremia (41%) and increased hepatic enzymes ALAT (41%), ASAT (45%) and LDH (62%). Dengue virus infection was diagnosed by means of a matching clinico-epidemiological history and positivity of specific serology and/or virus isolation. Hemorrhagic phenomena appeared in 10 of the 71 patients (14%), out of which one was diagnosed with DHF according to WHO criteria. All patients recovered fully. CONCLUSION: Pretravel advice should be given to all travellers to dengue-endemic areas. DF must be included in the differential diagnosis of patients returning febrile from tropical areas.     

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.     

Dengue fever evolving into systemic lupus erythematosus and lupus nephritis: a case report

Dengue viremia may be the trigger for immune complex formation in patients who are predisposed to developing autoimmune disease. We report a rare case of dengue virus infection evolving into systemic lupus erythematosus (SLE) and lupus nephritis. To the best of our knowledge this is the first case of dengue fever evolving into lupus nephritis. A 22 year old female presented with having had high grade fever, skin rash, breathlessness, retro-orbital pain, abdominal pain, arthralgias and myalgias for 10 days. She tested positive for dengue immunoglobulin M (IgM). She was given supportive treatment and was subsequently discharged. Four weeks later she developed recurrent fever, arthralgia, rash and anasarca. She was suspected as having SLE with active lupus nephritis. Antinuclear antibody (ANA), and anti double stranded deoxyribonucleic acid (anti dsDNA) titers were positive and complements were low. Renal biopsy showed diffuse proliferative glomerulonephritis grade IV. She was treated with steroids and immunosuppressants to which she responded. Dengue viremia incites antibody production, which if excessive causes deposition of viral antigen-antibody immune complexes. This could possibly lead to renal tubular damage and glomerulonephritis in susceptible individuals. Dengue fever leading to development of glomerulonephritis is rarely seen. Our patient developed dengue fever and after a month presented with manifestations of SLE and lupus nephritis. Both dengue fever and SLE have common manifestations of fever, arthralgia, rash, leucopenia with thrombocytopenia and serositis. Bacterial and viral infections may act as a 'trigger' for starting or relapsing lupus activity in genetically predetermined individuals. In our case it may be possible that dengue virus could have triggered a dysfunctional immune response, resulting in the developing of autoimmunity and SLE with lupus nephritis.     

Human immune responses to dengue viruses

Dengue fever (DF) and dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) are major public health problems in many areas of the world. We are analyzing the human immune responses to dengue viruses, in order to understand the mechanism of recovery from dengue virus infections and the pathogenesis of DHF/DSS. Human natural killer (NK) cells lyse dengue virus-infected cells to a greater degree than uninfected cells. Antibodies to dengue viruses augment the lysis of dengue virus-infected cells by NK cells. Dengue virus-infected monocytes produce high levels of interferon alpha (IFN alpha). DR+ lymphocytes also produce high levels of IFN alpha after contact with dengue virus-infected monocytes. The IFN alpha produced protects uninfected monocytes from dengue virus infection. These results suggest that NK cells and IFN alpha may play an important role in controlling primary dengue virus infection. Dengue virus-specific CD4+CD8(-)T lymphocytes and CD4(-)CD8+T lymphocytes are present in the peripheral blood mononuclear cell population from donors who were infected with dengue virus. Most of CD4+T lymphocytes are dengue serotype-crossreactive. They lyse dengue virus-infected autologous cells in an HLA class II-restricted fashion, and produce interferon gamma (IFN gamma). IFN gamma augments dengue virus infection of monocytic cells in the presence of antidengue virus antibodies by increasing the number of Fc gamma receptors. Dengue virus-specific CD8+T lymphocytes lyse dengue virus-infected autologous cells in an HLA class I-restricted fashion. These CD8+T lymphocytes are also dengue serotype-crossreactive.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Incidence, Characteristics, and Presentation of Dengue Virus Infections during Infancy

Infants are a vulnerable and unique population at risk for dengue in endemic areas. This report describes the incidence and presenting clinical features of infant dengue virus (DENV) infections from a prospective community-based study performed between January 2007 and May 2009 in the Philippines. DENV3 was the predominant infecting serotype over a wide spectrum of disease severity, ranging from inapparent infection to dengue hemorrhagic fever (DHF). In 2007, the incidence of inapparent DENV infections during infancy was 103 per 1,000 persons person-years and 6-fold higher than symptomatic dengue. The age-specific incidence of infant DHF was 0.5 per 1,000 persons over the age of 3–8 months, and it disappeared by age 9 months. A febrile seizure, macular rash, petechiae, and lower platelet count were presenting clinical features associated with DENV infection among infants with acute undifferentiated febrile illnesses. Community-based studies can help to delineate the incidence rates, disease spectrum, and clinical features of DENV infections during infancy.     

Dengue fever: diagnostic importance of a camelback fever pattern

We present a case of imported dengue fever in a 52-year-old man acquired during a recent trip to Ecuador. Fever in a returning traveler from tropical areas often presents a diagnostic problem for clinicians. Our patient presented with severe arthralgias and myalgias and had a camelback/saddleback fever pattern accompanied by relative bradycardia, which was a clue to the diagnosis. He had conjunctival suffusion and the truncal rash, but adenopathy was not present. He also had a generalized headache and abdominal pain. Nonspecific laboratory abnormalities included leukopenia, lymphopenia, atypical lymphocytes, thrombocytopenia, and mildly increased serum transaminases. Clinicians should consider dengue fever in the differential diagnosis in travelers returning from dengue fever endemic areas of Southeast Asia, Latin America, and Africa. Although early findings are nonspecific, a truncal rash accompanied by leukopenia and thrombocytopenia, if followed by biphasic fever pattern (ie, camelback/saddleback fever curve with relative bradycardia), suggest dengue fever as the primary diagnostic consideration.     

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.     

Secondary dengue virus type 4 infections in Vietnam

This study was designated to describe clinical and biological features of patients with a suspected diagnosis of dengue fever/dengue hemorrhagic fever during an outbreak in Central Vietnam. One hundred and twenty-five consecutive patients hospitalized at Khanh Hoa and Binh Thuan Provincial hospitals between November 2001 and January 2002 with a diagnosis of suspected dengue infection were included in the present study.Viruses were isolated in C6/36 and VERO E6 cell cultures or detected by RT-PCR. A hemagglutination-inhibition test (HI) was done on each paired sera using dengue antigens type 1-4, Japanese encephalitis (JE) virus antigen, Chickungunya virus antigen and Sindbis virus antigen. Anti-dengue and anti-JE virus IgM were measured by a capture enzyme-linked immunosorbent assay (MAC-ELISA). Anti-dengue and anti-JE virus IgG were measured by an ELISA test. Dengue viruses were isolated in cell culture and/or detected by RT-PCR in 20.8% of blood samples. DEN-4 and DEN-2 serotypes were found in 18.4% and 2.4% of the patients, respectively. A total of 86.4% of individuals had a diagnosis of acute dengue fever by using the HI test and/or dengue virus-specific IgM capture-ELISA and/or virus isolation and/or RT-PCR. The prevalence of primary and secondary acute dengue infection was 4% and 78.4%, respectively. Anti-dengue IgG ELISA test was positive in 88.8% of the patients. In 5 cases (4%), Japanese encephalitis virus infection was positive by serology but the cell culture was negative. No Chickungunya virus or Sindbis virus infection was detected by the HI test. In patients with acute dengue virus infection, the most common presenting symptom was headache, followed by conjunctivitis, petechial rash, muscle and joint pain, nausea and abdominal pain. Four percent of hospitalized patients were classified as dengue hemorrhagic fever. The clinical presentation and blood cell counts were similar between patients hospitalized with acute dengue fever and patients with other febrile illnesses.     

Emerging viral pathogens in long-term expatriates (II): dengue virus

Dengue virus infections have been well known for many years; still dengue virus is regarded as an ‘emerging’ pathogen, as the disease profile is changing. Its geographical range and oveall incidence, and the incidence of the associated complications, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), are on the increse. Modern-day travel and increasing urbanization seem to be the main contributing factors. In order to estimate the risk of infection during long-term stays in dengue-endemic countries, we tested sera obtained from 323 development aid workers and their family members who had spent on average 9.8 years in dengue-endemic regions for the presence of dengue virus antibodies. Dengue virus antibody screening was done by a commercially available immunofluorescence test (IF). Reactive samples were re-tested by an in-house IF and also tested for cross-reactivity to yellow fever virus using yellow fever IF and neutralization test (NT). Evaluation of the results revealed that the screening test has a specificity of at least 63.2%. In 12 of 19 initially positive cases crossreacting antibodies against yellow fever virus could be ruled out. Three cases remained indeterminable, whereas four of the reactive and 10 (out of 12) of the borderline reactive cases showed crossreactivity with yellow fever virus, probably due to previous vaceination. We found seroprevalence rates of 4.3% with no significant differences related to gender or area of upbringing. Scroprevalence rates were evaluated according to region of suspected or confirmed infection. In two cases the dengue infection had taken a classical clinical course; in another three cases an extraordinary febrile illness was reported in the history. None of the other seropositive individuals had a history of an illness possibly attributable to dengue virus infection. Our results show that there definitely is a risk for long-term expatriates to acquire (mostly non- or oligo-symptomatic) dengue infection, which might be important especially in the light of the supposed aetiology of DHF or DSS as a secondary infection with another dengue virus serotype.