Neurological manifestations in dengue patients

To determine the frequency and the natural history of neurological manifestations of dengue infection in Thai children, 1,493 children diagnosed with dengue infection by serology and admitted to the Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand from 1987 to 1998 were reviewed from prospectively recorded medical charts. There were 80 children identified with neurological manifestations, an incidence of 5.4% of all dengue patients. Of these, there were 41 males and 39 females, with ages ranging from 3 months to 14 years. They were categorized into 20 cases of dengue fever, 26 cases of dengue hemorrhagic fever and 34 cases of dengue shock syndrome. All cases experienced the neurological manifestations during the febrile stage of the illness. The patients were classified into an encephalitic group (called "dengue encephalopathy") (42), a seizure group (35) and a miscellaneous group (3). Encephalitic patients presented with alteration of consciousness (83.3%), seizure (45.2%), mental confusion (23.8%), nuchal rigidity (21.4%), spasticity of limbs (9.5%), positive clonus (4.8%), hemiplegia (2.4%) and positive kernig (2.4%), and were older than those in the other groups. Patients in the seizure group presented with seizure (100%) and positive clonus (2.9%). Abnormal laboratory findings included hyponatremia, abnormal liver enzymes and CSF pleocytosis. Dengue IgM and dengue PCR were not demonstrated in 16 CSF specimens. An autopsy finding of a child in the encephalitic group showed histologic evidence of encephalitis, the only case of confirmed dengue encephalitis in this study. One patient with encephalitic symptoms suffered from long-term neurological sequelae. The overall mortality rate was 5%. In conclusion, neurological manifestations including seizure and encephalopathy in children with dengue are not uncommon whereas dengue encephalitis is a rare entity.     

Etiology of obscure fever in children at a university hospital in northeast Thailand

Obscure fever is not an uncommon problem in Thailand. We studied 25 children with obscure fever admitted to Srinagarind (university) Hospital in Northeast Thailand. The etiology was identified in 52% of the cases: dengue (40%), leptospirosis (8%), and micrococcus septicemia (4%). Two cases with primary dengue infection developed dengue shock syndrome. The case with leptospirosis developed infection-associated, hemophagocytic syndrome. We found no cases of Japanese encephalitis, scrub typhus or murine typhus.     

Etiology of acute, non-malaria, febrile illnesses in Jayapura, northeastern Papua, Indonesia

We conducted a prospective, inpatient fever study in malaria-endemic Papua, Indonesia to determine non-malaria fever etiologies. Investigations included malaria blood films, blood culture, paired serologic samples analysis for dengue, Japanese encephalitis, leptospirosis, scrub typhus, murine typhus, and spotted fever group rickettsia. During 1997-2000, 226 patients (127 males and 99 females) 1-80 years of age (median age = 25 years) were enrolled. Positive blood cultures (n = 34, 15%) were obtained for Salmonella Typhi (n = 13), Escherichia coli (n = 8), Streptococcus pneumoniae (n = 6), Staphylococcus aureus (n = 5), Streptococcus pyogenes (n = 1), and Klebsiella pneumoniae (n = 1). Twenty (8.8%) patients were positive for leptospirosis by polymerase chain reaction. Eighty (35.4%) of 226 patients had ≥ 1 positive serology, diagnostic for 15 rickettsial and 9 dengue cases. Acid-fast bacilli-positive sputum was obtained from three patients. Most common confirmed (81 of 226, 35.8%)/suspected diagnoses were typhoid fever (n = 41), pneumonia (n = 29), leptospirosis (n = 28), urinary tract infections (n = 20), rickettsioses (n = 19), dengue (n = 17), and meningitis/encephalitis (n = 15). There were 17 deaths, 7 (46.7%) were caused by meningitis/encephalitis. Multiple positive serologic results and few confirmed diagnoses indicate the need for improved diagnostics.     

West Nile viral encephalitis mimicking hepatic encephalopathy

West Nile encephalitis (WNE) has become endemic in the United States since 1999. The clinical spectrum of WNE includes aseptic meningitis, meningoencephalitis, or encephalitis with or without flaccid paralysis. The severity of WNE ranges from asymptomatic serum conversion to severe neurologic deficits or a fatal outcome. Several systemic disorders may present with encephalitis as part of the clinical presentation, for example, Legionnaires' disease, neoplasms with metastases to the central nervous system, Mycoplasma meningoencephalitis, brucellosis, Listeria, Rocky Mountain spotted fever, ehrlichiosis, and malaria. The most common infectious causes of encephalitis that need to be differentiated from WNE include herpes simplex virus 1, meningoencephalitis, and enteroviral meningoencephalitis. We present a case of apparent hepatic encephalopathy secondary to pancreatic carcinoma with liver involvement that presented as hepatic encephalopathy mimicking WNE. We conclude that patients presenting with encephalitis in the summer months should have serum/cerebrospinal fluid serologic studies sent for WNE even if an alternate explanation seems to explain the clinical syndrome.     

The first report on human cases serologically diagnosed as Japanese encephalitis in Indonesia

Although Japanese encephalitis (JE) virus was isolated from mosquitos in 1974, human JE cases have never been reported in Indonesia in spite of the prevalence of anti-JE antibodies among human and pig populations as well as abundant JE vector mosquitos. In this report, we describe serological diagnosis of JE cases in Bali. Indonesia. using IgM-capture ELISA both on serum and cerebrospinal fluid (CSF) of the patients. In the first series of our investigation (Series 1), we examined serum specimens from 12 patients with clinical diagnosis of viral encephalitis, meningitis or dengue hemorrhagic fever (DHF), and found 2 possible JE cases. In the next series (Series 2), we examined both serum and CSF from encephalitis patients and gave laboratory diagnosis of JE. One of them was suspected to have concomitant or recent infection with dengue virus, probably type 3. These results strongly indicated that JE has been prevalent in Bali, Indonesia.     

Development of cross-reactive antibodies to plasminogen during the immune response to dengue virus infection.

The four serotypes of dengue virus (a mosquito-borne flavivirus) cause an acute febrile illness (dengue fever) or a more prolonged illness with plasma leakage resulting in hypovolemia (dengue hemorrhagic fever). Hemorrhage may accompany either. Epidemiologic data suggest a role for dengue antibodies in pathogenesis. Computer analysis revealed a 20-residue region of similarity in amino acid sequence between the dengue type 4 envelope glycoprotein (E) and a family of clotting factors, including plasminogen, the prime mediator of fibrinolysis. By use of synthetic peptides in ELISA, E antibodies that potentially bind plasminogen were detected in 75% of 40 Thai patients acutely infected with dengue virus type 1, 2, 3, or 4. Plasminogen cross-reactivity of dengue antibodies was shown to be specific for the related sites in E and plasminogen. The dengue E sequence with similarity to plasminogen is largely conserved within the currently known flavivirus E sequences. However, 15 Thai patients hospitalized for illness caused by Japanese encephalitis virus (a flavivirus not associated with hemorrhage) did not develop plasminogen-cross-reactive antibodies, and this finding correlated with failure of Japanese encephalitis virus antibodies to bind to the plasminogen-cross-reactive site in E.     

Acute undifferentiated fever caused by infection with Japanese encephalitis virus

To determine the proportion of acute undifferentiated fevers without neurologic deficits related to infection with Japanese encephalitis (JE) virus, flavivirus serology (dengue and JE) was performed in a cohort of 156 adults presenting to a hospital in Chiangrai, Thailand. Recent flavivirus infection was diagnosed for any individual with an IgM result > 40 units. A ratio of dengue virus IgM to JE virus IgM < 0.91 defined a JE virus infection. Diagnostic criteria for Japanese encephalitis were met in 22 individuals (14%), and were unequivocal in 8 patients. The admission findings in these eight subjects were similar to those described for other flavivirus infections. Thrombocytopenia was the most striking laboratory abnormality (median platelet count = 119,000/mm3, range = 44,000-236,000/mm3). Headache (75%), nausea (50%), myalgia (38%), rash (38%), and diarrhea (25%) were the most frequently encountered signs and symptoms. Infection with Japanese encephalitis virus is an underappreciated cause of acute undifferentiated fever in Asia.     

Etiology of encephalitis syndrome among hospitalized children and adults in Takeo,Cambodia, 1999-2000

Whether or not Japanese encephalitis virus (JEV) is an important causative agent of acute encephalitis in Cambodia remains unclear. This study was carried out to determine the cause of encephalitis syndrome among children and adults admitted to Takeo Provincial Hospital from October 1999 to September 2000. Ninety-nine cases were included in the study: 52 pediatric cases (12 were fatal) and 47 adult cases (10 were fatal). A causative agent such as human herpesvirus (HHV-3 or HHV-4), Cryptococcus neoformans, or Mycobacterium tuberculosis had been identified in 8 of the 11 adults who had human immunodeficiency virus type 1 (HIV-1). An infectious agent was identified in 35 (40%) of 88 HIV-1-seronegative patients (60% of the causes remains unidentified). These comprised 11 bacterial infections, 1 fungal infection, and 23 viral infections. The viral infections were 1 fatal HHV-4 infection, 5 dengue virus infections (2 fatal), 1 coinfection with flavivirus and alphavirus, and 16 presumptive infections JEV (no virus detected), one case of which was fatal. Infection with JEV, the principal cause identified in the 99 encephalitis syndromes, concerned 16 (31%) of 52 children.     

Clinico–epidemiological features of dengue fever in Saudi Arabia

ObjectiveTo highlight some clinical and epidemiological features of dengue fever.MethodsAll patients who were admitted to hospitals in Holly Mecca City, Saudi Arabia and were confirmed as dengue fever (DF) or dengue hemorrhagic fever (DHF) were included in this study. The data were collected from patient files and through direct interview with patients or their relatives. Cases were followed through their hospital stay. Routine laboratory investigations were done and diagnosis was confirmed by PCR.ResultsMost of cases admitted in stable condition (94.37%) and only one case (1.41%) died. Dengue-1 and 3 types were the prevalent dengue viruses and cases in age group 16-44 were the most frequent (70.40%). The most common symptoms was fever reported from all cases followed by headache (74.60%), myalgia and anorexia (67.60%), back pain (59.20%) and chills (54.90%). DF represented (60.57%) of the cases while DHF represented (39.43%). About half of cases had underground water tanks for human use, 5.60% had over house roof water tanks and 43.70% had both types, 16.90% of these tanks were uncovered. Approximately 70.00% of cases reported presence of small collection of water nearby houses and 46.80% reported the presence of mosquitoes within their houses.ConclusionsMost dengue fever cases might be endogenous in origin due to prevalence of mosquitoes and their breeding places within the houses and in nearby localities. Control of mosquitoes and their breeding places will contribute to prevention of dengue fever.     

Predictive diagnostic value of the tourniquet test for the diagnosis of dengue infection in adults

Objective To examine the accuracy of the admission tourniquet test in the diagnosis of dengue infection among Lao adults. Methods Prospective assessment of the predictive diagnostic value of the tourniquet test for the diagnosis of dengue infection, as defined by IgM, IgG and NS1 ELISAs (Panbio Ltd, Australia), among Lao adult inpatients with clinically suspected dengue infection. Results Of 234 patients with clinically suspected dengue infection on admission, 73% were serologically confirmed to have dengue, while 64 patients with negative dengue serology were diagnosed as having scrub typhus (39%), murine typhus (11%), undetermined typhus (12%), Japanese encephalitis virus (5%), undetermined flavivirus (5%) and typhoid fever (3%); 25% had no identifiable aetiology. The tourniquet test was positive in 29.1% (95% CI = 23.2–34.9%) of all patients and in 34.1% (95% CI = 27.0–41.2%) of dengue‐seropositive patients, in 32.7% (95% CI = 23.5–41.8) of those with dengue fever and in 36.4% (95% CI = 24.7–48.0) of those with dengue haemorrhagic fever. Interobserver agreement for the tourniquet test was 90.2% (95% CI = 86.4–94.0) (Kappa = 0.76). Using ELISAs as the diagnostic gold standard, the sensitivity of the tourniquet test was 33.5–34%; its specificity was 84–91%. The positive and negative predictive values were 85–90% and 32.5–34%, respectively. Conclusions The admission tourniquet test has low sensitivity and adds relatively little value to the diagnosis of dengue among Lao adult inpatients with suspected dengue. Although a positive tourniquet test suggests dengue and that treatment of alternative diagnoses may not be needed, a negative test result does not exclude dengue.     

Herpes simplex virus encephalitis in a renal transplant patient

The incidence of herpes simplex virus (HSV) encephalitis is estimated to occur annually in 2-4 cases per million population. HSV encephalitis is exceptional in renal transplant patients, we have found two previous reports after an extensive bibliography search. We report a case of a 47 years old women renal transplant recipient who presented 3 months after transplantation fever, stupor and aphasia. The diagnosis HSV encephalitis was achieved by PCR in cerebrospinal fluid and magnetic resonance imaging. She was treated with aciclovir for 4 weeks and recovered completely without neurologic sequelae.     

Mechanisms of hemorrhage in dengue without circulatory collapse.

To characterize the molecular basis for the hemostatic defects of dengue infections, a study was conducted in Bangkok, Thailand. Febrile children (n = 68) hospitalized with suspected dengue were enrolled before their clinical syndromes were classified as either dengue fever (DF) or dengue hemorrhagic fever (DHF). Hospital course and outcome were recorded; blood was obtained during the febrile illness (S1), after defervescence (S2), and 1 month after onset of disease (S4). Patients were classified as DF (n = 21) and DHF grades 1, 2, and 3; (DHF1, n = 8; DHF2, n = 30; and DHF3, n = 9). All had marked thrombocytopenia. Bleeding scores were assigned on the basis of bleeding site. Although there was no correlation between bleeding scores and pleural effusion index (a measure of vascular leakage) or bleeding scores and platelet counts, there was a correlation between pleural effusion index and platelet counts. Bleeding scores did not correlate with hemostatic data. Activated partial thromboplastin time was prolonged, with trends toward decreased fibrinogen and increased levels of prothrombin fragment F1.2 in the acute-phase samples. However, no factor level was dramatically decreased. We conclude that most patients with DF or DHF, even without overt hemorrhage, have consumptive coagulopathy. Nevertheless, hemorrhage in dengue without circulatory collapse is most likely due to activation of platelets rather than coagulopathy, which is well compensated. Our data suggest that vascular alteration may be the principal factor involved in the association of thrombocytopenia and hemorrhage with disease severity.     

Dengue and liver disease

Acute hepatitis and hepatic encephalopathy are rare manifestations of dengue haemorrhagic fever (DHF). We report 4 children aged 8 months to 3 y who presented with severe hepatic dysfunction. Three male infants had in addition hepatic encephalopathy and 2 of them succumbed to their disease suggesting that hepatitis with encephalopathy has a very high mortality.     

Dengue Hemorrhagic Fever in a Japanese Traveler with Pre-existing Japanese Encephalitis Virus Antibody

An adult Japanese man who had just returned from Thailand developed dengue hemorrhagic fever (DHF). A primary infection of dengue virus (DENV) was confirmed, specifically DENV serotype 2 (DENV-2), on the basis of the detection of the virus genome, a significant increase in the neutralizing antibody and the isolation of DENV-2. DHF is often observed following a secondary infection from another serotype of dengue virus, particularly in children, but this case was a primary infection of DENV. Japan is a non-endemic country for dengue disease. In fact, only Japanese encephalitis (JE) is known to be a member of the endemic flavivirus family. In this study, IgG antibody against Japanese encephalitis virus (JEV) was detected. JEV belongs to the family of dengue virus and prevails in Japan, particularly Kyushu. Among many risk factors for the occurrence of DHF, a plausible candidate could be a cross-reactive antibody-dependent enhancement (ADE) mechanism caused by JEV antibody. This indicates that most Japanese travelers who living in dengue non-endemic areas, particularly Kyushu, should be aware of the occurrence of DHF.     

An outbreak of West Nile fever among migrants in Kisangani, Democratic Republic of Congo

In February 1998, an outbreak of acute febrile illness was reported from the Kapalata military camp in Kisangani, the Democratic Republic of Congo. The illness was characterized by an acute onset of fever associated with severe headache, arthralgia, backache, neurologic signs, abdominal pain, and coughing. In 1 individual, hemorrhagic manifestations were observed. The neurologic signs included an altered level of consciousness, convulsions, and coma. Malaria was initially suspected, but the patients showed negative blood films and failed to respond to antimicrobial drugs. A total of 35 sera collected from the military patients in the acute phase were tested for the presence of IgM against vector-borne agents. Serum IgM antibodies against West Nile fever virus were found in 23 patients (66%), against Chikungunya virus in 12 patients (34%), against dengue virus in 1 patient (3%), and against Rickettsia typhi in 1 patient (3%). All sera were negative for IgM antibody against Rift Valley fever virus, Crimean Congo hemorrhagic fever virus, and Sindbis virus. These data suggest that infections with West Nile fever virus have been the main cause of the outbreak.     

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.     

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.     

Responses of neurologic complications of AIDS to 3'-azido-3'-deoxythymidine and 9-(1,3-dihydroxy-2-propoxymethyl) guanine. I. Clinical features

Fourteen patients with AIDS were treated for 23 neurologic complications: four episodes of acute meningoencephalitis; eight episodes of subacute encephalopathy; two cases of progressive multifocal leukoencephalopathy; and nine cases of polyneuropathy. Nine patients were treated with 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), one with 3'-azido-3'-deoxythymidine (AZT), and four initially with DHPG directed against cytomegalovirus (CMV) retinitis or encephalitis and subsequently with AZT against human immunodeficiency virus (HIV) encephalopathy. CMV retinitis was a helpful clinical observation indicating neurologic involvement. DHPG produced improvement in two of three cases of acute meningoencephalitis but was ineffective in cases of subacute encephalopathy or neuropathy. AZT therapy resulted in resolution in both of the two treated cases of acute confusional state and in two of the four treated cases of polyradiculoneuropathy with paraparesis but was ineffective in the late stage of subacute encephalopathy. These results suggest that CMV is important in some cases of acute meningoencephalitis, whereas HIV is a dominant pathogen in subacute dementia and polyneuropathy in patients with AIDS. DHPG may be beneficial in the former, whereas AZT appears to be effective in the latter complications.     

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.