First report of pneumonia and septic shock caused by Cedecea lapagei in Vietnam.

Cedecea lapagei is rarely known to cause infections in humans. We report the first case of pneumonia and septic shock caused by Cedecea lapagei in a 38-year-old man in Vietnam. Cedecea lapagei may be an emerging infectious agent in humans.

First report of infective endocarditis caused by Streptococcus pseudoporcinus in Vietnam.

We report a first case of Streptococcus pseudoporcinus bacteraemia causing infective endocarditis in a 40-year-old man in Vietnam. This is the second case of Streptococcus pseudoporcinus infective endocarditis in the literature. The patient was successfully treated by antibiotics, combined with aortic valve replacement. Streptococcus pseudoporcinus may be an emerging infectious agent causing endocarditis.

An evaluation of the usefulness of neuroimaging for the diagnosis of Japanese encephalitis.

Japanese encephalitis virus (JEV) is estimated to cause 30­50,000 cases of encephalitis every year. The disease occurs mainly in rural Asia and is transmitted to humans from birds and pigs by mosquitoes of the genus Culex. JE is diagnosed with antibody testing of the serum and CSF, but this is not available in many hospitals. Neuroimaging abnormalities, particularly thalamic hypodensity on computed tomography (CT) and hyperintensity on T2 weighted magnetic resonance imaging (MRI) have been described in case studies, but their usefulness for diagnosing JE is not known. We have therefore evaluated the usefulness of neuroimaging (CT and MRI) for the diagnosis of JE. The findings of thalamic lesions were compared with the final serological diagnosis in a cohort of 75 patients (children and adults) with suspected CNS infections in Southern Vietnam, a JEV endemic area. Thalamic lesions on CT and/or MRI combined had sensitivity 23% (95% confidence interval 12.9­33.1%), specificity 100%, positive predictive value 100% and negative predictive value 42.1% (95% confidence interval 30.2­53.8%) for a diagnosis of JE in this cohort. Over time, the thalamic lesions resolved in some patients. One patient showed disappearance of lesions on CT followed by reappearance of the lesions some time later, known as the fogging effect. In this setting, the presence of thalamic abnormalities suggested the diagnosis of JE, but their absence did not exclude it.

Polymorphisms of the gene coding for copper/zinc superoxide dismutase (SOD1) in patients with Japanese encephalitis.

Japanese encephalitis is the commonest form of encephalitis globally. Most cases develop characteristic encephalitis but some also present with flaccid paralysis. The paralysis is secondary to damage at the alpha motor neurone, the site that is also damaged in amyotrophic lateral sclerosis (ALS). The gene coding for superoxide dismutase 1 (SOD1) is thought to be involved in ALS and may also be linked to susceptibility to Japanese encephalitis. To investigate this possibility, polymorphisms in the SOD1 gene were investigated, in 61 cases of Japanese encephalitis, 61 matched controls and 171 population controls, in Vietnam. Novel polymorphisms, found only in three of the cases and one of the population controls, may be involved with susceptibility to Japanese encephalitis and potentially to other flavivirus infections that lead to damage to the cells of the anterior horn. Further research on this possible association is required.

Neurological manifestations of dengue infection.

BACKGROUND: Severe forms of dengue, the most important arboviral infection of man, are associated with haemorrhagic disease and a generalised vascular leak syndrome. The importance of dengue as a cause of neurological disease is uncertain. METHODS: During 1995, all patients with suspected CNS infections admitted to a referral hospital in southern Vietnam were investigated by culture, PCR, and antibody measurement in serum and CSF for dengue and other viruses. FINDINGS: Of 378 patients, 16 (4.2%) were infected with dengue viruses, compared with four (1.4%) of 286 hospital controls (odds ratio [95% CI] 3.1 [1.7-5.8]). Five additional dengue positive patients with CNS abnormalities were studied subsequently. No other cause of CNS infection was identified. Seven infections were primary dengue, 13 secondary, and one was not classified. Ten patients had dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF. 12 of the 21 had no characteristic features of dengue on admission. The most frequent neurological manifestations were reduced consciousness and convulsions. Nine patients had encephalitis. No patient died, but six had neurological sequelae at discharge. Phylogenetic analysis of the four DEN-2 strains isolated mapped them with a DEN-2 strain isolated from a patient with dengue haemorrhagic fever, and with other strains previously isolated in southern Vietnam. INTERPRETATION: In dengue endemic areas patients with encephalitis and encephalopathy should be investigated for this infection, whether or not they have other features of the disease.

Comparison of PanBio Dengue Duo IgM and IgG capture ELISA and venture technologies dengue IgM and IgG dot blot.

BACKGROUND: A number of commercial ELISA for dengue diagnosis have recently become available, though direct comparison between these assays have not been published. OBJECTIVES: The Venture Technologies Dengue IgM and IgG Dot Blot assays and the PanBio Dengue Duo IgM and IgG Capture ELISA were compared. STUDY DESIGN: Paired sera from patients with dengue (n=20) and Japanese encephalitis (JE, n=10), and single sera from patients with typhoid (n=10), leptospirosis (n=10) and scrub typhus (n=10) were assayed according to the manufacturer's instructions. RESULTS: The Dot Blot IgM ELISA showed higher sensitivity than the PanBio IgM ELISA (100 vs. 95%), while the PanBio IgM ELISA showed higher specificity in JE (100 vs. 20%) and non-flavivirus infections (100 vs. 97%). Defining elevation of either IgM or IgG as a positive result, the Dot Blot and ELISA tests both showed 100% sensitivity in dengue infection, while the PanBio test showed superior specificity in JE (70 vs. 0%) and non-flavivirus infections (100 vs. 67%). CONCLUSIONS: Both assays are useful aids to the serological diagnosis of dengue infection. The clinical setting, user preference and local conditions will be important in determining which test is more appropriate.

Fluid replacement in dengue shock syndrome: a randomized, double-blind comparison of four intravenous-fluid regimens.

Dengue hemorrhagic fever and dengue shock syndrome (DSS) are major causes of childhood morbidity and mortality in many tropical countries. Increased intravascular permeability leading to shock is the cardinal feature of DSS. Fluid resuscitation to counteract massive plasma leakage is the mainstay of treatment. A double-blind, randomized trial comparing four intravenous-fluid regimens for acute resuscitation of 50 children with DSS was conducted. Colloids (dextran 70 or the protein digest gelafundin 35,000) restored cardiac index and blood pressure and normalized hematocrit more rapidly than crystalloids (Ringer's lactate or 0.9%-weight/volume saline). Dextran 70 provided the most rapid normalization of the hematocrit and restoration of the cardiac index, without adverse effects, and may be the preferred solution for acute resuscitation in DSS. Further large-scale double-blind trials are required to provide an evidence-based approach to the management of DSS.

Evaluation of a new commercially available immunoglobulin M capture enzyme-linked immunosorbent assay for diagnosis of Japanese encephalitis infections.

A new commercial enzyme-linked immunosorbent assay (ELISA) for the diagnosis of Japanese encephalitis virus infections showed a sensitivity of 88% with sera and 81% with cerebrospinal fluid and a specificity of 97% with sera from patients with primary and secondary dengue virus infections. Specificity was 100% when samples from nonflavivirus infections were tested.

Comparison of PanBio dengue duo enzyme-linked immunosorbent assay (ELISA) and MRL dengue fever virus immunoglobulin M capture ELISA for diagnosis of dengue virus infections in Southeast Asia.

The performances of the MRL dengue fever virus immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) and the PanBio Dengue Duo IgM capture and IgG capture ELISA were compared. Eighty sera from patients with dengue virus infections, 24 sera from patients with Japanese encephalitis (JE), and 78 sera from patients with nonflavivirus infections, such as malaria, typhoid, leptospirosis, and scrub typhus, were used. The MRL test showed superior sensitivity for dengue virus infections (94 versus 89%), while the PanBio test showed superior specificity for JE (79 versus 25%) and other infections (100 versus 91%). The PanBio ELISA showed better overall performance, as assessed by the sum of sensitivity and specificity (F value). When dengue virus and nonflavivirus infections were compared, F values of 189 and 185 were obtained for the PanBio and MRL tests, respectively, while when dengue virus infections and JE were compared, F values of 168 and 119 were obtained. The results obtained with individual sera in the PanBio and MRL IgM ELISAs showed good correlation, but this analysis revealed that the cutoff value of the MRL test was set well below that of the PanBio test. Comparing the sensitivity and specificity of the tests at different cutoff values (receiver-operator analysis) revealed that the MRL and PanBio IgM ELISAs performed similarly in distinguishing dengue virus from nonflavivirus infections, although the PanBio IgM ELISA showed significantly better distinction between dengue virus infections and JE. The implications of these findings for the laboratory diagnosis of dengue are discussed.

Poliomyelitis-like illness due to Japanese encephalitis virus.

BACKGROUND: Acute flaccid paralysis remains common among Vietnamese children despite a pronounced fall in the incidence of poliomyelitis. METHODS: During 1995, all 22 children presenting with acute flaccid paralysis to a referral centre in Ho Chi Minh City, Vietnam, had virological cultures and antibody measurements done on serum, cerebrospinal fluid, and faeces. A year later the children were reassessed and electrophysiological studies were done. FINDINGS: Wild poliovirus type 1 was isolated from the faeces of only one patient, and non-polio enteroviruses from three patients. 12 (55%) of the 22 children with acute flaccid paralysis had evidence of acute Japanese encephalitis virus (JEV) infection, compared with only one (1%) of 88 age-matched hospital controls (children with diphtheria; p<0.0001). Compared with JEV-negative patients, weakness in JEV-infected children was more rapid in onset, tended to be asymmetrical, but was less likely to involve the arms. All 12 children with JEV infection were febrile at the onset of weakness, seven had acute retention of urine, and ten had CSF pleiocytosis. Seven of eight JEV-negative patients met the case-definition of Guillain-Barré syndrome, compared with only one of 12 JEV-positive children. At follow-up, patients with JEV infection had greater disability and were more likely to have muscle wasting than were JEV-negative children. Nerve conduction and electromyographic studies indicated damage to the anterior horn cells. INTERPRETATION: JEV causes an acute flaccid paralysis in children that has similar clinical and pathological features to poliomyelitis. In endemic areas, children with acute flaccid paralysis should be investigated for evidence of JEV infection.

Rapid diagnosis of Japanese encephalitis by using an immunoglobulin M dot enzyme immunoassay.

Japanese encephalitis (JE) occurs in rural settings in southern and eastern Asia, where diagnostic facilities are limited. For the diagnosis of JE virus (JEV) infection, we developed a nitrocellulose membrane-based immunoglobulin M (IgM) capture dot enzyme immunoassay (MAC DOT) that is rapid, simple to use, requires no specialized equipment, and can distinguish JEV from dengue infection. In a prospective field study in southern Vietnam, 155 cerebrospinal fluid (CSF) and 341 serum samples were collected from 111 children and 83 adults with suspected encephalitis. The JEV MAC DOT, performed on site, was scored visually from negative to strongly positive by two observers, and the results were compared subsequently with those of the standard IgM capture enzyme-linked immunosorbent assay. For the 179 patients with adequate specimens, the MAC DOT correctly identified 59 of 60 JEV-positive patients and 118 of 119 JEV-negative patients (sensitivity [95% confidence intervals], 98.3% [92.1 to 99.91%]; specificity, 99.2% [95.9 to 100.0%]; positive predictive value, 0.98; negative predictive value, 0.99). The MAC DOT also correctly identified three patients with dengue encephalopathy. Admission specimens were positive for 73% of JE patients. Interobserver agreement for MAC DOT diagnosis was excellent (kappa = 0.94). The JEV MAC DOT is a simple and reliable rapid diagnostic test for JE in rural hospitals.

Evaluation of a rapid immunochromatographic test for diagnosis of dengue virus infection.

A rapid (<7-min) immunochromatographic test for immunoglobulin M (IgM) and IgG antibodies to dengue viruses was evaluated by using hospital admission and discharge sera from 124 patients. The reference laboratory diagnosis was based on the results of virus isolation, hemagglutination-inhibition assay (HAI), and enzyme immunoassay (EIA). By the standard assays, patients experienced primary dengue virus infection (n = 30), secondary dengue virus infection (n = 48), Japanese encephalitis (JE) virus infection (n = 20), or no flavivirus infection (n = 26). The rapid test demonstrated 100% sensitivity in the diagnosis of dengue virus infection and was able to distinguish between primary and secondary dengue virus infections through the separate determinations of IgM and IgG. For all patients with primary dengue virus infection a positive test for IgM to dengue virus and a negative test for IgG to dengue virus were obtained, whereas for 46 of 48 patients (96%) with secondary dengue virus infection, a positive test for IgG to dengue virus with or without a positive test for IgM to dengue virus was obtained. The remaining two patients with secondary dengue virus infection had positive IgM test results and negative IgG test results. Furthermore, the rapid test was positive for patients confirmed to be infected with different dengue virus serotypes (12 infected with dengue virus serotype 1, 4 infected with dengue virus serotype 2, 3 infected with dengue virus serotype 3, and 2 infected with dengue virus serotype 4). The specificity of the test for nonflavivirus infections was 88% (3 of 26 positive), while for JE virus infections the specificity of the test was only 50% (10 of 20). However, most patients with secondary dengue virus infection were positive for both IgM and IgG antibodies to dengue virus, while no patients with JE virus infection had this profile, so cross-reactivity was only a concern for a small proportion of patients with secondary dengue infections. The rapid test demonstrated a good correlation with the reference EIA and HAI and should be useful for the rapid diagnosis of dengue virus infections.

Pharmacokinetics of oral and intravenous ofloxacin in children with multidrug-resistant typhoid fever.

The pharmacokinetics of oral and intravenous ofloxacin (7.5 mg.kg of body weight-1 given over 30 min) were studied in an open crossover study of 17 Vietnamese children, aged between 5 and 14 years, with acute uncomplicated typhoid fever. Following oral administration, the median (95% confidence interval [CI]) time to peak concentration of ofloxacin in serum (Cmax) was 1.7 h (1.4 to 1.9 h) and the mean (95% CI) Cmax was 5.5 mg.liter-1 (4.7 to 6.3 mg.liter-1) compared with a Cmax of 8.7 mg.liter-1 (7.6 to 9.7 mg.liter-1) following the intravenous infusion. The median (95% CI) total apparent volume of distribution following the first intravenous dose, 1.35 liter.kg-1 (1.17 to 1.73 liter.kg-1), was significantly larger than that following the second dose, 0.99 liter.kg-1 (0.86 to 1.17 liter.kg-1; P < 0.0005), although the estimates for systemic clearance were similar: 0.255 liter.kg-1 h-1 (0.147 to 0.325 liter.kg-1 h-1) compared with 0.172 liter.kg-1 h-1 (0.127 to 0.292 liter.kg-1 h-1; P = 0.14). The mean residence times (95% CI) following intravenous and oral administration were similar: 5.24 h (4.84 to 6.58 h) and 6.24 h (5.32 to 7.85 h), respectively. The mean (95% CI) oral bioavailability was 91% (74 to 109%). The peak concentrations in serum were 10 to 100 times higher than the maximum MICs for ofloxacin against multidrug-resistant Salmonella typhi isolated in this area. Although the systemic clearance values were higher than those reported previously for adults, these data overall suggest that weight-or area-adjusted dose regimens for the treatment of typhoid in older children should be the same as those for adults.