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1/46. Outbreak of Nipah-virus infection among abattoir workers in singapore.

    BACKGROUND: In March 1999, an outbreak of encephalitis and pneumonia occurred in workers at an abattoir in singapore. We describe the clinical presentation and the results of investigations in these patients. methods: Clinical and laboratory data were collected by systemic review of the case records. serum and cerebrospinal fluid (CSF) samples were tested for IgM antibodies to nipah virus with an IgM capture ELISA. Reverse-transcriptase PCR was done on the CSF and tissue samples from one patient who died. FINDINGS: Eleven patients were confirmed to have acute Nipah-virus infection based on raised IgM in serum. nipah virus was identified by reverse transcriptase PCR in the CSF and tissue of the patient who died. The patients were all men, with a median age of 44 years. The commonest presenting symptoms were fever, headache, and drowsiness. Eight patients presented with signs of encephalitis (decreased level of consciousness or focal neurological signs). Three patients presented with atypical pneumonia, but one later developed hallucinations and had evidence of encephalitis on CSF examination. Abnormal laboratory findings included a low lymphocyte count (nine patients), low platelet count, low serum sodium, and high aspartate aminostransferase concentration (each observed in five patients). The CSF protein was high in eight patients and white-blood-cell count was high in seven. Chest radiography showed mild interstitial shadowing in eight patients. magnetic resonance imaging (MRI) showed focal areas of increased signal intensity in the cortical white marker in all eight patients who were scanned. The nine patients with encephalitis received empirical treatment with intravenous aciclovir and eight survived. INTERPRETATION: Infection with nipah virus caused an encephalitis illness with characteristic focal areas of increased intensity seen on MRI. lung involvement was also common, and the disease may present as an atypical pneumonia. ( info)

2/46. Fatal encephalitis due to nipah virus among pig-farmers in malaysia.

    BACKGROUND: Between February and April, 1999, an outbreak of viral encephalitis occurred among pig-farmers in malaysia. We report findings for the first three patients who died. methods: Samples of tissue were taken at necropsy. Blood and cerebrospinal-fluid (CSF) samples taken before death were cultured for viruses, and tested for antibodies to viruses. FINDINGS: The three pig-farmers presented with fever, headache, and altered level of consciousness. myoclonus was present in two patients. There were signs of brainstem dysfunction with hypertension and tachycardia. Rapid deterioration led to irreversible hypotension and death. A virus causing syncytial formation of vero cells was cultured from the CSF of two patients after 5 days; the virus stained positively with antibodies against hendra virus by indirect immunofluorescence. IgM capture ELISA showed that all three patients had IgM antibodies in CSF against Hendra viral antigens. Necropsy showed widespread microinfarction in the central nervous system and other organs resulting from vasculitis-induced thrombosis. There was no clinical evidence of pulmonary involvement. inclusion bodies likely to be of viral origin were noted in neurons near vasculitic blood vessels. INTERPRETATION: The causative agent was a previously undescribed paramyxovirus related to the hendra virus. Close contact with infected pigs may be the source of the viral transmission. Clinically and epidemiologically the infection is distinct from infection by the hendra virus. We propose that this Hendra-like virus was the cause of the outbreak of encephalitis in malaysia. ( info)

3/46. diagnosis of nipah virus encephalitis by electron microscopy of cerebrospinal fluid.

    BACKGROUND: between 1998 and 1999, an outbreak of potentially fatal viral encephalitis erupted among pig farm workers in West malaysia, and later spread to singapore where abattoir workers were afflicted. Although Japanese encephalitis virus was initially suspected, the predominant aetiologic agent was subsequently confirmed to be nipah virus, a novel paramyxovirus related to but distinct from hendra virus. OBJECTIVE: to describe a case of nipah virus encephalitis in a pig farm worker from malaysia. STUDY DESIGN: the clinical, laboratory and radiological findings of this patient were scrutinized. Special emphasis was placed on the electron microscopic analysis of the cerebrospinal fluid (CSF) specimen from this patient. RESULTS: the neurological deficits indicative of cerebellar involvement were supported by the magnetic resonance imaging that showed prominent cerebellar and brainstem lesions. CSF examination provided further evidence of viral encephalitis. Complement fixation and/or RT-PCR assays were negative for Japanese encephalitis, herpes simplex, measles and mumps viruses. ELISA for detecting IgM and IgG antibodies against Hendra viral antigens were equivocal for the CSF specimen, and tested initially negative for the first serum sample but subsequently positive for the repeat serum sample. Transmission electron microscopy of negatively-stained preparations of CSF revealed enveloped virus-like structures fringed with surface projections as well as nucleocapsids with distinctive helical and herringbone patterns, features consistent with those of other paramyxoviruses, including hendra virus. CONCLUSION: this case report reiterates the relevant and feasible role of diagnostic electron microscopy for identifying and/or classifying novel or emerging viral pathogens for which sufficiently specific and sensitive tests are lacking. ( info)

4/46. Neonatal syncytial giant cell hepatitis with paramyxoviral-like inclusions.

    Syncytial giant cell hepatitis in the neonatal period has been associated with many different etiologic agents and may present initially as cholestasis. Infectious causes are most common and include: (1 ) generalized bacterial sepsis, (2) viral agents, (3) toxoplasmosis, (4) syphilis, (5) listeriosis, and (6) tuberculosis. Viral hepatitis may be due to cytomegalovirus, rubella virus, herpes simplex, HHV-6, varicella, coxsackievirus, echovirus, reovirus 3, parvovirus B19, hiv, enteroviruses, paramyxovirus, and hepatitis a, B, or C (rare). Giant cell hepatitis may result in fulminant liver failure with massive hepatocyte necrosis and severe liver dysfunction leading to death, resolution with severely compromised liver function, or liver transplantation. The authors report a 6-week-old male who had an unremarkable perinatal period, became jaundiced after developing diarrhea, and subsequently developed liver dysfunction with massively increased liver enzymes and a coagulopathy. Open wedge and core liver biopsies were performed to determine if the patient should be listed for liver transplantation. Giant cell hepatitis with a significant mixed lymphocytic and neutrophilic infiltrate was present on both the wedge and core biopsies. The residual 60% of hepatocytes had ballooning degeneration and many possessed pyknotic nuclei. The hepatocytes were arranged in a pseudoacinar pattern. Electron microscopy showed paramyxoviral-like inclusions in the giant cells, characterized as large inclusions with fine filamentous, beaded substructures (18-20 nm). paramyxoviridae are nonsegmented, negative-sense, single-stranded rna viruses. This family is divided into the paramyxovirinae subfamily containing respirovirus (sendai virus, parainfluenza virus type 3), rubulavirus (mumps, parainfluenza virus type 2), and morbillivirus genera (measles); and pneumovirinae subfamily (pneumovirus genus [respiratory syncytial virus]). Supportive care to determine if hepatic function resolves following the viral episode, liver transplantation with fulminant liver failure, and ongoing evaluation in those who recover to assess chronic liver disease are necessary. Ultrastructural evaluation may unmask the etiologic agent for hepatitis and direct therapy. ( info)

5/46. Intravenous ribavirin by constant infusion for serious influenza and parainfluenzavirus infection.

    Three patients with severe lower respiratory tract influenza or parainfluenzavirus infections were treated with continuous ribavirin infusion, given as a 5 mg/kg/hour (h) loading infusion for 8 h followed by 1.5 mg/kg/h for 2 to 6 days. This regimen was generally well tolerated. plasma ribavirin concentrations were 40 to 60 microM in two patients during the continuous infusion phase and lower concentrations were detectable in tracheobronchial secretions. In temporal association with ribavirin administration, viral shedding diminished in one patient and ceased in two patients, one of whom had developed virus resistant to amantadine. The strategy of continuous ribavirin infusion warrants controlled testing for its antiviral and possible clinical effectiveness. ( info)

6/46. Late presentation of nipah virus encephalitis and kinetics of the humoral immune response.

    nipah virus is a newly discovered paramyxovirus transmitted directly from pigs to humans. During a large encephalitis outbreak in malaysia and singapore in 1998-9, most patients presented acutely. A 12 year old child is described who developed encephalitis 4 months after exposure to the virus. She was diagnosed by a new indirect IgG enzyme linked immunosorbent assay (ELISA), which is also described. The late presentation and IgG subclass responses had similarities to subacute sclerosing panencephalitis. nipah virus should be considered in patients with encephalitis even months after their possible exposure. ( info)

7/46. Virus-induced asthma attacks.

    Viral respiratory tract infections are a common cause of asthma attacks. Study of this phenomenon has revealed multiple mechanisms and contributed to understanding of the increase in airway inflammation and bronchoconstriction observed in this context. Changes in the neural control of the airways contribute to bronchoconstriction, which is reflected in an increased efficacy of anticholinergic medications during acute asthma attacks. The ability to prevent or treat viral respiratory tract infections is currently limited. However, as more effective antiviral treatments and vaccines become available, such therapies are likely to be effective in patients with asthma. Clinical management of this problem is illustrated in this article by the case of a 40-year-old woman with history of mild asthma who was admitted to an intensive care unit with severe bronchospasm and an upper respiratory tract infection. ( info)

8/46. Nipah encephalitis outbreak in malaysia, clinical features in patients from Seremban.

    BACKGROUND: An outbreak of viral encephalitis occurred among pig industry workers in malaysia in September 1998 to April 1999. The encephalitis was attributed to a new paramyxovirus, nipah virus. This is a description of the clinical features of 103 patients treated in the Seremban Hospital with characterization of the prognostic factors. methods: Clinical case records and laboratory investigations were reviewed. The case definition was: patients from the outbreak area, direct contact or in close proximity with pigs, clinical or CSF features of encephalitis. RESULTS: The mean age was 38 years, 89% were male, 58% were ethnic Chinese, 78% were pig farm owners or hired workers. The mean incubation period was 10 days. The patients typically presented with nonspecific systemic symptoms of fever, headache, myalgia and sore throat. seizures and focal neurological signs were seen in 16% and 5% respectively. In the more severe cases, this was followed by drowsiness and deteriorating consciousness requiring ventilation in 61%. Autonomic disturbances and myoclonic jerks were common features. The mortality was high at 41%. Systolic hypertension, tachycardia and high fever were associated with poor outcome. On the other hand, 40% recovered fully. As for the other 19%, the residual neurological signs were mostly mild. CONCLUSION: nipah virus caused an encephalitis illness with short incubation period and high mortality. The prognosis for the survivors was good. ( info)

9/46. Acute disseminated encephalomyelitis associated with parainfluenza virus infection of childhood.

    Acute disseminated encephalomyelitis associated with the parainfluenza virus has rarely been reported in childhood. A 2.5-year-old girl with acute disseminated encephalomyelitis, who developed bilateral symmetrical lesions in the basal ganglion, thalamus, corpus callosum, cerebral subcortical white matter, and cerebellar medulla on brain magnetic resonance imaging is described. Serological confirmation of parainfluenza virus infection was made 2 weeks following the onset of neurological symptoms. Four months later, the patient had a full recovery. At present, 3 years later, no relapse has been reported and she is leading a normal life. Our case is of interest because of its rarity, the striking brain magnetic resonance imaging, and the good neurological outcome. ( info)

10/46. Speechless after bone marrow transplantation: a rare complication of parainfluenza virus related group in an adult.

    Upper respiratory tract (URT) viral infections may cause severe consequences during myeloablative bone marrow transplantation (BMT). We present a patient with parainfluenza virus (PIV) infection during the course of BMT. He remained relatively asymptomatic during the course of cytopenia, but presented with complete loss of voice and severe laryngitis a few days after engraftment, which is not usual for adult PIV infections. Seroconversion to PIV and marked increase in antibody titres was demonstrated, with complete lymphoid engraftment. Our case illustrated that the virulence of some URT viral infections depend on host immune factors, and may remain latent until graft versus host responses can be mounted. ( info)
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