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Biomedical subjects

K B Chua

Publications and source records attributed to K B Chua.

At least 37 records · Page 2Linked to original sources
PubMed2001

Tioman virus, a novel paramyxovirus isolated from fruit bats in Malaysia.

A search for the natural host of Nipah virus has led to the isolation of a previously unknown member of the family Paramyxoviridae. Tioman virus (TiV) was isolated from the urine of fruit bats (Pteropus hypomelanus) found on the island of the same name off the eastern coast of peninsular Malaysia. An electron microscopic study of TiV-infected cells revealed spherical and pleomorphic-enveloped viral particles (100--500 nm in size) with a single fringe of embedded peplomers. Virus morphogenesis occurred at the plasma membrane of infected cells and morphological features of negative-stained ribonucleoprotein complexes were compatible with that of viruses in the family Paramyxoviridae. Serological studies revealed no cross-reactivity with antibodies against a number of known Paramyxoviridae members except for the newly described Menangle virus (MenV), isolated in Australia in 1997. Failure of PCR amplification using MenV-specific primers suggested that this new virus is related to but different from MenV. For molecular characterization of the virus, a cDNA subtraction strategy was employed to isolate virus-specific cDNA from virus-infected cells. Complete gene sequences for the nucleocapsid protein (N) and phosphoprotein (P/V) have been determined and recombinant N and V proteins produced in baculovirus. The recombinant N and V proteins reacted with porcine anti-MenV sera in Western blot, confirming the serological cross-reactivity observed during initial virus characterization. The lack of a C protein-coding region in the P/V gene, the creation of P mRNA by insertion of 2-G residues, and the results of phylogenetic analyses all indicated that TiV is a novel member of the genus Rubulavirus.

Amino Acid Sequence↗
PubMed2001

Treatment of acute Nipah encephalitis with ribavirin.

Nipah virus, a newly identified paramyxovirus caused a severe outbreak of encephalitis in Malaysia with high fatalities. We report an open-label trial of ribavirin in 140 patients, with 54 patients who were managed prior to the availability of ribavirin or refused treatment as control. There were 45 deaths (32%) in the ribavirin arm; 29 deaths (54%) occurred in the control arm. This represents a 36% reduction in mortality (p = 0.011). There was no associated serious side effect. This study suggests that ribavirin is able to reduce the mortality of acute Nipah encephalitis.

Adult↗
PubMed2001

The presence of Nipah virus in respiratory secretions and urine of patients during an outbreak of Nipah virus encephalitis in Malaysia.

OBJECTIVES: To study the excretion of Nipah virus in the upper respiratory secretions and urine of infected patients in relation to other clinical features. METHODS: Isolation of Nipah virus from the respiratory secretions and urine was made in Vero cells and identified by indirect immunofluorescence assay using anti-Hendra specific hyperimmune mouse ascitic fluid and FITC-conjugated goat anti-mouse IgG. RESULTS: During the peak outbreak of Nipah virus encephalitis in Malaysia, Nipah virus was isolated from the upper respiratory secretions and urine in eight of 20 patients who were virologically and/or serologically confirmed to be infected with the virus. From these eight patients, Nipah virus was isolated from six throat swab specimens, three urine specimens and only one nasal swab specimen. The positive virus isolation rate was related to the collection of these specimens during the early phase of the illness (P = 0.068). The presence of serum anti-Nipah specific IgM appeared to reduce the chance of isolating the virus (P = 0.049). There was no significant difference in the isolation rate with respect to the age, gender, ethnic group and clinical features associated with grave prognosis and mortality outcome of the patients. CONCLUSION: This study shows that it is possible to be infected from secretions of infected patients, but epidemiological survey on close contacts so far did not suggest that human-to-human transmission is common.

Adolescent↗
PubMed2001

Comparison of the complete nucleotide sequences of echovirus 7 strain UMMC and the prototype (Wallace) strain demonstrates significant genetic drift over time.

The complete nucleotide sequences are reported of two strains of echovirus 7, the prototype Wallace strain (Eo7-Wallace) and a recent Malaysian strain isolated from the cerebrospinal fluid of a child with fatal encephalomyelitis (Eo7-UMMC strain). The molecular findings corroborate the serological placement of the UMMC strain as echovirus 7. Both Eo7-Wallace and Eo7-UMMC belong to the species human enterovirus B and are most closely related to echovirus 11. Eo7-UMMC has undergone significant genetic drift from the prototype strain in the 47 years that separate the isolation of the two viruses. Phylogenetic analysis revealed that Eo7-UMMC did not arise from recombination with another enterovirus serotype. The molecular basis for the severely neurovirulent phenotype of Eo7-UMMC remains unknown. However, it is shown that mutations in the nucleotide sequence of the 5' untranslated region (UTR) of Eo7-UMMC result in changes to the putative structure of the 5' UTR. It is possible that these changes contribute to the neurovirulence of Eo7-UMMC.

3' Untranslated Regions↗
PubMed2001

Complete nucleotide sequences of Nipah virus isolates from Malaysia.

We have completely sequenced the genomes of two Nipah virus (NiV) isolates, one from the throat secretion and the other from the cerebrospinal fluid (CSF) of the sole surviving encephalitic patient with positive CSF virus isolation in Malaysia. The two genomes have 18246 nucleotides each and differ by only 4 nucleotides. The NiV genome is 12 nucleotides longer than the Hendra virus (HeV) genome and both genomes have identical leader and trailer sequence lengths and hexamer-phasing positions for all their genes. Both NiV and HeV are also very closely related with respect to their genomic end sequences, gene start and stop signals, P gene-editing signals and deduced amino acid sequences of nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, glycoprotein and RNA polymerase. The existing evidence demonstrates a clear need for the creation of a new genus within the subfamily Paramyxovirinae to accommodate the close similarities between NiV and HeV and their significant differences from other members of the subfamily.

Base Sequence↗
PubMed2001

Emerging viral diseases of Southeast Asia and the Western Pacific.

Over the past 6 years, a number of zoonotic and vectorborne viral diseases have emerged in Southeast Asia and the Western Pacific. Vectorborne disease agents discussed in this article include Japanese encephalitis, Barmah Forest, Ross River, and Chikungunya viruses. However, most emerging viruses have been zoonotic, with fruit bats, including flying fox species as the probable wildlife hosts, and these will be discussed as well. The first of these disease agents to emerge was Hendra virus, formerly called equine morbillivirus. This was followed by outbreaks caused by a rabies-related virus, Australian bat lyssavirus, and a virus associated with porcine stillbirths and malformations, Menangle virus. Nipah virus caused an outbreak of fatal pneumonia in pigs and encephalitis in humans in the Malay Peninsula. Most recently, Tioman virus has been isolated from flying foxes, but it has not yet been associated with animal or human disease. Of nonzoonotic viruses, the most important regionally have been enterovirus 71 and HIV.

Animals↗
PubMed2001

Gastrointestinal manifestations of systemic lupus erythematosus.

Gastrointestinal symptoms are common in patients with systemic lupus erythematosus (SLE) and can be due to primary gastrointestinal disorders, complications of therapy or SLE itself. In this case report, we describe three different presentations and causes of gastrointestinal complaints in patients with SLE. Diagnostic and management problems are discussed.

Abdominal Pain↗
PubMed2001

Chikungunya infection--an emerging disease in Malaysia.

Many countries neighboring Malaysia have reported human infections by chikungunya virus, a mosquito-borne togavirus belonging to the genus Alphavirus. However, although there is serological evidence of its presence in Malaysia, chikungunya virus has not been known to be associated with clinical illness in the country. An outbreak of chikungunya virus occurred in Klang, Malaysia, between December 1998 and February 1999. The majority of the cases were in adults and the clinical presentation was similar to classical chikungunya infections. Malaysia is heavily dependent on migrant workers from countries where chikungunya is endemic. It is speculated that the virus has been re-introduced into the country through the movement of these workers.

Alphavirus Infections↗
PubMed2001

Serological evidence of hantavirus infections in Malaysia.

Hantaviruses are primarily rodent-borne and transmission is by inhalation of virus-contaminated aerosols of rodent excreta, especially urine and saliva. The genus Hantavirus, family Bunyaviridae, comprises at least 14 serotypes and the symptoms of clinical illness range from mild fever to severe hemorrhagic manifestations with renal complications. Many countries in Southeast Asia are unaware of the importance of hantavirus infections and give them low priority. Malaysia, like other countries in the region, has conducted very few studies on the epidemiology of hantaviruses - and even these were conducted in the 1980s. Using a more extensive range of hantavirus antigens, we conducted a seroprevalence study of rodents and humans and found further evidence of hantavirus infections. Moreover, the data from the antibody profiles strongly suggest the presence of different hantaviruses at the study sites.

Animals↗
PubMed2000

Nipah virus: a recently emergent deadly paramyxovirus.

A paramyxovirus virus termed Nipah virus has been identified as the etiologic agent of an outbreak of severe encephalitis in people with close contact exposure to pigs in Malaysia and Singapore. The outbreak was first noted in late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore. Electron microscopic, serologic, and genetic studies indicate that this virus belongs to the family Paramyxoviridae and is most closely related to the recently discovered Hendra virus. We suggest that these two viruses are representative of a new genus within the family Paramyxoviridae. Like Hendra virus, Nipah virus is unusual among the paramyxoviruses in its ability to infect and cause potentially fatal disease in a number of host species, including humans.

Animals↗
PubMed2000

Clinical features of Nipah virus encephalitis among pig farmers in Malaysia.

BACKGROUND: Between September 1998 and June 1999, there was an outbreak of severe viral encephalitis due to Nipah virus, a newly discovered paramyxovirus, in Malaysia. METHODS: We studied the clinical features of the patients with Nipah virus encephalitis who were admitted to a medical center in Kuala Lumpur. The case definition was based on epidemiologic, clinical, cerebrospinal fluid, and neuroimaging findings. RESULTS: Ninety-four patients with Nipah virus infection were seen from February to June 1999 (mean age, 37 years; ratio of male patients to female patients, 4.5 to 1). Ninety-three percent had had direct contact with pigs, usually in the two weeks before the onset of illness, suggesting that there was direct viral transmission from pigs to humans and a short incubation period. The main presenting features were fever, headache, dizziness, and vomiting. Fifty-two patients (55 percent) had a reduced level of consciousness and prominent brain-stem dysfunction. Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia and thus suggest the involvement of the brain stem and the upper cervical spinal cord. The initial cerebrospinal fluid findings were abnormal in 75 percent of patients. Antibodies against Hendra virus were detected in serum or cerebrospinal fluid in 76 percent of 83 patients tested. Thirty patients (32 percent) died after rapid deterioration in their condition. An abnormal doll's-eye reflex and tachycardia were factors associated with a poor prognosis. Death was probably due to severe brain-stem involvement. Neurologic relapse occurred after initially mild disease in three patients. Fifty patients (53 percent) recovered fully, and 14 (15 percent) had persistent neurologic deficits. CONCLUSIONS: Nipah virus causes a severe, rapidly progressive encephalitis with a high mortality rate and features that suggest involvement of the brain stem. The infection is associated with recent contact with pigs.

Adult↗
PubMed2000

The predictive value of uvulo-palatoglossal junctional ulcers as an early clinical sign of exanthem subitum due to human herpesvirus 6.

BACKGROUND: The clinical sign of uvulo-palatoglossal junctional (UPJ) ulcers was first noted in 1983 in a 5.5-month-old baby with exanthem subitum (ES). An earlier prospective clinical study showed that there was a strong association of UPJ ulcers and occurrence of ES with a positive predictive value of 95.3% and negative predictive value of 100%. OBJECTIVE: To determine the value of uvulo-palatoglossal junctional (UPJ) ulcers as an early clinical sign of exanthem subitum (ES) due to human herpesvirus 6 (HHV 6) infection. STUDY DESIGN: A case-control study of 20 febrile children with UPJ ulcers versus 26 febrile children without UPJ ulcers. These children were followed up for any development of ES and investigated for human herpesvirus 6 (HHV 6) as the causative agents of the febrile episodes. RESULTS: In this study, 20 out of 46 febrile children aged 3 months to 3 years with UPJ ulcers were virologically and/or serologically confirmed to be due to primary HHV 6 infection. The rest of the 26 children without ulcers did not have HHV 6 infection. Of the 20 children with UPJ ulcers, only 17 of the 19 children with adequate follow-up till subsidence of fever developed ES. None of the 26 children without UPJ ulcers developed ES. CONCLUSION: Statistically, there was a significant association of UPJ ulcers as an early sign of ES with a positive predictive value of 89.5% and negative predictive value of 100%. This finding also suggests that the presence of UPJ ulcers is a useful pathognomic clinical sign of symptomatic primary HHV 6 infection.

Antibodies, Viral↗
PubMed2000

High mortality in Nipah encephalitis is associated with presence of virus in cerebrospinal fluid.

During the outbreak of Nipah virus encephalitis in Malaysia, stored cerebrospinal fluid (CSF) samples from 84 patients (27 fatal and 57 nonfatal cases) were cultured for the virus. The virus was isolated from 17 fatal cases and 1 nonfatal case. There were significant associations between CSF virus isolation and mortality as well as clinical features associated with poor prognosis. In addition, there was a positive linear correlation of CSF virus isolation with age. There was no significant association between CSF virus isolation and the character of the CSF, presence of Nipah-specific antibody in the serum or CSF, duration of illness before collection of samples, or sex or ethnicity of the patients. This study suggests that high viral replication in the central nervous system may be an important factor for high mortality.

Adolescent↗
PubMed2000

Retrospective review of serologic rubella activity in University Hospital Kuala Lumpur.

A retrospective review of rubella serological results carried out in the Virus Diagnostic Unit, University Hospital Kuala Lumpur (UHKL) from January 1993 to September 1999 showed the presence of rubella infection annually which appeared to increase periodically every two to three years. There was no statistical significant difference in the rubella positive rate between male and female population aged 14 to 48 years. Congenital rubella infections (CRI) occurred in babies delivered in UHKL yearly from 1993 to 1998 with an average incidence rate of 48 per 100,000 deliveries. Peaks of rubella cases appeared to be followed by an increase in incidence of CRI cases 6 to 9 months later. The study showed that only 50.8% clinically diagnosed rubella was confirmed by laboratory finding. This study also showed an increase of rubella activity for the months of July, August and September 1999 and this may herald an increase of CRI cases in the coming millennium.

Adolescent↗
PubMed1999

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.

Adult↗