Publications on recent Malaysian Outbreaks

Publications on recent Malaysian Outbreaks


Recently there had been a flurry of publications regarding Nipah virus and the outbreak in Sarawak in medical journals. Here are some excerpts from these articles.

Nipah Virus

From The Lancet Interactive (Need to sign in by choosing a user name and password)

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.

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.

An interesting commentary, which summarises the Nipah outbreak, the previous two articles and highlighting concerns regarding emerging viruses in areas where facilities for viral isolation and identification are commonly under-developed.

From the Singapore Medical Journal ; VO L U M E  4 0 , I S S U E 05, May  1 9 9 9

The first two articles are commentaries, covering emerging viruses, the nipah virus and issues/concerns in handling the outbreak. The last is an original paper presenting the MRI findings of nipah virus. The abstract reads as follows:

Eleven abattoir workers in Singapore were infected in March 1999 by an outbreak caused by the Nipah virus. This newly discovered, Hendra-like paramyxovirus causes acute infection of the CNS. We present the magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) findings in a patient suffering from acute meningoencephalitis. Multiple small white matter lesions were detected on diffusion-weighted imaging (DWI) and T2-weighted images. There were no abnormalities detected on MRS. We believe this to be the first reported MRI findings in this novel zoonotic viral disease.

From a report submitted to the OIE Chapter of Scientific and Technical Review ( August 8, 1999 )

Summary

Since late 1998 to 1999, a new pig disease characterized by a pronounced respiratory and neurologic syndrome, sometimes with sudden death of sows and boars was noticed to spread among some pig farms in Peninsular Malaysia. The disease appeared to have close association with viral encephalitis epidemic in the pig farm workers. A previously unrecognized paramyxovirus, related to, but distinct from the Australian Hendra virus, was later identified in this outbreak. The new virus is named ‘Nipah’ and was confirmed by molecular characterization to be the same agent responsible for the human and pig disease. The new pig disease is proposed to be named as Porcine Respiratory and Encephalitis Syndrome or Barking Pig Syndrome in Peninsular Malaysia. This paper attempts to describe the new disease and some of the epidemiological findings among infected pigs as well as the control programmes which were instituted to contain the viruses in the national swine herd.

Sarawak Outbreak

From The Lancet Interactive

Background In mid-1997, several children died in Sarawak, Malaysia, during an epidemic of enterovirus-71 (EV71) hand, foot, and mouth disease. The children who died had a febrile illness that rapidly progressed to cardiopulmonary failure and the cause was not satisfactorily resolved. We describe the isolation and identification of a subgenus B adenovirus from the children who died.

Methods We studied two groups of children presenting to Sibu Hospital from April 14 to Sept 30, 1997. For children who died, the inclusion criterion was death after febrile illness, and for those who did not die it was acute flaccid paralysis (AFP). Serum and cerebrospinal fluid samples were tested for IgM antibodies to Japanese encephalitis and dengue viruses. Viruses isolated were identified by immunofluorescence, reverse-transcriptase PCR, or PCR and DNA sequencing.

Findings Enterovirus was isolated in three (19%) of 16 children who died and in none of the eight surviving children with AFP. However, an agent that was initially difficult to identify was found in ten (63%) children who died and five (63%) surviving children who had AFP. The agents isolated from ten (667%) of these 15 children were eventually identified as adenoviruses and were isolated mainly from clinically important sterile sites or tissues. All the enterovirus-positive children who died had this second agent.

Interpretation Our data raises doubts that EV71 was the only aetiological agent in these deaths.

Included in the article is an echocardiogram movie which shows the following : Echocardiogram of a 19-month-old boy (case 9) in cardiogenic shock. The globular left ventricle shows markedly impaired contractility, typical of the fatal cases in this study. The movie is in QuickTime format and compressed with Windows ZIP to reduce file size during download. Click on the links to begin downloading. We advise you not to attempt to download the 17.8 MB zip file if you have a slow internet connection.

It is interesting to note that more articles on Nipah have already been published whereas articles pertaining to the outbreak in Sarawak and Peninsular Malaysia have hardly been heard. The final word from the Ministry of Health on the so called "coxsackie"/"enterovirus 71" or an involvement of ? new adenovirus as may be the case in Sarawak is still pending. What is heartening is the JE/Hendra-like virus stand that we heard so often during the recent outbreak has finally been silenced by evidence based medicine. There is a lesson to be learnt ....................

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