Nipah and Hendra virus encephalitides
Nipah and Hendra are two related viruses of the Paramyxoviridae family that have their reservoir in large Pteropus fruit bats. Human disease manifests most often as acute encephalitis, which may be late-onset or relapsing, or pneumonia, with high mortality. Transmission from bats to human includes direct spread from consumption of food contaminated by infected bats’ secretions, and contact with infected animals: human-to-human spread can also occur.
Nipah and Hendra viruses are two new zoonotic viruses that have emerged in recent years. Both are paramyxoviridae family sharing many similar characteristics. Because of their homology, a new genus called Henipavirus (Hendra + Nipah) was created for these two viruses.
Hendra virus infection
Hendra virus was first isolated in an outbreak of acute respiratory illness involving horses in Australia in 1994. Horses may become infected by eating hay contaminated by uterine fluids and aborted fetal tissue from fruit bats. All human cases had been in close contact with bodily fluids from sick, moribund, or dead horses. Transmission from bats to humans, humans to horses, or humans to humans has not been documented. A horse trainer and stable hand were also infected, presenting with respiratory illnesses from which the horse trainer died. A second human death occurred in 1995, when a farmer who had been in contact with sick horses about a year earlier died from encephalitis. Another two deaths involving veterinary workers occurred in the Hendra virus outbreaks in July 2008 and July 2009, also in Australia. Thus, up to 2011, there have been 14 outbreaks of Hendra virus infection, all involving horses, 5 of these involving subsequent horse to human transmission, with 4 deaths among a total of 7 human cases.
Human patients developed flu-like or feverish illnesses about 2 weeks after exposure to sick horses, but in one case the incubation period was 1 year. Acute or insidious encephalitis then developed after a few days. A survivor suffered persistent residual sensorineural deafness. MRI scans showed hyperintense plaque-like cortical and basal ganglia lesions and perfusion scans suggested widespread cortical vasculitis with infarcts.
Nipah virus infection
In late 1998 to early 1999, there was an outbreak of viral encephalitis in several pig-farming villages in peninsular Malaysia which subsequently involved abattoir workers in Singapore. More than 300 patients were affected. Isolation of virus from cerebrospinal fluid specimens of several patients indicated that this was due to previously unknown Nipah virus.
Human Nipah virus infection was transmitted by close contact with infected pigs. Human-to-human transmission was thought to be rare, although the virus could be readily isolated from patients’ respiratory secretions and urine.
During the outbreak, more than half of the patients had affected family members, suggesting a high infection rate. Some of the household members had seroconversion without clinical disease, indicating subclinical infection at a ratio of asymptomatic vs symptomatic infection of 1 to 3. The infection involved all age groups.
The incubation period was less than 2 weeks in most patients. The clinical manifestations were those of an acute encephalitis with fever, headache, vomiting, and reduced level of consciousness. Distinctive clinical features were areflexia, hypotonia, and prominent autonomic changes such as tachycardia and hypertension. Segmental myoclonus found in about one-third of patients was characterized by focal, rhythmic jerking of muscles, commonly involving the diaphragm and anterior muscles of the neck. Respiratory tract involvement with cough was seen at presentation in 14% of patients. There were some patients who had nonencephalitic infection with seroconversion and systemic symptoms but no evidence of encephalitis.
The overall mortality of acute Nipah encephalitis was 40%. Severe brainstem involvement was associated with poor prognosis.
Cerebrospinal fluid examination was abnormal in 75% of patients with elevated protein levels or elevated white cell counts. Glucose levels were within normal limits. These features are nonspecific. IgM and IgG antibody detection in serum and cerebrospinal fluid were critical to the diagnosis of Nipah virus infection. The antibody test utilized an enzyme-linked immunosorbent assay (ELISA) test. The rate of positive IgM was 100% by day 12 of illness. For IgG, it was 100% by 4 weeks of illness.
Brain MRI in acute encephalitis showed multiple, disseminated, small discrete hyperintense lesions best seen in the FLAIR sequence particularly in the subcortical and deep white matter (Fig. 184.108.40.206). The lesions were likely to correspond to the microinfarctions noted in postmortem tissues. Similar changes were also seen in asymptomatic patients with Nipah virus infection.
Pathology and pathogenesis
Vasculitis of the medium-sized to small blood vessels in brain, causing thrombosis, and vascular occlusion with areas of necrosis and ischaemia, were the major findings (Fig. 220.127.116.11). There were also viral inclusions indicating direct viral involvement of the neurons. Vasculitis was also seen in lung and kidney.
Relapse and late-onset Nipah encephalitis
Close to 10% of patients suffered a second or even a third neurological episode months or years following recovery from acute encephalitis. About 5% who were either asymptomatic or only had mild nonencephalitic illness initially, also developed similar neurologic episodes (late-onset Nipah encephalitis) for the first time after a delayed period. Clinical, radiologic and pathologic findings indicate that relapse and late-onset Nipah encephalitis was the same disease process,which was distinct from acute Nipah virus encephalitis. The common clinical features were fever, headache, seizures, and focal neurological signs. There was an18% mortality. MRI showed patchy areas of confluent cortical lesions. Necropsy showed focal confluent encephalitis due to a recurrent infection.
The bat as reservoir host
As for Hendra virus, the reservoir of Nipah virus is fruit bats of the Pteropus species. Half-eaten fruits dropped by bats near pig farms may have infected an animal that subsequently ingested them. Pigs were the amplifying hosts for the virus. There was pig-to-pig transmission which subsequently spread to human.
Nipah encephalitis in Bangladesh and India
Eleven outbreaks of Nipah encephalitis have been reported in Bangladesh from 2001 to 2011. Two other outbreaks were reported from northeastern India, in Siliguri district in 2001, and Nadia district in 2007.
As in Malaysia, Nipah virus caused a fatal encephalitic illness in humans in Bangladesh and India. However, the Bangladeshi and Indian outbreaks showed prominent human-to-human spread of infection, with physicians who cared for the patients also affected. There was florid pulmonary involvement in some patients. Brain MRI in some patients showed confluent high signal lesions involving both grey and white matter, which is unlike the acute Nipah encephalitis in the Malaysian outbreak, suggesting some differences in the pathology from the Malaysian patients. The RNA of Nipah virus in Bangladesh and India was close to but not identical with that causing the outbreak in Malaysia. Pteropus bats were also the reservoir of Nipah virus in Bangladesh. There may be a variety of mode of transmission from bats to humans in the Bangladesh and Indian outbreaks. Consumption of raw date-palm juice and half-eaten fruits contaminated by secretions from bats are suggested modes of transmission.
Pteropus bats are widespread in large parts of Asia, Africa, and Australia. Nipah virus has been isolated in urine of Pteropus bats in Cambodia, and Nipah viral antigen has been found in saliva of Pteropus bats in Thailand. Serological evidence of Henipavirus infection has been reported in fruit bats from Papua New Guinea to Ghana, Africa from East to West, and Yunnan, China to Australia from North to South, indicating potential human Nipah virus infection elsewhere.
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