General observations
Like HeV, NiV induces syncytial cells in vascular tissues. It is primarily vasotropic and/or neurotropic in hosts, generating interstitial pneumonia or encephalitis. In nonporcine species, viral antigen is generally limited to small blood vessels or neurons. In cats and pigs, the antigen is also detectable in respiratory airways (Hooper et al. 2001).
Bats
Middleton and Morissy conducted an unpublished experiment showing that NiV could infect P. poliocephalus, and they were able to reisolate the virus (Hooper et al. 2001). Their observations are apparently the only ones on experimental NiV infections in bats. Virus has been isolated from the urine and chewed fruit (saliva) of P. hypomelanus (Chua et al. 2002).
Pigs
Necropsies of naturally infected pigs revealed lesions in the brain, the lungs, or both (Hooper et al. 2001). The main lesion is a moderate to severe interstitial pneumonia with widespread hemorrhages and syncytial cell formations in the endothelial cells of the pulmonary blood vessels. The lung, kidney, and brain tissues often develop generalized vasculitis with fibrinoid necrosis, hemorrhages, and infiltration of mononuclear cells. Viral antigens were concentrated in the lung epithelium and upper respiratory tract (Mod Nohr et al. 2000a).
In all age classes NiV infection causes an acute fever with respiratory involvement (the “barking cough”) and occasionally nervous signs (Field et al. 2001). Sows and boars sometimes die peracutely; sows in particular tended to develop neurologic signs and sometimes aborted in the first three months of pregnancy (Middleton et al. 2000, Mod Nohr et al. 2000a). Pigs four weeks to 6 months old tended to develop respiratory infections (Mod Nohr et al. 2000b). Not all infections produce symptoms: serologic studies found evidence of infection in most of the pigs on farms with infected humans, but only a minority of the pigs were observed ill and pig mortality rates were minimally higher than normal (~5% increase) (Chua et al. 2001). Mod Nohr et al. (2000a) report a 1-5% natural mortality rate and nearly 100% infection rate among weaners and porkers. The mortality rate among piglets is closer to 40%, but may result entirely or partially from infected sows’ reduced ability to nurse. However, seropositive, clinically healthy sows were observed nursing apparently healthy piglets.
Experimental infection via subcutaneous inoculation of 50,000 TCID50 has produced both the nervous and respiratory disease; the five in-contact and orally inoculated pigs did not develop clinical disease features (Middleton et al. 2000).1 In some orally exposed and in-contact pigs, there was active infection and virus excretion in respiratory discharges on days 4, 6, and 8 PI for oral exposure and 10 days PI for in-contact; Daniels reported 14 days PI for in-contact (Mod Nohr et al. 2000a). In all cases the virus was epitheliotropic in the respiratory epithelium, and in some cases it was also meningotropic. Multiplication occurred in tonsils and respiratory epithelium for in-contact pigs (Mod Nohr 1999). Virus was isolated from the lung, tonsil, and spleen of neurologic, subcutaneously inoculated pigs and from the tonsils and nasal mucus of orally challenged pigs. Seroconversion in challenged and in-contact animals coincided with elimination of virus from tissues. Jamaluddin has unpublished anecdotal evidence of vascular transmission of the virus across the placenta of pigs (Hooper et al. 2001). Virus has also been isolated from pig blood and saliva (Daniels et al. 2001, Middleton unpub.). Immunohistochemistry implies infection in CNS (including meninges), lung, kidney, and trachea (Daniels et al. 2001).
Cats
Immunohistochemistry was used to confirm one case of natural infection (Hooper et al. 2001). The necropsy showed generalized vasculitis most affecting the brain, kidney, liver, and to a lesser degree the lung.
Oronasal challenge experiments on two cats produced fever (Hooper et al. 2001). The gross lesions resembled those induced by HeV but also included ulcerative tracheobronchitis and moderately severe diffuse meningitis. The virus was demonstrated in renal glomureli by immunoperoxidase reactions and was reisolated in urine and mouth fluids (Hooper et al. 2001, Vadivale 1999) and also in the blood, spleen, and lymph node (AAHL, unpub. results, see Daniels et al. 2001).
Dogs
A naturally infected moribund dog was observed with clinical signs similar to those of canine distemper, including fever, respiratory distress, conjunctivitis, and mucopurulent nasal and conjunctival discharges. Necropsy showed severe pulmonary edema, some meningitis and hemorrhage, and necrosis and inflammation in the adrenal. Necropsy of another naturally infected dog that was found dead revealed the same signs and severe autolysis. Immunohistochemistry revealed NiV in canine CNS (including meninges), lung, spleen, kidney, heat, and adrenal; PCR showed NiV in dog kidney and liver (Daniels et al. 2001).
Horses
An infected horse displayed nonsupportive meningitis and areas of rarefaction in the parenchyma of the brain (Hooper et al. 2001).
Humans
Unlike HeV, NiV infection in humans is primarily encephalitic, not respiratory (Field et al. 2001). Necropsies of 33 fatal cases revealed mainly systemic endothelial infections accompanied by vasculitis, thrombosis, ischemia, and necrosis. Changes were most pronounced in the CNS, which was filled with extensive foci of rarefaction necrosis (Hooper et al. 2001, Lam and Chua 2002). The lung, heart, and kidneys were also involved (Chua et al. 1999). Chua et al. (2001) were able to isolate NiV from eight of 20 patients virologically and/or serologically confirmed to be infected. Virus was isolated in throat swabs from six patients, the urine of five patients, and the nose of one patient. Virus isolation failed after the seventh day of symptoms and was inversely correlated with the emergence of anti-NiV IgM. Virus isolation was not significantly correlated with any clinical features or disease outcome, and none of the patients had obvious nasal discharge or respiratory symptoms. Virus has also been isolated in CSF (Goh et al. 2000).
Most patients (92%) report falling ill within two weeks after contact with symptomatic pigs (Goh et al. 2000), though the incubation period can be up to a month (Chua et al. 1999) or as short as two days (Chong et al. 2002). The average in Seremban Hospital (n = 49) was 10 days (Chong et al. 2002). Symptoms include fever (3-14 days), headache, myalgia, drowsiness, and disorientation sometimes proceeding to a coma within 24-48 h (MMWR 9 Apr 1999). The mean time between the onset of symptoms and death is 10.3 days (range = 5-29), and recovering patients have a mean time of 14.1 days (range = 6-24) (Goh et al. 2000). The case fatality rate is 40% (Farrar 1999). Systolic hypertension, tachycardia, and high fever were associated with poor outcome; and 19% (n = 103) of patients in Seremban Hospital had mild residual neurological deficits (Chong et al. 2002). Old age and severe brain-stem involvement were also associated with poor outcome (Goh et al. 2000).
Of the 64 surviving patients admitted to the University Hospital in Kuala Lumpur in 1998, 12 suffered relapses of acute onset one year after the initial outbreak (Lam and Chua 2002). None had been reexposed to infected pigs. In all patients either neurologic symptoms reappeared after an initial illness, or there was a long latency period between the initial finding of seropositivity after exposure to the virus and the development of neurologic symptoms. These symptoms included the fever and disorientation of the typical cases and myoclonus. Goh et al. (2000) note relapses 13-39 days after initial mild illness in 3% of patients (n = 94).
1 However, Mohd Nor (1999) reports that AAHL found clinical signs 14-16 PI in orally challenged pigs and 7-10 days in parenterally challenged pigs.
Author: S. Cobey.