Vol

DEPARTMENT OF PATHOLOGY
The Johns Hopkins Medical Institutions

Vol. 20, No. 37
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Tuesday, September 11, 2001

A. Provided by Leslie Edwards Reger, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.

No information available.

B. The Johns Hopkins Hospital, Department of Pathology. Information provided by Anil V. Parwani, M.D., Ph.D.

West Nile Virus 2001 Organism: West Nile virus (WNV) is a member of the family Flaviviridae (genus flavivirus) that belongs to the Japanese Encephalitis virus serocomplex which also includes St.Louis encephalitis virus, Kunjin virus, and Murray valley encephalitis virus. All members of flavivirus are closely related antigenically, resulting in serological cross-reactions. The flavivirus genome consists of positive-sense, single-stranded RNA which is about 12,000 nucleotides in length. He genome encodes for three structural proteins and seven nonstructural proteins. The E glycoprotein is the most immuogenic protein and elicits most of the virus neutralizing antibodies. The virions are enveloped, icosahedral, and 40 to 50 nm in size. WNV was first isolated in the West Nile Province of Uganda in 1937. WNV is endemic in Africa, the Middle East and South East Asia. The virus is transmitted between Culex mosquitoes and wild birds, with sporadic infections of humans and other mammals. Once transmitted to a human host, the virus multiplies in the bloodstream and may eventually cross the blood-brain barrier. The incubation period is from 3 to 15 days.

Epidemiology: Past human outbreaks have been in South Africa (1974), and Israel (1954, 1957). However, since the mid-1990s some interesting epidemiologic trends have been noted. Firstly, there has been an increase in the frequency of outbreaks (Romania, Morocco 1996; Tunisia 1997; Italy 1998; Russia, France, USA 1999; Russia, France, USA 2000). Secondly, there has been an apparent increase in the severity of human disease with several hundred confirmed human infections (Romania 393 cases, Russia 942 cases, USA 83 cases (1999-2000). Finally, there has been a high number of avian deaths accompanying the human outbreaks, particularly in the USA and Israel. The WN virus responsible for the USA outbreak (NY99) is genetically indistinguishable from the virus first isolated from Romania outbreak in 1996 (ROM96). The closest relative of the NY99 virus has been a virus isolated in Israel (Isr98). Furthermore, the NY99 has remained genetically stable between the 1999 and 2000 USA outbreaks. The first potential case of WNV encephalitis in humans in Maryland was reported on 9/6/2001 in Baltimore in a 72 year old man. This is only the 10th case of WNV encephalitis in humans in 2001 in USA.

Clinical Manifestations: Most infections with WNV are mild leading to a rash, myalgias and lymphadenopathy. More serious infections produce a febrile illness associated with headache, arthralgia and conjunctivitis. Occasional complications include encephalitis or meningitis.

Diagnosis: Immunohistochemistry (IHC) using virus-specific Mabs on brain tissue has been very useful in identifying both human and avian cases of WN virus infection. Serum and CSF specimens may be tested for antibody to WNV using a antigen-capture ELISA test. Sequence analysis following PCR amplification may also be employed. CDC recommendations are to test paired acute and convalescent sera.

Treatment: Most infections of WNV are mild and self-limited. Severe cases require hospitalization and acute care. Recent reports have shown that viral replication is inhibited in vitro using ribavirin. Preventive measures are more successful in controlling infection rates. These include reducing exposure to mosquitoes by limiting outdoor activity after dusk, wearing long sleeve shirts and long pants, application of insect repellants. From a public health standpoint, eliminating sources of stagnant water and other mosquito breeding habitats and extensive early season larval control will greatly reduce the transmission of WNV.

References:

Petersen, LR and Roehrig, JT (2001). West Nile virus: a reemerging global pathogen. Emerging Infectious Diseases. 7(4):10.
Jordan I, Briese T, Fisher N eet al. (2000) Ribavirin inhibits West Nile virus replication and cytopathic effect in neural cells. J. Infect. Dis 182(4).
Tsai TF, Popovici F, Cernescu C et al. (1998) West Nile virus encephalitis epidemic in southeastern Romania. The Lancet 352:767-771.
MMWR . West Nile Virus Activity. Morb Mortal Wkly Rpt. July 27, 2001 50 (29); 617-619.