Two mosquito-borne diseases break past old geographic boundaries

HOUSTON "Mosquitoes are flying syringes,"

By | November 21, 2000

HOUSTON "Mosquitoes are flying syringes," declared Frank Cortez-Flores of Loma Linda University (California), and two mosquito-borne diseases have broken past old geographic boundaries to invade the US. The first, West Nile encephalitis, is a newcomer to the western hemisphere and thus has garnered the most headlines. The other, dengue fever, is considered the world's most important vector-borne viral disease affecting people, in terms of both morbidity and mortality.

The West Nile virus, native to Africa and undetected in the US until August 1999, is an example of an infectious agent that seems to be spreading beyond its previous boundaries, causing an 'emerging infectious disease'. Because of mutations and other changes in disease-causing organisms, and increases in international travel, the incidences of once-exotic diseases in new territories are increasing. Some suggest that global warming also contributes to the spread of these diseases.

West Nile virus is no stranger to Europe, having caused outbreaks of human and equine disease in the western Mediterranean and southern Russia in 1962-64, Belarus and Ukraine in the 1970s and 1980s, Romania in 1996-97, the Czech Republic in 1997 and Italy in 1998. But West Nile encephalitis hadn't appeared in the US until the summer of 1999, when it killed seven New Yorkers and caused serious illness in at least 62 others. West Nile and other types of mosquito-born encephalitis can cause brain inflammation, with symptoms including sustained fever, nervous tics, blurred vision or slurred speech. So far this year, West Nile virus has caused 16 people to become ill and led to one death.

Ian Lipkin and his team at the University of California at Irvine (UCI) and the Centers for Disease Control (CDC) in Fort Collins, Colorado, identified the West Nile virus as the agent responsible for the August 1999 encephalitis outbreak in New York. They also have developed a quick, accurate diagnostic technique that a hospital laboratory can use to determine the existence of West Nile infection.

The number of mosquito species carrying the virus has jumped from one in 1999 to eight in 2000, including mosquitoes that bite during the day as well as those that bite at dawn and dusk. And West Nile virus was found last winter in hibernating mosquitoes at three New York City sites, dashing hopes that winter conditions would terminate the outbreak.

In 1999, West Nile virus was detected in bird and animal blood as far south as Baltimore according to Stephen Ostroff, a CDC official who is federal co-ordinator for West Nile virus. The virus is present in hundreds of birds in New York, Connecticut, Rhode Island, Pennsylvania, the District of Columbia and Virginia. Robert McLean, director of the USGS National Wildlife Health Center in Madison, Wisconsin said that while crows are especially susceptible to the virus, many other bird species are also carriers. As birds migrate, mosquitoes in new areas may become infected and then carry that infection on to humans. McLean said, "We're concerned that the fall migration of millions of birds from and through the 400-mile-wide infected region in the northeastern United States may move West Nile virus southward along the Atlantic and Gulf coast states. West Nile virus has been isolated from more than 63 species of bird, including 53 free-ranging species from eight states. That means it's not a matter of if, but when, the virus will move south." In late September 2000, the reach of the virus extended as far south as North Carolina.

Other mammals besides man are at risk: horses, three species of bat, a racoon and an eastern chipmunk have all tested positive for the virus, McLean said.

Findings from a study conducted on human central nervous system cells suggest that the antiviral drug ribavirin may be an effective treatment for people suffering severely from West Nile encephalitis. Lipkin and a research team from the UCI and ICN Pharmaceuticals found that high doses of ribavirin inhibited West Nile virus replication and cytopathogenicity in human neural cells in vitro. Doses of the drug did not appear to cause any damage in cells not infected with West Nile virus indicating that treatment may produce few side effects in the central nervous system.

"To our knowledge this is the first drug to have specific activity against the West Nile virus," Lipkin said. "The results are encouraging and suggest that it may be possible to prevent deaths and illness from West Nile virus encephalitis." He cautioned that ribavirin has never been used on West Nile virus infections and has been known to produce some side effects, particularly anemia when used in high doses in other disease treatments. Therefore, physicians should monitor ribavarin treatments very closely.

Another mosquito-borne disease, dengue fever, is emerging as a major public health problem in south Texas and Florida, according to Cortez-Flores. "Although nearly eradicated in the 1960s, the Aedes aegypti mosquitoes that carry the disease are now present in abundant numbers in the Americas and the Caribbean and are present year round in the southernmost areas of Texas," he said. The increased disease incidence, combined with increased frequency of epidemic dengue cause by multiple virus serotypes, has increased the risk of epidemic dengue haemorrhagic fever, one of the leading causes of hospitalisation and death among children in Southeast Asia. "Although dengue fever is not endemic in the United States, imported cases in US residents returning from travel to endemic areas are diagnosed each year, and additional cases are probably undetected," Cortex-Flores reported. Other factors responsible for such increases include a greater than usual number of tropical storms and increasing urbanisation. "The mosquito is a highly domesticated urban species vector and is adapted to living with humans," Cortez-Flores noted.

Dengue fever is an acute viral illness with severe flu-like symptoms often accompanied by a rash on the feet or legs beginning three to four days after onset of fever. More severe forms are dengue haemorrhagic fever and dengue shock syndrome. The fatality rate for persons with untreated dengue haemorrhagic fever can be as high as 50%. Vascular collapse and hemoconcentration may require vigorous fluid replacement with a crystalloid solution such as lactated Ringer's, but over-hydration must be avoided.

Since 1993, Aventis Pasteur researchers have been developing an attenuated tetravalent dengue vaccine. T-cell assays suggest priming to all the dengue viruses among the tetravalent vaccine recipients. Clinical studies of various tetravalent dengue vaccines are in progress in Thailand.

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