/ 18 April 2005

New hope for Marburg virus drug

As the deadly outbreak of Marburg virus continues to claim lives in Angola, researchers have worked out how the closely related Ebola virus invades human cells, according to a report on the Science and Development Network website.

The findings could lead to a treatment for the diseases, which each kill up to 90% of those infected.

The researchers, led by James Cunningham of Harvard Medical School in the United States, showed that a human enzyme helps Ebola virus fuse with the cells of people it infects.

The enzyme, called cathepsin B, digests a protein the virus uses to attach to a human cell. This destabilises the cell’s outer membrane, allowing the killer virus to fuse with it.

In a laboratory experiment, the team treated kidney cells so that the enzyme would not function, and then exposed the cells to the virus. They found that this reduced the virus’s ability to multiply, and suggest the approach could lead to a drug against the virus.

Cunningham told SciDev.Net that his team is now testing whether the related Marburg virus uses the same strategy to invade human cells. Angola is currently suffering from the worst outbreak to date of the Marburg virus, with 215 dead. The vast majority of casualties were reported in the past month.

If blocking cathepsin B works against Ebola, it might also work against the Marburg virus, says Aman Javad, who studies Marburg at the United States Army Medical Research Institute of Infectious Diseases.

Javad points out that cathepsin enzymes are important for the body’s immune system, so blocking them could cause severe side effects. But he adds that because people infected with Ebola or Marburg virus usually only need treatment for 10 to 14 days, this could make any side effects acceptable.

The results were published online by the journal Science.

Symptoms

Both Ebola and Marburg viruses cause a fever, often accompanied by severe internal bleeding and shock. There is no vaccine or medical treatment and up to 80% of infected people die within three to seven days. Three-quarters of those affected are children under five.

Diagnosing an infection with the Marburg virus can be difficult, as its initial symptoms are similar to those of malaria or tuberculosis. They include diarrhoea, stomach pains, nausea, vomiting and severe chest pains. Moreover, before triggering any symptoms, the virus incubates for five to 10 days.

The World Health Organisation (WHO) believes the current outbreak began in October 2004 in Angola’s Uige province. Researchers in Uige and the Angolan capital, Luanda, are trying to develop faster methods of diagnosis so that infected people can be quarantined to stop the virus spreading.

Close contact with the bodily fluids of infected people, in hospitals or at burials, has in the past increased the risk of infection, according to the WHO. In addition, patients often have respiratory problems and can spread the virus by coughing and sneezing.

Health workers have been advised to wear masks and gloves, but workers in Luanda say there is a shortage of equipment.

Drugs and vaccines

A few research groups around the world are working on drugs and vaccines to fight the virus. One group in the United States showed last year that inactive virus particles injected into guinea pigs protected them from infection.

In addition, high-speed vaccines gave macaque monkeys protection from closely related Ebola infections only four weeks after a single jab, although previous vaccines took six months and multiple boosters to confer immunity, according to reports in Nature. However, the cost of vaccines is an enormous obstacle.

The virus was first identified in 1967 in laboratory workers in two German towns, Marburg and Frankfurt, and in Belgrade, former Yugoslavia. The outbreak was linked to monkeys imported from Uganda. People can also become infected by handling infected chimpanzees, gorillas and forest antelopes, as well as through contact with other people who carry the virus.

The WHO and the United Nations Children’s Fund are working with Angola’s ministry of health to formulate a national plan of action to control the current outbreak.

Ebola

An outbreak of the Ebola virus last year in southern Sudan infected at least 15 people, killing four of them. The WHO traced the Sudan outbreak to the town of Yambio near the Kenyan border. There have been eight epidemics in Gabon and the Congo since 1994, affecting at least 451 people and killing 351. Uganda was also hit in 2000 by an outbreak that killed 224 of 425 affected people.

Meanwhile, people in equatorial Africa could be at risk of catching the deadly Ebola virus from dogs, according to research that suggests the animals could carry the virus without showing signs of disease.

Research team leader Eric Leroy, of the International Centre for Medical Research in Franceville, Gabon, says his team decided to see whether dogs carried the virus after seeing them eat the carcasses of infected animals.

The team took blood samples from 300 dogs in three areas in French-speaking Gabon. Some were villages in the 2001 or 2002 epidemic zones, as well as Mekambo City, where human cases were also reported, but they also included two major towns, Libreville and Port Gentil, more than 600km away from the epidemic area.

The team found evidence that the dogs had been in contact with the Ebola virus in all the areas. To show this, they measured the amount of Ebola virus antibodies — proteins produced by the immune system when it encounters bacteria or viruses — present in the dogs’ blood.

”What is important is that the presence of Ebola virus antibodies in the dogs’ blood increases as you approach the zone of the epidemic,” says Leroy. This means that dogs could be used as an indicator both of Ebola virus activity in a region and of the risk of human infection there.

He add that the discovery of dogs showing signs of contact with the Ebola virus in areas that have not been declared to be affected by the disease suggests that the dogs might live ”in close contact” with the virus’s reservoir — the unknown animal species that is the source of continuing outbreaks.

Satellite mapping

Ebola and Marburg researchers are aided by an unlikely source. At the beginning of last year, satellites provided by the European Space Agency assisted Gabonese researchers to study outbreaks of the elusive Ebola outbreaks, which often occur in inaccessible areas.

Researchers hope that satellite mapping of changes in vegetation and other factors will identify a climatic trigger for the disease.

Gabon is a leading site for research into haemorrhagic fevers such as Ebola and Marburg. Scientists from Gabon, working with colleagues from Senegal, France, Germany and The Netherlands worked for four years to develop a new test that can diagnose the deadly Ebola virus earlier than before.

The test works by detecting viral genes in patients’ blood. The virus, like Marburg, has been difficult to diagnose in its initial stages, when patients show only common flu-like symptoms.

But humans are not the only primates suffering from Ebola. Reports in Nature say that chimpanzees and gorillas in West Africa are being severely threatened by both hunting and the Ebola virus. The bush-meat trade is decimating ape populations near towns, while Ebola is killing almost every animal in remote areas.

Both species in Gabon have diminished by about half over the past 20 years.

”Without aggressive investments in law enforcement, protected area management and Ebola prevention, the next decades will see our closest relatives pushed to the brink of extinction,” the researchers warn. — SciDev.Net