BioWorld International Correspondent

LONDON - Public health physicians now have a simple, accurate and rapid test to detect cases of plague, giving them a new tool to help control the disease. The test, said the researchers who developed it, could also be used in the event of a bioterrorist attack involving Yersinia pestis, the bacillus that causes the disease.

Plague, while still a terrifying disease for those who encounter it, is not the global killer it once was. In 1665, an estimated 100,000 people died of plague in London alone, and many more throughout the rest of Europe. Diarist Samuel Pepys wrote that by September of that year the grass grew "all up and down" the famous thoroughfare known as Whitehall because so many people had fled the city.

Although plague is still endemic in many countries in Africa, the Americas and Asia, in 1999, 14 countries reported just 2,603 cases to the World Health Organization, including 212 deaths.

Plague nevertheless remains a huge burden for those countries affected. Once a case is suspected, all contacts of the case, including family members and possibly every member of the village, should be treated with antibiotics. Local homes also have to be sprayed with insecticide to kill the rat fleas that transmit the disease.

That is expensive, so local doctors often delay acting until the infection has been confirmed by bacteriological tests, which can take more than a week in remote areas. In the case of true infection, such a delay can be fatal for the patient, and a large outbreak may result.

Now the new test makes it possible to diagnose the infection in just 15 minutes. Suzanne Chanteau, former head of the Plague Programme at the Institut Pasteur de Madagascar in Antananarivo, Madagascar, who developed the test, told BioWorld International, "Although it is obviously crucial for the patient to have a rapid diagnosis, the most important feature of this test is its ability to have an impact on public health by preventing large outbreaks of plague, and so diminishing the morbidity and mortality associated with these."

The test can also be used to prevent the first human cases of plague when an outbreak is imminent. Chanteau said, "This is a disease of rodents, spread by rat fleas. Death of rats precedes the first human cases of plague by about 10 to 15 days. When villagers start to see dead rats, they can now ask the health worker to test an animal by simply puncturing its body with a syringe. If the rats are positive, spraying homes with insecticide can kill the plague vectors - the fleas - immediately, even before the first human case is seen."

Chanteau and her colleagues report their evaluation of the test under field conditions in Madagascar in a paper in the Jan. 18, 2003, The Lancet titled "Development and testing of a rapid diagnostic test for bubonic and pneumonic plague."

When a flea infected with Yersinia pestis bites a human, the bacilli collect in a lymph node close to the bite. The node becomes enlarged, inflamed, very painful and eventually fills with pus. That is called a buboe and the person has bubonic plague.

Without antibiotic treatment, the infection spreads, involving the lungs. This is known as pneumonic plague, which is fatal, unless treated promptly with antibiotics. It is also highly infectious, so that those caring for the patient also develop pneumonic plague.

The test developed by Chanteau can be carried out on either a sample of sputum (in the case of suspected pneumonic plague) or on a sample of liquid from a buboe. It detects the F1 antigen of the bacillus. The test employs filter paper onto which is sprayed colloidal gold particles that have been conjugated to monoclonal antibodies that bind to F1. There are two lines of "capture antibodies." If the test is positive, two red lines appear (a control line and the line showing plague antibodies are present). If it is negative, only one red line (the control line) appears.

Investigations by Chanteau and her colleagues have shown that the test detected many different strains of Y. pestis from around the world. Their evaluation demonstrated that the sensitivity and specificity of the test were both 100 percent, and that the test detected 41.6 percent and 31 percent more positive clinical specimens than did more traditional bacteriological methods or ELISA tests, respectively.

Chanteau said, "We advise doctors to treat patients whose test is negative if they suspect clinically that they may have plague because the test can give a false negative result if the needle has failed to enter the center of the buboe." She hopes that further training will reduce this problem.

The test, as part of a kit containing everything needed to use it, is available in clinics in areas of Madagascar where plague is endemic. Chanteau said the challenge now is for international agencies such as the World Health Organization to find the funding needed to distribute it to all countries where plague occurs.