Scientists develop simple, rapid test for bubonic plague

LONDON -- Scientists have developed a simple and reliable test to rapidly diagnose plague, a sometimes deadly disease that authorities fear could be used in a bioterror attack.

Experts say the new test, described this week in The Lancet medical journal, could save lives and help control the disease in the developing world -- and fill an important need in global bioterrorism preparedness and response.

Plague is caused by the bacterium Yersinia pestis and is chiefly a disease of rodents. However, it can spread to humans, mostly through flea bites. About 3,000 people get infected each year, primarily in Africa, the Americas and Asia.

Doctors usually diagnose the disease by looking at symptoms and confirm it by laboratory tests. There is no immediate diagnostic test.

There are three main forms of plague in humans: bubonic, septicemic and pneumonic.

After the bacteria get into a person through a flea bite, they migrate to the nearest lymph nodes, where they cause a painful swelling or bubo, from which bubonic plague takes its name.

Bubonic plague is not contagious. Most cases are noticed at this point and treated with antibiotics. Without treatment the chances of dying from plague are between 15 percent and 30 percent in the bubonic stage. With treatment, nearly everyone can be saved.

Sometimes the bacteria then invade the bloodstream, where they multiply and spread throughout the body. The disease is then called septicemic plague. It is very hard to treat and once infection has progressed this far, death can come within two to four days of the onset of symptoms.

If the bacteria get to the lungs, the disease is called pneumonic plague, which is almost always fatal.

The plague then becomes highly contagious, spread through coughing and sneezing.

It is the pneumonic form of plague that authorities fear could be used in a bioterror attack. Antibiotics must be given within 24 hours after the symptoms start.

Although the test could help in more rapid diagnosis during a bioterror crisis, those who most need it are doctors in rural parts of the developing world, where most natural plague cases occur and labs are far from many communities. Late diagnosis is the major cause of death and spread of the disease.

In the study, scientists from the Pasteur Institute in France and from the Ministry of Health in Madagascar developed a simple dipstick test that recognizes a substance given off uniquely by the plague bacteria.

The substance, called F1 antigen, is plentiful in the blood and bubo fluid of infected people.

The scientists used the dipsticks in all suspected plague cases during 2000-2001 in 26 pilot sites in Madagascar ranging from district hospitals to rural health centers in remote areas. About 700 dipstick tests were done.

After about 15 minutes, the test strip shows either two pink lines for a positive, or one pink line for a negative result.

The accuracy of the tests was determined by comparing the results with lab results on the same samples.

The researchers found the tests were as good as lab tests.

"A rapid diagnostic test for plague should not depend on electricity, sophisticated equipment ... and it should be easily and rapidly performed at the bedside. This new rapid test produced reliable results within 15 minutes at remote facilities and seems to admirably fit this profile," concluded U.S. scientists who critiqued the study for The Lancet.

May Chu, one of the authors of the critique, said the test was very impressive for bubonic plague but that its usefulness for detecting pneumonic plague in a bioterror attack is not so clear.

About 80 percent of the people in the study had bubonic plague. Some had septicemic and a few had pneumonic plague. Cases of the latter two types of plague were more rare because people that sick are usually too ill to travel to a doctor.

Although the F1 antigen is present in phlegm, it is harder to detect there than in blood or pus, said Chu, chief of the diagnostic reference section of the division of vector-borne infectious diseases at the U.S. Centers for Disease Control and Prevention.

Chu, who was not involved in the research, said the test would need to be proven in more cases of pneumonic plague, and perhaps tweaked to detect other things, before it could be useful in a bioterror crisis.

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On the Net

Medline Plus Health Information on Plague:

www.nlm.nih.gov/medlineplus/plague.html