Striving to keep pace

Increased international travel and growing human contact with creatures of forests, swamps and jungles create more opportunities for new and potentially lethal infections to sweep the globe -- and contaminate our blood supply.

West Nile virus, SARS and monkeypox have all surfaced recently in the United States, and at least one, West Nile, can be spread through blood transfusions. But simply identifying such diseases doesn’t protect the approximately 15 million units of blood collected each year. Health officials must determine whether emerging infections can be contracted from transfusions and whether the threat warrants developing effective screening tests. Both processes can be complex, time-consuming and expensive.

“The hope and expectation is to do it quickly, but sometimes the science doesn’t permit it that quickly,” said Dr. Peter L. Page, senior medical officer for the American Red Cross in Washington, D.C.

West Nile virus, for example, was first identified in this country four years ago in New York. It wasn’t until last fall, however, that health officials discovered that several organ-transplant recipients had been infected by contaminated blood given by transfusion to organ donors. In November, the Food and Drug Administration urged test manufacturers to develop blood tests that could directly detect the mosquito-borne virus in time for the 2003 mosquito season. By July 1, two companies had met the challenge.

Public health officials consider that pace extraordinary, and the test is just now being used by blood donation centers nationwide.

Things moved more quickly than usual for two reasons. The West Nile virus had been genetically sequenced, so scientists had the virus’ entire blueprint in hand. And both companies had experience with polymerase chain-reaction technology, which makes millions of copies of tiny gene fragments so they’re easier to use in research.

Roche Molecular Diagnostics in Pleasanton, Calif., which began clinical trials on June 16, said its West Nile test also detects viruses for Japanese encephalitis, St. Louis encephalitis and Murray Valley encephalitis. Clinical trials of the other West Nile test, developed by Chiron Corp. of Emeryville, Calif., and Gen-Probe Inc. of San Diego, began June 18.

“In November, there was no test available. By July 1, it was up and running. That’s spectacular,” said Dr. Louis Katz, president of America’s Blood Centers, which represents 76 independent community blood centers nationwide. “But the reason we were able to respond to West Nile isn’t just because we’re good guys and we’re smart. It’s because the tools had matured.”

Decisions about whether to screen for a particular disease are made by the FDA, based on disease surveillance from the federal Centers for Disease Control and Prevention, with input from the blood-collection industry. The CDC has been busy in recent years monitoring U.S. outbreaks of anthrax, West Nile, SARS and monkeypox.

From the time the first cases are reported, CDC epidemiologists scramble to determine how -- and how easily -- they’re transmitted, said Dr. Matt Kuehnert, CDC’s assistant director for blood safety. They also must determine whether they can be spread by someone who is infected but has no symptoms, or hasn’t yet developed antibodies. With West Nile, 80% of infected people have no symptoms and could unwittingly donate contaminated blood.

Katz says the public health community is closely watching diseases transmitted to people from insects and animals in the developing world, because those could have an impact here. “Who knows what the next thing is that’s going to come out of south China, central Africa or the Amazon Basin?”

At this point, donated blood is screened for HIV, hepatitis B, hepatitis C and syphilis, as well as HTLV-1, which causes leukemia and lymphoma, and the related HTLV-2 virus. West Nile recently joined the list. But with many diseases, finding a test that’s specific enough to catch true cases and sensitive enough not to return too many false positives frequently remains elusive.

Antibody tests also have a built-in problem: Often, the body doesn’t make antibodies for days to weeks after infection, so many cases can be missed. They are generally considered harder to develop, because they need to be specific enough to identify only the disease in question, but also sensitive enough to pick up most cases.

Nucleic acid tests, such as the West Nile test, go after tinier targets, so they are more specific and more sensitive early in the course of infection.

In addition, officials must carefully balance the number of cases the screening will prevent against the amount of donated blood that will be lost due to false positives.

Then there’s the added expense. Test kit manufacturers pass their costs on to hospitals and insurance companies. In the case of West Nile testing, the American Red Cross estimates it’s adding $4.40 for every unit of blood. With agencies such as Medicare and Medicaid slow to increase reimbursements, hospitals often complain they’re being squeezed for a product that’s essential to at least a quarter of their procedures, Katz said.

While on the lookout for emerging diseases, epidemiologists, federal regulators and the blood-collection industry also worry about detecting established diseases with the potential to cause severe illness and death, including:

* Chagas disease. Caused by a parasite rampant in Central and South America and spread most often by bites, Chagas causes fever, weakness and potentially fatal heart or brain infections. The FDA doesn’t consider existing Chagas tests being used in places such as Brazil good enough.

* Babesiosis. An infection of red blood cells caused by a parasite, it’s spread by the same deer ticks that spread Lyme disease. It destroys blood cells and produces fever, muscle aches and sometimes anemia. In the last two decades, about 30 cases have been spread through contaminated blood.

* Malaria. Caused by four species of the Plasmodium parasite and spread mostly by mosquito bites, malaria takes hold in the liver, then invades red blood cells, causing them to burst. Infection creates chills, high fevers and eventually may produce anemia and an enlarged spleen. With no good test on the horizon, blood banks rely on donor health histories to screen out possibly infected people.

* Variant Creutzfeldt-Jakob disease. This human form of “mad cow” disease is a degenerative brain illness that typically starts with psychiatric symptoms that don’t appear until years after contaminated beef is eaten. Death results within months to a year after symptoms appear. It’s thought to be spread by prions, which are abnormal proteins, but scientists don’t yet know if prions are present in blood.