|Dr. Thomas Wellems leads NIAID’s Laboratory of Malaria and Vector Research. He and colleagues created the first rapid diagnostic test for malaria.
The World Health Organization recently announced that it had approved 15 additional rapid diagnostic tests (RDTs) for malaria, bringing
the total number that meet its performance criteria to 37. WHO called rapid tests a major breakthrough in malaria control, as they enable health workers to diagnose malaria accurately
in people living in remote rural areas, where most malaria cases occur.
Twenty-five years ago, the concept of a malaria
RDT was considered scientifically questionable.
Many experts doubted that RDTs could be as effective as using a microscope to visualize
malaria parasites in blood smears. However, a discovery made in NIAID laboratories helped change this perception.
During the mid-1980s, NIAID scientists Dr. Russell Howard and Dr. Thomas Wellems identified
and characterized a unique protein called Pf HRP-2, found in abundance in the deadliest malaria parasite, Plasmodium falciparum. They cloned and sequenced the gene that encodes Pf HRP-2 and confirmed that the gene was present in P. falciparum samples from around the world. The researchers then proposed a diagnostic test based on the Pf HRP-2 protein.
“Skepticism about the costs and practicality of RDTs was widespread,” says Wellems, who leads the NIAID Laboratory of Malaria and Vector Research, “but to us it didn’t seem far-fetched to think that new detection technologies could support tests that were cheap, gave immediate
results and provided sensitivities as good as standard microscopy.”
In 1986, Howard and Wellems filed a U.S. patent
claiming uses of cloned DNA from P. falciparum that encodes an antigenic, or immune-stimulating, portion of the Pf HRP-2 protein; the patent was approved in 1992. Joseph Perrone
of medical technology firm Becton, Dickinson
and Co. initiated discussions with Wellems in 1989 about collaborating on the development
of a rapid malaria test. BD ultimately licensed NIAID’s invention and a team of BD scientists, including S. Melissa Maret and Hans Feindt, used Pf HRP-2 to create ParaSight F, the world’s first malaria RDT.
ParaSight F hit the market in 1995 after successful
clinical testing in several malaria-endemic countries. The test was conducted by placing a strip of paper containing Pf HRP-2 antibody in a drop of blood, then applying to the reaction site a detection reagent containing red dye, followed by a wash reagent to remove any unbound reagents from the paper. The dye left a visible red band if the sample was positive for P. falciparum infection.
ParaSight F proved that it was possible to make a simple and accurate malaria diagnostic that didn’t require a microscope, electricity or lengthy training to perform. It seemed like the ideal tool for rural, malaria-endemic settings, where a lack of infrastructure forced health workers to treat patients based on presumptive malaria diagnoses.
However, the high cost of ParaSight F compared with the low cost of first-line malaria drugs like chloroquine hampered widespread adoption of the test. For cash-strapped malaria control programs,
it was cheaper to treat suspected malaria
cases than to obtain an accurate diagnosis. ParaSight F was not a commercial success and BD took it off the market in 2000.
Today, more than a decade after ParaSight F provided the prototype, malaria treatment
requires new and more expensive drugs because, in most settings, P. falciparum has become chloroquine-resistant. Because these new drugs must be used only when needed, it is more important than ever to make accurate field diagnoses of the illness. WHO estimates that less than one-third of fevers in malaria-endemic areas are actually caused by malaria.
“Artemisin-based combination therapies are now used against chloroquine-resistant malaria, but they are much more expensive than chloroquine, so subsidies to support their availability and diagnostic tests to assure their appropriate use are vital,” adds Wellems.
Today, companies from around the world use Pf HRP-2 detection to make malaria diagnostics
similar to ParaSight F. Competition among these manufacturers has led to tests with longer
shelf lives, better temperature tolerance and lower costs.
WHO estimates that 45 million malaria RDTs will be purchased worldwide this year. While ParaSight F was just a few years ahead of its time, the discoveries of NIAID researchers live on in many of today’s malaria RDTs, helping to accurately diagnose a disease that afflicts millions
of people each year.