FDA qualifies biomarker in controlled malaria infection trials
According to a news release from the University of Washington School of Medicine, a molecular test, proven more effective than thick blood smears at detecting malaria parasites earlier in an infection, has now received FDA qualification for certain types of clinical trials. This move, one of the first of its kind for a malaria biomarker, is important for efforts to develop vaccines and better drugs against the tropical disease.
The FDA’s Biomarker Qualification program listed the context in which the biomarker can serve as a monitor. Testing for the biomarker is now okayed for human challenge trials that involve controlled malaria infections and that are conducted in geographical locations where the parasite is uncommon.
In such trials, healthy volunteers between the ages of 18 to 50 receive sporozoites of Plasmodium falciparum. Sporozoites are the life-stage of the malaria parasite transmitted during mosquito bites.
The biomarker alerts researchers when to start anti-malarial treatment. The test can usually spot the subtle signs of a blood infection shortly after it starts, often before any symptoms appear.
“We can use this test to find malaria parasites in someone, even when the parasites are present in such small numbers that they are just a drop in the bucket,” said Dr. Sean Murphy, associate professor of laboratory medicine and of microbiology at the University of Washington School of Medicine.
Murphy, who is also with the Seattle Malaria Clinical Trials Center at the Fred Hutch Cancer Research Center, led the multi-institutional team that developed and assessed the new biomarker.
The results supporting the biomarker qualification of Plasmodium 18S rRNA are reported in the American Journal of Tropical Medicine and Hygiene.
“The older test to diagnose malaria in tropical countries and in travelers has been around for more than 100 years,” Murphy said. The need for a more sensitive test has become more pressing due to the rising number of clinical trials for malaria prevention and treatment.
“There are more potential drug therapies and vaccines in the pipeline than ever before,” Murphy said.
In such trials, for example, volunteer participants might receive an experimental drug or vaccine. After a few days, months or even a year later, they are purposely infected with the parasite. The researchers then check to see if the treatment prevented or stopped the infection.
Murphy explained how the new biomarker spots a malaria infection: The parasite, like almost all organisms, churns out RNA to copy instructions from its DNA code. The most abundant RNAs produced are ribosomal RNAs. These help make proteins, the workhorses of living cells. His team designed a molecular test (known formally as a reverse transcription polymerase chain reaction) that can both detect and amplify the parasites’ ribosomal RNA in a human blood sample. With this test, researchers can diagnose infections three to five days sooner than with the thick blood smear.
Murphy said that he and his collaborators are largely testing vaccines and drugs intended to block the parasites in the liver.
An advantage for participants and researchers is the elimination of the so-called “hotel phase” of malaria clinical trials, in which participants are housed in individual hotel rooms while they are most likely to have symptoms. In such studies, researchers are on hand 24/7 with lab equipment to do blood smears twice a day, or in the middle of the night if a participant woke up with a fever. The researchers are also nearby to offer immediate treatment for symptoms.
These small-scale challenge studies with local participants enable researchers to answer questions that would take much longer in a field study in the tropics. For instance: Should we give a bigger dose? Does the dose wear out too quickly? What type of dosing regimen works better?
By achieving the FDA biomarker qualification, Murphy said that they have not just empowered the malaria teams in Seattle, but also other groups to use the now-qualified biomarker to accelerate their own clinical trial submissions to the FDA.
