As U.S. health officials treat an Indian woman who entered the country with drug-resistant tuberculosis, scientists at Texas A&M Health Science Center are trying to develop faster and more accurate ways to diagnose the infectious disease.
The timely detection of TB remains one of the greatest difficulties in dealing with the condition. The main symptoms, like long-lasting cough and fever, are common to other illnesses. The bacteria are also slow-growing. That’s why patients with TB often aren’t diagnosed until they’ve had the infection for many months, risking infecting others. The increase in drug-resistant versions of the bug adds to the urgency in detecting TB more quickly.
Researchers, such as Jeff Cirillo and colleagues at the Texas A&M facility in Bryan, Texas, are working on faster, cheaper diagnosis alternatives. They have developed a test that signals when enzymes produced only by TB bacteria are present, whittling the process to just 10 minutes from several days. They now are studying how it could be used to determine drug-resistance as well.
“The challenge is absolutely the diagnosis,” says Andrew Steenhoff, a pediatrics professor at the Children’s Hospital of Philadelphia and TB specialist.
Tuberculosis can affect any organ in the body, but the most common—and most important, from a public-health perspective—is the lungs. TB isn’t as contagious as many other infectious diseases, like measles, but it is a particular concern for children and people with weakened immune systems. The bacteria are transmitted through the air, and infection occurs after spending significant time in a confined space. Transmission in public places, including airplanes, is unlikely but possible, Dr. Steenhoff says.
One-third of the world’s population has tuberculosis, though many carry it without displaying any symptoms. Between 1.5 and 2 million people a year die from it, the World Health Organization says.
Latently infected people cannot pass the disease on to others unless the tuberculosis, which can lie dormant in people for years, flares into acute disease, sometimes during a period of weakened immunity.
In recent years, strains of bacteria that are resistant to both the first and second line of conventional medications have emerged, raising a public-health alarm world-wide.
This month, a woman from India who had arrived at Chicago’s O’Hare Airport in April was found to have extensively drug-resistant TB after feeling ill and seeking treatment in May in McHenry County, Ill, according to a spokeswoman for the county health department. The woman, whose name hasn’t been released for reasons of patient confidentiality, was admitted to the hospital at the National Institutes of Health in Bethesda, Md. She is likely to remain there for weeks while doctors try to figure out which drugs work on her strain of TB, according to Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and a member of the infectious disease team treating her.
Meanwhile, the Centers for Disease Control and Prevention and state and local authorities are trying to trace all those she had contact with since her arrival in the U.S. to make sure they haven’t contracted the disease, says Philip LoBue, director of the tuberculosis-elimination division at the CDC.
The most accurate way of diagnosing TB today is to take a sample of mucus from the patient and grow the organism in culture tubes or plates. This method is usually positive in two to three weeks, but it can take up to eight weeks to say the result is definitely negative.
Another diagnostic technique, looking directly at the sputum after it’s been stained through a microscope, may miss half of all cases, according to Dr. LoBue. This technique is highly dependent on how many bugs are in the sample; bacteria could be missed if there aren’t many. X-ray also may be used for diagnosis, though facilities aren’t widely available around the world, experts say.
In the U.S., doctors perform chest X-rays on people with respiratory symptoms or a positive TB skin or blood test. But it isn’t possible to definitely determine whether an abnormality on a chest X-ray is due to TB and other respiratory infections or other lung diseases, Dr. LoBue says. The main advancement in TB diagnosis in recent years is in molecular testing, which identifies the bacteria through its DNA.
A device, called GeneXpert in the U.S. and endorsed by the World Health Organization, churns out a result within two hours. But experts say a need for alternative diagnostic methods remains.
The team at Texas A&M has been developing another approach using a compound that binds specifically to enzymes produced by TB bacteria. If TB bacteria are present, the combination, placed in a tube or cup, will light up and can be detected after 10 minutes using a battery-operated, portable light reader.
The main challenge in the research was configuring a compound that would bind to the TB enzyme but not to other enzymes, Dr. Cirillo says. The team spent about six years analyzing the structure of the TB enzyme.
One technique they used was crystallography, where they created a solid form of the enzyme, took an X-ray of it and scrutinized the position of every atom. The development of the light reader took an additional two years. They first published some of this work in 2010 in the Proceedings of the National Academy of Sciences.
The reader device, which is expected to cost $500, is being tested in World Health Organization-sponsored field trials in Africa. Earlier work was funded by the Wellcome Trust in the U.K., and the Bill and Melinda Gates Foundation. Each sample test is expected to cost $2 or less. The scientists hope the technique will be cost-effective and can be used widely across the globe.
Dr. Cirillo’s team is studying how the same technology could be used to determine which drugs the TB might be resistant to based on a simple rationale: If the bacteria die in the presence of a drug, they stop making the enzyme and the light ceases. They published early work demonstrating the concept in 2014 in the German journal Angewandte Chemie.
If subsequent research supports the accuracy of the drug-resistance test, clinicians could have results in two hours. Doctors today need six weeks to grow the bacteria and determine which drugs the patient requires.
“We’re always looking for better, simpler, cheaper and more rapid diagnostics,” says Dr. Fauci of the National Institute of Allergy and Infectious Diseases, who wasn’t involved in the work.
Source: The Wall Street Journal