USAid grant funds UC Davis partnership to improve TB diagnosis in Pakistan
Grant funds basic research, technology transfer
UC Davis and Pakistani researchers have received a grant from the U.S. Agency for International Development (USAID) to develop a better method for diagnosing tuberculosis that employs novel technology and is highly effective, affordable and portable, which will allow it to be deployed in remote, rural areas of the world.
In developing their new diagnostic methods, the researchers will use the latest technology that allows multiple tests to be performed from a single sample, and for the processing of hundreds of samples a day. The $400,000 award will support the development of a new, more specific TB test that can be performed using small blood samples from hundreds to thousands of individuals at once. The two-year grant will also support the transfer of this new technology to Pakistan, which has the sixth-highest incidence of TB in the world.
“If we are going to significantly slow the spread of TB in places like Pakistan, we need to be able to detect an infection at its earliest stages and identify those individuals who are infected but do not yet show signs of active disease,” said Paul Luciw, a microbiologist with the UC Davis Health System and Center for Comparative Medicine.
Luciw, who is also a professor in the Department of Pathology and Laboratory Medicine, will serve as the principal investigator in the United States. Azra Khanum, professor and chair of the Department of Biochemistry at the University of Arid Agriculture in Rawalpindi, will serve as the principal investigator in Pakistan.
— Imran Khan, associate director of the Department of Pathology and Laboratory Medicine's Clinical Proteomics Core and the Center for Comparative Medicine
The UC Davis team also includes Imran Khan, associate director of the Department of Pathology and Laboratory Medicine's Clinical Proteomics Core and the Center for Comparative Medicine, who is originally from Pakistan. According to Khan, the key to combating TB is a more efficient, cost-effective diagnostic test for TB.
“The current tests are inefficient, complicated and relatively expensive to perform in developing countries,” Khan said. The new multiplex test, he added, will be better, faster and, most likely, cheaper.
Luciw, Khan and their collaborators will be working to perfect a method for detecting multiple antibodies produced by the immune systems of exposed individuals in response to the bacterium, Mycobacterium tuberculosis, which causes TB.
“The current tests only detect a single antibody at a time,” Khan said. The multiplex test, he said, could allow researchers to simultaneously test a dozen or more antibodies in a single blood sample from a patient. “This would give us a complete range of antibodies in an infected individual and it will be specific enough that results will not be confounded by the responses to TB vaccine or other Mycobacterium species.”
The new test builds on successful diagnostic tests created by Luciw, Khan and other Center for Comparative Medicine researchers for the detection of various diseases, including TB, in non-human primates. This work was done in part at the California National Primate Research Center, a federally funded biomedical research facility affiliated with UC Davis.
The human TB test Luciw and Khan are developing uses xMAP technology created by Luminex, an Austin, Texas-based company. The technology utilizes sets of microspheres, invisible to the naked eye, coated with antigens specific to antibodies produced by patients in response to M. tuberculosis. Serum or plasma from a blood sample is mixed with a solution containing the bead sets. The sample is then placed in an instrument that uses lasers to identify the beads in which positive antibody/antigen reactions have taken place. The next-generation instrument from Luminex is expected to cost one-quarter of today's machine and, depending on the use of additional robotics, allow the simultaneous, bench-top analysis of thousands of samples per day.
Tuberculosis is an infectious disease, usually of the lungs, that is spread from person to person through the air when infected individuals cough, sneeze or talk. A person usually has to be exposed to an infected individual for some time in order to also become infected. For this reason, friends and family members of individuals with confirmed infections should be screened for TB.
In most cases, M. tuberculosis infection is kept in check by the body's immune system. In about 10 percent of cases, however, the infection breaks out into active TB disease, though it may take years for this to happen. In 2003, the World Health Organization estimated that less than half of the nearly 9 million new cases of TB were diagnosed using laboratory tests.
Currently, Pakistan contributes about 44 percent of the tuberculosis burden in the eastern Mediterranean region. The new approach could eventually help health-care workers there and throughout the developing world to better screen people who have come in contact with infected individuals.
“Ultimately, we hope to be able to survey populations, identify hotspots of infection and treat people who are infected before they can spread the disease,” Khan said.