NIAID outlines agenda for TB research

July 2008

The National Institute of Allergy and Infectious Diseases recently outlined research strategies necessary to combat the increased incidence of multidrug-resistant and extensively drug-resistant tuberculosis strains.

XDR-TB is defined as strains resistant to isoniazid, rifampin, any fluoroquinolone and at least one second-line injectable drug, including amikacin, kanamycin or capreomycin. Though the existence of such strains is not new, the NIAID researchers said these strains require response to prevent further spread. Such responses must begin with clearly outlined research goals.

“This is an NIAID research agenda,” Christine Sizemore, PhD, chief of the tuberculosis, leprosy and other microbacterial diseases section in the NIAID division of microbiology and infectious diseases, told Infectious Disease News. “Our goal is to create a foundation of knowledge for new health care interventions to improve health of people globally. We produce research agendas that, in turn, produce the information necessary to change treatment guides. The way this research agenda differs from other research agendas we have issued in the past is that it is specifically geared toward drug-resistant TB.”

The research agenda was published in The Journal of Infectious Diseases.

The NIAID research agenda includes several key strategies that experts say should be the focus of research in the coming years. They are as follows:

• Develop and test reliable technologies to rapidly diagnose TB and identify drug resistance.
• Define the most effective use of existing second-line anti-TB therapies and other antimicrobials available to treat drug-resistant TB and develop new chemotherapeutic agents, particularly against MDR-TB and XDR-TB.
• Understand the basic biology and immunology of host and pathogen that underlie the development and spread of MDR-TB.
• Understand the epidemiology of Mycobacterium tuberculosis, including host and strain characteristics that contribute to the development and spread of MDR-TB.
• Determine the influence of the overall immune status of the infected individual, other host factors and HIV coinfection on drug resistance and the outcome of TB chemotherapy.
• Develop effective chemopreventive and immunopreventive strategies for drug-susceptible and drug-resistant TB.

Speed is the key to diagnostics, according to Sizemore and her colleagues. Not only must clinicians be able to rapidly diagnose the strain and drug-resistance profile to appropriately treat the patient, but researchers also must improve the technology of TB diagnosis. Partnerships among biotechnology companies and researchers must be streamlined to speed up the progression from the lab to the market. NIAID encouraged researchers to explore tools used for diagnosing other infectious diseases and apply them to TB diagnosis.

Therapeutic Strategies

Current therapies need to be re-examined, and new ones need to be developed, according to the researchers. The institute is focusing on the physiology of TB and its interaction with the host. Also, antibiotics approved for the treatment of other diseases should be tested for efficacy against TB.

The researchers urged biologists to explore how host factors contribute to TB drug resistance.

Data regarding transmission and drug resistance of TB in different parts of the world are currently incomplete. Further epidemiological studies need to be conducted to grasp the severity and effect of the disease.

Data on TB patients coinfected with HIV are also limited. “Many basic facts regarding drug interactions, toxicities, achievable drug levels and drug metabolism remain to be determined,” Sizemore and her colleagues.

The capability of the current TB vaccine is limited. The development of an effective vaccine against all strains of TB could potentially have a larger effect on controlling the disease than any other area of research, according to the researchers.

“It is important to note that TB exists in the United States,” Sizemore said. “Depending on the part of the country, it is likely that physicians may encounter a TB patient. Physicians should be cognizant of the opportunities that are out there for understanding how best to deal with those patients. They should also be cognizant of where to refer patients in case they do not know how to treat them.”

Sizemore said that the NIAID document does not contain specific recommendations. “At the moment, this document will not affect clinical practice,” she said. “This is a research agenda and not a clinical care agenda. However, it is important to remain up to date on the most recent treatment recommendations in the TB arena.”

Although certain areas of research are limited, the researchers stressed the urgency of the TB threat and the importance of understanding the disease.

“TB is not gone. It is a reality and a big problem in the world. Knowledge of TB is a key component to any infectious disease portfolio,” said Sizemore.

For more information:

• Fauci A, Alston B, Barry C, et al. Multidrug-resistant and extensively drug-resistant tuberculosis: The National Institute of Allergy and Infectious Diseases research agenda and recommendations for priority research. J Infect Dis. 2008;19:1493-1498.