Amit P Shah
Mapping TB resistance (J Exp Med
2006; 12: 2578-2579)
Almost two-thirds of the global population is infected with M.
tuberculosis, yet the disease only manifests in
about 10% of infected individuals. To find genetic
variants controlling susceptibility to infection, a study was done in Cape
Town, South Africa, where TB is highly endemic like
in India. Although most subjects were likely to have been exposed to M.
tuberculosis, about 40% did not show delayed type
hypersensitivity (DTH) in a skin antigen test. The
researchers have identified one locus (6-Mbp
chromosome region, 11p14) that determines whether an individual will
respond to the TB skin test and a second (2.9-Mbp
5p15) that controls the extent of that response. The
results suggest that one major genetic locus controls
innate resistance to the pathogen in humans.
Comments This important finding may unveil cellular
mechanisms that might one day be manipulated to prevent TB—an
important goal given the recent rise in drug-resistant strains.
Also, these genetic factors
might contribute to whether an infected individual keeps the
bacterium dormant or develops the disease.
Faster detection of TB may be on the
horizon (Am J Resp Crit Care Med 2009; 180: 666-673)
Diagnosis of tuberculosis involves a long time period and in about half of
all people with active TB, the disease-causing bacterium cannot be
identified using sputum tests. European researchers have developed a new
test – M. tuberculosis specific enzyme linked
immunospot (ELISpot) assay - that can rapidly identify active tuberculosis
in people who have had negative sputum tests. In a study including 347
people, ELISpot results were positive in 65/71 cases (91.5 %) with active
pulmonary TB. A negative result almost excludes active TB.
Comments: The rapid diagnosis of pulmonary
tuberculosis is difficult when acid fast bacilli cannot be detected
in sputum smears. An ELISpot test detects
active TB by comparing the frequencies of TB-specific T-lymphocytes in the
blood with those in the lung, with results in a day. This can facilitate
Sputum Mycobacterium tuberculosis
mRNA as a marker of bacteriologic clearance in response to
anti-tuberculosis therapy (J Clin Microbiol
Messenger RNA is a marker of cell viability. Quantifying M.
tuberculosis mRNA in sputum is a promising tool for monitoring
response to AKT and evaluating the efficacy of individual drugs. In this
study, mRNA levels were measured in sputum specimens from patients with TB
receiving monotherapy in an early bactericidal activity study of
fluoroquinolones and in those receiving a standard rifampin-based regimen
in an IL-2 trial. Messenger RNA for the glyoxylate cycle enzyme isocitrate
lyase declined at similar rates in patients receiving isoniazid,
gatifloxicin, levofloxacin, and moxi-floxacin monotherapy. Isocitrate
lyase mRNA corre-lated highly with colony forming units in sputum prior to
therapy and during 7 days of monotherapy in all treatment arms. Isocitrate
lyase mRNA was detectable in sputum of culture-positive TB patients
receiving a rifampin-based regimen for 1 month. At 2 months, sputum for
isocitrate mRNA correlated more closely with growth in liquid culture than
did growth on solid culture medium.
Comments Isocitrate lyase mRNA appears to be a
reliable marker of M.
tuberculosis and when available, is of great importance to test the
efficacy of the treatment regime.