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Reinfection Explains All MDR/XDR TB Cases With HIV at South African Flashpoint
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15th Conference on Retroviruses and Opportunistic Infections
February 3-6, 2008
Boston
Mark Mascolini
Reinfection with a second Mycobacterium--not improper anti-TB therapy--accounted for all cases of multidrug-resistant or extensively drug-resistant TB (MDR or XDR TB) in a study in Tugela Ferry, KwaZulu Natal [1], the community where researchers first uncovered high rates of XDR TB in HIV-infected people 2 years ago.
Neel Gandhi (Yale University) and colleagues at the rural Tugela Ferry clinic sounded the alarm on high XDR rates in HIV-infected populations at the 2006 International AIDS Conference [2]. To figure out whether new MDR/XDR cases resulted from acquired resistance due to inadequate treatment or from reinfection with a second drug-resistant strain, Gandhi and colleagues genotyped Mycobacterium samples from 17 people. MDR TB is resistant to isoniazid and rifampin, while XDR TB is resistant to those two drugs, to fluorquinolones, and to injectable agents.
Tugela Ferry has a 355-bed government district hospital in which people with HIV fill 40% of the beds. Antenatal HIV prevalence stands around 25% in the region, where free antiretrovirals are available. This analysis included patients in whom resistance testing showed worsening susceptibility to anti-TB drugs, that is, evolution from susceptible TB to MDR or XDR TB, or evolution from MDR to XDR TB.
Of the 17 people studied, 15 had an HIV test result--all of them positive. Six study participants were women, median age stood at 36 years (range 26 to 45), and median CD4 count measured 86.5 cells (range 13 to 357). Only three people (20%) were taking antiretrovirals. In 7 people susceptible TB evolved to MDR TB, in 8 susceptible TB evolved to XDR TB, in 1 susceptible TB evolved to MDR then to XDR TB, and in 1 MDR TB evolved to XDR TB.
Comparing TB isolates collected before and after evolution to MDR or XDR TB, Gandhi found different genotypes in every pair of samples. In other words, the genotypes said all 17 people had picked up a second TB strain that explained the worsening susceptibility to anti-TB drugs. All 17 people were in the hospital at the time of their MDR or XDR diagnosis or between that diagnosis and follow-up culture. Fifteen of them (88%) died a median of 14 days after they gave a follow-up sputum sample.
Gandhi suggested that high HIV coinfection rates and hospital admission rates magnified the risk of reinfection with a second Mycobacterium. Genotyping also showed that the reinfections resulted from relatively few TB strains, a finding suggesting only a handful of common transmission sources. In theory, tighter infection control could limit the risk that a few highly resistant strains will get transmitted to people with more susceptible TB. Gandhi proposed four tactics to improve infection control:
· Reducing days spent in the hospital
· Improving ventilation and mask use in inpatient and outpatient areas
· Rapidly identifying and isolating patients with MDR/XDR TB
· Providing effective second-line therapy
The investigators also called for further studies to define MDR/XDR TB transmission patterns.
References
1. Andrews J, Gandhi N, Moodley P, et al. Exogenous re-infection with multidrug- and extensively drug-resistant TB among TB/HIV co-infected patients in rural South Africa. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 143.
2. Gandhi NR, Moll A, Pawinski R, et al. High prevalence and mortality from extensively-drug resistant (XDR) TB in TB/HIV coinfected patients in rural South Africa. XVI International AIDS Conference. August 13-18. Toronto. Abstract THLB0210.
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