Totally Drug-Resistant TB: A Patient Is Missing

There was a lot of interest in  in TDR-TB Friday; both The Leonard Lopate Show on WNYC and Science Friday kindly asked me to be on to talk about it. While I was waiting for the phone link to Science Friday to become live, an alarming bulletin arrived in my e-mail. The early-warning list ProMED reported that the existence of two additional cases of TDR-TB have been disclosed, in Bangalore, 600 miles from Mumbai where the first known Indian cases were identified. The patients, a 56-year-old man and a 29-year-old woman, had been coming to a hospital for directly observed administration of their TB for more than two years; they were initially recognized as MDR-TB patients, with disease that was highly resistant but not untreatable, but were not getting better. For the past two weeks, though, the man has not shown up, and no one appears to know where he is.

ProMED was conveying information reported by the newspaper Daily News Analysis India, which said:

Two confirmed cases with the deadly new strain of TB have been detected at the Rajiv Gandhi Institute of Chest Diseases (RGICD) in Bangalore. But the scarier scenario is this: one among them, a 56-year-old man (the hospital has not disclosed his name), has gone absconding, raising the threat perception many levels higher, considering that he could infect others with the deadly strain.
Shockingly, the RGICD has not intimated [meaning "notified" -- M.] the state health department. Dr Shashidhar Buggi, director, RGICD, said, “If they ask us, we will let them know. We are a national institute; if the state government asks us for the reports, we will definitely give it to them.”
This spells another concern. While one of the confirmed TDR-TB patients has gone missing, state health department officials remain in the dark.

In a later story (all posted on DNA India’s website), the obviously embarrassed public health authorities for the area engage in a blame game with the Bangalore hospital, first complaining that notice of the patients were not sent to the appropriate registries, and then charging that proper tests were not done to confirm totally drug-resistant TB, and that the patients probably have “only” the extremely drug-resistant form.
(Cheat sheet: Multi-drug resistance = to the three, four or five first-choice drugs; extremely drug-resistant = to all the first choice and some of the second-choice; totally drug-resistant, to everything available.)
In a commentary — the comments of ProMED’s volunteer moderators are always worth reading — Dr. Matthew Levison of Drexel University’s College of Medicine and School of Public Health notes the confusion:

The 3rd news report above raises questions about the validity of the TDR-TB diagnosis in these patients, stating that these diagnoses were based on lack of clinical response to drug therapy, not on drug susceptibility testing. We await further information to make sense of the situation.

This is an important point. The rapid molecular diagnostic tests for TB identify resistance to only one of the many drugs used against the disease; thus the gold standard for proving drug resistance in TB requires growing the patient’s strain out in culture, which can take weeks — TB is very slow-growing — and then exposing it to various antibiotics to see what works and doesn’t. In a comment posted Thursday night, the European Center for Disease Prevention and Control cautioned against using the term “TDR,” because there is no universally agreed definition or lab-result standards behind it.
By sheer bad luck, the TDR cases have become public in the same week that India expected to be exulting in the news of a year without new cases of polio. In the Globe and Mail, foreign correspondent Stephanie Nolan raises the possibility that Indian health authorities will downplay the TDR discoveries out of concern for stigma (a pattern that’s been seen with the bacterial-resistance “supergene” NDM-1):

The Indian government has yet to respond formally to the announcement that TDR-TB has been found here. Blessina Kumar, vice-chair of the global STOP TB campaign of the World Health Organization, said she feared that embarrassed officials from the national TB control program would attempt to deny its existence.
“The emergence of TDR-TB reflects directly on the efficiency of the [national TB] program and the public health system,” she said. “So there will be a reluctance to accept that it has now been found here. But now it is time to put in contingency efforts or it’s going to really blow out of proportion.”

Looping back to the first day’s news on TDR: A number of readers asked what happened to the 2009 cluster of 15 cases of untreatable TB in Iran. I tracked down one of the authors of the paper, Dr. Parissa Farnia of the Mycobacteriology Centre at Shahid Beheshti University, a lab that functions as the WHO reference center for Iran and so gathers as much information as possible on patients. By e-mail, she reminded me that almost half the patients were not Iranian, but had migrated from nearby countries, and added: “For those patients that were from Azerbaijan, Afghanistan, Iraq, only  their clinical files were available (because they just get hospitalized in our centre and left after 2-3 months of stay). Some of them left our country and [a] few have expired.”