Letter Re: So-Called Totally Drug-Resistant Tuberculosis in South Africa

Regarding your recent link to the US News article: “Doctors Struggling to Fight ‘Totally Drug-Resistant’ Tuberculosis in South Africa”, I would like to comment.  

As an infectious diseases research scientist with a specialty in tuberculosis (TB) the term “Totally Drug Resistant” peaked my interest, considering the World Health Organization (WHO) does not recognize this term.  To express the resistance to anti-TB drugs, we use very precise terms, where multidrug resistance (MDR-) represents resistance to two specific drugs, isoniazid and rifampin, and extensively-drug resistance (XDR-) is resistance to any of the second line drugs and one of the injectable drugs in addition to meeting the MDR qualifications. These terms have very explicit meanings and nomenclature criteria. 

The US News article cites a recent report published in the journal Emerging Infectious Diseases (EID).  I have few disagreements with the findings of this journal and Koebler’s report. In the original study DNA typing methods identified certain mutations in the bacteria. It assumed correlations between mutations and antibiotic resistance patterns. Although for few anti-TB drugs the relationship between a specific mutation and resistance to that particular drugs hold reasonably true, it is not necessarily always the case and there are instances where these methods do not always correlate actually clinical experiences. The best methods to predict resistance to a drug is antibiotic susceptibility testing, but again for many of anti-TB drugs there is no standard or reproducible method. Furthermore, the susceptibility testing, when available, involves each drug individually, whereas therapy is always administered as a combination of anti-TB drugs. Therefore, even if the laboratory data suggest presence of drug resistance to one drug, other drugs in the combination therapy may still be active, effectively controlling the disease and suppressing the selective pressures leading to resistance emergence.

In my opinion WHO does a great job by discouraging the use of term “totally drug resistance”, as these studied cases fit very well within the present terminology. In fact the EID paper uses this sensational term “Totally Drug-Resistant Tuberculosis” only in its title and abstract, truly only mentioning “this virtually untreatable form of TB” in reference XDR-TB. In the conclusion the authors acknowledge the lack of clinical evidence to support the gene-based assumptions. My ultimate concern as a researcher in this field is not the EID study, but rather propagating the wrong hysterical message to people who may not be able to tease out the actually scientific data.  It appears to me that telling half truths is not doing any social service. If one reads the other reports using this very specific term, evidence is present that even this form of tuberculosis is curable, although treatment approach might be different. To take quotes out of context, only skimming the title and concluding paragraph, is an injustice to the public at large who rely heavily on secondary sources for scientific information.  Although the emergence of resistance is a problem with tuberculosis, as with many other bacteria, attaching such a label sends a certain message and triggers frantic stigma to a real problem. There is effective treatment available for drug sensitive tuberculosis and individualized treatment for drug resistant tuberculosis with continuous efforts to develop better drug, doses and regimens. 

Regards, – C.S. and S.S. in Texas