How long are MDR-TB patients infectious on EFFECTIVE therapy?
I received this question from a doctor in Pakistan and thought it could be the basis for a good general discussion on the impact of treatment on TB transmission.
From: adeel tahir
Sent: Wednesday, June 13, 2012 6:07 AM
To: Edward Nardell
Subject: infectiousness of MDR-TB patients
Hope you are doing well. I am Dr. Adeel Tahir. I am a medical doctor from Pakistan and currently working as a public health specialist in a NGO in Pakistan. Now a days i am working on a randomized controlled trial about the duration of hospital stay of MDR-TB patients. For that i need some information about the infectiousness of MDR-TB patients after the start of treatment. I searched literature and internet but am unable to find authentic reference. So, i am emailing you to get help as you have vast experience in this are. It would be a great help if you send me some references that explains how long it will take for MDR-TB patient to be non-infectious after the start of treatment.
Thanking you in anticipation.
Dr. Adeel Tahir
BSc, MBBS, MScPH (Aus)
Public Health Specialist
Association for Social Development
You are correct, there is not much in the literature yet. I have researched this carefully because our own studies in South Africa suggest that, exactly like drug susceptible patients, patients on EFFECTIVE treatment for MDR-TB become almost immediately non-infectious, regardless of smear status. I emphasize EFFECTIVE, because treating XDR TB patients with an MDR regimen will not have the same immediate (or any) effect on transmission. I suspect that susceptibility to fluoroquinalones is essential for the almost immediate effect of treatment on transmission. Our data comes from our guinea pig studies in South Africa and I do plan to publish this, but have not gotten to it yet. The data on drug susceptible TB is very clear - with effective treatment drug susceptible patients cannot infect sentinel guinea pigs from the very day that treatment is started even though they remain smear and culture positive. There is no sound basis for the 2-week rule that is commonly used - although it does acknowledge that most drug-susceptible TB patients are non-infectious before sputum smear and culture converts to negative.
For MDR-TB it is only our data that shows a similar rapid response. For XDR our data suggests that MDR treatment is not similarly effective. So, we have RE-DISCOVERED what has been know from Richard Riley's work in the 50's - that the impact of treatment on transmission (aerosol) is much faster than the impact on sputum smear and culture, which in turn is much faster than the effect on cure. The most likely explanation for this immediate effect is that as respiratory droplets evaporate into droplet nuclei, as required for airborne transport, the drug concentration in these minute droplets soars since only water vapor comes off. We have a large study that is likely to be funded in South Africa to nail this down further, to demonstrate that for MDR TB, susceptibility to fluoroquinalones is essential for treatment to be effective in immediately stopping transmission.
The problem has been that until the advent of rapid molecular testing, diagnosing MDR TB and XDR TB took many weeks or months, so that EFFECTIVE treatment of drug resistant patients could not be assured. Now that rapid molecular testing is possible it should be increasingly possible to rely on rapid diagnosis and EFFECTIVE treatment as the most important kind of transmission control. In a USAID-funded project, we have translated these concepts into a new campaign to re-focus TB IC as F-A-S-T, standing for Find cases Actively by cough surveillance , Separate safely*, and Treat effectively based on rapid DSTs. Separation is only until effective treatment starts.
In summary, my answer to your question re. how much treatment is required for MDR treatment before transmission stops is: same day if treatment is EFFECTIVE, i.e., based on DSTs. If DSTs are not available, one must assume that some patients may remain infectious because they are not on EFFECTIVE treatment. In that case, the treatment duration is not based on treatment time, per se, but on diagnosis and DST turn-around time. There is no basis for 2 weeks, 4 weeks, or until smear or culture negative. We hope to publish this soon.
May I use your inquiry on GHDonline with my response?
Ed Nardell, MD
Edward A. Nardell, MD
Harvard Medical School
Harvard School of Public Health
Brigham & Women's Hospital
Partners In Health
641 Huntington Avenue
Boston, MA 02115