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Case Conferences

   

June 26, 2013

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Symptoms/radiography resolved 3 weeks later and no systemic symptoms.  Would anyone have started empiric MDR-TB therapy for ‘pleural TB’? LTBI therapy? Regimen? Can we rule out early active TB?  Risk of further drug-resistance acquisition if given monotherapy? ‘Watchful waiting’?
Hear the discussion on these questions and more!

     
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- Studies have proven that the treatment protocol for MDR TB can be significantly improved by including high-dose INH as an adjuvant.


-In India,under the RNTCP ,contacts are not routinely screened for LTBI nor are they given chemoprophylaxis.In the absence of symptoms and considering the risk of side effects and resistance with monotherapy ‘watchful waiting’ would have been the option here.
-As we have included ‘chemo-prophylaxis to patients with LTBI’ in our protocol what would be our strategy for HCWs with LTBI who have h/o exposure to patients with MDR TB?

     
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The two cases discussed were extremely interesting
case 1 : do you do drug resistence testing in all your patients before starting AKT?we start patients on AKT according to DOTs therapy and go for further studies if patient is not responding.
As the patients mycobacteria showed sensitivity to high dose INH and steptomycin,i feel it is correct to start with high dose of these drugh however we need to watch for toxicities,INH psycosis and neuropathy can be anticipated with more frequency with high doses.

case 2:In India many households have TB,however we do not treat latent TB as yet and so do not give prophylaxis to anyone as such.Rather many of our health care workers have developed TB.I was wondering if we should start prophylactic treatment to them so as to decrease the incident of recent increase in the number of active TB in health care workers
Here the patients X-ray was initially normal,however later there was blunting of CP angle.We would have liked to do an USG guided Pleural tapping for biochemical analysis like proteins and ADA and treat as an extrapulmonary TB if proteins were suggestive of exudative fluid and if ADA was high,and patient had fever and weight loss.
In absence of symptoms like more than 3 weeks of fever and weight loss,loss of appetite   and normal x-rays we would not treat such a case with AKT nor with LTB treatment

     
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case no1 - whether line probe assay can be used for MDR TB diagnosis?

case no2 - i agree with Dr. Basavraj Plural fluid analysis would have helped definitely Plural fluid ADA .sugar and protein level remarkably change he case pattern

     
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1. At present in India there is no serial TST or IGRA guidelines for detecting latent TB and also No treatment guidelines for LTBI. Hence doing it could be taken as a research proposal and find out its effects on FU and whether it would be cost effective to do it as a routine practise in all high risk groups and contacts. .
2.  Can Clofazamine be used in treating LTBI rather than INH?  Please comment.

     
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Studies have proven that the treatment protocol for MDR TB can be significantly improved by including high-dose INH as an adjuvant.


-In India,under the RNTCP ,contacts are not routinely screened for LTBI nor are they given chemoprophylaxis.In the absence of symptoms and considering the risk of side effects and resistance with monotherapy ‘watchful waiting’ would have been the option here.
-As we have included ‘chemo-prophylaxis to patients with LTBI’ in our protocol what would be our strategy for HCWs with LTBI who have h/o exposure to patients with MDR TB?


1)I would not agree that ‘studies have proven’ that high dose INH improves outcome of MDR cases in all situations.  Knowing the mutations involved with INH resistance can be helpful, as some mutations confer high degree of resistance that are highly unlikely to be overcome with high-dose INH.  In those situations, there is unlikely to be any benefit to adding high-dose INH.  There is limited data as well on how to handle situations when there is discordance between phenotypic DST results and molecular results.  With all of those things in mind, we do consider high-dose INH as adjunctive to MDR-TB, but we do not automatically add it into the regimen without considering these additional factors.  When we include it in the regimen, we do not ‘count’ it when constructing the remainder of the regimen since it’s role and efficacy is still uncertain.  In the future, we are likely to apply more MIC testing (rather than just one or two critical concentrations) to give more insight into the degree of benefit one might expect with higher doses of TB medications.  I should point out that in such cases, it would be routine to also conduct therapeutic drug level monitoring to ensure adequate drug levels. 

2)There is little evidence that treatment of LTBI (i.e. IPT) in patients in whom active TB is excluded generates any future resistance.  We have very low rates of development or progression to active TB in our contacts that screen positive for LTBI.  Our general program/approach is to conduct aggressive contact tracing of all active TB cases, with treatment of LTBI for all contacts that have evidence of tB infection with either TST or IGRA (all such pts get additional testing with CXR and symptom screens to rule out active TB before starting therapy).  Patients that are symptomatic would require further workup for active TB and would not get monotherapy/LTBI therapy before active TB is ruled out (e.g. sputum mycobacterial cultures).  LTBI therapy is generally very well tolerated with minimal side-effects.  We have less than 1-3% hepatotoxicity with 9 months of INH over the past decade of use; when hepatotoxicity occurs, it is usually low grade and resolves with cessation of therapy.  In our setting we would suggest that the risks of progression to active TB among contacts that newly convert their TST/IGRA (i.e. recent infection) outweigh the risks of side-effects.

3)HCW screening is a more complex question without a single simple answer.  Tests for LTBI do not distinguish between recent or remote infection.  In settings where a HCW is exposed multiple times to both drug-sensitive and drug resistant disease, the question of appropriate regimen is complex.  In our setting, we have a very low background rate of TST/IGRA positivity.  As such, if a HCW has known contact to a specific MDR-TB case, they would be offered an LTBI regimen that is likely to be active against the MDR-TB strain.  There is limited long term data on LTBI regimens for MDR-TB.  The Micronesia experience is the largest observational data available and suggests signficant efficacy of a 9 month regimen of Moxifloxacin plus either ethambutol or ethionomide (to date no contact that recevied this regimen has progressed to active TB).  However, in your setting with multiple exposures, one cannot easily conclude that a HCW’s LTBI is due to contact from an MDR TB index case or some other drug sesntive TB case.  In that setting, there have been some studies suggesting that IPT alone may still be of benefit (with the assumption that it is still more statistically likely that a person was infected from a drug sensitve case)

     
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sunita21 - 19 May 2014 10:22 AM

case no1 - whether line probe assay can be used for MDR TB diagnosis?

case no2 - i agree with Dr. Basavraj Plural fluid analysis would have helped definitely Plural fluid ADA .sugar and protein level remarkably change he case pattern

See the response above. We use alternate rapid molecular assays (genotyping or pyrosequencing) which are felt to have higher sensitivity and specificity than the commercial LPA.  Not all health dept labs perform LPA or other molecular tests (some use GeneXpert), but they are all networked together.  Samples can be sent from one lab to the regional or national reference lab and we can usually get a rapid molecular result of first and second line mutations within a few days.

     
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case 1 : do you do drug resistence testing in all your patients before starting AKT?we start patients on AKT according to DOTs therapy and go for further studies if patient is not responding.
As the patients mycobacteria showed sensitivity to high dose INH and steptomycin,i feel it is correct to start with high dose of these drugh however we need to watch for toxicities,INH psycosis and neuropathy can be anticipated with more frequency with high doses.

1)We do drug sensitivity testing on all patients using phenotypic culture based DST methods.  However, usually anti-TB therapy is initiated before the results are available.  In cases where there is strong suspicion of MDR-TB, we have access to the CDC’s rapid molecular resistance testing (molecular testing for both first and second line drugs).  This is best accomplished off of cultured isolates, but can also be attempted (with lower sensitivity) off of direct specimens. Some of our state labs (such as california) perform routine pyrosequencing on all samples (i.e. rapid molecular testing).  These assays are similar to LPA or GeneXpert but offer more extensive information on mutations and resistance (i.e. to both first and second line drugs).  For smear-positve cases, we can usually get rapid molecular resistance results within one to three days if needed. 


case 2
Here the patients X-ray was initially normal,however later there was blunting of CP angle.We would have liked to do an USG guided Pleural tapping for biochemical analysis like proteins and ADA and treat as an extrapulmonary TB if proteins were suggestive of exudative fluid and if ADA was high,and patient had fever and weight loss.

In absence of symptoms like more than 3 weeks of fever and weight loss,loss of appetite   and normal x-rays we would not treat such a case with AKT nor with LTB treatment

—See the discussion.  In this case, there was too little fluid to pursue an ultra sound guided tap.  As this was a case from South Africa, I cannot speak to the specifics of what was done to evaluate the size of the fluid, but I believe both a CT (to examine the possibility of a CT guided drainage catheter placement), and Ultrasound were peformed.  I would agree that if pleural fluid were available it could be sent for cell count, ph, as well as other biochemical analysis.  While ADA is sometimes used with modest sensitivity, it should be noted that the specificity is poor. 
In this case, the primary question was whether the transient pleural fluid represented any active bacillary replication which would impact on the consideration of ‘active Tb’ therapy vs latent tb therapy.  We do not start latent TB therapy in patient in whom active TB cannot be conclusively excluded. In this case, while there was not enough compelling evidence to start a treatment course for active TB, it led to discussion/consideration of whether LTBI therapy could be safely started (i.e. whether we felt confident that active tb was sufficiently excluded).  In our setting, if we have a convincing HCW exposure to a single case of MDR-TB, we routinely give LTBI therapy.  We have not had development of further resistance in that situation, nor have we had any instances (at least in my jurisdiction) to my knowledge of progression to active TB when appropriate LTBI therapy was initiated.

     
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Thank you, Dr. Maunank Shah for your prompt and enriching replies!

     
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Joined 2014-05-05

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Thank you Maunak