MDR-TB Treatment & Prevention

Dear Masoud, All,

Indeed, achieving universal access to diagnosis and treatment of MDR-TB is critical, and for that we need to scale-up access to quality diagnosis and treatment of MDR. From our combined experiences, Paul Farmer and I recently made the case for this in the NEJM, “Picking Up the Pace – Scale-up of MDR Tuberculosis Treatment Programs” (full text here: http://www.nejm.org/doi/full/10.1056/NEJMp1010023).

In this piece, we estimated that treatment of MDR-TB has been abysmal – barely 0.5% of the estimated 5 million new cases receive treatment through quality-assured second-line drugs. Addressing such a large gap will require transformation in four critical areas:

- Diagnostics: improve laboratory capacity and support, implement, and expand rapid molecular detection methods;

- Drug supply: the market failure for MDR-TB drugs, which has resulted in decades-old, off-patent, second-line TB drugs that cost more than USD 2,000 per year of treatment, needs to be properly addressed;

- Treatment implementation should be significantly accelerated through appropriate funding, long-term on-site assistance, and models that promote ambulatory delivery of care;

- Advocacy is crucial to MDR-TB treatment scale-up and should be increased.

We also showed the lessons learned and insights from five global initiatives: the GLC ...

Dear Masoud, All,

Indeed, achieving universal access to diagnosis and treatment of MDR-TB is critical, and for that we need to scale-up access to quality diagnosis and treatment of MDR. From our combined experiences, Paul Farmer and I recently made the case for this in the NEJM, “Picking Up the Pace – Scale-up of MDR Tuberculosis Treatment Programs” (full text here: http://www.nejm.org/doi/full/10.1056/NEJMp1010023).

In this piece, we estimated that treatment of MDR-TB has been abysmal – barely 0.5% of the estimated 5 million new cases receive treatment through quality-assured second-line drugs. Addressing such a large gap will require transformation in four critical areas:

- Diagnostics: improve laboratory capacity and support, implement, and expand rapid molecular detection methods;

- Drug supply: the market failure for MDR-TB drugs, which has resulted in decades-old, off-patent, second-line TB drugs that cost more than USD 2,000 per year of treatment, needs to be properly addressed;

- Treatment implementation should be significantly accelerated through appropriate funding, long-term on-site assistance, and models that promote ambulatory delivery of care;

- Advocacy is crucial to MDR-TB treatment scale-up and should be increased.

We also showed the lessons learned and insights from five global initiatives: the GLC, the GLI, PEPFAR, the GF, and UNITAID. Furthermore, some of the outcomes from these initiatives show that, when aligned with appropriate policies, resources, strategies, and technologies, universal MDR-TB care is possible.

This is a very timely discussion to have now as many of us are in Berlin for the Union conference.

Best regards,
Salmaan

Many challenges to delivery of quality MDR-TB care is discussed in this New Yorker piece:
A Deadly Misdiagnosis: Is it possible to save the millions of people who die from TB?
http://www.newyorker.com/reporting/2010/11/15/101115fa_fact_specter?currentPa...


- Difficulty diagnosing with sputum "The results are accurate little more than half the time;" and consequent errors in treatment


- Giving treatment to people with latent tb


- Lack of access to effective diagnosis despite new recent technology - this piece mentions GeneXpert which "allows doctors to diagnose TB in under two hours — without error or doubt" citing the NEJM paper: Rapid Molecular Detection of Tuberculosis and Rifampin Resistance http://www.nejm.org/doi/full/10.1056/NEJMoa0907847#t=article


But what would it take to bring this diagnosis tool to the people who need it most? A private-public partnership?


They make another critical point: the fact that rich people in the west rarely get the disease, thus TB receives "fewer resources, fewer research dollars, and less attention from the global health community than either AIDS or malaria—the two other most deadly infectious diseases," while the WHO estimates there will ten million new cases, "the largest number in history," in the ...

One thing that I would add to the steps that need to be taken in order to prevent MDR TB is: reinforcing the DOT during the primo-infection in order to avoid MDR-TB. The accompagnateurs or Community Health Workers should play a key role in making sure that the patients take their medicines every day and they go to the clinics where they are being follow up on a regular basis.
That's a great discussion. Keep it alive.

Thank you very much Junior for your intervention. Re-enforcing patient-centered
approaches is the key, health systems are often too rigid to accomodate the
patients' needs.


The question to all members of the community is how you define Universal Access
in your setting? Would the following definition be something to consider and
elaborate further? Suggestions are more than welcome.

"Universal Access is defined as evidence-based practices and services which are
available, accessible, affordable and acceptable by all people irrespective of
their age, sex, religion, origin, nationality, socioeconomic status or
geographic background."

Thank you and all the best,
Masoud

Dear Masoud,
I agree with you. We need to take into account the Universal Access aspect of the treatment. Let's say in the developing countries: MDR-TB treatment accessible, available,acceptable and affordable to all regardless of their age, sexe, religion and nationality. In Haiti for example up to 2005 there was only one center for the treatment of MDR-TB, now there are two. In Burundi there is only one and the demand in hospital beds is increasing every day. The approach must be patient-centered with a great involvement and participation of government officials. NGO only should not be implementing, monitoring and evaluating such programs. Psychologist should be involved in those programs based on national approach. Sustainability is a must.
Thank you.
Best,

Junior

I would like to join discussion and say that there are not only one source of MDR TB formation.

Besides of inadequate treatment (including deficiency of drugs, improper regimens and DOT problems) there is another great source of DR TB: in-hospital transmission, notably exogenous re-infection.

One recent estimate indicates "more than half of which (XDR TB) are likely to be nosocomially transmitted" (Basu S, Andrews J, Poolman E, et al. Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study.Lancet 2007; 370:1500–7).

It is important to treat MDR TB patients in ambulatory, preferentially at home, to decrease drug resistance transmission from DR TB to sensitive TB patients.

It is extremely important in countries where majority of patients are hospitalizing in TB hospitals.

So access to treatment should be accompanied with access to "non-transmissible MDR TB case management"

A.Pasechnikov,
TB Advisor
Primary Health Strengthening Project, Azerbaijan
Abt Associates Inc.
14/16 Khagani str., apt. 41, 1005 Baku
Tel +994 12 498 10 08
Fax +994 12 493 83 65
Mob +99450 235 75 23

Dear Pasechnikov, I understand your concerns about treating MDR TB patients ambulatory to decrease drug resistance transmission from DR TB to sensitive TB patients. However I have a concern here about people in the community where those MDR TB patients live. Don't you think that there is a high risk for family members and community members of those patients. The course of the treatment, for example in Haiti, last 18 to 24 months. I would say that there might be a first part of the treatment that can be done in hospital settings equipped to receive those patients in a specific MDR TB department in order to make sure that they are responding adequately to the treatment. And then after they go home and get their medicines from accompagnateurs or CHW who would do the DOT. I am saying this because I think that the health professional in the MDR TB unit will certainly know how to protect themselves against the infection but it is not sure that at the family and community level there are guarantees that can or will be done.
What are your thoughts on this.
Thanks for your involvement in this discussion.
Best,

Bazile

Dear Junior,
this is an "old" question: does isolation of TB patient decrease transmission to family members or community members? Indeed, time for delay in diagnosis in developing countries is about 2-3 month. Unfortunately this period is out of our control and enough for almost all contacts be infected. Isolation of index patient doesn't decrease rate of LTBI or active disease among contacts. One of the first studies confirmed these findings were conducted in Madrass by British Medical Research Council (Fox W, Ellard GA, Mitchison DA.Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications.Int J Tuberc Lung Dis. 1999 Oct;3(10 Suppl 2):S231-79).
>From the other hand, we have no enough evidence how well "good equipped settings" can protect against in-hospital transmission. Other big problem is cost-effectiveness of in-hospital treatment of MDR TB patients. So I believe that reasonable strategy can be as follow: ASAP start DOT of index case at home or in ambulatory point and manage contacts properly (regular examination, early diagnose of active disease and early initiation of treatment or preventive therapy if indicated and so on)

A.Pasechnikov,
TB Advisor ...

Dear Junior,
this is an "old" question: does isolation of TB patient decrease transmission to family members or community members? Indeed, time for delay in diagnosis in developing countries is about 2-3 month. Unfortunately this period is out of our control and enough for almost all contacts be infected. Isolation of index patient doesn't decrease rate of LTBI or active disease among contacts. One of the first studies confirmed these findings were conducted in Madrass by British Medical Research Council (Fox W, Ellard GA, Mitchison DA.Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications.Int J Tuberc Lung Dis. 1999 Oct;3(10 Suppl 2):S231-79).
>From the other hand, we have no enough evidence how well "good equipped settings" can protect against in-hospital transmission. Other big problem is cost-effectiveness of in-hospital treatment of MDR TB patients. So I believe that reasonable strategy can be as follow: ASAP start DOT of index case at home or in ambulatory point and manage contacts properly (regular examination, early diagnose of active disease and early initiation of treatment or preventive therapy if indicated and so on)

A.Pasechnikov,
TB Advisor
Primary Health Strengthening Project, Azerbaijan
Abt Associates Inc.
14/16 Khagani str., apt. 41, 1005 Baku
Tel +994 12 498 10 08
Fax +994 12 493 83 65
Mob +99450 235 75 23

Dear Pasechnikov,
Thanks for your input in this topic. It is true that time in delay of diagnosis of TB infection can be long in the developing world. However for MDR-TB the cost for lab work, medicines can be very high. That's why I mentioned that it is critical to ensure that the cases are appropriately treated because otherwise other people in the community and the family will be infected and the cost will be huge for the public and private system. For primo-infection TB I completely agree with home based or ambulatory treatment (and that's what is being done world wide)but for MDR-TB we need to bear in mind that it arises because of a problem some where in the course of the primo-infection TB treatment. And thus we need to seriously tackle the problem once it is identified. That should involve patients, health professional, patients' family members because sometimes there might be some reluctance expressed by patients toward hospitalization/isolation.
I have not yet read any article about how well good equipped settings can protect against in-hospital transmission of MDR-TB nonetheless use of respirators by health professionals (and even by patients), sensitization of health professionals ...

Dear Pasechnikov,
Thanks for your input in this topic. It is true that time in delay of diagnosis of TB infection can be long in the developing world. However for MDR-TB the cost for lab work, medicines can be very high. That's why I mentioned that it is critical to ensure that the cases are appropriately treated because otherwise other people in the community and the family will be infected and the cost will be huge for the public and private system. For primo-infection TB I completely agree with home based or ambulatory treatment (and that's what is being done world wide)but for MDR-TB we need to bear in mind that it arises because of a problem some where in the course of the primo-infection TB treatment. And thus we need to seriously tackle the problem once it is identified. That should involve patients, health professional, patients' family members because sometimes there might be some reluctance expressed by patients toward hospitalization/isolation.
I have not yet read any article about how well good equipped settings can protect against in-hospital transmission of MDR-TB nonetheless use of respirators by health professionals (and even by patients), sensitization of health professionals,use of UV lights, I think, can help in the prevention of infections.
Overall, I agree with the strategy of starting DOT ASAP after evaluating the understanding of the patients of their pathologies and the their adherence and then proper management of contacts can be done.
Thank you.

Bazile