Focus on TB DOTS

"Of those who did not receive DOT, 26% had treatment failure and 19% had relapse, while among those who did receive DOT less than 3% had relapse or failure"   INT J TUBERC LUNG DIS 4(5):409–413

Less than Daily Treatment is Less Effective

TB therapy is usually divided into two phases. The initial phase of two months and the continuation phase of 4 or 6 months.

In India, China and many other parts of the world, DOT is given three times a week to make DOT easier to deliver than giving it daily. However, evidence is emerging that three times per week treatment in the initial phase of therapy leads to more relapses and drug resistance especially if the patient is also infected with the AIDS/HIV virus. If the interruptions that occur when SAT is given in electronic medication monitors are kept to a minimum with the measures outlined above in 4a to 4d, Monitored SAT or Monitored Family DOT may cause less drug resistance than three times per week regular DOT. Furthermore, there is published evidence that some health workers engage in "compassionate cheating" and give the patients medication supplies to be taken at home and record that they gave DOT. This occurs 25.6% to 23% of the time.

Furthermore, many programs that call themselves DOTS programs don't give DOT at all.

Recently three times per week treatment In the initial phase of therapy has been shown to increase relapses, (Saltinti et al Am. J. Respir. Crit. Care Med.2006 174: 1067-1068) and increase drug resistance if the TB patients are HIV +. (Burman et al Am J Respir. Crit. Care Med.2006 173 350-356. (The articles are available at www.ecap.biz/dots.php)

In a three times per week DOTS program in the area surrounding Chennai India, 75% of the patients were cured (had negative smears at end of treatment), 1% had no end of treatment smear available, 16% defaulted, 4% failed, and 4% died. Of the 455 patients with susceptible organisms initially who were evaluated after treatment 11.2% relapsed and 2.2% had organisms resistant INH. (Thomas A et al Int J Tuberc Lung Dis 2005 (5) 556-561).

In a separate program in India 26.5% of the patients recorded as receiving DOT actually received SAT and accounted for 86% of the treatment failures and relapses. (Balasubramanian V.N et al Int J Tuberc Lung Dis 2000 4 (5) 409-412.) In Thailand 23% received DOT when community workers recorded that they gave DOT. (Pungrassami et al Int J Tuberc Lung Dis; 6 389-395.)

Monitored Family DOT

Most people live in families. DOT given by a family member has been tried but is controversial because no one can be sure the family member will consistently observe the patient taking medication. Combining Medication Monitors with Family DOT is attractive since the monitor would detect poor compliance and the family member in addition to the patient should be available for counseling when poor compliance is found.

In such a program the Clinic or Community worker would

1. Provide Fixed Dose Medications to be taken daily in medication monitors,
2. Choose a family member to observe the medication ingestion.
3. Carefully instruct the patient, family member, and the entire family about the importance of uninterrupted treatment.
4. Check the adherence record at the time of refill visits or home visits utilizing the LED display built into the monitor,
1. Initially see all patients at least once a week,
2. Subsequently, see patients with good records less often (every 2 weeks and then every 4 weeks)
3. Continue to see patients with poor records frequently with increased counseling.
4. Choose a different treatment observer or assume the task of the giving the DOT when compliance does not improve.
5. Extend the duration of therapy for poor compliers based on the monitor record.

Dealing with the Acquired Drug Resistance Issue

There are at least two causes for drug resistance when treating TB, 1) taking a single drug (monotherapy) and 2) interrupted therapy.

The reason Fixed Dose Combinations of drugs are used is to prevent the patient from taking a single drug. Whenever possible Fixed Dose Combinations should be used. Medication monitors should be designed to provide Fixed Dose Combinations. This is relatively non controversial since WHO advocates fixed dose combinations.

However, some interrupted therapy will occur with Medication Monitors. When promoting medication monitors you may be confronted with the following argument: Since the world is now faced with increasing amounts of drug resistant disease, all programs need to do everything possible to prevent treatment interruptions. Since the patient could miss doses if allowed to take self administer treatment (SAT) from medication monitors it may be argued that the use of such devices could lead to more drug resistance than strict DOT.

Why Electronic Compliance Monitoring?

Electronic Compliance Monitoring (ECM) is an effective and inexpensive means to support other support initiatives and provides an objective record of the dosing history during therapy.

Three studies of TB patient compliance in the United States and developing countries using electronic compliance monitoring devices provided four main findings: (a) medication monitors clearly identified poor compliers, (b) health professionals had only modest success in predicting compliance, (c) a poor monitor record in the initial period of therapy predicted poor compliance and defaulting later in therapy, and (d) counseling the patient based on the monitor record reduced defaulting.

eCAP and Med-ic can identify the good compliers who can take self administered treatment and the poor compliers that need special counseling, or directly observed therapy, and extensions in the duration of therapy.

Published Papers and Articles on DOTS

Viewpoint: Adapting to new international tuberculosis treatment standards with medication monitors and DOT given selectively (republished with permission by Dr. Moulding, UCLA)

New international standards no longer require directly observed therapy for all tuberculosis (TB) patients, but state that practitioners must be capable of assessing adherence and addressing poor adherence. Massproduced electronic medication monitors, which record removal of medication from a container, could help overcome the problem of assessing treatment adherence accurately even in poor countries. Both health facilities and community workers could dispense drugs for self-administered treatment in medication monitors and retrieve the adherence record with inexpensive built-in displays. These devices could keep the adherence record from the beginning of therapy for managing patients who move. Pharmacists using medication monitors could provide surveillance of self-administered treatment prescribed by private physicians with less adherent patients referred to the health departments. Less adherent patients could be managed with focused counselling, directly observed therapy when necessary, and extensions in treatment duration. Removal of the directly observed therapy burden would encourage patients to seek free high-quality supervised pubic care and help expand effective TB treatment services. If resources saved by giving less directly observed therapy were focused on poorly adherent patients, medication monitor-based programmes could create less acquired drug resistance than overwhelmed treatment programmes that attempt but fail to give uninterrupted directly observed therapy to all patients.

Predictors of relapse among pulmonary tuberculosis patients treated in a DOTS programme in South India

February 01 2008

To identify risk factors associated with relapse among cured tuberculosis (TB) patients in a DOTS programme in South India.

The Need to Perfect Intermittent Regimens for Tuberculosis

February 01 2008

Sixty years after the introduction of effective chemotherapy, the World Health Organization (WHO) estimates, based on surveillance and survey data, that the number of new tuberculosis (TB) cases has reached 8.9 million in 2004, with an annual rate increase of 0.6%...

Practice of directly observed treatment (DOT) for tuberculosis in southern Thailand: comparison between different types of DOT observers

February 01 2008

To compare the practice of actual directly observed treatment (DOT) and the observer sustainability for different types of observer.

Under- and over-consumption intermittent TB treatment among rural TB patients in south-west China

February 01 2008

To assess adherence to intermittent directly observed treatment (DOT) during the 2-month intensive phase of tuberculosis (TB) treatment in south-west rural China.

Acquired Rifamycin Resistance with Twice-Weekly Treatment of HIV-related Tuberculosis

February 01 2008

Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study....