Monitoring of patients on MDR-TB treatment

Clinical description

Patients to be initiated on second-line anti-TB medicines should have a thorough pre-treatment evaluation and, after initiation of treatment, should have regular scheduled clinical evaluations.

Pre-treatment evaluation and screening Pre-treatment assessment should be systematically conducted for all patients to identify those patients at greater risk of adverse effects, poor outcomes, and to establish a baseline for monitoring.

Before patients are started on MDR-TB treatment, health care workers should:

• Ensure that all details regarding the treatment are communicated to the patient

National Tuberculosis Control Programme 97

• Counsel and educate the patient and family member
• Confirm patient’s physical and work address
• Perform baseline clinical assessment including lab investigations
• Enquire about close contacts at home or work
• Arrange for screening of and testing of all contacts.

Treatment monitoring and follow up Each DR-TB patient should be monitored closely for signs of both treatment efficacy and adverse drug reactions. The success of the programme on treatment depends on the intensity and quality of monitoring and supervision activities.

• Patients should be assessed by trained DR-TB clinicians frequently during the

intensive phase.

• The responsible clinician should assess clinical, microbiologic and radiologic

response to treatment and encourage the patient to continue treatment.

• Treatment cards should be updated after each follow-up visit.

The monitoring should follow standard clinical assessment:

Clinical history

• Resolution or worsening of symptoms of TB (cough sputum production, haemoptysis,

chest pain, respiratory distress, fever, weight loss)

• Adherence (missed oral pill doses, missed injections, reasons)
• Drug adverse events
• Systematic assessment for co-morbid illness
• Pregnancy / family planning in reproductive-age women.

Physical examination:

Vital signs, anthropometry (height, weight, BMI, mid upper arm circumference), focused systemic examination (HEENT, CVS, respiratory, abdomen, skin, musculoskeletal, neurologic)

Laboratory monitoring:

Scheduled laboratory monitoring tests should be done for all DR-TB patients enrolled to treatment. The most important objective evidence of improvement is conversion of sputum smear and culture. Sputum smear is still very important because of shorter turnaround time and readily available in most healthy facilities. The recurrence of TB symptoms after sputum conversion may be the first sign of treatment failure.

98 National Tuberculosis Control Programme Table 10.5-1: Schedule for clinical monitoring in drug-resistant TB (ITR and conventional regimen)

Individualized /standardized regimen Parameter Baseline Intensive phase Continuation phase Clinical assessment Yes Weekly in the first month, then Monthly monthly Screening by DOT worker Yes At every DOT encounter At every DOT encounter Audiometry Yes Month 4 or 6 If clinically indicated Sputum smear Yes Monthly Monthly Sputum culture Yes Monthly Monthly Phenotypic DST Yes Repeat if smear or culture is positive Weight Yes Monthly Monthly Liver function tests Yes If clinically indicated If clinically indicated Serum Creatinine Yes Monthly, more frequently for HIV- If clinically indicated infected, diabetic and/or another high-risk group Serum potassium Yes Monthly If clinically indicated Thyroid stimulating Yes Every 3-6th month for patient Every 6 months hormone (TSH) receiving Eto/Pto and PAS HIV testing Yes If clinically indicated If clinically indicated Pregnancy test (women Yes If clinically indicated If clinically indicated aged 15-49 years)

Total blood count and Yes, for HIV+ If clinically indicated If clinically indicated haemoglobin or anaemia Chest X-ray Yes Baseline and every 6 months End of treatment Fasting Glucose level Yes At baseline, for diabetic patient and For patient receiving for patient receiving Gatifloxacin, Gatifloxacin, monitor glucose monitor glucose frequently frequently Lactic acid Yes For patient receiving Linezolid or ART For patient receiving Linezolid or ART * ECG is mandatory for patients on Bdq and or Dlm at baseline, week 2 and monthly while on either drug. ECG may be done more frequently in patients with low albumin (<3.4 g/dl), low electrolytes, hypothyroidism or heart conditions.

National Tuberculosis Control Programme 99 Table 10.5-2 DR-TB treatment monitoring schedule for the shorter DR-TB regimen *Prompt action on abnormal clinical or laboratory findings is essential **Circle each test completed Patient name: DR-TB registration number:

Age: Sex: Height:

Month/Year Examination Baseline 1 2 3 4 5 6 7 8 9 10 11 Clinical exam X X X X X X X X X X X X Adverse events X X X X X X X X X X X X Psychosocial, functional status X X X X X X X X X X X X Weight/body mass index (wt/ht2) X X X X X X X X X X X X Xpert MTB/RIF X SL LPA X Repeat if smear or culture positive or suspect failure Smear X X X X X X X X X X X X Culture X X X X X X X X X X X X Phenotypic DST X Repeat if smear or culture positive or suspect failure X-ray X X X Full blood count1 X X Creatinine, potassium 2 X X X X X X X X Liver function tests (ALT/AST) X X X X TSH X X X Fasting blood sugar X Vision test charts3 X Audiometry2 X X X X X X X HIV test4 X X Hepatitis B (HBsAg) X Pregnancy test 5 X CD4 count (HIV positive patients) X X Viral load (HIV positive patients) X X 1. Repeat FBC as necessary if HIV-infected (especial care in patient with AZT) or if basal result is low 2. Creatinine, potassium and audiometry should be done monthly while on injectable 3. Repeat vision testing if any change/complaint in acuity or color vision 4. If HIV negative at baseline, HIV testing should be repeated at month 3 and then every 6 months 5. Pregnancy test: at baseline, then offer use of effective contraceptives (Depo-Provera or Intra uterine device-IUD)

100 National Tuberculosis Control Programme General considerations during DR-TB patient monitoring

• For children, height and weight should be measured regularly to ensure that they are

growing normally and adjust the dosage accordingly.

• CXR may be unchanged or show only slight improvement (lesion regression may

require 3 to 9 months), especially in patients with chronic pulmonary lesions, thus regular CXRs may not add value unless a surgical intervention is being considered, or the patient’s clinical situation has worsened.

• The most important objective evidence of improvement is conversion of sputum smear

to negative.

• Most patients who are adherent to an effective regimen are expected to convert to

negative by month 3 of treatment.

• The recurrence of TB symptoms after sputum conversion may be the first sign of

treatment failure.

• Persistently positive cultures beyond the month 6 of treatment is a sign of likely

treatment failure. Non-tuberculous mycobacterial infection could also be a possibility.)

• For patients who remain smear- and culture-positive during treatment or for whom

treatment failure is suspected, second-line DST should be requested.

• Recurrence of positive cultures after culture conversion is a sign of likely treatment

failure, especially if it occurs after month 6 of treatment.

Post-treatment monitoring Post-treatment monitoring is important to:

• Assess for relapse
• Monitor adverse events like neuropathy, ototoxicity, hypothyroidism and psychosis
• Assess and manage sequelae of drug-resistant TB like bronchiectasis, pneumothorax

and lung fibrosis

• Contact screening.

Once the patient has completed the course of treatment, the assessment must be performed every six months during the following two years. The assessment should include the following examinations:

• Clinical history and focused physical examination
• Body weight and height
• Sputum smear examination and culture
• CXR
• DST (if culture result is positive).

If during post-treatment examination the patient shows evidence of active TB, a full course of treatment with an individually constructed regimen based on history and DST must be restarted.

National Tuberculosis Control Programme 101 Def inition of terms and treatment outcomes Culture conversion and reversion For a patient to be considered bacteriologically positive at the start of second-line treatment, the following criteria must be met:

• At least one pre-treatment specimen was positive for smear, Xpert MTB/RIF or culture
• The collection date of the sample on which the laboratory examination was performed

was <30 days before, or 7 days after, initiation of second-line treatment

• At least one sputum sample for smear and culture should always be taken at initiation

of MDR-TB treatment.

• Examinations are required at the start of treatment firstly to confirm the diagnosis of

TB and determine the infectiousness.

• Sputum smear positive forms are the most infectious.
• Both sputum smear and sputum culture testing should be used to monitor patients

throughout therapy.

• The monitoring of sputum culture is important for decisions on changes in treatment.

Sputum conversion: is defined as two sets of consecutive negative smears and cultures, from samples collected at least 30 days apart. The date of collection for the first sample is considered as the date of conversion.

Reversion (to positive): culture is considered to have reverted to positive when, after an initial conversion, two consecutive cultures, taken at least 30 days apart, are found to be positive. To define “treatment failed”, reversion should have occurred in the continuation phase.

Interim outcome indicators for MDR-TB Negative culture at month six: Proportion of microbiologically confirmed pulmonary MDR-TB cases registered and started on MDR-TB treatment who have a negative culture at month 6.

Positive culture at month six: Proportion of microbiologically confirmed pulmonary MDR-TB cases registered and started on drug-resistant TB treatment who have a positive culture at month 6.

Died at month six: Proportion of confirmed MDR-TB cases registered and started on MDR-TB treatment who died of any cause by the end of month 6.

LTFU at month six: Proportion of confirmed MDR-TB cases started on MDR-TB treatment who interrupted by the end of month 6.

Drug-resistant TB treatment outcomes All drug-resistant TB patients who are registered to receive treatment with second-line drugs should be assigned one of the following treatment outcomes upon completion or interruption of treatment by NTP or the decision clinical team.

102 National Tuberculosis Control Programme Table 10.5-3: Definition of treatment outcomes Treatment outcomes Definition Cured Treatment completed with evidence that three or more consecutive cultures taken at least 30 days apart are negative after the intensive phase.

Treatment completed Treatment completed without evidence of failure but NO record that three or more consecutive cultures taken at least 30 days apart are negative after the intensive phase.

Treatment failed Treatment terminated or need for permanent regimen change of at least two anti-TB drugs because of:

• lack of conversion by the end of the intensive phase, or bacteriological

reversion in the continuation phase after conversion to negative after in- tensive phase, or

• evidence of additional acquired resistance to fluoroquinolone or second-

line injectable drugs, or

• Adverse drug reactions.

Lost to follow-up (LTFU) A patient whose treatment was interrupted for two consecutive months or more.

Died A patient who dies for any reason during treatment.

Not evaluated Patient for whom no treatment outcome is assigned either due to being transferred out to other facility or still on treatment.