10.6 Patient monitoring

 

Patients should be assessed at baseline, then, regardless of the regimen prescribed, monitored throughout the course of treatment.

 

Monitoring includes:

• Assessment of treatment response.
• Detection of adverse effects and adherence issues.

For the schedule of follow-up examinations, see Appendix 15.  

 

Baseline and follow-up findings should be noted in the patient file to enable the detection and interpretation of potential changes.

10.6.1 Clinical visits

Baseline assessment

Assessment includes:

• Signs and symptoms of TB and severity (cough, fever, night sweats, weight loss, shortness of breath, ability to perform daily activities).
• Vital signs and weight.
• Comorbidities and other risk factors for adverse effects requiring monitoring schedule adaptation.
• Psychological assessment.

Other investigations may be needed depending on the drugs used in the regimen prescribed (Section 10.6.3).

 

Clinical assessment should be performed by a clinician. Psychological assessment should be performed whenever possible by personnel with appropriate training.

 

All patients starting treatment should be given the information they need to understand the disease and its treatment (Appendix 21).

Follow-up visits

Each follow-up visit includes assessing:

• Clinical progress, vital signs and weight. Dosages should be adjusted to the weight if necessary.
• Occurrence of adverse effects.
• Adherence to treatment (Appendix 22).
• Psychological condition.

 

Frequency depends on the patient’s clinical condition and evolution:

• A visit every week for the first month, every other week for the second month, then once a month if there is no particular problem.
• Additional visits may be required in case of comorbidities, severe or multiple adverse effects, pregnancy, etc.

 

Visits should coincide with bacteriological examinations and other investigations when possible.

 

The clinician should take into account any information and concerns regarding treatment tolerance and adherence reported by the patient or the team responsible for the patient’s follow-up and support.

10.6.2 Bacteriological tests

To assess treatment response in patients with:

• PTB: bacteriological tests are essential.
• EPTB: evaluation is based on clinical evolution. However, bacteriological tests are required if patients also develop PTB.

Baseline tests

Baseline tests are those performed on specimens collected just prior to treatment initiation. Baseline tests include:

• RMTs for detection of M. tuberculosis and rifampicin, isoniazid and fluoroquinolone resistance.
• Sputum smear microscopy.
• Culture and full phenotypic DST (pDST) or genome sequencing.

For more information, see Chapter 3.

 

If DST results are obtained on a specimen collected more than 2 to 3 weeks prior to treatment initiation, a new specimen should be collected just prior to treatment initiation. The new results are considered as baseline results.

Follow-up tests

• Microscopy: once a month until treatment completion. Although less reliable than culture, it provides immediate results which contribute to the assessment of treatment response. 
• Culture: once a month until treatment completion. Culture conversion and reversion are useful markers of whether the treatment is effective or not.
• Full pDST (or genome sequencing): if positive culture at Month 4 or later.
• RMTs: Xpert MTB/XDR (or GenoType MTBDRsl if Xpert MTB/XDR is not available) if positive microscopy at Month 4 or later, as it can detect resistance-conferring mutations not present at baseline (Chapter 3).

End-of-treatment tests 

Culture and microscopy should be performed at end of treatment, to confirm the end-of-treatment outcome (Chapter 17).

Post-treatment tests

For patients on BPaLM or BPaL regimen, culture and microscopy should be performed 6 and 12-month post-treatment completion, to detect a relapse.

10.6.3 Other investigations

Radiography

At baseline, then every 6 months:

• chest x-ray for patients with PTB,
• bone x-ray for patients with osteoarticular and spinal TB.

Electrocardiogram

Some TB drugs cause prolongation of the QT interval, which increases the risk of a potentially life-threatening ventricular arrhythmia, including torsade de pointes (TdP) [1] Citation 1. Roden DM. Drug-induced prolongation of the QT interval. New Engl J Med. 2004; 350: 1013-1022.
https://doi.org/10.1056/NEJMra032426 .

 

To monitor the QT interval, electrocardiogram (ECG) should be performed:

• At baseline in all patients taking QT-prolonging TB drugs

Then:

• Once a month in patients:
  • taking < 2 moderate or strong QT-prolonging TB drugs,
  • taking < 3 QT-prolonging drugs (TB and non-TB).
• Once a week for one month, then once a month in patients:
  • taking ≥ 2 moderate or strong QT-prolonging TB drugs,
  • taking ≥ 3 QT-prolonging drugs (TB and non-TB),
  • with other risk factors for QT prolongation or TdP:
    • a history of syncopal episodes, TdP or congenital long QT syndrome;
    • uncompensated heart failure, severe coronary disease, bradycardia;
    • untreated hypothyroidism.

 

Increased ECG monitoring is required in patients in whom a QT prolongation is detected.

 

For ECG reading, see Appendix 16.
For the management of QT prolongation, see Appendix 17.  
For the list of QT prolonging drugs, see Appendix 19.  

Brief peripheral neuropathy screen

For patients on linezolid: brief peripheral neuropathy screen (BPNS) at baseline, then once a month to detect peripheral neuropathy (Appendix 16).  

Visual function tests

For patients on drugs with ocular toxicity: visual acuity and colour vision tests (Ishihara test) at baseline, then once a month to detect the first signs of optic neuritis.

Audiometry

For patients on aminoglycosides: at baseline, then once a month to detect hearing loss. Monitoring is particularly important in children, as hearing loss in childhood has negative effects on development.

Full blood count

For all patients: haemoglobin, red and white blood cells, and platelets at baseline, then if indicated.

For patients on linezolid: every 2 weeks for the first 2 months, then once a month.

For patients on zidovudine (AZT): once a month for the first 2 months, then if indicated.

Liver function tests

For all patients: serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at baseline, then once a month.

Bilirubin, if AST and ALT are elevated, or if indicated.

Monitor liver function more frequently in case of increase in AST/ALT or other signs of hepatic disorder or risk factors, such as hepatitis B or C.

Serum creatinine and potassium level

For all patients: at baseline, then if indicated (e.g. patients with renal insufficiency).

For patients on aminoglycoside: once a month, or more frequently if indicated.

Creatinine clearance

For patients with renal insufficiency: at baseline. If < 30 ml/minute, the dose of certain TB drugs should be adjusted (Appendix 12).

Glycated haemoglobin (HbA1c) and/or blood glucose level (BGL)

For all patients: at baseline to detect diabetes. If diabetes is diagnosed, monitor according to standard protocols.

HIV, hepatitis B and C

For all patients with undocumented HIV hepatitis B and C status: at baseline; HIV test every 6 months in high HIV prevalence areas. Tests can be repeated in case of recent exposure.

CD4 and viral load

For HIV-infected patients: at baseline, then every 6 months.

Thyroid-stimulating hormone (TSH)

For patients on thionamides or PAS: at baseline, then every 3 months. 
If hypothyroidism is diagnosed: 4 to 12 weeks after levothyroxine initiation and after each levothyroxine dose adjustment until stable, then every 6 months until the end of TB treatment, or for as long as the patient takes levothyroxine. 

Pregnancy test

For all adolescents and women of childbearing age: at baseline, then if indicated.