Tuberculosis (TB)

A chronic infection caused by Mycobacterium tuberculosis complex. It commonly affects lungs but can affect any organ (lymph nodes, bones, meninges, abdomen, kidney).

For more information on the management of TB see:

• Manual of the National TB/Leprosy Programme (NTLP) in Uganda 3rd Edition, 2016
• TB Control & Community-based DOTS as an Essential Component of District Health Service
• TB Desk Aide

Cause

• Mycobacterium tuberculosis complex (e.g. tuberculosis,  bovis, M. africanum and M. Microti)

• Transmission by droplet inhalation (cough from a patient with open pulmonary TB); can also be through drinking unpasteurised milk, especially M.bovis

Clinical features

General symptoms

• Fevers especially in the evening, excessive night sweats
• Weight loss and loss of appetite

Pulmonary TB

• Chronic cough of >2 weeks (however, in HIV settings, cough of any duration)
• Chest pain, purulent sputum occasionally blood-stained, shortness of breath

Extrapulmonary TB

• Lymphnode TB: Localized enlargement of lymph nodes depending on the site affected (commonly neck)
• Pleural or pericardial effusion
• Abdominal TB: ascites and abdominal pain
• TB meningitis: subacute meningitis (headache, alteration of consciousness)
• Bone or joint TB: swelling and deformity

Complications

• Massive haemoptysis - coughing up >250 mL blood per episode
• Spontaneous pneumothorax and pleural effusion
• TB pericarditis, TB meningitis, TB peritonitis
• Bone TB: can be TB spine with gibbus, TB joints with deformity
• Respiratory failure

TB Case Definitions

Classification of TB Infection

Differential Diagnosis

• Histoplasma pneumonia, trypanosomiasis, brucellosis
• HIV/AIDS
• Malignancy
• COPD, asthma, bronchiectasis, emphysema etc.
• Fungal infection of the lungs e.g. Aspergillosis

Investigations for TB Infection

• Sputum smear microscopy for AAFBs (ZN stain)
  • one spot and one early morning sample. If one is positive, it is diagnostic for pulmonary TB. This test is widely available in many facilities with a laboratory.
  • Sputum samples for children can be collected by inducing sputum using sputum induction kits

• GeneXpert MTB/Rif: automated DNA test on body samples (sputum, lymphonodes tissue, pleural fluid, CSF etc) which can diagnose pulmonary TB and determine susceptibility to Rifampicin. It is superior to microscopy.
  • Genexpert MTB/Rif should be used as initial test for TB diagnosis among all presumptive TB
  • In facilities with no GeneXpert machines on site, microscopy can be used for TB diagnosis except in priority (risk) groups like: HIV positive patients, children <14 years, pregnant and breastfeeding mothers, health workers, contacts with drug resistant TB patients, re- treatment cases, patients from prisons or refugee camps, diabetics
  • For these priority groups, take a sputum sample and send to a facility with a geneXpert machine through the sample referral system (hub system).

• Other investigations
  • Can be used for sputum and GeneXpert negative patients or in case of extrapulmonary TB according to clinical judgement (Chest and spine X ray, abdominal ultrasound, biopsies etc)

• Sputum culture and Drug susceptibility test: is a confirmatory test for TB and also provides resistance pattern to TB medicines. Do this test for:
  • Patients with Rifampicin resistance reported with GeneXpert
  • Also patients on first-line treatment who remain positive at 3 months and are reported Rifampicin sensitive on GeneXpert
  • Patients suspected to be failing on first-line treatment

Note: All presumed and diagnosed TB patients should be offered an HIV test

TB may present at any age in children though the risk is highest below the age of 2 years. When compared to adults, children are more prone to TB infection, TB disease, and severe forms of TB disease.

Risk Factors

• Contact with infectious (pulmonary) case of TB
• Age < 5 years
• Immunosuppression (HIV, malnutrition, diabetes, etc).
• Age < 1 year and lack of BCG vaccination are risk factors for severe disease

Clinical Features

• Suspect TB in all children with
  • Fever > 2 weeks
  • Cough >2 weeks
  • Poor weight gain for one month
  • Close (home) contact of pulmonary TB

Investigations

• Bacteriological confirmation of TB is more difficult in children. The diagnosis of TB in children is dependent on conducting a detailed clinical assessment combined with available tests
• Whenever possible, GeneXpert should be performed
• TST is a good supportive test for TB diagnosis in children

Management

The principles and objectives of TB treatment are similar to those of adults. In addition, effective treatment of TB in children promotes growth and development.

Drug resistance is said to occur when TB organisms continue to grow in the presence of one or more anti-TB medicines.

• Although several factors can contribute to the development of drug-resistant TB, inadequate anti-TB treatment is probably the most important. Inadequate anti-TB treatment leads to mutation in drug-susceptibility bacilli making them drug resistant.

Risk factors for drug-resistant TB are:

• Chronic cases (still sputum smear-positive after completing a supervised retreatment regimen)
• Contact with known drug-resistant tuberculosis
• Retreatments (relapses, treatment after failures, return after loss to follow-up)
• History of frequent interruption of drug treatment
• HIV-positive patient presumed to have TB
• Patients who remain sputum smear-positive at month 2 or 3 of first-line anti-TB treatment
• Health care workers
• Patients from prisons or other congregate settings

Patients suspected to have DR-TB should be screened using rapid drug susceptibility testing (DST) of rifampicin (Xpert MTB/RIF)

• All patients who are drug-resistant TB suspects should therefore have sputum/other specimens taken for culture and DST in vivo

Patients with drug-resistant TB should be treated at specialised centers with approved regimens.

DRUG RESISTANT TB IS A MAJOR PUBLIC HEALTH PROBLEM. INADEQUATE TB TREATMENT IS THE MAJOR CONTRIBUTING FACTOR!

A post-TB patient is one who was successfully treated for TB but presents with respiratory symptoms (chest pain, shortness of breath, cough).

• Re-do standard TB diagnostic evaluation (sputum geneXpert and Chest X ray)
• If negative, evaluate for post-TB lung disease g. bronchiectasis, COPD, pulmonary hypertension.
• In most cases these patients have residual lung damage on Chest X-ray from previous TB, BUT they do not need retreatment if bacteriologically negative
• Counsel the patient and give supportive treatment.

General principles

• The country has adopted community-based TB It is recommended that all TB medicines are taken under direct observation by a treatment supporter (DOT) .
• Anti-TB drugs are given in fixed dose combination (FDC) regimens according to the patient’s TB classification
• Treatment is divided into 2 phases: an initial (intensive) phase of 2 months and a continuation phase of 4 months (longer in MDR-TB and severe forms of TB particularly TB meningitis and osteoarticular TB)
• TB treatment regimens are expressed in a standard format, e.g. 2RHZE/4RH where:
  • Letters represent abbreviated drug names
  • Numbers show the duration in months
  • / shows the division between treatment phases
• Anti-TB drugs have side effects and they should be managed appropriately (see next section)
• TB treatment monitoring should be done by clinical, sputum and where possible radiological
• A conclusion of ”treatment outcome” status should be done for every patient treated for TB

First line anti-TB medication

Important: The choice of regimen now depends on rifampicin sensitivity and not on the previous history of treatment:

• All patients without rifampicin resistance (either new or re-treatments) are treated with 1st line regimen.
• Patients with rifampicin resistance (either new or re- treatments) are treated with second line medication in a designated MDR-TB treatment facility.

Susceptible TB: 1st line treatment regimens

For patients without rifampicin resistance at gene Xpert (both new and re-treatment cases).

New cases not belonging to priority (risk) groups and in which diagnosis was done by sputum examination will also be treated with this regimen.

Retreatment cases

Rifampicin-resistant TB

Patients with rifampicin-resistant TB should undergo culture and Drug Sensitivity testing, and be treated with second line regimens according to national guidelines. Notify the relevant TB focal persons and organise referral to MDR-TB specialised centers for appropriate management.

Adjunctive treatment

Treatment

• Vitamin B6 (pyridoxine): 25 mg per day; given concomitantly with isoniazid for the duration of therapy, to prevent peripheral neuropathy
• Prednisolone in TB patients in whom complications of fibrosis are anticipated because of severe inflammation such as TB meningitis.
  • Prednisolone is given in a dose of 1-2 mg/kg body weight (not more than 60 mg/day) as a single dose for 4 weeks, and then tapered off over 2 weeks

Monitoring of susceptible TB

Laboratory Monitoring (For Pulmonary TB)

At the end of the initial 2 months:

• Sputum smear-negative; start continuation phase
• Sputum smear-positive; do GeneXpert
• If Rifampicin-resistant, refer for MDR-TB treatment and
• If Rifampicin-sensitive, continue with first-line treatment, explore adherence issues but repeat smear at 3 months 
• If positive, do DST 
• If smear negative continue with first-line treatment

At the beginning of 5 months:

• Sputum smear-negative, continue with continuation treatment
• Sputum smear-positive, diagnose Treatment Failure
• Take sputum for GeneXpert to rule out Rifampicin Resistance
• If Rifampicin Resistant, refer for DR treatment
• If TB detected but not Rifampicin Resistant, restart first line regimen but explore adherence issues

During the 6th month:

• Sputum smear-negative, complete treatment and declare cured or treatment completed
• Sputum smear-positive, diagnose treatment failure
• Take sputum for GeneXpert to rule out rifampicin resistance
• If Rifampicin-resistant, refer for MDR-TB treatment
• If Rifampicin-sensitive, restart first-line treatment, explore adherence issues

Clinical Monitoring (For all TB cases)

• Monitor well-being and weight gain
• Assess and reinforce treatment adherence
• Assess and manage side effects

Note: Radiological monitoring– this method should not be used as the sole monitoring tool

Management of treatment interruptions

Refer to NTLP TB treatment manual

Treatment outcomes

A conclusion should be made regarding treatment outcome of EVERY TB patient who has been started on anti-TB treatment.

Common Side Effects

Management of side effects

Hypersensitivity reaction

Most anti-TB drugs can cause hypersensitisation between week 3 and week 8 of treatment in order of frequency: ethambutol, pyrazinamide, rifampicin and isoniazid.

If mild (simple itchy rash), give antihistamine (e.g. chlorpheniramine) and moisturizer and continue treatment.

Severe reactions are characterised by

• Fever, headache, vomiting
• Macular dark erythematous rash which can progress to a Steven Johnson-Toxic Epidermal Necrolysis syndrome.

Treatment

• Stop all drugs immediately
• Manage supportively
• Refer for specialised management

Drug-induced hepatitis

Severe hepatic damage, presenting with jaundice, vomiting, severe malaise. In order of frequency, the implicated drugs are Isoniazid, Pyrazinamide, Rifampicin and Ethambutol.

Treatment

• Stop all drugs immediately
• Manage supportively
• When jaundice has resolved, re-introduce single drugs at 3-7 days interval, starting from the least likely involved
• If reaction very severe, do not try to restart pyrazinamide. If RH tolerated, do not try pyrazinamide
• Use alternative regimen avoiding the causative drug

Case diagnosis and management

• Isolation of sputum-positive cases
• Early detection of cases and initiation of appropriate TB treatment
• Treatment under directly observed treatment (DOT) and follow up to ensure adherence and cure

Contact tracing

• Tracing of contacts of pulmonary TB cases
• Routine screening of health workers for active TB

Preventive measures

• BCG vaccination at birth to prevent severe forms of TB
• Preventive therapy for categories at risk

General hygiene

• Avoidance of overcrowding
• Cough hygiene (cover cough with pieces of cloth, washing hands with soap, proper disposal of sputum)
• Avoid drinking unboiled milk
• Good nutrition
• Good housing condition with improved ventilation

Tuberculosis preventive therapy is recommended to prevent the development of active TB disease in an individual who has latent TB infection (LTBI).

Uganda NTLP National preventive guidelines recommend preventive therapy using a six month regimen of Isoniazid as monotherapy (Isoniazid preventive therapy, IPT) in the following categories: If:

• Persons living with HIV/AIDS
• Child < 5 years, contacts of pulmonary TB patients

Do not use IPT in cases of active TB

Do not use IPT in cases of active TB Do not use IPT in contacts of MDR-TB

Treatment

• Exclude active TB
  • Assess for cough, fever, weight loss and nights sweats (Children: cough, fever, poor weight gain)
  • If any of the TB symptoms are present, do clinical evaluation for TB
  • If none is present, TB is unlikely, then:
• Give isoniazid for 6 months
  • Adults: 5 mg/kg/day (maximum 300 mg)
  • Children: 10 mg/kg/day (max. 300 mg per day)
• Give Vitamin B6 (pyridoxine): 25 mg per day; given with isoniazid to prevent peripheral neuropathy

Note: HIV positive children < 1 year should receive IPT only if they have history of contact with TB case and active TB has been excluded