Tuberculosis Case Management

Diagnosis of TB

The presence of pulmonary tuberculosis should be suspected in individuals presenting with one or more of the following complaints:

Cough for 1 week or longer,
Night sweats,
Fever,
Loss of weight,
a BMI <17kg/m² or failure to thrive among children

Laboratory Investigations

Every effort should be made to bacteriologically confirm the diagnosis of TB, with rapid molecular test such as the Xpert MTB/Rif test being the preferred diagnostic test for patients being evaluated for tuberculosis. A specimen should be submitted for all cases being investigated for pulmonary TB as per TB diagnostic algorithm, in order to confirm the diagnosis of Tuberculosis. (see the National Tuberculosis and Leprosy Control Guidelines)

Chest X-Rays

Chest X-ray is recommended as a priority SCREENING test for persons classified as being at high risk for tuberculosis. The following persons are classified as being at high risk for tuberculosis:

Children under the age of 5 years.
People living with HIV
Those who are malnourished.
People above 60 years of age.
People with diabetes mellitus.
People who drink alcohol excessively
Miners and ex-miners
People in congregate settings.
Inmates and correctional facility communities.
Health care workers

Note: In the presence of clinical improvement, it is not necessary to monitor the response of pulmonary TB to treatment by chest x-rays.

Tuberculin Testing

Medicine	Dose	Frequency	Duration
Tuberculin, purified, (PPD) 1:1000 intradermal	0.1mL (=5TU)	-	-

Examine induration at 48-72 hours.

A positive tuberculin skin test (person with normal immunity: induration > 10 mm, person with defective immunity: induration > 5 mm) may indicate active infection (especially if strongly positive) , previous infection or previous BCG.
Absence of a response does not exclude TB because individuals with HIV may not have sufficient immunity for a positive skin test despite active TB.
If a child under 3 years of age has not had BCG, the Mantoux test may be useful.

Treatment Regimens for TB

One treatment regimen is now used in Zimbabwe for the treatment of drug sensitive TB, regardless of the treatment history. The regimen consists of a combination of the four first line medicines HRZE:

H= isoniazid E= ethambutol

R= rifampicin Z= pyrazinamide

These medicines are available as Fixed Dose Combination (FDC). See tables below for dosing.

The intention of these combination tablets is to improve compliance by reducing the number of tablets a patient takes, and to reduce the possibility of medicine resistance developing. The number of FDC tablets is determined by a weight range of each patient at the start of treatment

Treatment is the same for HIV infected people as for non-HIV

Treatment of Drug-Sensitive TB

All drug sensitive cases of TB regardless of site, severity or previous treatment history are treated using the regimens summarised below.

Treatment of Rifampicin Sensitive TB

Regimen

Intensive Phase

Continuation Phase

Adults (DOTS)

2HRZE/4HR

2 months HRZE

4 months HR

6 months HR

(for TB of meninges, bone, joint, pericardium, disseminated spinal disease, the continuation phase is extended)

Children

(DOTS)

2HRZE/4HR

2 months HRZE

4 months HR

10 months HR

(for patients with TB of the meninges, bone joint, pericardium, military TB or TB
spine the continuation phase is extended

General notes:

In all pulmonary tuberculosis cases, sputum smear examination is done at the end of two months, five months and at the end of treatment. Refer to the National Tuberculosis and Leprosy Management Guidelines for the management of a positive smear at any stage in the monitoring of treatment.
Children weighing less than 25kg receive paediatric FDC HRZ plus additional isoniazid and ethambutol.
Children weighing 25kg and above receive adult formulations and additional isoniazid.
The total duration of treatment is 6 months (exceptions noted in this section).
Children with tuberculous meningitis or pericarditis, disseminated or spinal disease with neurological complications should be given 10HR (continuous phase) i.e. 10 months of isoniazid and rifampicin under direct observation.
Adults with TB of meninges, bone, joint, pericardium, disseminated , or spinal disease should be given 6 HR (continuous phase) i.e. 6 months of isoniazid and rifampicin under direct observation.

Fixed Dose Combination of Anti-TB Medicines

The essential anti-TB medicines are available as FDCs such that each tablet has a combination of 2 (2-FDC), 3 (3-FDC), or 4 (4-FDC) medicines. The FDCs available in Zimbabwe are:

RHZE: Rifampicin, lsoniazid, Pyrazinamide and Ethambutol
RHZ: Rifampicin, lsoniazid and Pyrazinamide
RH: Rifampicin and lsoniazid

The number of FDC tablets is determined by a weight range of each patient at the start of treatment as shown in tables below.

All patients receiving isoniazid containing regimens should receive supplemental pyridoxine (see table below)

Paediatric medicines FDC dosing by weight band

Weight Band	Recommended Regimen
	Intensive Phase		Continuation Phase
	RHZ (75/50/150)	E (100)	RH (75/50)
4-7kg	1
8-11kg	2	2	2
12-15kg	3	3	3
16-24kg	4	4	4
25kgs and above	Use adult dosages and formulations

Adult FDC dosing by weight bands

Weight Band	Intensive phase – 2 months 2 (RHZE) daily (Isoniazid 75mg + Rifampicin150mg + Pyrazinamide 400mg + Ethambutol 275mg)	Continuation phase – 4 months 4 (HR) daily (Isoniazid 75mg + Rifampicin 150mg)
25-39kg	2	2
40-54kg	3	3
55-70kg	4	4
70kg +	5	5

Supplemental Pyridoxine dosing

Medicine

Dose

Frequency

Duration

Pyridoxine po

25mg – Adults

12.5mg - Paeds

once daily

For the duration of treatment with INH

Adverse Medicine Reaction

All suspected adverse drug reactions (ADR) must be reported to the Medicines Control Authority of Zimbabwe (MCAZ) using spontaneous Adverse Drug Reaction reporting forms or the MCAZ online reporting platform: https://e-pv.mcaz.co.zw

In the event of an adverse reaction to anti-TB medicines, stop all TB medicines and assess. If necessary, evaluate the liver function then reintroduce one medicine at a time and build up gradually. Start with isoniazid at 25mg - the least likely to cause a reaction and end with the most likely toxic e.g. pyrazinamide in jaundice/hepatoxicity. When the required dose has been achieved without any reaction, another medicine should be re-introduced in a similar manner - slowly, increasing the dose daily as per the example table below.

Approach to the management of Anti-TB induced hepatitis

Drug	Day
Day 1	INH 25mg
Day 2	INH 50mg
Day 3	INH 100mg
Day 4	INH 300mg
Day 5	INH 300mg + R 150mg
Day 6	INH 300mg + R, 300mg
Day 7	INH 300mg + R 450mg
Day 8	INH 300mg +R 600mg (depends on weight)
Day 9	INH 300mg + R 600mg + E 400mg
Day 10	INH 300mg +R 600mg + E 800mg
Day 11	INH 300mg +R 600mg + E 1.2g (depends on weight)
Day 12	INH 300mg +R 600mg + E 1.2g + Z 400mg
Day 13	INH 300mg + R 600mg + E 1.2g + Z 800g
Day 14	INH 300mg + R 600mg + E 1.2g + Z 1.2g
Day 15	INH 300mg + R 600mg + E 1.2g + Z 1.6g (depends on weight)

Refer to the National TB Guidelines and leprosy for further guidance on management of adverse event.

TB and HIV Co-Infection

Refer to the current national ARV guidelines as well as the TB manual. Also refer to the section on Antiretroviral therapy