Tuberculosis & HIV and AIDS

- Clinical Guidelines -

Launched October 2000

Contents

1. Background

Target audience
Purpose
Interaction of TB and HIV and AIDS

2. The Dots Strategy

The elements of DOTS
Patient-centred care

3. Diagnosis of TB in Adults

Diagnosis of pulmonary TB
New patients
Retreatment patients
Multidrug resistant TB
Diagnosis of extrapulmonary TB
TB meningitis
Tuberculous lymphadenopathy
Miliary TB
Tuberculous serous effusions
Tuberculosis of bones and joints

4. Diagnosis of HIV in Adult TB Patients

HIV counselling and testing

5. Treatment of TB in Adults

Directly observed treatment (DOT)
TB treatment regimens
New adult patients (Regimen 1)
Retreatment adult patients (Regimen 2)
Three times per week regimens
Side effects of anti-TB drugs
Cotrimoxazole prophylaxis

6. Contacts

Contact tracing
Prophylaxis for child contacts under 5 years old

7. Monitoring Progress in Pulmonary TB

New patients
Sputum microscopy at 2 months
Sputum investigations at 3 months
Sputum investigations at 5 months
Retreatment patients
Sputum investigations at 3 months
Sputum investigations at 7 months

8. Diagnosis of TB in Children

Diagnosis of TB other than TB meningitis in children
Clinical features
Tuberculin skin test
Chest radiography (x-ray)30
Contact history31
Impact of HIV on the diagnosis of TB in children31
A score system for the diagnosis of TB in children31
Diagnosis of TB meningitis in children32

9. Diagnosisi of HIV in Children
10. Treatment of TB in Children

Treatment of TB other than TB meningitis in children
Complications in children
Treatment of TB meningitis in children
Non drug treatment
Drug treatment
Management of complications of TB meningitis

11. TB Preventive Therapy

TB preventive therapy and health services
Eligibility for TB preventive therapy
Screen for TB symptoms
Chest x-ray
Tuberculin skin testing
TB preventive therapy regimen

12. Prevention and Treatment of other HIV-Related Opportunistic Infections
13. Protection from TB Infection

Consider HIV counselling and testing
Seek care if symptoms develop
Rapidly diagnose and treat infectious TB patients
Isolate TB suspects and patients
Implement environmental controls
Ensure proper disinfection
Use protective clothing
BCG vaccination may be considered but is not recommended
Screening of health care workers working with TB patients

14. Protection from HIV Infection
15. Continuity of Care

Follow admission and discharge criteria for TB patients
Create resource lists of services and facilities for referral
Encourage formation of community support services
Use available transfer forms
Improve co-ordination between services
Plan for high patient mobility
Communicate well with patients and provide health education
Make a home visit and verify contact details
Ensure adequate staff and transport

16. Non Tuberculous Mycobactarial Infections(NTM)

Annex 1 - Hospital admission and discharge criteria for TB patients
Annex 2 - TB patient transfer form
Annex 3 - Continuity of care report
Annex 4 - Provincial TB Coordinators

Tuberculosis & HIV and AIDS

- Clinical Guidelines -

1. BACKGROUND

Target audience

These guidelines are for the use of doctors and nurses who provide clinical care to tuberculosis (TB) patients and to patients living with HIV and AIDS. It should be feasible to implement the recommendations, at all levels of the health system including primary care level.

Purpose

Practical advice is offered on how to deliver care to patients with the symptoms of TB and HIV and AIDS and when to refer patients for more specialised care. For more comprehensive guidelines, refer to 'TB/HIV: A Clinical Manual' which is published by the World Health Organisation and is available from the Department of Health.

Interaction of TB and HIV and AIDS

• TB is the most common disease and the leading cause of death in people living with HIV and AIDS.
• It is caused by Mycobacterium tuberculosis, also known as TB bacilli.
• HIV, by attacking the immune system, makes a person who is infected with TB bacilli more likely to get sick with TB.
• TB can occur at any time, but often occurs early in the course of HIV disease.
• TB probably accelerates the progression of HIV disease.
• In the absence of HIV infection, only about 10% of people infected with TB bacilli get sick with TB during their lifetime. In people who are infected with HIV, about 50% may get sick with TB.
• About 40% of TB patients in South Africa are infected with HIV and this proportion is increasing rapidly.
• TB can be prevented in people living with HIV and AIDS using isoniazid prophylaxis.
• TB can be cured, whether a patient is infected with HIV or not, using Directly Observed Treatment, Short-Course (DOTS), with the same drugs for the same amount of time.

SUMMARY TB is the most common disease and the leading cause of death in people living with HIV and AIDS·HIV increases the risk of progressing from TB infection to TB disease· TB can be prevented in people living with HIV and AIDS using isoniazid prophylaxis· TB can be cured, whether a patient is infected with HIV or not, using Directly Observed Treatment, Short-Course (DOTS), with the same drugs for the same amount of time

2. THE DOTS STRATEGY

The elements of DOTS

"DOTS" means "Directly Observed Treatment, Short-course". It is an internationally recommended strategy for controlling TB. It has been effective in such diverse settings as China, Botswana and New York City. South Africa has been implementing DOTS since 1996.

The elements are:

• Political commitment - direct resources towards TB control including appointment of district coordinators.
• Identify infectious patients with sputum smear microscopy.
• Directly observe treatment and provide patient-centred care.
• Ensure drug supply and use of standardised anti-TB treatment regimens.
• Monitor treatment outcomes with the TB recording and reporting system (e.g. TB register).

Patient-centred care

An important factor in whether or not the patient will complete treatment is their relationship with their health worker.

Patient-centred care requires:

• Addressing each patient's needs.
• Always being friendly, courteous and encouraging.
• Explaining the importance of completing treatment.
• Discussing the patient's feelings, expectations and potential barriers that will prevent success from the outset. Most patients will be able to predict their own adherence accurately, taking their lifestyle, habits and past experience into account.
• Trying to ensure that the same health worker listens to the patient, monitors, encourages and provides feedback on progress. This will allow a bond to develop which may help to ensure completion of treatment.
• Should more than 2 doses of treatment be missed, making an extra effort to help the patient mobilise support to manage any problems.
• Making your services as convenient as possible for the patient, by keeping clinic waiting times short and making treatment accessible outside normal working hours.

SUMMARY The DOTS strategy is effective in curing TB. Completing TB treatment is difficult - address patients' needs to help them complete their treatment.

3. DIAGNOSIS OF TB IN ADULTS

Diagnosis of pulmonary TB

Symptoms and history

More than 85% of people with TB in South Africa, have TB of the lungs (pulmonary TB).

The symptoms of this TB are the same whether patients are infected with HIV or not:

• coughing for more than 3 weeks
• night sweats and fever
• loss of appetite and weight
• tiredness and weakness
• chest pain
• coughing up blood (haemoptysis)

TB of other organs (extrapulmonary TB) may also occur and is more frequent in people infected with HIV (see "Extrapulmonary TB" section).

In a patient with symptoms of TB, a careful history should be taken. The following are risk factors for TB:

• known or suspected HIV infection
• exposure to a pulmonary TB case, especially a sputum smear-positive case
• industrial silica dust exposure (e.g. in underground miners)

Physical examination

The physical signs of TB are non-specific and do not help to distinguish TB from other chest diseases.

Investigations

• New patients

New patients are patients who have never had more than 4 weeks of TB treatment in the past. For these patients, do:

• Sputum for smear microscopy

The best way to diagnose pulmonary TB is by sending the patient's sputum for smear microscopy (stained for acid-fast bacilli or AFB). Two sputum samples should be examined.

• If 2 sputum smears are positive, then treat as a new patient.
• If only one sputum smear is positive, then do a chest x-ray. If it is too difficult to obtain a chest x-ray, TB treatment may be initiated for a patient with a single positive sputum smear.
• If both sputum smears are negative, then give a one-week course of antibiotics and reassess.

• Sputum collection

In an outpatient setting, ask the TB suspect to give a sputum sample as follows:

• Label the container first with the patient's name, TB register number, clinic/hospital name, and "TB specimen".
• Bring the patient to a well-ventilated area, preferably outside without others watching. Sputum collection indoors without good ventilation increases the risk of transmitting TB to others.
• Demonstrate a deep cough, beginning with 3 deep breaths.
• Give the patient the container without the lid.
• Hold the lid yourself, ready to replace it immediately.
• Stand behind the patient.
• Ask the patient to cough up material from deep in the lungs and spit the sputum into the container.
• Instruct the patient to be very careful not to contaminate the outside of the container.
• Take the container from the patient and screw on the lid tightly.
• Send the container as quickly as possible to the laboratory. If the sample can not be sent immediately, then store it in the cold, preferably in a fridge.
• If results can be obtained the same day, ask the patient to wait for the results.
• Give the patient a container with instructions to cough up another sample into the container when they wake up the next morning, and to return the next day.
• In hospital, 2 early morning sputum samples should be collected.

SUMMARY Sputum smear microscopy is the best way to diagnose pulmonary TB. Collect 2 sputum samples. Proper sputum collection is crucial for TB diagnosis. Ensure that lids are tightly screwed onto sputum containers after sputum collection. If 2 sputum smears are positive, then treat as a new patient.

• Course of antibiotics

If the patient has 2 negative sputum samples, provide a 7-day course of broad-spectrum antibiotics (e.g. amoxicillin 250 mg three times per day). Reassess the patient after the course.

• Chest x-ray

Do a chest x-ray if the patient has:

• only one positive sputum smear or
• 2 negative sputum smears and continues to cough after a course of antibiotics.

If the patient has one positive sputum smear and a chest x-ray suggestive of TB, then treat as a new patient.

No chest x-ray pattern is absolutely typical of TB. Chest x-ray changes in TB/HIV patients reflect the degree of immunocompromise. In early HIV disease (mild immunocompromise), the appearance is classical:

• upper lobe infiltrates
• bilateral infiltrates
• cavitation
• pulmonary fibrosis and shrinking

In late HIV disease (severe immunocompromise), the appearance is atypical:

• interstitial infiltrates (especially lower zones)
• no cavitation

SUMMARY ·Do a chest x-ray if the patient has only one positive sputum smear OR if the patient has 2 negative sputum smears with no response to a course of antibiotics. ·No chest x-ray pattern is absolutely typical of TB. ·Chest x-ray patterns in TB/HIV patients with severe immunocompromise are often atypical. ·If a patient has one positive sputum smear and a chest x-ray suggestive of TB, then treat as a new patient.

• TB culture

If a patient has 2 negative smears, has not improved on a course of antibiotics and has a normal chest x-ray, reassess the diagnosis. If the chest x-ray is compatible with TB, collect 2 sputa and send one for sputum smear microscopy and one for TB culture.

• If either the sputum smear or the sputum culture is positive, then treat as a new patient.
• If a patient is severely ill, with 2 negative sputum smears and chest x-ray abnormalities consistent with extensive pulmonary TB (interstitial or miliary) then a medical officer may take the decision to treat for TB before culture results are available.
• Once the decision to treat has been taken, treatment should continue for the entire 6 months. No trials of therapy should be given.

SUMMARY Ideally, TB treatment should only be started if there is a positive sputum smear or culture. People living with HIV and AIDS are more likely to have smear-negative, culture-positive pulmonary TB. A medical officer may take the decision to treat a TB patient who is severely ill, with 2 negative sputum smears, with chest x-ray abnormalities consistent with extensive pulmonary TB.

• Retreatment patients

Retreatment patients are patients who have been treated for TB for more than 4 weeks in the past. They are more likely to have resistance to one or more of the anti-TB drugs, so their sputum should be sent for culture and susceptibility testing. People living with HIV and AIDS have an increased risk of recurrence of TB after completing TB treatment.

• Sputum for TB smear microscopy

• Collect one sputum sample for smear microscopy as described above.
• Give the patient 2 containers with instructions to cough up 2 samples into the container when they wake up the next morning.
• Send one of the 2 samples for smear microscopy.
• If 2 sputum smears are positive, then treat as a retreatment patient.
• If only one sputum smear is positive, then do a chest x-ray. If it is too difficult to obtain a chest x-ray, TB treatment may be initiated for a patient with a single positive sputum smear.
• If both sputum smears are negative, then give a one-week course of antibiotics and reassess.

• Sputum for TB culture and susceptibility

• Send the second early morning sputum sample for TB culture and susceptibility testing, if possible.
• If the culture is positive, then start on TB retreatment regimen.
• If there is resistance to anti-TB drugs, then refer to a medical officer.

• Course of antibiotics

• If 2 sputum smears are negative, then give a 7-day course of broad-spectrum antibiotics (e.g. amoxicillin 250 mg three times per day).
• Reassess the patient after a course of antibiotics.

• Chest x-ray

• Do a chest x-ray if the patient has:
• only one positive sputum smear or
• 2 negative sputum smears and continues to cough after a course of antibiotics.
• If the patient has one positive sputum smear and a chest x-ray suggestive of TB, then treat as a retreatment patient.
• If a patient is severely ill, with 2 negative sputum smears and chest x-ray abnormalities consistent with extensive pulmonary TB (interstitial or miliary) then a medical officer may take the decision to treat for TB before culture results are available. If there is no positive sputum smear or culture, then the patient should be treated with the new treatment regimen.

SUMMARY People living with HIV and AIDS are more likely to have a recurrence of TB after completing TB treatment All retreatment TB suspects should have sputum sent for culture and susceptibility testing The retreatment regimen should only be given to patients with a positive sputum smear or culture A medical officer may take the decision to treat a TB patient who is severely ill, with 2 negative sputum smears, with chest x-ray abnormalities consistent with extensive pulmonary TB. This patient should be given the new treatment regimen.

• Multidrug resistant TB (MDR TB)

Multidrug resistant TB (MDR TB) refers to TB which is resistant to at least isoniazid and rifampicin. It is difficult and expensive to treat. Currently, the cure rate of MDR TB patients is less than 50%. It is therefore essential to prevent its development.

• MDR TB is only diagnosed by TB culture and susceptibility testing.
• MDR TB can be prevented by treating TB patients with appropriate TB regimens (see "Treatment of TB" section), ensuring patient adherence to treatment by providing DOT (see "Directly Observed Treatment" section) and obtaining drug susceptibility tests when indicated (see "Monitoring TB Treatment" section).
• Refer MDR TB patients to a MDR TB unit where experienced clinicians can treat the patient according to the 'Guidelines for the Management of Drug-resistant Tuberculosis Patients in South Africa' which are available from the Department of Health. If you are unsure of which facility is designated as a MDR TB unit in your province, contact your Provincial TB Coordinator (a list of Provincial TB Coordinators is attached in Annex 4).

SUMMARY Multidrug resistant TB (MDR TB) is TB which is resistant to isoniazid and rifampicin. MDR TB patients should be referred to a MDR TB unit.

• Diagnosis of extrapulmonary TB

Common forms of extrapulmonary TB associated with HIV are: lymphadenopathy, pleural effusion, pericardial disease, miliary, meningitis.

• Extrapulmonary TB is common in HIV-positive patients.
• Many patients with extrapulmonary TB also have pulmonary TB so they should also be investigated for this (see "Pulmonary TB" section).
• Diagnosis of extrapulmonary TB is often difficult, so diagnosis may be presumptive, after excluding other conditions.
• The treatment of extrapulmonary TB is the same as the treatment for pulmonary TB (see "Treatment of TB" section).

• TB meningitis

TB meningitis is life threatening if not treated promptly.

• Patients present with gradual onset of headache and decreased consciousness.
• Examination reveals neck stiffness and positive Kernig's sign (flex one of the patient's legs at hip and knee with the patient lying on back, and then straighten the knee. Resistance to straightening the knee and pain in the lower back and posterior thigh suggest meningeal inflammation).
• Diagnosis rests on clinical grounds and lumbar puncture to examine cerebrospinal fluid (CSF) (elevated CSF white cells with predominance of lymphocytes, increased protein, decreased glucose and sometimes the presence of acid-fast bacilli).
• Always exclude cryptococcal meningitis by cryptococcal antigen test, if possible. If cryptococcal antigen test is not available, do CSF microscopy (India ink stain) and, if available, fungal culture.
• Patients with TB meningitis should be hospitalised.

• Tuberculous lymphadenopathy

• Persistent generalised lymphadenopathy (PGL) develops in up to 80% of HIV-infected individuals and requires no treatment. In PGL, lymph nodes are non-tender, <2 cm in size and symmetrical.
• Lymph node disease, including tuberculous lymphadenopathy, should be suspected if lymph nodes are tender, painful, nonsymmetrical, matted, fluctuant, rapidly growing or associated with fever, night sweats or weight loss.
• If clinical features suggest a cause of lymphadenopathy other than PGL, refer to a doctor who will do a needle (18G or 19G) aspirate of the lymph node (TB is diagnosed if the aspirated material is caseated and a smear of the aspirate reveals acid-fast bacilli).
• If no diagnosis is made after a needle aspirate, a lymph node biopsy should be done.
• Tuberculosis may also cause mediastinal or intra-abdominal lymphadenopathy that may be detected by X-ray, ultrasound or computerised axial tomography (CT scan). This may be treated empirically, unless the nodes are accessible to aspiration at a tertiary health facility where the process may be guided by CT scan, fluoroscopy or ultrasound.

• Miliary TB

Miliary TB results from widespread blood borne dissemination of TB bacilli ("miliary" means "like small millet seeds").

• Miliary TB is an under-diagnosed cause of end stage wasting in HIV-positive individuals.
• Patients present with fever, night sweats and weight loss and may have an enlarged liver and spleen (hepatosplenomegaly).
• Chest x-ray shows diffuse, uniformly distributed, small miliary nodules.
• Full blood count may show pancytopenia (this may also be seen as a result of HIV).
• Bacterial confirmation of the diagnosis is sometimes possible from sputum, CSF or bone marrow.

• Tuberculous serous effusions

Inflammatory tuberculous effusions may occur in any of the serous cavities of the body, i.e. pleural, pericardial or peritoneal cavities. They are a common form of TB in HIV-positive patients.

• Patients usually have systemic and local features.
• Microscopy of the aspirates from tuberculous serous effusions rarely show AFB because the fluid forms as an inflammatory reaction to TB lesions in the serous membrane.
• TB culture is of no immediate help because a culture result takes three weeks.
• The aspirate is an exudate (the protein content is more than 30g/L). A biochemistry lab is not required to diagnose an exudate. Let the aspirated fluid stand for while. If it clots, it is an exudate.
• In populations with a high prevalence of HIV, TB is the commonest cause of an exudative serous effusion.

• Tuberculous pleural effusion

• Typical clinical features are chest pain, breathlessness, tracheal and mediastinal shift away from the side of the effusion and decreased chest movement.
• Chest x-ray shows unilateral, uniform white opacity, often with a concave upper border.
• Diagnosis is done by pleural aspiration. The fluid is an exudate and is usually straw coloured. The white cell count is high (1 000 - 2 500 per mm3).
• If facilities are available, a closed pleural biopsy can be done with an Abrams needle for histological diagnosis. The yield is about 75% positive for TB.
• Differential diagnosis includes malignancy, post-pneumonic effusion and pulmonary embolism.

SUMMARY In a hospital or clinic serving a population with a high prevalence of TB you should treat a patient with a unilateral exudative pleural effusion with anti-TB drugs.

• Tuberculous empyema

• The physical signs are the same as those of a pleural effusion.
• If pleural aspiration reveals pus, it indicates an empyema. Send the pus to the laboratory for examination for TB, Gram stain and bacterial culture. The main differential diagnosis is bacterial empyema.
• A succussion splash is a splashing sound heard with the stethoscope while shaking the patient's chest. It indicates a pyopneumothorax (pus and air in the pleural space). After chest x-ray confirmation, insert a chest drain with underwater seal.

• Tuberculous pericardial effusion

• Diagnosis usually rests on suggestive systemic features and ultrasound.
• Cardiovascular symptoms include: chest pain, shortness of breath, cough, dizziness and weakness due to low cardiac output, leg swelling, right hypochondrial pain (liver congestion), abdominal swelling (ascites).
• Cardiovascular signs include: tachycardia, low blood pressure/pulsus paradoxus, raised jugular venous pressure, impalpable apex beat, distant heart sounds, pericardial friction rub, signs of right-sided heart failure (e.g. hepatosplenomegaly, ascites, oedema).
• Chest x-ray may show a large globular heart, clear lung fields, pleural effusion.
• ECG may show tachycardia, flattening of ST and T waves, low voltage QRS complexes.
• Treatment is the same as for all types of TB (see "Treatment of TB" section) but corticosteroids can be added. Treatment without pericardiocentesis usually results in resolution of tuberculous pericardial effusion.
• In cases of cardiac tamponade the effusion should be aspirated by a specialist.

SUMMARY In high TB/HIV prevalence populations, TB is the most likely treatable cause of pericardial effusion. It may be safer for the patient to start presumptive anti-TB treatment than to undergo diagnostic pericardiocentesis.

• Tuberculous ascites (TB peritonitis)

• Clinical features include systemic features and ascites. There may be palpable abdominal masses (mesenteric lymph nodes). Bowel obstruction may develop from adhesion of nodes to bowel; and fistulae between bowel, bladder and abdominal wall.
• Always do a diagnostic ascitic tap. The aspirated fluid is usually straw coloured, but is occasionally turbid or blood stained. The fluid is an exudate, usually with more than 300 white cells per mm3. White cells are predominantly lymphocytes (polymorphs predominate in spontaneous bacterial peritonitis which is a common complication of cirrhosis).
• Do a chest X-ray to look for pulmonary TB.
• Diagnosis is usually presumptive - in doubtful cases, a peritoneal biopsy may be considered at a hospital if a mini-laparotomy or laparoscopy can be performed.

• Tuberculosis of bones and joints

When primary TB occurs during childhood, bacilli often spread to the vertebrae and ends of long bones. Disease may either rapidly develop there or months or years later. The infection may spread locally causing arthritis.

• Weight-bearing bones and joints are the most commonly affected, with the spine most frequently affected, then the hip, the knee and the bones of the foot.
• In the spine, TB starts in the intervertebral disc, spreads along the ligaments and involves the adjacent vertebral bodies.
• Clinical features of spinal TB include: pain and swelling locally, sometimes an obvious lump or bend of the spine, stiff back, reluctance to bend the back, a child that refuses to walk, paralysis or weakness of the lower limbs due to pressure on the spinal cord.
• X-rays of the spine show disc space narrowing and erosion of the adjacent vertebral bodies.
• A well-fitted orthopaedic brace is sometimes needed to immobilise the affected area.
• Surgical treatment is necessary if there is compression of the spinal cord and the patient has weakness or paraplegia of the lower limbs. These patients should be referred to a specialist urgently.

SUMMARY People living with HIV and AIDS are more likely to develop extrapulmonary TB.·All forms of extrapulmonary TB in adults are treated with the new adult treatment regimen.

4. DIAGNOSIS OF HIV IN ADULT TB PATIENTS

Most HIV-positive TB patients have no symptoms or signs of HIV disease.

Symptoms

Symptoms suggestive of HIV infection are:

• weight loss
• diarrhoea (>1 month)
• pain on swallowing (suggests oesophageal candida)
• burning sensation of feet (suggests peripheral sensory neuropathy)

History

History suggestive of HIV infection include:

• herpes zoster (shingles)
• recurrent pneumonia
• bacteraemia
• sexual partner with HIV infection

Physical signs

Physical signs suggestive of HIV infection include:

• oral candidiasis
• oral hairy leukoplakia
• scar of herpes zoster
• Kaposi's sarcoma
• pruritic papular rash
• symmetrical generalised lymphadenopathy
• persistent painful genital ulceration

Investigations

HIV infection should be suspected if, during the course of other investigations, the following results are found:

• unexplained anaemia, leucopenia or thrombocytopenia
• bacteraemia

The definitive diagnosis of HIV infection rests on a positive HIV test.

SUMMARY Most HIV-positive TB patients have no symptoms or signs of HIV disease. Diagnosis of HIV infection is confirmed by a positive HIV test.

HIV counselling and testing

All TB patients in South Africa should receive HIV information and education. Given that about 40% of TB patients in South Africa are infected with HIV, HIV counselling and testing should be offered to all TB patients, if the following conditions are met:

• Testing is voluntary.
• Trained counsellors (not necessarily nurses) provide counselling.
• Pre-test counselling is provided to enable the patient to make an informed decision to have the test or not. The main issues for discussion are assessments of the following: the patient's likelihood of having acquired HIV infection, their knowledge about HIV and their ability to cope with the result.
• Post-test counselling is provided to discuss the result, share information, provide support and encourage safe sexual behaviour.
• Continuing clinical and counselling support is available for patients who are HIV-positive.

The potential benefits of HIV counselling and testing are:

• Improved health status through good nutritional advice and early access to prevention/treatment for HIV-related illness (e.g. TB preventive therapy).
• Ability to plan for HIV-related illness and death.
• Emotional support and better ability to cope with HIV-related anxiety.
• Awareness of safer options for reproduction and infant feeding.
• Motivation to initiate and maintain safer sexual and drug-related behaviours.

SUMMARY Voluntary HIV counselling and testing should be offered to all TB patients if pre- and post-test counselling by trained counsellors and continuing clinical and counselling support are available.

5. TREATMENT OF TB IN ADULTS

Directly observed treatment (DOT)

The best way to ensure that a TB patient completes TB treatment is with Directly Observed Treatment (DOT).

DOT means that every dose of treatment is seen to be swallowed by a treatment supporter. Every TB patient should have DOT. It is required for all smear-positive (infectious) TB patients.

DOT is organised as follows:

• Discuss with the patient who they would like as a treatment supporter.
• Treatment supporters can be any responsible person who the patient trusts such as a health worker, colleague, employer, traditional healer, friend, community member or family member.
• Explain to the treatment supporter how to give the correct doses of TB drugs, refer the patient to the clinic if they develop side effects, and how to fill in the Patient Treatment Card.
• Provide monthly supplies of drugs and review the Patient Treatment Card to make sure that treatment is going smoothly.
• Provide ongoing support to the patient and treatment supporter and follow up all problems and concerns.
• Trace the patient and ensure appropriate treatment supervision if the patient interrupts treatment.

The treatment supporter's responsibilities:

• Observing the TB patient as s/he swallows the daily dose of medication.
• Liasing with the health worker to ensure an uninterrupted supply of TB drugs.
• Advising the patient to attend the clinic if side effects develop, and reminding the patient of clinic appointments.
• Checking off the appropriate box on the Patient Treatment Card each time a dose of TB drugs is taken.
• Supporting and motivating the patient to complete treatment.
• Visiting the patient or informing the health worker on the second day if the patient did not show up to receive treatment.
• Informing the health worker if the patient moves or is unable to receive TB treatment for any reason.

The TB patient's responsibilities:

• Swallowing each dose of TB medication, reporting side effects and any other problems promptly to the supporter or health worker and attending the clinic for appointments.
• Informing the health worker or supporter if moving or unable to receive TB treatment for any reason.

The employer's responsibilities (for DOTS in the workplace):

• Supporting and encouraging DOTS in the workplace.
• Allowing time off for employees to meet with health workers about how to provide DOTS in the workplace.
• Allowing time off for employees to go to clinic and attempting to provide a private space where a TB patient can receive TB treatment.

SUMMARY Directly Observed Treatment (DOT) means that every dose of treatment is seen to be swallowed by a treatment supporter.

TB treatment regimens

TB treatment is the same for those who are infected with HIV and those who are not. Treatment is given five times per week in the intensive phase (the first 2 months of treatment in new patients and the first 3 months of treatment in retreatment patients).

Hospitalised TB patients can receive the same dosages 7 days per week. For continuation phase treatment (the last 4 months of treatment for new patients and the last 5 months of treatment for retreatment patients) can be given five times or three times a week. Ensure that you give the correct doses.

SUMMARY TB treatment is the same whether a patient is infected with HIV or not.

• New adult patients (Regimen 1)

• New smear or culture-positive and other serious pulmonary and extrapulmonary tuberculosis

Pretreatment Body Weight	2 Months Initial Phase (treatment given 5 times a week)	4 Months Continuation (treatment given 5 times a week)
	Combination tablet RHZE 120/60/300/200 mg*	Combination tablet RH 150/100 mg	Combination tablet RH 300/150 mg
<50 kg	4 tabs	3 tabs
>50 kg	5 tabs		2 tabs
* Ethambutol 225 mg in combination is also acceptable
R=rifampicin: H=isoniazid (INH): Z=pyrazinamide: E=ethambutol: S=streptomycin

• Retreatment adult patients (Regimen 2)

Smear or culture positive retreatment cases

Pretreatment Body Weight	2 Months Initial Phase (treatment given 5 times a week)		3rd Month (5 times a week)	5 Months Continuation Phase (5 times a week)
	RHZE 120/60/300/200 mg*	Streptomycin	RHZE	RH1 50/100 mg	E 400 mg	RH 300/150	E 400 mg
<50 kg	4 tabs	750 mg	4 tabs	3 tabs	2 tabs
>50 kg	5 tabs	1000 mg	5 tabs	4 tabs		2 tabs	3 tabs
Note: Streptomycin should be reduced to 750 mg per day to those older than 45 years and not be given to those over 65 years.* Ethambutol 225 mg in combination is also acceptable.

• Three times per week regimens

Three times per week regimen have been shown to be as effective as daily regimens. To avoid mistakes, the regimen should be applied to all patients at particular facilities. Furthermore, since different packaging is involved, the use and packing of 3 times per week regimens should be approved and co-ordinated at provincial level.

New adult regimen with 3 times per week continuation phase

Pretreatment Body Weight	2 Months Initial Phase (treatment given 5 times a week)	4 Months Continuation (treatment given 3 times a week)
	Combination tablet RHZE 120/60/300/200 mg	Combination tablet RH 150/100 mg	H100 mg	Combination tablet RH300/150 mg	H300 mg
<50 kg	4 tabs	3 tabs	1 tab
>50 kg	5 tabs			2 tabs	3 tabs

Retreatment adult regimen with 3 times per week continuation phase

Pretreatment Body Weight	2 Months Initial Phase (treatment given 5 times a week)		3rd Month (5 times a week)	5 Months Continuation Phase (3 times a week)
	RHZE 120/60/300/200 mg	streptomycin	RHZE	RH 150/100 mg	H 100 mg	E 400mg	RH 300/150mg	H 100mg	E 400mg
<50 kg	4 tabs	750 mg	4 tabs	3 tabs	1 tab	2 tabs
>50 kg	5 tabs	1000 mg	5 tabs				2 tabs	3 tabs	4 tabs

SUMMARY New adult TB patients are treated for 6 months. Retreatment adult TB patients are treated for 8 months.

Side effects of anti-TB drugs

The recommended TB drugs are safe, but the following should be noted:

• Streptomycin should not be used in pregnancy or over 65 years of age.
• Ethambutol should not be given to children under 8 years of age.
• Patients should be warned that their urine, and sometimes saliva, will be discoloured red (by rifampicin).
• Patients with impaired renal function should not be given ethambutol or streptomycin. Refer such patients.

Minor side effects:

• gastro-intestinal discomfort (any anti-TB drug)
• mild skin reactions (isoniazid and rifampicin)
• joint pains (pyrazinamide)
• flu-like symptoms (rifampicin)

These minor side effects are most common in the first month. Patients should be reassured that they are temporary and the importance of tolerating them should be explained. Additionally:

• Gastrointestinal symptoms may be minimised by taking the drugs with food, although drugs are best taken on an empty stomach.
• Symptoms may be less noticeable if drugs are taken before sleeping.
• Joint pains usually respond well to paracetamol.

Serious side effects of anti-TB drugs include:

• jaundice and hepatitis (isoniazid, rifampicin, pyrazinamide)
• rash and fever (isoniazid, rifampicin)
• bleeding tendency, shock and renal failure (rifampicin)
• impaired visual acuity and colour perception (ethambutol)
• giddiness, unsteadiness, ringing in the ears, deafness (streptomycin)

If patients develop any of the above serious side effects, stop drugs immediately and refer to a medical officer.

SUMMARY Serious side effects of anti-TB drugs are rare - they include hepatitis, impaired visual acuity and deafness. If serious side effects occur, stop anti-TB drugs immediately and refer to a medical officer.

Cotrimoxazole prophylaxis

Cotrimoxazole is highly effective in preventing pneumocystis carinii pneumonia and toxoplasmosis. It also has activity against pneumococcus, Salomonella and Nocardia.

The 'HIV and AIDS Clinical Care Guidelines for Adults' recommends cotrimoxazole 960 mg (either 3 times per week or 5 times per week) to all HIV-positive patients (whether they have TB or not) who:

• have a CD4 count less than 200 cells/cubic mm or
• have clinical signs of advanced immune deficiency (e.g., oropharangeal candidiasis) or
• have already had peumocystis carinii pneumonia or toxoplasmosis

A study in Abidjan, Cote d'Ivoire (Sassan-Morokro et al, 12th World AIDS Conference, Geneva 28 June-3 July 1998, Abstract #12461) found that daily cotrimoxazole (960 mg) prophylaxis among HIV-infected TB patients started one month into anti-TB treatment decreased mortality by 48% from 21.6 per 100 person-years to 11.3 per 100 person-years. It also decreased hospitalisation by 44%.

The spectrum of HIV-related opportunistic infections in South Africa may be different from the spectrum in Cote d'Ivoire. It is therefore not known whether providing cotrimoxazole prophylaxis to HIV-infected TB patients in South Africa will also decrease mortality and hospitalisations. However, cotrimoxazole prophylaxis is being recommended for any HIV-positive people with advanced immune deficiency and TB is a sign of immune deficiency in people living with HIV. It is therefore recommended that all HIV-positive TB patients be offered cotrimoxazole prophylaxis as follows:

• Wait until the patient has completed one month of TB treatment - this is to be able to differentiate between side effects from anti-TB drugs and side effects from cotrimoxazole.
• Counsel patients on the effectiveness and side effects of cotrimoxazole (i.e., explain to patients that cotrimoxazole can help prevent pneumonia and other infections, that it is only effective while the patient takes it so that it should be taken for the rest of their lives and that it can cause a rash and other side effects).
• If a patient chooses to accept it, provide cotimoxazole 960mg either 3 times per week (Monday, Wednesday, Friday) or 5 times per week (daily from Monday to Friday).

6. CONTACTS

Contact tracing

Contacts are people were living in the same house as a TB patient while the patient was smear-positive. Contacts are at risk of becoming infected with TB.

• Advise patients to bring any contacts under 5 years old to the clinic for assessment.
• Advise patients to tell contacts who are older than 5 years old to come to the clinic if they develop TB symptoms.
• Put contacts up to 5 years old on TB prophylaxis.
• Contacts of any age who are known to be HIV-positive should be asked to come to the clinic to assess if they should start TB preventive therapy (see "Eligibility for TB Preventive Therapy" section).
• Your first priority is to cure new smear-positive (infectious) TB patients. Contact tracing is a lesser priority.

SUMMARY Contacts up to 5 years old should be put on TB prophylaxis. Contacts of any age who are known to be HIV-positive should be asked to come to the clinic to assess if they should start TB preventive therapy.

Prophylaxis for child contacts up to 5 years old

TB prophylaxis for children < 5 years old

R = rifampicin H = isoniazid

7. MONITORING PROGRESS IN ADULT PULMONARY TB

During TB treatment, all pulmonary TB patients should be monitored by sputum smear microscopy. In some cases, sputum culture and susceptibility testing is necessary. Monitoring TB is done the same way whether a patient is infected with HIV or not.

SUMMARY Monitoring TB is done the same way whether a patient is infected with HIV or not.

• New patients

• Sputum microscopy at 2 months

• At 2 months, send 2 sputum samples for smear microscopy for all new patients.
• If both smears are negative, then start the continuation phase of treatment (see "Treatment of TB - New Adult Patients" section).
• If one or both of the 2-month smears is positive, then give a third month of intensive phase treatment.

• Sputum investigations at 3 months

• Send 2 sputum samples for smear microscopy at 3 months only if one or both of the 2-month smears was positive.
• If both 3-month smears are negative, then the continuation phase of treatment should be given for 3 months (not 4 months), so that a total of 6 months of treatment is given.
• If one or both of the smears is positive, then a sputum sample should be sent for TB culture and susceptibility and the continuation phase should be started.
• If the TB bacilli are susceptible to all anti-TB drugs, the continuation phase should be continued.
• If the TB bacilli are resistant to any of the anti-TB drugs, the patient should be referred to a medical officer.

• Sputum investigations at 5 months

• Send 2 sputa for smear microscopy for all new patients.
• If both smears are negative and the patient is clinically well continue treatment until 6 months and register the patient as cured.
• If one or both of the 5 month smears is positive, then register the patient as a treatment failure, send sputum for culture and susceptibility, re-register the patient as a retreatment patient and start the retreatment regimen (see "Treatment of TB - Retreatment Adult Patients" section).

SUMMARY Send 2 sputa for smear microscopy at 2 months and at 5 months for all new patients. If a patient has a positive sputum smear at 2 months, give an extra month of intensive phase treatment and send 2 sputa for smear microscopy at 3 months. If a patient has a positive sputum smear at 3 months or at 5 months, send sputum for culture and susceptibility testing.

• Retreatment patients

• Sputum investigations at 3 months

• Send 2 sputa for smear microscopy at 3 months for all retreatment patients.
• If both smears are negative, start continuation phase (see "Treatment of TB - Retreatment Adult Patients" section).
• If one or both smears are positive, send sputum for culture and susceptibility and start continuation phase.
• If the TB bacilli are susceptible to all anti-TB drugs, continue continuation phase.
• If the TB bacilli are resistant to any of the anti-TB drugs, refer to a medical officer.

• Sputum investigations at 7 months

• Send 2 sputa for smear microscopy at 7 months for all retreatment patients.
• If both smears are negative, continue treatment until 8 months and register the patient as cured.
• If one or both of the smears are positive, register the patient as a treatment failure and refer to a medical officer.

SUMMARY Send 2 sputa for smear microscopy at 3 months and at 7 months for all retreatment patients. If a patient has a positive smear at 3 months, send sputum for culture and susceptibility testing. If a patient has a positive smear at 7 months, refer the patient to a medical officer.

8. DIAGNOSIS OF TB IN CHILDREN

Diagnosis of TB other than TB meningitis

The diagnosis of TB in children can be difficult; easy to over-diagnose but also easy to miss.

• Bacteriological confirmation of pulmonary TB in children is usually not possible because under the age of ten years, children with pulmonary TB rarely cough up sputum.
• Children usually swallow their sputum. Gastric aspiration and laryngeal swabs may be used to identify swallowed organisms in the diagnosis of pulmonary TB in children, although this is not currently recommended.
• The diagnosis of TB in children revolves around: the clinical features, tuberculin skin test, chest X-ray, history of contact with a sputum positive pulmonary TB case.

• Clinical features

• Decrease in weight, loss of appetite and failure to thrive without any obvious explanation. The 'Road to Health' card can help to identify these children. Growth percentiles remaining the same or decreasing for two or more months must be investigated. If no cause is obvious, then TB should be suspected.
• Cough for more than two weeks and chest pain.
• An audible wheeze which does not respond to bronchodilators is suggestive of airway compression which is the result of enlarged intra-thoracic glands.
• Repeated respiratory tract infections which do not respond to treatment.
• Painless swelling of the lymph nodes - enlarged matted glands in the neck commonly occur.
• Two or more episodes of fever without any obvious cause such as malaria or acute respiratory infection.
• Non-specific signs include: steady high fever, rapid pulse, vomiting and diarrhoea, cyanosis (blueness of the lips).
• The two forms of TB which are most dangerous to children are: TB meningitis and miliary TB (see "Diagnosis of TB Meningitis in Children" and "Diagnosis of Extrapulmonary TB" sections).

• Tuberculin skin test

• The tuberculin skin test measures the body's immune response to an injection of tuberculin purified protein derivative (PPD).
• The Mantoux Test injects a known amount of PPD between the layers of skin (intradermally). Ensure that the injection goes into and not under the skin. Measure the reaction to the test at the site of injection 48-72 hours later.
• TINE/MONO tests use instruments which are impregnated with PPD and need only to be pressed into the skin of the forearm. The area of induration is measured 72 hours later.
• Measure the diameter of the reaction at widest point of the raised, thickened area (induration). For the Mantoux and Monotests, record the result in millimetres, rather than positive or negative. For the Tine test, measure the amount of blistering (see Table below).
• To help measure accurately, mark the edges of the induration at the widest point with a pen (two point pen method) and measure the exact distance between the two points.

What does a positive tuberculin skin test mean?

• A positive test indicates infection with TB, but not necessarily TB disease.
• In a young child a strongly positive skin test would indicate recent (6 weeks or more) infection. This is a risk factor for progression to disease. In the presence of other features (i.e. history, TB contact, signs and symptoms of TB and x-ray changes) a positive tuberculin skin test is suggestive of TB disease.
• A positive reaction occurs after previous BCG immunisation and should remain positive for several years thereafter. This reaction is usually a weaker reaction than the reaction to natural infection with M. tuberculosis.
• A positive reaction is only one piece of evidence in favour of the diagnosis.

Tuberculin Test	Previous BCG	No previous BCG	HIV+
Mantoux	15 mm or more	10 mm or more	more 4 mm
Monotest	8 mm or more	4 mm or more	uncertain
TINE test	Blistering and confluent swelling	ring of induration	uncertain

What does a negative tuberculin skin test mean?

• A negative tuberculin skin test does not exclude TB.
• Various conditions may cause a negative reaction even if a child has TB. If the chest X-ray is typical of TB and the skin test is negative, TB can be diagnosed.
• Conditions which may suppress the tuberculin skin test and give a false negative result include: HIV infection, malnutrition, severe viral infections (eg. measles, chicken pox), cancer, immunosuppressive drugs (eg. steroids), severe disseminated TB.

Chest Radiography (x-ray)

Changes on x-rays are often non-specific, so TB should not be diagnosed from x-rays alone. The most common x-ray signs are:

• A broad mediastinum due to enlarged hilar or mediastinal glands. The enlarged hilar glands may compress the airway and cause obstruction and lobar collapse.
• Miliary infiltrations in the lungs.
• Pleural effusions which usually occur in children older than six years.
• X-rays can be helpful but results depend on the quality of the x-ray and the expertise of the doctor who reads it.

• Contact History

• A history of close contact (family member, person living in the same household, friend, caretaker) with a person who has smear positive TB increases the likelihood of the child being infected with TB.

The impact of HIV on the diagnosis of TB in children

HIV makes the diagnosis of TB in children even more difficult for the following reasons:

• Several HIV-related respiratory diseases, including TB, may have similar symptoms.
• Weight loss is a common problem in HIV-positive children due to chronic diarrhoea.
• The interpretation of the tuberculin skin test is even more unreliable than usual. An immunocompromised child may have a negative tuberculin skin test despite having TB.
• The radiological features of TB in HIV positive children with TB are often atypical.
• Differential diagnosis of pulmonary TB in HIV-infected children: bacterial pneumonia, viral pneumonia, fungal lung disease, pneumocystis carinii pneumonia, pulmonary lymphoma.
• If you are unsure of the diagnosis, treat the child with antibiotics for 5-7 days and repeat the chest X-ray after two weeks.

• A score system for the diagnosis of TB in children

A score system is one way of trying to improve the diagnosis of childhood TB by the careful and systematic collection of diagnostic information. It will aid clinical judgement. The table below shows a score chart for the diagnosis of childhood TB:

SCORE SHEET FOR TB IN CHILDREN
A score of 7 or more indicates a high likelihood of TB
Feature	0	1	2	3	4	Score
	< 2	2-4		> 4
Nutrition[% weight or age]	> 80%	60-80%		< 60%
Family history of TB	None	Reported by family		proved sputum positive
Tuberculin test			Weeks of illness	Positive
Malnutrition				not improving after 4 weeks
Unexplained fever			No response to treatment
LOCAL
				Lymph nodes
				Joint or bone swelling
				Abdominal mass or ascites
				CNS signs, Abnormal CSF
					Angle deformity of spine
					TOTAL
Name of Child………………………………
Date………………………………………….	Completed by………………………………

How to apply/read score system

Example: Score the following patient for TB:

A young child has weight loss (weight < 60% for age) with no family member with TB, skin test is not available, has bouts of unexplained fever with no response to antibiotic and positive lymph nodes in the neck.

	FEATURE	SCORE
	Weight less than 60%	3
	Family history of TB	0
	Tuberculin Test	0
	Unexplained fever, no response to treatment	2
	Lymph nodes	3
	TOTAL	8

Any score of 7 or more is suggestive of TB!

Diagnosis of TB Meningitis in Children

TB meningitis is a very serious form of TB in children. Complications include obstruction of cerebrospinal fluid (CSF) flow, hydrocephalus, inappropriate antidiuretic hormone secretion, hemi- or quadriplegia, convulsions, deafness, blindness and mental retardation.

Symptoms

• Headache
• Irritability
• Drowsiness
• Convulsions
• weight loss

History

• contact with a TB patient

Physical Signs

• signs of meningeal irritation (neck pain and resistance to neck flexion)
• cranial nerve palsies
• altered level of consciousness

Investigations

• lumbar puncture (CSF findings: raised protein, low glucose, low chloride, lymphocytes predominate, gram stain negative. Acid fast bacilli are seldom found)
• Mantoux test positive (see above)
• chest x-ray may be abnormal (see above)

9. DIAGNOSIS OF HIV IN CHILDREN

See 'Paediatric HIV and AIDS Guidelines'.

10. TREATMENT OF TB IN CHILDREN

Treatment of TB Other Than TB Meningitis in Children

Treatment of TB in Children (Regimen 3)

Pretreatment body weight	2 months initial phase (5 times a week)	4 months continuation phase (5 times a week)
	RHZ60/30/150 mg	RH60/30 mg
3 - 4 kg	½ tablet	½ tablet
5 - 7 kg	1 tablet	1 tablet
8 - 9 kg	1 ½ tablets	1 ½ tablets
10 -14 kg	2 tablets	2 tablets
15 - 19 kg	3 tablets	3 tablets
20 - 24 kg	4 tablets	4 tablets
25 - 29 kg	5 tablets	5 tablets
30 - 35 kg	6 tablets	6 tablets

R = rifampicin:H = isoniazidZ = pyrazinamide

Treatment of TB in Children with 3 times per week Continuation Phase

Pretreatment body weight	2 month initial phase (5 times a week)	4 months continuation phase (3 times a week)
	RHZ60/30/150 mg	RH60/60 mg
3 - 4 kg	½ tablet	½ tablet
5 - 7 kg	1 tablet	1 tablet
8 - 9 kg	1 ½ tablets	1 ½ tablets
10 - 14 kg	2 tablets	2 tablets
15 - 19 kg	3 tablets	3 tablets
20 - 24 kg	4 tablets	4 tablets
25 - 29 kg	5 tablets	5 tablets
30 - 35 kg	6 tablets	6 tablets

R = rifampicin H = isoniazidZ = pyrazinamide

• Treatment of Complications in Children

In patients with large hilar and mediastinal glands which are causing potentially life threatening airway compression effects (like wheezing and lobar collapse), as well as patients with symptomatic pleural effusions:

• Prednisone 2-4 mg/kg/24 hours, orally, in 3 divided doses for 4-6 weeks. They can be added to the anti-TB drugs. Taper to stop over 2 weeks.

Treatment of TB Meningitis in Children

• Non drug treatment

• Monitor neurological status at least daily.
• Ensure adequate nutrition. This may require naso-gastric feeding initially.
• Manage hydrocephalus. This may require CSF shunting or repeated lumbar punctures.
• Monitor liver function. Most of the drugs used are hepatotoxic.
• Provide physio- and occupational therapy.

• Drug treatment

3 Month Initial Phase:

Rifampicin, oral, 20 mg/kg/day as a single daily dose
Isoniazid, oral, 20 mg/kg/day as a single daily dose
Pyrazinamide, oral, 40 mg/kg/day as a single daily dose
Ethionamide, oral, 20 mg/kg/day as a single daily dose (maximum 2 gm per 24 hours)

6 Month Continuation Phase:

Rifampicin, oral, 20 mg/kg/day as a single daily dose 5 days per week
Isoniazid, oral, 20 mg/kg/day as a single daily dose 5 days per week
Ethionamide, oral, 20 mg/kg/day as a single daily dose 5 days per week (maximum 2 gm per 24 hours)

Steroids

If steroids are required, then give:

Prednisone 2-4mg/kg/24 hours, orally, in 3 divided doses for 4-6 weeks. Then taper to stop over 14-21days.

• Management of Complications of TB Meningitis in Children

A medical practitioner should manage these complications of TB meningitis in a referral health facility.

• Hydrocephalus

• Acetazolamide 100 mg/kg/24 hours, orally, in 3 divided doses (maximum 1 gm per 24 hours)
• Furosemide, oral, 1-2 mg/kg/24 hours as a single dose for at least 4-6 weeks.
• Refer non-communicating hydrocephalus for ventriculo-peritoneal shunt.

• Acute convulsions

• Diazepam 0.2 - 0.3 mg/kg slowly IV.
• Maintenance therapy with phenobarbitone 5-10mg/kg/24 hours, orally, in 2 divided doses until patient is free of convulsions for 2 weeks. Taper to stop over 1 week.

• Severe cerebral oedema

• Consider as part of the management of raised intracranial pressure if there is an acute deterioration of the level of consciousness.
• Elevate head of bed + 15 degrees.
• Maintain PaCO2 between 28-30mmHg (intubate and ventilate if necessary)
• Mannitol 1g/kg IV over 1 hour (do not repeat)
• Furosemide 1mg/kg IV (do not repeat)
• Avoid fluid overload. Limit total daily fluid intake (IV + oral) to 75% of maintenance requirements for age to minimize the effects of inappropriate antidiuretic hormone secretion.

11. TB PREVENTIVE THERAPY

TB Preventive Therapy and Health Services

TB can be prevented in people living with HIV and AIDS by offering isoniazid prophylaxis (TB preventive therapy). In these individuals, TB preventive therapy decreases the risk of TB disease and should be part of a package of care for people living with HIV and AIDS.

TB preventive therapy should only be offered in the following situations:

• Voluntary HIV counselling and testing by appropriately trained staff is available.
• Patients can be followed monthly to exclude active TB disease and side effects.
• The provision of preventive therapy does not interfere with the detection and cure of infectious (smear-positive) pulmonary TB cases.
• The local AIDS programme takes responsibility for implementation and there is strong collaboration with the TB programme.

Practically, this means that TB preventive therapy will not be offered initially in all public health services. It can be considered in services which have staff who can be trained in HIV counselling, where TB services are functioning well, and where monthly follow up is possible. It will be piloted in HIV/TB pilot districts and may be considered in occupational health services (including mines), in prison health services, and for health care workers.

If your health service is interested in offering TB preventive therapy, then contact your Provincial HIV and AIDS/STD Coordinator and your Provincial TB Coordinator to ensure proper co-ordination and monitoring.

SUMMARY TB preventive therapy should only be offered by a health service if it does not interfere with the detection and cure of infectious pulmonary TB cases and if patients can be followed monthly to exclude active TB disease.

• Eligibility for TB Preventive Therapy

TB preventive therapy has been proven to prevent TB in HIV-positive patients with greater benefit seen in those who have positive tuberculin skin tests. An HIV-positive individual should be counselled on TB preventive therapy. The counselling should explain that TB preventive therapy decreases the risk of getting TB but that TB may still occur despite it. It should also explain that there is a small risk of hepatitis as a side effect of taking isoniazid.

If the individual would like to receive TB preventive therapy, the following steps should be followed:

• Screen for TB symptoms

• Determine if the patient has symptoms of TB. The symptoms of pulmonary TB are the same whether patients are infected with HIV or not:

• cough
• night sweats and fever
• loss of appetite and weight
• tiredness and weakness
• chest pain
• coughing up blood (haemoptysis)
• TB of other organs (extrapulmonary TB) may also occur and is more frequent in people infected with HIV
• If the patient does have TB symptoms, investigate for TB (see "Diagnosis of TB in Adults" section) or refer to health services which diagnose and treat TB.
• If the patient does not have TB symptoms do a chest x-ray, if possible.

• Chest x-ray

• If possible, a chest x-ray should be done to rule out TB lung disease in asymptomatic patients.
• If the chest x-ray shows abnormalities consistent with TB, do not start TB preventive therapy and investigate further for TB.

• Tuberculin testing

The World Health Organisation (WHO) and the Joint United Nations Programme on HIV and AIDS (UNAIDS) have recommended that in areas where the prevalence of TB infection is greater than 30%, tuberculin testing is not required for screening for TB preventive therapy. However, clinical trials have shown that the benefit of TB preventive therapy is only significant in HIV-positive people with positive tuberculin skin tests.

In South Africa, the prevalence of TB infection is approximately 60%. Although tuberculin testing is suggested, it is not required for screening for TB preventive therapy. If your health service chooses to use tuberculin skin testing to screen for TB preventive therapy, then do the following:

• If the patient does not have symptoms of TB and has a normal chest x-ray, do a tuberculin skin test. If there is induration greater than or equal to 5 mm (tuberculin test positive) and there are no TB symptoms, start TB preventive therapy.
• If the tuberculin skin test is negative, do not start TB preventive therapy.

SUMMARY TB preventive therapy should be offered to HIV-positive patients with no symptoms of TB and a normal chest x-ray. If tuberculin testing is done, TB preventive therapy should be offered to tuberculin-positive people living with HIV with no symptoms of TB and a normal chest x-ray.

TB Preventive Therapy Regimen

Before starting TB preventive therapy, and on a regular basis, the patient should be counselled on HIV, the symptoms of side effects of isoniazid (particularly hepatitis), the symptoms of active tuberculosis and the importance of seeking care if they develop those symptoms while on preventive therapy.

For HIV-positive patients with no TB symptoms:

• Give isoniazid (INH) 5 mg/kg (maximum 300 mg) daily for 6 months.
• Give 1 month supply to the patient at a time. Ask the patient to return on a monthly basis.
• Advise the patient to return immediately if TB symptoms develop.
• At each monthly visit, monitor adherence and determine if the patient has symptoms of TB or is experiencing side effects to isoniazid (major: jaundice, or vomiting and confusion from hepatitis; minor: burning sensation in feet from peripheral neuropathy).
• If, at any time during the 6 months of preventive therapy, the patient develops TB symptoms, stop TB preventive therapy and investigate for TB.
• If the patient develops peripheral neuropathy, give pyridoxine 10-25 mg daily.
• If the patient develops hepatitis, stop TB preventive therapy and refer to a medical officer.
• If the patient interrupts therapy, they should be counselled on the importance of adherence and may be restarted with the aim of providing at least 6 months of isoniazid during a one year period.
• If the patient interrupts therapy twice, despite counselling, then preventive therapy should be stopped.
• Maintain individual patient records and record the following: attendance at scheduled appointments, adherence (proportion of doses taken), toxicity and withdrawals from therapy due to toxicity
• Maintain a TB preventive therapy register and monitor the following:
• number of persons started on TB preventive therapy
• number of persons interrupting TB preventive therapy, for which reasons
• number of persons completed preventive therapy
• Keep track of the number of suspected TB cases in screening, the number of suspected TB cases during preventive therapy, and the number of individuals presenting to TB services who have previously taken preventive therapy.

SUMMARY Give isoniazid 5 mg/kg (maximum 300 mg) daily for 6 months. See the patient on a monthly basis. If TB symptoms develop, stop TB preventive therapy and investigate for TB. If the patient develops hepatitis, stop TB preventive therapy and refer to a medical officer.

12. PREVENTION AND TREATMENT OF OTHER HIV-RELATED OPPORTUNISTIC INFECTIONS

See 'HIV and AIDS Management Guidelines'.

See cotrimoxazole prophylaxis in the 'Treatment of TB in Adults' section.

13. PROTECTION FROM TB INFECTION

Health care workers who are in contact with TB patients are at increased risk for TB infection and TB disease. Those involved in autopsies, drainage of TB abscesses and cough-inducing procedures (bronchoscopy, aerosolised pentamidine treatment) are at high risk. HIV-infected health care workers have a particularly high risk of TB.

In order to limit transmission of TB in health facilities and to protect health care workers, these measures should be followed:

• Consider HIV counselling and testing

• Any health care worker in TB wards, general medical wards, outpatients clinics or laboratories which do TB microscopy should seriously consider seeking voluntary confidential HIV counselling and testing. If HIV-positive, they should be moved or given other responsibilities to minimize your contact with TB suspects or TB patients.
• In settings where there is stigmatisation of HIV-infected individuals, health care workers may be unwilling to be tested for HIV. Help decrease stigma through ongoing education and counselling.
• Many health care workers may be concerned that confidentiality of a positive test result will be difficult to maintain, because people will assume they are HIV-infected if they are moved away from contact with TB patients. This is a difficult issue to resolve. One possibility is to also offer such a move to other health care workers with increased risk for TB, such as diabetics and people on corticosteroids.

• Seek care if TB symptoms develop

• Any health worker should seek care and be investigated for TB as soon as they develop TB symptoms. If they delay, they will increase the severity of the disease and will increase the risk of infecting others.

• Rapidly diagnose and treat infectious TB patients

• Rapidly diagnose and treat infectious TB patients. The sooner they are diagnosed and started on treatment the sooner they will become non-infectious.
• Instruct patients to cover their mouths when coughing.
• Collect sputum properly outdoors (see "Diagnosis of Pulmonary TB - Sputum collection" section).
• Decrease delays in sputum collection and delivery. If possible, sputum samples should be transported to a microscopy centre daily, and the results should be sent back from the laboratory on the same or the next day.
• In hospitals, assign a staff member the responsibility of "cough officer" to collect sputum, deliver results back to the ward and ensure that smear-positive pulmonary TB patients are registered and started on treatment as soon as a diagnosis is made.
• As soon as sputa results are received at a clinic, trace smear-positive patients and ask them to return to the clinic to start treatment.
• Ensure directly observed treatment. If patients interrupt treatment, they may become infectious.

• Isolate TB suspects and patients

• Separate coughing patients from others in waiting rooms.
• Triage coughing patients to be assessed by a health care worker quickly.
• Do not admit TB suspects for investigation in hospital if they can be investigated as outpatients. This will decrease the number of potentially infectious patients who are admitted.
• Isolate TB suspects who are admitted to hospital from other patients, especially other TB patients and immunocompromised patients (patients who are known or suspected to have HIV, diabetics, patients on systemic corticosteroids). If isolation rooms are not available, TB suspects could be kept in one area of a ward which is screened off from other sections of the ward.
• Give at least 2 weeks of sick leave to smear-positive TB patients. If patients are still coughing or are too ill to return to work then their sick leave should be extended. There is almost no increased risk of TB disease among family contacts of patients treated at home.
• Isolate smear-positive pulmonary TB patients from other patients (especially immunocompromised patients) for at least 2 weeks or until their cough resolves. Establishing a TB ward best does isolation of TB patients. Smear-negative and extrapulmonary TB patients need not be isolated, but they can also be treated in a TB ward.
• If possible, isolate TB patients who are infected with HIV in single rooms to limit their exposure to air-borne pathogens.

• Implement environmental controls

• Isolation rooms, TB wards, general medical wards, outpatient clinics and rooms in which sputum induction procedures are carried out should have windows that open to the outside and doors to other parts of the hospital which are kept closed most of the time. Exhaust fans which move air from inside to outside should also be installed. Isolation rooms should ideally be located on higher floors.
• Hospital TB wards should have large windows to let plenty of sunlight in. The latter is a cheap form of ultraviolet light, which has a germicidal effect on TB bacilli.
• Ultra-violet lights are not currently recommended because, although there is experimental evidence that ultra-violet lights can kill TB bacilli, there is no evidence of their effectiveness in reducing TB transmission in practice. UV lights are expensive, difficult to maintain and potentially harmful if not installed properly.
• Guidelines for laboratory safety are covered in the "Training Manual for Tuberculosis Microscopy Centres" available from the Department of Health.

• Ensure proper disinfection

• Wash hands with an appropriate disinfectant or alcohol rub if your hands have contacted the patient without gloves.
• All equipment used on TB/HIV patients should either be autoclaveable or disposable. None of the equipment should be reused except sphygmomanometers or other equipment which is applied to the unbroken skin of the patient.
• Clean thermometers with soap and water and then soak in 70% alcohol for 10 minutes after each use.

• Use protective clothing

• The effectiveness of high efficiency particulate air-filter (HEPA) respirators (masks which filter particles 1 micron in size with 95% efficiency) in preventing TB transmission has not been quantified. These masks are very expensive (US$5-7) and are therefore not affordable for most health facilities in South Africa.
• If HEPA respirators can be provided, they should be used by staff who are involved in high risk situations, such as procedures which produce respiratory aerosols (autopsies, draining TB abscesses, bronchoscopy, administering aerosolized pentamidine, endotracheal suction), working with multidrug resistant TB patients and ambulance staff who are transporting coughing TB patients.
• Masks should be discarded after being used in a high risk procedure and should generally not be worn for more than 10 minutes.
• Masks are not currently recommended for use in outpatient clinics or TB wards with drug-susceptible TB patients.
• Surgical masks are less than 50% effective in preventing the inhalation of droplet nuclei containing TB bacilli and are therefore not recommended for staff or visitors to TB wards.
• The use of surgical masks by TB patients with a productive cough who are being transported to other areas of the hospital for investigations may help to reduce TB transmission.
• Wear gloves when handling objects contaminated by sputum.

• BCG vaccination may be considered but is not recommended

• Most people in South Africa receive BCG vaccination at birth.
• BCG revaccination is not recommended.
• BCG should not be given to HIV-positive individuals because it may cause disseminated BCG infection.
• If a health care worker who works with TB patients did not receive BCG at birth, counselling could be offered on its possible benefits and risks. If the health care worker is interested in receiving BCG vaccination, then a tuberculin skin test should be done. If the skin test is negative, then BCG could be administered.

• Screening of health care workers working with TB patients

• No regular screening is required.
• Pre-employment tuberculin skin test may be done to detect past infection and a baseline chest x-ray may be done.
• Serial tuberculin testing is not recommended. The only situation in which it should be considered, is in HIV-positive health care workers in settings where decisions for provision of TB preventive therapy are based on tuberculin results (see "TB Preventive Therapy" section).
• Regular questionnaires on symptoms of TB and regular weighing to detect unexplained weight loss could also be considered, although these have not been proven to be effective.
• Annual chest x-ray screening is not recommended. A few early lesions may be detected by chest x-ray, but in the absence of symptoms, it is difficult to determine the significance of the x-ray findings.
• Tuberculin skin tests may be done on termination of employment. If the test is positive, and the pre-employment test was negative, and if the health care worker subsequently gets sick with TB, they are eligible for compensation according to the Compensation for Occupational Injuries and Diseases Act. A chest x-ray may be done on termination of employment to compare to the pre-employment chest x-ray.

SUMMARY HIV-positive health care workers should avoid contact with TB patients. Health care workers should seek care if they develop TB symptoms. The best way to prevent TB transmission is to rapidly diagnose and treat infectious TB patients. Isolation of TB patients prevents TB transmission to other patients. TB wards should have large windows with good ventilation and sunlight. If available, HEPA masks should be used by health care workers in high risk situations.

14. PROTECTION FROM HIV INFECTION

HIV is transmitted through unprotected sexual intercourse, contaminated blood products and from mother to child in pregnancy and breastfeeding. The biggest risk of HIV transmission when treating TB patients is through a needle stick injury with the intramuscular injection of streptomycin in the adult retreatment regimen. When administering these injections remember to:

• Practice universal blood and body fluid precautions on all patients, regardless of HIV status.
• Wear gloves during the injection and when handling any blood-contaminated materials, such as swabs, cotton wool, bandages, dressings and instruments or when handling any body fluids.
• Use a new needle for each injection.
• After injection, do not replace the cover (sheath) of the needle unless there is a special apparatus which will hold the sheath.
• If a needle must be re-sheathed, do not hold the sheath with your other hand. It is better to place it in a sheath holder, or on a flat surface, while you insert the needle into the sheath.
• All needles must be discarded into a protected container.
• Never discard a used needle or sharp instrument into a dustbin, paper bag or plastic bag.

SUMMARY Practice universal blood and body fluid precautions. Wear gloves when injecting streptomycin. After injection, it is better not to replace the cover of the needle. Discard the needle into a protected container.

15. CONTINUITY OF CARE

A major problem which is faced by health care workers and TB/HIV co-infected patients is the lack of continuity of care in South Africa. It is important for the following reasons:

• For the patient, it helps maintain health and relieves anxiety.
• For health care workers, it assists in the provision of high quality care.
• For communities, it limits the spread of disease - eg. adequate follow up of TB patients will prevent TB transmission, improve TB cure rates and prevent the development of multidrug resistant TB.
• Ensuring continuity of care should be a shared responsibility of patients, health care workers and communities:
• Patients should learn the symptoms of HIV and AIDS/STD/TB, seek care if they develop them, and follow health care workers' recommendations on when to come for appointments and go to referral facilities.
• Health care workers should provide high quality services, and should communicate well with patients, and staff from other facilities.
• Communities should ensure that appropriate services are available for their members who require care and support.
• Continuity of care for patients co-infected with HIV and TB can be improved in the following ways:

• Follow admission and discharge criteria for TB patients

The National TB Control Programme has developed admission and discharge criteria for TB patients (see Annex 1) which incorporate several important principles for referral as follows:

• Priority for admission should be given to new smear-positive pulmonary TB patients.
• Only patients who are sick enough to require hospital care or who do not have access to community-based care should be admitted to hospital
• Patients referred for admission should be accompanied by a completed TB transfer form (see Annex 2).
• The decision to admit an HIV-infected TB patient should be made in the same way as for any other TB patient, but staff who work with HIV-infected patients require ongoing training and support to deal with the medical and social implications of AIDS, and patients require counselling.
• Discharge planning should be started on admission and completed within 2 weeks of admission and should include recruitment of a treatment supporter, health education of the patient and the treatment supporter, and communication with the patient's chosen outpatient clinic to ensure continued treatment and monitoring.
• Patients should be discharged as soon as the patient is medically stable and either able to care for himself or has access to family or community-based care and is willing and able to access treatment and to be monitored either by going to a clinic or by receiving visits from a treatment supporter.

• Create resource lists of services and facilities for referral

• Obtain a copy of the resource list for HIV and AIDS and STD services, 'South African AIDS Network: A Directory of the National AIDS Database, 1997' from the Department of Health.
• Collaborate with other role players (government departments, community based organisations, non-governmental organisations, private organisations) to create a district level resource list for HIV and AIDS/STD/TB which lists the type of service, the name of a contact person, the telephone number, and how to refer a person to the service.

• Encourage formation of community support services

• Encourage the formation of community support services (directly observed TB treatment, home based care, palliative care, counselling, nutritional assistance, spiritual support and economic support) and provide them with technical assistance.

• Use available transfer forms

• For TB patients, whether they are infected with HIV or not, use the 'Patient Transfer Form' (GW 20/14) (see Annex 2) which is available from the Department of Health.
• Give this transfer form to the patient and send a duplicate to the referral facility on discharge to ensure that health care workers there receive all the information they need to provide continuing care.
• If you feel that the form does not provide sufficient space or information, add a referral letter with more details.
• For HIV-infected patients, consider giving the following information with the patient's consent: the date of the patient's first positive HIV test, the history of opportunistic infections, the current immune status (lymphocyte count, +/-CD4, +/- viral load), current medications for prophylaxis and treatment, and details on the patient's support network (with whom there is shared confidentiality of the patient's HIV status).
• Consider measuring the proportion of patients who are lost to follow up after being discharged from hospital using the "Loss to follow up form" (see Annex 3).

• Improve co-ordination between services

• Ensure good communication and collaboration when referring patients between community services, clinics, hospitals, districts and provinces.
• Organise monthly meetings of key role players (district coordinators, health care workers from public and private hospitals and clinics, laboratories, community-based organisations, non-governmental organisations) to improve communication and co-ordination.
• If possible, telephone the referral facility to tell them when a patient is being transferred to their care.

• Plan for high patient mobility

• When a patient is started on TB treatment or the management of other HIV-related diseases, ask the patient about their current employment and social circumstances. Try to determine if it is likely that the patient will move in the near future.
• Provide all TB patients with the "Patient Treatment Card" (GW 20/15) and encourage them to carry it at all times. This card has most of the information required for any facility to continue providing appropriate TB treatment to the patient.
• Counsel patients on the importance of continuity of care and encourage them to come to the clinic before moving so that they can receive a transfer form and a sufficient supply of medications.

• Communicate well with patients and provide health education

• Good communication with patients is essential to provide them with adequate information and support. Listening to a patient's concerns is time well spent.
• Improved communication will increase trust, relieve anxiety and increase the likelihood that a patient will report any problems which may interfere with treatment.
• Provide health education on the symptoms of AIDS, STDs, TB and other opportunistic infections and encourage patients to seek care if those symptoms develop. If patients present to health facilities at an early stage they have a better chance of being cured.

• Make a home visit and verify contact details

• If possible, conduct a home visit to verify the patient's address and to assess the patient's home environment and support network.
• Home visits may be done by anyone on the health management team including doctors, nurses, social workers, health educators or community health workers.

• Ensure adequate staff and transport

• Ensure adequate staff and drug supplies in clinics so patients can confidently seek care at primary health care level instead of going directly to hospitals.
• When possible, transport discharged patients from hospitals to the referral clinics to decrease loss to follow up.

SUMMARY Continuity of care can be improved through following admission and discharge criteria, creating resource lists, using available transfer forms, improving communication with patients and between service providers.

16. NON TUBERCULOUS MYCOBACTERIAL INFECTIONS (NTM)

Non tuberculous Mycobacterial infections (NTM) are generally considered as a single group, although the individual organisms vary in clinical significance, the treatment of choice and the response to treatment in patients.

• NTM organisms are less pathogenic than M. tuberculosis and rarely cause disease in otherwise healthy individuals. HIV-positive patients and mine workers are at increased risk for NTM.
• NTM is usually diagnosed after receiving the result of a Mycobacterial culture which was sent for detection of M. tuberculosis.
• A NTM isolate on culture does not necessarily imply NTM disease since transient, harmless, sputum or urine carriage can occur and many NTM species are widely distributed in the environment and can colonise water systems, giving a high potential for specimen or laboratory contamination.
• The diagnosis of NTM disease should be based on repeated identification of the same NTM organism from more than one specimen whenever possible - inappropriate treatment of a non-pathological isolate will result in the patient being unnecessarily exposed to a lengthy, potentially toxic and costly drug regimen and may delay diagnosis of the true cause of illness.
• The most common manifestations of pathogenic NTM infection in HIV-negative individuals are pulmonary disease resembling TB in adults and lymphadenitis in children.
• Soft tissue and musculoskeletal infections, usually following trauma or surgery, can also occur.
• Advanced HIV infection causes a greatly increased susceptibility to Mycobacterium avium disease, usually presenting as a disseminated infection with no pulmonary focus.
• NTM disease is not transmitted from one person to another. Infection is acquired from organisms in dust and water.
• Refer patients with NTM to a TB referral centre. NTM should not be treated at primary health care level.

SUMMARY NTM is uncommon but HIV-infected patients and mine workers are at increased risk for it NTM is diagnosed by Mycobacterial culture·Refer patients with NTM to a TB referral centre

Annex 1

Hospital Admission and Discharge Criteria for Tuberculosis Patients

Aim

To ensure that TB hospital beds in South Africa are used optimally by:

• Ensuring successful completion of the intensive phase of TB treatment in new smear-positive TB patients, where access to clinic or community-based treatment support (direct observation) is difficult.
• Providing appropriate and effective care for TB patients who are sick enough to require hospitalisation, until they are well enough to be treated at the clinic or in the community.
• Ensuring that patients who are referred to and from hospitals are not lost to follow up by implementing appropriate referral mechanisms.

Choice of Hospital for Referral