Tuberculosis

Tuberculosis - in association with NICE

د. حسين محمد جمعه
اختصاصي الامراض الباطنة
البورد العربي
كلية طب الموصل
2011

Learning bite

The treatment you prescribe for a particular patient depends on what system in the body is affected. For example, you should give patients with active meningeal tuberculosis:
• A treatment regimen, initially lasting 12 months, comprising isoniazid, pyrazinamide, rifampicin, and a fourth drug (for example, ethambutol) for the first two months, followed by isoniazid and rifampicin for the rest of the treatment period and
• A glucocorticoid at a typical dose, adults - equivalent to prednisolone 20-40 mg if on rifampicin, otherwise 10-20 mg, children – equivalent to prednisolone 1-2 mg/kg, maximum 40 mg (you should normally withdraw the steroid slowly, starting within two to three weeks of initiation).

Learning bite

You should consider a thrice weekly dosing regimen (using the dosages given in the British National Formulary) for patients receiving directly observed therapy. This is not absolutely required but it is the first choice.
Each patient with tuberculosis should know who their named key worker is and how to contact them. This key worker should help educate the patient with the aim of achieving full concordance.

Learning bite

For patients of any age with HIV infection and latent tuberculosis you should give six months of isoniazid alone. Interactions with anti-retroviral drugs inhibit the use of other agents, for example rifampicin. Paraesthesiae is more common in those with HIV, so pyridoxine is given to prevent isoniazid induced peripheral neuropathy.


Learning bite
If a pupil is diagnosed with sputum smear positive tuberculosis, the rest of their class (if there is a single class) or the rest of the year who share classes should be assessed as part of contact tracing.
Clinicians conducting contact tracing in a school should consider extending it to include children and teachers involved in extracurricular activities and non-teaching staff, on the basis of:
The degree of infectivity of the index case
The length of time the index case was in contact with others
Whether contacts are unusually susceptible to infection
The closeness of contact

Learning bite

Rifampicin induces hepatic enzyme activity and therefore accelerates the metabolism of combined and progesterone only oral contraceptives.
Pyrazinamide can cause hyperuricaemia and attacks of gout.
You can give standard doses of rifampicin, isoniazid, and pyrazinamide to patients with renal impairment. You should reduce the dose of ethambutol and streptomycin for patients with renal impairment and you should monitor their serum concentrations of these drugs

Learning bite

The man completed his treatment successfully without directly observed therapy. You should remember that directly observed therapy is not the only way to improve concordance. Improving concordance is one of the most important ways to reduce the prevalence of tuberculosis and this is something that all healthcare professionals can contribute to. Think about how you could help patients.
Consider the effect of
Environmental
Financial
Psychosocial

factors personal to the patient and how they may reduce adherence.

Could you advise them about:
Transport to and from the clinic?
Housing benefit?


If you are unsure whether a patient is taking their treatment, you can try the following strategies:
Reminder letters in appropriate languages
Health education counselling
Patient centred interviews
Home visits
Patient diaries
Random urine tests and other monitoring (for example, pill counts).

Learning bite

In children unable to expectorate sputum, induction of sputum should be considered if it can be done safely, with gastric washings considered as third line.

Learning bite

The following are risk factors for drug resistance:
History of prior treatment for tuberculosis
History of prior treatment for tuberculosis that failed
Contact with a patient known to have drug resistant tuberculosis
Being born in a foreign country, particularly high incidence countries
HIV infection
Living in London
Age (highest rates occur between ages 25 and 44)
Being male


Learning bite
You should normally stop drug treatment of peripheral lymph node tuberculosis after six months, regardless of the appearance of new nodes, residual nodes, or sinuses draining during treatment.
If there is a persisting discharging sinus then it may be sensible to reinvestigate with culture.

You should treat patients with active peripheral lymph node tuberculosis who have had an affected gland surgically removed with the standard recommended regimen. A six month, four drug initial regimen (six months of isoniazid and rifampicin supplemented in the first two months with pyrazinamide and ethambutol) should be used to treat active respiratory TB in: adults not known to be HIV positive, adults who are HIV positive, children.

Learning bite

groups of people with latent tuberculosis who are at increased risk of going on to develop active tuberculosis, include people who:
Have had a HIV infection
Have had a solid organ transplantation
Are injecting drug users
Have a haematological malignancy
Have had a jejuno-ileal bypass
Have had a gastrectomy
Are receiving treatment with anti-tumour necrosis factor alpha.

Learning bite

Routine BCG vaccination is no longer recommended for children aged 10-14 years.
Healthcare professionals should opportunistically identify unvaccinated children older than four weeks and younger than 16 years who are at increased risk of tuberculosis and who would have qualified for neonatal BCG vaccination, and provide Mantoux testing and BCG vaccination (if they are Mantoux negative).

BCG vaccination should be offered to people who are 35 years or younger, if they are previously unvaccinated and have lived with someone with active respiratory tuberculosis and they have a negative Mantoux test.
BCG vaccination should also be offered to people who are 36 and older and who are healthcare or laboratory workers (who have contact with patients or clinical materials) if they are previously unvaccinated and have lived with someone with active respiratory tuberculosis and they have a negative Mantoux test.


Key points
Managing patients with active tuberculosis
You should use a six month regimen (six months of isoniazid and rifampicin supplemented in the first two months with pyrazinamide and ethambutol) to treat active respiratory tuberculosis in:
Adults not known to be HIV positive
Adults who are HIV positive
Children.

For patients with active meningeal tuberculosis, you should offer:

A treatment regimen, initially lasting for 12 months, comprising isoniazid, pyrazinamide, rifampicin, and a fourth drug (for example, ethambutol) for the first two months, followed by isoniazid and rifampicin for the rest of the treatment period
A glucocorticoid at usual doses with gradual withdrawal of the glucocorticoid considered, starting within 2-3 weeks of initiation.

Improving concordance

Directly observed therapy is not necessary for most patients with active tuberculosis. You should think about all patients' likelihood of concordance with treatment. You should particularly consider directly observed therapy for the following groups of patients:
Homeless people (who live on the street or in shelters) with active tuberculosis.

Patients who are likely to have poor concordance, in particular those who have a history of not taking medications.
All patients with tuberculosis should know who their named key worker is and how to contact them. This key worker should help the patient take their tablets as prescribed.
People who arrive in the UK from countries of high prevalence should undergo screening for tuberculosis.

BCG vaccination for neonates

For any neonate at increased risk of tuberculosis you should discuss BCG vaccination with the parents or legal guardian.
Primary care organisations with a high incidence of tuberculosis should consider vaccinating all neonates soon after birth.


In areas with a low incidence of tuberculosis, primary care organisations should offer BCG vaccination to selected neonates who:
Were born in an area with a high incidence
Have one or more parents or grandparents who were born in a high incidence country.Have a family history of tuberculosis in the past five years.

Clinical tip

Don't forget your employees. Employees new to the NHS who will be working with patients or clinical specimens should not start work until they have completed a tuberculosis screen or health check, or documentary evidence is provided of such screening having taken place within the preceding 12 months.

DOT should be considered for patients who have adverse factors on their risk assessment, in particular:
• Street or shelter dwelling homeless people with active TB .
• Patients with likely poor adherence, in particular those who have a history of non-adherence .
• All prisoners with active or latent tuberculosis.

Offer new entrants from high incidence countries who are aged 16-35 either an interferon gamma test alone or a dual strategy (Mantoux test followed by interferon gamma test if Mantoux is positive (6 mm or greater)) is recommended as the first step in screening new entrants.
Chest x ray was previously recommended as the first step. This is no longer the case.

There are no absolute rules about the contents of the cerebrospinal fluid in tuberculous meningitis, but typically there is low glucose and raised protein.
White cells may be few or absent. If they are present then lymphocytes usually predominate.

Stage 1 tuberculous meningitis is characterised by the typical symptoms of meningitis; headache, neck stiffness, and photophobia
Stage 2 is defined by an alteration of consciousness or the presence of one or more cranial nerve lesions
Stage 3 is characterised by coma


Surgical intervention for possible tuberculous lymphadenitis often results in a chronically discharging sinus, which can take months to heal and which leaves an unsightly scar. It is best avoided except when an environmental mycobacterium has been isolated (in this circumstance complete excision of the gland should be carried out).
A fine needle aspiration from the wall of the abscess offers the best hope of a positive culture in the presence of sterile pus.

According to randomised controlled trials treatment for six months is sufficient for tuberculosis at any site except the central nervous system.

You should take blood for liver function tests before starting treatment and you should warn patients to stop treatment and seek medical advice if they have nausea or jaundice. Once treatment is started, and provided pretreatment liver function is normal, biochemical monitoring is not required. Patients invariably show some rise in liver enzyme levels on treatment, but an acceptable upper level has not been agreed. It is safest to tell patients to stop treatment and to return to the clinic if nausea or jaundice occurs.

Conversion of sputum from smear and culture positive to negative is the only reliable way of determining the effectiveness of treatment. Weight gain can be a good clinical indication of successful treatment. But symptomatic improvement may be masked by side effects of treatment such as nausea. The chest x ray may improve with treatment but it is a poor indicator because permanent fibrosis and scarring may have occurred before treatment has started.

Nausea and flushing are common side effects of pyrazinamide and probably occur in at least one in five patients. Side effects are more common in elderly people. If the patient reports nausea you should check liver function to ensure that drug related hepatitis is not occurring. Nausea can often be controlled with antiemetics.

A combination of pleural biopsy for histology and culture will provide the diagnosis in 80-90% of patients.

The new guidelines are clear: any person younger than 16 years with a positive tuberculin skin test but normal chest x ray should be given preventive therapy with three months of isoniazid and rifampicin or six months of isoniazid.

A number of studies have shown that smoking increases the risk of tuberculosis two- to fivefold. A study in India showed that tuberculosis is the most common cause of death in smokers.
This is probably due to suppression of alveolar macrophages by substances in the cigarette smoke.

In about 50% of patients with pulmonary tuberculosis the sputum smear test will be negative. 30% of patients treated for pulmonary tuberculosis are culture negative.
This is because over 10 000 bacteria per ml of sputum are needed to give a positive smear. Increasingly in the white population of the UK a positive smear results from an environmental mycobacterium such as M kansasii or M avium, not M tuberculosis. So a sputum smear test cannot definitively confirm the diagnosis of tuberculosis.


Only a positive culture definitely confirms tuberculosis. The use of liquid media has sped up this process from many weeks to two to three weeks. Enhanced surveillance has shown that as many as 30% of patients treated for pulmonary tuberculosis are culture negative.

Guidelines from the National Institute for Health and Clinical Excellence (NICE) advise that a positive tuberculin skin test should be followed by a positive gamma interferon blood test (if available) to confirm the presence of tuberculosis infection.

You should treat patients with active peripheral lymph node tuberculosis who have had an affected gland surgically removed with the standard recommended regimen.

HIV infection is by far the strongest risk factor for tuberculosis: it increases risk by about 100-fold.
The next highest risk is jejunal bypass surgery, which increases risk by about 20-fold for reasons we don't understand.
Diabetes and smoking both increase risk by between two- and fivefold (by depressing host immunity).
Being tall and thin increases risk by about
1.3- to 1.5-fold.
Having chronic renal failure, silicosis increases the risk of developing active tuberculosis.

The BCG vaccination usually renders the tuberculin skin test weakly positive: a grade 1 or 2 Heaf test or up to 14 mm on Mantoux testing. But this is by no means the rule; some skin tests may be negative and some strongly positive. The absence of a positive skin test does not mean that the BCG vaccination has not "taken." The new gamma interferon blood tests will help to distinguish between a skin test rendered positive by BCG vaccination alone and one rendered positive by genuine infection with M tuberculosis because the
blood tests use antigens specific to the tuberculosis bacteria and not to the BCG vaccine.

Although rare, optic neuritis is a serious side effect of ethambutol.

At doses of 15 mg/kg it is likely to occur only in the elderly. When the drug used to be used at doses of
25 mg/kg the side effect occurred more frequently.

BCG is a live attenuated vaccine. Patients with HIV infection should not receive it.