Tuberculosis

Tuberculosis is an infectious disease that is caused by the tubercle bacillus, Mycobacterium tuberculosis. The principal route of infection is the respiratory tract through the inhalation of infected air droplet nuclei.

Infection may rarely occur through the gastrointestinal tract from the ingestion of infected unpasteurised milk. Exposure to infection may lead to infection which may be latent.

Subsequent progression to active disease occurs in approximately 100/o during the lifetime in people with a latent infection and an intact immune system. Progression of a latent infection occurs at a higher rate in individuals infected with the Human lmmunodefi ciency Virus.

In HIV-infected patients, pulmonary tuberculosis is the commonest form of tuberculosis.

Pulmonary Tuberculosis

Pulmonary tuberculosis classically presents with symptoms of prolonged cough (>2 weeks duration), which is usually productive; and with or without a history of haemoptysis, fever, night sweats and loss of weight. Radiological changes that occur include cavitation, parenchymal infiltrates and lymphadenopathy. Sometimes Chest X-rays may not show any abnormality. Radiological findings in HIV-infected individuals depend on the degree of immunosuppression. Atypical findings are more common in these patients.

Clinical features
Pulmonary Tuberculosis accounts for approximately 80% of the cases of tuberculosis, with smear-positive tuberculosis being the major source of infection. Extra-pulmonary tuberculosis may involve many sites of the body such as the pleura, pericardium, lymph nodes, meninges, bones, gastrointestinal tract, genito-urinary system, epididymis, eyes and skin.

Pleural tuberculosis

Pleural tuberculosis may present with a cough which may be non-productive, pleuritic chest in dent pain, systemic symptoms of fever and night sweats.

Pericardial tuberculosis

Pericardial tuberculosis may present with chest pain or with features of tamponade such as dyspnoea, tachycardia, hypotension, pulsus paradoxus and sudden collapse of the patient.

Lymph node tuberculosis

Lymph node tuberculosis may affect any site though it is more common in the cervical region. Lymph nodes are usually painless. Where caseation with liquefaction and sinus formation occurs, they may be painful.

Meningeal tuberculosis

Meningeal tuberculosis is usually of insidious onset with symptoms of headache, neck stiffness, indent vomiting and disordered consciousness.

Bone tuberculosis

Bone tuberculosis may affect any bone though it is more common in the thoracolumbar spine leading to gibbus formation due to vertebral collapse and may result in paraplegias. Osteomyelitis and cold abscess formation may also occur.

Gastrointestinal tuberculosis

Gastrointestinal tuberculosis may affect any part of the gastrointestinal tract, though intestinal involvement presenting as diarrhoea, malabsorption, intestinal obstruction and ascites are common.

Genito-urinary tuberculosis

Genito-urinary tuberculosis involving the kidneys may be asymptomatic, causing symptoms such as haematuria and sterile pyuria with extensive renal involvement. Infertility, salpingitis and tubal abscess are presentations of infection of the fallopian tubes while epididymal tuberculosis may present as painless swellings. Phylectenular conjunctivitis, iritis and choroiditis are manifestations of eye infection.

Dermal tuberculosis

Dermal tuberculosis may include lupus vulgaris and erythema nodusum.

Adrenal tuberculosis

Adrenal tuberculosis may cause Addison's disease.

Complications

Complications of pulmonary tuberculosis include pneumothorax, empyema or pyopneumothorax and laryngitis with advanced disease. Respiratory failure and right ventricular failure may develop as a late complication due to extensive pulmonary destruction and fibrosis.

Colonization of cavities with Aspergillus fumigatus may occur resulting in haemoptysis.

Constrictive pericarditis is a complication of TB. Meningeal tuberculosis as a result of TB of the spine may result in permanent neurological deficits. Gastrointestinal tuberculosis may lead to the development of ascites and malabsorption.

Diagnosis

Take good history, chest x-ray, sputum smear, ESR and Hb. Tuberculin test to make an informed decision.

Management

Treatment
Treatment of tuberculosis should be based on the demonstration of the mycobacteria by both sputum smear histology and culture. Clinical and radiological findings of dual HIV/TB infection have changed. Identification of smear-positive cases should form the basis for treatment as these are cases responsible for continued transmission of infection. In the presence of a clinical picture, treatment may be started using standard treatment Directly Observed Therapy (DOTs). The basic principle underlying the treatment of tuberculosis is the use of multi-drug treatment regimen for a prescribed period to avoid the development of drug resistance. There is no place for the use of monotherapy in the treatment of tuberculosis nor for a trial of treatment.

Drugs
Treatment for tuberculosis is provided free of charge in all public health institutions. The basis of treatment for tuberculosis is the use of multi-drug treatment for 8 months. Directly Observed Treatment (DOTs) is the mechanism by which the supervision of each dose of the drug occurs, ideally by a member of the health care staff or by family, friends or community health workers.

Treatment is divided into an Intensive phase in which the patient should visit the clinic daily for review and medication for the first two months, followed by a continuation phase of 6 months whereby the patient visits the clinic once every 4 weeks to collect drugs.

Pyridoxine supplement of 50mg daily should be given throughout treatment and especially so in lactating and pregnant women.

Corticosteroids are indicated in meningeal and pericardial tuberculosis and should be started at the same time as antituberculosis therapy. There may be a need for pericardiocentesis in TB pericarditis.

For adults and children, treatment of tuberculosis has been classified into two categories as follows:

Adults	Adults	Paediatrics	Paediatrics
Category I	Category II	Category I	Category II
New smear positives (+) Smear negative (-) and extrapulmonary	Smear + re-treatment cases including treatment failure, treatment after default, and relapses for smear-positive cases	New uncomplicated cases of TB	Re-treatment cases and severe, complicated TB. i.e., TB meningitis, miliary TB, spinal TB

a) Recommended Adult Treatment Dosage
Category I: New smear-positive patients

Weight in kg	Intensive Phase 2 Months	Continuation Phase 6 Months
	RHZE	EH
30-37	2	1
38-54	3	2
55-70	4	3
>70	5	3

R – Rifampicin, H – Isoniazid, Z – Pyrazinamide, E – Ethambutol, S – Streptomycin.

Category II: Smear positive re-treatment patients

Weight in kg	Intensive Phase 3 Months				Continuation Phase 5 Months
	2 months			1 month
	RHZE+S			RHZE	RHE
30-37	2	0.5g	2	2
38-54	3	0.75g	3	3
55-70	4	1.0g	4	4
>70	5	1.0g	5	5

Recommended Paediatric Treatment Dosage for Newly diagnosed, Uncomplicated Tuberculosis

Weight in kg	Intensive Phase 2 Months		Continuation Phase 4 Months
	RH+Z		RH
6-11	½	½	½
12-18	1	1	1
19-26	1½	1	1½
27-37	2	1½	2
>38	3	2	3

Pregnancy and Breastfeeding:
The standard regimen (above) may be used during pregnancy and breastfeeding; Pyridoxine supplements are advisable. Streptomycin should not be given in pregnancy.

In exceptional circumstances, Ethambutol can be used in young children (e.g. drug resistance ). However, care is needed in young children receiving this drug because of the difficulty involved in obtaining reports of visual symptoms and in testing eyesight.

MultiDrug-Resistant Tuberculosis (MDR-TB)

Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis that is resistant to two or more of the primary drugs isoniazid and Rifampicin used for the treatment of tuberculosis. In Zambia, the Chest Diseases Labora tor y reported Multi-drug resistant (MDR) that is resistance was 1.8% for new cases and 2.3% for previously treated cases 2003.

All suspected MDR-TB specimen should be referred to the national TB reference laboratory. MDR-TB patients should be referred for specialist treatment and where appropriate facilities for infection control exist.

Use at least four drugs with either certain or almost certain, effectiveness. Drug Susceptibility Testing (DST) should generally be used to guide therapy. Ciprofloxacin must not be used as an antituberculosis agent because of its weak efficacy compared with other fluoroquinolones. Patients should be treated for 18 months of past culture conversion. There is a role for adjunctive measures such as surgery and nutritional and social support which should be used appropriately.

Treatment involves the use of drugs from group 1 to group 4. Group 1 drugs are first-line drugs to which resistance has not been documented. Efficacy for a first-line drug should be questioned if it was used in a previously failed regimen despite a DST report to the contrary.

Group 2 drugs are the injectables either Amikacin or Kanamycin. Capreomycin may be used when there is resistance to Amikacin or Kanamycin.

Group 3 drugs include fluoroquinolones such as moxifloxacin, gatifloxacin, levofloxacin and ofloxacin.

Group 4 drugs are added based on estimated susceptibility, drug history, efficacy, side-effect profile and cost.

Ethionamide or Prothionamide is often added because of low cost; however, these drugs do have some cross-resistance with Isoniazid. Cycloserine is used often in conjunction with either Ethionamide or Prothionamide when group 4 drugs are required.

Group 5 drugs are not recommended by WHO for routine use in MDR-TB treatment because their unclear efficacy regimens are unclear in humans.

Most of these drugs are expensive, and in some cases require intravenous administration. However, they can be used in cases where adequate regimens are impossible to design with the drugs from group 1-4.

Group 5 include Clofazimine, Linezolid, Amoxicillin/clavulanate, Thioacetazone, Imipenem/cilastatin, high-dose Isoniazid, Clarithromycin.

Extensively Drug-Resistant Tuberculosis (XDR-TB)

Recognized earlier in 2006 in South Africa, extensively drug-resistant TB (XDR-TB) is MDR-TB that is also resistant to three or more of the six classes of second-line drugs. Currently, there is no documented evidence of XDR -TB in Zambia.

Tuberculosis and Immunocompromised Patients

All TB diagnosed patients should be counselled and tested for HIV. Immunocompromised patients may develop tuberculosis owing to reactivation of previously latent disease or due to new infection. Multi-resistant Mycobacterium tuberculosis may be present or the infection may be ca use d by other mycobacteria e.g. M. avium complex in which case specialist advice is needed.

Culture should always be carried out and the type of organism and its sensitivity confirmed. Minimum duration of treatment of 9 months is currently recommended for M. tuberculosis infection as re-infection is a common feature in these patients.

In TB/HIV co-infection, treat all patients for TB regardless of CD4 count. Start ART as soon as TB medications are tolerated (usually within 2 – 3 weeks). AR is not required for all patients with CD4 count >350 and no other Stage III or IV illness. Use an Efavirenz-based ART regimen. If patient has renal insufficiency ABC + 3TC + EFV is an alternative option.

In patients already on ART. Start TB treatment immediately. If on LPV/r-containing ART regimen, start Rifabutin in place of Rifampicin or add Ritonavir 300mg BD or double the dose of LPV/r. Evaluate for clinical failure and consider for second-line ART in consultation with HIV specialist.

If pregnant woman on ART, refer to the section of this guideline on HIV/AIDS Treatment or refer to HIV specialist. If on anti-TB treatment and tests positive for HIV, start ART as soon as baseline laboratories and treatment preparation completed.

Monitoring

Since Isoniazid and Rifampicin are associated with liver toxicity, the hepatic function should be checked before and during treatment with these drugs. Patients on dual treatment of HIV and TB are likely to have liver/renal toxicity and should therefore be monitored closely.

Supportive
Non-adherence is the major reason for the failure of otherwise effective drug regimens to achieve high cure rates in the management of tuberculosis. Both patient-related and service-related factors contribute to poor patient compliance. Hence, the education of both healthcare staff and patients is an important part of the management package. An adequate system of defaulter-tracing would also contribute to higher cure rates. In areas with high rates of dual HIV/TB co-infection, nutritional support and integration of Home-Based Care units and the treatment of tuberculosis is important to ensure that supervision of treatment occurs. Hospitalisation during the first two months of treatment is not routinely done and is reserved for those who are severely ill or who have complications of the disease.

Prevention
The most effective method of preventing the spread of tuberculosis is the detection and effective treatment of the infectious cases, i.e. the smear-positive cases. The effectiveness of vaccination using BCG is controversial with results of efficacy studies varying from 0% to 80%. The current WHO recommendation is that BCG should be given at birth to infants in high prevalence areas but avoided where the HIV disease is symptomatic.

Poor hygiene, malnutrition and overcrowding in places such as prisons, orphanages, boarding schools and others facilitate the spread of tuberculosis. Hence the fight against should involve the improvement of socio-economic factors. In the case of childhood TB, contact tracing of an adult should be made, as well a drug treatment.

Prophylaxis
If a child is exposed to positive pulmonary TB, particularly under 5 years of age, provide prophylactic treatment with Isoniazid 5mg/kg orally once daily for 6 months.