TUBERCULOSIS / MedUrgent

TUBERCULOSIS

Tuberculosis is caused by mycobacteria species, 3 of which are responsible for the disease in man, these are:

Mycobacterium tuberculosis which are the major cause of infection. Mycobacterium bovis which is endemic in cattle. This type may be spread to man by drinking contaminated milk.

Opportunistic mycobacteria which are rare. They may cause pulmonary or general infections in the immunocompromised patient. The organism is transmitted by droplets, oral-fecal route or inoculation through abraded skin. Once the bacilli have entered the body, unless certain conditions are made appropriate, the clinical illness will not necessarily ensue. These conditions are:

1- Age: the very young and old are more susceptible.

2- Sex: males are more at a risk, although in the past it used to be opposite.

3- Natural resistance.

4- Standard of living.

5- Patients own health status: diabetes mellitus, gastric surgery, AIDS or Immunosuppressive drugs may all encourage the infection.

PATHOLOGY

The initial 'primary' tuberculosis infection is usually in the lungs, but could be in the tonsils or alimentary tract. Infection of the regional lymph nodes with caseation, invariably accompanies the primary lesion. This usually heals but at times it may do so incompletely or not at all. When healing is incomplete, viable bacilli may find their way into the bloodstream. From there they may cause haematogenous lesions in other organs e.g. lungs, bones, joints and kidneys.

If healing does not occur, particularly when the infected is an adolescent, then the infection may lead to fulminant progressive pulmonary tuberculosis. Complications that are seen include pulmonary collapse by compression of a bronchial segment by a lymph node or perforation of bronchial wall and thus further dissemination occurs. These may lead to pericarditis, cold abscess formation or meningitis which may develop in acute miliary tuberculosis.

Other cases of progressive pulmonary tuberculosis are either due to reactivation of an incompletely healed primary focus or recent reinfection. Post primary pulmonary tuberculosis consists of a tubercles cavity from which, the caseous material can be drained into a bronchus. If the plan becomes infected, pleurisy as well as effusion or tubercles empyema may result as a consequence. In this form, dissemination to other organs via the blood is uncommon

Fate of Primary Complex: 

1- Heals by fibrosis and calcification

2- Remains dormant for years 

3- Progresses: 

 a- Local: consolidation, cavitation, bronchopneumonia or pleural effusion

 b- Lymphadenitis: Leading to partial or complete brochialobstruction, bronchitis. endobronchial TB and brochogenic spread to other parts of the lung C-Heamatogenous spread: Localised at apex of the lung (Simon focus), spread within 3-6 months to cause military TB and TB meningitis. Late spread (2-6 years) leads to tubercular lesions in the bones, joints, genitourinary system and brain (tuberculoma). Diagnostic Methods: 

*First line:

a- Clinical features (prolonged fever, persistent cough for more than 2 weeks and loss of weight)

b- History of contact with positive case of TB

C-Positive Mantoux test (<5mm: -ve; 5-10mm: probable; >10mm: +ve)

d- Positive X-ray findings (hilar lymphadenopathy+/- parynchymal shadows)

e- Positive stain of aspirates (gastric aspirate, sputum, bronchial aspirate, CSF, urine, peritoneal aspirate...).

f Accelerated BCG reaction: Papule within 1-2 days, a pustule within 5-7 days and a scab or nodule within 10-12 days. It is positive even in malnourished children.

*Second line:

a- Positive Fine Needle Aspirate Cytology

b- Positive biopsy findings

C- Positive culture findings (Lowenstien-Janssen media, Bactec method, Septic check AFB system, MGIT system)

d- PCR

*Third line:

a- ELISA

b- GLC (Gas Liquid chromatography)

Monteux test: 2 TU of Purified Protein Derivative (PPD) is injected intradermal on the anterior aspect of the left forearm using 0.1 ml of a standard solution and the response is read after 48-72 hours. An induration of > 10 mm is positive, 10-5m is doubtful, <5 mm is negative. in Heaf test a six needles spring loaded gun is used to inject PPD.

BCG. (Bacillus Calmette-Guerin, attenuated Bovine tubercular bacilli), 0.1 ml is given intradermal on the anterior aspect of the left forearm at birth. A papule appears after one week, ulcer at 2-6 weeks and a scab or nodule at 12 weeks. Protection extends to 15-20 years. Mild complications might occur including deep ulceration, axillary lymphadenitis, keloid formation and BCGiosis Constitutional symptoms 

CLINICAL PICTURE

This varies according to the type of tuberculosis. In general, features have either local or systemic effects. The local effect is cough which may be productive of sputum and haemoptysis. The systemic effects are anorexia, weight loss, lassitude, sleep sweats and evening pyrexia. PRIMARY PULMONARY 

TUBERCULOSIS

This is usually asymptomatic and it may pass unnoticed unless a chest X-ray or a tuberculin test is done at the same time. In some patients, there may be slight fever for 7-14 days, and possibly a dry cough. The WBC is usually normal but the ESR is high. Erythema nodosum, can be detected (bluish-red, raised tender cutaneous lesions) on the shin of the tibiae or thighs. Sometimes they are associated with fever and polyarthralgia. These lesions may be the first sign to appear and the Tuberculin test (Mantoux Test) is frequently strongly positive. Primary tuberculosis may heal completely or become progressive and cause complications such as:

• Lobar or segmental collapse.

• Pleurisy or pleural effusion.

• Pos-primary pulmonary tuberculosis.

• Acute miliary tuberculosis

• Tuberculous meningitis.

The three most important diagnostic methods for primary tuberculosis are:

1- Chest X-ray showing lymph node enlargement (more noticeable in children), and pulmonary lesions (more conspicuous in adults).

2- Tuberculin test. (mantoux test): a positive test in an unvaccinated child is a sign of active disease.

3- Bacteriological examination: laryngeal swabs or gastric washings may show

the organisms, and therefore give absolute proof.

The prognosis is excellent as it responds well to chemotherapy.

Acute Miliary T.B

This occurs mainly in children, young adults and elderly individuals. The disease may be preceded by a few weeks of vague malaise. The symptoms then rapidly occur with severe pyrexia, tachycardia and night sweats. Loss of weight is noted, as well as a progressive anemia.

Respiratory symptoms are cough and breathlessness. The lungs may not show any physical signs; but occasionally, wide-spread crepitations may be heard. Hepatosplenomegaly might be present, as well as leukocytosis. Diagnosis be suspected by the symptoms but confirmation requires:

1. Chest X-ray is very important as it shows is the symmetrical mottling of lungs characteristic of military tuberculosis.

2. Ophthalmoscopy may show the choroidal tubercles

3. Bacteriological culture.

4. Liver biopsy in difficult cases. 5. Tuberculin test (Mantoux Test) may be negative; however, this does not exclude the disease as the sensitivity may become depressed in the course of the disease especially in the later stages.

The prognosis has improved greatly with chemotherapy, provided the diagnosis is done at an early stage. Mortality rate was almost 100% in the past.

Post-primary pulmonary tuberculosis

This is the main cause of the increased mortality and morbidity rates associated with the disease. The onset is slow, and the symptoms which develop gradually including cough which is not troublesome until in a later stage. This becomes productive of mucoid and then purulent sputum and can be associated with haemoptysis. Breathlessness is usually a late symptom, unless there is pneumothorax and there may be pleuritic pain due to pleurisy.

The earliest physical sings are a few crepitations over the lung apex. This is, lately, followed by signs of consolidation, cavitation and fibrosis.

Diagnosis is usually done by radiology, even before the symptoms appear, and this is the most important investigation for this condition and also for follow up. ill-defined opacities, usually in the upper lobes are seen. In more severe cases, the opacities will be more widespread and bilateral signs of pleural effusion and pneumothorax may also be found.

The diagnosis of this condition is usually based on these findings:

• Persistent cough

• Fever (nocturnal) • Spontaneous pneumothorax.

• Haemoptysis

• Lethargy

• Pleural pain not associated with acute illness.

• Weight loss.

In the presence of any of these symptoms, a chest x-ray should be done immediately. If signs are observed, a confirmation is done by three sputum specimens for smear or culture, and laryngeal swabs can be taken for the same purpose.

Complications

- Pleurisy with or without effusion.

- Pneumothorax - Ischio-rectal abscess

- Tuberculous laryngitis

- Tuberculous enteritis

- Respiratory failure - Right heart failure

- Fungal colonization of cavities Prognosis has improved with chemotherapy and as long as the bacilli are not resistant, then the outcome is good. Complications may be avoided if 'he disease is recognized and treated at a reasonably early stage.

Non-pulmonary tuberculosis:

This may occur in different organs:

• Castrorintestinal: is rare. Presents with diarrhea, malabsorption, intestinal obstruction and ascites. 

• Pericardium: may lead to pericarditis or tampona .

• Genito-urinary: rarely gives rise to symptoms until the lesions become extensive. It may cause haematuria, increased frequency, sterile pyuria, and infertility.

• CNS: miliary tuberculosis and could prove fatal or lead to permanent neural deficits. Lymphnodes: is a very common manifestation, especially in Asians.

• Bone & Joints: is also common and can cause Pott's disease, pyoarthrosis, osteomyelitis and cold abscess.

• Other Organs: such as the skin (lupus vulgaris) and adrenal glands may be affected. SUDAN NATIONAL TUBERCULOSIS CONTROL PROGRAMME

According to the NTCP, the following case definitions are to be used:

1-Pulmnary Tuberculosis (PTB): rerefers to disease involving the lung parenchyma.

Pulmonary Tuberculosis, sputum smear positive:

a- Two or more initial sputum smear examinations positive for AFB, or

b- One sputum smear examination positive for AFB plus radiographic abnormalities consistent with active PTB as determined by a clinician, or

C- One sputum smear positive for AFB plus sputum culture positive for M.tuberculosis.

Pulmonary tuberculosis, sputum smear negative:

a- Does not meet the above criteria

b- More common in children.

2. Extrapulmonary Tuberculosis (EPTB): Involves organs other than the lungs e.g. pleura, lymph node genitourinary tract, skin, joints and bones.

Severe forms of EPTB:

Includes miliary, disseminated, meningeal, pericardial, pleural (bilateral or extensive), spinal, intestinal and genitourinary.

Less severe forms of EPTB:

Includes lymph nodes, unilateral pleural effusion, bones (excluding spine) peripheral joint and skin. Categorization of TB patients:

CAT 1:

- New smear positive patient

- New smear negative PTB with extensive parenchymal involvement

- Concomitant HIV disease or severe form of EPTB

CAT 2:

- Previously treated sputum smear positive PTB

- Relapse

- Treatment after default

- Treatment failure of CAT 1

CAT 3:

- New smear negative PTB (other than in CAT 1)

- Less severe forms of EPTB.

CAT 4: - Chronic (sputum positive after supervised treatment)

- Proven or suspected Multi-Drug Resistant TB case.

WHO Diagnostic Criteria

1-Suspected TB: 

Any child with history of contact with confirmed case of pulmonary TB who:

a-Is not gaining normal health after Measles or Whooping cough

b-Has loss of weight, cough or wheeze and not responding to antibiotic therapy for respiratory disease.

C-Has painless superficial lymph node enlargement 

2-Probable T.B:

A suspected case and any of the following:

A-Positive Mantoux test

B-Suggestive X-ray findings

C-Suggestive Biopsy findings

D-Therapeutic response to treatment

3-Confirmed TB:

A-Detection of tubercle bacilli by microscopy or culture

B-Identification of tubercle bacilli as mycobacterium by culture TUBERCULOSIS IN CHILDREN • Infection is usually from an adult or elderly, post primary infected child or contaminated milk.

• Most common is age 1 - 4 years.

• A strongly +ve Mantoux test in a non-vaccinated child is indicative.

• Sputum smear is usually negative (gastric lavage may be more helpful). 

• Primary TB may present as unilateral lymphadenopathy or a complex formed of a hilarl mediastinal lymphadenopathy and a small opacity in the lung (Primary Complex).

• Acute disseminated post-primary TB includes miliary TB with or without meningitis.

• Diagnosis of PTB(Primary TB) requires a chest X-ray

• For treatment of TB meningitis, Streptomycin is used instead of Ethambutol because Ethambutol does not cross the blood brain barrier.

• Children in contact with infectious adults should receive Isoniazid 5mg/ kg/day for 6 months.

• Breast feeding mothers and lactating mothers with TB should have a full course of TB treatment. Their babies should be given prophylactic Isoniazid for 6 months and the BCG vaccine should be postponed until the end of Isoniazid prophylaxis.

Sudanese National Protocol for Diagnosis of TB Scoring System Score points (Age <5yrs): History of contact , Mantoux +ve 2, Cough 2, Weight Loss 3, Fever 1, Total > 5 Score point(Age >5yrs): History of contact 2, Mantoux +ve 2, Cough 1, Weight Loss 3, Fever 2, Total > 5.

WHO Diagnostic Criteria Suspected TB

1. History of contact with confirmed case of pulmonary TB

2. Poor weight gain

3. Weight loss

4. Cough/wheeze: not treatment responding to antibiotics

5. Lymphadenopathy

 

Probable TB

*Suspected case +:

1- Positive Mantoux test

2- X-ray is suggestive 3- Biopsy is suggestive 4- Responding to anti TB

Confirmed TB

1-Smear :positive for TB bacilli

2-Biopsy positive for TB bacilli

3-Culture:positive for TB bacilli

TREATMENT

A. Isolation of the patient is not necessary unless there are complications of the disease or small children at home are at risk. Rest is also of no use unless there are certain circumstances such as skeletal tuberculosis.

B. Specific chemotherapy is the most important means of treatment. This is based on a thorough knowledge of the available drugs so as to provide the best combination of therapy. The five drugs most commonly used are rifampicin, isoniazide ethambutol, streptomycin and pyrazinamide. There is also thiacetazone, which is cheap and widely used in the developing countries.

The basis of treatment is an initial stage using several drugs, followed by a continuation stage using a reduced number of drugs to avoid resistance.

The characteristic of the above drugs are mentioned in the table below.

They should be used on once daily doses.

Anti-TB drugs

• Streptomycin (S) 15 mg/kg Side-effect Deafness, Dizziness

• Rifampicin (R) 10 mg/kg Side-effect Hepatitis, shock.pupura and acute renal failure

• Pyrazinamide (Z) 25 15 mg/kg Side-effect Jaundice and joint pains(high uric acid)

• Ethambutol (E) 15 mg/kg Side-effect Visual impairment, nausea and abdominal pain

• Isoniazid (H) 5 mg/kg Side-effect Jaundice, burning sensation in feet (give B6) Ready-made combined tablets include:

-REFINAH (RH): Rifampicin 150 mg plus INH 75 mg

-ETHINAH (EH): Ethambutol 400 mg plus INH 150 mg

The total daily dose should be calculated according to body weight.

The treatment regimens are either short or long:

The short is of a 6 month duration using ethambutoal/ streptomycin, isoniazid, rifampicin and pyrazinamide as initial stage for 2 months. Continuation stage for 4 months = isoniazid + rifampicin

OR

A 9 month duration regimen, using ethambutol/ streptomycin, isoniazid and rifampicin for a period of 2 months, as an Initial stage. Continuation stage for 7 months using isoniazid and rifampicin

These are virtually 100% effective. If a person is not trusted to take his treatment, then they are kept in hospital for the first two months or supervised. Then for 10 months: twice weekly regime of 1g streptomycin, 15 mg/kg isoniazid and 10 mg pyridoxine.

The long treatment regimens are less expensive, and used in the developing countries. These take 12 months and are either.

a) Streptomycin 1g/M, isoniazid 15mg/kg +and pyridoxine 10 mg twice weekly

OR

 b) Isoniazid 300mg and thiacetazone 150 mg daily. The first is nearly 100% effective in the absence of primary drug resistance, while the latter is only 80-95% effective.

Sputum samples are usually negative within 6 months of treatment, unless the strain is resistant to the drugs. For such cases, additional drugs are used. These are:

• Sodium aminosalicylate (PAS) in a dose of 5g twice daily orally

• Ethionamide or prothionamide in a dose of 0.75-19 once daily orally

• Capreomycin in a dose similar to above i.m.

• Cycloserine in a dose similar to above orally.

• Corticosteroids may be used to suppress cell-mediated reactions induced by the bacilli, but they may also promote a rapid dissemination of infection unless given in conjunction with an effective anti-tubercles drug. In acute pulmonary tuberculosis, it may reduce the fever and may help in producing a dramatic improvement of the radiological picture.

• Prednisolone is usually given in a dose of 20mg daily for 6-12 weeks. When given in combination with chemotherapy, they may minimize fibrous tissue formation. They should always be administered when there is evidence of ureteric obstruction, as they help relieve the need for surgery.

• Surgical treatment: for pulmonary resection, nephrectomy, abscess drainage or nodulectomy when deemed necessary.

• The re-treatment regimen consists of 5 drugs in the initial phase and 3 drugs in the continuation phase.

• Directly Observed Treatment (DOT) is required to motivate patients to continue treatment, ensures the accountability of TB services and to prevent emergence of drug resistance.

Management of CAT 1 and CAT 3:

CAT 1 Patient New smear +ve patients, Smear-ve with extensive parenchymal involvement, Concomitant HIV disease -Severe form of EPTB give 2 HRZS and 6 HE 

CAT 3 New smear -ve PTB (other than in CAT 1), Less severe forms of EPTB give 2HRZS and 6 HE *Second line drugs: Cycloserine, ethionamide, kanamycine

*Third line drugs: Cipofloxacine, Ofloxacin, Clarithromycin, Omefloxacin Rifabutin, Rifabentine 

CHEMOPROPHYLAXIS

Isoniazid: 5mg/kg orally, daily for one year.

This is considered in:

• Non-vaccinated tuberculin positive children below 3 years

• Unvaccinated contacts who are tuberculin positive

• Immunocompromised patients

• Adolescents with high tuberculin sensitivity

• The same dose, but for 6 weeks may be used for infants of highly infectious parents.

PREVENTION

• Continuous checking of the tuberculin index.

• Improvement of the socio-economic status of family or community. • Case finding must be a continuous activity.

• Chemotherapy for infected individuals. • Isolation of patients (not so important).

• BCG vaccination: 0.1 ml intradermaly of a freeze-dried vaccine at the junction of the upper and middle thirds of the upper arm. May, rarely, cause lymphadenopathy or abscess formation. Protection is for 7 years and incidence of infection is reduced by 50-80%.

• Chemoprophylaxis when indicated.

• Elimination of the bovine infection.