Tuberculosis

Notes
  • TB is caused by Mycobacterium tuberculosis (MTB); mainly MTB hominis although MTB bovis can cause disease in human as well.
  • MTB hominis infection is transmitted through the droplet infection when a person with pulmonary TB coughs, sneezes or spits. MTB bovis infection is transmitted through consumption of unpasteurized milk.
  • Besides the lungs (Pulmonary TB, 90% of all TB cases globally and 80% in Kenya), TB can affect other organs of the body (Extrapulmonary TB) including kidney, spine, lymph notes and brain.
  • Statistics: Global TB burden - 9.6M cases (2014); global TB mortality rate - 1.5M deaths; Kenya TB mortality - 9,400 excluding HIV + TB and 8,100 HIV + TB only (2014); Kenya TB prevalence including HIV TB – 120,000 cases or 0.27% of the population (2014); Kenya TB incidence including in HIV – 110,000 ( in HIV – 40,000); % of TB cases that are MDR-TB in Kenya – 2.2 (2014);  MDR-TB cases among notified TB cases – 1400 (2014); Rifampicin Resistance TB (RR-MDR) in Kenya – 23,865 (2014); proportion of global population with latent TB infection (LTBI) – 33% (out of which 10% will develop into TB disease, even a higher % among immunocompromised patients); TB risk – HIV (26 to 31times), diabetes (3 times),  tobacco, children (likely to have more severe form of TB), alcoholism, corticosteroids, infliximab, silicosis and overcrowding.
Symptoms
  • Pulmonary TB;

_Asymptomatic cases (about 25%)

_Cough for 3 wks or more.

_Cough with phlegm/sputum and blood (hemoptysis)

_Chest pains

_Weakness

_Weight loss

_Fever and night sweats

_dyspnea

_Rarely, massive bleeding when pulmonary artery is eroded

  • Extrapulmonary TB;

_(It occurs mainly in immunosuppressed persons and young children)

_TB pleurisy

_TB arthritis with swollen painful joints

_TB peritonitis with ascites

_TB meningitis

_TB ulcer (painless ulcer near the lymph nodes)

_Lymphadenopathy

_Disseminated TB (miliary TB)

  • Complications of MTB include:

_Lung fibrosis

_Lung abscess

_Spontaneous pneumothorax

Diagnosis
  • TB is more challenging to diagnose in children than in adults.
  • Though clinical diagnosis is not easy, MTB should to be suspected in those with signs of lung diseases or symptoms, such as coughs, that last longer than 2 wks
  • Mantoux tuberculin skin tests (though not so useful as those immunized may give false positive results and false negative results in cases of sarcoidosis, Hodgkin lymphoma, malnutrition, and active TB).
  • Sputum smear microscopy (repeated 3 times, 2 sputum spots and one in the morning)

_After being treated with acidic solution MTB, the acid alcohol fast bacillus (AAFB), retains Ziehl–Neelsen (Z-N) or Kinyoun stains.

  • Culture of the clinical sample such as sputum, pus, or a tissue biopsy (such as lymph node biopsy);

_It takes 2 to 6 wks to get results.

  • Interferon-gamma release assays (IGRAS). This test is only useful when it is used with Mantoux tuberculin skin tests.
  • Chest x-ray
  • Body fluid for biochemistry
  • The GeneXpert™ test platform

_This is a relatively new molecular test for TB which diagnoses TB by detecting the presence of TB DNA and resistance to Rifampicin. (It purifies, concentrates, amplifies  and identifies targeted nucleic acid sequences in the MTB genome, and provides results from unprocessed sputum samples in less than 2 hrs, with minimal hands-on technical time).

_GeneXpert™ is more reliable and sensitive than sputum microscopy and faster than MTB culture (2hrs against 6wks) though its widespread use is limited by its high costs.

Prevention
  • Early case detection
  • Vaccination of infants (BCG)
Management
  • Directly Observed Treatment (DOT) is the mainstay of the TB management. It involves a designated health worker, or a trained volunteer meeting routinely at a specific place with a patient to observe him/her taking the medications.
  • It is important to follow the National Treatment Guidelines when managing MTB.
  • It is also important to trace the treatment defaulters to avoid the spread of MTB drug resistance in a community.
  • Monitor therapy by carrying out sputum smear at months 2, 5 and 6 for a 6 – month regime; 2, 5 and 8 an 8 – month regime and 3, 5 and 8 an 9 – month regime
  • Treatment of MTB depends on the class in which a case belongs. Cases are classified as follows;

_New (N) case: This is a patient who has never been treated for MTB before.

_Relapse (R) case: This is a patient who had MTB that had been diagnosed, treated and declared cured but later diagnosed as having MTB again

_Transferred in (TI) case: This is a patient who had been diagnosed and was under treatment in one county / institution but has been transferred to another county / institution to continue with treatment.

_Treatment resumed (TR) case: This is a patient who interrupted treatment and was declared “out of control” but has now resumed treatment.

_Other (O) cases:  other patients with MTB.

  • Regimens for treating MTB disease have have two Phases:

_An intensive phase of 2 months (administered under DOT)

_A continuation phase of either 4 or 7 months (patients to collect drugs fortnightly)

  • Drugs used in the management of MTB and their abbreviations

 

Drug

STD

Strength

Abbrev.

Ethambutol

275mg

E or EMB

Isoniazid

75mg

H or INH

Pyrazinamide

400mg

Z or PZA

Rifampicin

150mg

R or RIF

Streptomycin

1gm

S

  • Rx of the new MTB case;

_Tabs RHZE (Fixed dose combination, FDC) daily x 2/12 then  RH x 4/12 or  EH x 6/12.

  • Rx of relapse (R), treatment failure (F) or treatment resumed (TR) cases;

_Tabs  SERHZ daily x  2/12 then  ERHZ daily x 1/12 then  ERH daily x 5/12.

  • Formulation, patients’ weight and dose:

_RHZE (FDC) tabs daily:  2 for 30-39kg, 3 for 40-54kg and 4 for over 55kg

_RHZ (FDC) tabs daily:  2 for 30-39kg, 3 for 40-54kg and 4 for over 55kg

_RH (FDC) tabs daily:  2 for 30-39kg, 3 for 40-54kg and 4 for over 55kg

_RHE (FDC) tabs daily:  2 for 30-39kg, 2 for 40-54kg and 2 for over 55kg

_S daily:  0.5gm for 30-39kg, 0.75gm for 40-54kg and 1gm for over 55kg

  • Types of Drug Resitant TB and their management;

_Multi-Drug Resistant-TB (MDR-TB) occurs when there is resistance to at least isoniazid and rifampicin (both).

_When MDR-TB is suspected, culture and sensitivity is conducted.

_ Use at least 3-5 of the following drugs
*An aminoglycoside that include;

**Streptomycin 

**Amikacin

**Capreomycin

**Kanamycin

*A fluoroquinolone such as:

**Levofloxacin 

**Ciprofloxacin 

**Ofloxacin

*Pyrazinamide 

*Ethambutol

*Cycloserine

*Para-aminosalicylic acid

_MDR-TB is treated for 18-24 months under DOT and monitored for another 2yrs.

_Sometimes surgical resection of an infected lung may reduce the MTB burden in patients with MDR-TB.

_Extensively Drug Resistant - TB (XDR -TB) occurs when there is TB resistance to rifampicin, isoniazid, one of the fluoroquinolones and at least one of the second line injectable TB drugs (amikacin, kanamycin or capreomycin)

_XDR_TB is managed in the same way the MDR-TB but it has higher mortality.

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