Tuberculosis Diagnosis and Treatment
Diagnosis:
Sputum smears: 3 sputum samples should be examined whenever a cough has been present >2 weeks. Patients should submit 3 specimens within 24 hours: 1 sputum at first presentation (spot), the 2ndthe next morning (morning) and the 3rd during following day (spot). 80% of cases will be detected with the first sputum, 15% with the second and 5% with the third.
-looking for acid fast bacilli via Ziehl-Neelsen staining: specific, but not sensitive, particularly if disease has not cavitated
-diagnosis of sputum negative TB: if 3 samples are negative and your suspicion is high, reassess the patient and repeat sputum exam after 1-2 weeks, following a trial of antibiotics and obtained chest xray. Consider alternative diagnoses such as: pneumonia, asthma, chronic bronchitis, bronchiectasis, lung cancer or abscess, non TB complications of HIV
Chest xray: There is no CXR appearance typical for PTB! A normal chest xray makes pulmonary TB less likely but chest xrays cannot distinguish reliably between TB and other diseases.
- cavitations are fairly specific for TB, but are often absent particularly in HIV
Tuberculin skin testing (TST): indicates exposure to TB but not necessarily active disease
-Generally not used in adult patients at BMC.
Culture of M.Tb: takes 4-12 weeks; more modern methods with liquid media or BacTec are more rapid and can provide results in <2 weeks.
ESR: nonspecific and should not be used as a routine diagnostic tool
Categories:
Category I – New smear positive PTB or new patients with severe forms of EPTB
Category II – Relapse, treatment failure, or sputum smear positive after default
Category III – New sputum smear negative PTB or less severe forms of EPTB
Category IV – Chronic cases
Severe forms EPTB – meningitis, military, pericarditis, bilateral or large effusions, spinal, intestinal, GU tract
Relapse – smear positive after cure
Treatment Failure – a patient who remains smear positive after 5 months of therapy
Default – a patient who stopped therapy for > 2 months
Treatment:
Aims of treatment: to cure the patient, to prevent transmission in the patient’s family and community, and to prevent development of resistant bacilli
Principles of anti TB therapy:
-use at least 2 drugs to which the organism is presumed to be sensitive
-administer treatment for 6-9 months (for pulmonary and extrapulmonary TB)
-ensure the patient completes the full course of therapy
Anti-TB:
-Izoniazide (H) – very potent; Major side effect liver toxicity. Peripheral neuropathy more common in diabetics, malnourished, alcoholics, HIV (in these patients give pyridoxine (vitamin B6) 25-100 mg OD)
-Rifampin (R) – very potent; high rate of drug interactions (induces CYP450 and lowers levels of NVP, OCPs, warfarin and anticonvulsants), can also cause hepatitis, red urine and N/V
-Pyrazinamide (Z) - may cause arthralgias, hepatitis
-Ethambutol (E) – less potent and main role is prevention of resistance to other drugs; may cause optic neuritis
-Streptomycin (S) – injectable; can cause ototoxicity/vertigo, local numbness at injection site, renal toxicity; contraindicated in pregnancy
Steroids: Consider adding steroids if TB meningitis, TB pericarditis (to prevent restrictive pericarditis), pleural TB with large effusion, IRIS
- rare indications: TB laryngitis, massive lymphadenopathy renal TB, adrenal TB
Treatment Regimens:
Category I/III regimen: 2 RHZE/4 RH
- in adults, fixed drug combinations (FDCs) are used
- 4FDC RHZE contains R150mg/H75mg/Z400mg/E275mg
- for adults > 50kg: 4 tabs OD x 2 months
- for adults 31-50kg: 3 tabs OD x 2 months
- 2FDC RH for daily use contains R150mg/H75mg
- same as above
Category III: 2SRHZE/1RHZE/5RH3E3
Category IV: no treatment currently available
Drug resistance: About 5% of TB in Tanzania is resistant to INH. Resistance to both INH and rifampin (so called MDR TB – Multi Drug Resistant TB) occurs in 1%. Extended Drug Resistant (XDR TB) which is resistant to INH, rifampin and streptomycin is increasingly being reported in some parts of the world but has not been reported in TZ.
TB Preventative Measures
1) Early diagnosis and treatment*
2) DOT to assure that medications are taken*
3) Isolation of sputum positive patients in the first 2 weeks of treatment (when possible)
4) BCG immunization in infants
5) Screening families and close contacts of smear positive patients to detect other cases of TB.
6) INH prophylaxis in select populations (like HIV+)
* also help in reducing development and spread of MDR-TB
HIV and Tuberculosis
TB incidence has increased up to 6 fold in areas affected by HIV. TB is the most common cause of death in patients with HIV and the mortality of TB in the setting of HIV is much higher than TB in the absence of HIV. The main mechanism involved is suppression of cell-mediated immunity by HIV which impairs the immune response to TB and leads to increased rates of reactivation of latent TB. Primary TB is also possible. The HIV epidemic has also decreased the average age of TB patients.
Differences in TB among HIV positive patients
Presentation:
-extra pulmonary TB is more common in this population (40% vs 10% in the general population) so symptoms/signs are often nonspecific
Diagnosis:
The diagnosis of TB in HIV+ patients is difficult due to 3 main reasons:
1) CXR findins are often non-specific - HIV positive patients are less likely to produce upper lobe disease or cavities. More commonly have hilar adenopathy, effusions, miliary disease or opacities in lower/middle lobes.
2) Sputum for AFB is often negative, particularly if CD4 < 350
3) The possibility of other opportunistic infections (such as PCP) which can present with many of the same features of TB.
Treatment: same drug regimen in HIV patients and non HIV patients
-recurrence rates and re-infection is higher in HIV patients
-mortality during and after treatment is also higher in HIV patients
-rifampin lowers serum levels of most protease inhibitors and nevirapine; for this reason, patients on NVP should be switched to EFV if starting anti-TB
-if TB and HIV are diagnosed at he same time, anti-TB should be started immediately and ART should be delayed for at least 2 weeks (if CD4<50) or 2 months (if CD4>50) to prevent IRIS.
Tuberculosis Clinical Cases
Case 1
30 yo male with history of HIV positive (CD4 - 500) on ARV’s presents with nonproductive cough x 2 months. He is not producing any sputum and there is no blood associated with the cough. No complaints of shortness of breath or chest pain. He also complains of intermittent fevers and night sweats. He also complains of fatigue and malaise.
1. What is your differential diagnosis for this patient?
2. What diagnostic tests do you want to order?
You order a chest xray and it shows a right upper lobe opacity. His sputum comes back positive for acid fast bacilli.
1. What is the diagnosis?
2. What treatment do you want to offer this patient?
3. How long do you want to treat this patient for?
4. What side effects will you warn him about?
Case 2
40 yo female with history of HIV (CD4 100) and tuberculosis presents to your outpatient clinic with complaints of rash and reddish looking urine. She has been taking her 4 drug regimen for tuberculosis for 4 months now and has not had any problems. She describes the rash as diffuse, on her arms and legs and is not itchy. The rash has been there for a week and she noticed the reddish looking urine for 3 weeks.
1. What is the most likely cause of the patient’s symptoms?
2. How do you want to management this patient?
3. Should she discontinue any of her medications? Why?
