Dr.

Waqar Munir

42 years old Filipino lady, working as a housemaid for 3 years, underwent preemployment checkup during change of sponsorship in April 2011 and was found to have bilateral apical infiltrates on chest radiograph. She admitted at that time to having mild on and off cough but no fever or night sweats. Sputum smear & culture (2 sets) was done which was negative at 6 weeks. A Quantiferon test was positive in April 2011 and patient was diagnosed as ?latent tuberculosis infection.

She received Isoniazid 600mg twice per week and Rimactazid (INH + Rifampin) 600/300 twice per week (INH 1800 mg / wk & Rifampin 600 mg / wk) since 2nd June 2011 for 6 months and was due to finish her course of anti tuberculous agents on 2nd December 2011 as DOTS. Patient started to feel nauseated and fatigued at the end of October. LFTs were normal and she was reassured at TB Clinic, however she continued to have symptoms.

She was referred to A&E on 23/11/2011 with four days history of severe nausea, loss of appetite, fatigue and one episode of vomiting containing blood. No bleeding from any other site.

She also complained of mild right sided abdominal pain and noticed yellowish discolouration of her sclera and tea coloured urine.
Patient is non-Alcohol consumer and nonsmoker and no history of blood transfusion or extramarital relations or IV drug abuse.

T) 36.5 oC SpO2) 99% RA

B/P) 97/64 Ht) 157cm

H/R) 68/min R/R) 18/min Wt)54.4kg

Generally, she was conscious and oriented to time, place and person. She had yellowish discoloration of sclera and skin. No lymph node enlargement and JVP was not raised. Chest, CVS & CNS : No abnormality detected. Abdomen: soft, lax, non distended with mild tenderness at right hypochondrium and epigastrium. Liver was palpable 2 finger breadth below right costal margin with firm rounded edge and mild tenderness. Liver span 14cm. No ascities.

CBC: W: 4.7 S/E: BUN: 1.8 HCO3: 26

Hb: 12.8
Cr: 48

MCV: 82
Na: 141

PLT: 178
K:5.2

LFT: ALT: 926 AST: 847 Direct: 162 Alb:34 Coag: PT: 13 APTT: 38

ALP: 165

T.Bilirubin: 192

INR: 1.3

USG Abdomen: mild coarse liver. Autoimmune workup: negative ANA: 1:160 IgG: 2640

Hep. A B C & E Serology: negative Adenovirus, EBV, CMV: negative USG Doppler of Liver/ Portal system: Normal

Patient was admitted to medical unit as case of drug-induced hepatitis. Anti-TB medications were stopped 2 days before coming to the hospital as patient had already completed 5.5 months of therapy. LFTs and Coagulation profile was followed daily which showed a rise.

However the patient started to improve clinically and her symptoms resolved. She was followed up closely by GI team. Gradually her LFTs and Coagulation Profile started to decline and patient was discharged on 08/11/2011 with followup after 1 week of her LFTs in the clinic.

The New England Journal of Medicine, Vol 365, Dec 8, 2011

Timothy R. Sterling, M.D., M. Elsa Villarino, M.D., M.P.H., Andrey S. Borisov, M.D., M.P.H., Nong Shang, Ph.D., Fred Gordin, M.D., Erin BlivenSizemore, M.P.H., Judith Hackman, R.N., Carol Dukes Hamilton, M.D., Dick Menzies, M.D., Amy Kerrigan, R.N., M.S.N., Stephen E. Weis, D.O., Marc Weiner, M.D., Diane Wing, R.N., Marcus B. Conde, M.D., Lorna Bozeman, M.S., C. Robert Horsburgh, Jr., M.D., Richard E. Chaisson, M.D., for the TB Trials Consortium PREVENT TB Study Team*

Funded by the Centers for Disease Control and Prevention

Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion.

open-label, randomized noninferiority trial compared 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combinationtherapy group) with 9 months of selfadministered daily isoniazid (300 mg) (isoniazid-only group)

subjects at high risk for tuberculosis enrolled from United States, Canada, Brazil, and Spain. followup for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%.

Tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points.

Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001).

Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P = 0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001).

The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important.