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INTERNATIONAL SCENARIO ONE-THIRD OF THE WORLD POP I.E. 1.9B IS INFECTED WITH M.TUBERCULOSIS GLOBAL PRAVELANCE 1S 16-20M 9M NEW CASES ADDED EVERY YEAR.

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Presentation on theme: "INTERNATIONAL SCENARIO ONE-THIRD OF THE WORLD POP I.E. 1.9B IS INFECTED WITH M.TUBERCULOSIS GLOBAL PRAVELANCE 1S 16-20M 9M NEW CASES ADDED EVERY YEAR."— Presentation transcript:

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3 INTERNATIONAL SCENARIO ONE-THIRD OF THE WORLD POP I.E. 1.9B IS INFECTED WITH M.TUBERCULOSIS GLOBAL PRAVELANCE 1S 16-20M 9M NEW CASES ADDED EVERY YEAR (INC. 136/100000) 1.82M DEATHS FROM TB 12% OF HIV DEATHS ATTRIBUTABLE TO TB 95% OF NEW CASES AND DEATHS OCCUR IN DEVELOPING COUNTRIES

4 22 HIGHBURDEN DISEASE COUNTRIES INDIA CHINA INDONESIA NIGERIA BANGLADESH ETHIOPIA PHILIPPINES PAKISTAN SOUTH AFRICA CONGO RUSSIAN FEDERATION KENYA VIET NAM UR TANZANIA BRAZIL UGANDA ZIMBAVAA MOZAMBIQUE THAILAND AFGHANISTAN CAMBODIA MYANMAR

5 Estimated TB incidence rate, 2005 No estimate 0–24 50–99 100– or more 25–49 Estimated new TB cases (all forms) per population The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO All rights reserved

6 STATUS OF TB IN PAKISTAN RANK: 8 TH AMONGST 22 HBD COUNTRIES PAKISTAN CONTRIBUTES 43% OF THE TUBERCULOSIS BURDEN IN THE EMRO REGION PREVALANCE OF TB 1.5 M INCIDENCE: 181/ POPULATION NEW CASES EVERY YEAR 3 OUT OF 4 PATIENTS ARE ADULTS (15-59) ECONOMICALLY PRODUCTIVE AGE GROUP

7 Punjab Accounts for > 50 % of disease burden in country I.E.1.5 million cases. Fifty percent of patients are females new smear positive cases every year. STATUS OF TB IN PUNJAB

8 Tuberculosis - 2 main types 1.Mycobacterium tuberculosis - most common infection in humans. 2.Mycobacterium bovis (animal form) is responsible for an increasing proportion of human TB cases. 3.More recently, M. tuberculosis has been documented in a free-ranging animal, the banded mongoose.

9 Banded Mongoose

10 Possible Implications Expansion of ecotourism, excalating human populations, and changes in land-use practices have increased the possible disease threat humans pose to wildlife.

11 Source: Zoonotic Tuberculosis in Developing Countries. EID - CDC. AGRICULTURAL HEALTH IS NOT PREPARED TO FACE RE-EMERGING ZOONOSIS In 22/34 countries of Latin America and the Caribbean Tuberculosis Milk Aerosols Milk Aerosols Food Water

12 Source: Zoonotic Tuberculosis in Developing Countries. EID - CDC LOSSES DUE TO TUBERCULOSIS Argentina suffers US$63 million in losses annually 30 million deaths in the world from

13 Source: Promed TRADE AND TOURISM CHALLENGE AGRICULTURAL AND PUBLIC HEALTH West Nile Virus New York, ,324 bird cases 57 equine cases 19 human cases 4 dead

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19 AFB smear AFB (shown in red) are tubercle bacilli

20 Reporting on AFB Microscopy Number of bacilli seenResult reported None per 100 oil immersion fieldsNegative 1-9 per 100 oil immersion fieldsScanty, report exact number per 100 oil immersion fields per oil immersion field2+ > 10 per oil immersion field3+

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24 Diagnosis of Pulmonary TB Cough 3 weeks AFB X 3 Broad-spectrum antibiotic days If symptoms persist, repeat AFB smears, X-ray If consistent with TB Anti-TB Treatment If 1 positive, X-ray and evaluation If 2/3 positive: Anti-TB Rx If negative:

25 Chemotherapy Era Streptomycin (s) – 1940 INH (H) – 1952 PAS Standard chemotherapy was effective but unpleasant. Initially H.S.PAS 3 months, continuation phase H + PAS – 15 months.

26 Current Standard Chemotherapy (WHO/IUATLD RECOMMENDATIONS) Rich countries –Initial phase 2 HRZE/S –Continuation phase4 HR Poor countries –Initial phase 2 HRZE –Continuation phase6 H.T./H.E.

27 Tuberculosis is a disease of great antiquity Evidence in Egyptian and precolumbian mummies. Before the availability of drugs, diagnosis of T.B. – a life time sentence. Bed Rest, good diet, sanatoria on hillsides – only available treatment.

28 Collapse Therapy Artificial Pneumothorax Pneumoperitoneum Phrenic Crush Thoracoplasty Plombage

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30 Tuberculosis & Diabetes Mellitus BOTH T.B. & DIABETES MELLITUS - COMMON CLINICAL PROBLEM IN DEVELOPING COUNTRIES LIKE PAKISTAN. DIABETICS HAVE A HIGHER RATE OF T.B. BY A FACTOR OF THREE.

31 REASONS FOR HIGH INCIDENCE OF T.B. IN DIABETICS NOT CERTAIN MAY BE DUE TO:- POOR GLYCEMIC CONTROL DUE TO DEFECT IN T. CELL ALVEOLAR MACROPHAGES ACTIVATION IN DIABETICS

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33 Anti Tuberculosis Treatment and Diabetic Control 1.Rifampicin - causes hyperglycemia due to:- *increased metabolism of oral hypoglycemic agents - as a liver microsomal enzyme inducer. *Initial hyperglycemia - unknown mechanism. Patients needs high dose of oral hypoglycemic agents 2.High incidence of peripheral neuropathy with INH, Ethambutol and Ethionamide. So pyridoxine must be advised with ATT. 3.Ethionamide causes hypoglycemia so critical control of blood glucose level.

34 Relapse of Tuberculosis Relapse should be less than 1% Resistance studies should be obtained. If previous treatment adequate: 1/3 rd patients have drug resistance. If previous treatment inadequate: Resistance in 2/3 rd of patients, initial therapy should be for presumed drug resistance.

35 Liver Impairment Drug induced hepatotoxicity 3-5% in the population.In our population it is around 9% (Haq M.U, Rasul S*, Iqbal Z.H. Ch. MK, Bhatti A.H, Anwar N, Nasir Incidence of Hepatitis in patients taking Anti- tuberculosis treatment. Annals KEMC, June- Dec. 1996;49 – 51) Drug induced Hepatitis – stop the regimen. Start- Ethambutol, Streptomycin and ofloxacin.

36 Pregnancy Primary TB drugs are safe- no evidence of teratogenecity. Rifampicin, INH, Ethambutol, PZA – all safe. Streptomycin: may produce ototoxicity of fetus not recommended. Preferable :-Female married patients avoid pregnancy during treatment course.

37 Pregnancy Rifampicin baby: Rifampicin decreases the efficacy of oral contraceptives. Pregnancy may occur while taking contraceptive pill. Hence dose of pill should be doubled or alternative methods used. If pregnancy occurs – then treat with ATT. First time diagnosis of TB during pregnancy give ATT. Dot not advise termination of pregnancy.

38 HIV Infection The normal regimen is as effective as in HIV negative patients. Adverse reactions to thiacetazone are common. Higher relapse rates are found, so that treatment may be prolonged.

39 Silicosis More prone to active pulmonary tuberculosis Difficult to treat i)Function of alveolar macrophages is impaired. ii)Massive fibrosis may prevent penetration of drugs to the site. Forty percent of silicosis patients had active TB in Hong Kong. More relapse. Prolonged treatment required.

40 MULTI DRUG RESISTANCE (MDR) Defined as resistance to both isoniazed and rifampicin with or without the presence of resistance to another drug.

41 Factors contributing to MDR TB Non compliant patient –Multifactorial (Interruption, Selection of Drugs, Premature cessation of treatment) Inadequate regimen. Prolonged treatment. Exposure to an MDR TB patient (Lack of facilities to isolate the patient)

42 Factors contributing to MDR TB (Contd.) Asian origin. Homelessness. Drug abuse. HIV. Adverse reaction to anti T.B. drugs.

43 Development and spread of drug-resistant tuberculosis Colony of mycobacterium tuberculosis Resistant mutants Secondary (multiple) Drug-resistant tuberculosis Primary (multiple) Drug-resistant tuberculosis More Primary (multiple) Drug-resistant tuberculosis Natural mutations Selection of resistant strains by inadequate treatment Transmission in droplets HIV Infection Inadequate infection control Diagnostic delay Further transmission

44 Drug Resistance Status in Pakistan In 1967: 87% of isolates from treated patients resistant to one or more drugs. In 1989: 31.6% in treated patients Resistance to H: Primary Secondary Resistance Resistance %57% %52.6% % %53% Recommendations:- Initial phase 3 HRZE (S) Continuation phase 6 HRE

45 Primary and secondary resistance to individual drugs DrugCase with Resistance Primary Resistance Secondary Resistance UnknownP-Value N%N%N%N% H <0.001 R NS Z NS E NS S <0.001 PAS <.05 TH NS ETH NS NS = NOT SIGNIFICANT, N = NUMBER Biomedica Vo. 11 (Jul, Dec 1995)

46 Drug resistance in North West Frontier Province, Pakistan, 1994 Drug Primary resistance (%) Acquired resistance (%) Streptomycin1046 Isoniazid157 Rifampicin350 Pyrazinamide357 Ethambutol1150 Thiacetazone230 Percentage resistant to one drug8.8 Percentage resistant to two to four drug12.7 Percentage resistant to five drugs20.0 Percentage resistant to six drugs8.8 Source, Tuberculosis in Pakistan A. Javaid and M. Amjad in clinical tuberculosis ed.. P.D.O.Davies. 2 nd ed. 1998

47 Resistance pattern of 228 culture positive cases to various antituberculosis drugs. DRUGAll PatientsPrimaryAcquired P Value N=228 Cases N=123 Cases N=105 Percent resistant Isoniazid % (36)7.31% (9)25.71% (27) <. 001 Rifampicin (MDR) Isoniazid 25.43% (58)21.13% (26)30.47% (32).10 Rifampicin25.00% (57)15.44% (19)36.19% (38)<.001 Streptomycin 24.12% (55)16.26% (20)33.30% (35)<.01 Pyrazinamide21.49% (49)11.38% (14)36.19% (38)<.001 Ethambutol10.00% (23)04.87% (06)16.19% (17)<.01 Shamshad Rasul, Iffat Shabbir, Rizwan Iqbal et al: Trends in multidrug resistant tuberculosis, Pakistan Journal of Chest Medicine, Volume 7, No. 3, 2001, 1-28

48 Primary Drug Resistance At JPMC Karachi INH 16% Rifampicin 07% Ethambutol 02% Streptomycin 03% MDR 01% Rano Mal,Nadeem Rizvi,Shahina Qayyum SAARC JTB,L DIS&HIV/AIDS (1)20-23

49 Pattern of drugs resistance among mycobacterium tuberculosis isolates (1998 to 2002) YearNo of patients (MDR) H + R IsoniazidRifamp icin Pyrazin amide Strepto mycin Ethamb utol % (41) 22.91% (55) 22.5% (54) 29.16% (70) 17.5% (42) 10.41% (25) % (36) 25.43% (58) 25% (57) 21.49% (49) 24.12% (55) 10.08% (23) % (38) 26% (62)28.15 % (67) 26.89% (64) 25.21% (60) 15.54% (37) % (35) 27.35% (58) % (64) 31.13% (66) 26.88% (57) 16.50% (35) % (35) 25% (57)27.63 % (63) 29.38% (67) 22.36% (51) 14.47% (33) Rizwan Iqbal, Iffat Shabbir et al: TB drug resistance alarming challenge – answer DOTS., Pakistan J. Med. Res. Vol. 42 No.3, 2003,

50 Gulab Devi Chest Hospital, Lahore From 01 July 2004 to 31th June, Isolates of Mycobacterium TB 116 Resistant to Rif & INH(MDR)27 (23.27 %) Resistant Pattern of individual drugs Resistant to Rifampicin38.79% Resistant to Isoniazid42.42% Resistant to Streptomycin37.06% Resistant to Ethambutol18.96% Resistant to Thiacetazone21.55% Resistant to Pyrazinamide58.62%

51 Management of MDR - T.B. 1.Detailed evaluation regarding history, clinical examination and previous treatment 2.Culture and sensitivity pattern.

52 Principles of MDR TB management At least 4 drugs to be given never used before. An injectable should be used ___ one of the aminoglycosides not used earlier. Never add a single drug to a failing regimen ____ a minimum of 2 drugs be added. DOTS Plus Must Duration of therapy 18 – 24 months.

53 Second Line Antituberculosis drugs DrugsDaily DoseAdverse Effects Ethionamide mg P.O. (In divided doses if necessary) Gastrointestinal intolerance hepatitis, endocrine disturbances, hypersensitivity Cycloserine250 – 750 mg P.O. (In divided doses adjust for renal impairment) Neurological and Psychiatric Disturbances Capreomycin15 mg / kg i.m.Hearing loss, Vestibular Amikacin Kanamycin 5 days a week (adjust for renal impairment) Renal toxicity Electrolyte disturbances

54 Second Line Antituberculosis drugs (Contd.) DrugsDaily DoseAdverse Effects Para – AminoSalicylic Acid g P.O. (In divided doses) Gastrointestinal intolerance hepatitis, Hypersensitivity Ciprofloxacin Ofloxacin Levo Floxacin 500 – 1000 mg P.O. 400 – 800 mg p.o. 500 mg P.O. Gastrointestinal intolerance headache, Restlessness, Hypersensitivity, Drug interactions Clofazimine100 – 300 mg q.d.s. P.O. Abdominal pain, Skin Discoloration (both dose related) photosensitivity

55 Recommended Regimens for the Treatment of Tuberculosis in problem cases Initial Phase Continuation Phase IndicationDuration, Drugs Duration Drugs MonthsMonths Failure and relapse* Standard 3 HRZES** 5 HRE retreatment (susceptibility testing unavailable) Resistance to H + R Throughout (12-18) ZE + O + S (or - another injectable agent) Resistance to all first Throughout (24) 1 injectable agent*** of these 4: ethionamide, cycloserine, PAS, O * Regimen is tailored according to the results of drug susceptibility results. ** Streptomycin should be discontinued after 2 months *** Amikacin, Kanamycin or Capreomycin. Treatment with all of these agents should be discontinued after 2-6 months depending on patients response and tolerance.

56 Regimen for the Treatment of MDR tuberculosis Resistance to Initial phaseContinuation phase Minimum DrugsdurationDrugsDurationin months Isoniazid1. Aminoglycoside 31. ethionamide 18 rifampicin and2. Pyrazinamide 32. Ofloxacin; 18 streptomycin3. Ethionamide 33. ethambutol; Ofloxacin 3 5. Ethambutol 3 Isoniazid1. aminoglycoside 31. ethionamide 18 rifampicin, 2. ethionamide 32. Ofloxacin; 18 streptomycin and3. pyrazinamide 33. Cycloserine; 18 ethambutol4. ofloxacin 3 5. cycloserine 3

57 Prevention for MDR TB Proper management – DOTS. Proper regimens. Adequate dosage (Fixed dose combination – A partial solution) Treatment should consider patients needs, constraints, preferences and confidentiality.

58 Prevention for MDR TB (Contd.) Early case detection of primary MDR cases. Education of medical and paramedical professionals in all aspects to be maintained or reemphasized. Free treatment and other incentives for the patients.

59 Renal Impairment Rifampicin, INH, PZA, Eithionamide and Prothionamide eliminated almost entirely by normal routes – Hepatic metabolism or billiary excretion. In severe renal failure – INH dose be reduced to 200 mg daily with pyridoxine supplementation. No adjustment required, if patient on hemodialysis.

60 Renal Impairment Streptomycin and other amino glycosides – need dose adjustment. Streptomycin injections should be spaced, so that trough levels of the drugs does not exceed 4mg/L. In patients on dialysis, streptomycin should be given 6-8 hours prior to dialysis. Ethambutol excreted predominantly by kidney. The dose needs to be adjusted (decreased).

61 Renal Impairment Ethambutol If renal clearance ml/min, 25mg/kg three times a week. If renal clearance ml/min, above dose twice a week. If renal clearance <10-25 ml/min, a dose of 15 mg / Kg at 36 to 48 hours interval. Patients on thrice weekly hemodialysis, 25 mg / Kg 4 to 6 hours before the procedure.

62 Renal Impairment Thiacetazone, PAS Partly excreted through kidney unchanged partly metabolized through liver. Therapeutic index for thiacetazone is low, generally not recommended.

63 PRE DOTS SCENARIO Low Priority by Policy makers Reliance on specialized units not accessible to all Inappropriate diagnostic procedures and over reliance on x-ray Lack of recording,reporting and Evaluating system Use of non standardized drug regimen Non existent supervision

64 TB Control: The 5 components of DOTS TB Register Political commitment Diagnosis by microscopy Adequate supply of the right drugs Directly observed treatment Accountability

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