DRUG RESISTANCE IN PULMONARY TUBERCULOSIS AT INSTITUTE OF CHEST DISEASES SINDH, KOTRI

 ABDULLAH JAN PATHAN, M. YOUSAF MEMON, ABRAR KHAN

 ABSTRACT:

            A retrospective study of OPD and ward of Institute of Chest Diseases Sindh, Kotri showed that 1156 (67.2%) out of 296OPD cases were admitted with male to female ration 3:1 during the year 1991. It comprised of 820 AFB positive and 336 AFB negative cases. 874 (75.6%) completed five drugs short courses regimen (SHRZE) for two months while 40 (3.4%) died and 242 (20.9%) left the hospital against medical advise. Only 12 (1%) virgin cases were noted while the rest were noted while the rest were on irregular an inadequate chemotherapy before. Out of 792 positive cases, 662 (83.6%) converted to negative while 130 (16.41%) remained positive. The resistance to short course chemotherapy is affecting almost one-sixth population of highly infectious cases and reflects on poor treatment program because of ‘doctors’ error (bad chemotherapy with regard to dosage, rhythm and duration) and patients’ poor compliance.

 INTRODUCTION:

Institute of Chest Diseases Sindh, Kotri is a 204 bedded hospital which serves as the chief referral centre for cases of pulmonary tuberculosis in Sindh excluding Karachi. A retrospective study was undertaken at this Institute for the year 1991 from January to December to assess the proportion of positive cases on direct microscopic examination of sputum smear for AFB, the rate of sputum conversion with short course chemotherapy, the proportion of non-conversion, number of caes who could not complete supervised chemotherapy and finally the district-wise distribution of cases. All the admitted cases were treated with five drugs short course regimen (SHRZE) for two months intensive phase. All drugs were given in a single dose early in the morning on empty in dosage as recommended by WHO Model Prescribing Information Drugs used in Mycobaterial Dieseases, Geneva 1991.

1.                  Inj-Streptomvein.     15 mg/kg body wt. I.M. daily

2.                  Rifampicin  10 mg/kg body wt. Daily orally

3.                  I.N.H.   5 mg /kg body wt. Daily orally

4.                  Pyrazinamide  30 mg/kg body wt. Daily orally

5.                  Ethambutol    25mg/kg body wt. Daily orally.

 The converters were discharge on HE for six months continuation phase while non-converters were advised to continue on HRE. This study concluded a high emerging rate drug resistance due to prior ineffective chemotherapy.

 Patients & Methods:

1.                  Case records of patients admitted at the Institute of Chest Diseases Sindh Kotri during January 1991 to December 1991 were analysed for:-

1.                  Date of admission.

2.                  Date of discharge.

3.                  Sputum status at the time of admission

4.                  Sputum status tat the time of discharge.

5.                  Drug history at the time of admission

6.                  Chemotherapy given during stay at the institute.

7.                  Sex proportion.

8.                  Number of details.

9.                  Number of LAMA cases

 II.                 Out-Patients Department records was analysed for:-

1.                  Total number of out-door patients.

2.                  District wise distribution.

3.                  Sex proportion.

4.                  Sputum status.

 Iii         Record of Laboratory was also examined for confirming the             sputum status in ward case and out patients department records.

Tory method used for sensitivity testing and differs from laboratory to laboratory. However, a laboratory to laboratory. However, a laboratory report of resistance in a pretreatment specimen does not necessarily mean that there will be a poor therapeutic response to drug concerned. Clinically resistance may be primary, initial or acquired. Primary resistance occurs in patients who have not received any tuberculosis chernotherapy before. It compares of natural resistance eof wild strain and infection with drug resistance organism from another patient with secondary resistance. Initial drug resistance is labeled in a drug resistance is not obtained reliably. It will include both primary and undisclosed acquired resistance. Acquired secondary drug resistance is due to exposure of tubercle bacilli to irregular and inadequate chemotherapy with regard to dosage, rhythm and duration and patients error (non-compliance). This acquired resistance may be to a single drug or two or three drugs. Drug resistance occurs by mutation and the drug acts as a selective agent. All large bacterial populations contain a minute proportion of mutants which are not susceptible to a bacteria population. Hence, drug resistance is the result of selective process by which the non-susceptible mutants are singled out through the elimination of susceptible majority .Therefore antituberculous drugs are used in combination to prevent the emergence of resistance.

 The emergence of secondary drug resistance in a patient receiving chemotherapy is a serious event and is a menace to the tuber culosis control program. In 1156, admitted patients only one percent cases has not taken any antituberculous chemotherapy before. While 99 percent cases who go admission were likely to have acquired drug resistance to one or more drugs. Hence, we started chemotherapy with five drugs (SHRZE) to minimize the emergence of drug resistance further. Our stand has also been vindicated in the recent WHO publication viz. WHO model prescribing information: Drug Used in My-cobacterial Diseases (1991).

After five drugs supervised chemotherapy to 792 AFB positive cases for two months, 84$ (662) converted to negative on direct smear microscopy while about 16.4% (130) showed not bacteriological conversion. Bacteriological conversion. Bacteriological conversion rate with short course chemotherapy is definitely very high but 16.4% noncomversion is also not low though it has to be further evaluated on susceptibility tests yet it correlates the Lahore TB study (1986) wherein 16.6% failed to convert when treated with three drugs short course regimen (HRE/HRZ)⁹.16.4% drug resistance and 99% cases with bad chemotherapy are of great concern in the present activities of tuberculosis control. Gryzbowski has outlined the impact of a tuberculosis epidemic on a populaiton¹⁰. There is an initial soaring increase in mortality which reaches a plateau and subsequently declines without intervention. This is because of elimination of susceptible and natural selection. The decline in cordiality continues under natural conditions. Its rate can be accelerated by good chemotherapy with proper doses and proper regimen for adequate time while bad chemotherapy wil increase the pool of tuberculosis patients including resistant cases. So with a poor treatment pogarmme we actually cause epideminologic harm and slow down or even reverse the steady natural decline of tuberculosis. Inadequate treatment policy saves lives but

 RESULTS

During the year 1991 through January to December, 2966 chest symptoms motivated cases reported at the out patient department of institute and were subjected to following screening tests:- 

1.      Direct microscopic examination of sputum for AFB.

2.      Chest radiograph: PA view.

 Out of 2966 cases, 152 (5.12%) had no disease as evidenced by negative sputum for AFB and chest radiograph. 2814 (94.87%) were labeled as suspects on chest X-ray, out of which 820 (27.65%) were positive for AFB on sputum smear microscope while the rest 1994 were negative for AFB and included cases of chronic fibrocaseous disease, pleural diseases etc.

 Out of 2966 OPD cases, 1156 were admitted in the hospital including 820 (70.93%) sputum positive and 336 (29.07%) AFB negative cases. The male and female ratio was 2:1 and 3:1 in OPD and admitted cases respectively.

 Out of 1156 admitted cases, 40 (12 AFB +ve and 28 AFB – ve cases) or 3.45% became serious and died in the hospital. On the other hand 242 (16 AFB+ve and 226 AFB- ve) or 20.93% left the hospital against the medical advise. Remaining 874(75.6%) cases among which 82 (7.09%) were AFB – ve and 792 (68.51%) were AFB + ve, completed two month’s supervised short course chemotherapy in the hospital.

 At the time of discharge 662 (83.59%) out of 792 AFB + ve cases converted to negative while130 (16.41%) remained positive for a AFB.

DISCUSSION

Drug resistance in tuberculosis is the decrease in sensitivity of tubercle bacilli to anti tuberculosis drugs while it is reasonably certain that the concerned strain is not from the sample of wild strain which has never come into contact with drugs². Drug resistance for each drug is defined by the labora creates an appreciable proportion of chronic excretors of tubercle bacilli, often resistance to more than one drug. Thus the situation becomes worse than if no programme would have existed as sources of infection become more and more primary and acquired drug resistant failure and drug resistance urges for more efforts to control the disease by organizing good national chemotherapy policy and training and retraining of doctor’s.

 REFERENCES

 1.                  WHO Model Prescribing information 1991. Recommended treatment regimens for tuberculosis. In Drug used in Mycobacterium Diseases. WHO, Geneva, pp. 12.

2.                  Citron KM, Grilling DJ. Tuberculosis. In: Weatherall DJ, Ledingham JGL, Warral DA (eds.). 2^nd Ed, Oxford Textbook of Medicine. 1987; 1:5, 280.

3.                  Crofton J. Douglas A. Respiratory. 3^rd Ed; pp. 127-128, 1981.

4.                  Seaton A, Seaton D, Leithch AG, Crofton & Douglas, Respiratory Disease, 4^th Ed, pp. 434-435, 1989.

5.                  Gangadharm PRJ. Drug Resistance. In: Rao KN, Sen PK, Pamra SP et al (eds.). Textbook of tuberculosis. pp. 125-126,1981.

6.                  Toman K. Tuberculosis. Case finding and treatment. WHO, Geneva.pp.84-85, 1979.

7.                  Wolinsky E. tuberculosis. In: Wuyngaarden JB, Smith LH, Cecil (eds.). Textbook of Medicine, 7^th Ed, pp.298-1626, 1985.

8.                  WHO Model Prescribing Information 1991. Treatment of Relapsing and unresponsive disease, WHO Geneva, pp. 10.

9.                  Aziz A, Ishaque M, Akhund Retail. Tuberculosis in Pakistan Lahore Tuberculosis Study. Am Rev Respi Dis. 1986; 1056-1061.

10.              Grzybowski S. A look at the world situation. In: Pathan Aj, Ilyas M. Jan’s Treatise on Epidemiology & Control of tuberculosis. pp. 63-66, 1988.

11.              WHO 9^th Report of WHO Expert Committee on Tuberculosis 1974. Technical Report Series No. 552, WHO Geneva.