Radiological changes and progress in patient with pulmonary Tuberculosis following treatment with daily versus intermittent short course regimens

This is a prospective comparative randomized study carried out at Kosti teaching hospital 20062008. Objectives: to determine the radiological findings and to evaluate the radiological progress in patient with pulmonary Tuberculosis treated with daily versus intermittent short course regimens. Methodology: A total of 275 smear positive new cases of Tuberculosis were enrolled and randomized in to two groups, intermittent group (A) and daily regimen group (B) .X-Ray film was done initially and at the end of treatment for each patient. Results: It was found that 31% of the X-Ray films were normal. Concerning the progress of minimal lesion significantly high percentage improved to normal X-Ray 58% in group A and 53 % in group B , 42 % in group A and 40 % in group B stayed as minimal lesion. The results of far advanced lesion revealed that intermittent regimen improved 16.6% of the films to normal and minimal lesion , 8.3 % to moderate lesion, 33.3 % moderately advanced lesion and 25 % remained unchanged, while in the daily regimen , 21 % improved to normal and minimal lesion , 5.2 % to moderate lesion , 27 % to moderately advanced lesion and 27.6 %. Statistical analysis revealed a significant difference between the two groups. Conclusion: Conversion of minimal lesions to normal X-Ray was significantly higher in the intermittent group and the conversion of far advanced lesions to normal was significantly higher in the daily regimen.

in Saudi Arabia near complete or complete clearance of chest X-Ray was detected in 43.5% of patients 2 . WHO has been propagating the use of intermittent supervised treatment for all cases including children 3 . In the United States, chest radiography is often considered a reliable and an important investigation for diagnosis of Tuberculosis 4 and lymphadenopathy may persist for several years after treatment 5,6 . In Abuja, Nigeria Chest X-rays were graded by two readers 7 . In USA chest radiographs help in the diagnosis of pulmonary TB, but may be normal and the rate of normal Chest X-rays among persons with culture-confirmed pulmonary TB was high 8 . This study aimed to determine the radiological findings and to evaluate the efficacy of intermittent TB therapy compared to the currently adopted daily short course R regimen in regards to: the radiological progress. introduced to the study .. The patients were randomized using lottery into two groups : Group (A) the intermittent regimen group these patients were treated using Ethambutol( 20mg/kg ) , Rifampcin( 10mg\kg)\ Isoniazid( 6mg/kg ) and Pyrazinamide ( 25mg/kg ) for two months as an initial phase then were given the minimum intermittent dosage of Rifampcin 900mg( 30mg/kg)\ Isoniazid 450mg( 15mg/kg ) twice weekly ( about 12 tablets\ week )for four additional months . 128 patients were enrolled. Group (B) the short course daily regimen group these patients were treated using Streptomycin (15mg ) , Rifampcin (10mg/kg ) \ Isoniazid (6mg/kg) and Pyrazinamide ( 25mg/kg ) for two months as an initial phase then rifampcin (10mg/kg)\ Isoniazid (6mg/kg ) once daily (about 21 tablets\ week) for four additional months , 147 patients were enrolled.

Material and Methods
Directly Observed Therapy (DOT) and closed supervision was applied. The patients were supplied with food supplied for the patient and his \ her family during the course of treatment. 71 patients (55.5%) were cured the treatment in group A (intermittent regimen group) and 67 patients (45.6%) in group B (daily regimen group). Chest X-ray was done in a posterioanterior position for each patient initially before starting the treatment and another one by the end of the treatment (after six months). X-Ray films were processed as follows: -X-ray films were reported by an expert radiologist then the initial and the final X-ray films were compared for the patients who completed the course of therapy using the following scores according to TB : -Minimal: For single lesion left, right, upper or lower.
-moderate: for two lesions in two lungs.
-Moderately advanced lesions: for more than two lesions in different zones (bilateral lesions).
-Far advanced lesion: involve two lungs in two different zones. A written consent from the local health authority was already taken and each patient was informed and consented. The raw data were introduced into SPSS program for the performance the descriptive and comparative analysis. The data comparison was carried out by Pearson Chi square and pair independent sample student T-test. The level of significance (P<0.05). The results:    The results of moderately advanced lesion revealed that both regimen cause an improvement of 17 % of this these types of lesion to normal, 28%, in the intermittent group and 33 % in the daily group were converted to minimal lesion, 22 % of the intermittent group were converted to moderate lesion, 33% and 50 % of the intermittent and the daily group successively were not changed 9 . The results of far advanced lesion revealed that intermittent regimen improved 16.6% of the X-Ray films to normal and minimal lesion , 8.3 % improved to moderate lesion , 33.3 % improved to moderately advanced lesion and 25 % remained unchanged , while in the daily regimen , 21 % were improved to normal and minimal lesion , 5.2 % to moderate lesion , 27 % to moderately advanced lesion and 27.6 % remained unchanged statistical analysis revealed significant difference between the two groups figure (6).

Discussion
Tuberculosis is now acknowledged to be one of the world`s biggest and most pressing health problem. The global burden of the disease based on data from 1990 showed that approximately 46.5 million disability adjusted life years were lost due to Tuberculosis. This study focused on chest radiographic changes as one of the cost effective tools to assess treatment outcome among the two study groups, and though it is seldom possible to make confident diagnosis or declare cure only on radiological grounds, however the extent and pattern of the disease among the intermittent chemotherapy group and the standard daily regimen group was assessed by double reading of CXR by two independent observers to reduce observer errors. It is important to note that radiological changes are not merely drugs related. According to the classification of the national TB Association of the USA, which has proved useful for clinical and research purposes, about 2/3 of our study population revealed moderate and far advance radiological pattern (fig 1). High percentage of far advanced lesion was detected among X-Ray films compared to minimal lesion 22.5% to 16.6% respectively; this indicates that the patients in the study area are late comers. Delay in diagnosis may be attributed to patients delay or health institutions delay. It was found that 31% of the films showed normal X-Ray which is higher than the situation in USA stated by Pepper and coworker 8 who mentioned that normal chest X-Ray among patients with culture-confirmed pulmonary TB was 13%. The inconsistency of these results and the situation in USA is due to the high sensitivity of culture and the difference of the cultureconfirmed diagnostic facilities between Sudan and USA. The high numbers of normal CXR (Fig1) found in this study may be due to localized postprimary endobronchial tuberculosis. Given positive sputum for AFB and normal CXR 5 many investigators revealed that enlargement of hilar or paratracheal lymph nodes is unusual in European adults. In our study like other Asian and African countries lymphadenopathy is a usual finding reference. TB limited to lower zones of the lung though unusual, it was found in 30 % in this study.
Many studies from northern Africa, Asia and Poland have investigated and described intermittent regimens as satisfactory 6 . Bronchiectesis was not detected in this study even in patients followed up for 18 months after completion of their regimen, which is different from 7% bronchiectesis found in Jordan 10 . Table (1).

Conclusion and recmmendations
Radiologically the twice weekly 6 month intermittent is as effective as the daily regimen. Delay in case identification was observed and it may be due to patients faults in the study, the high percentage of normal X-Ray (30%) needs further investigation for those smear positive and normal X-Ray. Adoption of intermittent chemotherapy in Sudan is cost effective and strongly recommended.