Therapeutic Efficacy of Fully Intermittent Regimen For Neuro TB – A Field Study In S.India

Venugopal K., District T.B centre, Alappuzha.

KEY WORDS
Neuro TB, DOTS, ATT, Intermittent regim
 

INTRODUCTION

Neuro tuberculosis is the most serious form of tuberculosis which need more intensive and prolonged therapy. Even with prompt and adequate treatment, the mortality rate goes up to 30%. It constitute approximately 15% of extra pulmonary cases or about 0.7% of all clinical tuberculosis2. CNS tuberculosis may be in the form of meningitis, intracranial tuberculoma and spinal tubercular arachnoidits and rarely tuberculous encephalopathy. Diagnosis is usually based on clinical presentation, CSF study and neuro imaging. CSF study remains the principle diagnostic tool in TBM3. CSF shows pleocytosis with lymphocytes, elevated protein ranging from 60 to 400 mg% or even higher, sugar between 20 to 40%. It is sterile on routine bacterial culture. Demonstration of tubercle bacilli by AFB staining or culture remains the most important step of CSF study but its yield is much low4. CSF may be normal in CNS tuberculoma and tubercular encephalopathy. Neuro imaging shows basal  exudates, hydrocephalus, infarcts, tuberculomas, brain edema etc. CT scan may also be normal. Conventionally neuro tuberculosis is treated with initial intensive therapy with multiple drugs followed by INH and Rifampicin for at least one year or even longer. The rate of hepato toxicity in adults receiving INH is 1% and doubles with the addition of rifampicin5. Outcome of CNS tuberculosis depends on the age of the patient, duration of illness, clinical stage at time of treatment initiation, the extent of arachnoiditis, vascular complication, hydrocephalus and increased intra cranial tension. The incidence of residual neurological deficits after recovery varies from 10 to 30%5.

With the introduction of Revised National TB Control Programme, Neuro Tuberculosis is categorized among extra pulmonary seriously ill6, recommending 2HREZ 3 /4HR3 with extension for 3 more months. But neurologists and physicians are reluctant to accept the intermittent regime, considering the seriousness of the condition and lack of published studies to prove the effectiveness of intermittent regime in this situation.

With our best efforts, we could not find a single study in the literature proving the efficacy of fully intermittent short course therapy in Neuro TB. So the present study was planned.

AIM OF STUDY

To determine the treatment outcome of Neuro tuberculosis patients put on DOTS.

SUBJECTS AND METHODS

All Neuro tuberculosis patients registered for DOTS in the various TUs of Alappuzha District during the period January 2002 to December 2002. DOTS therapy was given as per RNTCP guidelines7. Diagnostic algorithm and follow up of RNTCP were followed. Data were collected from TB register. An effort was made to evaluate case history, and investigation findings and to examine the patients was done by reviewing them 6 to 12 months after stopping treatment. A co-ordinated effort of Medical Officer Tuberculosis Control and Senior Treatment Supervisors were utilized.

Govt. of India has given directions to all health department to provide intermittent short course regimen drug for all type of TB cases including Neuro TB. Besides all cases were given DOTS treatment as per decision of District TB Control Society. We also obtained informed consent from all patient for DOTS therapy.

RESULTS

Thirty-two cases were registered in the four Tuberculosis Unit of Alappuzha District during the year 2002. This formed 8 % of the total of 419 extra pulmonary cases registered in the District in above year. 17 were males and 15 females. The age distribution was 16 years to 76 years. 50% belong to the age group 31 to 50 years

All deaths were investigated. In two cases ATT was started empirically after surgery for intracranial space occupying lesions (SOL). Among the rest, two deaths occurred with in first week of starting the treatment and the other after three months of treatment.

Among the 26 patients who completed treatment only 15 patients could be available later for further follow up and 13 were referred from medical college Alappuzha and Kottayam and two from District Hospital. Decision to start ATT was taken by physician with post graduate qualification or neurologist.

Majority of them presented with headache, vomiting, fever and altered sensorium. CSF study was abnormal in all except one. The total count varied from 70 to 660 with the mean value of 272. Lymphocyte predominance was seen in eleven cases (73%). A low sugar value below 40mg % was seen in only 4 cases (26%). Protein values  ranged from 17 to 575 mg %. It was elevated in only 11pateints (63%). Routine Bacterial Culture was sterile in all the cases. But none was send for AFB culture or staining. Chest X-ray was abnormal in 3 cases (20%). HIV screening done in 7 cases were negative. CT was suggestive in 3 cases .

Of the 15 cases interviewed only one had sequelae of hemi paresis and two were complaining of persistent headache. So overall sequelae was negligible compared to many previous studies.

DISCUSSION

India is among the nations of high incidence of TB. Usually there are 20% of extra pulmonary cases of which 15% will be Neuro tuberculosis. So in Alappuzha alone there were 419 extra pulmonary cases put on DOTS in 2002. So an expected incidence of 63 cases of Neuro TB would have occurred during 2002. But the actual number of Neuro TB cases registered for DOTS were only 32  and 4 cases were registered for daily treatment initially. Thus the chance for under diagnosis is more than that of over diagnosis. 22 cases received DOTS from volunteers (Aganawadi workers), 10 from health staff. 70% cases received actual DOTS.

Even though RNTCP recommendation is for 8 - 9 months treatment, two received treatment only for 6 months (probably due to lack of awareness of this recommendation )8. Four patients were changed to daily regimen.

All of them belonged to younger age and 3 had clinical jaundice and one with persistent vomiting. Medical College Authority made the alteration of regimen. There is a high incidence of hepatitis noticed in the study group and all three were 15 to 22 year age group (75%). No other side effect occurred necessitating change of regimen.

81% treatment completion was obtained in our study which is much higher than that in NTCP regime. A meta analysis of NTCP studies showed completion of only 50% 8. High rate of completion seen in this study could probably due to easy availability of drugs and supervision of drug intake. The mortality rate was only 16% which was much lower than the previously reported ones. One of the known variables of mortality ie, the stage of the disease at time of initiation of treatment, could not be evaluated at the time of study 9,10.

There was only one defaulter who defaulted after four days of treatment. He was later traced to have completed treatment from Private Hospital. Thus the default rate was only 3% which is negligible when compared to that in unsupervised regime which goes up to 50% 8. In the present study the survival with sequele is only 9% compared to up to 57% in previous studies11.

With the intermittent short course regime, the total drug consumed by the patient is almost half that with the conventional daily regime. So the toxicity is less and cost of therapy is considerably low. So this regime can be universally recommended for all cases of tuberculosis, including Neuro tuberculosis.

CONCLUSIONS

1. DOTS regime is effective for Neuro tuberculosis.

2. Default rate is negligible with the above regime.

3. Prospective studies on effectiveness of DOTS in Neuro TB should be undertaken.

4. A diagnostic algorithm for the diagnosis of extra pulmonary tuberculosis should be included in the RNTCP guidelines.

References:

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2. Prabhakar S, Thussu A CNS Tuberculosis Neurology India 1997 Volume 45 : 132 to 140.

3. S. Sathya Sri, Text book of pulmonary and extra pulmonary tuberculosis (ISBN81-85017-70-0) 1993 : 190-192 Interprint, New Delhi.

4. G. K. Ahuja , K. K. Mohan , K. Prasad and M. Behari. Diagnostic criteria for tuberculous meningitis and their validation . Tubercle and lung disease,  1994, 75, 149-152.

5. Balasubramanian R; Ramachandran R. Management of non-pulmonary forms of tuberculosis: review of TRC studies over two decades. Indian J Pediatr. 2000; 67 (2 Suppl) : S34- 40 (ISSN: 0019-5456)

6. Central TB Division, DGHS, Ministry of Health & Family Welfare, Govt. of India. Managing Revised National Tuberculosis Control Programme in Your Area Module 1- 4., January 1998.

7. Central TB Division, DGHS, Ministry of Health & Family Welfare, Govt. of India. RNTCP Technical Guidelines for Tuberculosis Control, May 1997.

8. Renga Rao, Tuberculosis Control Services In India -Genesis, Progress And Future Ind J Tub, 2003,50,65.

9. Fallon RJ ,et al Treatment and prognosis in tuberculous meningitis. J Infect 1981 : 3: 39-44

10. Wang JT, Hung CC, Sheng WH, Wang JY, Chang SC, Luh KT., Prognosis of tuberculous meningitis in adults in the era of modern antituberculous chemotherapy, J Microbiol Immunol Infect. 2002 Dec;35(4):215-22.

11. Karande S, Gupta V, Kulkarni M, Joshi A., Prognostic clinical variables in childhood tuberculous meningitis: An experience from Mumbai, India. Neurol India. 2005 Apr-Jun;53(2): 191-6.
 

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