[Show abstract][Hide abstract] ABSTRACT: The currently recommended treatment for lymph node tuberculosis is 6 months of rifampicin and isoniazid plus pyrazinamide for the first 2 months, given either daily or thrice weekly. The objective of this study was to assess the efficacy of a 6-month twice-weekly regimen and a daily two-drug regimen.
Patients with biopsy confirmed superficial lymph node tuberculosis were randomly allocated to receive either a daily self-administered 6-month regimen of rifampicin and isoniazid, or a twice-weekly, directly observed, 6-month regimen of rifampicin and isoniazid plus pyrazinamide for the first 2 months, in Madurai, South India, Patients were followed up for 36 months after completing treatment.
Of 277 enrolled patients, data was available for analysis in 268. At the end of treatment, 116 of 134 [87%; 95% confidence interval (CI) 81-93%] patients in each treatment group had a favourable clinical response; 14 (11%; 95% CI 6-16%) and 17 (13%; 95% CI 7-19%) patients had a doubtful response, and 4 (3%; 95% CI 0-6%) and 1 (1%; 95% CI 0-2%) patients had an unfavourable response among those treated with the daily and twice-weekly regimen, respectively. During 36 months after completion of treatment, five patients [2 (2%; 95% CI 1-3%) and 3 (2%; 95% CI 1-3%) patients treated with the daily and twice-weekly regimen, respectively] had relapse of lymph node tuberculosis, of 260 assessed. Adverse reactions probably attributable to the treatment regimens occurred in 1% of the patients treated daily and in 11% of those treated twice-weekly (P < 0.001). At the end of 36 months after treatment, 126 of 134 (94%; 95% CI 90-98%) and 129 of 134 (96%; 95% CI 94-98%) of the patients treated with the daily and twice-weekly regimen, respectively, had a successful outcome.
Both the self-administered daily regimen and the fully observed twice-weekly regimen were highly efficacious for treating patients with lymph node tuberculosis and may be considered as alternative options to the recommended regimens.
Tropical Medicine & International Health 12/2005; 10(11):1090-8. · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Poor bioavailability of rifampicin (R) in combination with other anti-tuberculosis drugs such as isoniazid (H), pyrazinamide (Z), and ethambutol (E) is a subject of much concern for the last few decades. This could be due to an interaction between R and other drugs. An investigation was therefore undertaken to examine the bioavailability of R in the presence of H, Z and E or a combination of the three drugs.
The study included eight healthy volunteers, each being investigated on four occasions at weekly intervals once with R alone and with three of the four combinations on the three remaining occasions. A partially balanced incomplete block design was employed and the allocation of R or the drug combinations was random. Plasma concentrations of R at intervals up to 12 h were determined by microbiological assay using Staphylococcus aureus as the test organism. The proportion (%) dose of R as R plus desacetyl R (DR) in urine excreted over the periods 0-8 and 8-12 h was also determined. Bioavailability was expressed as an index (BI) of area under time concentration curve (AUC) calculated from the plasma concentrations or proportion of dose of R excreted as R plus DR in urine with the combinations to that with R alone.
The bioavailability indices based on AUC were 0.96 with RE, 0.76 with RH, 1.08 with RZ and 0.65 with REHZ. The indices based on urine estimations (0-8 h) were similar, the values being 0.94, 0.84, 0.94 and 0.75, respectively. A second investigation revealed that the decrease of bioavailability of R with H was not due to the excipients present in H tablets.
Isoniazid alone or in combination with E and Z reduces the bioavailability of R. Urinary excretion data offer a simple and non invasive method for the assessment of bioavailability of R.
The Indian Journal of Medical Research 09/2003; 118:109-14. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tribal villages in the jungles of the Jawadhu hills, South India.
To estimate the prevalence of tuberculosis (TB) infection and disease in a remote tribal population.
A cross-sectional survey with two-stage screening for identification of cases. A stratified probability proportional sample with the hamlet as the unit.
Among 56 revenue divisions with a population of about 66,000, 24 revenue divisions were selected. Among 26,320 persons registered, children < 10 years were tuberculin tested and reactions were read after 72 hours. Those over 15 were X-rayed, and tuberculosis symptoms were investigated. Sputum was collected from those with abnormal X-ray or symptoms and examined for smear and culture positivity and sensitivity.
Of the 6952 children tested and read, 5% had BCG scars and the prevalence of infection was 5%. The annual risk of infection was 1.1. Among adults, the prevalence of bacillary cases was 8/1000 and X-ray cases 29/1000. The prevalence of bacillary disease was higher among males, particularly with increasing age. Thirty symptomatic cases had normal X-rays and 63 X-ray cases had no symptoms. Thus prevalence would have been underestimated if either method had been used alone for screening. Isoniazid resistance was seen in 12% of patients, two of whom also had rifampicin resistance (2.6%).
The prevalence and pattern of tuberculosis in this tribal group is similar to that observed in non-tribal areas.
The International Journal of Tuberculosis and Lung Disease 03/2001; 5(3):240-9. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To estimate the rate of development of active tuberculosis (TB) in a cohort of human immunodeficiency virus (HIV) positive patients, and to identify the characteristics of these patients.
A total of 175 HIV-positive individuals were recruited from clinics for sexually transmitted diseases and followed up for 31 +/- 6.8 months. Clinical examination, chest X-ray, sputum smear for acid-fast bacilli and culture for mycobacteria and HIV serology were performed at the time of registration and repeated periodically.
Seventeen patients had TB at intake and another 24 developed TB during follow-up, giving a breakdown rate of 6.9/100 person-years (p-y) (95% confidence interval [CI] 4.1-9.6). The attack rates were similar in tuberculin positive (7.1/100 p-y, 95%CI 3.4-10.8) and negative (6.7/100 p-y, 95%CI 2.6-10.8) patients. There was a trend towards higher mortality in patients who developed TB (10.5/100 p-y, 95%CI 4.8-15.2) compared to those who did not (6.1/100 p-y, 95%CI 3.2-8.8).
The results of this study provide information regarding the high risk of development of active tuberculosis and its associated mortality in HIV-infected persons. The risk of developing TB appears to be equally high in tuberculin positive and negative individuals, suggesting that new infections could play a major role in this susceptible population.
The International Journal of Tuberculosis and Lung Disease 10/2000; 4(9):839-44. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) continues to be a major health problem in India. There has been no perceptible change in the epidemiology of TB since the National Sample Survey 1956-57. Detection of cases has been low over the years since the inception of National TB control programme in 1962 due to passive case finding and high drop out rates among sputum positive patients. Shortening the course of chemotherapy with regimens containing bactericidal and sterilising drugs helped in improving the treatment adherence of patients and cutting down the chain of transmission substantially. Further it is advisable to implement properly the directly observed short course treatment (DOTS) as per WHO guidelines to prevent the development of multidrug resistant TB (MDRTB). Proper management of RNTCP and prevention of MDRTB are all the more important in areas where there is high prevalence of HIV/AIDS co-infected with TB. New vaccine development is also a priority area for research. There is an urgent need for health systems research built into the ongoing programme with proper managerial inputs.
Journal of the Indian Medical Association 04/2000; 98(3):123-5.
[Show abstract][Hide abstract] ABSTRACT: A total of 446 lymph node biopsy specimens showing histological evidence of tuberculosis were classified into four groups based on the organization of the granuloma, the type and numbers of participating cells and the nature of necrosis. These were, hyperplastic (22.4%)--a well-formed epithelioid cell granuloma with very little necrosis, reactive (54.3%)--a well-formed granuloma consisting of epithelioid cells, macrophages, lymphocytes and plasma cells with fine, eosinophilic caseation necrosis, hyporeactive (17.7%)--a poorly organized granuloma with macrophages, immature epithelioid cells, lymphocytes and plasma cells and coarse, predominantly basophilic caseation necrosis and nonreactive (3.6%)--unorganized granuloma with macrophages, lymphocytes, plasma cells and polymorphs with non caseating necrosis. Though the number of bacilli in the sections differed in each group, there were no differences in culture positivity, Mantoux reaction or the clinical features. It is likely that the spectrum of histological responses seen in tuberculous lymphadenitis is the end result of different pathogenic mechanisms underlying the disease.
The Indian Journal of Medical Research 07/1999; 109:212-20. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We performed a randomised, controlled clinical trial to compare ambulant short-course chemotherapy with anterior spinal fusion plus short-course chemotherapy for spinal tuberculosis without paraplegia. Patients with active disease of vertebral bodies were randomly allocated to one of three regimens: a) radical anterior resection with bone grafting plus six months of daily isoniazid plus rifampicin (Rad6); b) ambulant chemotherapy for six months with daily isoniazid plus rifampicin (Amb6); or c) similar to b) but with chemotherapy for nine months (Amb9). Ten years from the onset of treatment, 90% of 78 Rad6, 94% of 78 Amb6 and 99% of 79 Amb9 patients had a favourable status. Ambulant chemotherapy for a period of six months with daily isoniazid plus rifampicin (Amb6) was an effective treatment for spinal tuberculosis except in patients aged less than 15 years with an initial angle of kyphosis of more than 30 degrees whose kyphosis increased substantially.
Journal of Bone and Joint Surgery - British Volume 06/1999; 81(3):464-71. · 2.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study assesses bioavailability indices for rifampicin, isoniazid and pyrazinamide when administered to healthy volunteers separately or in a fixed triple-drug formulation, Rifater 125 SCT.
To compare the pharmacokinetics of rifampicin, isoniazid and pyrazinamide based on their blood concentrations up to 12 hours with the proportions of the doses of the drugs and their metabolites excreted in urine up to 12 hours, and to assess the bioavailability indices for the free and fixed triple drug formulations.
An open cross-over study was conducted in 18 healthy volunteers with normal hepatic and renal functions to whom the drug combinations were administered in free and fixed dose formulations a week apart, to the same subject.
Concentrations of the three drugs/metabolites were assessed in blood and urine. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both the free and the new fixed triple drug formulation.
Human bioavailability studies provide direct straightforward information, particularly when studying compounds such as rifampicin and other major anti-tuberculosis drugs. The results of the present study indicate that the pharmacokinetic properties of rifampicin, isoniazid and pyrazinamide as assessed after individual and combined administration do not change when combined in a single pharmaceutical preparation. The bioavailability indices calculated based on plasma concentrations and urinary levels for all three drugs compared well.
The International Journal of Tuberculosis and Lung Disease 03/1999; 3(2):119-25. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Influence of HLA-DR antigens and lymphocyte responses in pulmonary TB patients.
To elucidate the role of HLA-DR genes/gene products on lymphocyte responses to Mycobacterium tuberculosis antigens and mitogens, the present study was carried out in pulmonary tuberculosis during active and cured stage of the disease.
Serological determination of HLA-DR antigens was carried out in 50 active TB patients, 44 cured TB patients and 58 normal healthy control subjects. The influence of HLA-DR antigens on peripheral blood lymphocyte responses to M. tuberculosis culture filtrate antigens and mitogens such as phytohaemagglutinin (PHA) and concanavalin-A (Con-A) was studied in the patients as well as normal healthy control subjects.
Of all the DR antigens studied, patients (active TB and cured TB) with DR2 antigen showed an increased lymphocyte response (stimulation index) to a higher dose of antigenic (10 micrograms/ml) stimulation. A significantly lower lymphocyte response to antigen and mitogens was seen in HLA-DR3 positive normal healthy subjects than non-DR3 (DR3 negative) subjects.
The present study suggests that HLA-DR genes/gene products may be playing an immunoregulatory role in eliciting an immune response against M. tuberculosis antigens and mitogens induced lymphocyte response in pulmonary TB patients and normal healthy subjects.
[Show abstract][Hide abstract] ABSTRACT: To understand whether the presence of cold reactive lymphocytotoxic antibodies (LCA) (reactive at 15 degrees C) in the system has any effect on immunity to tuberculosis lymphocytotoxic antibodies to adherent cells (enriched-B cells) and non-adherent cells were studied in active-TB (n = 42) and inactive-TB (cured) patients (n = 49) and healthy controls (n = 32). The plasma samples of inactive-TB patients showed higher percentage of positivity for lymphocytotoxic antibodies (36.7%) than the active-TB patients (21.4%) and control subjects (18.8%). No significant difference on antibody and lymphocyte response against Mycobacterium tuberculosis culture filtrate antigens was observed between LCA positive and LCA negative active-TB patients and normal healthy controls. Further, determination of HLA-DR phenotype of the patients and control subjects showed that individuals positive for lymphocytotoxic antibodies were more among HLA-DR2 positive and DR7 positive active-TB patients and control subjects than non-DR2 and non-DR7 subjects. The present study suggests that the cold reactive lymphocytotoxic antibodies may be against B-lymphocytes and persistent for a longer time. HLA-DR2 and -DR7 may be associated with the occurrence of LCA activity. Further, the presence of LCA has no immunoregulatory role on immunity to tuberculosis.
The Indian Journal of Medical Research 02/1999; 109:5-10. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 15-year clinical follow-up of tuberculous lesions of the lumbosacral region.
To verify the hypothesis that the lumbar lordosis and the specific biomechanics of the lumbosacral region influence and alter the healing pattern and progress of the disease when compared with their effects in other regions of the spine.
An estimated 2 million or more patients have active spinal tuberculosis, and the global incidence of the disease is increasing. The involvement of the lower lumbar region and the lumbosacral junction is relatively rare, with few reports in English literature.
Of a total of 304 patients forming a part of a controlled clinical trial comparing two forms of therapy in spinal tuberculosis, 53 patients had involvement of L3 and below. The following data were studied in these patients: age at start of treatment, number of vertebra involved, vertebral body loss, progress of the angle of kyphosis, and anterior and posterior growth of the involved segment during a period of 15 years. Student's t test for independent samples was used for statistical analysis.
The fourth lumbar vertebra was the most common vertebral segment involved, and the lumbosacral junction was affected in 12 patients. The average pretreatment kyphosis was 6.4 degrees and increased to 10.2 degrees at the end of 15 years. The average kyphotio angle per vertebral body loss was 4.9 degrees, far less than in the dorsolumbar region in which kyphotic angles of 27-30 degrees have been reported. Children younger than 10 years old differed in clinical appearance and progress compared with those older than 17 years. They not only showed more extensive involvement but also had more deformity with the same vertebral loss. Twelve patients less than 10 years old had an average involvement of 3.1 vertebral bodies and an average vertebral loss of 2.2 bodies. In comparison, the average number of vertebrae involved was 1.9 (P < 0.01) and the vertebral body loss was only 0.87 (P < 0.01) in patients older than 17 years. Also, the average kyphosis was 6.4 degrees compared with only 4.2 degrees (P < 0.01) in adults. In patients older than 17 years, there was no change after 2 years, by which time the collapse was complete. Four of 12 patients less than 10 years old, showed progressive kyphosis caused by continued growth of posterior parts of the body (i.e., sequestrated hemivertebrae).
In tuberculosis of the lumbosacral region, the development of kyphosis is minimal in patients older than 17 years, when growth has already stopped, and deformity is expressed more as foreshortening of the trunk. Children younger than 10 years old have more severe involvement with increased tendency toward greater kyphosis. They are also prone to progressive deformity through the years when the anterior growth plates are destroyed. Surgery is indicated in this group to prevent greater deformity.
[Show abstract][Hide abstract] ABSTRACT: Association of HLA-DR2 genes/gene products has been shown with pulmonary tuberculosis (PTB) patients in India. In the present study, the influence of HLA-DR2 and non-DR2 genes/gene products on immunity to tuberculosis has been studied. Plasma samples of -DR2 positive patients (active and inactive TB) showed a higher antibody titre to Mycobacterium tuberculosis culture filtrate antigens than non-DR2 (-DR2 negative) patients. Immunoblot analysis revealed a trend towards an increased percentage of DR2 positive patients recognizing 38, 32/34 and 30/31 kDa antigens of M. tuberculosis than DR2 negative patients. A low spontaneous lymphoproliferative response (without antigen stimulation) was seen in HLA-DR2 positive active TB patients than HLA-DR2 negative patients. However, the antigen stimulated lymphocyte response was higher in the -DR2 positive patients (active and inactive TB) when compared to non-DR2 patients. Further, an inversional correlation between antibody titre and spontaneous as well as antigen induced lymphocyte response (measured by 3H thymidine uptake and expressed as counts per minute) was seen in HLA-DR2 positive active PTB patients than non-DR2 patients. The present study suggests that HLA-DR2 genes/gene products may be associated with a regulatory role in the mechanism of disease susceptibility to tuberculosis. The genes while augmenting the humoral immune response, they suppress the spontaneous and antigen induced lymphocyte response in -DR2 positive patients with active disease.
The Indian Journal of Medical Research 06/1998; 107:208-17. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HLA-A, -B, -DR and -DQ antigen profile was studied in pulmonary tuberculosis patients (n = 209) and their spouses (family contacts; n = 50) and healthy volunteers (n = 72). An increased frequency of HLA-A-10, B7, B15, DR2 and DQ1 was seen in the pulmonary-TB (PTB) patients when compared to the total control subjects (n = 122). However, a significant increase was seen only with HLA-DR2 (P < 0.001; Pc < 0.01; Relative Risk 2.3) and -DQ1 (P < 0.005; Pc < 0.015; Relative Risk 2.8). Among the spouses and the corresponding patients, a similar increase of HLA-DR2 was seen. A decreased frequency of HLA-A19, B8, B17, B35, DR5 and DR6 were seen in PTB as compared to control groups. The present study suggested that HLA-DR2 and DQ1 genes/gene products may be associated with the susceptibility to tuberculosis either alone or in combination with other HLA or non-HLA genes.
The Indian Journal of Medical Research 05/1998; 107:155-8. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Twenty three clinical isolates M. tuberculosis and the reference strain, M. tuberculosis H37Rv were tested for their susceptibility to trifluoperazine (TFP) by the standard broth dilution method and the bioluminescence assay. The results showed that in 15 of the 23 isolates, the minimal inhibitory concentration (MIC) was identical in both the methods and in the remaining 8 isolates the difference in the MIC values between the methods, was less than two fold and was not significant. The findings suggest that the measurement of adenosine triphosphate (ATP) by bioluminescence assay can be employed as an alternative method for the rapid screening of clinical isolates for their susceptibility to anti-mycobacterial agents.
The Indian Journal of Medical Research 02/1998; 107:75-7. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper reports the feasibility of involving unpaid National Service Scheme (NSS) male student volunteers in a city-based tuberculosis (TB) programme in supplying drugs and retrieving non-complaint TB patients. Twenty-five students were selected after assessing their attitude and were trained on TB drug delivery, home visits and motivation of non-compliant patients. Twenty-three sputum positive patients identified in a medical camp were started on an 8-month short-course chemotherapy regimen. Students supplied the drugs on a weekly basis and defaulters were visited. The treatment completion rate was 83% and defaulter retrieval was 57%. All patients had sputum smear conversion by 2 months and one relapsed during the 24-month follow-up.
The International Journal of Tuberculosis and Lung Disease 01/1998; 1(6):573-5. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intraspecies differentiation was studied on 68 M. tuberculosis strains obtained from 6 states of India by restriction fragment length polymorphism (RFLP) using a direct repeat probe (DR probe) hybridised with Alu I digest of DNA. Most strains showed polymorphism based patterns that comprised between 2 to 7 bands and were grouped into 26 RFLP types. Of the 11 strains tested from Amritsar, 8 were RFLP type 5; the remaining 3 were of type 11 and were exclusively confined to this region. The strains from other regions were more heterogeneous. We confirm that DR-associated RFLP can be an excellent tool for the differentiation of M. tuberculosis strains. Depending on their geographical origin, these strains can be differentiated to a large extent by DR fingerprinting.
The Indian Journal of Medical Research 12/1997; 106:447-54. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Late onset paraplegia is a neurological complication that develops after a variable period in a patient with healed tuberculous disease of the vertebrae. In this retrospective analysis clinical features, imaging in diagnosis and treatment of this condition are described among 5 cases seen over a period of 5 years. This complication occurred even after successful treatment of initial spinal lesions with rifampicin-containing regimens. Magnetic resonance imaging was useful in pinpointing the exact pathology; one case had syrinx and two cases had marked internal gibbus with cord atrophy. Of the two cases who accepted surgical treatment, one improved.
The International Journal of Tuberculosis and Lung Disease 11/1997; 1(5):468-73. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy of 9-month short-course chemotherapy (SCC) and to study the pattern of neurological recovery in patients with Pott's paraplegia.
Patients with recent onset of spastic paraplegia due to clinically and radiologically active spinal tuberculosis involving vertebral bodies of level D4-L1 were treated with streptomycin, rifampicin, isoniazid and ethambutol daily for the first 2 months, followed by rifampicin plus isoniazid twice weekly for the next 7 months. The study was conducted in 2 phases. In the first phase 10 patients were admitted to the open trial where all patients had undergone modified Hong Kong surgery in addition to chemotherapy. In the next phase 23 patients enrolled in the study were randomly allocated to receive either chemotherapy alone or surgery plus chemotherapy. All the patients were followed for 5 years from the start of treatment. A scoring system was devised to predict neurological recovery.
In all, 33 patients were admitted and treated with SCC. Thirteen patients were allocated to the chemotherapy (CHEM) regimen; of these 3 patients had to be operated upon for clinical deterioration; the remaining 20 had surgery plus chemotherapy; 4 were excluded for various reasons, leaving 29 patients in the analysis. None relapsed requiring treatment.
A combination of surgery (when indicated) and SCC of 9 months' duration is effective in the treatment of Pott's paraplegia. All patients had neurological recovery by the end of 9 months; 8 recovered with chemotherapy alone. Complete motor recovery was seen in 62% by the 3rd month and 90% by the 6th month.
The International Journal of Tuberculosis and Lung Disease 05/1997; 1(2):152-8. · 2.76 Impact Factor