Short-course Chemotherapy For Pulmonary Tuberculosis Research Articles

Two-year follow-up of persons with HIV-1− and HIV-2-associated pulmonary tuberculosis treated with short-course chemotherapy in West Africa

To assess the response to therapy for tuberculosis using rifampicin-containing short-course chemotherapy, and to compare recurrence and mortality rates in seronegative persons and those with HIV-1, HIV-2, and dual serologic reactivity in West Africa. A cohort of 835 adult patients (167 HIV-1-positive, 143 HIV-2-positive, 243 dual-reactive, 282 HIV-negative) with smear-positive pulmonary tuberculosis was followed for 2 years under programme conditions. Standard self-administered treatment was daily rifampicin and isoniazid for 6 months, and in addition pyrazinamide during the first 2 months. Outcomes evaluated were rates of completion of therapy, cure, failure of treatment, recurrence after cure, and mortality. HIV-positive patients had lower rates of completion of therapy (65-73%) than seronegative patients (79%), mainly because of increased mortality. Among patients completing therapy, failure of treatment was similarly low in HIV-positive (2%) and seronegative patients (1%). Recurrence rates after cure did not differ significantly in the 18 months of follow-up in the four serologic groups (3-7%). The respective mortality rates for HIV-1-positive, HIV-2-positive, and dually reactive patients were 20.3, 8.3, and 25.5 per 100 person-years (PY), compared with 2.2 per 100 PY among seronegatives. Rifampicin-containing short-course chemotherapy for pulmonary tuberculosis is associated with similar cure and recurrence rates in HIV-positive and HIV-negative persons completing 6 months of therapy. HIV-2 infection is associated with more favourable survival than HIV-1 infection or dual reactivity, even when AIDS-defining illness is already present. However, mortality is significantly increased in all seropositive groups compared with HIV-negative tuberculosis patients; thus, establishing the causes of this increased mortality is a priority.

Chemotherapy for Tuberculosis in Infants and Children

Active tuberculosis is diagnosed in more than 1100 children annually in the United States. The therapy for patients with tuberculosis has undergone major changes during the past decade, including demonstration of the efficacy of multidrug, short-course chemotherapy for pulmonary tuberculosis in adults.1 At least nine studies of 6-month antituberculosis chemotherapy have demonstrated comparable results in children.2-10 The purpose of this statement is to give revised recommendations for treatment of tuberculosis in infants and children. These recommendations have been formulated in collaboration with the Division of Tuberculosis Elimination of the Centers for Disease Control and the American Thoracic Society. MICROBIOLOGIC RATIONALE FOR TREATMENT Laboratory observations of Mycobacterium tuberculosis and clinical therapy trials have led to a hypothesis concerning the populations of tubercle bacilli and the actions of various antimycobacterial drugs and drug combinations.11,12 Mycobacteria replicate slowly, can remain dormant for prolonged periods, and can be killed by drugs only during replication. In the host, bacilli live in several sites: open cavities, closed caseous lesions, and within macrophages. Each site contains bacilli with a different population size, metabolic activity, and rate of replication. Open cavities, which are rare in infants and children, have the largest number of mycobacteria. Naturally occurring drug-resistant mutants of M tuberculosis occur within large bacterial populations even before chemotherapy is started. The number of drug-resistant mutants is proportional to the size of the mycobacterial population; thus, they are common in open cavities, but less common in caseous lesions and within macrophages. Mutants naturally resistant to two drugs are virtually nonexistent.

Short-course chemotherapy for pulmonary tuberculosis under routine programme conditions: a comparison of regimens of 28 and 36 weeks duration in Algeria

Two chemotherapy regimens of 28 weeks (6M) and 36 weeks (8M) duration were compared in patients with previously untreated pulmonary tuberculosis in 30 health districts of Algeria. In the 6M regimen, patients received isoniazid plus rifampicin daily throughout with streptomycin and pyrazinamide in addition for the first 8 weeks. In the 8M regimen patients received isoniazid daily throughout plus rifampicin for the first 16 weeks and streptomycin and pyrazinamide as well for the first 8 weeks. The districts were allocated to apply either the 6M or the 8M regimen to all eligible patients. However, 22% of eligible patients were not admitted, the most common reason being oversight on the part of the personnel in the local health centres.A total of 2218 (977 6M,1241 8M) patients was admitted and the results were assessed 2 years after the due date of completion of chemotherapy, irrespective of whether or not management had deviated from the study protocol. An appreciable proportion of patients (25% of 6M, 29% of 8M) could not be assessed because they failed to attend for follow-up or the collection of specimens was overlooked or because of difficulties in the transport of specimens to the reference laboratory in Algiers, and a further 5% and 4% of patients died. Of those who were assessable 7 (1 %) of 731 6M and 15 (2%) of 875 8M were classified as having an unfavourable response during or after chemotherapy because they had one or more positive cultures. In addition 16 (2%) 6M and 18 (2%) 8M patients had received additional chemotherapy for failure, relapse or the development of non-pulmonary lesions but had achieved a favourable status.Of 1018 (488 6M, 530 8M) patients assessed who had fully sensitive strains pretreatment and completed treatment as planned, 97% in both series had a favourable status 2 years after their chemotherapy was due to be completed. In patients with initial strains resistant to isoniazid the results were less good in the 8M than the 6M series: none of the 19 6M compared with 5 of 26 in the 8M series having an unfavourable outcome suggesting that the duration of rifampicin may have been important in patients with initial isoniazid resistance.A slightly higher proportion of patients on the 8M regimen defaulted during chemotherapy (9.3% compared with 6.7% in the 6M regimen) but there was no difference between the regimens in other measures of compliance.

Controlled Clinical Trial of Levamisole in Short-course Chemotherapy for Pulmonary Tuberculosis: A Kenyan/Zambian/British Medical Research Council Collaborative Study

The effect of adding a once-weekly dose of levamisole for 4 or 8 wk to a 6-month antituberculosis chemotherapy regimen has been studied in a double-blind, placebo-controlled clinical trial. All patients received the same daily chemotherapy regimen of streptomycin, isoniazid, rifampin, and pyrazinamide for 8 wk followed by thiacetazone and isoniazid for 18 wk, the first 10 wk being given fully supervised on an inpatient basis in hospital and the remainder to be self-administered at home. In 504 patients with fully susceptible strains pretreatment assessed at the end of chemotherapy, there was no evidence of an advantage to the patients receiving levamisole for 8 wk (L8 series) or 4 wk (L4 series) when compared with those receiving placebo only (L0 series) in terms of the rate of achievement of sputum culture negativity or of radiographic improvement at independent assessment. The bacteriologic relapse rates in 2 yr of follow-up were also similar in the three series, namely, 8% for the 144 patients in the L8, 5% for the 152 in the L4, and 8% for the 160 in the L0 series. There was thus no evidence of benefit from levamisole in the dosage schedule studied. The frequency of adverse reactions to the antituberculosis drugs was unaffected by levamisole. None of 424 patients receiving levamisole had adverse reactions attributable to the drug.

LONG TERM RESULTS OF SHORT-COURSE CHEMOTHERAPY FOR PULMONARY TUBERCULOSIS (Second study-A) Results up to 6 Years after the End of Treatment with 4-6 Month Chemotherapy for Pulmonary Tuberculosis

LONG TERM RESULTS OF SHORT-COURSE CHEMOTHERAPY FOR PULMONARY TUBERCULOSIS (Second study-A) Results up to 6 Years after the End of Treatment with 4-6 Month Chemotherapy for Pulmonary Tuberculosis

The case for short-course chemotherapy of pulmonary tuberculosis.

The treatment of tuberculosis was revolutionised in the late 1940s and early 1950s by the introduction of potent chemotherapeutic agents. These transformed the near-fatal prognosis of the disease to one in which a virtually 100% cure is attainable. Recent developments have made the attainment of this aim more likely. By means of wellplanned, systematic controlled clinical trials, much light has been shed not only on the efficacy, but also on the basic mechanisms of different chemotherapeutic regimens. These trials have also led to fruitful collaboration between research workers in Western and in developing countries. Regimens elaborated for prosperous nations have been modified for use in developing countries; in turn, studies carried out in developing countries have influenced the conduct of chemotherapy in the West. As a result of well-applied chemotherapy, the prevalence of tuberculosis has fallen dramatically in Western countries. In the developing world, however, the disease remains a major cause of illhealth and death. Much of this persistent morbidity and mortality is due to inadequate resources, inappropriately deployed.

Follow-up Study of Short-Course Chemotherapy for Pulmonary Tuberculosis

Follow-up Study of Short-Course Chemotherapy for Pulmonary Tuberculosis

Clinical Experience of Short-Course Chemotherapy for Pulmonary Tuberculosis

Clinical Experience of Short-Course Chemotherapy for Pulmonary Tuberculosis

Preliminary Results of Six-month Regimens Studied in the United States and in Poland

The Tuberculosis Control Division of the Centers for Disease Control is involved with two studies of short-course chemotherapy for pulmonary tuberculosis. One is being carried out in the United States and the other in Poland. All short-course regimens being studied are of six months’ duration, and all include rifampin (R) and isoniazid (I) administered daily or intermittently for the entire duration of treatment. Some regimens also included supplemental drugs. This report presents the results of these short-course regimens 18 months after completion of therapy.

Short-course chemotherapy in pulmonary tuberculosis

The research Committee of the B.T.A. aun cree que las recomendaciones de 1976 de 9 meses de quimioterapia con rifampicina e isoniazida más etambutol en los dos primeros meses es el método preferible para el tratamiento de la tuberculosis pulmonar en el Reino Unido.

SHORT-COURSE CHEMOTHERAPY IN PULMONARY TUBERCULOSIS: A controlled trial by the British Thoracic Association (third report)

SHORT-COURSE CHEMOTHERAPY IN PULMONARY TUBERCULOSIS: A controlled trial by the British Thoracic Association (third report)

Side-effects of drug regimens used in short-course chemotherapy for pulmonary tuberculosis. A controlled clinical study

An analysis is presented of the side effects which occurred in 530 patients treated with 6 months chemotherapy for newly detected pulmonary tuberculosis. Five treatment regimens were used. The initial phase of treatment consisted of daily isoniazid, rifampicin and ethambutol (HRE) or isoniazid, rifampicin, streptomycin and pyrazinamide (HRRSZ) given for 2 months. The second phase of treatment consisted of isoniazid and rifampicin given twice weekly (H 2R 2) or isoniazid, rifampicin and ethambutol given daily (4HRE) or intermittently (H 1,R 1E 1 or H 2R 2E 2) for 4 months. Side effects were detected in 66 (12.4%) patients. Hepatotoxic reactions occurred in 48 (9 %) patients, mainly of a mild and transient nature and the majority were attributable to isoniazid. The ‘flu like’ syndrome occurred in only 2 patients both during the daily phase of treatment, and it was not encountered in patients taking rifampicin intermittently (dose 600 mg). Inclusion of pyrazinamide in the initial phase of 1 regimen did not result in an increase of frequency of side effects. In 56 % of patients on pyrazinamide the serum uric acid concentration was elevated but there was no arthralgia. Drug toxicity leading to alteration or withdrawal of treatment occurred in only 10 (1.8 %) patients. This study shows that with these 6 month regimens the overall risk of drug toxicity was low, and less than that associated with more conventional treatment regimens.

SHORT-COURSE CHEMOTHERAPY IN PULMONARY TUBERCULOSIS: A Controlled Trial by the British Thoracic and Tuberculosis Association

A regimen of rifampicin plus isoniazid, supplemented in the first two months by ethambutol or streptomycin, was given for six, nine, twelve, or eighteen months in a controlled study of 696 patients with culture-positive pulmonary tuberculosis. The results obtained in the thirty-three months since the start of treatment when all the patients in the six-month and nine-month groups had completed at least two years and those in the twelve-month group had completed twenty-one months of post-chemotherapy follow-up revealed no relapses among patients receiving nine months 1 chemotherapy and a 1% relapse-rate in the twelve-month group. The same regimen given for only six months resulted in a relapse-rate of 5% during the subsequent twenty-seven months. There were adverse effects with streptomycin but not with ethambutol. It is concluded that treatment with rifampicin plus isoniazid for nine months, supplemented by ethambutol in a dose of 25 mg/kg for the first two months, is now acceptable as standard chemotherapy for pulmonary tuberculosis in Britain.

Short-course chemotherapy for pulmonary tuberculosis.

Short-course chemotherapy for pulmonary tuberculosis.

SHORT-COURSE CHEMOTHERAPY IN PULMONARY TUBERCULOSIS: A Controlled Trial by the British Thoracic and Tuberculosis Association

The results of short courses of chemo-therapy using rifampicin plus isoniazid, supplemented for the first two months by streptomycin or ethambutol, in patients with newly diagnosed pulmonary tuberculosis, have been studied. 174 patients with little or no cavitation received six months chemotherapy. 1 (0·6%) failed to convert to culture negative during treatment and 5 (3%) relapsed in the twelve months after the end of treatment. In 177 patients with similar disease, twelve months chemotherapy was 100% effective in rendering the sputum culture negative and in preventing relapse in the six months after the end of treatment. 151 patients with more extensive cavitation received chemotherapy for nine months: this was 100% effective in sputum conversion and in preventing relapse in the nine months after the end of treatment. In 155 patients with similar disease, the eighteen-month regimen was uniformly successful in sputum conversion. The rifampicin plus isoniazid regimen was well tolerated, producing adverse effects which warranted withdrawal from the study in only 3·6% of patients. Comparison of ethambutol with streptomycin as a third drug given for the first eight weeks showed no significant difference in the rate of sputum conversion nor in the incidence of relapse. Streptomycin produced significant adverse effects in 8% of patients whilst ethambutol caused none. Chemotherapy with rifampicin plus isoniazid for nine months, supplemented initially by ethambutol, is more acceptable than standard chemotherapy for eighteen months, is highly effective in sputum conversion, and has resulted in no relapses over a nine-month follow-up period. Further follow-up is being continued to confirm that relapse does not occur.