Intervention Review

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Regimens of less than six months for treating tuberculosis

  1. Hellen Gelband*

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 21 JAN 2009

Assessed as up-to-date: 15 JUN 1999

DOI: 10.1002/14651858.CD001362

Database Title

Additional Information

How to Cite

Gelband H. Regimens of less than six months for treating tuberculosis. Cochrane Database of Systematic Reviews 1999, Issue 4. Art. No.: CD001362. DOI: 10.1002/14651858.CD001362.

Author Information

  1. Resources for the Future, Washington, DC, USA

*Hellen Gelband, Resources for the Future, 1616 P Street NW, Washington, DC, 20192, USA. Hgelband@aol.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 21 JAN 2009

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ARTICLE TOOLS

Summary (55K)Standard (173K)Full (211K)
 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Treatment for active pulmonary tuberculosis (TB) is a very long process compared with treatments for most other bacterial diseases, with "short-course" treatment recommended by WHO lasting 6 months. The success of short-course chemotherapy in randomized trials in the 1970s and 1980s led to randomized trials of even shorter regimens-from 3 to 5 months-which are the subject of this review. On completion of these trials in the late 1980s, the general consensus was of disappointment, because relapse rates were significantly higher than with 6 months of treatment. As a result, shorter courses were rejected and are not the norm anywhere today.

A key reason for the failure of 6-month regimens is that it is difficult for people to complete such a long course of treatment. In most cases, people feel quite well after the first month or two of treatment, when most of the tubercle bacilli have been killed, and there is a natural tendency for patients to stop taking drugs, and programs in many parts of the world are short of resources to provide them. A great deal of effort has been made worldwide to improve adherence to 6-month regimens (including the WHO-recommended approach of "directly-observed therapy"), but incomplete therapy is still an enormous problem, both in terms of leaving individuals still infected and in fostering the development of drug-resistant bacilli.

If shorter regimens can be used with better adherence than 6-month regimens, and if drug resistance is not enhanced, there may still be a practical reason to use regimens shorter than 6 months in some places.

The purpose of this review is to reexamine these trials with 2 main aims: first, to determine whether the consensus view is supported by the totality of the data; and second, to gain insight into whether further trials under program conditions might be useful to determine if adherence is enhanced with shorter regimens enough to offset the higher relapse rates. This is important because success rates in TB control programs fall far short of what can be achieved in trials under ideal conditions because it is so difficult to maintain adherence to 6-month (or longer) regimens.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms

To determine the effectiveness of any TB treatment regimen lasting <6 months.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomized trials comparing two or more TB regimens, in which at least one regimen was <6 months and it was compared with at least one regimen that lasted longer. The comparator did not have to be 6 months, as long as there was a longer vs. shorter comparison (i.e., a trial could compare a 3-month regimen with a 4-month regimen, or a 5-month vs. a 7-month regimen).

 

Types of participants

Any patients with active TB, including those with drug-resistant bacilli and any previous treatment. Active TB is defined as having at least one of the following positive: sputum smear; sputum culture; radiographic evidence of active disease.

 

Types of interventions

All regimens that would have been considered appropriate at the time the trial was carried out were acceptable. All the shorter regimens contain the following 4 drugs, with their accepted abbreviations:

S: Streptomycin
H: Isoniazid
R: Rifampicin
Z: Pyrazinamide

A form of standard notation for TB regimens is used in the table and figures. The initial number denotes the number of months for that regimen or phase. The letter "I" after the letters (which stand for each drug in the regimen) denotes intermittent treatment (which was twice or thrice weekly in the trials reviewed). If no "I" is present, the regimen or phase is daily. The number of days per week drugs are given also may be denoted by a subscript after the regimen

As an example, 2SHRZ/2HRI denotes a regimen of streptomycin, isoniazid, rifampicin, and pyrazinamide given daily in the 2-month initial phase, followed by isoniazid and rifampicin given intermittently in the 2-month continuation phase.

 

Types of outcome measures

 

Primary

1. Relapse: Single positive sputum culture, single positive sputum smear with symptoms, within 12 months of completion of successful treatment (i.e., cure), when reported. In some trials, results are given only for periods other than 1 year.

2. Toxicity: Adverse drug reactions that require interruption, alteration, or complete cessation of treatment.

 

Other

1. Sterilizing efficacy at end of treatment (defined as sputum culture negative immediately after completion of treatment).

2. Death: Deaths recorded during and up to 12 months following completion of treatment.

 

Search methods for identification of studies

Search strategy: MEDLINE 1955 to May 2004; Cochrane Central Register of Controlled Trials (CENTRAL); Cochrane Infectious Diseases Specialized Register; existing reviews, and researchers who had been involved in identified trials.

 

Data collection and analysis

The inclusion criteria were applied to all identified trials by the author. Each included trial was assessed in terms of adequacy of concealment of allocation, generation of allocation sequence and follow up of subjects, using the protocol of the Cochrane Infectious Diseases Group.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification.

Seven trials, published between 1979 and 1989, are included in the review. They were carried out in the following countries: 3 trials in India; 2 trials in Hong Kong; 1 trial in Singapore; and 1 trial in Germany.

In all trials, drug taking was fully supervised in outpatient departments or clinics. A few patients in some of the trials were hospitalized during all or part of the course of treatment, but the vast majority (more than 95% in all trials reporting this figure) were treated as outpatients.

Five of the trials had 3 or more treatment arms. In three of these (South India 1986, South India 1989, Singapore 1991), two or more arms were of the same duration, but differed either in the specific drugs used or in having daily vs. intermittent dosages. In these cases, the arms of identical length are combined into a single group for comparison. In the other two trials with multiple comparisons (Hong Kong 1979, Hong Kong 1989), the arms are of different lengths and are included as separate comparisons. The trials are all relatively small by today's standards, with between 50 and 250 individuals in most treatment arms. In all the trials, individuals who did not complete a large percentage of the treatment were excluded from the analysis, others were excluded for other reasons, and still others lost to follow-up (see "Methodological quality").

The patients in all except the two Hong Kong trials were sputum smear positive. In the Hong Kong trials, patients were sputum smear negative. Some were culture positive and some culture negative, but all had radiologic evidence of active disease.

In the trials in which it was reported, about 10-15% of patients had bacilli resistant to isoniazid or at least one other drug (see Appendix 1). Only one trial (Germany) reported excluding patients with drug-resistant bacilli.

A number of drug regimens were used, most but not all containing rifampin and pyrazinamide (see table of included studies).

France 1976 and East Africa 1978 (see table of excluded studies) are excluded because they compared regimens of equal length. The French trial was the first published report of shorter regimens, and provided the impetus for the later trials. It compared 3 months of daily streptomycin, isoniazid, and rifampicin with the same drugs given 3 times per week for 3 months. These 3-drug regimens are less effective than the 4-drug regimens used in the other trials, so the results are of less interest to the subject of this report, in any case. The East Africa study compared 4-month regimens with and without rifampicin in the continuation phase, with the result clearly favoring the inclusion of rifampicin.

 

Risk of bias in included studies

All studies used some form of random allocation, but only one (Singapore 1981) specified the method used (sealed envelopes provided by the Medical Research Council in London). One trial (Agra 1981) mentioned that a placebo was given to the shorter-duration treatment group to make the total lengths of treatment equal. No other mention or suggestion of blinding was mentioned in any study.

About 10% of all eligible patients (after exclusions for pre-randomization ineligibility were already taken into account) entered in 5 of the trials were not included in relapse analyses for a variety of reasons, by far the most important being "defaulting" on treatment (patients either completely lost to follow-up or who took less than a pre-specified proportion of scheduled treatments). Adverse reactions were the second most important reason. The overall proportions not included in relapse analyses were much higher in two trials: Germany 1986 (18%) and Singapore 1981 (23% not seen at 30-month follow-up). There was no evidence of higher default rates (or other losses) in longer compared with shorter treatment arms in the trials. The small trials sizes and the sometimes large number of exclusions lead to less confidence in the results than the reported precision suggests.

No trial presented an intention-to-treat analysis, nor were the data reported in sufficient detail to be able to conduct such an analysis.

The trials are of similar quality. Failure to analyze the data according to intention-to-treat (or provide the data in a form that such an analysis could be conducted) is, by today's standards, a major failing, but at the time the trials were done, this would not have been a major criticism. Except for the German trial, all the trials were done with involvement of the British or Indian Medical Research Councils, both of which were using state-of-the-art methodology at the time the trials were initiated, which was in a relatively short span of years. There is no apparent reason to exclude any trials from the analyses on the basis of quality, but the lack of intention-to-treat analyses must temper any conclusions drawn from these trials.

 

Effects of interventions

Relapse rates at one year (or more, depending on reporting) are consistently higher after shorter duration treatment regimens, regardless of the specific comparison made in terms of the details of the regimens or the types of patients randomized in individual trials. There appears to be no threshold for regimens of less than 6 months, i.e., the longer the regimen, the lower the relapse rate. These trials do not provide information about a possible threshold after treatment for 6 months or longer.

Nonetheless, the relapse rates were all quite low. Relapse rates after longer (comparison) regimens were all less than 10% at 1 year (or more) (ranging from 0% to 7%), and in the shorter treatment arms, they were 10% or less for eight comparisons (ranging from 1% to 9%) and 18% in the one remaining comparison (S. India 1986). It must be borne in mind that these relapse rates are based only on study participants who complied fully with the treatment protocol (in most cases meaning having taken at least 75-90% of scheduled treatments), and that failure rates based on intention-to-treat analyses (which cannot be carried out based on published data) could be higher, taking into account lack of adherence to the regimen as well as drug failure.

There was little or no difference in the rates of adverse reactions or toxicity requiring a change of regimen or discontinuation of treatment, with the exception of one trial (Hong Kong 1979) in which significantly fewer changed or discontinued treatment in the 2-month regimen than in the 12-month regimen, but these were small numbers (6/299 vs 17/299).

The regimens were all very good in terms of sterilizing efficacy after completion of treatment. The reported sterilizing efficacy for each arm of each trial is:

Agra
3-month regimen: 99%
4.5 month regimens (combined): 100%

Germany (all results at 3 months only)
3-month regimen: 94%
6-month regimens (combined): 99%

Hong Kong 1979
2- and 3-month regimens: 100%

Hong Kong 1989
2-, 3-, and 4-month regimens: 100%

S. India 1983
Initially drug sensitive infections:
5-month regimen: 97%
7-month regimens (combined): 98%
Initially drug resistant infections:
combined 5- and 7-month regimens with R: 85%
7-month regimen without R: 57%

S. India 1986
3-month regimen: 96%
5-month regimen with R: 99%
5-month regimen without R: 97%

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms

The trials reviewed here were begun 15 to 20 years ago and their results convinced tuberculosis control researchers that regimens shorter than 6 months produced results inferior to the then-standard 6-month regimens. This systematic review supports that conclusion, at least for treatment under the best conditions that could be devised, and including in the analyses only individuals who received all or most of the prescribed regimens. That said, the failure rates at one year for shorter regimens under these ideal conditions were still very low by field standards: less than 10% in all trials except one (which had an 18% relapse rate) compared with relapse rates from 0-7% in the longer arms. Although the numbers were small, nearly all relapses were with drug-sensitive strains which could be retreated with the same drugs.

Nearly all study participants with initially drug-sensitive bacilli were sputum culture negative at the end of treatment, regardless of the length of treatment. This was not true of all those with initially drug-resistant bacilli, but this was not reported separately in most papers. These data demonstrate, however, that sterilizing efficacy at the end of treatment is not a sensitive indicator of the risk of relapse.

Few deaths were reported in any trial (and overall, more due to other causes than to TB), so no analysis of the effect on death of different lengths of treatment would be useful.

The results of this review cannot be applied directly to decide on appropriate regimens for TB control programs. They do indicate that the longer patients take anti-TB drugs, the lower the relapse rates, at least up to 6 months. The variety of comparisons, ranging from the shortest, 2 vs. 3 months; to the longest 5 vs. 7 months are consistent in showing that longer is better. Because the short regimens are not all compared with the currently recommended 6-month short course regimen, it is not possible to know how much better the 6-month regimen is. However, there seemed to be two good reasons to include all the trials, rather than to limit them to those that used a standard 6-month regimen as comparison. First, it is useful to look at a range of shorter vs. longer comparisons to determine whether the effect seen is consistent (which it was in this case). The second reason may be less compelling for some: it is of historical interest to gather these similar trials together so that the world's literature (which is somewhat old in terms of clinical trials) on shorter treatments is reviewed and available for current researchers to know what has been done.

The patients in these trials were supervised much more closely than is possible under programme conditions, so the trials cannot answer the important question of whether adherence to treatment would be better with shorter regimens. One of the main reasons to revisit these trials was to determine whether regimens shorter than 6 months worked well enough to consider using them in the field, where, in fact, adherence might be better.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms

 

Implications for practice

These data confirm that longer periods of treatment are likely to result in lower relapse rates in a variety of patients with active TB, but that shorter regimens (as short as 3 months for patients with initially sputum smear positive active disease) are almost as effective.

The trade off between potentially better adherence to a shorter regimen (which has not been demonstrated) and a slightly higher relapse rate may still result in an overall better (or equal) result in the program setting. However, evidence on this question is currently lacking.

 
Implications for research

This review has demonstrated that TB treatment regimens shorter than the current standard of 6 months are not as good as longer regimens at preventing relapse. However, because of the serious problem of adherence to treatment over long periods of time, what is achieved in programmes is usually less than the optimal. It may be that a larger proportion of the scheduled doses may be taken if the overall treatment period is shorter. This could result in success rates that are equivalent or even higher than those currently achieved with a nominal 6-month regimen.

This review provides support for a trial of shorter vs. 6-month treatment regimens under the conditions of an actual TB control programme.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms

I would like to thank Dermot Maher, Henry Mwandumba and Merrick Zwarenstein for their helpful comments.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms
Download statistical data

 
Comparison 1. 2 months vs longer
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Relapse within 12 months of finishing treatment1529Peto Odds Ratio (Peto, Fixed, 95% CI)6.10 [2.19, 17.01]
 2 Toxicity requiring interruption, alteration, or cessation1598Peto Odds Ratio (Peto, Fixed, 95% CI)0.37 [0.16, 0.85]

 
Comparison 2. 3 months vs longer
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Relapse within 12 months of finishing treatment52588Peto Odds Ratio (Peto, Fixed, 95% CI)3.67 [2.42, 5.58]
 2 Toxicity requiring interruption, alteration, or cessation42918Peto Odds Ratio (Peto, Fixed, 95% CI)1.09 [0.87, 1.38]

 
Comparison 3. 4 months vs longer
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Relapse within 12 months of finishing treatment2887Peto Odds Ratio (Peto, Fixed, 95% CI)3.64 [1.71, 7.75]
 2 Toxicity requiring interruption, alteration, or cessation11114Peto Odds Ratio (Peto, Fixed, 95% CI)0.97 [0.63, 1.49]

 
Comparison 4. 5 months vs longer
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Relapse within 12 months of finishing treatment1390Peto Odds Ratio (Peto, Fixed, 95% CI)2.24 [0.90, 5.59]
2 Toxicity requiring interruption, alteration, or cessation00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Appendix 1. Patients with drug-resistant bacilli at start of trial (%)

TrialNo. patients (%)
Agra 1981Not available
East Africa 197864/619 (10.3)
Germany 1986None (excluded)
Hong Kong198983/542 (15.3)
Hong Kong 197944/274 (16.1)
Singapore33/363 (9.1)
S. India 198664/469 (13.6)
S. India 198398/628 (15.6)


 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Last assessed as up-to-date: 15 June 1999.

DateEventDescription
13 October 2008AmendedConverted to new review format with minor editing.


 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Protocol first published: Issue 1, 1999
Review first published: Issue 4, 1999

DateEventDescription
31 October 2005AmendedNew studies found but not yet included/excluded.


 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms

I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of the review (e.g. employment, consultancy, stock ownership, honoraria, expert testimony).

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Internal sources

  • No sources of support supplied

 

External sources

  • Department for International Development, UK.
  • World Health Organization, Switzerland.

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
Agra 1981 {published data only}
  • Mehrotra ML, Gautam KD, Chaube CK. Shortest possible acceptable, effective ambulatory chemotherapy in pulmonary tuberculosis. Am Rev Respir Dis 1981;124:239-244.
Germany 1986 {published data only}
  • Eule H, Beck H, Evers H, et al. Daily ultrashort chemotherapy and intermittent short-term chemotherapy with 4 drugs of communicable pulmonary tuberculosis treated for the first time. Results of a cooperative multicenter study [Tagliche ultrakurze Chemotherapie und intermittierende Kurzzeit-Chemotherapie mit 4 Medikamenten bei erstbehandelten ansteckenden Lungentuberkulosen]. Z Erkrank Atm org 1986;167:29-41.
Hong Kong 1979a {published data only}
  • Hong Kong Chest Service, Tuberculosis Research Centre, Madras, India, and British Medical Research Council. Sputum-smear-negative pulmonary tuberculosis: Controlled trial of 3-month and 2-month regimens of chemotherapy. Lancet 1979;i:1361-1363.
Hong Kong 1979b {published data only}

 

Hong Kong 1989a {published data only}
  • Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council. A controlled trial of 3-month, 4-month, and 6-month regimens of chemotherapy for sputum-smear-negative pulmonary tuberculosis. Am Rev Respir Dis 1989;139:871-876.
Hong Kong 1989b {published data only}

 

S. India 1983 {published data only}
  • Santha T, Nazareth O, Krishnamurthy S, et al. Treatment of pulmonary tuberculosis with short course chemotherapy in South India--5-year follow up. Tubercle 1989;70:229-234.
  • Tuberculosis Research Centre. Study of chemotherapy regimens of 5 and 7 months' duration and the role of corticosteroids in the treatment of sputum-positive patients with pulmonary tuberulosis in South India. Tubercle 1983;64:73-91.
S. India 1986 {published data only}
  • Balasubramanian R, Sivasubramanian S, Vijayan VK, et al. Five year results of a 3-month and two 5-month regimens for the treatment of sputum-positive pulmonary tuberculosis in South India. Tubercle 1990;71:253-258.
  • Tuberculosis Research Centre, Madras and National Tuberculosis Institute, Bangalore. A controlled clinical trial of 3- and 5-month regimens in the treatment of sputum-positive pulmonary tuberculosis in South India. Am Rev Respir Dis 1986;134:27-33.
Singapore 1979a {published data only}
  • Singapore Tuberculosis Service/British Medical Research Council. Clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis. American Review of Respiratory Diseases 1979;119:579-585.
  • Singapore Tuberculosis Service/British Medical Research Council. Clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis: the results up to 30 months. Tubercle 1981;62:95-102.
  • Singapore Tuberculosis Service/British Medical Research Council. Long-term follow-up of a clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis. American Review of Respiratory Diseases 1986;133:779-783.
Singapore 1979b {published data only}

 

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
East Africa 1978 {published data only}
  • East African and British Medical Research Councils. Controlled clinical trial of five short-course (4-month) chemotherapy regimens in pulmonary tuberculosis. Lancet 1978;ii:334-338.
France 1976 {published data only}
  • Kreis B, Pretet, Birenbaum J, et al. Two three-month treatment regimens for pulmonary tuberculosis. Bull Int Union Tuberc 1976;51:71-75.

References to studies awaiting assessment

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
Bock 2001 {published data only}
  • Bock NN, Rogers T, Tapia JR, Herron GD, DeVoe B, Geiter LJ. Acceptability of short-course rifampin and pyrazinamide treatment of latent tuberculosis infection among jail inmates. Chest 2001;119(3):833-7.
Borisova 2003 {published data only}
  • Borisova MI, Stakhanov VA, Sharkova TI, Ivashchenko NA. The use of fenazid in patients with pulmonary tuberculosis with poor isoniazid tolerance [Primenenie fenazida u bol'nykh tuberkulezom legkikh s plokhoi perenosimost'iu izoniazida]. Problemy Tuberkuleza 2003;7:34-7.
Gravendeel 2003 {published data only}
  • Gravendeel JM, Asapa AS, Becx-Bleumink M, Vrakking HA. Preliminary results of an operational field study to compare side-effects, complaints and treatment results of a single-drug short-course regimen with a four-drug fixed-dose combination (4FDC) regimen in South Sulawesi, Republic of Indonesia. Tuberculosis 2003;83(1-3):183-6.
Hernandez 1993 {published data only}
  • Hernández Forero JC. A controlled clinical trial of 4 months regimens in the shortened treatment of tuberculous pleural efusion. Apresentada a Universidad El Bosque. Facultad de Medicina para obtençao do grau de Postgrado Medicina Interna [Estudio clínico controlado de un esquema de 4 meses en el tratamiento acortado de la tuberculosis pleura]. Bogotá, D.C, 1993.
Jasmer 2002 {published data only}
  • Jasmer RM, Saukkonen JJ, Blumberg HM, Daley CL, Bernardo J, Vittinghoff, E, et al. Short-course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: a multicenter clinical trial. Annals of Internal Medicine 2002;137(8):640-7.
Lwilla 2003 {published data only}
  • Lwilla F, Schellenberg D, Masanja H, Acosta C, Galindo C, Aponte J, et al. Evaluation of efficacy of community-based vs. institutional-based direct observed short-course treatment for the control of tuberculosis in Kilombero district, Tanzania. Tropical Medicine and International Health 2003;8(3):204-10.
    Direct Link:
Matteelli 1999 {published data only}
  • Matteelli A, Olliaro P, Signorini L, Cadeo G, Scalzini A, Bonazzi L, et al. Tolerability of twice-weekly rifabutin-isoniazid combinations versus daily isoniazid for latent tuberculosis in HIV-infected subjects: a pilot study. International Journal of Tuberculosis and Lung Disease 1999;3(11):1043-6.
Mawer 2001 {published data only}
  • Mawer C, Ignatenko N, Wares D, Strelis A, Golubchikova V, Yanova G, et al. Comparison of the effectiveness of WHO short-course chemotherapy and standard Russian antituberculous regimens in Tomsk, western Siberia. Lancet 2001;358(9280):445-9.
Sanchez 2004 {published data only}
  • Sanchez-Arcilla I, Vilchez JM, Garcia de la Torre M, Fernandez X, Noguerado A. Treatment of latent tuberculosis among homeless population. Comparison between wo therapeutic approaches [Infeccion tuberculosa latente en poblacion indigente. Comparacion de dos pautas terapeuticas]. Medicina Clinica (Barc) 2004;122(2):57-9.
Teo 2002 {published data only}
  • Teo SK, Tan KK, Khoo TK. Four-month chemotherapy in the treatment of smear-negative pulmonary tuberculosis: results at 30 to 60 months. Annals of the Academy of Medicine, Singapore 2002;31(2):175-81.
Yu 2001 {published data only}
  • Yu D, Wang J, Hu X. Clinical research of pasinizid on retreated sputum positive pulmonary tuberculosis in senilities. Zhonghua Jie He He Hu Xi Za Zhi 2001;24(10):608-10.
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