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"DOTS-plus" strategy hard to implement
- Jaime E Ollé-Goig (23 September 1998)
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Multidrug resistant TB in Western Siberia
- N Banatvala (7 October 1998)
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Big problems in Moldova
- Nick Banatvala (15 October 1998)
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The WHO treatment regimens need revision
- S K Agarwal (12 June 2000)
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Re: "DOTS-plus" strategy hard to implement
- Fuad Mirzayev (18 February 2004)
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Jaime E Ollé-Goig
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EDITOR- Farmer & Kim propose in their recent article a " DOTS- plus" strategy to attempt controlling multidrug resistant tuberculosis (MDRT)1. As much as I sympathize with them, after following several patients with MDRT and watching them die, I would like to express my concern and skepticism towards such a proposal being implemented in low income areas. The development of MDRT is a complex multifactorial process and the wide distribution of new drugs will not solve the issue. Need to generate an income, family duties, religious misconceptions, social stygma and mismagement by health practitioners constitute only a limited list of some of the obstacles that patients must face before achieving a successful outcome of their treatment. Anti-tuberculosis drugs used for the treatment of MDRT are not very effective, have frequent undesirable effects and must be given for prolonged periods of time. Who will supervise such complex regimens? Who will observe the prescribers? Directly observed therapy (DOT) requires directly observed doctors (DOD)2 but DOTS-plus will make double DOD mandatory. We must always attempt to treat and cure the individual patient but initiating a "DOT-plus" strategy at a national level is, at present, a dream; it risks diverting our limited resources and causing epidemiological havoc. We should not awaken one day only to realize that our dream has become a microbiological nightmare. Jaime E Ollé-Goig, MD, MPH Apartado postal 9802 Santo Domingo, Dominican Republic References. 1. Farmer P, Kim JY. Community based approaches to the control of multidrug resistant tuberculosis: introducing "DOTS-plus". BMJ 1998; 317:671-674. 2. Ollé-Goig JE. Non-compliance with tuberculosis treatment; patients and physicians. Tuberc Lung Dis 1995; 76:277-278. |
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N Banatvala
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Dear Sir "Hot zones" of ongoing multidrug resistant tuberculosis (MDR TB) transmission are resulting in calls for "directly observed treatment, short course (DOTS)-plus".1 We present data demonstrating high levels of MDR TB in the Tomsk region of Western Siberia in the Russian Federation, an area where a DOTS programme is now in operation. As part of a quality control programme, cultures were obtained from the Central Bacteriological Laboratory at the oblast TB dispensary. The first set of 83 cultures was a cross sectional sample comprising all those being analysed in the laboratory at the end of June 1994. These were tested at a WHO Mycobacterium Reference Unit by the modal resistance ratio method. The = second set of 92 comprised samples from new cases identified between April and August 1997 which were tested in a second WHO Reference Laboratory by the proportion method. There were two aspects of these surveys that were particularly striking. First, initial resistance was high. In 1994, 20 individuals had not been treated before and initial resistance to any drug was detected in 6 (30%). A similar level of initial resistance (37%) was found in 1997. Second, MDR (isoniazid + rifampicin +/- other agents) was detected in 14.6% of the 1994 isolates and resistance to three or more antimicrobials in 19.5%; these isolates were mostly from males with a long treatment history (more than one year or multiple treatment events). 36.6% of isolates from this patient group were MDR. In 1997 5.4% were MDR and resistance to three or more antimicrobials was detected in 20.4%. Individual resistances in 1994 were: streptomycin 46.3%, isoniazid 57.3%, rifampicin 14.6%, ethambutol 15.9% and pyrazinamide 4.9% and in 1997: streptomycin 24%, isoniazid 28%, rifampicin 6%, ethambutol 6%, ethionamide 20% and PAS 1%. These data suggest that large numbers of strains of TB resistant to one or more antimicrobials are circulating in the Tomsk community. Many of the individuals from whom our samples came had very long treatment histories and a record of poor compliance. Many were homeless persons, ex-prisoners or alcoholics, individuals that are difficult both to screen and to treat. As part of the reform programme Tomsk laboratories now use internationally accepted methods of determining drug resistance and in future we will be able to determine trends in MDR TB from local laboratory data. From now on we will be in a position to ensure that DOTS with short course chemotherapy is recommended on the basis of epidemiological and microbiological data rather than mere dogma, and that the DOTS framework is expanded to DOTS-plus where necessary. The challenge now is to identify the economically appropriate infrastructure and technical support required for a DOTS-plus strategy in a country that is experiencing dire financial collapse. Yours sincerely Dr. T.D. Healing, Epidemiologist MERLIN (Medical Emergency Relief International), 14 David Mews, Porter Street, London, W1M 1HW, UK Dr. N.A. Sakseltseva, Consultant Medical Microbiologist Tomsk TB Dispensary, Tomsk, Russian Federation Dr. P.A. Jenkins, Consultant Medical Microbiologist formerly of the Mycobacterium Reference Unit,Public Health Laboratory, University Hospital of Wales, Cardiff, UK Professor F. Portaels, Consultant Medical Microbiologist Institute of Tropical Medicine, Department of Microbiology, Mycobacteriology Unit, Antwerp, Belgium Dr. N. Banatvala Project manager, Tomsk TB Health Sector Reform Programme MERLIN (Medical Emergency Relief International) 14 David Mews, Porter Street, London, W1M 1HW, UK Acknowledgement This document is an output from a project funded by the UK Department for International Development (DFID) for the benefit of developing countries. The views are not necessarily those of DFID. Reference 1. Farmer P, Kim JK. Community based approaches to the control of multidrug resistant tuberculosis: introducing "DOTS-plus". BMJ 1998:317:671-4. |
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Nick Banatvala
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Dear Sir With greater access to the former Soviet Union our knowledge of the the perilous state of tuberculosis control is being increasingly established. This is likely to result in an expansion of the list of multidrug resistant tuberculosis (MDR-TB) "hot spots".1-3 In 1997, MERLIN undertook two assessments in Moldova. In parallel with Russia and other countries in the former Soviet Union, Moldova has seen an increase in tuberculosis notification rates from 40 per 100,000 in 1990 to 59 in 1996. The increase follows socio-economic dislocation, collapse of the economy, a shortfall in the health care budget and decline in the coverage and efficacy of the national tuberculosis control programme. The Soviet-based control programme bears high manpower and estate costs, with active case finding by radiology and treatment in hospital where drug regimens and adjunct therapies are managed according to a complicated case classification. In 1996 it was decreed that the programme should be restructured to follow international guidelines (passive case-finding by smear microscopy, out-patient short-course chemotherapy). Tuberculosis rates are especially high in prisons (increasing from 270 per 100,000 in 1992 to 2640 per 100,000 in 1996). Of a quasi-random sample of 14 isolates obtained from the Moldova prison TB hospital, 12 (86%) were both isoniazid and streptomycin-resistant and 9 (64%) were also rifampicin-resistant. Such high rates of MDR-TB pose a threat to the civilian population as prisoners are released into the community. Coupled with insufficient funding to maintain or restructure the control programme, there is potential for a massive MDR problem. In the presence of high levels of MDR-TB, the introduction of directly observed treatment, short course (DOTS) programme4 in Moldova with limited drugs may not lead to patient cure but would increase the pool of infectious cases and so would itself run the risk of promoting MDR-TB.5 It is then only a matter of time before countries in western Europe start seeing the importation of MDR-TB from former Soviet Union countries. The situation in prisons presents a special problem in the design and implementation of a national control strategy to which a targeted pilot "DOTS-plus"1 approach offers a partial solution. The resources required will be great but in the long term must surely be cost effective. Yours sincerely Dr Valeriu. Krudu, Chief Microbiologist, Moldova Prison Service, Chisinau, Moldova Denis Tracey, Consultant in Public Health Medicine Highland Health Board, Inverness IV2 3HG John Paul, Consultant Microbiologist Brighton Public Health Laboratory, BN2 5BE Francis Drobniewski, Head, Mycobacterium Reference Laboratory, Dulwich Public Health Laboratory, London SE22 8QF Nick Banatvala, Medical Adviser Medical Emergency Relief International (MERLIN), 14 David Mews, London W1M 1HW References 1 Farmer P, Kim JK. Community based approaches to the control of multidrug resistant tuberculosis: introducing "DOTS-plus". BMJ 1998:317:671-4. 2 Conninx R, Pfyffer GE, Mathieu C, et al. Drug resistant tuberculosis in prisons in Azerbaijan: case study. BMJ. 1998:316:4123-5. 3 Anti-tuberculosis drug resistance in the world. The WHO/IUTLD global project on anti-tuberculosis resistance surveillance, 1994-1997. World Health Organisation: Geneva 1997. 4 World Health Organisation. Treatment of tuberculosis: guidelines for national programmes. 2nd Edition, World Health Organisation, Geneva 1997. 5 Farmer P, Bayona M, Becerra M et al. The dilemma of MDR-TB in the global era. J Tuberc Lung Dis. 1998;2:1-8. |
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S K Agarwal, Prof Department of Chest Diseases, Banaras Hindu University, Varanasi 221 005, India
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The Editor- Paul Farmer is strongly in favour of introducing “ DOTS- plus” to treat multidrug-resistant tuberculosis ( MDR-TB ) in the “ hot zones” of the world [1]. On July 5 – 6, 1999 the World Health Organization (WHO) Working Group on DOTS-Plus for MDR-TB and the Program in Infectious Diseases and Social Change at Havard Medical School (PIDSC) hosted a meeting to advance the prospects of patients with MDR-TB in resource poor countries. This is definitely a good move. Now it has become clear that we have to think about MDR-TB in a new way. In the past, we have seen it as a virtual death sentence for the people in developing countries. It has become essential to revise the treatment regimens recommended by the WHO in 1997 [2] for each treatment category. Patients of treatment failure are still being prescribed only first-line antituberculosis drugs as this is being recommended by the WHO in 1997 [2]. Failure to manage patients with MDR-TB has multiple potentially
damaging implications : A DOTS-plus program based on individual treatment of MDR-TB is a
complex process. It will require References : 1. Farmer P, Kim JY. Community based approaches to the control of multidrug-resistant tuberculosis : introducing “ DOTS plus”. BMJ 1998; 317: 671-674 ( 5 September ) 2. World Health Organization.Treatment of Tuberculosis: Guidelines for National Programmes. WHO/TB/97.220 |
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Fuad Mirzayev, ... 1477 Beacon street, Brookline, MA 02446
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It was very interesting to read comments from Dr. Jaime E Ollé-Goig but it also was rather difficult to agree with them. DOTS+ is not an easy undertaking indeed and major resources are required including prolonged efforts by medical professionals even in the resource-limited settings. Thinking about resources we may may make a mistake and start to conclude using some well known principles for organisation of health programs. Of course it is the best to cover with your curative action the majority of the population than to spent somewhat scarce funds for the risk oriented strategy, i.e. for sometimes (for now) the only minute tail of your clients' distribution...But let's never forget that tuberculosis (and MDR TB as well) is an infectious disease. Competing interests: None declared |
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