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Rapid Responses: Rapid Responses published:
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Vaccines in the fight against TB
- Douglas B Young (6 May 2008)
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TB MDR incidence in Rome.
- Nazario Bevilacqua, Gina Gualano ,Monica Sane Schepisi , Enrico Girardi , Francesco N. Lauria . (23 May 2008)
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Point of care testing to improve treatment completion
- Dr. Graham F. Cope, Dr Ruth Whitfield, Associate Specialist in Respiratory Medicine, Mayday University Hospital, Surrey CR7 7YE (5 June 2008)
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Re: TB MDR incidence in Rome. Correction to list of authors
- Sharon Davies (10 June 2008)
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Douglas B Young, Fleming Professor of Medical Microbiology Imperial College London SW7 1AA
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Dear Sir, A recent article in the BMJ (“Increasing antituberculosis drug resistance in the United Kingdom: analysis of national surveillance data,” by Michelle E Kruijshaar, et al, 1 May 2008) concludes that improved early case detection, rapid testing of susceptibility to drugs, and improved treatment completion is necessary to combat the surge in drug-resistant tuberculosis in England, Wales and Northern Ireland. As the authors conclude, the world needs simpler, faster drug regimens that treat all forms of TB and rapid and more accurate diagnostic tools to quickly detect TB and its drug-resistant forms. Additionally, and urgently needed, is a new tuberculosis vaccine that will be effective in preventing all forms of TB. The currently available TB vaccine was developed over 85 years ago and is unreliable against the most common form of the disease – adult pulmonary TB, which kills over a million people worldwide year. Efforts are underway in the United Kingdom and globally to discover and develop new tuberculosis vaccines. Clinical studies for new vaccine candidates are being led by Oxford University, GlaxoSmithKline, the Aeras Global TB Vaccine Foundation and others in Africa, Europe, India and the United States. It is encouraging that the Department for International Development’s new research strategy includes support for TB vaccine research. Effective prevention in the form of a new TB vaccine, combined with better diagnostics and treatment, will be crucial to stem this terrible epidemic. Yours faithfully, Douglas B. Young, Fleming Professor of Medical Microbiology, Imperial College London Competing interests: None declared |
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Nazario Bevilacqua, Medical Doctor National Institute for Infectious Diseases, Lazzaro Spallanzani, Rome Italy (00149), Gina Gualano ,Monica Sane Schepisi , Enrico Girardi , Francesco N. Lauria .
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Sir, Kruijshaar ME and colleagues in their paper published online on may 1 2008, reported a very small increase of antituberculosis multidrug resistance (MDR-TB) among patients in the United Kingdom from 1998 to 2005. This increase was associated with increasing numbers of cases from sub-Saharan Africa and the Indian subcontinent. Despite an increment of 46.3% of the overall Tuberculosis (TB) cases incidence from 1998 to 2005, the TB MDR cases never exceeded the number of 50 patients per year. In Rome, Italy, we observed a sharper increase in MDR-TB incidence. In the last 5 years (2003-2007), 601 culture proven TB patients were cared for at the National Institute for Infectious Diseases L. Spallanzani in Rome (INMI). Out of them 25 (4.16%) had MDR-TB, a proportion just slightly higher of that estimated for Italy (3.3%). During this period the proportion of MDR-TB rose from 1.8% in 2003 to 6.4% in 2007. Age of MDR-TB patients ranged from 15 to 51 years with a mean of 22 years; 12 were women and 4 were coinfected with HIV. Strains of M tuberculosis isolated form MDR-TB patients were resistant on average to 3 first line TB drugs, and one strain had a resistance pattern matching the definition of “extremely drug-resistant” TB; 14 patients had received a previous antituberculosis treatment. A diagnostic delay affected most of the patients with a mean of 72 days (range from 39 to 360 days). Only 2 patients (8%) were born in Italy, 12 (48%) were from Eastern Europe, 6 (24%) from South America and 5 (20%) from Africa and Asia. Foreign born patients were living in Italy on average 13 motnhs (range from 1 month to 7 years) 8 patients were lost to the follow up (32%) and one non-HIV died for respiratory complications in spite of converting to negative sputum culture. Our data show that the increase in MDR-TB in Rome is primarily related to migration from countries with high prevalence such as Romania, Perù and Ukraine. This observation underlines the importance of improving the quality of TB care in high MDR-TB burden countries and of setting up surveillance for possible spread of MDR-TB strains in low incidence countries. 1. Zignol M, Hosseini MS, Wright A, Weezenbeek CL, Nunn P, Watt CJ, Williams BG, Dye C. Global incidence of multidrug-resistant tuberculosis. J Infect Dis. 2006 Aug 15;194(4):479-85. 2. WHO/IUATLD Global Project on Anti-tuberculosis. Anti-Tuberculosis drug resistance in the world. Fourth Global Report. Drug Resistance Surveillance 2002-2007. World Health Organization 2008. 3. EuroTB and the national coordinators for tuberculosis surveillance in the WHO European Region. Surveillance of tuberculosis in Europe. Report on tuberculosis cases notified in 2006. Institut de veille sanitaire, Saint-Maurice, France. March 2008 (www.eurotb.org). Competing interests: None declared |
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Dr. Graham F. Cope, Honorary Senior Research Fellow University of Birmingham, B15 2TT, UK, Dr Ruth Whitfield, Associate Specialist in Respiratory Medicine, Mayday University Hospital, Surrey CR7 7YE
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We read with interest the article by Kruijshaar et al, (BMJ 31st May 2008), which highlighted the global increase in the resistance to antituberculous drugs. The paper discussed the point that resistance is probably related to increased numbers of patients with drug resistance arriving in the UK from sub-Saharan Africa and the Indian subcontinent, and that control measures to prevent outbreaks of resistant infection are inadequate. In addition further support needs to be given to ensure that patients complete their treatment. We are addressing this final point by utilising a point of care urine test to monitor isoniazid treatment. The test called IsoScreen, developed at the University of Birmingham, is a disposable device that contains the reagents for the Arkansas method, which is a colorimetric assay to detect the presence of isoniazid metabolites (1). The 5-minute test turns the urine sample a dark blue colour if the drug has been taken within the last 24-48 hours. We are embarking on a study to examine further the time frame of the sensitivity of the test and its relationship with acetylator status. The initial trial of the test compared it with orange staining of the urine by rifampicin, a drug given in combination with isoniazid. This staining is frequently used as a means of monitoring treatment adherence. Urine samples from 191 patients undergoing treatment for TB were screened, of those 43.5% had orange staining, while IsoScreen was positive in 93.2% of cases. Staining is known to persist for only a few hours after ingestion, while the IsoScreen test remains positive for 24 hours or longer. The results also showed that 6.8% of patients had not taken their isoniazid for 24 hours or longer, so failing to adhere correctly to the daily dose regimen. The test can be used routinely by nursing staff to obtain an immediate assessment of adherence. This allows those patients who are suspected of not taking their drugs correctly to be identified and either given further information, or placed on the DOT programme to ensure they take their drugs correctly. Our studies have shown that IsoScreen can play a useful role in supporting medical and nursing staff to ensure completion of treatment and so reduce the risk of further outbreaks of drug resistant tuberculous infections. References 1. Whitfield R, Cope GF. Point of care test to monitor adherence to anti-tuberculous treatment. Annals of Clinical Biochemistry 2004; 41: 411- 413 Competing interests: Dr Cope is the inventor of the IsoScreen tests and is a director of GFC Diagnostics Ltd (www.gfcdiagnostics.co.uk), the manufacturer and distributor of the test. We would like to acknowledge the financial support provided by the Sir Halley Stewart Trust |
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Sharon Davies, letters editor BMJ
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In their rapid response to the article “Increasing antituberculosis drug resistance in the United Kingdom ...” by Kruijshaar et al, Dr Bevilacqua and colleagues inadvertently left off as an author Dr Fabrizio Palmieri, from the Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy. The order of authors should read: Nazario Bevilacqua, Gina Gualano, Monica Sane Schepisi, Fabrizio Palmieri, Enrico Girardi, and Francesco N Lauria. Competing interests: None declared |
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