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Knowledge for XDR Tuberculosis Control Today

Posted by plosmedicine on 31 Mar 2009 at 00:30 GMT

Author: Andrea Gori
Position: MD
Institution: San Gerardo Hospital, University of Milan, Bicocca, Monza, Italy
Additional Authors: Fabio Franzetti, Enrico Girardi
Submitted Date: September 28, 2008
Published Date: October 1, 2008
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

To the PLoS Medicine Editor,

As Dr.Gavin Yamey MD MA MRCP Senior Editor, would like to offer us the opportunity to submit an electronic letter in response to the PLoS Medicine paper “XDR-TB in South Africa: No Time for Denial or Complacency” by Singh JA, Upshur R, Padayatchi N. Vol. 4, No. 1,e50 doi:10.1371/journal.pmed.0040050, we thank you for the opportunity to submit our response.
The recent emergence of highly drug-resistant tuberculosis in South Africa has highlighted the serious implications posed by the tuberculosis epidemic on global public health efforts. The reappearance of XDR tuberculosis is reminiscent of the worldwide multidrug-resistant tuberculosis outbreaks in the early 1990s. We believe that what has been done in controlling MDR TB outbreaks in the developed world could provide crucial assistance in outlining the critical issues and priorities for XDR tuberculosis control strategies in all African countries.
We submit this article for publication, as “letter to the editor”, in PLoS Medicine considering the interest in supporting XDR tuberculosis control wordwide.
This paper has not been published nor submitted elsewhere. All the authors have contributed significantly to the work, and they have participated in the design, execution, and analysis of the paper and have seen and approved the final version. None of the authors of the paper have any conflict of interest.

Yours sincerely,

Andrea Gori1, MD, Fabio Franzetti2, MD, Enrico Girardi3, MD

1Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milan, Bicocca, Monza, Italy. 2Chair of Infectious Diseases and Tropical Medicine, Department of Clinical Sciences, “Luigi Sacco” Hospital, University of Milan, Milan,Italy. 3Department of Epidemiology and Preclinical Research,Clinical Epidemiology Unit, National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.

Andrea Gori, M.D.

Division of Infectious Diseases
Department of Internal Medicine,
“San Gerardo” Hospital,
University of Milano-Bicocca
Via Solferino, 16 - 20052 Monza (Milano) - Italy
Phone : ++39 039 2333794 Fax : ++39 039 2333898

The spread of XDR tuberculosis in South Africa [1] has highlighted once more the serious implications posed by the tuberculosis epidemic on global public health efforts. The reappearance of XDR tuberculosis is reminiscent of the worldwide emergence of MDR tuberculosis strains in the early 1990s [2].
Actually, based on current terminology, a portion of MDR TB cases observed during the past decade would today be classifiable as XDR cases.
In 1998, we described the emergence of a nosocomial outbreak of MDR tuberculosis involving HIV patients in Italy [2]. The Milan outbreak was caused by a single “extremely” drug resistant strain, which was resistant to all tested first and second line drugs. One hundred and twenty-one HIV-positive and 5 HIV-negative cases were identified. 76% had a documented exposure to an XDR case within an infectious diseases ward, with a median of 36 days of duration of exposure. The case fatality rate was 72% within 6 months of diagnosis and 93% within 1 year. Median survival from diagnosis of XDR tuberculosis was 94 days. Since HAART was not available when the outbreak started, patients were treated with sub-optimal antiretroviral treatments. All patients were severely immunosuppressed (median CD4+ 12/mm3), two-thirds of whom were either not on HAART, or began therapy late.
Most of these patients were HIV-infected, however, the true extent of XDR strains spreading in the HIV-negative population remains to be determined. Among the HIV-negative health care workers exposed to XDR tuberculosis who underwent tuberculosis screening, recent infection was documented in 52%. Such subjects most likely became carriers of potentially untreatable XDR strains. Thus, one could speculate that the ongoing XDR outbreak will likely continue in the future, and that, since diagnosed infections represent a small proportion of total XDR infections, we are currently observing the mere tip of the XDR iceberg.
In response to the outbreak, several control measures were implemented in Milan hospitals. A sharp decrease in incidence was observed in our hospital following adherence to basic administrative and source-control measures. Nevertheless, small numbers of cases continued to be recorded, up until 1997, when HAART were made available. Consequently, the numbers of severely immunosuppressed HIV-infected patients decreased dramatically, as did hospital admission rates for patients with symptomatic HIV disease. It is therefore arguable that final eradication of the outbreak was favoured by the use of HAART.
Together, these two outbreaks demonstrate that, geographical location notwithstanding, unless control measures are rapidly implemented, many sub-Saharan countries are likely to experience similarly catastrophic scenarios in the near future. While HIV treatments are becoming more widely available in developing countries, often many immunosuppressed HIV-infected patients remain in close contact within health facilities, prior to achieving HAART-induced immune reconstitution. This enormously increases the risk of nosocomial tuberculosis transmission in settings where tuberculosis remains an endemic disease.
Moreover, any improvement of TB control measures will be only partially effective if all interventions will not be accompanied by a reduction in the pool of highly susceptible HIV-infected individuals. This second, crucial goal, can only be brought about by preventing new infections, and by making HAART widely accessible to those in need of it.

1. Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, et al.. (2006) Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 368: 1575-80.
2. Franzetti F, Gori A, Iemoli E, Meraviglia P, Mainini F, et al. (1999) Outcome of multidrug-resistant tuberculosis in human immunodeficiency virus-infected patients. Clin Infect Dis 29: 553-60.

Competing interests declared: None of the authors of the paper have any conflict of interest.