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   Author  Topic: Totally drug-resistant TB emerges in India ?  (Read 3700 times)
Fritz
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Totally drug-resistant TB emerges in India ?
« on: 2012-01-14 19:24:33 »
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This isn't news to many, especially in India; but it does make me reflect on Gaia's ability to defend herself. Nature 1 Humans 0 ... yet again.

Cheers

Fritz


Discovery of a deadly form of TB highlights crisis of 'mismanagement'.

Source: Natrure
Author: Katherine Rowland
Date: 2012.01.13


An untreatable form of tuberculosis has been found in India.
Atul Loke/Panos

Physicians in India have identified a form of incurable tuberculosis there, raising further concerns over increasing drug resistance to the disease1. Although reports call this latest form a “new entity”, researchers suggest that it is instead another development in a long-standing problem.

The discovery makes India the third country in which a completely drug-resistant form of the disease has emerged, following cases documented in Italy in 20072 and Iran in 20093.

However, data on the disease, dubbed totally drug-resistant tuberculosis (TDR-TB), are sparse, and official accounts may not provide an adequate indication of its prevalence. Giovanni Migliori, director of the World Health Organization (WHO) Collaborating Centre for Tuberculosis and Lung Diseases in Tradate, Italy, suggests that TDR-TB is a deadlier iteration of the highly resistant forms of TB that have been increasingly reported over the past decade. “Totally resistant TB is not new at all,” he says.

Since the 1960s, two drugs — isoniazid and rifampicin — have been the standard TB treatment. Although episodes of resistance cropped up periodically, during the 1990s the incidence of multiple drug resistance grew significantly, leading researchers in 2006 to refer to it as extensively drug-resistant tuberculosis (XDR-TB). Surveillance data from the WHO indicate that XDR-TB is present in at least in 58 countries, with an estimated 25,000 cases occurring each year.

Epidemiologist Carole Mitnick of Harvard Medical School in Boston, Massachusetts, agrees that TDR-TB is not new, and points to the history of XDR-TB. “When XDR-TB was first named, it was a phenomenon that had existed but hadn’t gotten much attention before. TB in general doesn’t receive a lot of attention,” she says.

Inadequate care

Part of the increase in drug resistance is related to complications that arise in treating patients who are also infected with HIV — 13% of TB cases, according to the WHO. However, the greatest part of the problem results from the management of the disease.

Although the WHO describes TB as a “disease of poverty”, drug-resistant varieties might best be understood as resulting from poor treatment. According to a 2011 WHO report, fewer than 5% of newly diagnosed or previously treated patients are tested for drug resistance. And it is estimated that just 16% of patients with drug-resistant TB are receiving appropriate treatment.

“The cases are a story of mismanagement,” says Migliori. “Resistance is man-made, caused by exposure to the wrong treatment, the wrong regimen, the wrong treatment duration.”

In the management of TB, many factors affect whether the disease is cured or becomes resistant to treatment. Drug misuse or mismanagement can result if a patient does not follow a full course of treatment, or if the correct drugs are not available or patients with undiagnosed resistant TB receive inappropriate therapies.

Part of the problem also relates to TB testing. The WHO recommends sputum smear microscopy, a test developed more than one hundred years ago, as the standard diagnosis. Although inexpensive, this method is prone to false negatives, does not provide information on drug susceptibility, and test results can take several weeks — a large window of time for a patient to potentially receive the wrong drugs or transmit the infection. However in 2010, the WHO approved a new rapid and fully automated test, known as Xpert, which assesses resistance to the first-line drug rifampicin. As of July 2011, 26 countries are using Xpert and 145 are eligible to purchase kits at a reduced price.
Drug dearth

The fact that no new first-line TB drugs have been developed for half a century has probably contributed to the emergence of strains that are unresponsive to treatment, says Mitnick. “If you keep using the same drugs for that long, resistance is inevitable.”

Tuberculosis trails behind only HIV as the world’s leading cause of death from infectious disease. But in spite of its impact on human health and economic growth, it has not ranked among the pharmaceutical industry's priorities.

“The pharmaceutical industry had scant interest in TB for decades,” says Richard Chaisson, director of the Center for TB Research at the Johns Hopkins School of Public Health in Baltimore, Maryland. “The industry pretty much concluded it wasn’t an attractive market, there was not enough potential profit.”

But with a growing number of public–private partnerships in research, Chaisson says, industry interest is “an order of magnitude greater than it was a decade ago”.

As of 2011, there were 10 new or repurposed TB drugs in clinical trials that have the potential to either shorten treatment duration or improve therapy for resistant TB. Late-stage studies include a phase III trial by Bayer to assess whether its antibiotic moxifloxacin can help to reduce the duration of standard therapy from 6 months to 2. And both Tibotec and Novartis are in phase II trials for products that may be useful in treating drug-resistant forms.
« Last Edit: 2012-01-14 20:58:32 by Fritz » Report to moderator   Logged

Where there is the necessary technical skill to move mountains, there is no need for the faith that moves mountains -anon-
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Re:Totally drug-resistant TB emerges in Ind
« Reply #1 on: 2012-01-14 20:58:04 »
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[Fritz]Seems the Globe and Mail article was wanting .... TDR-TB is a funding strategy not a new strain and hardly from India

The European Respiratory Journal (ERJ)
Source: http://www.ersj.org.uk/content/29/3/423.full#sec-5

<snip>
XDR-TB EPIDEMIOLOGY AND SPREAD

Due to its fairly recent definition, information about XDR-TB is still scattered and incomplete. The CDC study 7 reported that XDR-TB had been observed in all continents. Unpublished analysis of that data reveals that some 17 countries had at least one case of XDR-TB. More representative information from some countries has described the frequency of XDR-TB. For instance, in the USA, 4% of the MDR-TB strains isolated between 1993 and 2004 were XDR-TB. In Asia, data are available from South Korea 7, where 15% of the MDR-TB strains isolated in 2004 were XDR, and also Iran 10, where 12 (10.9%) of 113 MDR-TB strains isolated were XDR. In Hong Kong, nine out of the 75 MDR-TB strains (12%) had extensive drug resistance, defined as simultaneous resistance to ethionamide, amikacin, ofloxacin and cycloserine 11. In Europe, representative data are available from Latvia 7, where 19% of the MDR strains isolated from 2000–2002 were XDR. In addition, XDR-TB was signalled from Russia (one XDR case resistant to ethionamide, kanamycin and ofloxacin, identified out of the 77 MDR strains tested 12) and Norway, where an outbreak of 23 cases (15 of them being XDR) has been ongoing for >10&#8197;yrs 13.

In Africa, data are currently only available from South Africa 14. In the Msinga district, KwaZulu Natal (KZN), out of 1,539 TB cases diagnosed between January 2005 and March 2006, 542 were culture positive, 221 were MDR with 53 “possible” XDR cases. Out of the 53 XDR patients, 52 died (with a median survival time after sputum smear sample collection of only 16 days). In total 44 cases tested were infected with HIV: 15 died while receiving antiretroviral treatment and two of them were healthcare workers (HCW). Of the XDR patients, 26 (51%) were new cases. Although 64% of XDR cases had been admitted to hospital before the diagnosis of TB, a third of them (36%) had no history of hospitalisation and may have acquired infection at community level. Spoligotyping results demonstrated that 85% of the 46 XDR strains tested belonged to the KZN family, and amongst the remaining 15%, some belonged to the Beijing family of strains. The strains were all resistant to all first-line drugs and to two classes of second-line drugs: aminoglycosides (kanamycin and amikacin) and fluoroquinolones. The strains were susceptible to ethionamide and cycloserine; however, the validity of DST for these drugs is uncertain. Susceptibility to capreomycin and para-aminosalycilic acid was not tested, as these drugs were not, until recently, available in South Africa. The available information on the global spread of MDR and XDR-TB is summarised in figure&#8197;3&#8659;; note that out of the 21 countries where at least one XDR-TB case was notified, 10 are in, or bordering, Europe.
<snip>


<snip>
CONCLUSIONS

The evidence available shows that extensively drug-resistant tuberculosis is present in Europe, mainly as a result of poor clinical and control practices. Preliminary anecdotal evidence suggests that some extensively drug-resistant strains in Europe (from Italy, for example) may, in fact, be “XXDR” or “extremely drug-resistant”, i.e. resistant to all first- and second-line drugs available. Basic science will need to provide a key contribution in developing new diagnostics, new drugs and, ultimately, a vaccine with which to fight tuberculosis. Unfortunately, several more years will be necessary to develop them. Even when new drugs are available, without a sound public health approach to using them, they may be rapidly lost. This has already happened to some of the key old drugs, “burnt” as a result of clinical and public health malpractices in many settings. Science is crucial but alone it is not sufficient to control the extensively drug-resistant tuberculosis epidemic. Exactly 125 years after Robert Koch's discovery of Mycobacterium tuberculosis (the milestone of modern control of TB) the “white plague” is still affecting mankind. While waiting for the much desired new diagnostic, treatment and prevention tools, public health is asked to provide a prompt response and curb the extensively drug-resistant epidemic using the available tools because affected people are dying today. The respiratory medicine specialists' contribution is crucial to win this battle.
<snip>
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Where there is the necessary technical skill to move mountains, there is no need for the faith that moves mountains -anon-
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