CABI Blog

This is about TB or more precisely Extremely Drug Resistant Tuberculosis (XDR-TB). It’s the kind of “reaction rant” you can find in the columns of the UK’s newspaper The Times (hence the title) but with a difference: I have CABI’s Global Health database to back me up.

The context
TB first became multidrug resistant (MDR-TB) in the 1990’s as a result of people  who did not complete their full antibiotic course, allowing time for resistant forms to take over. MDR-TB is resistant to at least 2 of the so called first-line antibiotics commonly used for TB BUT XDR-TB goes further: it is resistant to the first-line drugs (any fluoroquinolone) and at least one of the second-line drugs. In otherwords, its resistant to the drugs that are used to treat MDR-TB.   With the limited treatment options for XDR-TB, this once treatable infection could become as deadly in developed countries as it was in the early 20th century, back to the stage of the sanatorium and a quiet life if you were lucky.  In India, a recent tertiary hospital study found that 42% of patients with XDR-TB died.

I was going to write about this a month ago as I had just read a brief item in Nature concerning  a young man spending his honey moon in quarantine in Rome, Italy.  What amazed me was that he’d flown from the USA to Greece & then onto Italy to get married knowingly diagnosed with TB (bad enough but presumably taking his pills and he’d been told he was not currently infectious). According to the Nature news item, within a few days of his travel, the CDC in the USA discovered his TB was XDR which means, as I already said, there are very few drugs to sort it out. What really shook me was that according to this article, Mr Andrew Speaker was told to get back to the USA immediately for lifesaving treatment but was banned from flying USA airlines and he’d ended up flying via Canada.

My immediate thoughts were “ what on earth was he doing flying anywhere with such an infectious disease, what about his bride catching it, what were the authorities doing to let him travel” (you can catch TB, whatever the strain, by sharing air with an infected person) AND “excuse me can’t you get lifesaving treatment in Europe”, followed rapidly by “typical of US -centric thinking to consider US airline passengers only (i.e. on no account fly on them) and only the US can treat you!”[Dear USA, please forgive me for jumping to conclusions, blame Nature, see later].

I really felt like writing a letter of complaint to the Times (hence the title of this piece, except of course, to be accurate I’d be Incensed of Thame).

Andrew Speaker’s actions as far as I could see from this article lacked common sense, consideration for others and a lack of understanding of his disease. More blame seemed to lie with those giving him medical advice. However, according to a commentary in JAMA (Markel et al, JAMA  2007,Vol 298, No. 1, 83-86) which discussed this case & the ramifications for public health law (the rights of the individual vs the rights of the population), it would appear that the US authorities weren’t so blinkered or inconsiderate, just inefficient.  You see, the plot thickened. According to JAMA, it would appear that the authorities told Mr Speaker prior to his departure for his wedding trip in Greece & Italy NOT to travel but seek specialist treatment.  He deliberately left early before they had time to put him on a “no fly” list.  Finally tracked down to Italy, he was told of his danger to others & to report to the Italian authorities. Instead he flew home via Canada, driving across the US border. He wilfully caused a global crisis which highlighted glaring errors in the US public health system.

But there’s more. I write this now because I was not alone in those first immediate reactions. Reading the BMJ (BMJ (news) 2007, Vol 335, No. 7612, 177), I see that the US congress & his fellow air passengers also considered these actions totally irresponsible. And no doubt the Canadians complained bitterly. The US congress have just held hearings to assess how their health agencies failed us all (unable to stop him flying, couldn’t locate him on flights, slow to make him NO FLY, slow to notify WHO, Europe and Canada and finally the border guards did not detain him as he drove into the US). His fellow flight passengers are suing this young man (who turns out to be a lawyer, which may be the only fortunate thing for him). His life saving treatment was to have the upper lobe of his right lung removed.

You can see how seriously this XDR-TB is taken by the WHO and others if you follow the Reference List links below to records in our Global Health database (1,2,3,4,5,6,8). It first grabbed my attention reading about the reports in South Africa. Then it hit our newspapers when the Guardian wrote an article on possible detention of people with XDR-TB in South Africa, based on an article in PLOS Medicine (7,9)  As is clear now, XDR-TB is not confined to South Africa: its appeared in many countries but is of particular concern in eastern Europe, South Africa and Asia. In 2006, WHO issued a global alert.

And whilst I’ve got your attention, I feel it important to make several points about the common or garden variety of TB, that its’ the second greatest killer, after AIDS, worldwide. That this applies particularly to those countries suffering the ravages of HIV/AIDS as this increases susceptibility to TB. That the DOTS (Directly Observed Treatment Short Course) strategy employing a standardised treatment for 6 months, was devised by the WHO to ensure that people completed antibiotic treatment because if you don’t, then you get the disease again but this time its the MDR form and you increase the chance of resistant strains of TB circulating (which is how we ended up with XDR-TB in the first place).  That 20% of cases are MDR, 2% of cases are XDR.  That this leaves 78% of TB cases the kind which is amenable to vaccination and inexpensive drugs and DOTS. That despite this, 1.6 million people die annually because they can’t access these drugs, as most live in the developing world.

Moving on. In the developed world, a rising number of people contract TB because their immune systems are compromised through immunosuppressive drugs, substance abuse or HIV/AIDS. Complacency, as exemplified by Andrew Speaker who grew up in a world transformed by antibiotics, amongst the general public about infectious diseases generally is rife. That complacency especially regarding "ordinary” TB is no longer acceptable.

And here is another example rather closer to home. I received a BCG vaccination to protect me against TB at age 12, and children in adjacent counties to Oxfordshire still receive this BUT, guess what, Oxfordshire does not consider it necessary. Relying on everyone else to keep up herd immunity. It never occurred to me that my daughter had not received a BCG until it was brought to my attention by the nurse who was immunising us for a trip to Dubai!

Consequently my daughter is supposed to go off to University, unprotected.  As parents, if we worry at all about diseases at college, we worry about STIs (sexually transmitted infections) and possibly meningitis, but who’s telling them about TB. She’ll mix with people who come from countries where TB is endemic or on the rise, or who travel regularly there to visit relatives. Most TB cases in this country can all be described as imported.

So guess what, I am going to have her privately immunised. None of us should be complacent about TB.

Refs(* Global Health database content freely available through Google)

1. Shah, N. S. et al, Worldwide emergence of extensively drug-resistant tuberculosis

Emerging Infectious Diseases, 2007, Vol. 13, No. 3, pp. 380-387.

2*.  Sharma M. et al, Mycobacterium tuberculosis induces high production of nitric oxide in coordination with production of tumour necrosis factor-a in patients with fresh active tuberculosis but not in MDR tuberculosis. Immunology and Cell Biology, 2004 (Vol. 82) (No. 4) 377-382

3.* Urabe, K. et al, Epidemiology of cutaneous tuberculosis in Japan: a retrospective study from 1906 to 2002. International Journal of Dermatology, 2004 (Vol. 43) (No. 10) 727-731

4.*  Sotgiu, G. et al, Detection of isoniazid and rifampin resistance in Mycobacterium tuberculosis strains by single-strand conformation polymorphism analysis and restriction fragment length polymorphism. Microbiologica, 2003 (Vol. 26) (No. 4) 375-381

5. Gandhi, N. R. et al, 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 (British edition), 2006, Vol. 368, No. 9547, pp. 1575-1580

6. Masjedi, M. R. et al, Extensively drug-resistant tuberculosis: 2 years of surveillance in Iran. Clinical Infectious Diseases, 2006, Vol. 43, No. 7, pp. 841-847

7. WHO Guidance on human rights and involuntary detention for XDR-TB control

8. Singh J.A. et al, XDR-TB in South Africa: No Time for Denial or Complacency PLoS Medicine Vol. 4, No. 1, e50 doi:10.1371/journal.pmed.0040050

9. Stop TB Forum: http://www.healthdev.org/eforums/stop-tb

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