Published Date: 2008-03-22 22:00:18
Subject: PRO/EDR> Tuberculosis, XDR - UK (Scotland) ex Somalia
Archive Number: 20080322.1094
TUBERCULOSIS, XDR - UNITED KINGDOM (SCOTLAND) EX SOMALIA
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Fri 21 Mar 2008
Source: The Guardian [edited]
A man in his 30s is in isolation at a hospital in Glasgow and is
being treated with a cocktail of antibiotics in an effort to control
[extensively] drug-resistant tuberculosis (XDR-TB), the Guardian has
learnt. A spokeswoman at Gartnavel general hospital confirmed the
case and said health officers were tracing people who may have come
into close contact with the man.
This is the 1st time a patient has been diagnosed and treated for
XDR-TB in the UK. [According to the BBC News, although "this is the
1st case of its kind reported in the UK since the revised definition
of XDR-TB was published by the World Health Organization in 2006 --
an earlier case in 2003 was retrospectively identified as XDR-TB
- Mod.ML]. The World Health Organisation has warned of the danger
that XDR-TB poses because of the ease with which the airborne disease
can travel in an era of mass migration and global travel.
Tuberculosis is spread only through close and prolonged contact with
other people, such as in a family or among children in a school, so
there is no suggestion that a single case could spark an epidemic.
The arrival of XDR-TB in the UK is, however, a warning of the need
for greater vigilance against the disease. "XDR-TB is an extremely
serious form of TB," said Professor Peter Davis, a Liverpool
consultant and secretary of TB Alert in the UK. "It is quite
prevalent in other parts of the world. We have got to be aware of
it." Drugs could contain the disease, but not cure it, he said. About
half of those who were infected would survive.
Strains of [multi-drug resistant, or MDR-] TB, which are resistant to
the 2 main antibiotics [isoniazid (INH) and rifampin] used to treat
it have been spreading across the globe and complicating treatment
for some years. About 1 percent of the 8497 cases reported in the UK
in 2006 showed multiple drug resistance. XDR-TB, however, is a new
and still more alarming phenomenon, showing resistance to both 1st
[INH and rifampin] and [the] 2nd-line drugs [fluoroquinolones, and at
least one of the 3 injectable anti-tuberculosis drugs capreomycin,
kanamycin, and amikacin]. Treatment takes 12 to 18 months and costs
more than GBP 100 000 [USD 198 300 ] per patient. An outbreak would
place a huge financial burden on local health authorities.
The man, a Somali, was screened for infectious diseases on arrival at
Heathrow in November last year . An X-ray revealed TB scars on
his lungs, but the disease was not active. The patient, thought to
have claimed political asylum, told doctors he had recently undergone
a 6-month course of treatment for TB and, following an immigration
interview, he was allowed to travel to Scotland. In January  he
was admitted to Gartnavel after the disease reactivated in his lungs.
Cultures later revealed the XDR strain, and health officials were
called to trace his close contacts to prevent an outbreak.
Dr Oliver Blatchford, a consultant at the Greater Glasgow and Clyde
NHS public health unit, said: "XDR-TB is no more infectious than
ordinary TB, but does require different treatment. The contacts of
this case are being screened in the same way as ordinary TB contacts
and will be monitored closely to ensure that any further cases are
identified early and treated quickly."
XDR-TB 1st came to public attention in 2006, when a cluster of cases
was reported in KwaZulu Natal in South Africa. All 53 patients were
HIV-positive and 52 of them died within 25 days. Dr. Paul Nunn, head
of the WHO's TB resistance team, warned that the cases were "raising
the spectre of something that we have been worried might happen for a
decade -- the possibility of virtually untreatable TB". The WHO
estimates there are 9 m[illion] cases of TB in the world, with
perhaps 2 percent being XDR-TB. A report in February  found
that 44 countries had experienced cases. Many cases will have been
missed because the correct tests will not have been carried out when
the patient failed to respond to treatment.
The more usual multi-drug resistant form of TB is a strain that is
now resistant to rifampicine and isoniazid, the standard antibiotics
used to treat TB. But there are good 2nd-line drugs -- taken as a
"cocktail" -- that can cure it. Even ordinary TB requires a 6-month
course of antibiotics, and it is essential the course is completed.
It has been patients' failure to adhere to treatment regimes that has
allowed the drug resistance to develop. The best that doctors can do
for patients with the XDR-TB is to contain the disease. In some
cases, the affected part of the lung can be cut out, but often the
disease has spread too far.
Health Protection Agency figures show a small drop in UK TB cases.
The 8497 cases notified to the agency last year  were down by
0.7 percent on the previous year's total.
[Byline: Aidan Jones and Sarah Boseley]
[This Somali political asylum seeker is reported to have recently
completed a 6-month course of treatment for tuberculosis before
arrival in the U.K.; he likely declared he was asymptomatic and had
only a pulmonary scar indicative of old tuberculosis when he was
permitted to enter the U.K. in November 2007. The exact components of
this patient's regimen are not stated, but should have included INH,
rifampin, pyrazinamide (PZA) and ethambutol. The 6-month regimen is
only designed to treat disease due to drug-susceptible strains of
_Mycobacterium tuberculosis_, although initial resistance to INH does
not compromise the outcome for this 4-drug regimen. However, initial
resistance to rifampin does compromise the outcome of the 6-month
regimen. Susceptibility to PZA is also essential for the 6-month
regimen to be effective.
In all likelihood, this Somali patient had XDR-TB to begin with, was
given the 6-month regimen inappropriately in the absence of
drug-susceptibility testing, and was mistakenly assumed to have
inactive disease when he entered the U.K. in November 2007 (which
raises the issue of possible exposure of airplane passengers to
XDR-TB). He unlikely developed XDR-TB as a result of non-adherence to
the 6-month treatment regimen when he relapsed only 2 months later.
Such non-adherence would not easily explain acquisition of resistance
to the fluoroquinolones and at least one of the 3 injectable
anti-tuberculosis drugs capreomycin, kanamycin, and amikacin.
Development of XDR-TB usually follows the inappropriate use of these
2nd-line drugs in a patient for whom 1st-line drugs are failing.
Patients then spread the infection to close contacts, who acquire
primary XDR tuberculosis
From a prior ProMED-mail post 20080228.0813, "according to the WHO
survey, which involved 90 000 patients in 81 countries from
2002-2006, about one in 20 new cases of tuberculosis worldwide is
multidrug-resistant (MDR).., or approximately 450 000 of the 9
million new tuberculosis cases that are detected each year." In
another international, retrospective survey of nearly 18 000 TB
isolates collected from 2000 through 2004, 20 percent of samples were
MDR-TB, and 10 percent of these (or 2 percent overall) were XDR-TB
(MMWR Morb Mortal Wkly Rep 2006; 55(11):301-5, available at
Although XDR-TB is present throughout the world, the international
survey suggested that it is most common in Asia and Eastern Europe.
Up to 25 percent of cases are reported to be XDR in some localities;
e.g., Baku, the capital of Azerbaijan, and Papua New Guinea. In fact,
because of poor surveillance and lack of resistance testing, the
frequency of MDR and XDR TB in many parts of the world is unknown and
may be much higher than has been as yet reported.
Anti-TB drug-susceptibility testing should be performed on initial
_Mycobacterium tuberculosis_ isolates from all TB patients. Isolates
obtained after relapse or apparent treatment failure should also be
tested for drug susceptibility. As pointed out in the prior
ProMED-mail post 20080228.0813, a recent study (Pillay M, Sturm AW.
Clin Infect Dis. 2007; 45: 1409-14) postulated that the introduction
of the 6-month directly observed therapy-based tuberculosis-control
programs in the absence of susceptibility testing or drug resistance
surveillance was instrumental in the development of XDR in a highly
transmissible strain in KwaZulu Natal, South Africa. - Mod.ML]