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Published Date: 2008-02-08 22:00:16
Subject: PRO/EDR> Tuberculosis, MDR - South Africa
Archive Number: 20080208.0521

TUBERCULOSIS, MDR - SOUTH AFRICA
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Date: Fri 8 Feb 2008
Source: Aidsmap News [edited]
<http://www.aidsmap.com/en/news/42AFD58C-B358-4E35-9229-C19A09320351.asp>

Further evidence that infection control in South African hospitals is
vital for containment of the country's growing epidemic of
drug-resistant tuberculosis was presented to the Fifteenth Conference
on Retroviruses and Opportunistic Infections on Wednesday [6 Feb
2008], with the finding that every case of multi-drug resistant
tuberculosis analysed in one rural hospital was the result of
re-infection, not poor drug adherence. Multi-drug resistant
tuberculosis [MDR TB] is a growing problem in South Africa, and in
2006 researchers revealed that an outbreak of extensively
drug-resistant TB [XDR TB] had claimed more than 50 lives in less
than a year in one hospital in the province of KwaZulu-Natal.

Since that report drug sensitivity testing of tuberculosis (TB)
bacteria isolates in the province have revealed that in 2006 alone,
2476 patients had [MDR TB] compared with just 124 cases in the whole
of the United States in 2006. A total of 539 cases of MDR TB were
reported between June 2005 and August 2007 from one hospital alone,
the Church of Scotland hospital in Tugela Ferry, a small town deep in
the rural uplands of KwaZulu-Natal. The Church of Scotland hospital
was the site which 1st identified the outbreak of [XDR TB], although
not the source for an epidemic that became apparent throughout South
Africa once TB specialists began a systematic search for extensive
drug resistance in September 2006.

Prior to the Tugela Ferry outbreak, the conventional wisdom in the TB
world had been that MDR TB was largely a product of poor adherence to
the 6-month regimen of TB drugs required to cure the disease. World
Health Organisation advice has long emphasised the importance of
directly observed therapy to ensure that TB drugs are taken. However,
research at the Church of Scotland hospital indicated that the XDR TB
outbreak was attributable to airborne infection with the
drug-resistant strain, often in the hospital.

The findings led to a call for better infection control in crowded
hospitals that may house dozens of TB patients alongside hundreds of
HIV-positive patients who are highly susceptible to rapid TB
progression if they contract the infection. In Tugela Ferry the
roll-out of antiretroviral therapy had paradoxically assisted the
spread of XDR TB; one cluster of patients who died rapidly from XDR
TB were members of an ARV support group, and it was the rapid decline
of several patients previously doing well in this group that alerted
health care workers that something was amiss. But even after the
warnings about the need for improved infection control, hospitals in
southern Africa have been slow to change their ways.

In order to investigate the risk of MDR TB infection more
systematically, Dr. Neel Gandhi of Albert Einstein Hospital, New
York, set out to look at patients with a prior history of TB who had
eventually been diagnosed with MDR or XDR TB, to see what proportion
were becoming superinfected with drug-resistant strains, as opposed
to suffering the consequences of TB treatment failure. Using
retrospective medical records from the Church of Scotland hospital,
Dr. Gandhi and colleagues looked for patients with a prior TB
diagnosis who had subsequent evidence of a second diagnosis of MDR or
XDR TB, confirmed by drug sensitivity testing.

The researchers identified 17 patients, 88 percent of them
HIV-positive, who had been identified with MDR or XDR TB a median of
150 days after a previous TB isolate had been found to be
drug-sensitive. The 2nd isolate was available in each case because
doctors had spotted signs of deterioration, often after several
months of clinical improvement on TB treatment. Adherence to TB
treatment was considered to be good in all cases, Dr. Gandhi told
reporters. They carried out genetic matches of the drug-sensitive and
drug-resistant TB strains to determine whether they had evolved, or
whether the drug-resistant strain was completely unrelated. In every
single case the drug-resistant strain was significantly different,
and represented evidence of an 'exogenous' infection (superinfection)
with drug-resistant TB.

Out of 17 patients, 15 died within 14 days of the collection of the
sputum sample that subsequently yielded the drug-resistant TB isolate
invariably prior to the return of a diagnosis of MDR TB from the laboratory.

Speaking at a press conference, Dr. Gandhi said the findings
underlined the critical importance of infection control measures in
containing MDR and XDR TB. He said that wards containing 40 to 70
beds were commonplace, and that hospitals needed to look at ways of
identifying TB patients promptly and separating them from others, as
well as ensuring good infection control in settings where TB patients
were grouped together. The patients who developed drug-resistant TB
in this study had spent a median of 25 days in hospital, he pointed out.

He described how, at his hospital, a 'cough officer' was responsible
was identifying coughing patients on the wards, separating them from
others, ensuring that they wore a surgical mask, and referring them
to a doctor for urgent evaluation of their TB status. Minimising
hospital admissions and the time spent in hospital could also help,
as could the introduction of outdoor waiting areas.

Reference
Gandhi N et al. Exogenous re-infection with multi-drug and
extensively drug-resistant TB among TB/HIV co-infected patients in
rural South Africa. Fifteenth Conference on Retroviruses and
Opportunistic Infections, Boston, abstract 143, 2008.

[Byline: Keith Alcorn]

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Communicated by:
ProMED-mail
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[In the early 1990's, nosocomial outbreaks of multidrug-resistant
tuberculosis (MDR-TB) occurred in New York City and Miami
(<http://www.cdc.gov/mmwr/preview/mmwrhtml/00015030.htm> and
<http://iier.isciii.es/mmwr/preview/mmwrhtml/00020788.htm>). During
these outbreaks, latent and active tuberculosis developed in exposed
healthcare workers (HCW) and patients, some of whom were
HIV-infected. HIV-infected HCW and patients frequently developed a
fulminant, fatal clinical course of tuberculosis, similar to that
described in the above news release. In addition, as described in the
above news release, some exposed HIV-infected patients with
well-documented tuberculosis later develop superinfection with an
outbreak-associated strain (Small PM, Shafer RW, Hopewell PC, et al.
Exogenous reinfection with multidrug-resistant _Mycobacterium
tuberculosis_ in patients with advanced HIV infection [see comments].
N Engl J Med 1993; 328:1137-44).

Investigations of these outbreaks at the time found the following
contributory factors:
1. Delayed diagnosis of MDR-TB attributed to:
- Atypical clinical presentation and non-specific radiologic
findings of tuberculosis in patients with HIV/AIDS; e.g., cavitation
on chest radiograph was not present in more than 90 percent of cases,
most of whom had HIV/AIDS
(<http://www.cdc.gov/mmwr/preview/mmwrhtml/00015030.htm>).
- Delayed microbiologic diagnosis of TB, e.g., acid-fast bacilli
(AFB) were not detected in sputum smears or sputum smears were not
routinely examined for AFB.
- The prolonged time taken to complete and verify
drug-susceptibility testing and report the results to hospitals
and clinicians (almost 2 months). Until the pattern of drug
resistance is known, no reliably effective therapeutic regimens can
be prescribed and patients remain infectious.
2. Delayed institution of tuberculosis isolation while awaiting diagnosis.
3. Inadequate tuberculosis isolation, e.g., inadequate numbers of
appropriate rooms for tuberculosis isolation; tests of direction of
air flow with smoke tubes indicating that many tuberculosis isolation
rooms had positive pressure relative to hallways
(<http://gateway.nlm.nih.gov/MeetingAbstracts/102204076.html>); doors
to isolation rooms left open; HCW and visitors entering tuberculosis
isolation rooms wearing no masks or using masks improperly; and
patients in tuberculosis isolation leaving their rooms without wearing masks
(<http://gateway.nlm.nih.gov/MeetingAbstracts/102204076.html>).
4. Clustering of highly susceptible patients (e.g.,
immunocompromised, HIV-infected patients) in the vicinity of
inadequately isolated patients with contagious tuberculosis
(<http://gateway.nlm.nih.gov/MeetingAbstracts/102204076.html>).

In 1990 the U.S. CDC issued guidelines for preventing transmission of
tuberculosis in health care settings (Dooley SW Jr, Castro KG, Hutton
MD, Mullan RJ, Polder JA, Snider DE Jr. Guidelines for preventing the
transmission of tuberculosis in health care settings, with special
focus on HIV-related issues. MMWR Morb Mortal Wkly Rep. 1990;
39(RR-17):1-29) and revised these guidelines in 1994 (Guidelines for
preventing the transmission of Mycobacterium tuberculosis in health
care facilities, 1994. MMWR Morb Mortal Wkly Rep. 1994; 43(RR-13):1-132).

This experience in the U.S. highlighted the following:
- HIV-infected persons, particularly those with severe
immunosuppression, are especially susceptible to life-threatening
nosocomially transmitted tuberculosis.
- Infection-control precautions to prevent transmission of
_Mycobacterium tuberculosis_ to patients and HCW should be
implemented promptly on suspicion of the diagnosis of clinically
active tuberculosis. Tuberculosis isolation precautions should
include use of a private room with negative pressure in relation to
surrounding areas and a minimum of 6 air exchanges per hour.
(Cohorting AFB smear-positive patients together, some of whom may
have drug-susceptible and some MDR or XDR TB with different
drug-resistance patterns may lead to superinfection). Air from the
tuberculosis isolation room should be exhausted directly to the
outside. Persons entering the tuberculosis isolation room should use
disposable particulate respirators that fit snugly around the face.
Tuberculosis isolation precautions should be continued until there is
clinical and microbiologic evidence of reduced infectiousness.
- Anti-TB drug-susceptibility testing should be performed on initial
_M. tuberculosis_ isolates from all TB patients. Isolates obtained
after relapse or apparent treatment failure should also be tested for
drug susceptibility. Drug- susceptibility testing should be completed
rapidly, and results should be reported promptly to the health-care
provider and the health department.
- All hospital personnel, including volunteers, who may be exposed
to patients with suspected or known TB should be educated about the
medical consequences of becoming infected with MDR-TB and should
follow appropriate precautions for minimizing such exposure. In this
regard, a recent study documented inadequate knowledge and practice
concerning tuberculosis among recent Pakistani medical school graduates
(<http://www.thenews.com.pk/print1.asp?id=74470>).

Implementation of an appropriate TB control program has been shown
to decrease nosocomial tuberculosis infections
(<http://www.annals.org/cgi/content/full/122/9/658> and
<http://www.annals.org/cgi/content/abstract/122/2/90?ck=nck>).
However, in resource-poor countries, the availability of adequately
educated and trained health care personnel, laboratory facilities
capable of rapidly diagnosing MDR TB, adequately engineered
negatively pressured single-bedded tuberculosis isolation rooms, an
adequate supply of personnel protective equipment (e.g., N95 face
respirator masks), and an adequate supply of fully potent 1st and
2nd-line anti-TB drugs may be an overwhelming challenge. Even in the
relatively resource-rich U.S., a national survey in 1993 documented
that only about 73 percent of U.S. hospitals had rooms with
tuberculosis isolation facilities (Rudnick JR, Kroc K, Manangan L,
Banerjee S, Pugliese G, Jarvis W. Are U.S. hospitals prepared to
control nosocomial transmission of tuberculosis? {Abstract}. In:
Program and abstracts of the Epidemic Intelligence Service 42nd
annual conference. Atlanta: US Department of Health and Human
Services, Public Health Service, CDC, 1993:60), and laboratories had
limited ability to isolate, identify, and determine antimicrobial
susceptibility of _M. tuberculosis_ isolates (Huebner RE, Good RC,
Tokars JI. Current practices in mycobacteriology: results of a survey
of state public health laboratories. J Clin Microbiol 1993;31:771-5). - Mod.ML]

See Also