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TB: a major challenge for SA

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"Pulmonary tuberculosis" Film chest x-ray show interstitial infiltration both lung due to mycobacterium tuberculosis infection
"Pulmonary tuberculosis" Film chest x-ray show interstitial infiltration both lung due to mycobacterium tuberculosis infection

Medical ethics and other experts say tough isolation measures, involuntary if need be, are justified to contain a deadly, highly contagious and drug-resistant mutant strain of tuberculosis and to prevent "a potentially explosive international health crisis" brewing in South Africa.

They warn that new variations of the disease now defeat many of the world's existing drugs and "the forced isolation and confinement of extensively drug-resistant tuberculosis (XDR-TB) and multiple drug resistant tuberculosis (MDR-TB) infected individuals may be a proportionate response in defined situations given the extreme risk posed."

In a report, co-authors Ross Upshur, MD, Director of the University of Toronto Joint Centre for Bioethics, and South Africa-based HIV-AIDS experts Jerome Amir Singh and Nesri Padayatchi, MD, say the world community urgently needs to help isolate and contain the threat.

"The South African government's initial lethargic reaction to the crisis and uncertainty amongst South African health professionals concerning the ethical, social and human rights implications of effectively tackling this outbreak highlights the need to address these issues as a matter of urgency lest doubt and inaction spawns a full-blown XDR-TB epidemic in South Africa and beyond," the paper says.

The World Health Organization (WHO) announced in September 2006 that yet another deadly new strain of XDR-TB had been detected in Tugela Ferry, a rural town in KwaZulu-Natal (KZN) province, epicenter of South Africa's HIV/Aids epidemic. Eight days later, the WHO urged a response to the outbreak akin to recent global efforts to control SARS and bird flu.

The new strain appeared within a year of a study showing 221 of 544 TB patients in KZN province had MDR-TB (unresponsive, at a minimum, to front-line drugs rifampicin and isoniazid). Among the 221 cases, 53 were extensively drug-resistant – resistant to rifampicin and isoniazid and to three or more of the six potential second line drug options.

Of the 53 XDR-TB patients, 44 were tested for HIV; all were infected with that disease too. The median survival from the time of sputum specimen collection was just 16 days for 52 of the 53 infected individuals, including six health workers and those reportedly taking anti-retroviral drugs.

"Such a fatality rate for XDR-TB, especially within such a short period, is unprecedented anywhere in the world," the authors warn.

They note that South Africa is among the world's fastest growing tourist destinations, home to millions of migrant labourers, with ports and roads servicing several African countries.

"Cumulatively, these factors make for a potentially explosive international health crisis. The threat to regional and global public health is thus clear and further underlined by reports that XDR-TB is now considered endemic to KZN… reported in at least 39 hospitals throughout the province and in other parts of the country."

South African XDR-TB cases numbered 300 in December 2006 and at least 30 new cases of XDR-TB are now reportedly detected each month in KZN alone, according to the paper.

XDR-TB diagnoses to date (that require specialised laboratory facilities) "likely represent a small proportion of the true extent of the problem. The number of persons harbouring latent infections is unknown (and likely unknowable at present)," they add.

Factors fuelling the outbreak
Isolated cases of XDR-TB are documented in other countries, including Canada. However, the situation in South Africa represents "the world's first recognised instance of extensive transmission of MDR- and XDR-TB," says Dr Upshur. "Isolated cases do not so clearly raise the host of public health issues we discuss."

According to the paper, "factors that facilitate the spread of tuberculosis are well known and abundantly present in sub-Saharan Africa. Alongside inadequate health care systems response, poverty and global inequity contribute to the worsening global TB situation."

Low TB cure rates (only about half of South Africa's adult patients are cured each year, compared with 80 percent in countries with better resources) and the HIV epidemic have contributed to South Africa's MDR- and XDR-TB outbreak, the authors say. Underlying factors include:

  • Inappropriate treatment (e.g. the wrong choice of drugs, dosage or treatment duration)
  • Programme factors (e.g. irregular drug supply, incompetent health personnel, lack of infection control in institutions), and
  • Patient factors (e.g. poor adherence, mal-absorption).

Meanwhile, South African policies stipulate that those hospitalised at state expense lose their social welfare benefits during hospitalisation (the median stay for a suspected case of MDR-TB: almost 200 days). As a result, many patients forego hospitalisation and frequently default on treatment adherence. About one in six of the country's patients default on the six-month first-line treatment while almost a third default on second-line treatment.

These same patients "typically utilise public transport, and seek or continue… employment. In so doing, they pose a significant public health risk to their families, co-workers, local community and wider public," the paper says.

Impoverished TB patients need "some form of incentive and encouragement… to enter and remain in the health system, although admittedly, their confinement could conceivably be indefinite or until they die."

The authors say South Africa urgently needs to:

  • Reduce crowding in hospitals where TB patients are being treated;
  • Drastically expand tests and surveillance of the disease;
  • Rethink counselling, treatment, reporting and tracing strategies;
  • Find ways to reduce public exposure to MDR- and XDR-TB patients during the period it takes to diagnose the disease;
  • Accommodate the interests of patients in a sensitive and humane manner.

Given the "grave threat" posed by these TB strains, "the government ought to consider how it prioritises hospital resources. At minimum, XDR-TB patients… should be housed in facilities independent of both MDR-TB and immunocompromised (HIV) patients. The containment of such infectious XDR-TB patients may arguably take precedence over… those with full-blown Aids."

Human rights, ethics and XDR-TB containment
The paper says South African officials have raised human rights concerns in dealing with the country's outbreaks but concede forcible treatment may be a viable option.

"An important question is the extent to which judicially-sanctioned restrictive measures should be employed to control what could develop into a lethal global pandemic," the authors say. "Ultimately in such crises, public health interests must prevail over individual rights."

Other questions include what do with suspected TB sufferers while they await test results and the conditions and duration of clinical surveillance once a case is confirmed. Ideally, confirmed cases "should be isolated in an acute admissions setting," the authors say, adding that XDR-TB patients should be quarantined separately from MDR-TB "as the latter is potentially curable."

WHO guidelines recommend that ambulatory MDR-TB patients do not mix with the general public, but offer no advice should voluntary measures fail. Such a situation arose when a Johannesburg XDR-TB patient refused hospitalisation and discharged herself. Although forcibly hospitalised five days later, "it's unknown how many people she may have infected in the months between her sputum sample being taken and her eventual diagnosis, and before she was traced after her self-discharge."

The authors say involuntary restrictive measures "may increase disincentives to seek care. However, if due care is taken to provide for the rights and needs of those so detained and therapeutic goals are kept paramount, such measures could play an important role of containing XDR-TB."

"We would not argue for forcible treatment of MDR-TB or XDR-TB patients, simply restriction of mobility rights of such individuals," the authors say, adding that detained patients need legal council, given the uncertainty of the duration of restrictions. They also raise the possibility of independent tribunals to oversee the process.

The paper says authorities have "a strong reciprocal obligation" to support isolated patients with humane and decent living conditions. The duty of patients not to infect others can only be expected if the community shares the burdens involved.

TB threat could derail Aids efforts
"XDR-TB is a serious global threat with the potential to derail efforts to contain HIV/Aids. Broadly disseminated XDR-TB will prove to be a much more serious public health threat owing to its mode of transmission," says JCB Director Ross Upshur.

"The emergence of XDR-TB is also an uncomfortable reminder of the failure of health systems to control problems at a tractable scale. If, in the recent past, TB were to have been adequately managed when it was completely drug sensitive, we would not be in such a dire situation. We should begin to contemplate the response when we move to the predictable next phase: completely drug-resistant tuberculosis (CDR-TB)."

"Given the South African government's poor track record in dealing with the country's HIV/Aids epidemic and what is at stake if it adopts a similar lethargic and denialist response to the country's XDR-TB outbreak, the international community must be vigilant in monitoring the government's response to this emerging crisis," says Dr Padayatchi, Deputy Director of the Centre for Aids Programme of Research in South Africa (CAPRISA).

"Containing XDR-TB and selected MDR-TB will require an interdisciplinary approach and the synergistic co-operation of all organs of the state, including, in particular, the judiciary, as well as various government departments. Moreover, the government should urgently consider devising strategies to control the disease amongst particularly high risk groups such as prisoners and migrant labourers, which might necessitate the involvement of prisoner advocacy groups and neighbouring countries, respectively."

Says JCB associate and co-author Jerome Singh of CAPRISA: "If WHO is sincere in calling for the XDR-TB outbreak in South Africa to be treated in the same light as SARS and bird flu, then global efforts to develop rapid diagnostic tests and novel treatment regimens must be stepped up. Poor countries need equipment to address these challenges – not just to diagnose and monitor the disease at hospitals but potentially at border posts and airports.

"The experience of Canada and other countries affected by SARS, including the way ethical and legal issues related to control measures were handled, could prove valuable in dealing with South Africa's XDR-TB outbreak." – (EurekAlert!)

Source: PLoS Medicine

January 2008

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