omegainvest.co.za — 11/24/2007
SCIENCE AND DENIAL: WE'VE BEEN THERE BEFORE
Virginia van der Vliet
Haven't we been down this road before - telling the world's top scientists that we know more about a disease than they do?
On Friday, 9 November, contradicting the opinion of tuberculosis experts gathering for a conference in Cape Town, who believe the drug resistant varieties of TB now proliferating in South Africa, are a sign of failure to treat TB successfully in patients the first time round, our Minister of Health told a press briefing that the scientists were "with respect, ill-informed". Those scientists and researchers who suggested programmes were failing were unable "to differentiate between fiction and fact" (Di Caelersin The Independent on Saturday, 10 November 2007).
Hopefully for SA, this opinion was just the chronic contrarianism of Dr Manto Tshabalala-Msimang at work rather than the view of her health department generally. In a country racked by one of the world's worst TB caseloads, travelling in tandem with a huge HIV/AIDS epidemic, we cannot afford yet another round of denial. The 38th Union World Conference on Lung Health (8-12 November 2007) took place in Cape Town, attended by about 3000 TB and HIV/AIDS researchers,government ministers, health officials, activists, and people living with these diseases from over 100 countries.
Presentations at the Cape Town conference, and in associated satellite gatherings, suggested a new urgency in TB research, spurred on by the challenge of co-infection with HIV, and the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) TB strains. (See AIDSAlert18 October 2006 for background.)
South Africa was chosen as the venue in part to highlight the growing threat of drug resistant TB forms in those countries also affected by HIV.
5 MILLION SOUTH AFRICANS WITH HIV
With over 5 million South Africans infected with HIV, and perhaps half the population having been exposed to TB and carrying latent infection, held in check by functioning immune systems, the scope for TB disease when the immune system collapses under the onslaught of HIV is enormous. Already, as Nils Billo, of the International Union Against Tuberculosis and Lung Disease, and one of the conference organisers noted, one third of the world's 40 million people with HIV also have TB; in South Africa, 60% are infected with both diseases. The death rate is five times higher for those co-infected than for those with TB alone.
NEW PLAN FOR TB IN S.A.
The New National Strategic Plan for TB for SA 2007-2011 was unveiled the day before the conference. In a statement issued on 7 November, the health department said: "The plan acknowledges the close connection between TB and HIV and AIDS and the challenges of managing cases of co-infection. It provides for appropriate interventions to deal with HIV and TB co-infection".
That will be fiendishly difficult. Quite apart from medical challenges which remain unresolved for each infection in its own right, the combination, especially in the face of rising levels of drug-resistant TB, presents novel problems at every level, from diagnosis to treatment. According to World Health Organisation (WHO) statistics, 90% of people living with HIV/AIDS in Africa die within months of contracting TB.
Yet TB, apart from it in its drug-resistant forms, is curable, even in people with HIV. The obvious response would seem to be to treat the two together. Billo, for instance, says those found to be infected with one should be tested for the other, yet this "has not yet been implemented programmatically in most of the countries".
Barbed wire around HIV/AIDS
Practical though this may sound, at least in SA, it runs up immediately against the barbed wire that surrounds HIV/AIDS. As Thami Mseleku, director general of South Africa's Department of Health told Inter Press Service November 8, 2007) the stigma around HIV/AIDS meant "people are reluctant to get tested for TB because they do not want to be associated with HIV/AIDS".
Treating the two together meant: "it could be interpreted as if HIV and TB were inseparable, but if you have TB you also have HIV. We think this could discourage people from testing for TB".
A more fundamental problem is the turf wars fought between HIV/AIDS and TB programmes, a territorial jealousy that was claiming thousands of lives world-wide
as the programmes failed to collaborate. Paula Fujiwara, of the International Union Against Tuberculosis and Lung Disease, commented:
"In the activities with TB patients in getting access to HIV care, when (HIV programmes) found that we could actually do something, they started getting scared as if we were taking over their territory". Given that the lives this petty wrangling puts at risk, Fujiwara is right to describe it as "scandalous", but it stems in part from TB's long neglect. As she says: "HIV has always been the big kid on the block, with TB being the little brother. HIV programmes and organisations seem to be afraid that TB takes away attention and finding".
Foolish
That would be a foolish attitude. If we are to deal with HIV/AIDS and its depredations, TB surely is the place to start, and HIV programmes should be pushing for this. According to Alasdair Reid, HIV/TB advisor to UNAIDS, in 2005 only 7% of HIV patients worldwide were tested for TB.
SA's new strategic plan, says Mseleku, will aim at "functional integration" of TB and HIV activities in health facilities." The focus will be to increase HIV testing uptake by TB patients, CD4 testing and assessment of all co-infected patients, provision of treatment and prevention therapy for other opportunistic infections and antiretroviral treatment for all infected patients".
The plan also aims for a 70% case detection rate, a cure rate of 85% and treatment success of more than 85%. Given that the cure rate was 57.6% and treatment completion 70.8% in 2006, there is a long way to go. Failure to meet these goals will surely mean an ever faster growth of drug resistant TB forms, with their deadly knock-on effect on HIV/AIDS mortality.
Whatever our Minister of Health's opinions, it is clear that South Africa has a growing problem with MDR TB (resistant to isoniazid and rifampicin) and XDR TB (resistant to both these, to any fluoroquinolone, and to second line drugs, making it virtually impossible to put together the potent "drug cocktail" necessary to ensure treatment does not simply create even more resistant forms). While XDR TB had been reported in 37 countries by May 2007, the largest cluster was the 53 cases reported in the Tugela Ferry, KwaZulu-Natal; in all, that province has reported more than 200 cases. (Health Department statistics record more than 390 cases so far this year in South Africa; other reports say more than 480).
'Ill-informed'?
Were the scientists who blamed the rise of these resistant TB forms on the failure of existing programmes "ill-informed" as the minister suggested? An article in the
latest edition of the journal Clinical Infectious Diseases (1 December 2007) offers strong evidence to the contrary. Using TB bacteria isolates collected from 1994 to 2002 in KwaZulu Natal, Manormoney Pillay and A. Willem Sturm, of the Medical Microbiology Department at the University of KwaZulu Natal, demonstrated that resistance to a growing number of drugs began in one strain (FIS/LAM4/KZN) as early as 1994, with the first XDR isolate discovered in 2001.
The authors conclude as follows: "Drug resistance to as many as seven drugs developed in [this strain] in slightly more than a decade." Significantly, it coincided with the introduction of more vigorous directly-observed-therapy [DOTS} in the absence of susceptibility testing or drug resistance surveillance. The authors believe that because patients were not tested for drug resistance at the beginning of treatment cycles, those who were already resistant to some of the drugs in the standard 'cocktail', went on to develop resistance to remaining drugs and then to similarly untested second-drug regimes as well.Resistant forms were passed on in hospital settings with inadequate infection control, and in the patients' communities. The growing pool of HIV-infected people, susceptible to TB infection, exacerbated the situation, which in part accounts for the heaviest HIV load and the heaviest XDR-TB load coinciding in KwaZulu-Natal.
'Poor adherence to TB treatment'
A statement on XDR-TB from the Department of Health in September 2006, acknowledged the problem was "caused by poor adherence to TB treatment among other things". Combined with a 'one-size-fits-all' initial treatment regime, without first assessing whether a patient has a strain already resistant to some of the drugs, it is a recipe for ever more lethal variants. Branding scientists who warn of this as 'ill-informed' will do nothing to solve the problem. Worldwide, 96% of TB still responds to the basic drugs when these are properly used. The nightmare would be if MDR- and XDR-TB were to overtake ordinary TB because we failed to heed warnings.
The conference , however, did suggest some hopeful developments. Doctors currently are armed with a vaccine that is 80 years old,drugs that have been around for 40 years, and antiquated, diagnostic procedures that not only can take weeks to produce results, but, in the case of those with HIV, are not reliable. The emergence of drug-resistant strains has made new approaches and treatments a matter of urgency.
The current 4-drug standard TB regime requires patients to take drugs for 6-8 months. However, when they start to feel better after a few weeks, many failed to adhere to the full course, leading to relapse and drug resistance. Two new drugs for inclusion in existing cocktails are being tested and may reduce treatment length to around 4 months.
Moxifloxacin
One, moxifloxacin, is already being used for other respiratory conditions, and some doctors are using it off-label to treat MDR-TB. It is entering Phase III clinical trials with TB patients. The other, PA-824, is undergoing Phase IIa Early Bacterial Activity study in TB patients enrolled at two sites in Cape Town; it will be evaluated for short term potency given as a single drug. New methods of drug delivery, e.g. nano-based systems, could mean anti-TB drugs could be used in reduced doses, perhaps once a week rather than the current daily doses.
Providing prophylactic treatment with isoniazid, the TB drug, to HIV patients was favoured by some, but others felt that this would lead to further drug resistance, and possibly mask the symptoms of TB. Professor Greg Husseyof the Southern African TB Vaccine Institute also offered some hope that the new vaccine currently being tested at their vaccine site in Worcester would not only be effective but, unlike the current vaccine, safe for people with HIV.
Better diagnostic methods also are critical.While HIV can
be diagnosed in minutes, standard TB testing invented 120 years ago fails to detect TB in 40 to 80% of those co-infected with HIV. More sophisticated sputum tests need laboratories and may take weeks to process. Chest x-rays in HIV patients are also less useful because they tend to have TB "disseminated" through the body rather than presenting as the typical lung disease.
Raft of new measures
Currently, a raft of new diagnostic measures from breath and urine analysis to a desktop machine that could read TB DNAand tell which drugs the strain is sensitive to, are all under development, but improvements can't come soon enough for those battling the disease.
As MDR- and XDR-TB grow, there is also growing debate on whether isolating infected patients in hospitals and clinics is ethical, or indeed practicable. At the Brooklyn Chest Hospital in Cape Town, for instance, a section of the facility has been fenced off under guard to house XDR-TB patients, after some patients absconded. Cut off in the dreary buildings for at least 6 months, perhaps 2 years, of often unpleasant treatment, it is easy to see why it is hard to persuade them to stay away from jobs and family in a place where many die.
Increasingly, the call is for people to be treated more effectively - but in their communities. As numbers rise, the question will anyway become academic, as there are just not enough beds to isolate the people. Better education and infection control, better drugs, earlier diagnosis and better support to encourage people to adhere to treatment would be a more acceptable solution to many.