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MORE EVIDENCE SUPPORTS ISONIAZID FOR TB PREVENTION IN PEOPLE WITH HIV
19 February 2010, Keith Alcorn

Two new studies presented this week at the 17^th Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco add weight to a growing expert consensus that isoniazid preventive therapy (IPT) should be provided to people with HIV in order to reduce the risk of developing active tuberculosis (TB).

Although, as TB expert Richard Chaisson pointed out at an expert discussion on IPT prior to the conference, IPT is proven to reduce the incidence of TB in people with HIV, there are still many unanswered questions, including its effect on overall mortality, the optimum TB preventive regimen, and the effect of IPT on secondary transmission of TB in the household and among close contacts.

The studies presented this week offer new insights about the additive benefit of IPT in people taking antiretroviral drugs, and provide evidence about a potential alternative to the use of isoniazid alone.

IPT in people taking antiretroviral therapy

Dr Craig Innes of the Aurum Institute in South Africa presented results of an observational analysis of patients receiving IPT through a workplace programme in South Africa.

The study looked at the effect of IPT on mortality in a population of South African adults, predominantly male (93%), who started antiretroviral therapy (ART) between January 2004 and December 2007, comparing outcomes in those who received IPT and those who did not.

Individuals receiving health care through the Aurum programme were eligible for ART if they had a CD4 count below 250 cells/mm3 without symptoms, if they had WHO (World Health Organisation) stage 4 disease, or if they had WHO stage 3 disease with a CD4 count below 350 cells/mm3.

Isoniazid preventive therapy was recommended if a patient had no history of TB in the past three years and if current TB could be excluded, although prescription was less than universal due to fears of isoniazid resistance among some physicians if they could not exclude active TB.

The study population comprised 3258 patients who started ART, of whom 910 received IPT. The only significant differences between those who received IPT and those who did not were history of previous TB ever (2.5% vs 8.9%), WHO stage 3 or 4 disease (30% vs 50%) and haemoglobin (13.4 vs 12.9) (all differences p < 0.001).

The study showed a significantly lower mortality rate for those who received IPT: across a number of analyses, which adjusted for potential confounding factors, the risk of death was approximately halved if an individual received IPT in addition to antiretroviral therapy.

In the first analysis, which included individuals with a previous history of TB and which adjusted for age, WHO disease stage, CD4 count, haemoglobin count and year of ART commencement, the risk of death was 53% lower in those who received IPT (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.30-0.72, p<0.001).

Some patients received IPT despite guidelines indicating that they should not, and this might have diluted the effect of IPT that would be observed if the guidelines had been strictly observed. In a sensitivity analysis which excluded those with a prior history of TB, the risk of death was 54% lower, indicating no substantive effect of prior TB (HR 0.46).

Another way of looking at the question of whether, if used strictly according to guidelines, the results might turn out differently, is to exclude all patients who had symptoms associated with TB at ART commencement, no matter when they received IPT. This would tend to cast a wider net for those patients who had active TB when exposed to isoniazid, and who might therefore have shown less benefit.

In this analysis, the risk of death was 53% lower (HR 0.47, 95% CI 0.28-0.79, p = 0.05).

Only when participants were stratified according to whether they commenced IPT within three months of starting ART, or delayed IPT for more than three months, did a marginal difference emerge. Those who started IPT less than three months after ART had a 61% reduction in the risk of death, whereas those who started IPT more than three months after ART had a 46% reduction in the risk of death when compared to those who did not receive IPT.

The chief limitations of the study are its observational nature – there could have been biases in who received IPT, although the analyses controlled for known confounding factors – and the fact that causes of death were not captured in this study. It is not clear whether the effect of IPT on mortality is solely driven by a reduction in TB-related deaths, or whether protecting IPT has a wider effect.

The interaction between ART and tuberculin skin test status

The Aurum Institute study did not control for tuberculin skin test (TST) status, a test that can positively confirm that someone is latently infected with TB. In the BOTUSA IPT study, (which compared 6 and 26 months of IPT in people with HIV), previously presented at the World Lung Health conference in Cancun in December 2009, and presented again this week at CROI, TST-positive patients who received antiretroviral therapy alongside six months of isoniazid experienced a 50% reduction in the risk of developing active TB during the three-year follow-up period when compared to people who received six months of isoniazid alone.

In TST-positive people who received 36 months of isoniazid however, the additional benefit of antiretroviral therapy was marginal, reducing the likelihood of developing active TB by just 4% in comparison to the no-ART group.

In TST-negative people – those who either had no prior exposure to TB, or else hadn’t enough immune function to respond to TB antigens in the skin test – antiretroviral therapy halved the risk of developing active TB in those who received six months of isoniazid, and reduced the risk of active TB by around 45% in those who received 36 months of isoniazid when compared to isoniazid alone.

A new regimen for TB prevention?

A randomised study conducted by the Tuberculosis Research Center in Chennai, India, showed that a six-month course of isonaziad and ethambutol, another antibiotic used in TB treatment, was just as effective as a 36-month course of isoniazid in people with HIV, most of whom were not receiving antiretroviral therapy.

The Indian study was designed to test whether an alternative regimen to isoniazid alone was safe and effective in a setting where 15 to 20% of patients have isoniazid-resistant TB at diagnosis, and where rifampicin, another TB drug tested as a preventive measure, is strictly reserved for treatment of active TB in order to limit the development of resistance to the drug. The study was also deisgned to compare the feasibility of a short-course regimen of six months against a longer-term regimen that might be expected to offer greater protection against exposure to TB during the study period itself, especially in immunosuppressed people who may be at higher risk of rapid TB progression.

The study was conducted by the Tuberculosis Research Center in Chennai, and began recruiting patients for the three-year study between 2001 and 2005.

All participants had TB confirmed by sputum culture wherever possible, and the study excluded any person with HIV who had a previous history of TB.

During the study patients received a clinical review every three months to check for symptoms of TB and other health problems, and underwent chest X-ray every six months.

Participants were randomised to receive a daily regimen of isoniazid 300mg and ethambutol 800mg for six months, or 36 months of isoniazid alone, and all patients with a CD4 count below 250 cells/mm3 received cotrimoxazole. Antiretroviral therapy became available in the public sector in 2004 to patients with WHO stage 4 disease, or WHO stage 3 disease and a CD4 count below 200 cells/mm3).

The study randomised 683 patients, and 37 cases of TB occurred during the three years of follow-up, 16 of which were bacteriologically confirmed. The incidence of TB was not significantly different in the two arms of the study (2.4 cases per 100 person years in the ethambutol arm, 1.6 cases per 100 person years in the isoniazid arm), and death rates were also similar.

The low rates of TB in the study compared to the historical incidence previously measured in the Chennai cohort (6.9 cases per 100 person years) may in part be attributable to the screening by culture at baseline. Screening picked up 30 cases of active but asymptomatic TB that otherwise would have developed into incident TB cases during the trial.

In both arms, most cases of TB – and most deaths – occurred during the first 12 to 18 months of follow-up, but only three deaths were a result of TB.

Regardless of the regimen received, individuals with a baseline CD4 count had a fourfold higher incidence of TB, while TST-positive individuals (TST >5mm) had a 40% higher risk of developing TB.

Among the TB cases that were bacteriologically confirmed, six had isoniazid resistance (five in the ethambutol arm and one in the isoniazid arm).

There was no difference in the development of adverse events between the two arms: three severe events occurred in the ethambutol arm and two in the isoniazid arm, and overall the regimens were very well-tolerated. Rates of adherence were also very high, with around 93% in each arm judged to be more than 80% adherent by unannounced home visit pill counts.

Dr Swaminathan commented that the high adherence rates, the high study retention and the low rates of TB in the study may have been due to the high level of preparation and screening that patients received before entering the study. Patients in the trial received free HIV care, and for many, it may have been their first experience within the Indian health system of good-quality care and support, leading to a high level of patient loyalty to the programme, and a reluctance to be referred on for care at other centres when the trial was over.

Aurum acknowledges aidsmap news as the source of this article

AMCLI - ASSOCIAZIONE DEI MICROBIOLOGI CLINICI ITALIANI
17 February 2010

LINDA-GAIL BEKKER: CONFRONTING THE TB/HIV CO-INFECTION EPIDEMIC
13 February 2010, Kelly Morris

THIBELA TB - THE PATH TOWARDS RESULTS
February 2010

After nearly 5 years, the Thibela TB intervention stage of the project is drawing to a close. Starting in early 2005 with the Tau Tona mine shaft near Carletonville, the Thibela project has worked its way across 15 clusters to end with the Bambanani Mine near Welkom, in the Free State Province.

The last official study participant will take his last dose of Isoniazid (INH) in the intervention at Bambanani on the 28th of February 2010. "This is a major milestone for Thibela TB", said Dr. Dave Clark, Aurum's Deputy CEO. "The team has enrolled over 30,000 participants into the program to take preventive INH, a significant achievement in the fight against TB in our country."

What has been quite remarkable at the final intervention cluster is the astounding number of volunteers for Thibela TB - over 95% of the workforce at Bambanani - evidence of a community mobilization phenomenon unheard of in clinical trials before. "I am so proud of my team in achieving this together with the people of Bambanani", said Flora Popane, Regional Project Manager for the Free State. Towards the end of this last cluster, >75% of volunteers were retained on the study, further evidence of a job well done.

Elsewhere in the study, the switch to the measurement periods of the protocol have gone well, with two shafts completing the final culture prevalence survey and several others underway or in final stage planning for primary and secondary end point measurement.

Another key component of the main part of the study has been the Electronic Data Capture system. This system has been steadily gathering enormous amounts of data from all the participants at the various sites. The main study database will also capture its last live details on the 28th February. Trisha Crawford, Thibela's Senior Data Manager, and her team have set the very ambitious task of getting to database lock by the end of March 2010 and right now, they are on track to achieving this goal. A locked database is key for investigators to begin the challenging, but pivotal task, of analyzing the data goldmine that has come from all the work so far.

"We are finally at the beginning of the end in this audacious study. I too am very proud of all this remarkable team has achieved across the various regions. We are also grateful to the thousands of mineworkers who have risen up to fight TB. We now have to finish what we have so painstakingly put together over the last few years. But I know I can count on my team to see this through to the final analysis", adds Gavin Churchyard, Thibela TB principal investigator. The study is set to publish final results early in 2012, but hopefully much interim information on lessons learned and other research questions will come from the data in the next two years.

Aurum acknowledges CREATE as the source of this newsletter

THE JOURNAL OF INFECTIOUS DISEASES
8 February 2010, Richard E Chaisson and Gavin J Churchyard

The catastrophic collision of tuberculosis and human immunodeficiency virus (HIV) has yielded an extraordinary burden of suffering and death at both the individual and population levels. The convergence of these twin epidemics resulted in 1.8 million deaths due to tuberculosis disease in 2007, 24% of which were among people with HIV infection, whereas among the 2 million deaths of people with AIDS, 22% were caused by tuberculosis infection. Tuberculosis is thus the leading cause of death in people with HIV/AIDS, and HIV infection contributes to a substantial proportion of tuberculosis deaths. Interventions to control tuberculosis and HIV therefore need to take into account the unique and deadly synergy between these 2 infections.

There are many challenges that clinicians and public health programs must confront when trying to manage and prevent HIV-related tuberculosis, including prompt diagnosis, effective treatment, and successful prevention strategies. One problem that receives little attention is recurrence of tuberculosis following completion of treatment. Historically, patients properly treated with a 4-drug regimen have a very high treatment success rate and very low (2%–3%) incidence of recurrence. In HIV-infected patients, the risk of recurrent disease is higher, and previous work has demonstrated that this can be due to treatment failure, emergence of drug resistance during therapy, or reinfection with a new strain of Mycobacterium tuberculosis. Recurrence of tuberculosis after treatment among both HIVinfected and HIV-uninfected individuals is not a trivial problem. On a patient level, recurrent tuberculosis requires another round of treatment with a regimen that, in many parts of the world, is more toxic, takes longer to complete, and may, ironically, amplify drug resistance. On a public health level, recurrent tuberculosis may account for 10%–30% of all cases within some weaker tuberculosis control programs, particularly those that do not use at least 6 months of rifampin treatment, and contributes to ongoing transmission of infection to contacts of cases in the home, community, and health facilities, largely from HIV-uninfected patients.

In this issue of the Journal are 2 articles that examine the epidemiological profile of recurrent tuberculosis in populations with a high prevalence of HIV infection. Narayanan et al from India report on 2 cohorts of patients with tuberculosis who were followed up for recurrence and then underwent DNA typing of initial and recurrence M. tuberculosis isolates to distinguish exogenous reinfection from relapse. Among HIV-infected patients whose initial episode of tuberculosis was deemed cured, 14% experienced a recurrence of tuberculosis, of which just over half of infecting strains typed. Among these, 22 (88%) of 25 cases were due to reinfection with a different strain of M. tuberculosis. In a sample of HIV-uninfected patients with recurrent tuberculosis (rates of recurrence are not reported for these patients), only 9% of second episodes were due to reinfection, with the remainder being relapses of the initial infection. One possible explanation for the difference in levels of relapse among HIVuninfected patients is that many were treated with nonstandard, abbreviated regimens that included ofloxacin in a clinical trial that failed to include an appropriate control regimen; these relapsesmay simply have been the result of inadequate therapy. Importantly, one-fourth of HIV-related recurrences were with multidrug-resistant strains of M. tuberculosis, with a smaller number of resistant recurrences found among HIV-uninfected patients.

Although rates of recurrent tuberculosis cannot be compared by HIV status in this report, it is clear that recurrent disease is more common than would be expected among HIV-infected patients with tuber culosis in this Indian setting, and that almost all recurrences are due to exogenous reinfection. Narayanan et al used rigorous typing methods, with 3 independent techniques, and took great care to exclude the possibility of laboratory contamination. Although the study breaks no new ground with respect to the existence of exogenous M. tuberculosis reinfection causing disease, particularly in HIVinfected patients, it is nonetheless noteworthy for documenting the potential frequency of this phenomenon in developing countries, where recurrences are generally attributed to treatment failure due to either noncompliance or drug resistance. In this study, all of the multidrug-resistant recurrences among HIV-infected patients were reinfections, whereas both multidrug-resistant cases among HIV-uninfected patients were due to acquired or amplified resistance during treatment. These data confirmwhat has been inferred from outbreaks of multidrug and extensively drug-resistant tuberculosis among people with HIV infection in other settings: that much drug-resistant tuberculosis in HIV-infected patients is transmitted from others, rather than acquired by ineffective or insufficient therapy.

A second article in this issue of the Journal, by Glynn et al, reports on rates of recurrent tuberculosis in mine workers in South Africa. These authors followed 2 cohorts of tuberculosis patients—one with HIV infection and one without, whose illness was initially diagnosed and who underwent HIV testing in the 1990s—and determined the rates of recurrent disease that occurred at least 2 years following cure of the initial episode. The authors assumed that these late recurrences were due to reinfection rather than relapse, on the basis of previous observations, supported by the data from Narayanan et al, that almost all relapses occur in the first 2 years following treatment. Glynn et al found recurrence rates of 24.4 cases per 100 person-years at risk for initially HIV-infected miners following their index episode and 4.7 cases per 100 person-years at risk among those who were HIV-negative at the index episode. Strikingly, rates of recurrent tuberculosis were dramatically higher than incident tuberculosis rates among both HIV-infected and HIVuninfected miners. These results are consistent with those from a study of another high tuberculosis transmission setting where reinfection rates following treatment exceeded rates of incident disease.

The work of Glynn et al requires more assumptions about the source of recurrence and has less direct evidence than the study by Narayanan et al. No DNA typing was performed to confirm that recurrences were actually reinfections and not relapses; repeat HIV testing was not performed among the initially HIV-seronegative men, despite known high rates of HIV acquisition during the time of the study; and considerable attrition from the cohorts over time occurred, which could affect incidence estimates. Despite these limitations, the study demonstrates convincingly that recurrent tuberculosis is exceedingly common among miners in South Africa and is seen in both HIVinfected and HIV-uninfected men. Work by the same group and others previously documented high rates of reinfection in this setting, so it is quite credible that a large proportion of these recurrent cases were, indeed, new infections.

What can be done to reduce the frequency of recurrent tuberculosis, whether due to relapse or reinfection, in patients with and without HIV infection? In fact, quite a lot can be done, and the evidence base for a number of interventions is robust. First, ensuring completion of appropriate therapy for all patients with tuberculosis is extremely important. Although rates of treatment completion worldwide are now close to 85% for patients cared for in directly observed treatment shortcourse programs, the real completion rate when all patients are accounted for is substantially lower, particularly in Africa. Failure to complete tuberculosis treatment is associated with very high rates of recurrent disease, especially in HIV-infected patients. In addition, although 5.5% of all new tuberculosis cases worldwide have multidrug or extensively drugresistant disease, only a tiny fraction of these are actually detected and receive appropriate treatment. Improving case detection, easier access to care, improving cure rates with community-based interventions, developing new effective shorter regimens, and conducting baseline drug susceptibility testing will all reduce relapses and the evolution of drug resistance. Earlier detection of multidrugresistant tuberculosis, through use of rapid rifampin resistance assays such as line probe assays, and earlier effective treatment should also reduce recurrence due to reinfection with multidrug-resistant tuberculosis in HIV-infected patients. Because reinfection is common in HIVinfected patients in high burden settings, secondary preventive therapywithisoniazid is another strategy for reducing recurrences. One small controlled trial and one observational study have documented the effectiveness of secondary isoniazid for reducing recurrences in patients with HIV-related tuberculosis. In a nonendemic setting, the risk of recurrence among HIVinfected persons was reduced with longer duration of tuberculosis treatment.

Low CD4 cell counts are a major predictor of recurrent tuberculosis due to both relapse and reinfection in HIV-infected patients, and treatment with antiretroviral therapy decreases the likelihood of recurrence by at least 50%. Widespread use of antiretroviral therapy for all HIV-infected patients with tuberculosis is now supported by evidence from a clinical trial and from observational studies. Scaling up antiretrovirals for patients with tuberculosis will also reduce recurrent disease, as suggested by a study in Rio de Janeiro, Brazil.

A critically needed intervention to reduce reinfection tuberculosis is the implementation of infection control measures in clinical and community settings. Because patients with tuberculosis and with HIV infection congregate in the same clinic waiting rooms, offices, laboratories, and hospital wards in much of the world, ongoing transmission is a significant cause of new disease, especially drug-resistant disease, as Narayanan et al demonstrate. HIV and antiretroviral clinics in resource-poor settings have unwittingly become cauldrons of tuberculosis transmission, seriously undermining the impact of HIV therapies. The first step in reducing institutional and community transmission of M. tuberculosis infection is the detection of prevalent, undiagnosed cases and the initiation of appropriate therapy. Administrative measures to separate infectious patients from others, engineering and air flow management ranging from opening windows and doors to more sophisticated air handling techniques, and the use of personal protective equipment in more exposure-intense situations are all approaches that need to be ramped up worldwide, given the clear evidence of nosocomial transmission of tuberculosis infection among those with HIV infection.

Finally, what about vaccination as a strategy for preventing recurrent tuberculosis infections? Both Narayanan et al and Glynn et al suggest that development of a therapeutic vaccine or immunotherapy as an adjunct treatment for tuberculosis might help reduce relapse and reinfection episodes in those with exquisite susceptibility to the disease. Although this is an attractive concept in theory, the feasibility of this approach is currently quite limited. What is eminently sensible, however, is a primary vaccine for tuberculosis that prevents the development of disease in the first place. The current tuberculosis vaccine, BCG, appears to protect infants from severe forms of disease but does not prevent pulmonary tuberculosis in adults. We know from previous experience that a preventive vaccine can work, but in the case of BCG the protective effects of the vaccine most likely have become attenuated because of continuing evolution during laboratory passage. Thus, prospects for new pre- and postexposure preventive vaccines are bright. The potential for an effective primary vaccine to control initial and thus recurrent tuberculosis, especially among HIV-infected persons, is enormous. After all, the best way to ensure that patients avoid a second episode of tuberculosis is to make certain that the first episode never occurs.

Aurum acknowledges Chicago Journals as the source of this article

"WHAT WILL IT TAKE TO CONTROL TB?"
1 February 2010, Richard Chaisson, MD

DR PAUL DAVIS ON SAFM, HEALTH UPDATE
14 January 2010

PROVIDER-INITIATED SYMPTOM SCREENING FOR TUBERCULOSIS IN ZIMBABWE: DIAGNOSTIC VALUE AND THE EFFECT OF HIV STATUS
1 January 2010

SOUTH AFRICA: NEW TECHNOLOGY COULD REVOLUTIONISE TB DIAGNOSIS
31 December 2009

A new technology being pioneered in South Africa may make screening for tuberculosis (TB) faster, cheaper and more reliable – and it’s all based on technology found on a typical trip through airport security.

The new computer diagnostic system known as TBDx takes digital pictures of sputum samples and searches them for TB’s structural “fingerprint.” Some airport scanners work in much the same way, searching luggage for the structural fingerprints of plastic explosives, for example.

The system is being pioneered by health research organisation, the Aurum Institute in partnership with South Africa’s National Health Laboratory Services (NHLS) and imaging specialists, Guardian Technologies International, and is the first in the world to pair advanced imaging technology with a digital microscope.

A prototype is already in the works and once fully automated will be able to run independently 24-hours a day. It has already proven 10 percent more effective at identifying TB bacilli than conventional TB tests which rely on laboratory technicians to manually load slides and look for the bacilli under a microscope.

With its combination of sensitive diagnostic technology and labour-saving automation, TBDx could revolutionize TB testing in high burden countries like South Africa that have seen a resurgence of TB in the last decade on the back of the HIV/AIDS epidemic.

About 70 percent of South Africans diagnosed with TB are co-infected with HIV and, despite being curable, the disease is the country's leading natural cause of death and one of the main factors behind South Africa's declining life expectancy.

“The diagnosis of TB is fraught with difficulties,” Dr David Clark, Deputy CEO of the Aurum Institute told IRIN/PlusNews.

He noted that current methods of TB diagnosis continue to rely on technology developed by Robert Koch, the German physicist who discovered TB a century ago. “If we were going to fight a war today with equipment we used 100 years ago, we’d be mad,” he said.

Testing the possibilities

TBDx can be operated by personnel with no special skills, freeing up a scarce supply of lab technicians to do other important work. It may also greatly improve working conditions for lab technicians who currently spend hours hunched over microscopes searching for tiny TB bacilli.

“Out of 100 slides that come to you...maybe six percent will be positive," said Clark, describing work in a high-volume laboratory. “The rest of your day is spent searching for something that isn’t there. These are highly trained technicians that could be doing other things.”

The new technology does not entirely do away with the need for skilled technicians. It can be set to flag slides that are difficult to diagnose – a function that Clark described as a potentially valuable training tool.

South Africa’s NHLS is waiting for the new technology to be costed before making a decision about whether to adopt it nationally, but TBDx is likely to be more cost effective than the current labour-intensive method of TB testing which costs about US$3 per slide.

“We will have to do the operational research and cost-effectiveness studies, but it’s very promising,” said Gerrit Coetzee, head of the National TB Reference Laboratory of the NHLS. He added that TBDx’s potential to increase lab productivity, and improve and standardise diagnosis were among its main draws.

If the NHLS does choose to adopt the technology, a national rollout is still at least three years away, according to Coetzee. The system would most likely be piloted in high volume laboratories before being scaled-down for use at lower levels of the health system.

Aurum acknowledges PlusNews as the source of this article

IZINDABA - COLLABORATIVE PUSH TO ADDRESS TB CRISIS ON MINES
December 2009

After a century of failed tuberculosis control strategies on South Africa’s mines, and three major but ineffective enquiries and commissions, a government-led ‘TB in Mines Task Team’ is being set up to address the deepening HIV driven crisis.

This was revealed by Professor Gavin Churchyard, CEO of the Aurum Institute for Health Research, a not-for-profit public benefit organisation with roots in the mining industry. He was addressing the annual Investigators Meeting of the international Consortium to Respond Effectively to the AIDS/ TB Epidemic (CREATE) in Cape Town in mid-October.

Churchyard revealed that the HIV-fuelled TB epidemic, compounded by rising drug resistance, is now estimated at 3 500 per 100 000 mine workers, with 40% of all autopsies on men who die working on the mines revealing they had TB.

Migration from rural areas throughout southern Africa to Gauteng and surrounding industrial areas to work in the mining, building and other dominant sectors is a major driver of the rampant TB epidemic.

Dr Lindiwe Mvusi, Director of TB Control and Management in the national department of health and chairperson of the new ‘TB in Mines Task Team’, said because the pandemic embraced all South Africa’s neighbouring countries it demanded a regional, multistakeholder response.

A third delegate at the meeting, an ‘anxious and concerned’ Deputy Health Minister, Dr Molefi Sefularo, said national TB prevalence had increased nearly threefold in the past decade. South Africa was now among the 10 worst performing countries on TB control, and Statistics SA had found that for every 100 deaths in 2006, 13 were from TB, making it the leading cause of death.

Churchyard said less than 1% of all HIV-infected individuals in this country were accessing proven safe and effective isoniazid preventive TB therapy (IPT), a situation he calls ‘inexcusable’.

Aurum acknowledges Izindaba as the source of this article

SOUTH AFRICA: NEW TECHNOLOGY COULD REVOLUTIONISE TB DIAGNOSIS
31 December 2009

HOPE FROM AN OLD REMEDY
11 December 2009, Jacqui Pile

A new way of tackling tuberculosis (TB) in the gold mining industry could cut prevalence rates and the cost of the treatment, compensation and management of TB among SA's mineworkers.

SA's gold mining industry has the highest incidence of TB in the world, with 3%-6% of the industry's 120 000 workers developing the active disease each year. This compare s with a TB incidence of about 0,96% in the general population and negligible rates in developed nations.

TB is legally defined as an occupational disease. In terms of present legislation claimants can obtain compensation from government for pain and suffering, medical expenses and loss of earnings. However, mining companies pay for compensation through contributions to the compensations fund. A study in 1994 by the Chamber of Mines showed that the annual cost of preventing, treating and compensating TB and providing management for the disease across the mining industry was about R700m/year.

The Aurum Institute, a specialist research organisation that focuses on TB and HIV prevention and treatment, estimates that the disease now costs the industry more than R1,2bn/year.

"Over the past two decades, the mining industry has implemented world-leading TB control programmes - but in the era of HIV, these are having little impact on controlling the disease," says Dave Clark, deputy CEO of the Aurum Institute.

The growth of HIV and TB are closely linked (see graph). In the context of reduced immunity linked to the HIV epidemic, TB has become the No 1 cause of death, according to Stats SA. It killed 13 of every 100 people who died in 2006.

The World Health Organisation estimates that almost 1% (461 000) of South Africans develop TB annually, and 40% of HIV-positive patients die of TB.

"Even with the best TB control programmes in force, people living with HIV/Aids are at very high risk of developing active TB over time," says Clark.

It's worse in the mining industry, where a history of migrant labour and the housing of workers in hostels has helped spread the disease. Silicosis, a lung disease caused by workers inhaling dust underground, also creates a "scaffold" in the lungs on which TB bacteria can thrive and multiply. "Our mines are dealing with a triple epidemic of HIV, TB and silicosis," says Clark.

But a study done in the 1950s among Alaskan Eskimos offers some hope. It involved administering daily doses of the TB drug Isoniazid as a prophylaxis to prevent TB. After taking the drug for a number of months, TB infection rates in the Eskimo population were radically reduced, by up to 60%. And the protective effect of Isoniazid prophylaxis was shown to persist for more than a year. Now the Aurum Institute is replicating the study in SA.

After securing funding in 2004 of US$27m over seven years from the Consortium to Respond Effectively to the Aids & TB Epidemic, the Aurum Institute began its Thibela TB programme. It used Isoniazid as a prophylaxis at some of SA's biggest gold mines, including those of AngloGold Ashanti, Gold Fields and Harmony. More than 30 000 workers have received the drug over the past four years.

The project had challenges, but it has achieved a volunteer participation rate of 95%. "That's basically unheard of, and represents a phenomenon that could possibly be harnessed to address the prevention of other diseases in communities, too," says Clark.

If the programme is successful, it could help prevent the disease in areas with high TB rates until a vaccine is developed. TB vaccines are being tested, but most are years away from being ready for mass deployment.

"Even if there is a drop of 30% in TB incidence, it would have a huge impact on the mining industry - not only for the bottom line, but in terms of workers' lives too," says Clark.

Aurum acknowledges Financial Mail as the source of this article

TUBERCULOSIS AND HIV WITHIN PRISONS SKYROCKETING, A PUBLIC HEALTH THREAT
7 December 2009, Mara Kardas-Nelson

Overcrowding, low access to health care, lack of political will and the prominence of high-risk populations among prisoners all contribute to a "perfect storm" for HIV and TB infection among prison populations worldwide, researchers announced at the 40th Union World Conference on Lung Health this Saturday in Cancun, Mexico.

Dr Fabienne Hariga of the UN Office on Drugs and Crime and UNAIDS’ Dr Alasdair Reid both highlighted dismal health statistics for those behind bars. According to Hariga, up to 65% of some prison populations are infected with HIV.

Adding to this, says Reid, TB rates in prisons are up to fifty times higher than in the general population. Increased rates are found in prisoners who have served longer sentences, tying TB acquisition with prison time. Prisoners are also more likely to die from TB and/or default from treatment than non-incarcerated populations.

Dr Hariga insists that such poor indicators not only pose a threat to prisoners’ health, but the health of the general public as well. Given the high rate of return to society, prisoners’ HIV and TB are easily spread to communities.

Prison staff are also affected by the high incidence of HIV and TB. Dr Salome Charalambous of South Africa, speaking about HIV and TB prison projects sponsored by the country’s Department of Corrections and the Aurum Institute, notes that many prison staff supported greater testing, treatment and infection control because of concerns over their own health.

"Prisons are not isolated from the community," says Hariga. "You have people working in [them], you have prisoners moving in and out very often."

But despite dismal health statistics, effective penal reform that includes increasing health services for prisoners is far from a reality. Dr Hariga claims that "there is a lack of interest" among policy makers, resulting in a shortage of funds to address health problems for prisoners. "In many places in the world, there is no health-in-prison programme," she states.

The difficult nature of prison populations also contributes to the low number of programmes. Dr Charalambous cited logistical concerns that hampered the testing and treatment of prisoners in the South Africa study, who are often moved from prison to prison or released, interrupting HIV and TB follow-up and treatment.

In large part due to this mobility, 21% of patients initiated onto ART within one of the study’s programmes were lost. In another prison, seven of the 22 prisoners who were called for follow-up had been transferred prior to undergoing review.

In order to combat low programme retention, the ongoing study only enrolls prisoners with a sentence of four months or longer. Researchers also "tag" those enrolled, alerting prison authorities not to transfer them unless essential for trial purposes.

Additionally, using symptom-based diagnosis to identify possible TB patients is difficult among prison populations. In the South Africa study, 46% of patients demonstrated any symptom for TB, while 37% displayed a trio of symptoms.

However, Charalambous surmises that some of these can be attributed to the prison environment in general rather than TB infection specifically, and therefore states, "symptom screening might not be as effective in this environment."

Despite these challenges, Dr Charalambous is hopeful that prisoners present a captive audience for TB and HIV testing and treatment. Her study suggests that prisoners may be responsive to such programmes: in one site, 98% of prisoners agreed to join. Dr Reid agrees, claiming that prisons offer unique opportunities for treating marginalised populations.

In order to encourage more prison health programmes, Dr Reid calls for further research that assesses the rate of acquiring HIV and TB behind prison bars: while data that demonstrates the high rate of both infections among prison populations is readily available, numbers that point to prisons as conducive to their spread is harder to find.

In order to fuel political will, Reid condones the "advocacy, naming and shaming" of countries who boost some of the worst indicators for prisons with regards to overcrowding, HIV and TB, and human rights violations. "Global reporting is essential to get countries to take this seriously," he says.

References

Charalambous, S. TB-HIV in prisons and the community response: the case of South Africa. Presented at the 40th Union World Conference on Lung Health, 2009.
Hariga, F. Access to HIV and TB services in prison setting, injecting drug users in prisons: myths and realities. Presented at the 40th Union World Conference on Lung Health, 2009.
Reid, A. Guidelines and advocacy: HIV/TB, prisons, IDU and poverty. Presented at the 40th Union World Conference on Lung Health, 2009.

Aurum acknowledges NAM as the source of this article

TREATING OURSELVES OUT OF THE HIV/AIDS CRISIS - HYPOTHETICALLY
1 December 2009, Annabel Jacobs

Mail & Guardian Online - Johannesburg, South Africa
The scenario: all South Africans are tested for HIV annually and every person who tests positive is immediately given antiretroviral therapy (ART).

According to a controversial mathematical formula known as the Granich model, more colloquially known as the "test and treat" strategy, this approach could lead to a 95% reduction in new HIV cases in South Africa within 10 years -- and could see an end to the country's Aids epidemic by 2050.

The hotly debated model was published in the prestigious British medical journal, The Lancet, earlier this year, using data from South Africa and Malawi to demonstrate its impact. The "test and treat" approach is gaining support to such a great degree that the authoritative National Institutes of Health (NIH) in the United States has allocated funds and resources for in-depth studies into it; pilot studies are under way in New York's Bronx district and in Washington DC. According to Professor Gavin Churchyard, from the Johannesburg-based health research organisation the Aurum Institute, additional studies will be carried out in Vancouver in Canada and Hlabisa in KwaZulu-Natal.

"The question is: can we treat our way out of this epidemic?" asks Dr Guy de Bruyn, programme director of HIV prevention studies at the Perinatal HIV Research Unit at the University of the Witwatersrand. De Bruyn, who strongly supports the "test and treat" approach, says that current HIV prevention and treatment strategies will not make a positive impact in South Africa "if we don't manage to decrease the number of new infections and deaths".

Success with current methods is extremely limited, with 1500 new South African infections and 750 people dying every day from Aids-related complications.

Recently, the head of the US National Institute for Allergies and Infectious Diseases, Dr Anthony Fauci, affirmed in an NIH press release: "[The] test and treat [model] potentially could represent an important public health strategy for fighting HIV/Aids."

Chief author of The Lancet study, World Health Organisation medical officer Dr Reuben Granich and his four co-writers base their predictions on scientific evidence that ART is remarkably effective at reducing the amount of virus in an HIV-infected person's blood. This ensures the person is significantly less infectious -- even if the person has unsafe sex. When placed on ART soon after infection, and if the individual takes his or her treatment correctly (even within multiple concurrent sexual relationships and without correct and consistent condom use), the chance of an HIV-positive person infecting his or her partner is often reduced to almost zero.

The researchers say that it's been widely proved that people newly infected with HIV are most infectious and if those people, who mostly are unaware that they're infected with the virus, receive HIV treatment, it could lead to a major reduction in infections.

Based on his experience of several HIV testing projects in Soweto, De Bruyn is convinced that it's possible to get all South Africans to test for HIV through the mobilisation of community leaders, the use of mobile testing clinics and post-test support groups. "Creative strategies such as refusing to renew citizens' driver's licences without them first producing proof that they have gone for an HIV test, and testing people at fast-food stands can also be considered," De Bruyn says.

But the contentious model presents many ethical as well as operational challenges, such as the cost of treatment and testing.

"Each HIV test costs about R96. To test everyone above 15 in South Africa will amount to R3,8-billion and almost 154 000 tests per day," says Wits Clinical HIV Research Unit deputy director Dr Francesca Conradie.

"How do you get all adults in this country tested for the virus once a year if most of them have up until now been reluctant to or even refused to go for a test? If you force them to, you are infringing on their human rights. And, without test results, you can't treat anyone," Conradie says.

It is estimated that 700 000 South Africans are on ART. For the Granich model to be effective, 5,8-million (the estimated number of HIV-infected people in the country) would need to be on ART -- more than eight times the current number. "South Africa simply has too many HIV-infected people for this strategy's implementation to be practical. We're not the US where the numbers are manageable," Conradie says.

Granich and his colleagues point out that, although the model would require more money in the short term, the financial burden would be alleviated as the number of infections start to decline and fewer people would need treatment.

But, Conradie says: "We should rather put all our efforts into well-established prevention methods such as medical male circumcision, which reduces men's risk to contract HIV by 60%."

Aurum acknowledges Mail & Guardian as the source of this article

TAXI OPERATORS AND TRADERS MARCH IN SOLIDARITY AND SUPPORT OF MAKING HEALTH SERVICES ACCESSIBLE
1 December 2009

1/12/09, Johannesburg, South Africa – Leaders of the taxi associations and drivers, informal traders and staff of the Metropolitan Trading Company marched from Bree Street Taxi Rank to Mary Fitzgerald Square today to show their support for the Aurum Institute Emthonjeni Clinic and deliver a memorandum to Qedani Mahlangu, MEC of Health and Social Development (Gauteng) this World AIDS Day.

Taxi operators and traders march in solidarity and support of making health services accessible

The Aurum Institute’s "Emthonjeni" - an inconspicuous health centre providing screening for HIV, TB, STI’s, hypertension and diabetes too taxi operators, traders and commuters, was established in 2008 as a partnership between The Aurum Institute and Metropolitan Trading Company.

"People work here and thousands arrive for work and leave for work from this place," said Alfred Xolani Sam, CEO of the Metropolitan Trading Company.

"They can do their shopping here. So it is logical that the can access health services here too. And having this service here makes it anonymous. People feel comfortable here," continued Xolani Sam.

Eleven Taxi Associations and one Trader Association operate from the Metro Mall Taxi Rank in Bree Street, Johannesburg Inner City. This translates into 4500 taxi drivers transporting approximately 500,000 commuters to and from the rank daily. The drivers and queue marshals are based at the rank or are on the road for extended hours each day, Monday through to Saturday.

Recently published research (The Lancet, 17 October, 2009) has shown that health services need to be made accessible for men in particular to use them. Men, traditionally the breadwinners, aren’t easily able to get access health services. Aurum’s Emthonjeni is taking critical health services to the people. (See Lancet report attached)

Taxi operators and traders march in solidarity and support of making health services accessible

Between March 2008, and May 2009, 14 494 people (57% men) were tested for HIV and received their results, of which 2432 (17%) were positive. 1784 of these are now in HIV care and 1069 have started antiretroviral therapy.

Says Bulelani Kuwane, Deputy Programme Director, the Aurum Institute’s Emthonjeni: "We believe that initiatives like this have potential to promote knowledge of HIV status among men and facilitate earlier access to antiretroviral therapy, thus reducing mortality."

The memorandum handed to the MEC stated the Taxi Associations strongly support the establishment of a clinic at the taxi rank to provide basic health services to taxi operators, traders and commuters. However people that need treatment are referred to government clinics for this and access to treatment is a challenge because of the nature of the work that taxi operators and traders do. The memorandum is calling for the Gauteng Department of Health and Social Development to support the Aurum Institute’s Emthonjeni by providing medication and laboratory services.

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