New tuberculosis infections have declined around the world – except in Sub-Saharan Africa. And the explosion of drug-resistant TB strains in South Africa and other countries have led to some patients being diagnosed with totally drug-resistant TB (TDR-TB), according to a 70-page commission report on drug-resistant TB (DR-TB) published in The Lancet to mark World TB Day, reports Health-e News.
Also, a Treatment Action Campaign survey found TB infection control at SA clinics to be ‘exceedingly poor’ – patients can contract the disease while waiting in clinics for medical treatment.
“We do have this phenomenon of incurable TB – despite having some access to newer drugs. Patients are even failing treatment on the more potent regimens. And it’s going to continue,” lead author Professor Keertan Dheda is quoted in the report as saying.
Globally, only 5% of TB is drug-resistant. But in countries like South Africa, resistant strains are spreading. They are expensive, time-consuming and difficult to treat. According to the humanitarian organisation Medicines Sans Frontières (MSF), in 2015, 20,000 people in the country were diagnosed with some form of DR-TB.
The report says while most of these people had multi-drug resistant TB (MDR-TB) – resistant to two of the most effective anti-TB drugs – or extensively drug-resistant TB (XDR-TB) – resistant to four of the most effective anti-TB drugs, a small fraction was totally drug resistant.
“This expansion of resistance has ushered in an era of programmatically incurable tuberculosis, in which insufficient effective drugs remain to construct a curative regimen,” noted the commission authors. “It’s incurable in the sense that the drugs available on national TB programmes aren’t able to cure these patients,” explained Dheda, who heads up the division of pulmonology at the University of Cape Town.
The report says even though patients in South Africa have access to the new anti-TB drugs, there are patients for whom no drug regimen will work. “Already, we have seen patients who have failed on regimens containing bedaquiline, suggesting resistance to the drug,” he said.
According to Dheda and the commission report, there have already been several cases around the world of resistance to both bedaquiline and delamanid.
For patients diagnosed with incurable TB there are few options, said Dheda, as “the sheer extent” of South Africa’s TB problem means that TB hospitals – with proper infection control measures in pace – are over-crowded.
“The problem is so big we have to send patients home. We give them advice on infection control – like keep the door and windows open. But often people’s lived circumstances make these demands unrealistic. Sometimes there are five or six people sleeping in the same room. They need to work. They need to look after their families,” he said.
But, the report says, patients sent home risk transmitting these incurable strains to other people in the community. Research done by Dheda in two provinces suggests this is already happening in South Africa.
“We need long term voluntary facilities where patients can work and lead a dignified life. We also need palliative care facilities – with adequate infection control,” he said. “Currently in South Africa, there is no government-funded entity where people in this position can die with dignity.”
According to the commission, other measures like wider access to screening and treatment and going to find potential patients in the community before waiting for them to come to the clinic – when they are very sick and infectious – could help avert a situation where incurable TB becomes common-place.
“Every year, strains of drug-resistant tuberculosis will emerge that are more transmissible, more difficult to treat, and more widespread in the community. Yet we also have more tools at our disposal than ever before,” said Dr David Dowdy from Johns Hopkins Bloomberg of Public Health in the US. He said the epidemic is at a “crossroads” where, over the next decade the world could see a DR-TB epidemic “of unprecedented global scale” or the situation will be reversed – as evidence shows it can be.
“The difference between the two outcomes lies less with the pathogen and more with us as a global tuberculosis control community and whether we have the political will to prioritise a specific response to the disease. Drug-resistant tuberculosis is not standing still; neither can we.”
* Meanwhile, a spot survey of clinics across the country showed tuberculosis infection control was exceedingly poor meaning patients can contact the infectious disease while waiting in clinics for medical treatment. The Times reports that the Treatment Action Campaign (TAC) sent members to clinics around the country to measure TB control measures and of the 158 clinics assessed‚ 114 were deemed as “red”‚ meaning not enough was done to stop the spread of TB in these crowded places.
“We have the knowledge and the tools to stop the spread of TB‚ but we aren’t using them‚” said Sibongile Tshabalala‚ TAC deputy general secretary. “Instead what we see on the ground are horrendously packed clinics with all the windows shut. We don’t see any posters telling people to cover their mouths if they cough or sneeze. We see people with TB symptoms sitting among those without‚ coughing and not being offered masks or tissues.”
The report says the TAC’s concern is not unfounded. TB is spread in crowded locations including schools‚ prisons and clinics.
Work on how people in KwaZulu-Natal contracted extremely drug resistant TB was recently published in the New England Medical Journal. Local and international scientists analysed the genotypes of the XDR-bacteria and linked infections scientifically and were able show most people got this deadly TB from people in their household‚ but a fair amount contracted it in hospitals.
Members from TAC branches in the Eastern Cape‚ Limpopo‚ Mpumalanga‚ Free State‚ Gauteng‚ KwaZulu-Natal‚ and Western Cape visited clinics in their neighbourhoods this month and then answered the following questions: Are the windows open? Is there enough room in the waiting area? Are there posters telling you to cover your mouth when coughing or sneezing? Are you seen within 30 minutes of arriving at the clinic? Are people in the clinic waiting area asked if they have TB symptoms? Are people who are coughing separated from those who are not? Are people who cough a lot or who may have TB given tissues or TB masks?
The report says when the answers were “no” more than three times‚ the TAC decided the facility was red.
The facilities with great TB control measures were: Brealyn Clinic (EC)‚ Daveyton East Clinic (GP)‚ Eshowe Hospital (KZN)‚ King DiniZulu Clinic (KZN)‚ Letitia Bam Day Hospital (EC)‚ Mjejane Clinic (MP)‚ Mpoza Clinic (EC)‚ Nelspruit Community Health Centre (MP)‚ Nkensani Gateway Clinic (LP)‚ Nolungile Youth Clinic (WC)‚ Nomzano Clinic (EC)‚ Qaukeni Clinic (EC)‚ Senyorita Clinic (FS)‚ Site B Clinic (WC)‚ Thelkwane Clinic (MP).
“While we stress that this is by no means a scientific survey and the results are not generalisable to the rest of the public healthcare system‚ it does suggest that infection control is a significant problem in many public sector health facilities.
“As a result‚ we demand that government carries out a full audit of all public buildings in South Africa‚ including schools‚ clinics‚ hospitals‚ correctional facilities and home affairs facilities‚ to assess whether sufficient TB infection control measures are in place‚” said Yawa.
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms—including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions—are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues.
Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Ruth McNerney, Megan Murray, Jennifer Furin, Edward A Nardell, Leslie London, Erica Lessem, Grant Theron, Paul van Helden, Stefan Niemann, Matthias Merker, David Dowdy, Annelies Van Rie, Gilman K H Siu, Jotam G Pasipanodya, Camilla Rodrigues, Taane G Clark, Frik A Sirgel, Aliasgar Esmail, Hsien-Ho Lin, Sachin R Atre, H Simon Schaaf, Kwok Chiu Chang, Christoph Lange, Payam Nahid, Zarir F Udwadia, C Robert Horsburgh Jr, Gavin J Churchyard, Dick Menzies, Anneke C Hesseling, Eric Nuermberger, Helen McIlleron, Kevin P Fennelly, Eric Goemaere, Ernesto Jaramillo, Marcus Low, Carolina Morán Jara, Nesri Padayatchi, Robin M Warren