tag:theconversation.com,2011:/us/topics/tb-treatment-23570/articlesTB treatment – The Conversation2023-03-23T07:51:28Ztag:theconversation.com,2011:article/2021512023-03-23T07:51:28Z2023-03-23T07:51:28ZTB kills 75,000 children in Africa every year: how this can stop<figure><img src="https://images.theconversation.com/files/516948/original/file-20230322-26-dpm8er.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">There have been substantial improvements in some areas of TB therapeutics. </span> <span class="attribution"><span class="source">Punit Paranjpe/AFP via Getty Images</span></span></figcaption></figure><p><em>Tuberculosis (TB) is a preventable and curable disease. Half of the world’s 30 highest TB burden countries are in Africa. In many of these countries, TB is the leading cause of death across age groups, but especially among children. Globally, TB is the <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-disease-burden/2-2-tb-mortality">leading cause of death</a> by any single infectious agent (above COVID-19 and HIV).</em></p>
<p><em>The people most affected by TB are often the most socio-economically marginalised, with the fewest reserves to take them through the treatment journey. This is extremely challenging, with complex, often delayed diagnosis, many months of treatment, and often long-term effects after treatment. The Conversation Africa’s Ina Skosana spoke to Graeme Hoddinott, a socio-behavioural science lead at the Desmond Tutu TB Centre, Stellenbosch University, and an African Academy of Sciences ARISE Fellow.</em></p>
<hr>
<h2>What’s the TB burden among young people?</h2>
<p>In Africa, of the <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-disease-burden/2-1-tb-incidence">three million people</a> who develop TB disease every year, nearly 160,000 are children 0-4 years old, and another 160,000 are 5-14 years old. Every year, about <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-disease-burden/2-2-tb-mortality">500,000 people in Africa</a> die because of TB. Children make up 15% (75,000) of these deaths. </p>
<p>Less than half of the children aged 0-14 who have TB are diagnosed – so they never even start treatment.</p>
<h2>What are some of the drivers?</h2>
<p>TB is transmitted between people through the air. When a person with TB coughs or breathes out, some of the TB bugs are expelled to float in the air. If someone else then breathes the bugs in, they cause a new infection. There are several factors that increase the risk of TB transmission. These include actions that increase the number of bugs in the air, such as not wearing a mask and coughing more. And actions that increase exposure, such as spending long periods of time breathing the air in. </p>
<p>A person might breathe the TB bugs in (that is, become infected), but not become ill. This is known as latent TB. Sometimes, though, the TB bugs are able to multiply and escape the body’s immune system. As the number of bugs increases, the person begins to experience symptoms such as coughing, drenching sweats and weight loss. This is then called TB disease. </p>
<p>A variety of factors increase the risk of progressing from TB infection to disease. These are factors that might impede the body’s natural immune functioning, such as undernourishment or smoking. </p>
<p>Children (especially young children) have less developed immune systems. This makes their chance of progressing from infection to disease higher than it is for adults. </p>
<p>Prevention of infection can be done through reducing risks of transmission, for example by opening windows to allow the bugs to blow away. Also, if a person with TB is on treatment, then the number of bugs they expel is dramatically reduced. That’s why it’s important to get an early diagnosis and start treatment.</p>
<p>Where there is an exposure risk, we can also use medicines to reduce the chance of developing disease – this is called TB preventive therapy. The most recent World Health Organization <a href="https://apps.who.int/iris/bitstream/handle/10665/331170/9789240001503-eng.pdf">guidelines</a> suggest that preventive therapy be offered to everyone who has significant exposure risk to an adult or adolescent with TB. For example, think about young children who are sharing a bed with their mother. If she has TB, then the child should be offered preventive therapy, as should other people who share their home. </p>
<p>Unfortunately, in most settings in Africa, implementation of TB preventive therapy is either non-existent or extremely sub-optimal. Historically, the only available TB preventive regimen was a once-daily treatment for six months that is burdensome to administer; new regimens are becoming available. Unfortunately, the limited resources available to TB services have prioritised TB treatment and not prevention. </p>
<h2>Where are the gaps?</h2>
<p>There have been <a href="https://www.nejm.org/doi/10.1056/NEJMoa2104535">substantial</a> <a href="https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-017-2377-x">improvements</a> in some areas of <a href="https://www.ingentaconnect.com/content/iuatld/ijtld/2023/00000027/00000003/art00005;jsessionid=2sjtfaionun19.x-ic-live-03">TB therapeutics</a>, with <a href="https://erj.ersjournals.com/content/48/5/1503">shorter</a>, more <a href="https://www.ingentaconnect.com/content/iuatld/ijtld/2023/00000027/00000002/art00006">palatable</a> regimens and more <a href="https://www.ingentaconnect.com/content/iuatld/ijtld/2023/00000027/00000001/art00005">easy-to-use</a> <a href="https://www.ingentaconnect.com/content/iuatld/ijtld/2022/00000026/00000012/art00006">formulations</a>. However, these are not universally available and are still not optimal. Even “shorter” treatment is four months long. Health systems are poorly equipped to support continuity of care when patients (including children and adolescents) move between facilities.</p>
<p>Far too many children who initiate both TB preventive therapy and TB treatment <a href="https://www.jahonline.org/article/S1054-139X(22)00778-9/fulltext">are lost</a> to <a href="https://www.ingentaconnect.com/content/iuatld/pha/2022/00000012/00000004/art00003">follow-up</a>. TB programmes across the world have yet to operationalise the high-minded ideals of “<a href="https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0001357">patient-centred care</a>”. The experiences of adolescents and young people (10-24 years old) accessing TB services are often especially <a href="https://www.jahonline.org/article/S1054-139X(22)00778-9/fulltext">problematic</a>. For example, <a href="https://www.mdpi.com/2076-0817/10/12/1591">adolescents report</a> being assumed to have HIV, being shouted at for being sexually active (even if they are not) and being told to access TB services at times when they are in <a href="https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0000989">school</a>. </p>
<p>There is also limited integration between health services and other sectors (like basic education) to make care easier to get. There remain <a href="https://www.ingentaconnect.com/content/iuatld/ijtld/2017/00000021/a00111s1/art00013">high rates</a> of TB-associated <a href="https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1250-8">stigma</a>, and the <a href="https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-018-0777-3">costs of TB care</a> (economic, social and psychological) can be <a href="https://thorax.bmj.com/content/76/4/387">catastrophic and long-lasting</a>. </p>
<h2>How must TB programmes be tailored?</h2>
<p>A fraction of the funding and collective effort that was mobilised for COVID-19 could realistically push towards TB elimination. Perversely, instead, resources redirected towards COVID-19 have <a href="https://www.theglobalfund.org/en/news/2021/2021-09-08-global-fund-results-report-reveals-covid-19-devastating-impact-on-hiv-tb-and-malaria-programs/">set the global TB programme back</a> by a decade’s worth of progress. </p>
<p>TB programmes must be tailored by listening to the preferences and priorities of people affected by TB, by working to address the real-world limitations experienced by frontline health services, and by continuing to develop better, more acceptable therapeutics; especially medicines that are more acceptable for children and easier for caregivers to prepare and administer. </p>
<p>But really all of that can only make a big difference if we all wake up to this leading cause of death, especially among children, and care more.</p><img src="https://counter.theconversation.com/content/202151/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Graeme Hoddinott is a fellow of the African Research Initiative for Scientific Excellence (ARISE) programme. His ARISE research is focused on optimising care for adolescents with tuberculosis. The ARISE programme is implemented by the African Academy of Sciences (AAS) with support from the European Commission and the African Union Commission.</span></em></p>Less than half of the children aged 0-14 who have TB are diagnosed – so they never even start treatment.Graeme Hoddinott, Socio-behavioural Scientist and Senior Researcher, Stellenbosch UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2019662023-03-23T04:26:00Z2023-03-23T04:26:00ZTB in children isn’t being controlled - it’s key to fighting the disease for everyone else<figure><img src="https://images.theconversation.com/files/516613/original/file-20230321-22-zvqx0x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In many developing countries TB vaccination for children after birth is mandatory.</span> <span class="attribution"><span class="source">Paul Kane/Getty Images</span></span></figcaption></figure><p>World TB Day on March 24th will commemorate the day in 1882 when <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/00000222.htm#:%7E:text=On%20March%2024%2C%201882%2C%20Robert,of%20Tuberculosis%22%20(1).">Professor Robert Koch</a> announced in Berlin that he had discovered the microbial cause of tuberculosis (TB), <em>Mycobacterium tuberculosis</em>. </p>
<p>Effective treatment for TB has been available since <a href="https://pubmed.ncbi.nlm.nih.gov/26653188/#:%7E:text=In%201952%2C%20isoniazid%20opened%20the,aminosalicylic%20acid%2C%20which%20it%20replaced.">1952</a>. But it continues to be the <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-disease-burden/2-2-tb-mortality">world’s top cause of death</a> from a single infectious disease. </p>
<p>In <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886961/#:%7E:text=In%201993%2C%20the%20WHO%20declared,deaths%20in%20the%20coming%20years.">1993</a> TB was declared a global public emergency of international concern and still is 30 years on. The focus at that time was on adult TB. At the time childhood TB was not thought to be important. Accurate evidence of the scale of the problem wasn’t available. Over the ensuing decade, thousands of African children died of TB and TB/HIV co-infection every year. </p>
<p>It took visionary leadership from African scientists and pathologists to conduct a large, <a href="https://www.unza-uclms.org/Chintu-Zumla%202002%20Zambia.pdf">landmark autopsy study</a> in 2002 on 164 children who had died of respiratory illness in Lusaka, Zambia. The study found that 25% of deaths were due to TB. It was only then that the World Health Organization (WHO) recognised that TB in children was a <a href="https://apps.who.int/iris/bitstream/handle/10665/89506/9789241506137_eng.pdf?sequence=1">neglected disease</a>. </p>
<p>Despite that recognition, serious investment into early diagnosis, treatment and prevention of childhood TB have not been forthcoming. Systemic health services challenges and lack of <a href="https://pubmed.ncbi.nlm.nih.gov/34794675/">adequate knowledge around the disease</a> also hamper improvements. </p>
<p>Based on <a href="https://scholar.google.co.uk/citations?hl=en&user=wsJ2kMQAAAAJ">our</a> combined four <a href="https://scholar.google.com/citations?user=4_DvHm0AAAAJ&hl=en">decades</a> in TB <a href="https://www.researchgate.net/scientific-contributions/Francine-Ntoumi-38611208">research</a> we believe that the burden of childhood TB can be one of the indications of a <a href="https://pubmed.ncbi.nlm.nih.gov/24932504/">failing TB control programme</a> in any setting. </p>
<p>In 2021, an estimated <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022">10.6 million people</a> fell ill with TB worldwide. This was made up of six million men, 3.4 million women and 1.2 million children. Of the <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-disease-burden/2-2-tb-mortality">1.6 million people</a> who died in 2021, 240,000 were children. Almost all were undiagnosed before death. </p>
<p>This reflects the dire need to prioritise childhood TB. Its early detection and treatment must be part of the global strategy to end TB. </p>
<h2>Key challenges in childhood TB</h2>
<p><strong>Early diagnosis and treatment:</strong> The symptoms of TB in adults is fairly well described, leading to definitive diagnosis and treatment. But TB in children can easily be missed. This is because the symptoms are similar to other childhood illnesses. As a result, diagnosis and treatment are delayed. </p>
<p>Diagnosing TB in children is difficult for a number of reasons. The most vulnerable children present with non-specific symptoms. Chest x-rays are the textbook way to diagnose TB. But these are not always available in rural settings. There have been numerous studies evaluating <a href="https://pubmed.ncbi.nlm.nih.gov/36314546/">new tests and algorithms</a>. But the ideal test for childhood TB has not yet been found because the test must be easy to use at points of healthcare, affordable, with simple non-invasive sample collection. </p>
<p><strong>TB vaccination:</strong> The age-old Bacille Calmette-Guerin (BCG) vaccine remains the only licensed vaccine. It only provides some protection in early childhood. But it’s <a href="https://pubmed.ncbi.nlm.nih.gov/32305522/">not effective in preventing active disease</a> in older children and adults. </p>
<p>In many developing countries BCG vaccination for children after birth is mandatory. But vaccine coverage varies across countries. For national TB control programmes to work there must ensure high vaccination coverage. </p>
<p>New vaccine development for TB has not been a priority. There are 16 candidate vaccines that have reached proof of concept stage based on <a href="https://pubmed.ncbi.nlm.nih.gov/36866744/">recent efforts</a>. But more investment for facilitating their evaluation in clinical trials is required.</p>
<p><strong>Funding to meet global targets:</strong> Adequate funding is required to fight childhood TB. The global <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022">targets set in 2018</a> aimed to treat 40 million people with TB disease between 2018–2022. This target included 3.5 million children with drug sensitive TB and 115,000 children with drug-resistant TB.</p>
<p>But <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022">progress in many areas of TB control have stalled – or been reversed</a>. This has mainly been due to the COVID-19. This calls for renewed efforts to funding TB control adequately again. </p>
<p>In addition, US$ 1.3bn per year was needed to achieve <a href="https://www.stoptb.org/sites/default/files/UN%2520Declaration%2520on%2520TB.pdf#page=9">these targets </a>. US$ 2bn would go to TB research annually within the same five year period of 2018–2022. An assessment of the shortfall is urgently required as total investments into TB control globally fell from US$6.0 billion in 2019 US$5.4 billion in 2021, which is <a href="https://www.who.int/news-room/fact-sheets/detail/tuberculosis#:%7E:text=Investments%20in%20TB%20Prevention,%20Diagnosis%20and%20Treatment%20and%20Research">less than half</a> what is needed annually. </p>
<p><strong>Clinical practice and community prevention:</strong> Health workers in parts of the world including countries in Africa have limited knowledge and practice in <a href="https://pubmed.ncbi.nlm.nih.gov/35197164/">managing childhood TB</a>. Contact screening and family-centred approaches are an important part of reducing the burden of TB in childhood. It’s essential to improve understanding of childhood TB from training institutions and clinics – all the way down to the community.</p>
<p><strong>Use of new technologies in testing and diagnosing childhood TB:</strong> Most children with TB present with negative results on microscopy of their respiratory fluids while radiographs are unreliable as they rarely definitive. <a href="https://www.ghspjournal.org/content/1/1/18">GeneXpert</a> is currently the most widely used tool for diagnostic accuracy of TB. But affordability and maintenance mean that it’s not practical to roll it out in settings that have few resources. </p>
<p>The best option in our view is <a href="https://www.frontiersin.org/articles/10.3389/fmicb.2022.855988/full">metagenomic next-generation</a> sequencing. This enables broad identification of pathogens and antimicrobial resistant genes directly from clinical samples within 24 hours. But these technologies are not readily available in low-middle income countries where the TB burden is the highest. Some children with respiratory symptoms may have mixed infections. Accurate diagnosis of multiple infections in a child will lead to proper management of the sick child with respiratory symptoms and reduction in mortality due to untreated infections including TB. </p>
<h2>Next steps</h2>
<p>To efficiently fight childhood TB, programmes must ensure the following:</p>
<ul>
<li><p>good coverage of BCG vaccine </p></li>
<li><p>new, more effective TB vaccines need to be developed as well as enhancement of BCG</p></li>
<li><p>good clinical training and practice for managing patients</p></li>
<li><p>deployment of highly sensitive diagnostic methods</p></li>
<li><p>efficient community prevention programmes including contact tracing, and </p></li>
<li><p>proper treatment of diagnosed children. </p></li>
</ul>
<p>Funders and donors should provide enough resources to enable global targets to be met. And enough money is required to mitigate the impact of emergencies such as the COVID-19 pandemic and economic downturns.</p><img src="https://counter.theconversation.com/content/201966/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Progress in many areas of TB control stalled or reversed mainly because of the COVID-19 pandemic and the recent geo-political situations.Tom Nyirenda, Extraordinary Senior Lecture in the Department of Global Health , Stellenbosch UniversityAlimuddin Zumla, Professor of Infectious Diseases and International Health, UCLFrancine Ntoumi, Research Group Leader, Institute for Tropical Medicine , University of TübingenLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1942652022-12-01T15:21:49Z2022-12-01T15:21:49ZMini bio-devices could help TB patients stick to their treatments<figure><img src="https://images.theconversation.com/files/496953/original/file-20221123-12-8elsb5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Handheld devices like this one, used for testing blood sugar levels, could help TB patients monitor their own drug levels.</span> <span class="attribution"><span class="source">Andrey_Popov/Shutterstock</span></span></figcaption></figure><p>Imagine the scenario: you’ve been told you have a disease that will kill you. But, the doctor adds, your life can be saved if you diligently take your medication. Don’t skip a day, don’t skip a dosage. Soon, however, you discover that the medication has a slew of side effects, including a loss of appetite, fatigue, and nausea. So you do stop.</p>
<p>This process plays itself out every day among people who have been diagnosed with tuberculosis (TB). Treatment <a href="https://www.cdc.gov/tb/topic/treatment/tbdisease.htm#">lasts for months</a>. The adherence rate is low. Numbers are hard to come by. But one <a href="https://link.springer.com/article/10.1186/1471-2458-11-393">national survey</a> in China – which is among the <a href="https://www.who.int/china/health-topics/tuberculosis">30 high-burden</a> TB countries that account for 87% of the world’s estimated cases – showed that as many as 73% of TB patients had, at the time of the survey, interrupted or suspended treatment. </p>
<p>South Africa is another of those 30 high-burden countries. The <a href="https://www.nicd.ac.za/wp-content/uploads/2021/02/TB-Prevalence-survey-report_A4_SA_TPS-Short_Feb-2021.pdf">First National TB Prevalence Survey</a> of 2018 found a prevalence rate of around 737 per 100,000 people, among the highest in the world. Again, numbers are hard to determine, but <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410008/">one study</a> looking at co-infection between extensively drug-resistant tuberculosis (XDR-TB) and HIV found that only around 70% of patients stuck to the optimal six-month treatment.</p>
<p>This poses risks for the individual and for entire communities. It is associated with higher transmission rates, fatalities, soaring costs for TB treatment programmes as well as the development of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561400/">multi-drug resistant strains</a>.</p>
<p>Multiple approaches are being taken to improve adherence to medication. These include the use of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462706/">higher doses</a> of certain medications in the hope of reducing treatment duration, although <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462706/">side-effects</a> like hearing loss have been reported, as has the building up of resistance to drugs.</p>
<p>Building on the sequencing of the human genome and improved technologies to determine individual genetic variations, there has been a growing movement towards personalised or precision medicine and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297695/#">personalised treatment regimens</a>. This works on the premise that medical treatments, including those for TB, can be customised to an individual patient. Hurdles include the costs involved in making those technologies accessible, and understanding how to tailor treatments to each person. </p>
<p>In the case of TB, there are also <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982531/">other factors</a> to consider, like variation in the disease-causing strain and individual drug-metabolising capacity.</p>
<p>That’s where <a href="https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elan.202060384?af=R">my work</a> comes in. I am working to develop technologies that can accurately and reliably calculate an individual’s drug-metabolising capacity by measuring the “leftover” drugs in the TB patient’s blood or urine samples. The method involves the use of enzyme-based biosensors – a device used to detect chemical or biological substances. A popular application for such devices is the rapid detection of glucose levels in diabetics.</p>
<p>The results from my tests are promising. They reflect what other scholars doing similar experiments around the world show: these enzymatic biosensors could soon (scientists don’t like timelines) become a crucial weapon in efforts to make it easier for TB patients to adhere to their treatments.</p>
<h2>Finding the right enzyme</h2>
<p>One element of my work is to determine the right enzyme, already present in the human body, to include in the biosensor and serve as an amplifier or enhancer.</p>
<p>Biosensors should not be confused with the devices in which they sit – like the portable finger-prick testing kits used by diabetics, for example. They are simply a part of those devices. </p>
<p>Biosensors are typically made up of an electronic part, namely the transducer, that converts energy from one form to another; and a biological element such as an enzyme or even an antibody that acts as the sensor. </p>
<p>The electrochemical sensor itself does most of the hard measuring work. Essentially, the biological recognition element (the enzyme or antibody) interacts with the chemical component that you are seeking to identify and track, while the biological response is converted into an electric signal by the transducer, giving essential measurements. The biological element – in our case, the enzyme – simply boosts the signal.</p>
<p>My go-to enzyme is called CYP3A4. It forms part of a group of enzymes named cytochrome 450 or CYP450, which are known to play a key part in the <a href="https://pubmed.ncbi.nlm.nih.gov/23333322/">absorption of drugs</a> – and not just TB drugs. Because these enzymes react with 50% of all prescribed medication, they serve as a useful detector of the drug’s presence in a sample. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/tb-prevention-has-relied-on-the-same-vaccine-for-100-years-its-time-for-innovation-164735">TB prevention has relied on the same vaccine for 100 years. It's time for innovation</a>
</strong>
</em>
</p>
<hr>
<p>What makes CYP3A4 so useful is that it reacts with all four of the first-line drugs used to treat TB: namely isoniazid, ethambutol, pyrazinamide and rifampicin. </p>
<p>For purposes of <a href="https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elan.202060384?af=R">my study</a>, I developed a sensor by modifying the surface of a working electrode with nanoparticles of a range of materials. The enzyme was then electrostatically applied to this electrode. The completed biosensor was then tested on my samples: synthetic urine and plasma spiked with the four drugs.</p>
<p>My results showed that the biosensor could detected the drug “remnants” in my samples with high levels (90% and above) of accuracy. </p>
<h2>Real-world value</h2>
<p>So, what would the value of such a biosensor be in the real world? For one thing, it could allow clinicians to gauge whether a patient is a fast or poor metaboliser of the medication. </p>
<p>Typically, fast metabolisers quickly absorb the drugs, and only small vestiges remain in a blood or urine sample. They are likely to have few side effects since their bodies would not allow a build-up of the drug in their systems. However, they may need to take medication more regularly to make up for this quick absorption. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-key-to-treating-tb-may-be-in-a-common-carbohydrate-what-we-know-so-far-188412">The key to treating TB may be in a common carbohydrate. What we know so far</a>
</strong>
</em>
</p>
<hr>
<p>Poor absorbers, on the other hand, do not process the drugs well enough to do much good. The drug then builds up in the body and can lead to adverse side effects. These patients may require lower or less regular dosages.</p>
<p>There is even the potential that such enzyme-based biosensors could be put in devices that patients can use on their own, much like diabetics use monitors to measure their glucose levels. People with TB can then then do the same, modifying their regimens based on the readings and their doctors’ guidance. </p>
<p>Such improved management can, ultimately, keep adherence rates from slipping – which is good news for TB patients, their communities and public health systems across the world.</p><img src="https://counter.theconversation.com/content/194265/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Candice Franke receives funding from the National Research Foundation of South Africa. </span></em></p>There are several reasons that TB patients don’t or can’t adhere to their treatment.Candice Franke, Lecturer, University of the Western CapeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1884122022-08-16T14:41:17Z2022-08-16T14:41:17ZThe key to treating TB may be in a common carbohydrate. What we know so far<figure><img src="https://images.theconversation.com/files/479161/original/file-20220815-25-i854zg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">New remedies are needed as rates of multi-drug resistant TB rise.</span> <span class="attribution"><span class="source">Jarun Ontakrai/Shutterstock</span></span></figcaption></figure><p><a href="https://link.springer.com/article/10.1007/s00289-021-03860-1">Curdlan</a> is a popular carbohydrate in the food industry. Its name is derived from the word “curdle”, and as it suggests, it’s widely used as a thickener and stabiliser in everything from sausages to milk substitutes.</p>
<p>More recently, it has caught the eye of the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273257/">pharmaceutical industry</a>. That’s because curdlan, itself produced by bacteria, is able to trigger an antibacterial response in a range of environments and organisms. Among other uses, researchers are <a href="https://link.springer.com/article/10.1186/s13048-020-00626-7">looking at curdlan</a> as a possible treatment for cancers and <a href="https://www.sciencedirect.com/science/article/pii/S0144861714003828?casa_token=5A9L_uGxF5oAAAAA:56_9Q91nCk3cSJdLaXa0eZPp4iDXAs5b8XUUNQuwfhPdSl5Jg9w2wfxyjejHNCm7V8N5sH4iDrY">other diseases</a>.</p>
<p>One of those diseases is tuberculosis (TB), the infection responsible for <a href="https://www.frontiersin.org/articles/10.3389/fmicb.2017.02284/full">killing more people</a> than any other infectious disease in human history. <a href="https://www.nicd.ac.za/wp-content/uploads/2021/02/TB-Prevalence-survey-report_A4_SA_TPS-Short_Feb-2021.pdf">South Africa</a> has one of the world’s highest TB burdens – along with 29 other countries including India and China. These countries contribute 86% of the globe’s <a href="https://www.who.int/news-room/fact-sheets/detail/tuberculosis#:%7E:text=In%202020%2C%20the%2030%20high,Nigeria%2C%20Bangladesh%20and%20South%20Africa.">10 million annual TB cases</a>. South Africa’s combined burden of TB, TB/HIV and multi-drug resistant TB (MDR-TB), driven by socioeconomic factors and its high HIV <a href="https://worldhealthorg.shinyapps.io/tb_profiles/?_inputs_&entity_type=%22country%22&lan=%22EN%22&iso2=%22ZA%22">numbers</a>, is especially worrying.</p>
<p>Existing remedies made up of cocktails of antibiotics are not effective against MDR-TB. This has sparked interest in finding alternative treatments. It’s why our research group at the School of Pharmacy at the University of the Western Cape, and others, are beginning to test the efficacy of curdlan as a potential drug candidate. </p>
<p>In a <a href="https://pubmed.ncbi.nlm.nih.gov/34534573/">recent paper</a>, for instance, we show very promising results for the potential treatment of TB using curdlan-based nanoparticles.</p>
<h2>How TB infects</h2>
<p>Our work centres on developing host-directed therapies using curdlan. Such treatments essentially let the human <a href="https://www.frontiersin.org/articles/10.3389/fmicb.2017.02284/full">immune system</a> do the heavy lifting. This is done by activating its natural antibacterial mechanisms while controlling the inflammation that results from such activation. Inflammation is a signal that the immune system is working. But if inflammation is out of control it can cause major damage to human tissue, as seen in severe <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2020.01446/full#:%7E:text=Accumulating%20evidence%20suggests%20that%20some,%2C%20TNF%2D%CE%B1%2C%20and%20VEGF">COVID-19 infections</a>.</p>
<p>Research has already shown that host-directed therapies hold <a href="https://www.frontiersin.org/articles/10.3389/fcimb.2020.618414/full">immense potential</a> for the <a href="https://link.springer.com/article/10.1007/s11095-018-2528-9">treatment of TB</a>.</p>
<p>To understand how these therapies work, it’s important to understand how TB infection unfolds in the human body.</p>
<p>Primary TB infection occurs when a person inhales aerosol droplets, released by contagious individuals, that contain <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>). This is the bacterium that causes TB. Once inhaled, <em>M.tb</em> quickly makes its way to the lung’s alveolar space, made up of tiny air sacs that sit at the end of the bronchioles, which are the air passages inside the lungs.</p>
<p>Here it is absorbed by what’s known as alveolar macrophages, the lung cells that are usually the first line of defence against pollutants and pathogenic organisms. Typically these macrophages would trigger an immune response in the body. But <em>M.tb</em> has evolved so cannily that it eludes or switches off this immune-triggering response in the macrophages. These alveolar macrophages become its infection headquarters; the bacterium remains concealed within these cells.</p>
<p>For any treatment to be successful, it has to navigate a <a href="https://www.frontiersin.org/articles/10.3389/fcimb.2020.618414/full">host of obstacles</a> to reach <em>M.tb</em>. It must make its way through complex lung lesions, then penetrate the cell membrane of macrophages and other host cells, and finally be taken up by the <em>M.tb</em> sitting within these cells.</p>
<p>That’s where nanoparticles enter the picture.</p>
<h2>Tiny ‘snipers’</h2>
<p>Nanoparticles are extremely small. They range from between one to 100 nanometres; for some perspective, there are a million nanometres in a single millimetre. In theory, and as is being shown in <a href="https://iopscience.iop.org/article/10.1088/1361-6528/ac7885/meta?casa_token=FjKJlNwJcFYAAAAA:CzLeHNZ_j9uFpGYgd9UnvJr-RBFnO8NoKhxymb8JcyrujuK0bISE6sP6vEIeYC8NvPcPJkLuIMA">laboratories</a> and existing treatments for other conditions like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720743/">cancer</a>, nanotherapies allow drugs to target pathogens with sniper-like accuracy. They also have the potential to tackle patient non-compliance that can lead to drug resistant TB.</p>
<p>The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449995/">reasons</a> for non-compliance are varied and complex, but the duration of the therapy itself is a factor. Existing treatments require that, depending on the severity and progress of the disease, patients take many drugs over as many as six months. The <a href="https://www.who.int/news-room/fact-sheets/detail/tuberculosis">course of treatment</a> for MDR-TB lasts up to 24 months. </p>
<p>This high pill load, together with sometimes toxic side effects, has been shown to overwhelm patients. Many do not return to clinics and hospitals for check-ups, especially when they feel better after a few weeks. Some stop taking their medication. This could be behind the rise of drug resistant strains. Such non-compliance is also believed to be the cause of South Africa’s comparatively <a href="https://www.copenhagenconsensus.com/publication/south-africa-perspective-tuberculosis#:%7E:text=TB%20is%20South%20Africa's%20leading,to%20bring%20it%20under%20control.">high TB mortality</a>.</p>
<p>Traditional drugs are taken orally or intravenously. They travel throughout the body via the blood circulatory system. Many drug molecules do not reach their targets, staying in the body where they cause several negative side effects. That’s where nanoparticle-based treatments have the <a href="https://www.tandfonline.com/doi/abs/10.1517/17425247.2014.846905">upper hand</a>: they are extremely targeted and their release into the system is very controlled. Smaller doses are required and there is less dispersion around the body, meaning fewer side effects.</p>
<h2>Promising findings</h2>
<p>All these factors suggest that nanoparticle-based treatments may be the right approach to take against TB. And two interesting findings from our study bolster the case.</p>
<p>One, we observed the production of what’s known as pro-inflammation cytokines, a signalling molecule that triggers an antibacterial effect in immune cells. This meant that the nanoparticles were doing what they were meant to do.</p>
<p>Secondly, we found that the <em>M.tb</em> bacteria in the immune cells were considerably reduced over a 72-hour period. </p>
<p>These results suggest that curdlan nanotherapeutics are an avenue worth exploring in treating TB. There is much more work to be done, but it’s an important step towards tackling TB – in South Africa and everywhere else.</p><img src="https://counter.theconversation.com/content/188412/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Admire Dube receives funding from the Fogarty International Center of the National Institutes of Health (K43TW010371) and the National Institute of Allergy and Infectious Diseases (5R01AI152109). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.</span></em></p>As antibiotics lose their power to treat some forms of TB, interest in the antibacterial powers of curdlan is rising.Admire Dube, Associate Professor, Pharmaceutical Sciences, University of the Western CapeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1817722022-06-01T19:29:18Z2022-06-01T19:29:18ZInhaled vaccine for COVID-19: The pandemic accelerated decades of research leading to jab-free vaccine now in human testing<figure><img src="https://images.theconversation.com/files/466340/original/file-20220531-16-inp8qq.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5000%2C3697&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Inhaled vaccine delivery could take on not only COVID-19, but also other respiratory infections, including tuberculosis.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/inhaled-vaccine-for-covid-19--the-pandemic-accelerated-decades-of-research-leading-to-jab-free-vaccine-now-in-human-testing" width="100%" height="400"></iframe>
<p>No one wanted COVID-19. The pandemic has created misery, death and hardship, and it isn’t finished yet.</p>
<p>Still, the lingering crisis has generated opportunities, by expediting research that may benefit humanity far beyond the pandemic. Inhaled vaccines are one example. I am part of a multidisciplinary team working to make these a practical reality, much sooner than would have been the case without the pandemic.</p>
<figure class="align-right ">
<img alt="A grouping of rod-shaped bacteria coloured orange, against a black background" src="https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=747&fit=crop&dpr=1 600w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=747&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=747&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=939&fit=crop&dpr=1 754w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=939&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=939&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Magnified image of the bacteria that causes tuberculosis.</span>
<span class="attribution"><span class="source">NIAID</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We are now in the early stages of testing a next-generation COVID-19 vaccine that our earlier research in animals suggests will <a href="https://doi.org/10.1016/j.cell.2022.02.005">last longer, be more effective and stand up well to future variants</a> of the COVID-19 virus.</p>
<p>Before COVID-19 emerged, my colleagues and I at McMaster University were working to develop a new inhaled form of vaccine delivery that could finally take on one of the most challenging respiratory infections: tuberculosis, still a scourge in <a href="https://www.who.int/health-topics/tuberculosis#tab=tab_1">low- and middle-income countries</a> and in remote areas. In Canada it <a href="https://www.sac-isc.gc.ca/eng/1570132922208/1570132959826">disproportionately affects people living in Inuit Nunangat and First Nations living on reserve</a>. </p>
<p>After decades of work, progress was steady, but slow. The lack of urgency to solve a problem that mainly affects <a href="https://doi.org/10.1183/09031936.00173608">people living in poor conditions</a> had made it difficult to generate the resources and momentum needed to complete our research.</p>
<h2>The urgency of COVID-19</h2>
<p>The COVID-19 pandemic, being truly global, created the demand for vaccines, such as the now-familiar ones from <a href="https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines.html">Pfizer, Moderna and AstraZeneca</a>. These vaccines have got us through the immediate crisis, as the virus was spreading rapidly, and have served us well, preventing serious illness and death in countries where vaccines were available.</p>
<p>These vaccines represent great strides, but they are <a href="https://doi.org/10.1136/bmj-2021-068632">not as effective in all populations</a>, nor are they as robust <a href="http://doi.org/10.1056/NEJMoa2119451">against new variants</a> as they are against the original strain of SARS-CoV-2, the virus that causes COVID-19.</p>
<p>Our research suggests that the next-generation COVID-19 vaccine we are currently testing will be more effective for longer, and will protect against new variants. </p>
<p>Our team, which includes experts in pathology and molecular medicine, infectious diseases, immunity and aerosol particles, has taken the progress we’d made toward a tuberculosis vaccine and quickly adapted the same approach to COVID-19. This <a href="https://doi.org/10.1172/jci.insight.155655">delivery system can be transformative</a>. </p>
<p>This promising science presents an opportunity to make a lasting and wider impact beyond COVID-19. While we still need to understand more fully how these vaccines work, my colleagues and I are optimistic this will finally give us a step up in controlling tuberculosis and other lung infections. </p>
<h2>An inhaled COVID-19 vaccine</h2>
<p>We are <a href="https://www.cbc.ca/news/canada/hamilton/hamilton-mcmaster-university-inhaled-covid-19-vaccine-1.6276462">conducting human trials</a> of our new COVID-19 vaccine. The Phase 1 clinical study is evaluating safety, as well as testing for evidence of immune responses in the blood and lung. Our new multivalent vaccine, manufactured for our clinical trial in the <a href="https://mirc.mcmaster.ca/research/services/vector-laboratory">Robert E. Fitzhenry Vector Laboratory</a>, targets multiple viral proteins, both the spike protein on the surface and proteins inside the virus. </p>
<p>With new variants, mutations occur in the spike protein on the outside of the virus. This makes the current vaccines less effective because they target only the spike protein. However, other proteins inside the virus stay the same. <a href="https://brighterworld.mcmaster.ca/articles/researchers-to-begin-human-trials-for-promising-new-inhaled-covid-19-vaccines-designed-to-combat-variants-of-concern/">Targeting multiple proteins means that if clinical trials show that our multivalent COVID vaccine</a> is effective, it will still protect against infection with new variants as they come along. </p>
<figure>
<iframe src="https://player.vimeo.com/video/652221887" width="500" height="281" frameborder="0" webkitallowfullscreen="" mozallowfullscreen="" allowfullscreen=""></iframe>
<figcaption><span class="caption">McMaster University video explaining how the new vaccine would be delivered by aerosol inhalation directly into the lungs.</span></figcaption>
</figure>
<p>In addition to being a friendlier way to take a vaccine, the inhaled form requires much less vaccine — as little as one per cent of what is currently being used in the present vaccines.</p>
<p>The new process delivers the vaccine directly to where the body will use it: the mucosal surface of the airways. This means <a href="https://doi.org/10.1016/j.cell.2022.02.005">less waste and more benefit, lower costs and reduced side-effects</a>.</p>
<p>The vaccine triggers an immune response in the cells lining the lungs to directly protect against COVID-19. This mucosal vaccination could also protect against other respiratory infections, from the common cold to influenza and bacterial pneumonia by rapidly calling on a range of immune cells that are at the ready as the first line of defence against infection. This lasting and broad form of general protection against infection is called <a href="https://ciiid.washington.edu/content/what-innate-immunity">innate immunity</a>. </p>
<p>When the virus particles in the vaccine are taken up by immune cells in the lung, they recruit more cells from elsewhere in the body and together they generate a strong immune response. The process involves a very beneficial type of cell called memory T cells, which, once recruited and activated, stay in the lung, and remain ready to face the infection. </p>
<h2>Decades of research</h2>
<p>Our <a href="https://globalnexus.mcmaster.ca/impact-areas/vaccine-innovation-roll-out/">multidisciplinary team</a> has arrived at the threshold of introducing this potentially transformative vaccine by pivoting decades of research. The antecedent of this work, the development of the viral vector, dates back more than 50 years to <a href="https://theconversation.com/how-the-puzzle-of-viral-vector-vaccines-was-solved-leading-to-todays-covid-19-shots-167341">the work of molecular biologist Frank Graham</a>, who created a microscopic Trojan horse by using a human adenovirus to carry critical viral genes safely into the body.</p>
<p>If we are able to show the new inhaled vaccine is safe and effective, as we anticipate, the payoffs can be huge in terms of human health, medical costs and better quality of life overall, especially for vulnerable populations. We are hopeful that greatly reduced costs for production, storage and shipping of the new vaccine product will allow greater access in developing and remote areas.</p>
<p>No one wanted this pandemic, but when at last it’s over, a new generation of vaccines targeting lung infections means we may all be able to breathe again, in all senses of the expression.</p><img src="https://counter.theconversation.com/content/181772/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fiona Smaill receives funding from:.
Canadian Institutes of Health Research </span></em></p>An inhaled COVID-19 vaccine would go directly to where the body would use it: the mucosal surface of the airways. This could mean less waste and more benefit, lower costs and reduced side-effects.Fiona Smaill, Professor of Pathology and Molecular Medicine, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1551532021-03-14T09:06:04Z2021-03-14T09:06:04ZFirst ever national survey shows the extent of South Africa’s TB problem<figure><img src="https://images.theconversation.com/files/388535/original/file-20210309-13-19yndw4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The WHO recommends that TB prevalence surveys be done in high burden countries. </span> <span class="attribution"><span class="source">Spencer Platt/Getty Images</span></span></figcaption></figure><p>South Africa’s long-awaited <a href="https://www.knowledgehub.org.za/system/files/elibdownloads/2021-02/A4_SA_TPS%20Short%20Report_10June20_Final_highres.pdf">tuberculosis (TB) prevalence survey</a> results were recently released. This is the first national prevalence survey of its kind for TB in South Africa. </p>
<p>TB prevalence surveys are difficult and expensive to do, and so are not carried out routinely, but have been done in many high burden countries following a World Health Organisation (WHO) <a href="https://www.who.int/publications/i/item/9789241598828">recommendation in 2007</a>. In the absence of prevalence survey data, TB estimates are based on the reported numbers of people treated for TB, adjusted to take account of the estimated number of people who have TB but don’t access treatment.</p>
<p>The results show that South Africa has a far higher number of people with TB than previously thought. And many people are living with TB who have not been diagnosed or treated. </p>
<p>It shows that prevalence of TB in South Africa in 2018 was 737 per 100,000. Prevalence was lowest in younger people (15-24 years) and peaked in those between the ages of 35 abd 44, and adults older than 65. </p>
<p>The survey was conducted between 2017 and 2019 by the South African Medical Research Council, Human Sciences Research Council and the National Institute for Communicable Diseases on behalf of the Department of Health. South Africa, along with other countries, routinely reports to the WHO the number of people who attend clinics and start TB treatment. But this regularly reported number misses many other people who have TB. </p>
<p>To be included in the TB statistics reported to the <a href="https://www.who.int/publications/i/item/9789240013131">WHO</a>, someone has to have visited the clinic for care, had their sputum tested, received a positive result and started TB treatment. People can be lost at any step in this process and their number may not be reflected in the national statistics. </p>
<p>People with TB who are missed or whose treatment is delayed may suffer prolonged ill-health. They may be unable to undertake normal daily activities, and be unable to work, resulting in economic hardship for themselves and their families. In addition, the longer a person has untreated TB, the more likely they are to pass the infection to other people and continue the cycle. </p>
<p>TB prevalence surveys like this one are important because they give a truer picture of the burden of disease. They are conducted in a random sample of people, selected from clusters that represent all provinces and socio-demographic groups in South Africa. </p>
<h2>New burden</h2>
<p>More than 35,000 people participated in this survey. This is a massive undertaking and the only way to get a more accurate picture of how many people in the country truly have TB.</p>
<p>This knowledge is critical because TB remains one of the leading causes of death in South Africa. It claims more lives annually than the <a href="https://sacoronavirus.co.za/">COVID-19 pandemic</a> has so far. This is despite TB being a curable disease. </p>
<p>The more accurate data that is now available indicates that there were 360,000 new cases of TB in 2019 – a good deal higher than the previous estimate of 301,000 TB cases in 2018.</p>
<p>Based on the new prevalence data, the WHO estimates that in 2019, <a href="https://tbfacts.org/tb-statistics-south-africa/">58,000</a> people died of TB in South Africa and <a href="https://apps.who.int/iris/bitstream/handle/10665/337538/9789240016095-eng.pdf">1.4 million people</a> died from TB globally. </p>
<p>TB is airborne and highly infectious. It spreads when an infected person coughs, sneezes, or even speaks, and people nearby breathe in the bacteria. It is important to understand what the levels of infection are in the country, especially because some people live with TB for a long time before they start treatment. This can be months or even years. Some people never get a diagnosis and never start treatment. They may be infectious and pass TB on to other people. They may also have damage to their lungs that is not picked up but may have long-term health consequences. By understanding the true rate of TB in South Africa, we can come up with better ways to find and treat all the people who have TB.</p>
<p>The prevalence survey also flags some important trends. Most of the people whose TB disease was “missed” are men and are HIV-negative. This is similar to <a href="https://pubmed.ncbi.nlm.nih.gov/27598345/">findings</a> from other countries in Africa. It is also backed by preliminary results from <a href="https://pubmed.ncbi.nlm.nih.gov/32802963/">Vukuzazi</a>, a large-scale community health screening survey we conducted in northern KwaZulu-Natal. </p>
<p>Our <a href="https://www.abstractserver.com/TheUnion2018/TheUnion2018_Abstracts_Web.pdf#page=605">previous research</a> has also shown that HIV-negative men are less likely than HIV-positive people or HIV-negative women to attend clinics for health checks. More effort needs to be put into finding and treating people with active TB. In particular, there is an urgent need for research to figure out how to reach HIV-negative men who rarely visit clinics.</p>
<p>An important finding of the national TB prevalence survey is that most of the people found to have TB in the survey did not report having the <a href="https://tbfacts.org/tb/">classic symptoms</a> of TB. These include cough, fever, night sweats and weight loss. This means that we need new diagnostic tools for TB that can help screen large numbers of people, even those who don’t have symptoms. The Department of Health has emphasised the use of chest X-rays for screening for TB. Because of the logistics involved, this will be challenging to implement, especially in under-served, rural areas of the country. Research into new, accurate and mobile diagnostics should be a priority.</p>
<h2>The COVID-19 impact</h2>
<p>COVID-19 has had a devastating impact on the number of people getting tested and treated for TB. According to <a href="http://www.samj.org.za/index.php/samj/article/view/13137">new research</a>, testing rates for TB have dropped by up to 50% in the year since South Africa’s COVID-19 lockdown. </p>
<p>Additionally, far fewer people have accessed treatment for TB since March 2020. </p>
<p>Unfortunately, this means that current rates of TB are likely to be even higher than those identified during the pre-COVID-19 era. </p>
<p>Even in light of the economic and health challenges presented by COVID-19, the South African health community must maintain a focus on finding and treating TB. The national TB prevalence survey provides very useful information to guide how to do this.</p><img src="https://counter.theconversation.com/content/155153/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Emily Wong and members of her laboratory receive funding from the National Institute of Allergy and Infectious Diseases and the Fogarty International Center of the National Institutes of Health, the Bill and Melinda Gates Foundation, the South African Medical Research Council and the African Academy of Sciences.</span></em></p><p class="fine-print"><em><span>Alison Grant receives funding from Economic and Social Research Council (UK), National Institute of Allergy and Infectious Diseases (USA), Bill and Melinda Gates Foundation, Wellcome Trust. </span></em></p>South Africa’s long-awaited TB prevalence survey results were recently released. They reveal that the country has a much higher burden of TB than previously thought.Emily B. Wong, Assistant Professor, Africa Health Research Institute (AHRI)Alison Grant, Professor of International Health at LSHTM and Member of Faculty, Africa Health Research Institute (AHRI)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1283272020-01-13T14:40:03Z2020-01-13T14:40:03ZPreventing TB: a big drug price cut paves the way for global scale-up<figure><img src="https://images.theconversation.com/files/305249/original/file-20191204-70105-5do0uo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Nic Bothma/EPA</span></span></figcaption></figure><p>Lengthy negotiations ended in good news recently when the price of rifapentine, a lifesaving antibiotic, was <a href="https://www.theguardian.com/global-development/2019/oct/31/antibiotic-price-drop-could-stop-millions-from-developing-tuberculosis">marked down by 66%</a> by its manufacturer Sanofi. When combined with another antibiotic (isoniazid), rifapentine can prevent tuberculosis (TB) disease. The move was announced at the <a href="https://hyderabad.worldlunghealth.org/">Union World Conference on Lung Health</a> in October 2019. </p>
<p>Talks to lower the price from US$45 to US$15 for a three-month course took more than a year to complete and involved Sanofi, Unitaid and the Global Fund to Fight Aids, Tuberculosis and Malaria, in collaboration with the Stop TB Partnership’s Global Drug Facility and the United States PEPFAR initiative. </p>
<p>Now we – those of us who have been working to bring preventive therapy to the people whose lives depend on it – must roll up our sleeves and make it happen.</p>
<p>Advocates have been pressing for the price of rifapentine to be lowered ever since scientific proof of its effectiveness was <a href="https://www.researchgate.net/publication/275300925_Rifapentine_Pharmacokinetics_and_Tolerability_in_Children_and_Adults_Treated_Once_Weekly_With_Rifapentine_and_Isoniazid_for_Latent_Tuberculosis_Infection">published </a>in <a href="https://www.researchgate.net/publication/306024372_Rifapentine_for_the_Treatment_of_Latent_Tuberculosis">peer-reviewed</a> journals. Three months of treatment with rifapentine plus isoniazid was shown to be just as effective and less toxic than one year of therapy with isoniazid alone (the previous standard). The reduction in treatment time alone provides an obvious improvement. </p>
<p>The obstacles to getting more people treated begin with locating those at greatest risk and then expanding capacity in preventive treatment programmes to serve them.</p>
<h2>Who needs the drug?</h2>
<p>TB is one of the top ten causes of death from an infectious agent worldwide, killing approximately <a href="https://www.who.int/tb/publications/factsheet_global.pdf?ua=1">1.5 million people</a> in 2018. The disease hits especially hard in impoverished regions, where poorly ventilated and overcrowded living and working conditions, inadequate nutrition, the prevalence of other diseases like HIV, and insufficient or non-existent health care all make it far worse than it could be. </p>
<p>Most TB cases in 2018 were in <a href="https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1#page=15">South-East Asia (44%) and Africa (24%)</a>. Combined, the two regions accounted for nearly two thirds of all the world’s TB cases. </p>
<p>TB is highly contagious and spread by a cough or sneeze. Family members and other close contacts of people with the disease are at the highest risk of infection. People who contract TB don’t always get sick immediately. Instead, a TB infection can lie dormant for years until other stresses activate it. People living with HIV are at greater risk of developing TB and are 20 to 37 times more likely to move from the TB infection stage to active TB disease. New HIV infections have been <a href="https://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf">decreasing globally</a> but sub-Saharan Africa still saw more than <a href="http://apps.who.int/gho/data/view.main.HIVINCIDENCEREGIONv?lang=en">one million new HIV infections</a> in 2018. </p>
<p>In February 2018, the World Health Organisation (WHO) reviewed its <a href="https://apps.who.int/iris/bitstream/handle/10665/260233/9789241550239-eng.pdf;jsessionid=B5140E3D51E6DB954062BC3A6F75F7E1?sequence=1">guidelines for preventing TB disease</a>. The guidelines now include <a href="https://www.impaact4tb.org/https-www-impaact4tb-org-wp-content-uploads-2018-08-njie-2018_amjprevmed_3hp-srma_-pdf/">three months of rifapentine and isoniazid</a> taken weekly for people living in countries with a high TB burden. This regimen is known as 3HP. </p>
<p>The WHO recommends that anyone living with HIV and those living in the same household as a person with TB disease should receive TB preventive therapy. The theme of 2019’s <a href="https://www.who.int/westernpacific/news/events/detail/2019/12/01/western-pacific-events/world-aids-day-2019">World AIDS Day</a> was “Ending the HIV/AIDS epidemic: Communities make the difference”. Reaching this goal requires that preventive treatment programmes engage with communities to develop, refine and bring to scale interventions designed to meet the needs of people with and vulnerable to HIV and TB. These interventions should ensure that people living with HIV do not die of TB.</p>
<p>Importantly, the 3HP regimen can be administered along with dolutegravir, a better antiretroviral drug which is <a href="https://www.timeslive.co.za/sunday-times/lifestyle/health-and-sex/2019-11-28-its-highly-effective-cheaper-sa-to-launch-advanced-new-hiv-drug/">now being provided in South Africa</a> and globally. The combination is an effective tool for keeping vulnerable people as healthy as possible. The reduced amount of time needed for treatment – three months as opposed to six months of isoniazid only, the current standard of care – increases the likelihood that patients will complete treatment.</p>
<h2>Treating more people</h2>
<p>All prevention programmes must begin with finding the people who need TB preventive therapy. People living with HIV can be identified through HIV clinics. Contacts of people with TB disease can be identified by investigating affected households. People must always be screened for TB before starting TB preventive therapy.</p>
<p>In 2018, the member states of the United Nations committed to expanding the number of people receiving preventive treatment to <a href="http://www.stoptb.org/global/advocacy/unhlm_targets.asp">at least 30 million by 2022</a>. But the world is nowhere close to meeting that goal. It will take a lot of work to achieve these targets, and until then millions of people will remain at risk of TB disease.</p>
<p>With the price break on Sanofi’s rifapentine product Priftin, TB preventive treatment can now be made available in many more places. If Priftin has not been approved for use in a country that needs this treatment, national TB programmes can work with the WHO and local regulatory authorities to process waivers – as <a href="https://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/regulator-waives-off-clinical-trials-clears-sanofi-tb-drug/articleshow/71931597.cms">India</a> did.</p>
<p>Treatment for latent TB infection has been available since the 1950s, yet very few people who could benefit from TB preventive therapy are taking it. Hundreds of thousands of lives are unnecessarily at risk. This price break – making a shorter and equally effective treatment more affordable – is a perfect opportunity to make a dent in these numbers.</p><img src="https://counter.theconversation.com/content/128327/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gavin Churchyard does not work for, or own shares in any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment. Sanofi donated isoniazid and rifapentine for various studies. Gavin Churchyard consulted without payment for Sanofi.</span></em></p>Obstacles to getting more people with TB treated extend beyond cost. It starts with locating people at greatest risk and expanding preventive treatment programmes.Gavin Churchyard, Honorary Professor, School of Public Health, University of the Witwatersrand and CEO, Aurum InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1141032019-03-27T13:30:50Z2019-03-27T13:30:50ZScientists are developing new, exciting strategies for the fight against TB<figure><img src="https://images.theconversation.com/files/266127/original/file-20190327-139361-27hj79.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Chest x-ray showing TB infection in the lungs.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Tuberculosis (TB) is a lung disease caused by the bacterium <em>Mycobacterium tuberculosis</em>. It’s transmitted through air droplets when an infectious person coughs or sneezes. The disease can be treated, but it’s a long process with the drugs that are currently available. It remains a major health problem: globally, about <a href="https://www.who.int/tb/publications/global_report/tb18_ExecSum_web_4Oct18.pdf?ua=1">1.6 million</a> died from it in 2017. </p>
<p>Most of these deaths occurred in the developing world. The African continent has a <a href="https://afro.who.int/health-topics/tuberculosis-tb">particularly severe</a> TB burden. This is worsened by the emergence of multidrug-resistant TB; patients with this form of the disease respond poorly to the usual first-line drugs. TB and HIV <a href="https://www.who.int/hiv/topics/tb/en/">co-infection</a> is also a big problem. </p>
<p>There are some glimmers of hope. Globally, TB related deaths dropped by <a href="https://www.who.int/tb/post2015_TBstrategy.pdf?ua=1">33%</a> between 2000 and 2017. There’s also a new push from the <a href="https://www.who.int/tb/post2015_TBstrategy.pdf?ua=1">World Health Organisation (WHO)</a> to reduce new TB cases by 90% by 2035. But for this to happen, new therapies and diagnostic tools are needed.</p>
<p>There are some promising therapies in the pipeline, particularly when it comes to host-directed therapies and biomarkers. The first refers to drugs that strengthen the immune system and reduce lung damage. Biomarkers are blood- or tissue-based indicators that tell clinicians about the presence of latent (or dormant) TB, the development of active TB and its progression.</p>
<p>Governments, global funding agencies, national research councils and the private sector now need to invest resources in developing these therapies to the point where they can be used widely. This is crucial if the WHO’s ambitious targets are to be met.</p>
<h2>Host-directed therapies</h2>
<p>In TB treatment, host-directed therapies have two major goals. One is to stimulate key components of the immune system to control TB infection. The other involves limiting damage to the lung tissue in a bid to slow down TB’s progression. </p>
<p>Host-directed therapies can also be combined with standard treatment regimens. This will likely shorten the current course of TB treatment, which at its shortest lasts for about six months.</p>
<p>Some of the host-directed therapies that are <a href="https://www.ncbi.nlm.nih.gov/pubmed/26184493">currently being investigated</a> include:</p>
<ul>
<li><p><a href="https://www.ncbi.nlm.nih.gov/pubmed/21998409">Vitamin D</a>, which induces specific immune molecules that have protective effects against the TB bacteria.</p></li>
<li><p>Non-steroidal <a href="https://www.ncbi.nlm.nih.gov/pubmed/25986592">anti-inflammatory drugs</a> (ibuprofen, zileuton and aspirin). These work by suppressing excessive inflammation and tissue pathology and reduce bacterial burdens in the lung.</p></li>
<li><p><a href="https://www.ncbi.nlm.nih.gov/pubmed/24133190">Statins</a> reduce cholesterol levels and limit bacterial growth in the body’s immune cells.</p></li>
<li><p><a href="https://www.thelancet.com/action/showPdf?pii=S1473-3099%2816%2900078-5">Angiogenesis inhibitor (Bevacizimub)</a> is a drug that works by blocking formation of new blood vessels (neovascularisation) in <a href="https://www.ncbi.nlm.nih.gov/pubmed/27043495">lung granulomas</a> (small areas of inflammation). It might improve anti-TB drug penetration into granulomas and increase air supply.</p></li>
</ul>
<h2>Diagnostics and biomarkers</h2>
<p>Treating TB is only one part of the puzzle. Proper, timely diagnosis and a good understanding of the disease’s progression in an individual patient are also important.</p>
<p>The disease is currently diagnosed in several ways. These include viewing a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705651/">sputum sample</a> under a microscope; through <a href="https://www.tbfacts.org/tb-tests/">a skin test</a>; or through <a href="https://www.tbfacts.org/tb-tests/">a blood test</a>.</p>
<p>But biomarkers could hold useful answers, too. About <a href="https://www.ncbi.nlm.nih.gov/pubmed/27822210">one-third </a>of the world’s population is infected with the bacterium that causes TB. Between 5% and 10% of these latently infected individuals will develop the active disease in their lifetime. Biomarkers could be used to reliably predict who these individuals are. The individuals could then be treated preemptively.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/266129/original/file-20190327-139361-1agnlps.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/266129/original/file-20190327-139361-1agnlps.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=191&fit=crop&dpr=1 600w, https://images.theconversation.com/files/266129/original/file-20190327-139361-1agnlps.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=191&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/266129/original/file-20190327-139361-1agnlps.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=191&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/266129/original/file-20190327-139361-1agnlps.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=240&fit=crop&dpr=1 754w, https://images.theconversation.com/files/266129/original/file-20190327-139361-1agnlps.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=240&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/266129/original/file-20190327-139361-1agnlps.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=240&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A representation different stages of TB.</span>
<span class="attribution"><span class="source">Pai et al, 2016</span></span>
</figcaption>
</figure>
<p>There have been exciting studies along these lines. These have identified the gene and protein signatures associated with the <a href="https://www.ncbi.nlm.nih.gov/pubmed/27017310">sub-clinical</a> stage of TB – that is, latently infected individuals on the brink of converting to active TB. Such signatures are evident in patients’ blood as early as 200 days before the onset of active TB. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Metabolite+changes+in+blood+predict+the+onset+of+tuberculosis">Metabolic biomarkers</a> associated with the pre-symptomatic stage of TB have also been identified. Again, these are detectable before the onset of the active disease.</p>
<p>However, the pipeline for biomarkers that can detect other forms of TB, among them the drug-resistant variety, is weak. More work remains to be done in this area.</p>
<h2>Investment needed</h2>
<p>Studies like these, and others, require <a href="https://www.ncbi.nlm.nih.gov/pubmed/27784885">increased investments</a> from a number of funders. These are crucial if scientists are to take their findings into the clinical trial stages and eventually develop tools that can be used in everyday TB diagnosis and treatment.</p>
<p>This is imperative if the world is to end TB.</p>
<p><em>Sephekana Samuel Mohapi, a Master’s student in the University of Cape Town’s Department of Pathology, contributed to this article.</em></p><img src="https://counter.theconversation.com/content/114103/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mohlopheni Jackson Marakalala receives funding from the Wellcome Trust, South African Medical Research Council and National Research Foundation. </span></em></p>The push to end TB requires significant investment into the research and development of new diagnostics and treatments.Mohlopheni Jackson Marakalala, Associate professor, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1137912019-03-21T12:56:36Z2019-03-21T12:56:36ZTB doesn’t only attack the lungs – other organs are also vulnerable<figure><img src="https://images.theconversation.com/files/264670/original/file-20190319-60959-gqhblx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">X-rays, CT scans or MRIs may be necessary to detect TB in organs other than the lungs.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><em>The world marks <a href="https://www.who.int/news-room/events/detail/2019/03/24/default-calendar/world-tb-day-2019">World Tuberculosis (TB) Day</a> on March 24 every year. Most people assume that TB only affects the lungs – but the disease can also attack other organs. The Conversation Africa’s Ina Skosana spoke to Professor Nazir Ismail to find out more. Professor Ismail works and conducts his research in South Africa, one of the world’s TB hot spots.</em> </p>
<p><strong>What parts of the body does TB affect?</strong></p>
<p>TB most commonly affects the lungs – what’s known as the body’s pulmonary system. But it affects other organs too, what’s known as extrapulmonary TB.</p>
<p>Other organs that can be affected include the lining covering the lungs (pleural TB); the central nervous system (TB meningitis); bone and joints (musculoskeletal system); lymph nodes; abdomen – where the liver, spleen and the intestines can be affected (abdominal TB); kidney and bladder (urogenital TB); and blood. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/264651/original/file-20190319-60975-108312d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/264651/original/file-20190319-60975-108312d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=360&fit=crop&dpr=1 600w, https://images.theconversation.com/files/264651/original/file-20190319-60975-108312d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=360&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/264651/original/file-20190319-60975-108312d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=360&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/264651/original/file-20190319-60975-108312d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=452&fit=crop&dpr=1 754w, https://images.theconversation.com/files/264651/original/file-20190319-60975-108312d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=452&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/264651/original/file-20190319-60975-108312d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=452&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Global TB incidence.</span>
<span class="attribution"><span class="source">WHO Global TB report 2018</span></span>
</figcaption>
</figure>
<p>A <a href="http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742014000100014">study</a> conducted in Johannesburg showed that the most common sites of extra pulmonary TB were the pleura (39.1%), lymph nodes (31.0%), blood (21.8%), central nervous system (7.3%), and abdomen (2.9%). </p>
<p>Another <a href="https://medpharm.tandfonline.com/doi/full/10.1080/23120053.2017.1403207#.XI_uvCgzZPY">study</a> conducted in the KwaZulu-Natal province also showed pleural TB to be the most common form of extra pulmonary TB (36% of patients).</p>
<p><strong>How common is this form of TB? What causes it?</strong></p>
<p>According to the <a href="https://www.who.int/tb/publications/global_report/tb18_ExecSum_web_4Oct18.pdf?ua=1">World Health Organisation’s most recent TB report</a>, extrapulmonary TB accounted for 14% of TB cases recorded globally in 2017. Across the African continent, extrapulmonary TB accounted for 16% of the 1 323 450 cases recorded. In South Africa it accounts for 11% of all TB cases reported. </p>
<p>Importantly – unlike pulmonary TB, which is spread through the air from person to person – extrapulmonary TB is not infectious.</p>
<p>A key risk factor for developing extrapulmonary TB is a compromised immune system which is why it is more common in patients infected with HIV. It can also occur in people with diabetes, cancer, low body weight and chronic kidney disease. Smoking and the use of drugs that can suppress the immune system also increase the risk of extrapulmonary TB.</p>
<p>Though the risk factors differ, all types of TB develop in the same way. TB infection occurs when a person inhales droplet particles containing the TB bacterium. Once inhaled, the bacteria then heads for the lungs. If the immune system is fully functional, several mechanisms are put in place by the body’s response to the foreign agent to contain the bacteria. The end result is usually a walled off “granuloma”, preventing the TB bacteria from multiplying and making the person ill. </p>
<p>In some patients, the TB escapes to another part of the body before the lungs can wall it off. In healthy people with strong immune systems, other organs or systems will put up a “barrier” that’s similar to the lung’s granuloma. </p>
<p>But if this defence mechanism fails, the bacteria multiply and cause disease in that specific organ system. This is called primary TB and is usually seen in young children. </p>
<p>Sometimes, a person can successfully wall off TB when they are healthy. But as their immune system weakens – because of old age, or conditions like HIV and diabetes – the wall can break down. If that happens, the bacteria can multiply and lead to active disease. </p>
<p><strong>How is extrapulmonary TB diagnosed and treated?</strong></p>
<p>Clinicians find it challenging to diagnose extrapulmonary TB. This is because the patient doesn’t present with the typical signs and symptoms of pulmonary TB – chronic cough, fever, loss of weight and night sweats. In some cases, the presenting signs and symptoms can be very vague and can mimic other conditions. All this means the clinician must have a strong suspicion that their patient has extrapulmonary TB to even start seeking this diagnosis.</p>
<p>Investigations include X-rays, CT scans or MRIs and sending appropriate specimens to the laboratory to detect the TB bacterium. The type of specimen that should be sent depends on the organ system involved. For example, in the case of lymph node TB, a biopsy (tissue specimen) of the lymph node should be sent to the laboratory; in the case of pleural TB, pleural fluid should be sent for testing. </p>
<p>It is important to note that in certain instances, even though the laboratory result might be negative, the clinician may still opt to treat for tuberculosis based on the high clinical suspicion, constellation of clinical signs and symptoms; and adjunct special investigations (biopsy, CT scans).</p>
<p>The drugs used to treat extrapulmonary TB are the same as those used for the treatment of pulmonary TB. The only difference is that the duration of treatment for extrapulmonary TB is longer and depends on the organ system involved. Most extrapulmonary TB is treated for nine months but can sometimes be longer. Treatment is taken orally and is a combination tablet that is dosed based on a person’s weight. Hospital admission is not required for treatment unless the patient is severely ill. Patients can continue to take their medication at home. </p>
<p><strong>How does a person know they’ve got it?</strong></p>
<p>The presentation of extrapulmonary TB depends on which organ is involved. An example is lymph node TB on a person’s neck which would present as a noticeable growth or lump. There are multiple causes for such a growth, one of which is TB, which the doctor would know to investigate. Thus seeking medical advice early when you are unwell is an important starting point.</p><img src="https://counter.theconversation.com/content/113791/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nazir Ismail receives funding from the South African Government and other International Funding agencies (Newton Fund, CDC etc). </span></em></p>TB outside the lungs accounted for 14% of TB cases recorded globally in 2017.Nazir Ismail, Head of the Centre for Tuberculosis, National Institute for Communicable DiseasesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1137652019-03-20T14:49:25Z2019-03-20T14:49:25ZMajor battles have been won against TB. But the war isn’t over<figure><img src="https://images.theconversation.com/files/264362/original/file-20190318-28496-km7u59.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">TB, which is caused by the bacterium Mycobacterium Tuberculosis, is a leading cause of death.
</span> <span class="attribution"><span class="source">Kateryna Kon/Shutterstock</span></span></figcaption></figure><p>The suffering and massive loss of life caused by Tuberculosis (TB) are proof that humanity hasn’t prioritised the development of tools to eliminate <a href="https://www.cdc.gov/tb/worldtbday/history.htm">a disease dating back 9 000 years</a>. Two stark facts highlight this: most of the antibiotics used to treat TB were developed decades ago. And, until very recently, some diagnostic approaches being used were a century old. </p>
<p>There’s a chronic funding gap for TB research and development. The Global TB Alliance estimates that it’s as high as <a href="https://www.tballiance.org/news/closing-tb-funding-gap">$1.3 billion per year</a>. </p>
<p>While still inadequate, there has been a shift towards reducing the <a href="http://www.treatmentactiongroup.org/content/tbrd2018?eType=EmailBlastContent&eId=7dac4161-dc99-43a2-9447-4d18aeb4c8ac">funding gap</a> over the last two years. This, together with invigorated research strategies from large funding organisations such as the <a href="https://www.niaid.nih.gov/sites/default/files/TBStrategicPlan2018.pdf">National Institutes for Allergy and Infectious Diseases</a>, point to a shift in the TB landscape.</p>
<p>As a consequence, there have been some exciting and positive movements on both treatment as well as prevention aspects.</p>
<p>There’s also a growing appreciation that focusing on ensuring good treatment outcomes alone won’t be enough to eliminate TB. The disease has to be viewed as continuum of care. Attention must also be given, for example, to how people access healthcare services and where they are lost in the system. </p>
<h2>The pandemic</h2>
<p>TB, caused by the bacterium <em>Mycobacterium tuberculosis</em>, killed <a href="https://www.who.int/news-room/fact-sheets/detail/tuberculosis">1.6 million</a> people in 2017, the highest number of deaths caused by a bacterial infectious disease. In addition, 10 million were infected with TB bacteria, the majority being poor people in the developing world. </p>
<p>In Southern Africa, high rates of HIV infection have been the primary driver of TB disease to the point where the region is now home to the world’s worst HIV-TB epidemic. </p>
<p>In 2017, <a href="https://www.who.int/tb/areas-of-work/children/en/">1 million children</a> were infected with the TB bacteria and 233 000 died of the disease. The scourge of drug resistant TB has necessitated treatment with antibiotics that cause side effects such as deafness, leading to extraordinary levels of human suffering. There were almost half a million of these cases in 2017. </p>
<p>Signs of fresh energy to deal with the problem appeared on the horizon with the first WHO global ministerial conference in Moscow in 2017. Representatives from 120 nations adopted a <a href="https://www.who.int/tb/features_archive/Online_Consultation_MinisterialConferenceDeclaration/en/">declaration</a> to rapidly achieve universal health coverage for eliminating TB. </p>
<p>A year later, the United Nations held its first ever high-level meeting on TB. The UN convened the <a href="https://www.who.int/tb/features_archive/UNGA_HLM_ending_TB/en/">General Assembly</a> with the goal of establishing an accountability framework to drive the goal of ending TB. </p>
<p>The meeting identified a number of clear threats. The main ones were:</p>
<ul>
<li><p>The rapid rise of drug resistance, </p></li>
<li><p>An increase in TB incidence in vulnerable populations including children, healthcare workers and people living with HIV, and</p></li>
<li><p>A disproportionate disease burden among the poorest countries with crippled public healthcare systems. </p></li>
</ul>
<h2>Vaccine and prevention</h2>
<p>Two new TB vaccine studies have created a great deal of excitement about the development of a vaccine that would prevent infection or disease. </p>
<p>The first <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1714021">study</a> looked at how revaccination with the current vaccine <a href="https://www.cdc.gov/tb/publications/factsheets/prevention/bcg.htm">BCG</a> resulted in the protection of adolescents from infection. This suggests that BCG revaccination maybe be a useful TB prevention strategy. </p>
<p>The second involved a <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1803484">clinical trial</a> of a new vaccine candidate. This showed that it was possible to prevent adults who were infected with TB bacteria from developing active TB. </p>
<p>These two studies have raised hope that creating a new TB vaccine is a definitive possibility. </p>
<h2>Treatment breakthroughs</h2>
<p>Advances have also been made on the treatment front.</p>
<p>A recent <a href="https://www.spotlightnsp.co.za/2019/03/12/new-science-highlights-from-croi2019/">study</a> shows that it’s possible to prevent people with HIV from developing active TB disease. The study showed that it is safe to administer antiretroviral therapy combined with a preventive TB treatment commonly known as the 3-HP to people living with HIV. </p>
<p>Now that the safety of this treatment has been shown, the next step would be for the National Department of Health to consider the feasibility of making these drugs available to people with HIV through the public system. </p>
<p>Research also suggests that the two new TB drugs that have emerged recently, <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30106-3/abstract">Bedaquiline and Delamanid</a>, can be administered together safely. This has important implications for creating new treatment options for drug resistant TB. </p>
<p>Interesting scientific advances have emerged such as boosting the immune system with an approach called <a href="https://onlinelibrary.wiley.com/doi/abs/10.15252/embr.201846613">immunotherapy</a>, to fight TB. This approach uses structures that are released by immune cells infected with TB bacteria to boost the activity of the immune response. </p>
<p>In South Africa, recent <a href="https://www.nature.com/articles/s41467-018-07635-7">studies</a> have reported clinically useful <a href="https://www.atsjournals.org/doi/abs/10.1164/rccm.201711-2340OC">biomarkers</a> that predict future outcomes of infection and disease. These have also increased scientists’ understanding of underlying TB disease mechanisms. </p>
<h2>Way forward</h2>
<p>These positive movements signal a shift in the landscape. But the world can’t afford to be complacent. We cannot afford to lose momentum after coming so far. All nations, especially TB endemic countries, need to take up the call for action laid out in the UN declaration. </p>
<p>But the world won’t simply treat its way out of the epidemic with antibiotics. Interrupting transmission, developing a vaccine, protecting vulnerable populations, developing new diagnostics and better treatment regimens are all required for controlling the epidemic. </p>
<p>Innovative and cost effective diagnostic and case finding approaches are desperately needed to strengthen health care systems together with more investment in research and development. </p>
<p>Finally, we all need to advocate for more resources and better patient support. TB is everyone’s problem – not just the poor and forgotten.</p><img src="https://counter.theconversation.com/content/113765/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bavesh Kana consults for the Medical Research Council of South Africa. He is a founding member of Smartspot Quality CC. He receives or has received funding from the National Research Foundation, the United States National Institutes of Health, the Centre for the AIDS Programme of Research in South Africa (CAPRISA), the Bill and Melinda Gates Foundation, the Howard Hughes Medical Institute, the South African Medical Research Council, and the National Health Laboratory Services Research Trust. He is a member of the South African national TB Think Tank. </span></em></p>In Southern Africa, high rates of HIV infection have been the primary driver of TBBavesh Kana, Head of the Centre of Excellence for Biomedical TB Research, University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/967742018-05-27T10:54:45Z2018-05-27T10:54:45ZThe remarkable story of hope: how attitudes to drug-resistant TB changed<figure><img src="https://images.theconversation.com/files/219460/original/file-20180517-26295-sh78mm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A woman with her treatment regime for extensively drug-resistant TB in Khayelitsha, Cape Town. </span> <span class="attribution"><span class="source">MSF</span></span></figcaption></figure><p>The informal settlement of Khayelitsha in Cape Town is the latest site of a <a href="http://www.endtb.org/clinical-trial">multi country trial</a> that aims to transform the treatment for drug-resistant tuberculosis (DR-TB). </p>
<p>The endTB clinic was officially opened by <a href="https://www.msf.org.za/about-us">Doctors Without Borders (MSF)</a> and the City of Cape Town and will test five new drug regimens in Peru, Lesotho, Kazakhstan, Georgia and South Africa. </p>
<p>The current standard treatment for drug-resistant TB is arduous. It can last for between nine and 24 months, and includes a painful daily injection for up to six months which can cause hearing loss and other serious side effects in up to 60% of patients. </p>
<p>Even worse, standard treatment is only successful in about half of all cases. </p>
<p>The trial will use bedaquiline and delamanid – the first TB drugs to have been developed in almost 50 years –- in experimental new treatments with other drugs such as clofazimine, linezolid, fluoroquinolones and pyrazinamide, with the aim of finding at least one new treatment that is shorter, more effective and less toxic than the current treatment. </p>
<p>The experimental treatments are all-oral, meaning the toxic injectable that has been used in drug-resistant TB treatment for over half a century is not incorporated. </p>
<p>If the trial proves successful, it will be a major revolution in the treatment of the age-old disease. But it won’t be the first. There have been several over the past 100 years and we’ve come a long way. But the fact that the current treatment can only be administered by injection, and that nearly two thirds of people who are treated go deaf, elegantly explains why we’ve still got a long way to go.</p>
<p>There’s reason for optimism. Over the last 20 years I’ve seen a dramatic change in attitude towards people with drug resistant TB – from the World Health Organisation (WHO) right down to health workers in the smallest clinic. This gives me great hope that we’re on the right track to institutionalising care that has the patient at the very centre.</p>
<h2>A misconception</h2>
<p>I first witnessed South Africa’s rapidly growing drug-resistant TB epidemic during in 1999 while working in <a href="https://www.msf.org.za/about-us/where-we-work/south-africa">Khayelitsha</a> with MSF. Khayelitsha was then – and remains – one of the highest TB and drug-resistant TB burden settings in the world.</p>
<p>The dominant but incorrect view of the World Health Organisation at the time was that drug-resistant TB was the patients’ fault because they didn’t take their treatment properly. Another line of argument was that it was due to health service issues, including bad quality drugs or wrong prescriptions.</p>
<p>Patients with drug-resistant TB were seen as “defaulters” who created their own disease. They were stigmatised and stripped of their right to dignity and freedom of movement. Typically they were confined to hospitals, or locked up in sanatoriums, often against their will.</p>
<p>These misconceptions meant that preventing people from acquiring drug-resistant TB was the priority. Treatment wasn’t, because existing regimens were believed to be sufficient. This in turn disincentivised the development of new ways to fight drug-resistant TB.</p>
<p>At the time drug-resistant TB was essentially a medical blind spot. The extent of it was underestimated across the world. The WHO’s annual drug-resistant TB reports spoke of “hot spots” – identifying South Africa and Egypt as the main ones in Africa. But in fact these were the few places in Africa then testing for TB drug resistance, and the problem was actually far, far worse.</p>
<p>The tide started to turn in 2000. </p>
<h2>Diagnostic revolution</h2>
<p>In the early 2000s a decision was finally taken to tackle the problem. After the fall of the Berlin Wall it emerged that many parts of Eastern Europe – particularly but not exclusively prisons – also had high rates of drug-resistant TB. Evidence was also emerging of high rates of drug-resistant TB in areas with high numbers of patients also living with HIV. </p>
<p>It was clear that this was not an isolated epidemic, and that drug resistant TB needed to be tackled head on. </p>
<p>The first big breakthrough was in 2006 when scientists developed the ability to speed up and expand the diagnosis of drug-resistant TB. They used genotypic testing: diagnostic tools that enable clinicians to diagnose and confirm drug resistance in TB cases in just a few hours, avoiding weeks of waiting for results from scientists in central laboratories.</p>
<p>By 2011, South Africa was going all out to identify how big the epidemic was, with a nationwide roll out of nearly <a href="http://www.stoptb.org/wg/gli/assets/html/day%203/Stevens%20-%20South%20Africa.pdf">800 GeneXpert machines</a>. </p>
<p>Within just a few years, the world had started to realise the scale of the problem. Today, the <a href="http://www.who.int/tb/publications/global_report/en/">WHO estimates</a> there are 19 000 new drug-resistant TB cases a year in South Africa alone.</p>
<p>Mapping the scale of the problem also made the pharmaceutical market for drug-resistant TB more lucrative. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/219455/original/file-20180517-26290-1o2mgkf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/219455/original/file-20180517-26290-1o2mgkf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/219455/original/file-20180517-26290-1o2mgkf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/219455/original/file-20180517-26290-1o2mgkf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/219455/original/file-20180517-26290-1o2mgkf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/219455/original/file-20180517-26290-1o2mgkf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/219455/original/file-20180517-26290-1o2mgkf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A woman waits for her appointment at the clinic in Khayelitsha in the Western Cape.</span>
<span class="attribution"><span class="source">MSF</span></span>
</figcaption>
</figure>
<p>There’s been another reason for the changes in attitude to drug-resistant TB – the courageous decision of MSF’s first drug-resistant TB patients from Khayelitsha to speak out. Ten years ago when drug-resistant TB patients were being blamed for their condition it was unheard of for a patient to raise their voice. </p>
<p>But patients like <a href="https://www.theguardian.com/global-development-professionals-network/2014/jul/07/tb-south-africa-patents-drug-resistance-phumeza-tisile-medicins-sans-frontieres">Phumeza Tisile from Khayelitsha</a>, who went permanently deaf from the daily kanamycin injections, became powerful public advocates for better treatment. By 2014 Phumeza -– then cured of XDR-TB after two years of treatment – delivered 50,000 signatures on the drug-resistant TB manifesto at the <a href="http://www.msf.org/en/article/phumeza-takes-tb-petition-world-health-assembly-delegates">World Health Assembly</a>, calling on members to radically improve care.</p>
<p>As a result of her actions others started to object to the treatment – a dynamic similar to what happened among people living with HIV in South Africa in the early 2000s. Today drug-resistant TB survivors don’t feel ashamed to say they want a less toxic, shorter treatment, and to demand that their basic rights are respected. By speaking out they’ve made sure that a much more patient-centred approach is been put in place. </p>
<p>But care still remains inadequate. It’s still too long, painful and too toxic.</p>
<p>This makes the endTB trial and its ambitious aim of finding new treatment regimens that are demonstrably safe and effective, shorter and able to be taken orally all the more important. If the trial achieves its aims, it will take forward the ongoing revolution in tackling this form of TB.</p><img src="https://counter.theconversation.com/content/96774/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eric Goemaere does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Treatment for drug-resistant TB remains problematic as the painful daily injectable patients receive for at least six months leaves more than 60% deaf.Eric Goemaere, Honorary senior lecturer in the School of Public Health and Family Medicine, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/736092017-03-12T10:20:21Z2017-03-12T10:20:21ZWhy a test that tells when TB is cured is needed to help tackle resistance<figure><img src="https://images.theconversation.com/files/160322/original/image-20170310-3703-1clqol4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>-<em>Every day more than <a href="http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1">6 million people</a> across the world who have TB are subject to a standard treatment regime. This lasts at least six months. The medication must be taken diligently every day to prevent drug-resistance from developing. Shortening the treatment period has become a top priority within TB research. US and South African scientists are embarking on a clinical trial to try and find a solution. The Conversation Africa’s Health and Medicine Editor Candice Bailey asked Gerhard Walzl to explain the importance of the trial.</em></p>
<p><strong>What are the current challenges around TB treatment?</strong></p>
<p>In 2015 there were an estimated <a href="http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1">10.4 million new TB cases</a> worldwide. Six countries accounted for 60% of them: India, Indonesia, China, Nigeria, Pakistan and South Africa. </p>
<p>TB treatment is long and complicated to administer. It also has severe side effects. </p>
<p>To prevent the disease from reoccurring after treatment patients must take a combination of different antibiotics for at least six months. But the side effects linked to this antibiotic combination often include mild but annoying symptoms. In rarer cases the side effects can be severe and can include jaundice due to drug-induced liver disease. </p>
<p>The milder side effects include a general feeling of unwellness with nausea or loss of appetite, dizziness, skin rashes, sensations like pins and needles in the limbs or around the mouth, or flu-like symptoms. This often leads people, particularly in the later stages of the treatment period, to stop taking the medication. The problem is that this can result in multi-drug-resistant TB (MDR-TB) developing. </p>
<p>In 2015 there were an estimated <a href="http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1">480 000 new cases of multidrug-resistant TB</a> (MDR-TB). </p>
<p>To treat drug-resistant TB can take up to two years – and is even more complex, expensive and toxic. There’s also a staggering cost attached to this treatment, which poses a significant challenge to governments, health systems and other payers. </p>
<p>In addition many patients are unable to even access treatment. Among those who do receive treatment for MDR TB, only 50% survive.</p>
<p><strong>Can this lengthy process be shortened?</strong></p>
<p>Shortening of standard treatment has become a top priority within TB research. </p>
<p>According to the studies, 95% of TB patients are cured with six-month courses while only 80% to 85% of patients are cured with shorter courses. </p>
<p>What this means is that most patients are cured after four months. The challenge is that scientists are unable to tell beforehand which patients belong to which group.</p>
<p>If it were possible to identify the patients who only require four-month therapy we would be able to reduce treatment duration in the vast majority of patients. </p>
<p><strong>How have scientists tried to reduce treatment time and why has it not worked? How can this be changed?</strong></p>
<p><a href="http://www.sciencedirect.com/science/article/pii/000709718190022X">Previous</a> <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1407426">studies</a> into the viability of shortening treatments to four months have been unsuccessful. New drugs were used in <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1314210#t=article">four-month treatment regimens</a> in the hope that they could replace the longer treatments. But the rates at which the infection recurred were unacceptably high. Our hypothesis is that not all patients are suitable for shortened treatment regimens, regardless of the effectiveness of the new drugs and that a more individualised approach might be required.</p>
<p>Over the next five years the Predict-TB consortium, which includes five TB research groups in Cape Town, five in China and three institutions in Europe will address the problem. </p>
<p>The project will develop a smart set of treatment stopping criteria that are based on special lung scans (PET/CT imaging) as well as a point-of-care device which can measure the immunological markers that contribute to the decision on whether or not to stop treatment. These are proteins in the blood, whose levels are affected by inflammation and their levels will be measured by strip tests, similar to finger stick tests used to measure blood sugar levels. </p>
<p>These parameters will answer two key questions: is it possible to identify patients who are cured during a shorter treatment duration, and what combination of parameters can best identify these patients?</p>
<p><strong>If treatment could be shortened, what would that mean for the treatment of TB?</strong></p>
<p>This new method –if successful -– could be a true game changer. It will advance treatment standards from the current practice of “one size fits all” to precision-guided individualised therapy. This will allow for shortened treatment in a significant proportion of drug sensitive TB patients.</p>
<p>The benefits would extend beyond patients, who would receive treatment for shorter periods and with better completion rates. Reducing the TB burden will also have an effect on the economic situation in many developing countries and less drug resistance will benefit public health on a global scale.</p><img src="https://counter.theconversation.com/content/73609/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gerhard Walzl works for Stellenbosch University. He receives funding from the Bill and Melinda Gates Foundation, the EDCTP, the NIH, the South African National Research Foundation and the Medical Research Foundation. He contributes to the National TB Think Tank. </span></em></p>Shortening the treatment period has become a top priority within TB research but studies to date have been unsuccessful.Gerhard Walzl, Head of the Immunology Research Group at the Division of Molecular Biology & Human Genetics, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/631312016-10-10T17:39:36Z2016-10-10T17:39:36ZFresh effort in quest to find a drug that cracks resistant TB<figure><img src="https://images.theconversation.com/files/140910/original/image-20161007-21430-1nmm9yf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Reuters/Mike Hutchings</span></span></figcaption></figure><p>A significant amount of tuberculosis research in recent years has been focused on combating the bacterial lung disease by treating it with drugs that are used to treat other diseases and conditions. There is still no cure and more drugs are urgently needed to meet the acute demand of the disease. </p>
<p>The problem has been exacerbated by the discovery of drug-resistant tuberculosis in 2006. It is now an escalating global threat. Each year more than 9 million people are infected with TB and another 1.5 million die. At least 4% of people diagnosed for the first time and up to 20% of those treated for the disease have “<a href="http://www.who.int/tb/challenges/mdr/MDR_TB_FactSheet.pdf">multiple-drug-resistant TB</a>”. About 9.7% of these also have “<a href="http://www.tbfacts.org/xdr/#sthash.k20TRGTx.dpuf">extensively-drug-resistant TB</a>”.</p>
<p>Most TB treatments target bacteria that actively grow in the body. Four major classes of strong antibiotics are used: isoniazid, rifampin, fluoroquinolones, and aminoglycosides. But for patients who do not respond to these key treatments the outlook is grim. </p>
<p>New drugs are being developed but they need to go through rigorous and lengthy safety, efficacy and compatibility tests. This affects how fast they come onto the market.</p>
<p>Re-purposing antibiotics or combining commercially available products which are not earmarked for TB with the current and new anti-TB regimens could, however, solve this problem. </p>
<p><a href="http://www.nejm.org/doi/full/10.1056/NEJMc1513236">Our study</a> found that if re-purposed antibiotics were administered in the first 14 days of treatment they had the same effect as both established TB drugs and new drugs. Our study focused on the first 14 days of treatment because in that period it is still safe to give only one drug and to be able to measure its effect. </p>
<p>If these re-purposed antibiotics prove effective beyond the first two weeks, they could be added to the much needed arsenal of drugs to fight the deadly disease. </p>
<h2>Understanding antibiotics</h2>
<p>Various classes of antibiotics have a spectrum of micro-organisms that they can kill. </p>
<p>In the last two decades of TB research, researchers have investigated the viability of various antibiotics which were not originally meant to treat TB. <a href="http://www.webmd.com/brain/news/20130826/fda-strengthens-fluoroquinolone-warning">Fluoroquinolones</a> are a good example. They are a class of antibiotics that are administered to treat urinary tract infections. <a href="http://www.atsjournals.org/doi/full/10.1164/rccm.201308-1446ED#.V_eHouB97IU">Studies</a> have shown that some fluoroquinolones work well for TB if they are taken over several months.</p>
<p>But some antiobiotics, such as those derived from pencillin such as beta-lactams, have been shown to be ineffective. Two clinical trials have been done – one in 1997 and 2001 – with a commonly used antibiotic called amoxcillin/clavulanic acid and also known as amoxiclav or augmentine. One took place in the <a href="http://www.jstor.org/stable/4481488?seq=1#page_scan_tab_contents">US and Turkey</a> and the other in <a href="http://www.tandfonline.com/doi/abs/10.1080/00365540152029954">South Africa</a>. Both found that the bacteria that causes TB overpowered the beta-lactams. </p>
<p>But we retested more beta-lactams in the laboratory. Our results show that more modern beta-lactams could perhaps overcome the TB bacteria’s defences.</p>
<h2>The tests</h2>
<p><a href="task.org.za">Our laboratory</a> does clinical trials to find better TB treatments. For this particular study we wanted to establish whether a new beta-lactam, which is commercially available and safe, could be used for TB treatment.</p>
<p>We randomly allocated two groups of 15 patients who had TB with either a combination of re-purposed antibiotics or existing TB treatments. We limited the trial to 14 days. We tested three beta-lactams: one, meropenem, we administered intravenously, and two we administered orally, amoxicillin–clavulanic acid and faropenem. The sputum samples of patients was analysed.</p>
<p>We <a href="http://www.nejm.org/doi/full/10.1056/NEJMc1513236">found</a> that when combined two specific beta-lactams – meropenem and amoxicillin–clavulanic acid – were able to break through the bacteria’s defence. As a combination, meropenem, which is commonly used for severe infections, combined with amoxicillin/clavulanic acid was as active over the first 14 days of treatment as the established drugs (rifampicin and pyrazinamide) and the novel drugs (bedaquiline and delamanid). </p>
<p>Intravenous meropenem treatment was as active as the most successful drugs on the market for TB treatment. The more practical oral treatment (faropenem) was not active because not enough of the drug was taken up into the body. But both treatments were well tolerated. </p>
<h2>Next steps</h2>
<p>Our study only looked at the effectiveness of the two drugs in the first two weeks of treatment. </p>
<p>The effectiveness of the antibiotics do not guarantee a relapse-free cure for TB. Longer trials are now needed to determine how beta-lactams can contribute to the treatment of TB. </p>
<p>But based on these results, an intensive search for an orally active beta-lactam for TB treatment has begun. The next oral beta-lactam test will be done in 2017 and the results should be available towards the end of that year. Once a drug has been found that can be taken orally and has the same effect as the treatment given intravenously larger studies in combination with other drugs will follow. It might nevertheless be several years before beta-lactams become part of standard treatment.</p><img src="https://counter.theconversation.com/content/63131/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andreas Henri Deacon received a grant from the European and Developing Countries Clinical Trials Partnership.</span></em></p>Antibiotics that were not originally earmarked to treat TB have shown the first signs of effectiveness and could be added to the much-needed arsenal of drugs to fight the deadly disease.Andreas Henri Diacon, Scientist with the Division of Molecular Biology and Human Genetics and Director of TASK Applied Science, Stellenbosch UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/623782016-07-18T18:19:05Z2016-07-18T18:19:05ZScientists are combining forces to tackle the deadly duo of TB and HIV<figure><img src="https://images.theconversation.com/files/130713/original/image-20160715-2122-r5mgza.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Africa Centre for Population Health</span></span></figcaption></figure><p><em>TB and HIV are, separately, two of the deadliest infections in the world. They kill around 3 million people every year. Combined, they are even more dangerous. Tackling the problem of HIV and TB co-infection presents both diagnostic and therapeutic challenges.</em> </p>
<p><em>That’s why a new US$79-million centre, the Africa Health Research Institute, has been established in KwaZulu-Natal, South Africa. It will combine the efforts of two leading research organisations – the Africa Centre for Population Health and the KwaZulu-Natal Research Institute for TB-HIV (K-RITH). Incoming Africa Health Research Institute Director Professor Deenan Pillay explains the importance of this new research venture to KwaZulu-Natal, South Africa and the world.</em></p>
<p><strong>Why is HIV and TB co-infection a challenge?</strong></p>
<p>HIV and TB form a lethal combination, each speeding the other’s progress. TB is the leading cause of death among people living with HIV. It accounts for one in four HIV-related deaths. There are huge challenges in accurately diagnosing TB in people living with HIV, and then properly treating the co-infections. </p>
<p>The drugs that are used to treat TB must be taken for at least six months. Patients with drug resistant strains are sometimes treated for longer than two years, and have to use drugs which are more toxic. Anti-TB drugs may interact badly with antiretroviral drugs and both TB drugs and antiretrovirals have side effects, which means people often don’t adhere to their treatment regimes. </p>
<p><strong>What are the co-infection rates in South Africa and how do they compare to the rest of the world?</strong></p>
<p>Despite advances in antiretroviral therapy and talk of the ‘end of Aids’, HIV and HIV-related TB remain devastating diseases. </p>
<p>According to the World Health Organisation at least one-third of the 37 million people living with HIV worldwide are infected with latent, or inactive, TB. Globally, people living with HIV are 26 times more likely to develop active TB than those without HIV. </p>
<p>South Africa is the epicentre of HIV and TB co-infection. Of the 22 high burden TB countries the World Health Organisation lists, South Africa is ranked third. And more than 70% of patients with TB in South Africa are also HIV infected. TB is among the leading causes of death in the country. </p>
<p>KwaZulu-Natal (KZN), a province on the east coast of South Africa, has the highest rates of HIV and TB in the country. It also has one of the highest prevalence rates of TB globally. The largest outbreak of extensively drug resistant TB (XDR-TB) in history occurred in the province in 2006, while uMkhanyakude district, the area of northern KZN where the Africa Centre is based, has the highest prevalence of drug resistant TB in the country.</p>
<p><strong>What prompted the centre and how will it actively help target co-infection?</strong></p>
<p>The Africa Health Research Institute will use an interdisciplinary approach to fight HIV and TB, bringing together leading researchers from different fields.
The Africa Centre, a population studies research centre, has existed since 1999. It has 16 years of detailed population data from more than 100 000 participants, and has been at the forefront of describing the development of the HIV epidemic and the positive impact that HIV treatment has had, both in terms of reducing the number of new infections and reducing mortality. </p>
<p>K-RITH was formed in 2009 in response to the devastating outbreak of XDR-TB in KZN. It is focused on the basic science of TB and HIV biology and pathology and has world-class laboratory facilities, including Biosafety Level 3 labs, which allows scientists to safely work with TB. </p>
<p>Bringing the two together links population and lab research to create an interdisciplinary “population to laboratory – and back to population” approach to addressing the TB and HIV co-epidemic. This is the first institute of its kind in the world where the highest class of lab research can be applied to such large population longitudinal surveillance.</p>
<p>In the past the Africa Centre has been able to describe the changes in the rates of new HIV infections and how that has affected the population. The Africa Health Research Institute can now look at why there are changes and can develop tools to do trials on that population. We are moving from observing, to doing something about it. </p>
<p><strong>What are your targets?</strong></p>
<p>The Africa Health Research Institute’s goals include providing the research to significantly reduce new HIV infections and new TB infections – based on developing optimal drugs, vaccines and trials of interventions and research of on-the-ground impact. </p>
<p>It is an important component of the South African effort to fight HIV and TB. The prevalence of infection is so high that we are in a good position to do the research and apply the findings not just to sub-Saharan Africa, but to areas across the world where HIV and TB is less prevalent but still a challenge. </p>
<p>The institute will also help develop the next generation of African scientists.</p><img src="https://counter.theconversation.com/content/62378/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Deenan Pillay is the incoming Director of the Africa Health Research Institute. He has received funding from Wellcome Trust, the Bill and Melinda Gates Foundation, the UK MRC, and NIH.
The new venture is made possible through R1.2-billion in grants from Wellcome Trust and the Howard Hughes Medical Institute, with UCL (University College London) and the University of KwaZulu-Natal as significant academic partners.
</span></em></p>A new centre in South Africa will work to significantly reduce emerging HIV and TB co-infections.Deenan Pillay, Director of the Africa Centre for Population Health and Professor of Virology, University of KwaZulu-NatalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/589612016-05-26T16:31:13Z2016-05-26T16:31:13ZHow DNA holds the key to improving drug-resistant TB treatment<figure><img src="https://images.theconversation.com/files/124158/original/image-20160526-22068-4zjq65.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Tuberculosis (TB) is one of the most deadly infectious diseases in the world. It is caused by a bacteria that infects and gradually destroys the lungs, and is transmitted when someone with TB coughs or spits or sneezes – and someone else inhale the germs. More people <a href="http://www.who.int/mediacentre/news/releases/2015/tuberculosis-mortality/en/">die from TB</a> than from HIV/AIDS. Despite this, there is currently no effective vaccine against TB, and most of the drugs that we use to treat it were developed more than 40 years ago. </p>
<p>The emergence of drug-resistant strains of TB now pose an additional major threat to public health worldwide. </p>
<p>Part of the problem is the way we test people for TB. The best way to treat patients with drug-resistant TB is to put them on the right drugs immediately after they are diagnosed. </p>
<p>But to test if a TB strain is resistant to a particular antibiotic is unfortunately a lengthy process. It includes isolating the bacteria from the cough sample, growing it and then sampling all the different drugs to see which can stop the bacteria from growing. Because the TB bacteria grows very slowly this process can take several weeks, and patients are often needlessly given drugs with severe side effects while waiting for their results. </p>
<p>There is only one rapid assessment widely available in hospitals in South Africa and it’s limited because it only tests for resistance to one drug. </p>
<p>We have just completed a new study that shows we could use <a href="http://www.nature.com/ng/journal/v48/n5/abs/ng.3548.html">genomics</a> to cut the testing process down to a matter of days. By extracting and analysing DNA directly from the sputum of someone who has TB, in less than a week scientists will be able to tell which strain of TB the person has, whether it is resistant to drugs – and how it should be treated.</p>
<h2>The problem of drug resistance</h2>
<p>Drug resistance is one of the many challenges to controlling TB. TB treatment requires a combination of four drugs over six months. There are several drugs that can be used in this combination. These are known as first-line drugs. But due to treatment being lengthy, many TB patients don’t complete this course. As a result drug-resistant strains of the bacteria emerge in their bodies. </p>
<p>Treating drug-resistant TB is extremely difficult because doctors have to use a different set of drugs, known as second-line drugs. These are stronger but less effective. They are also more toxic. They have many side-effects, including deafness and severe depression. These drugs also have to be taken for at least 18 months – which is often the reason patients fail to complete their treatment correctly. The bacteria continues to mutate and the result is what we call extensively drug-resistant TB. </p>
<p>These strains are resistant to the best first- and second-line drugs and they can be transmitted to healthy individuals. There are few drugs left to treat patients with extensively drug-resistant TB and up to 75% of <a href="http://www.sciencedirect.com/science/article/pii/S0140673613626756">patients</a> die if infected with this strain of TB.</p>
<h2>What we found</h2>
<p><a href="http://www.nature.com/ng/journal/v48/n5/abs/ng.3548.html">We analysed</a> the DNA sequences of 498 drug-resistant strains of TB to see if we could identify the mutations that cause resistance. </p>
<p>What we found was that for both the first- and second-line drugs we could predict pretty well whether the strain was resistant or not – just from the DNA sequence alone. We were also able to find new mutations that cause resistance to a particularly toxic drug called <a href="http://www.tandfonline.com/doi/abs/10.1586/14787210.2016.1116385">cycloserine</a>, which can cause suicidal depression. </p>
<p>The ultimate aim of a rapid drug resistance test can only be achieved if we can identify all the mutations that cause resistance. This research takes us another step forward in this direction. The information can be used to develop the next generation of rapid molecular TB diagnostic tests, which will allow us to use toxic drugs like cycloserine in only those patients who will benefit from the drug.</p>
<h2>Working around resistance</h2>
<p>In one of our <a href="http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001880">previous studies</a>, we traced the emergence of drug-resistant TB back to the 1950s in South Africa’s KwaZulu-Natal province. The findings highlighted the inevitability of drug resistance, as the bacteria that causes TB seems to be able to develop resistance to every new drug we throw at it. </p>
<p>This is particularly important now as there are now two new drugs that have been developed to treat TB: <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1313865">bedaquiline</a> and <a href="http://www.nejm.org/doi/full/10.1056/Nejmoa1112433">delamanid</a>. If we don’t use these drugs extremely carefully resistance will develop rapidly and we will be back to square one.</p>
<p>Using advanced genome sequencing technologies will ultimately help us reach a much faster diagnosis, and ensure that treatment is optimal. Patients will be able to get a personalised set of drugs that will definitely work for them and avoid getting toxic drugs that don’t benefit them. In this way we’ll also hopefully guard against new resistant strains of TB developing.</p><img src="https://counter.theconversation.com/content/58961/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alex Pym works for K-RITH. He receives funding from National Institutes of Health (NIH), South African Medical Research Council (SAMRC) and K-RITH. </span></em></p>A new study shows that by using genomics, you can cut down the lengthy process of testing for drug-resistance TB to a matter of days.Alex Pym, Investigator, KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Associate Professor in the Department of Medical Microbiology at the Nelson R. Mandela School of Medicine, University of KwaZulu-NatalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/544182016-02-10T15:51:21Z2016-02-10T15:51:21ZProgress report on promises made to improve South Africa’s health services<figure><img src="https://images.theconversation.com/files/110983/original/image-20160210-12185-fbf9go.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><em>Over the last three years South Africa’s President Jacob Zuma has made several promises to improve health care in his annual state of the nation address. This includes fighting TB, improving life expectancy and reducing maternal, infant and under five mortality. Health and Medicine Editor Candice Bailey asked a panel of academics to assess whether the promises have been kept.</em> </p>
<p><strong>In 2013 the president spoke of integrating HIV and TB services because of the high co-infection between the two. Has this happened? Did it work?</strong></p>
<p><em>Professor Jill Murray</em>: The government has moved very well to integrate HIV and TB services. The latest figure from the South African Department of Health is that <a href="http://www.tbfacts.org/tb-statistics-south-africa/">73%</a> of patients who have TB are also HIV positive. </p>
<p>Obviously problems arise in integrating these services. Both TB and HIV were previously stand-alone programmes and each had their own dedicated staff, budgets and sites. In combining the two there have been issues around upskilling the doctors and the nurses who are responsible for implementing the programmes at grass roots. They have also had to explain to patients why the programmes need to be joined. All of this takes time. But integrating the services is happening well across the country. </p>
<p><strong>In 2015, he promised to implement TB programmes for prisoners, mine-workers and mining town communities. Has it happened?</strong></p>
<p><em>Professor Jill Murray</em>: Although these programmes have been slow to start - this is a conversation that has been happening for about seven or eight years - they have picked up pace recently and there is a big push for implementation over the coming year. </p>
<p>Various international donors are working the with governments of 10 Southern African countries and will be granting money for project implementation within the next month or so. </p>
<p>The programmes will be put in place across southern Africa as many of the region’s miners are migrants. It therefore doesn’t help to only implement programmes in South Africa. TB knows no borders. It is also important to note that the programmes will involve identifying former miners who have developed mine related diseases and helping them to access compensation. </p>
<p><strong>Improving South Africa’s life expectancy from 60 years in 2012 to 63 by 2019 was on the top of the president’s agenda in 2014. Are we on track?</strong></p>
<p><em>Professor Robert Pattinson</em>: Yes, we are on track to meet and exceed this target. The 2013 Rapid Mortality Surveillance <a href="http://www.mrc.ac.za/bod/RapidMortalitySurveillanceReport2013.pdf">Report</a> shows that the life expectancy at birth in 2013 was 62.2 years. This is broken down into 59.4 years for men and 65.1 years for women. One would reasonably expect the trend to continue. The major reason for this is the success of the HIV screening and treatment programme.</p>
<p><strong>Zuma has pushed to further reduce child and maternal mortality by improving quality of care in the public sector. Is this happening?</strong></p>
<p><em>Professor Robert Pattinson</em>: Yes, the number of maternal and child deaths for each birth has been dropping rapidly. The maternal mortality ratio has dropped from 252 deaths for every 100 000 live births in 2009 to around 197 per 100 000 live births in 2012. In that four year period, there were 424 fewer maternal deaths. This averages 85 fewer deaths per year from 2009 to 2014. </p>
<p>The under 5 mortality rate has dropped to 41 deaths for every 1 000 births from 56 for every 1 000 births. Similarly, the infant mortality rate came down from 39 deaths for every 1 000 infants that were born to 29 for every 1 000 births. In terms of newborn deaths, in 2009, there were 14 deaths for every 1 000 births. This dropped to 11 by 2013, according to the latest <a href="http://www.mrc.ac.za/bod/RapidMortalitySurveillanceReport2013.pdf">statistics</a>. </p>
<p>The major reason for these declines has been the success of the HIV screening and treatment programme. The programme would not be successful if the health care professionals were not providing quality of care in this programme. Unfortunately the reduction in child deaths seems to be levelling off. </p>
<p><strong>In 2015 he also said that Ketlaphela, a state-owned pharmaceutical company, would start supplying antiretrovirals to the Department of Health. What’s happened?</strong></p>
<p><em>Professor Fatima Suleman</em>: The government’s Ketlaphela project is an ambitious one. If it is successful, it will mean that active pharmaceutical ingredients, which are in all drugs, will be manufactured in South Africa. This is good for two reasons. We will have our own antiretrovirals, malaria and tuberculosis drugs which will cut down costs, but it would also increase the country’s ability to supply increasing domestic and global demands for drugs. </p>
<p>But the project has been beset by teething problems. It was supposed to be up and running by 2015 but it has stalled because the preferred international technology and investment partner <a href="http://mg.co.za/article/2013-05-24-00-arv-plan-bounces-back">pulled out</a>. The new plan, based on a report by <a href="https://www2.deloitte.com/content/dam/Deloitte/global/Documents/Life-Sciences-Health-Care/gx-lshc-2015-life-sciences-report-south-africa.pdf">Deloitte and Touche</a> is to have the project running by 2017, with new investment and technology partners.</p><img src="https://counter.theconversation.com/content/54418/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jill Murray has received funding from the South African Mine Health and Safety Council and does voluntary work for the Democratic Alliance.</span></em></p><p class="fine-print"><em><span>Fatima Suleman is the chairperson of the National Pricing Committee. </span></em></p><p class="fine-print"><em><span>Robert Pattinson receives funding from SAMRC, UKAid, European Union, CDC, UNICEF and WHO. He is a member of the National Committee for the Confidential Enquiries into Maternal Deaths.</span></em></p>In a bid to improve health care in South Africa, President Jacob Zuma has made several promises in the last three years. Some have materialised faster than others.Jill Murray, Honorary Associate Professor in the School of Public Health, University of the WitwatersrandFatima Suleman, Associate Professor of Pharmaceutical Sciences in the School of Health Sciences, , University of KwaZulu-NatalRobert Pattinson, Director, Maternal and Infant Health Care Strategy Extramural Unit, SAMRC, University of PretoriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/523842016-02-08T04:30:16Z2016-02-08T04:30:16ZSouthern Africa’s retrenched miners face a future without health care<figure><img src="https://images.theconversation.com/files/106066/original/image-20151215-23182-1n3ugll.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Anglo American's plans to reduce its operations will have an impact on the provision of health services to miners. </span> <span class="attribution"><span class="source">Reuters/Siphiwe Sibeko </span></span></figcaption></figure><p><em>Two of the world’s mining heavyweights have announced production cuts and staff cutbacks. These moves by <a href="https://www.jacarandafm.com/news-sport/news/bhp-billiton-cut-hundreds-jobs/">BHP Billiton</a> and <a href="http://www.fin24.com/Companies/Mining/why-anglo-is-forced-to-cut-85-000-jobs-20151209">Anglo American</a> will have a major impact on efforts to contain TB and HIV as mining houses have become integral to the provision of health care in southern Africa. The disease burden is high among the <a href="http://www.southernafricatrust.org/wp-content/uploads/2015/04/world-bank-tb-in-the-mining-sector.pdf">region’s</a> 490 000 miners in the gold, platinum and coal industries. They carry one of the highest TB/HIV <a href="http://www.health-e.org.za/wp-content/uploads/2014/04/Hamonization-report.pdf">co-infection rates</a> globally, ranging from 50% to 77%. The Conversation Africa health and medicine editor Candice Bailey asked Dr Liesl Page-Shipp to unpack the problem.</em></p>
<p><strong>How big is the burden of HIV/TB in the mining sector?</strong></p>
<p>Mine workers have different health risks, depending on whether they work in gold, platinum, coal or other commodities. Their living conditions may also be a risk factor. Gold mining poses the highest risk for <a href="http://oem.bmj.com/content/48/1/53.short">silicosis</a>. This in turn gives them a higher chance of being infected with TB. </p>
<p>Globally TB affects <a href="http://www.southernafricatrust.org/wp-content/uploads/2015/04/world-bank-tb-in-the-mining-sector.pdf">128</a> in every 100 000 people. In sub-Saharan Africa this figure is more than double at <a href="http://www-wds.worldbank.org/external/default/WDSContentServer/WDSP/IB/2014/03/24/000456286_20140324170149/Rendered/PDF/862020BRI0WB0R00Box382165B00PUBLIC0.pdf">350</a> people for every 100 000. In South Africa, the prevalence is <a href="http://www-wds.worldbank.org/external/default/WDSContentServer/WDSP/IB/2014/03/24/000456286_20140324170149/Rendered/PDF/862020BRI0WB0R00Box382165B00PUBLIC0.pdf">948</a> cases for every 100 000 people. </p>
<p>In some mines this rate is reported to be up to between <a href="http://www-wds.worldbank.org/external/default/WDSContentServer/WDSP/IB/2014/03/24/000456286_20140324170149/Rendered/PDF/862020BRI0WB0R00Box382165B00PUBLIC0.pdf">2500 and 3000</a> cases for every 100 000 people. This is 10 times the emergency <a href="http://www.who.int/tb/features_archive/tb_emergency_declaration/en/">threshold</a> set by the World Health Organisation.</p>
<p><strong>How important are mining houses in providing health care?</strong></p>
<p>Some mining houses provide a high standard of health care for their employees through on-site 24-hour primary health clinics, which are linked to secondary or tertiary hospitals. </p>
<p>These clinics provide a full package of health care services including anti-retroviral treatment, TB treatment and monitoring and treatment for chronic diseases like hypertension and high blood pressure. The service is available to all employees including migrant labourers from <a href="http://www.health-e.org.za/2014/03/26/sadc-harmonise-tb-treatment-cross-border-referrals/">neighbouring countries</a> such as Lesotho, Swaziland and Mozambique. About <a href="http://mg.co.za/article/2013-09-13-00-marikana-was-not-just-about-migrant-labour">30%</a> of mine workers in South Africa are migrant labourers.</p>
<p>But in some instances mine workers are totally dependent on local Department of Health facilities. Mine workers who require services access these facilities in their own time using often limited resources. </p>
<p><strong>How vulnerable are people to mine closures? Will they lose treatment?</strong> </p>
<p>Many will be vulnerable to treatment being interrupted or discontinued. Robust referral systems within South Africa and across borders are missing. Issues of stigma and disclosure to families may pose additional barriers to continued treatment for TB and HIV once miners return home. In addition, mine workers may come from areas with poor access to comprehensive medical care. This would restrict their options for HIV and TB screening, diagnosis and treatment.</p>
<p>Governments and mining houses in the region have recognised some of the challenges around poor access to care. There has been a commitment from governments to adopt a coordinated response to managing TB in the mining sector. In 2012, heads of state signed the SADC Declaration on TB in the Mining <a href="http://www.stoptb.org/assets/documents/news/Declaration%20on%20Tuberculosis%20in%20the%20Mining%20Sector2012English.pdf">Sector</a>. This was followed by a <a href="http://www.health-e.org.za/wp-content/uploads/2014/04/Hamonization-report.pdf">framework</a> to manage TB and a Code of <a href="http://www.hivsharespace.net/system/files/MSH%20Fact%20Sheet%20TB%20in%20Mining%20Sector%20March%202015%20web.pdf">Conduct</a> on TB in the mining sector. More recently the Global Fund against TB and malaria has awarded a grant for TB in the mining sector in Southern Africa <a href="https://TIMSSA.co.za">Programme</a>. </p>
<p>A multi-sectoral response is required to adequately respond to the challenges. This will need to include mining companies, health departments, labour departments and civil society.</p><img src="https://counter.theconversation.com/content/52384/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Liesl Page-Shipp does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The closure of several mines in South Africa and production cuts could have a detrimental impact on the health of miners who rely on in-house HIV and TB treatment programmes.Liesl Page-Shipp, Director: Health Programmes in Special Populations, Aurum InstituteLicensed as Creative Commons – attribution, no derivatives.