tag:theconversation.com,2011:/uk/topics/tb-in-africa-27417/articlesTB in Africa – The Conversation2017-03-12T10:20:21Ztag: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/583432016-05-15T14:17:54Z2016-05-15T14:17:54ZAfrican scientists make headway in grasping persistent TB bacteria<figure><img src="https://images.theconversation.com/files/122143/original/image-20160511-18165-1f3bukt.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>The arrival of drug-resistant tuberculosis has significantly complicated global efforts to decrease the scourge of the disease. </p>
<p>Each year more than nine million people are infected with TB and another 1.5 million die. But the latest figures show that at least 20% of people diagnosed with the disease have “multiple-drug-resistant” TB. And <a href="http://apps.who.int/iris/bitstream/10665/191102/1/9789241565059_eng.pdf?ua=1">about 9.7%</a> of these also have “extensively-drug-resistant TB”. </p>
<p>TB is caused by bacteria that attacks the lungs. Most TB treatments target bacteria that actively grow in the body. But a very important subset of bacteria is able to survive treatment. These are known as persistent bacteria. </p>
<p>Though these persistent bacteria only represent a very small proportion of the bacteria that causes TB, failing to get rid of them can have devastating consequences. They are responsible for lengthy drug treatment, and could contribute to drug resistance. They therefore should also be the target of TB therapies. </p>
<p>The challenge with these persistent bacteria is that they are very difficult to isolate. This makes it difficult to study them and therefore difficult to develop drugs to kill them.</p>
<p>As a team of scientists at Stellenbosch University in South Africa, together with colleagues at Imperial College London, we found a new way to identify, isolate and target persistent bacteria. <a href="http://mic.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000288#tab2">Our technique</a>, which has never before been applied in TB research, will help scientists understand why some bacteria respond to treatment and others become resistant.</p>
<h2>How this bacteria works</h2>
<p>Persistent bacteria plays a particularly important role in latent TB – when bacteria that can cause TB hibernate in the body. Someone with latent TB will not have any clinical symptoms and will therefore not know that he or she has the disease. Latent TB can survive in the body for decades and only flare up when someone’s immune system is compromised. </p>
<p>Latent TB can therefore progress to full-blown disease in people who have compromised immune systems. These are often people who have HIV/AIDS, suffer from malnutrition, are ageing or have a substance-abuse problem. About one-third of the world’s population carries latent TB. </p>
<p>Conventional thinking has held that persistent bacteria are also present in people who have latent TB. These bacteria are thought to either stop growing or are slowly growing, although they still survive in the body. </p>
<p>But <a href="http://www.cell.com/trends/microbiology/abstract/S0966-842X(14)00070-5?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0966842X14000705%3Fshowall%3Dtrue">emerging research</a> has started to question this assumption on two fronts: </p>
<ul>
<li><p>Some research shows that proportions of the bacteria continue to grow while others die.</p></li>
<li><p>Other research argues that the bacteria do not grow.</p></li>
</ul>
<p>Understanding the bacteria present in latent TB is important to choose the best TB treatments. This is especially important because of the difficulties associated with treating persistent bacteria that can survive treatment.</p>
<p>For this reason <a href="http://mic.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000288#tab2">our research</a> is focused on finding ways to study and target persistent bacteria. We used specific bacteria-associated labels and sophisticated laser-based methods to identify and isolate this bacteria. </p>
<h2>A new method to study persistent bacteria</h2>
<p>The technique, known as fluorescence dilution, uses two fluorescent proteins to label the bacteria. One protein tracks live bacteria and the other measures its growth. It is applied to identify and isolate individual bacteria to study it. </p>
<p>The technique can best be described as using “micro-tweezers” to physically pick out the slow-growing bacteria from the rest. This enables us to find the hard-to-identify persistent bacteria. </p>
<p>We were able to do this by applying the same approach that’s been used to isolate the bacteria that causes food poisoning, Salmonella. This involves subjecting the bacteria to conditions that come closest to those found in the body as opposed to conditions in the laboratory.</p>
<p>Using this technique, we found that when bacteria entered a specific type of white blood cell, a population of non- or slowly-growing persistent bacteria appeared. White blood cells play a critical role in defending the body against invading bacteria. In the laboratory we use them to mimic the environment found in the body.</p>
<p>This finding is important because it shows that the numbers of persistent bacteria increase by being inside white blood cells. This means that the host’s own defences can help the bacteria to survive TB treatment.</p>
<h2>Hope for the future</h2>
<p>These are only the first steps, but this technique offers unique opportunities to deepen scientists’ understanding of why and how the body’s response to TB treatment results in drug resistance.</p>
<p>We can now, for example, begin to study what drives bacteria into a latent state. Once we understand this better it will be possible to begin designing drugs that better manage latent TB. Importantly, this could help decrease the amount of time it takes to treat TB as well as minimise drug resistance.</p><img src="https://counter.theconversation.com/content/58343/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jomien Mouton receives funding from the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa that was awarded to Samantha Sampson, award number UID 86539 and the NRF Scarce Skills Postdoctoral fellowship, award number 96831. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NRF.</span></em></p><p class="fine-print"><em><span>Samantha Sampson receives funding from the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa, award number UID 86539. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NRF.</span></em></p>South African scientists have found a way to single out the problematic parts of the bacteria causing TB that results in drug resistance.Jomien Mouton, Postdoctoral research fellow in the MRC Centre for Tuberculosis Research, Stellenbosch UniversitySamantha Sampson, Associate Professor, SARChI Research Chair in Mycobactomics, Stellenbosch UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/592852016-05-11T17:15:25Z2016-05-11T17:15:25ZAfrican scientists a step closer to testing for TB in a matter of minutes<figure><img src="https://images.theconversation.com/files/122164/original/image-20160511-18135-1dj7391.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>Tuberculosis ranks alongside HIV/AIDS as a leading cause of death worldwide. According to the <a href="http://www.who.int/mediacentre/factsheets/fs104/en/">World Health Organisation</a>, 1.5 million people died from TB in 2014. The challenges in tackling the disease include the facts that people are tested too late and that the turnaround for most tests is long. To remedy this a point-of-care rapid diagnostic test for TB has been developed by a multinational team of scientists led by researchers at Stellenbosch University in South Africa.
One of its co-inventors, Professor Gerhard Walzl, spoke to The Conversation Africa’s health and medicine editor Candice Bailey.</em></p>
<p><strong>How have TB tests been done up until now and what are the challenges?</strong></p>
<p>There are three main tests that are currently in use. </p>
<p>A culture test – the most sensitive – requires people to produce a sputum sample that is sent to a centralised laboratory where a culture test is done. A positive result shows up after ten days. A confirmed negative result takes up to 42 days. </p>
<p>The problem with this test is that it is only available in centralised laboratories, which means patients must make several trips to a hospital or health facility to get their results. And it is very expensive. </p>
<p>Then there is the sputum microscopy test. This is widely used in Africa. It requires the sputum slides of each patient to be individually checked. </p>
<p>The test is inexpensive. But it is labour intensive, which means that only a limited number of smear tests can be assessed a day. In addition, it only has a 60% sensitivity rate. </p>
<p>On top of this, the test poses particular challenges for children and for people living with HIV. </p>
<p>In the case of young children, samples need to be taken from their stomachs as they cannot follow instructions to produce a good quality sputum sample. This requires the use of a nasal tube, which is not pleasant for the child or the health-care worker. </p>
<p>The test also isn’t effective for people living with HIV. This is because their sputum often has low levels of the bacteria, which can lead to a false negative test result. </p>
<p>There is also a molecular test that detects bacterial DNA in the sputum sample. This test only takes two hours to produce a result and although it speeds up the detection of TB, it is not widely available to people in rural areas as instruments are placed in a centralised manner.</p>
<p><strong>How will your test change this?</strong></p>
<p>If <a href="http://www.ncbi.nlm.nih.gov/pubmed/27146200">our test</a> is accepted after clinical trials are completed it will be able to provide almost immediate results. People will be able to be diagnosed and start treatment in a single visit to a health-care facility.</p>
<p>The test is done with blood obtained from a finger prick and can make a TB diagnosis in less than an hour. The diagnostic test is a hand-held, battery-operated instrument that will measure chemicals in the blood of people with possible TB. This test will not have to be done in a laboratory and health-care workers will be able to perform it with minimal training.</p>
<p>It is a low-cost screening test and has the potential to significantly speed up TB diagnosis in resource-limited settings. </p>
<p><strong>At what stage is the test?</strong></p>
<p>The test is still in development. We have patented the biosignature, which identifies the levels of chemicals in the blood of a patient. A biosignature consists of a combination of chemicals and indicates a disease state. This signature was discovered by African scientists. The inventors included South African, Cameroonian and Ethiopian scientists. </p>
<p>The test’s accuracy and efficacy will be tested in five African countries over the next three years. We will recruit 800 people who have TB symptoms from Namibia, the Gambia, Uganda, Ethiopia and South Africa. </p>
<p>Clinical research sites will be set up or strengthened in all five countries. And participating countries will be able to use the data generated from this project. </p>
<p>We are still trying to improve the signature by adding additional markers. In addition, we would like to optimise and fine tune the device to enable it to measure the signature on a strip similar to a pregnancy test or a glucose test strip. </p>
<p><strong>Why is the test important for South Africa?</strong></p>
<p>South Africa has the highest TB rates in the world. Each year between 450,000 and 500,000 people develop TB. This gives the country an incidence rate of <a href="http://www.who.int/tb/publications/global_report/gtbr15_annex04.pdf?ua=1">834 infections</a> for every 100,000 people. On the rest of the continent, the incidence rate is between <a href="http://www.who.int/mediacentre/factsheets/fs104/en/">300 and 600 infections</a> for every 100,000 people. In <a href="http://data.worldbank.org/indicator/SH.TBS.INCD">China</a> the incidence is 68 for every 100,000 people and in most European countries it is less than ten for every 100,000 people. </p>
<p>One of the challenges in South Africa is that people in remote areas with high TB incidence still do not benefit from newer developments in TB testing. As a result they face long diagnostic delays and often need to come back to clinics on several occasions before they are diagnosed.</p>
<p>This test will mean that health-care workers with minimal training can use the test at grassroots level and get immediate access to screening test results. </p>
<p>It would also reduce the cost of testing for TB. Our test would initially cost US$2.50 per test. With commercialisation that price could drop significantly. Currently the culture test costs $45 per test while the DNA sample test costs $12 per test. </p>
<p><strong>How does this test fit into the bigger picture of dealing with TB?</strong></p>
<p>The test would be used best as a screening test. This is because it can identify people who need further investigation and can screen out those who don’t. So far we have been able to identify 70% of patients who do not need further testing. </p>
<p>The <a href="http://www.who.int/tb/publications/Final_TB_Screening_guidelines.pdf">World Health Organisation</a> has identified a screening test as important for high-prevalence areas, for those who are in contact with people who have TB, those living with HIV, homeless people, immune-compromised people and those living in areas with poor access to diagnostic services.</p><img src="https://counter.theconversation.com/content/59285/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gerhard Walzl receives funding from the European & Developing Countries Clinical Trials Partnership (EDCTP), (grant DRIA2014-311), which funds the ScreenTB trial, the South African National Research Foundation and the South African Medical Research Council. He is the co-inventor of the biosignature that forms the test that has been submitted as part of an international patent application.</span></em></p>African scientists have developed and patented a test for TB that overcomes two major challenges with current methods: it delivers quick results and is much cheaper.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.