tag:theconversation.com,2011:/africa/topics/xdr-tb-26013/articlesXDR-TB – The Conversation2017-06-01T14:01:51Ztag:theconversation.com,2011:article/781122017-06-01T14:01:51Z2017-06-01T14:01:51Z“Missing” TB cases are a huge problem. What Kenya needs to do to find them<figure><img src="https://images.theconversation.com/files/171321/original/file-20170529-25236-2a37ln.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Kenya needs to improve efforts to reach, treat and cure all TB patients.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><em>Tuberculosis (TB) is one of the <a href="http://www.who.int/mediacentre/factsheets/fs104/en/">top ten</a> causes of death worldwide. People with TB can infect up to <a href="https://www.cdc.gov/globalhivtb/who-we-are/resources/keyareafactsheets/finding-the-missing-4-million.pdf">10 to 15 </a> people annually if they are in close contact with them. Breaking the transmission cycle is key to fighting the disease. For that to happen diagnosis needs to be stepped up. The Conversation Africa’s Health Editor Joy Wanja Muraya spoke to Dr Jane Ong'ango on strategies to find the missing TB cases in Kenya.</em></p>
<p><strong>What is the burden of tuberculosis globally and in Kenya ?</strong></p>
<p>Great progress has been made to <a href="http://www.who.int/tb/en/">control and eliminate </a>TB. However it remains one of the top infectious diseases causing death. It disproportionately affects the <a href="http://www.who.int/bulletin/volumes/86/9/06-038737/en/">world’s poor</a> and is rated as one of the top 10 causes of death worldwide. In 2015 TB caused more deaths <a href="http://www.who.int/mediacentre/factsheets/fs310/en/">than HIV</a>. There were an estimated <a href="http://www.npr.org/sections/goatsandsoda/2015/10/28/452565249/tb-is-now-the-top-infectious-killer-even-though-deaths-are-down">10.4 million</a> cases across the world that year. </p>
<p>Global efforts to reduce illness and deaths from TB are part of the <a href="http://www.who.int/tb/End_TB_brochure.pdf?ua=1">sustainable development goals</a> and the World Health Organisation’s <a href="http://www.who.int/tb/post2015_strategy/en/">End TB Strategy</a>. The objectives of these two global efforts is to eliminate TB globally by <a href="https://sustainabledevelopment.un.org/?menu=1300">2030</a> through the reduction of TB deaths by 90% and the reduction of TB incidence by 80% compared with levels in 2015.</p>
<p>A tuberculosis prevalence <a href="http://nltp.co.ke/">survey</a> done in Kenya 2016 showed a prevalence rate of 558 tuberculosis cases per 100,000 population. This is double the 2015 WHO estimate of <a href="http://www.health.nsw.gov.au/Infectious/tuberculosis/Documents/countries-incidence.pdf">233</a> cases per 100,000 population. Tuberculosis is the <a href="http://hennet.or.ke/wp-content/uploads/2015/02/KENYA_HEALTH_POLICY_29-01-2014.pdf">fourth </a> biggest killer in Kenya after HIV/AIDS, maternal deaths and lower respiratory infections.</p>
<p>Based on the TB cases identified by the health system in 2015, the prevalence survey showed that every year about <a href="https://www.kma.co.ke/presentations/JaneRahediKMA%20meetingPP21042017jro.pdf">40%</a> of TB cases remain undetected in Kenya. This means that nearly half of the number of people with TB disease are undetected and not on treatment. They are considered as missing TB cases.</p>
<p><strong>Who constitutes the ‘missing’ TB cases?</strong></p>
<p>This is the gap between the estimated number of people who become ill with TB in a year and the number of people who were diagnosed and treated by the national TB programmes. </p>
<p>In 2015 the World Health Organisation estimated that there were about <a href="http://www.un.org/news/dh/pdf/english/2010/17052010.pdf">4.3</a> million people “missing across” the world. India, Indonesia and Nigeria accounting for almost half of them.</p>
<p>Finding the missing cases is critical to eliminating TB because they actively contribute to transmitting the disease to others.</p>
<p><strong>Where are the missing cases?</strong></p>
<p>A majority (<a href="http://nltp.co.ke">75%</a>) of individuals who have TB usually have TB related symptoms which could include any of the following; cough of any duration, night sweats, weight loss, fatigue, fever, and shortness of breath. Among these individuals the severity of the symptoms differ, despite this all should be screened for TB at the earliest possible time from when the symptoms develop. </p>
<p>In addition about a <a href="http://www.kma.co.ke/presentations/JaneRahediKMA%20meetingPP21042017jro.pdf">quarter</a> (25%) of individuals with TB do not have symptoms and will thus continue to spread the bacteria in the community. The missing TB cases may either have symptoms or not and could be found within three scenarios in the community which include;</p>
<ul>
<li>Individuals in the community with non severe symptoms, and therefore do not seek care.</li>
<li>Individuals at work, school, home or clinics are presumed not to have TB and hence not screened.</li>
<li>Individuals seek care for TB symptoms at health facilities, but do not get diagnosed.</li>
</ul>
<p><strong>What can we do to find the missing TB cases?</strong></p>
<p>There is need to provide<a href="https://www.standardmedia.co.ke/ureport/story/2000197762/i-suffered-out-of-ignorance-and-why-you-don-t-need-to"> public awareness</a> on Tuberculosis including having targeted messages for the vulnerable populations to encourage people to seek early intervention for any TB related symptom. </p>
<p>Health facilities should screen all persons with TB symptoms within their various departments to reduce possible chances of missing the cases. In addition to symptom screening there is need to expand use of Chest X-ray and avail GeneXpert as the first <a href="http://www.nation.co.ke/health/Advanced-diagnostic-tool-gives-hope-to-TB-patients/3476990-3876552-5t2bbjz/index.html">diagnostic</a> test for all presumed TB cases.</p><img src="https://counter.theconversation.com/content/78112/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jane Rahedi Ong'ang'o 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>About three million people globally are ‘missed’ each year for Tuberculosis diagnosis. Many of them will die, some will get better, others will continue to infect others.Jane Rahedi Ong'ang'o, Public Health Specialist, Senior Research Scientist, Kenya Medical Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/750102017-03-23T14:25:59Z2017-03-23T14:25:59ZLatest transmission patterns for drug resistant TB pose a new challenge<figure><img src="https://images.theconversation.com/files/162151/original/image-20170323-3535-3wutte.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 emergence of drug resistant tuberculosis has resulted in scientists taking a more aggressive and urgent approach to research into the development of the disease. </p>
<p>As the number of drug resistant TB cases has continued to rise, so has the need for rapid diagnosis, new treatment and new strategies that could help contain the disease. </p>
<p>Globally TB still kills <a href="https://www.newscientist.com/article/dn28405-tuberculosis-now-leading-cause-of-death-from-infectious-disease/">more people each year</a> than any other infectious disease, including HIV/AIDS. In 2014, an estimated <a href="http://apps.who.int/iris/bitstream/10665/191102/1/9789241565059_eng.pdf">1.4 million people</a> lost their lives to TB. In addition 500,000 people were diagnosed with multidrug-resistant tuberculosis (MDR-TB). </p>
<p>In South Africa, 20,000 MDR-TB cases were detected in 2014 though there were many more undetected cases. Of these 20,000 detected cases, 8% were thought to be extensively or totally drug resistant.</p>
<p>MDR-TB occurs when patients inappropriately or incorrectly use antimicrobial drugs or prematurely interrupt their treatment. Further resistance to the drugs used to treat MDR-TB results in extensively drug resistant TB (XDR-TB). When this happens the patient is resistant to at least four of the antibiotics that make up the first set of drugs used to treat TB, known as the first line regimen. </p>
<p>However, recent molecular and epidemiological <a href="http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30079-6/fulltext">studies</a> have challenged this belief. They suggest that in most regions of the world, drug-resistant TB is now predominantly caused by transmission. An estimated 95% of new MDR-TB strain cases are as a result of the drug resistant bacteria spreading from one person to the next.</p>
<p><a href="http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30079-6/fulltext">New research</a> on the spread of MDR-TB has raised even more concerns. Until recently it was thought that drug-resistant strains of TB were less transmissible, that both MDR-TB and XDR-TB were only acquired by people as a result of poor compliance to treatment. </p>
<p>This means that the ease in which normal TB is commonly transmitted also applies to both MDR-TB and XDR-TB as well. This poses additional challenges to managing the disease.</p>
<h2>The challenge with transmission</h2>
<p>TB – under normal circumstances – is highly infectious. It’s commonly spread through the air from one person to another. The TB germs enter the air when a person with active TB coughs, sneezes or speaks. People nearby may breathe in these germs and become infected, and subsequently develop active disease.</p>
<p>At present, when patients with either XDR-TB or incurable TB who have failed treatment are discharged back into their communities, they pose a risk of infecting fellow community members. This inevitably increases the number of infections. </p>
<p>Patients are more likely to suffer psychologically, abandon treatment, and generally show very poor treatment outcomes as a result of being isolated in XDR-TB treatment hospitals, or at home, for a long period of time. Other <a href="https://www.pressreader.com/south-africa/citypress/20170226/281728384293476">studies</a> have shown that decentralising treatment may yield equivalent results to keeping them in hospital. </p>
<p>Taking into consideration both the patient’s well-being as well as that of the communities in which they live, means that public health specialists need to develop ingenious interventions that will be beneficial for all.</p>
<p>These strategies must include new detection and intervention technologies targeting transmission and voluntary long-term community based and palliative care facilities so that discharged patients can spend their last days with their families. </p>
<h2>Tackling the issue</h2>
<p>Although South Africa – which is often considered the TB capital of the world – has made some noticeable headway in managing TB – between 2000 and 2015, an estimated <a href="http://www.who.int/mediacentre/factsheets/fs104/en/">49 million lives</a> have been saved through TB diagnosis and treatment. But the rise of drug resistant TB threatens these significant gains. </p>
<p>Public health officials have found that despite drug-resistant TB comprising less than 5% of the total TB caseload in the country, it consumes around 40% of the total TB budget. And the very heart of the health system is further affected as TB continues to claim the lives of a large number of healthcare workers. </p>
<p>To tackle the problem, a dynamic change in discourse is needed. The focus must be on how to respond to the emerging complexities that TB presents.</p>
<p>Governments must also develop and roll out improved diagnostic technologies. This would result in governments actively finding cases, developing better drug dosing and administration strategies, and improving the healthcare system. They should also provide infection control solutions to healthcare workers, and make more effective treatment and newer drugs more widely available to the entire population. </p>
<p>This requires a multi-pronged approach that should include a reduction in poverty and overcrowding, and other drivers of TB like HIV and smoking. </p>
<p>Strategies that will develop new rapid diagnostic tools are just as important in the fight against the scourge of drug resistant TB. Although the government has made some efforts in containing the spread of drug-resistant-TB by means of rolling out new generation diagnostic technology, more needs to be done to develop and deploy more comprehensive diagnostic tools, and better TB drug development and education.</p><img src="https://counter.theconversation.com/content/75010/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Keertan Dheda receives funding from the South African Medical Research Council, the South African National Research Foundation, EDCTP, NIH and the Oppenheimer Foundation.</span></em></p>To tackle TB a dynamic change in discourse is needed. The focus must be on how to respond to emerging complexities the disease presents.Keertan Dheda, Head of the Division of Pulmonology, University of Cape TownLicensed 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/566952016-03-23T04:04:16Z2016-03-23T04:04:16ZThe fight against TB shifts to fixing the immune system, not only bacteria<figure><img src="https://images.theconversation.com/files/116045/original/image-20160322-32320-bavjy6.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A pair of lungs infected with TB. </span> <span class="attribution"><span class="source">shutterstock</span></span></figcaption></figure><p>Tuberculosis (TB) has managed to remain a major global health problem, despite 100 years of research and more than 50 years of treatment being available. It still claims up to 1.5 million lives each year.</p>
<p>Although there have been ongoing efforts that provide some hope in the fight against the disease, the TB drug pipeline remains thin and vaccine development slow as resistance grows. </p>
<p>More than 9.6 million new TB cases were recorded in 2014. This prompted the Stop TB Partnership and the World Health Assembly to set a target of reducing TB-related deaths by 95% and cases by 90% by <a href="http://stm.sciencemag.org/content/7/276/276fs8.full">2035</a>. But new therapeutic and diagnostic interventions – including an effective vaccine – are urgently needed if these goals are to be achieved. </p>
<p>Recently there has been an increasing focus on alternative treatment strategies known as <a href="https://www.ncbi.nlm.nih.gov/pubmed/26184493">host-directed therapies</a>. These are mostly drugs and therapies that have been developed to treat other diseases and conditions such as diabetes or inflammation and then re-purposed to tackle TB.</p>
<p>What makes these therapies unique and important is that after 60 years of targeting the bacteria that kills TB, these treatments open a new door in the fight against infection. They focus on fixing the body rather than the bacteria. </p>
<p>If successful, these alternative treatments will add huge value by addressing the clinical demands around treating TB. </p>
<h2>Alternative approaches</h2>
<p>Host-directed therapies work differently from TB drug treatments. TB treatment drugs target the bacteria that causes TB. Host-directed therapies focus on areas in the lung that encourage the TB infection. They have two major goals: </p>
<ul>
<li><p>to improve the state of the immune system, which must be intact to fight off TB; and</p></li>
<li><p>to limit lung tissue destruction.</p></li>
</ul>
<p>Limiting tissue destruction is important because it prevents the disease from progressing. Tissue destruction can be the result of an overwhelming inflammation that destroys important cells in the immune system where the infection occurs. This may lead to cavities forming in the lung. The bacteria that causes TB is then able to disseminate throughout the lung and is coughed out through the airway. </p>
<p>A number of host-directed therapies currently being investigated could potentially be used for <a href="https://www.ncbi.nlm.nih.gov/pubmed/26184493">adjunctive TB therapy</a>. These 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>the diabetes drug, <a href="https://www.ncbi.nlm.nih.gov/pubmed/25411472">metformin</a>, which has been shown to enhance the body’s immune responses and decrease the TB bacterial loads in the lung;</p></li>
<li><p>non-steroidal <a href="https://www.ncbi.nlm.nih.gov/pubmed/25986592">anti-inflammatory drugs</a> that limit inflammation and tissue pathology. Inflammation leads to lung damage and progression of the disease; and</p></li>
<li><p><a href="https://www.ncbi.nlm.nih.gov/pubmed/24133190">statins</a> that reduce cholesterol levels and limit bacterial growth in the body’s immune cells. Cholesterol is known to encourage the growth of bacteria. </p></li>
</ul>
<p>When these therapies are used in combination with standard treatment regimens that target the bacteria, they are likely to shorten the current course of treatment. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/1mRTm6qPu1c?wmode=transparent&start=110" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Mohlopheni Marakalala speaks about host directed therapies at the Next Einstein Forum.</span></figcaption>
</figure>
<h2>Why we need alternatives</h2>
<p>There are several challenges that affect TB eradication. </p>
<p>First, the TB burden has been aggravated by HIV co-infection. HIV compromises the immune response required to protect a person against TB. This increases vulnerability to the disease. The World Health Organisation’s most recent <a href="http://www.who.int/tb/publications/global_report/gtbr2015_executive_summary.pdf">global TB report</a> shows that of the TB-related deaths in 2014, just under 27% of patients were HIV-positive. This is a slight increase <a href="http://apps.who.int/iris/bitstream/10665/91355/1/9789241564656_eng.pdf">from 2012</a>.</p>
<p>A second challenge is drug resistance. </p>
<p>First-line drug regimens have saved millions of lives but have been marred by non compliance and inconsistent use. TB patients who fail to adhere to their drug regimens often develop drug resistant TB. This means they have to go onto second-line drugs which are more expensive and may take even longer to complete.</p>
<p>Further resistance to second-line drugs leads to extensively drug-resistant TB (XDR-TB). This is more difficult to treat. </p>
<p>Drug resistance has led to a number of patients not responding to current treatment protocols, which is why there is a dire need for more treatment options.</p>
<p>The third challenge is that there is no adequate vaccine for adults.</p>
<p>The only approved TB vaccine, Bacille Calmette-Guérin, introduced 95 years ago, reduces the risk of TB in children. But it does not help adults with lung TB. An efficacious vaccine that provides a reliable protection against pulmonary TB is essential to eradicate TB. </p>
<p>In the past ten years, there has been some progress in developing a vaccine. A new candidate, <a href="https://www.ncbi.nlm.nih.gov/pubmed/23391465">MVA85A</a>, reached a phase 2b clinical trial. </p>
<p>Although MVA85A failed the clinical end point trial due to limited efficacy, several lessons were gained from the study. These will be highly beneficial in guiding future vaccine development efforts. </p>
<p>Currently over a dozen preventive vaccine candidates are progressing through the <a href="https://www.ncbi.nlm.nih.gov/pubmed/21798463">development pipeline</a>, providing some hope in achieving the 2035 targets.</p>
<h2>Other interventions that could help</h2>
<p>There are several other areas that need to be looked at to help eradicate TB. </p>
<p>First, the rapid diagnostic tools that can detect latent TB, drug-susceptible TB and drug-resistant TB need to be improved to detect the disease earlier. </p>
<p>Second, patients that do not respond to current treatments due to drug resistance do not have any other alternatives. A new strategy is needed here. </p>
<p>Finally, combination therapy hasn’t been cracked. This would shorten treatment protocols, thus improving adherence.</p><img src="https://counter.theconversation.com/content/56695/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mohlopheni Marakalala has previously received funding from the South African National Research Foundation and the Medical Research Council. </span></em></p>There is an increasing focus on alternative treatment strategies, developed to treat other diseases and conditions but re-purposed to tackle TB.Mohlopheni Jackson Marakalala, Senior Lecturer and Group Leader in the Division of Immunology, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.