tag:theconversation.com,2011:/fr/topics/latent-tb-27419/articleslatent TB – 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/1919152022-11-29T14:32:01Z2022-11-29T14:32:01ZSouth Africa’s prisons are a breeding ground for the spread of TB. Our model shows how<figure><img src="https://images.theconversation.com/files/488556/original/file-20221006-24-3ly4qx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People in prison are more at risk of TB than the general population.</span> <span class="attribution"><span class="source">Stephane de Sakutin/AFP via Getty Images</span></span></figcaption></figure><p>South African prisons are famously overcrowded. Prison populations are believed to exceed capacity by an overall 33%, although that number jumps to over 200% at some facilities, according to <a href="https://www.sabcnews.com/sabcnews/overcrowding-in-the-countrys-prisons-is-now-at-33-lamola/#:%7E:text=The%20Eastern%20Cape%2C%20the%20Western,and%20Mount%20Frere%20at%20243%25.">recent reports</a>.</p>
<p>The confined, often overcrowded conditions of prisons make them a <a href="https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(21)00025-6/fulltext">breeding ground</a> for disease. In particular, they are a high-risk environment for the spread of infectious diseases such as tuberculosis (TB) – a leading cause of death in South Africa. TB spreads in the air when a person with the disease coughs, speaks, or sings. </p>
<p>In South Africa’s general population TB prevalence is <a href="https://theconversation.com/first-ever-national-survey-shows-the-extent-of-south-africas-tb-problem-155153">737 per 100,000</a> people – one of the <a href="https://apps.who.int/iris/bitstream/handle/10665/341980/9789240029439-eng.pdf?sequence=1&isAllowed=y">highest</a> in the world. </p>
<p>A global <a href="https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(21)00025-6/fulltext">review</a> found that people in prison were more at risk of TB than the general population. But very little is known about the TB prevalence in South Africa’s prisons. A <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087262#:%7E:text=Studies%20from%20Sub%2DSaharan%20African,survey%20from%20Zambia%20%5B9%5D.">2010 study</a> of the country’s largest prison found that 38.6% of the study participants showed at least one symptom of TB. Only 1% of participants were receiving TB treatment. </p>
<p>In two <a href="https://www.hindawi.com/journals/jam/2018/3420528/">separate</a> <a href="https://www.naturalspublishing.com/files/published/p91le7563uyz2k.pdf">papers</a> we built models to better understand how TB is spread in a crowded environment, such as a prison. Our findings make it clear that as long as there is an influx of infected patients, TB cannot be eliminated. It will continue to spread through the influx of new carriers or new potential hosts. This in turn increases the risks of drug-resistant and multi-drug-resistant variants of TB developing.</p>
<p>Mathematical epidemiological modelling is a great tool for predicting the behaviour of a disease over a period of time. Models are not meant to treat the disease. But they inform public health decisions and policy. Models can be modified to suit a certain behaviour of the disease, specific lifestyle factors in the population and certain interventions by public health authorities. The accuracy of forward projections depends on the quality and quantity of the available (historical) data. </p>
<p>Mathematical models are able to inform us of the likelihood that, with or without control strategies such as screening and vaccination, the disease can be eliminated or will persist at a specified level of endemicity.</p>
<h2>Modelling in crowded environments</h2>
<p>Over the past few years, we and other researchers have been modelling the transmission of TB, using compartmental models. This is a modelling technique commonly applied in epidemiology to predict the spread of an infectious disease.</p>
<p>The technique derives its name from the fact that the population is divided into “compartments” according to the disease status of individuals: </p>
<ul>
<li><p>those who are susceptible </p></li>
<li><p>those who are infectious </p></li>
<li><p>those who have recovered. </p></li>
</ul>
<p>We then applied this technique to what is known as a crowded environment. This can be anything from an open-air concert to a mining population to a prison – any place where people could potentially gather <em>en masse</em> and in close proximity.</p>
<p>A key objective of the modelling study is what is known as the stability analysis of the disease-free equilibrium state, or the point where the disease is no longer found within that environment. This is because it is important to understand how the disease can possibly be eliminated from the population. There is a lot of maths involved. </p>
<p>In a <a href="https://www.hindawi.com/journals/jam/2018/3420528/">2018 paper</a> we looked at the inflow of infected patients into a prison, computing what the impact would be on the broader prison community. </p>
<p>In a <a href="https://www.naturalspublishing.com/files/published/p91le7563uyz2k.pdf">more recent paper</a> – in the interests of better accuracy – we added further complexity by developing a novel two-group model that mirrors the dynamics of TB in a prison system. </p>
<p>Our model, in addition to the compartmentalisation, further divides the prison population into two groups: sentenced individuals, and remanded individuals awaiting trial. </p>
<p>The model showed mathematically that when infected people continue to enter the system, the disease cannot be eliminated. It also showed that the average time inmates spend in prison could make a difference to TB dynamics – but this needs further study.</p>
<h2>Next steps</h2>
<p>There are a number of solutions.</p>
<p>The World Health Organization recommends early diagnosis, equitable access to health services, and the co-management of TB and HIV.</p>
<p>At the top of the list is the universal screening of those coming into the system. Research shows that this commonly <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907552/">proposed measure</a> can reduce the number of infectious individuals and help eliminate the disease.</p>
<p>Hand in hand with this should be a strategy to admit infected inmates to a prison facility which has an elimination plan in place, such as treatment for latent cases. </p>
<p>Providing comprehensive curative and preventive services for cases is vital if TB is to be eliminated in prisons.</p><img src="https://counter.theconversation.com/content/191915/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>The overcrowded conditions of prisons make them a high-risk environment for the spread of infectious diseases such as TB.Sibaliwe Maku Vyambwera, Lecturer in Mathematics, University of the Western CapePeter Joseph Witbooi, Professor, University of the Western CapeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1793992022-03-23T14:35:02Z2022-03-23T14:35:02Z‘Test and treat’ is being used to tackle HIV. Why not TB?<figure><img src="https://images.theconversation.com/files/453803/original/file-20220323-25-dtr5u6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Indian Community health volunteers verbally screen high risk populations for TB.</span> <span class="attribution"><span class="source"> SANJAY BAID/EPA-EFE</span></span></figcaption></figure><p>Worldwide, tuberculosis (TB) remains a significant cause of disease and deaths. Around <a href="https://cdn.who.int/media/docs/default-source/hq-tuberculosis/tb-report-2021/factsheet-global-tb-report-2021.pdf?sfvrsn=86011b1e_5&download=true">9.9 million</a> people had the disease in 2020. The burden is higher in low- and middle-income countries. Africa accounts for <a href="https://www.who.int/publications/digital/global-tuberculosis-report-2021/tb-disease-burden/incidence">25%</a> of TB cases. </p>
<p>TB is caused by a bacterium called <em>Mycobacterium tuberculosis</em>. Not everyone who gets infected with the bacterium will get sick. Once infected, a person has a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105930/">5%-15% lifetime risk</a> of developing active TB disease. Risk factors that contribute to people’s susceptibility to getting ill with TB include HIV infection, diabetes mellitus, malnutrition, alcoholism and rheumatoid arthritis.</p>
<p>Based on my experience of researching and being involved in TB programmes in Africa over the past two decades I would argue that TB control should take a leaf out of the approach adopted for HIV. </p>
<p>In the HIV care field, the <a href="https://www.unaids.org/sites/default/files/media_asset/201506_JC2743_Understanding_FastTrack_en.pdf">current UNAIDS strategy is to “test and treat”</a>. This approach involves widespread, community-based HIV testing. People testing positive for HIV are immediately placed on antiretroviral therapy. </p>
<p>This strategy has two key benefits: protection from HIV infected persons progressing to AIDS, and a lowered risk of infecting others. This, in turn, will decrease the global HIV burden, and lead to improved health of the infected persons and less transmission to the uninfected.</p>
<p>What if the global TB management community adopted a similar strategy? </p>
<p>Something akin to this is already implemented in high income countries. Many routinely screen immigrants for <em>Mycobacterium tuberculosis</em> infection, and offer preventive treatments to those who test positive. This contributes to less TB disease in these countries. </p>
<p>There are a number of limitations to this strategy. These include the large population vulnerable to infection, the risk of drug resistance, as well as the probability of re-infection. Nevertheless, a ‘test and treat’ approach could – if widely implemented – limit TB disease in low- and middle-income countries. </p>
<h2>Current strategies</h2>
<p>In high-income countries people at high risk of TB disease <a href="https://pubmed.ncbi.nlm.nih.gov/30833050/">undergo screening programmes</a> even when they have no symptoms. Those who test positive for <em>Mycobacterium tuberculosis</em> infection are given preventive treatment for 3-9 months depending on the regimen. </p>
<p>This strategy has contributed to limiting active TB disease.</p>
<p>The idea has been mooted for developing countries, but it has not yet been introduced comprehensively.</p>
<p>In low- and middle-income countries screening for infection and offering preventive medication are limited. These services are mainly promoted for children who have been in contact with an adult with TB disease, as well as people with HIV. </p>
<p>Even this isn’t implemented across the board. </p>
<p>In Africa people are only screened once they show symptoms, such as a cough. Even then there is often a delay in confirming a diagnosis, and sometimes even in initiating appropriate treatment. By the time the person starts any TB treatment, they may have infected a number of other people. This could be in their homes, in schools as well as in work places and social meeting places.</p>
<p>A <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223966">study</a> done in Uganda showed that the risk of children getting TB infection after exposure to an adult in the home increased with age. With an additional risk factor such as overcrowding, under nutrition and HIV infection, household contacts of a TB patient stand a chance of getting active TB diseases over time.</p>
<h2>Limitations</h2>
<p>Introducing a ‘test and treat’ approach would seem a logical way to go. There are, however, a number of factors that could make such a strategy difficult:</p>
<p>Firstly, the populations at risk are large and the testing and treatment programmes are not easily affordable for many governments in Africa. This is true of HIV too. But those tackling HIV have nevertheless moved towards a global test and treat strategy.</p>
<p>Secondly, the drugs used for TB prevention are the same ones used for treatment. If the “healthy persons” offered TB preventive treatment do not take their medicines diligently it would promote drug resistance, with disastrous consequences for the treatment of those with TB disease.</p>
<p>Thirdly, if a person takes medication for tuberculosis preventive treatment, (usually 1 or 2 types of pills), when they are in early stages of unnoticed tuberculosis disease which requires 4 types of pills, this may inadvertently lead to suboptimal treatment of the early tuberculosis disease, with risk of negative consequences to the person due to inadequate treatment, and to others with TB disease in the long run due to “drug resistance”.</p>
<p>Fourthly, there is a risk of a person who has been given TB preventive treatment being reinfected, thus potentially requiring repeat preventive medication. But again we need to learn from the HIV community, where this has not hindered them in the test and treat strategy. </p>
<p>Despite these challenges I believe there is nevertheless merit in considering the “test and treat strategy” towards global TB control. But this would need the concerted effort of all players.</p><img src="https://counter.theconversation.com/content/179399/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Harriet Mayanja-Kizza is based at the Uganda CWRU Research Collaboration (UCRC) - a Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) Partner Site. She receives funding from NIH, EDCTP, CDC, BMGF funding for different tuberculosis related collaborative studies</span></em></p>In high-income countries people at high risk of TB disease undergo screening programmes even when they have no symptoms.Harriet Mayanja-Kizza, Professor of Medicine, College of Health Sciences, Makerere UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1567612021-03-22T15:06:20Z2021-03-22T15:06:20ZTB treatments are notoriously hard to stick to: shorter regimens offer a breakthrough<figure><img src="https://images.theconversation.com/files/388553/original/file-20210309-21-1jpbbky.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">If left untreated, latent TB infection can progress to TB disease.</span> <span class="attribution"><span class="source">Mujahid Safodien/AFP via Getty Images</span></span></figcaption></figure><p>Tuberculosis (TB) is a major cause of illness and death around the world. In <a href="https://www.who.int/news-room/fact-sheets/detail/tuberculosis">2019</a>, 10 million people fell ill with TB and close to 1.4 million people died. Most (95%) of the cases are in low- and middle-income countries.</p>
<p>It’s estimated that a quarter of the global population is infected with TB – that’s <a href="https://www.tballiance.org/why-new-tb-drugs/global-pandemic#:%7E:text=The%20World%20Health%20Organization%20estimates,the%20bacteria%20that%20causes%20TB.">around 1.8 billion</a> people. Most infected people have no symptoms and are not contagious. Most of them don’t even know they’re infected – their TB is latent. If left untreated, latent TB infection can progress to TB disease, which makes people sick and can be transmitted from one person to another. This risk is higher among people with HIV and children younger than five who share a home with people who have confirmed pulmonary TB. </p>
<p>Despite these high numbers, TB research has suffered from critical under-funding for years. As a result the development of tools to prevent and control TB has been lagging. For example, the Bacille Calmette Guerin (BCG) vaccine has been in use for nearly a century and is effective in preventing severe disease in infants and young children. But it provides poor levels of protection against lung disease in adolescents and adults. </p>
<p>Treatment of TB infection remains the best option to preventing those infected from getting the disease. Yet <a href="https://www.impaact4tb.org/why-prevention/">very few people</a> who are eligible for TB preventive treatment are taking it. Where treatment has been initiated, <a href="https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-020-09902-z">completion rates have generally been poor</a> because of the long duration of regimens. The previous standard of care – isoniazid preventive therapy – was long and complex, with people required to take a pill daily for six to 36 months. </p>
<p>Now shorter regimens are being developed. My colleagues and I are <a href="https://www.impaact4tb.org/who-we-are/">part of a project</a> to look at ways of scaling up affordable short course preventive therapy for TB. The aim of the four-year research project is to identify and provide new, shorter treatment options for people with latent TB infection. The goal is to slow – and ultimately stop – the flood of new TB cases. </p>
<p>The project has started by rolling out a new regimen targeting people with HIV and children under five in 12 high-burden countries. These include Pakistan, Zimbabwe, Malawi, Indonesia, Cambodia, Kenya, and Ethiopia. All have started scaling up the short-course regimens. South Africa, Namibia, Lesotho and Eswatini will also begin in 2021 through support from <a href="https://www.who.int/tb/publications/2018/latent-tuberculosis-infection/en/">development</a> <a href="https://za.usembassy.gov/our-relationship/united-states-presidents-emergency-plan-for-aids-relief-pepfar-2/pepfar-community-grants-program/">partners</a>. </p>
<p>It could be a game changer for two reasons. The first is that the short-course three month or one month regimens can prevent TB in even more people than the current six month regimen. And because it means that people are much more likely to complete their treatments.</p>
<h2>New developments</h2>
<p>Preventive treatment is given to people who are infected with TB, or those who have been exposed to the bacteria and are at a high risk of developing TB disease. This is critical to prevent progression from latent infection to disease and has been recommended for the past 23 years. </p>
<p>Without treatment, 5% to 10% of people with TB infection will develop active TB. </p>
<p>The efficacy of combination therapies with isoniazid and rifampicin (3HP) in preventing TB was established in 2018 after large, multi-country <a href="https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(20)30032-1/fulltext">clinical trials</a>. This was followed by the <a href="https://www.who.int/tb/publications/2018/latent-tuberculosis-infection/en/">WHO publishing updated guidelines</a> that recommended TB preventive treatment options that could help overcome several challenges. One included taking medication for extended periods of time. </p>
<p>This catalysed further innovations to reduce the number of pills needed to take, and the length of time they needed to take them. This included an ultra-short regimen that combined isoniazid and rifapentine, taken once daily for one month (1HP). </p>
<p>The short-course regimens offer clear advantages in terms of improved adherence and completion rates due to the shorter duration of treatment and the child-friendliness.</p>
<p>The fixed dose combination treatments reduce the pill burden for adults taking 3HP from nine pills to three pills per week and for adults taking 1HP from six pills to four pills. These fixed dose combination treatments are likely to improve treatment completion and health outcomes.</p>
<p>These regimens can be used by people living with HIV – TB prevalence is high in this population group. The choice of regimen should be informed by multiple factors including age, potential side effects, interactions with other medications and individual preferences. </p>
<p>Their <a href="https://www.impaact4tb.org/wp-content/uploads/2019/06/LTBIBrief_0607.pdf">introduction will be needed</a> if the global target of ending TB by 2030 are to be met.</p>
<h2>The hope</h2>
<p>Introducing shorter regimens, and ramping up to 3HP in 2021, will offer several advantages at both the clinical and programmatic levels. </p>
<p>By using short-course 3 month or 1 month regimens we can prevent TB in even more people than the current six month regimen. We can double or triple the numbers in the same time period. </p>
<p>Once a child-friendly and affordable fixed dose combination becomes available, 3HP can become the preferred regimen for TB preventive treatment across all ages. Children younger than 15 accounted for <a href="https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf#page=30">12% of the 10 million</a> estimated to have been ill with TB in 2019 and an estimated 227 360 died from TB. By ensuring that children who need preventive treatment get it, death due to TB can be reduced. </p>
<p>This will significantly facilitate delivery of TB preventive treatment and support a family-centred approach to TB infection management.</p><img src="https://counter.theconversation.com/content/156761/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Violet Chihota is a member of the South African National TB Think Tank. </span></em></p>Until vaccines that are capable of protecting all populations against TB are developed, treatment is the best option to preventing infection.Violet Chihota, Lead Senior Scientist, Aurum InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1084192019-01-29T23:35:54Z2019-01-29T23:35:54ZFighting tuberculosis: Databases are new and powerful weapons<figure><img src="https://images.theconversation.com/files/255907/original/file-20190128-108338-1h3er27.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Using databases and community partnerships, we can end TB in Canada. </span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Tuberculosis (TB) is one of the <a href="https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death">top 10 global causes of death</a>. It is caused by bacteria that first settle in the lungs and spread through the air and is passed on when a person with an active infection coughs or sneezes. People can also pass on TB when they are not themselves sick, if they have a “sleeping” or “latent” infection. </p>
<p>Treatments have been available since the 1940s and TB can be treated before an infected person feels symptoms. However, TB continues to spread in Canada and globally.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1046512762011209728"}"></div></p>
<p>It is extremely important that people with active and latent TB infections receive treatment to eliminate the bacteria. The World Health Organization’s <a href="https://www.who.int/tb/post2015_strategy/en/">End TB Strategy</a> aims to drastically reduce TB deaths and new cases by the year 2035. It identifies local databases as essential for meeting this goal. </p>
<p>I recently <a href="http://umanitoba.ca/faculties/health_sciences/medicine/units/chs/departmental_units/mchp/Infographic_Launch-MBTB.html">completed a study</a> with First Nations representatives, research experts, and Dr. Pierre Plourde, medical health officer and medical director of integrated tuberculosis services at Winnipeg Regional Health Authority, to investigate TB in Manitoba.</p>
<p>We found that although treatment of latent TB infections is on the rise, there is still a lot of work ahead. Rates have yet to reach the recommended 80 per cent completion target. </p>
<p>People with active TB have more emergency room, hospital and family physician visits before receiving a diagnosis. Each visit is an opportunity for diagnosis and monitoring the progression of treatment. </p>
<h2>Health databases are vital</h2>
<p>We used Manitoba’s administrative health databases to investigate use of the health system by people with active and latent TB. We looked at the characteristics of people who have come in contact with TB. And we examined the health outcomes of people with active and latent TB infections. </p>
<p>Manitoba’s <a href="http://umanitoba.ca/faculties/health_sciences/medicine/units/chs/departmental_units/mchp/media_room/media/MCHP_MBTB_SupplementaryContent_TB_Reg_2015.pdf">TB Registry</a> database takes account of all individuals who have been diagnosed with an active TB infection and those who have received treatment for latent TB infection. </p>
<p>Linking the TB Registry to other health and social databases tells us a lot about who in Manitoba has TB and what health services these people receive. Active TB disproportionately affects Indigenous people, and populations born outside of Canada. </p>
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<p>Indigenous people make up only four per cent of the Canadian population. However, surveillance data provided by the Public Health Agency of Canada indicates that more than a fifth of reported cases of active TB affect Indigenous persons. </p>
<p>These databases are essential for surveillance, research and program evaluation that can inform local strategies to end TB. </p>
<h2>Patients must complete treatments</h2>
<p>Treating people with latent TB is important for preventing new TB cases, but this is easier said than done. Those with latent TB need to be on medication for several months to completely get rid of their infection, even while they don’t feel sick. </p>
<p>It can be difficult to stick with the treatment for that long, especially when the side effects may cause the person to feel unwell. </p>
<p>The <a href="https://www.who.int/tb/strategy/end-tb/en/">World Health Organization recommends</a> that more than 80 per cent of patients treated for latent TB infection need to complete their treatments to prevent the spread of the disease. </p>
<p>Rates are increasing but there is still a ways to go to meet the recommendations. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/more-than-one-in-100-nunavut-infants-have-tb-94104">More than one in 100 Nunavut infants have TB</a>
</strong>
</em>
</p>
<hr>
<p>TB registries and other databases can help. But there is still more work to be done to ensure all populations are captured in the data for early detection of TB. </p>
<h2>Early identification is key</h2>
<p>Steps can be taken for better use of the data available — to set up programs to identify people who have a latent TB infection across Manitoba as early as possible. </p>
<p>Partnerships with communities most impacted by TB are essential to ending TB through earlier diagnosis and improved delivery of known effective treatments. </p>
<p>Data can help us to learn more about the impacts of TB in the community. Building partnerships with members of the community to interpret data and have input about the data collected helps everyone to work together to end TB. This will reduce missed or delayed diagnoses and enable faster delivery of care.</p>
<p>Strong partnerships with First Nations leaders, governments and researchers, along with quality health data, are key to preventing, treating and ultimately putting an end to tuberculosis in Canada. </p>
<p>With the support of partners we can make better use of the data we have to identify active and latent TB infections and to improve how people with infections use the health-care system. Together we can end tuberculosis in Canada.</p><img src="https://counter.theconversation.com/content/108419/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The ‘Exploring Tuberculosis Treatment, Management, and Prevention in Manitoba’s Administrative Health Data’ report was prepared at the request of Manitoba Health, Seniors and Active Living (MHSAL), a department within the Government of Manitoba, as part of the contract between the University of Manitoba and MHSAL. It was supported through funding provided by MHSAL to the University of Manitoba (HIPC 2015/2016-64). The results and conclusions are those of the authors and no official endorsement by MHSAL was intended or should be inferred. Data used in this study are from the Manitoba Population Research Data Repository housed at the Manitoba Centre for Health Policy, University of Manitoba and were derived from data provided by MHSAL, as well as the Winnipeg Regional Health Authority, the Department of Families, Manitoba Education and Training, Manitoba Justice, Vital Statistics and Statistics Canada. Strict policies and procedures were followed in producing this report to protect the privacy and security of the Repository data.</span></em></p>In Manitoba, Canada, researchers have used health databases to better understand how people with tuberculosis interact with the health-care system.Lisa Lix, Professor of Community Health Sciences & Senior Research Scientist with Manitoba Centre for Health Policy, University of ManitobaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/751212017-03-24T14:45:53Z2017-03-24T14:45:53ZNew study helps crack the problem of diagnosing TB in people with HIV<figure><img src="https://images.theconversation.com/files/162373/original/image-20170324-12136-e244ve.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>Diagnosing TB in people who have HIV has been a challenge because they often have low levels of the bacteria in their system. This has been a serious problem for a country like South Africa where 454,000 people are infected with TB each year, half of whom are HIV positive. The Conversation Africa’s Health and Medicine Editor Candice Bailey spoke to Professor Bavesh Kana about a landmark study that provides a solution to tackling this diagnostic problem.</em> </p>
<p><strong>What has the traditional thinking been on TB bacteria and how it grows?</strong></p>
<p>The diagnosis of people infected with the tuberculosis bacteria can show either that they are “active” or “latent” carriers of the disease. People with “active” disease display well known symptoms such as persistent coughing, fever, night sweats and weight loss. </p>
<p>“Latent” infection on the other hand is not associated with any clinical symptoms. People who have latent infection carry a 10% lifetime risk of developing active disease through a process called reactivation. This risk is increased when a person’s immune system is compromised by an HIV-infection or advancing age, for example. </p>
<p>To diagnose TB, one has to identify the bacteria from a sample of sputum. For this, it must be replicated by culturing them in a laboratory. Replicating bacteria are important because they aid the diagnostic process and without them, it’s difficult to diagnose TB. </p>
<p>Traditionally, it was thought that people who had active TB harboured bacteria that were easy to replicate through culturing. The thinking was that people with latent infection had dormant bacteria that could not replicate, which are difficult to culture. </p>
<p>To a great extent, this dogma wasn’t underpinned by extensive experimental evidence. This is mainly because its been difficult to model TB disease in small animals or in a laboratory. </p>
<p><a href="http://www.atsjournals.org/doi/abs/10.1164/rccm.201604-0769OC">Our research</a>
shows that these initial views were somewhat simplistic. </p>
<p><strong>What did your research find?</strong></p>
<p>Our research opens a new door to cracking the very difficult problem of diagnosing people who have low levels of TB bacteria, for example people who are HIV positive. </p>
<p>Our findings challenge the conventional thinking because we discovered that patients with active TB in reality harbour mixtures of both replicating and non-replicating organisms. This finding is significant because it will now be possible to diagnose people who previously would have gone undetected. It’s important to emphasise though, that a single TB diagnostic test will unlikely be enough to diagnose all TB disease profiles.</p>
<p>In our study, we explore the presence of non-replicating bacteria that are unable to grow under standard laboratory conditions. We term these as Differentially Culturable Tubercle Bacteria (DCTB).</p>
<p>We analysed the sputum from TB diseased people who had not started treatment and were able to detect varying combinations of up to five operationally distinct categories of Differentially Culturable Tubercle Bacteria. </p>
<p>We expect that detection of differentially culturable bacteria will now make it possible to diagnose people who have low levels of bacteria, for example older people, children and those who are HIV-positive.</p>
<p><strong>How was the research done?</strong></p>
<p>We approached various clinics in Soweto and identified a cohort of TB patients who had drug sensitive TB disease but had not started extensive TB treatment. Many had HIV. </p>
<p>Their sputum samples were subjected to the standard TB tests which includes laboratory culturing. We also applied a growth stimulating technique to the specimen to see if it could be cultured under different circumstances. We were surprised when we uncovered new populations of bacteria that were not detected using standard laboratory culturing. </p>
<p>We compared the results of the different tests with and without growth stimulatory factors to quantify the proportions of replicating and non-replicating bacteria in each sample. We found that using our specialist growth technique, we could more accurately predict the presence of TB disease. </p>
<p><strong>Why is it significant?</strong></p>
<p>This study has highlighted a previously unknown complexity in the bacterial populations linked to active TB disease. Our research opens new avenues to explore alternate mechanisms for diagnosing and detecting TB bacteria.</p>
<p>More importantly, these findings can be used to develop new ways of understanding how patients respond to treatment. Related to this, is the ability to better assess the efficacy of new TB drugs using the methods employed in our study.</p><img src="https://counter.theconversation.com/content/75121/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bavesh Kana receives funding from:
The South African Department of Science and Technology
The National Research Foundation
The South African Medical Research Council
The National Health Laboratory Service
The Howard Hughes Medical Institute
The Bill and Melinda Gates Foundation
The Division of Aids (DAIDS) and the National Institutes of Health (USA)
The Centre for Aids Prevention Research in South Africa
He is affiliated with:
The University of the Witwatersrand
The National Health Laboratory Service
The Centre for Aids Prevention Research in South Africa</span></em></p>Scientists have struggled to diagnose TB in people with compromised immune systems because of the low levels of the bacteria in their body.Bavesh 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/587982016-05-29T17:19:11Z2016-05-29T17:19:11ZInflammatory proteins offer insights into how TB spreads in the lungs<figure><img src="https://images.theconversation.com/files/124383/original/image-20160528-888-1pq2dvo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">One-third of the world’s population is latently infected with the bacteria that cause tuberculosis.</span> <span class="attribution"><span class="source">shutterstock</span></span></figcaption></figure><p>Tuberculosis – the bacterial lung disease – remains a leading global health problem more than a century after it was first discovered. It is still responsible for about <a href="http://www.who.int/mediacentre/factsheets/fs104/en/">1.5 million deaths</a> every year. The problem is aggravated by drug resistance and HIV/AIDS co-infection. </p>
<p>According to the <a href="http://www.who.int/mediacentre/factsheets/fs104/en/">World Health Organisation</a>, one-third of the world’s population is latently infected with the bacteria that cause TB. Only between 5% and 10% of these people develop the active TB disease in their lifetime. </p>
<p>The rest of the latently infected population will never develop the active disease. This is because they’re protected by a strong immune system that helps the body to defend itself against the infection.</p>
<p>Scientists still do not fully understand why people with latent TB develop active TB. <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144869/">Ongoing research</a> has centred on understanding the state of the immune system and what goes wrong that results in the TB worsening. </p>
<p>Our <a href="https://www.ncbi.nlm.nih.gov/pubmed/27043495">research</a> looked at one component of the immune system and found that there were proteins in the body that promote lung inflammation which helps the bacteria that causes TB to spread throughout the lung.</p>
<p>Now that we have identified these proteins that are associated with disease progression, the next step is to find the drugs that will inhibit these proteins and limit lung inflammation. </p>
<p>Although most TB drugs have been focused on tackling the bacteria, these new drugs are likely to help, along with currently available treatments, shorten the treatment course. </p>
<h2>Immune response against TB</h2>
<p>To fight TB infection, cells of the immune system are recruited to the area where the bacteria is located in the lung. These cells then form wall-like structures around the bacteria to confine it. These wall-like structures are called <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872107/">granulomas</a>. </p>
<p>As the disease progresses the granulomas can undergo changes. Initially, some of the cells in the granulomas die and form a mass structure where bacteria can thrive. Subsequently cavities are formed in the granulomas. This allows the bacteria to spread throughout the lung. Through these holes, the bacteria can also escape to the airways and be coughed out. This leads to the bacteria spreading and infecting other people.</p>
<p>Although granulomas are formed to contain the bacteria, their deterioration may result in lung tissue destruction and worsening of the disease. </p>
<p>The detailed mechanisms behind granuloma formation and dissociation during disease progression are still poorly understood. Our <a href="https://www.ncbi.nlm.nih.gov/pubmed/27043495">study</a> tried to understand why the granulomas deteriorate. </p>
<p>We looked at the proteins and lipids present in various regions of the granuloma. We analysed granulomas from tissues removed from TB patients who had undergone surgery because of severe lung damage.</p>
<h2>Analysing the inflammation</h2>
<p>We used <a href="http://www.ncbi.nlm.nih.gov/pubmed/27043495">tools</a> that allowed us to analyse all the proteins associated with each region of a specific granuloma type. More than 3000 proteins were identified across all granuloma types. </p>
<p>Within this list some of the proteins belonged to a category of pro-inflammatory proteins, which encourage inflammation – or tissue damage – in the lung, and anti-inflamatory proteins that are known to limit inflammation. We found that the proteins that encouraged inflammation were close to the granulomas that had deteriorated while the proteins that fought inflammation where closer to the areas that were intact. </p>
<p>One of the proteins we found <a href="https://www.ncbi.nlm.nih.gov/pubmed/22304914">LTA4H</a> (leukotriene A4 hydrolase) promotes the release of pro-inflammatory lipids called <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Resolving+inflammation%3A+dual+anti-inflammatory+and+pro-resolution+lipid+mediators">leukotrienes</a> which drive inflammation in the lung.</p>
<p>Another pro-inflammatory protein we found was <a href="https://www.ncbi.nlm.nih.gov/pubmed/23582643">TNF</a>. In moderate amounts this protein is important for early response to infection but in excess it can promote tissue damage. </p>
<p>This balance between pro and anti-inflammatory proteins signals are important for the disease outcome, as exaggerated inflammation could eventually lead to tissue destruction. If this balance is not attained the TB disease may become worse.</p>
<h2>Therapies that limit inflammation</h2>
<p>Recently TB research efforts have focused on the development of <a href="http://theconversation.com/the-fight-against-tb-shifts-to-fixing-the-immune-system-not-only-bacteria-56695">immune-specific</a> treatment strategies that help the body to control infections. Such strategies are known as host-directed therapies. </p>
<p>Host-directed therapies in TB have two major approaches:</p>
<ul>
<li><p>improving the immune system; and </p></li>
<li><p>limiting lung tissue destruction that speeds up the disease progression. </p></li>
</ul>
<p>Our study identified some protein candidates that could be explored in guiding development of host-directed therapies that hamper inflammation during TB disease. </p>
<p>By limiting inflammation, these therapies are likely going to inhibit tissue destruction and reduce bacterial spread throughout the lung.</p>
<p>A number of host directed therapies are currently under investigation for potential use as <a href="https://www.ncbi.nlm.nih.gov/pubmed/26184493">adjunct TB therapies</a>. Host-directed therapies that are currently explored include <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Host-directed+therapies+for+infectious+diseases%3A+current+status%2C+recent+progress%2C+and+future+prospects">imatinib, verapamil, metformin and ibuprofen</a>. </p>
<p>These molecules work by modulating inflammation and activating anti-bacterial defences within immune cells. Those that work by limiting tissue damage include <a href="https://www.ncbi.nlm.nih.gov/pubmed/24990750">Zileuton</a>, which blocks leukotriene synthesis and reduce lung bacterial growth and damaging pathology. </p>
<p>In addition, other non-steroidal anti-inflammatory drugs such as <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Host-directed+therapies+for+infectious+diseases%3A+current+status%2C+recent+progress%2C+and+future+prospects">Aspirin</a> are been explored for their ability to reduce inflammation.</p>
<p>Success of these efforts will surely add huge value in addressing the clinical demands in the treatment of TB. Currently, the disease is treated with first-line drugs that target the bacteria, but are also marred by the problem of drug resistance. </p>
<p>A number of patients respond poorly to standard treatment protocols due to drug resistance. Host-directed therapies will provide much-needed treatment alternatives for such patients.</p><img src="https://counter.theconversation.com/content/58798/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mohlopheni Marakalala receives funding from the Medical Research Council of South Africa.</span></em></p><p class="fine-print"><em><span>Hlumani Ndlovu receives funding from University of Cape Town Research Council. </span></em></p>Scientists have found proteins in the body that promote lung inflammation which helps the bacteria that causes TB to spread throughout the lung.Mohlopheni Jackson Marakalala, Senior Lecturer and Group Leader in the Division of Immunology, University of Cape TownHlumani Ndlovu, Senior Postdoctoral Fellow in TB Immunopathogenesis, University of Cape TownLicensed 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.