tag:theconversation.com,2011:/institutions/aurum-institute-2420/articlesAurum Institute2021-03-22T15:06:20Ztag: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/1283272020-01-13T14:40:03Z2020-01-13T14:40:03ZPreventing TB: a big drug price cut paves the way for global scale-up<figure><img src="https://images.theconversation.com/files/305249/original/file-20191204-70105-5do0uo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Nic Bothma/EPA</span></span></figcaption></figure><p>Lengthy negotiations ended in good news recently when the price of rifapentine, a lifesaving antibiotic, was <a href="https://www.theguardian.com/global-development/2019/oct/31/antibiotic-price-drop-could-stop-millions-from-developing-tuberculosis">marked down by 66%</a> by its manufacturer Sanofi. When combined with another antibiotic (isoniazid), rifapentine can prevent tuberculosis (TB) disease. The move was announced at the <a href="https://hyderabad.worldlunghealth.org/">Union World Conference on Lung Health</a> in October 2019. </p>
<p>Talks to lower the price from US$45 to US$15 for a three-month course took more than a year to complete and involved Sanofi, Unitaid and the Global Fund to Fight Aids, Tuberculosis and Malaria, in collaboration with the Stop TB Partnership’s Global Drug Facility and the United States PEPFAR initiative. </p>
<p>Now we – those of us who have been working to bring preventive therapy to the people whose lives depend on it – must roll up our sleeves and make it happen.</p>
<p>Advocates have been pressing for the price of rifapentine to be lowered ever since scientific proof of its effectiveness was <a href="https://www.researchgate.net/publication/275300925_Rifapentine_Pharmacokinetics_and_Tolerability_in_Children_and_Adults_Treated_Once_Weekly_With_Rifapentine_and_Isoniazid_for_Latent_Tuberculosis_Infection">published </a>in <a href="https://www.researchgate.net/publication/306024372_Rifapentine_for_the_Treatment_of_Latent_Tuberculosis">peer-reviewed</a> journals. Three months of treatment with rifapentine plus isoniazid was shown to be just as effective and less toxic than one year of therapy with isoniazid alone (the previous standard). The reduction in treatment time alone provides an obvious improvement. </p>
<p>The obstacles to getting more people treated begin with locating those at greatest risk and then expanding capacity in preventive treatment programmes to serve them.</p>
<h2>Who needs the drug?</h2>
<p>TB is one of the top ten causes of death from an infectious agent worldwide, killing approximately <a href="https://www.who.int/tb/publications/factsheet_global.pdf?ua=1">1.5 million people</a> in 2018. The disease hits especially hard in impoverished regions, where poorly ventilated and overcrowded living and working conditions, inadequate nutrition, the prevalence of other diseases like HIV, and insufficient or non-existent health care all make it far worse than it could be. </p>
<p>Most TB cases in 2018 were in <a href="https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1#page=15">South-East Asia (44%) and Africa (24%)</a>. Combined, the two regions accounted for nearly two thirds of all the world’s TB cases. </p>
<p>TB is highly contagious and spread by a cough or sneeze. Family members and other close contacts of people with the disease are at the highest risk of infection. People who contract TB don’t always get sick immediately. Instead, a TB infection can lie dormant for years until other stresses activate it. People living with HIV are at greater risk of developing TB and are 20 to 37 times more likely to move from the TB infection stage to active TB disease. New HIV infections have been <a href="https://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf">decreasing globally</a> but sub-Saharan Africa still saw more than <a href="http://apps.who.int/gho/data/view.main.HIVINCIDENCEREGIONv?lang=en">one million new HIV infections</a> in 2018. </p>
<p>In February 2018, the World Health Organisation (WHO) reviewed its <a href="https://apps.who.int/iris/bitstream/handle/10665/260233/9789241550239-eng.pdf;jsessionid=B5140E3D51E6DB954062BC3A6F75F7E1?sequence=1">guidelines for preventing TB disease</a>. The guidelines now include <a href="https://www.impaact4tb.org/https-www-impaact4tb-org-wp-content-uploads-2018-08-njie-2018_amjprevmed_3hp-srma_-pdf/">three months of rifapentine and isoniazid</a> taken weekly for people living in countries with a high TB burden. This regimen is known as 3HP. </p>
<p>The WHO recommends that anyone living with HIV and those living in the same household as a person with TB disease should receive TB preventive therapy. The theme of 2019’s <a href="https://www.who.int/westernpacific/news/events/detail/2019/12/01/western-pacific-events/world-aids-day-2019">World AIDS Day</a> was “Ending the HIV/AIDS epidemic: Communities make the difference”. Reaching this goal requires that preventive treatment programmes engage with communities to develop, refine and bring to scale interventions designed to meet the needs of people with and vulnerable to HIV and TB. These interventions should ensure that people living with HIV do not die of TB.</p>
<p>Importantly, the 3HP regimen can be administered along with dolutegravir, a better antiretroviral drug which is <a href="https://www.timeslive.co.za/sunday-times/lifestyle/health-and-sex/2019-11-28-its-highly-effective-cheaper-sa-to-launch-advanced-new-hiv-drug/">now being provided in South Africa</a> and globally. The combination is an effective tool for keeping vulnerable people as healthy as possible. The reduced amount of time needed for treatment – three months as opposed to six months of isoniazid only, the current standard of care – increases the likelihood that patients will complete treatment.</p>
<h2>Treating more people</h2>
<p>All prevention programmes must begin with finding the people who need TB preventive therapy. People living with HIV can be identified through HIV clinics. Contacts of people with TB disease can be identified by investigating affected households. People must always be screened for TB before starting TB preventive therapy.</p>
<p>In 2018, the member states of the United Nations committed to expanding the number of people receiving preventive treatment to <a href="http://www.stoptb.org/global/advocacy/unhlm_targets.asp">at least 30 million by 2022</a>. But the world is nowhere close to meeting that goal. It will take a lot of work to achieve these targets, and until then millions of people will remain at risk of TB disease.</p>
<p>With the price break on Sanofi’s rifapentine product Priftin, TB preventive treatment can now be made available in many more places. If Priftin has not been approved for use in a country that needs this treatment, national TB programmes can work with the WHO and local regulatory authorities to process waivers – as <a href="https://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/regulator-waives-off-clinical-trials-clears-sanofi-tb-drug/articleshow/71931597.cms">India</a> did.</p>
<p>Treatment for latent TB infection has been available since the 1950s, yet very few people who could benefit from TB preventive therapy are taking it. Hundreds of thousands of lives are unnecessarily at risk. This price break – making a shorter and equally effective treatment more affordable – is a perfect opportunity to make a dent in these numbers.</p><img src="https://counter.theconversation.com/content/128327/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gavin Churchyard does not work for, or own shares in any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment. Sanofi donated isoniazid and rifapentine for various studies. Gavin Churchyard consulted without payment for Sanofi.</span></em></p>Obstacles to getting more people with TB treated extend beyond cost. It starts with locating people at greatest risk and expanding preventive treatment programmes.Gavin Churchyard, Honorary Professor, School of Public Health, University of the Witwatersrand and CEO, Aurum InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/523842016-02-08T04:30:16Z2016-02-08T04:30:16ZSouthern Africa’s retrenched miners face a future without health care<figure><img src="https://images.theconversation.com/files/106066/original/image-20151215-23182-1n3ugll.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Anglo American's plans to reduce its operations will have an impact on the provision of health services to miners. </span> <span class="attribution"><span class="source">Reuters/Siphiwe Sibeko </span></span></figcaption></figure><p><em>Two of the world’s mining heavyweights have announced production cuts and staff cutbacks. These moves by <a href="https://www.jacarandafm.com/news-sport/news/bhp-billiton-cut-hundreds-jobs/">BHP Billiton</a> and <a href="http://www.fin24.com/Companies/Mining/why-anglo-is-forced-to-cut-85-000-jobs-20151209">Anglo American</a> will have a major impact on efforts to contain TB and HIV as mining houses have become integral to the provision of health care in southern Africa. The disease burden is high among the <a href="http://www.southernafricatrust.org/wp-content/uploads/2015/04/world-bank-tb-in-the-mining-sector.pdf">region’s</a> 490 000 miners in the gold, platinum and coal industries. They carry one of the highest TB/HIV <a href="http://www.health-e.org.za/wp-content/uploads/2014/04/Hamonization-report.pdf">co-infection rates</a> globally, ranging from 50% to 77%. The Conversation Africa health and medicine editor Candice Bailey asked Dr Liesl Page-Shipp to unpack the problem.</em></p>
<p><strong>How big is the burden of HIV/TB in the mining sector?</strong></p>
<p>Mine workers have different health risks, depending on whether they work in gold, platinum, coal or other commodities. Their living conditions may also be a risk factor. Gold mining poses the highest risk for <a href="http://oem.bmj.com/content/48/1/53.short">silicosis</a>. This in turn gives them a higher chance of being infected with TB. </p>
<p>Globally TB affects <a href="http://www.southernafricatrust.org/wp-content/uploads/2015/04/world-bank-tb-in-the-mining-sector.pdf">128</a> in every 100 000 people. In sub-Saharan Africa this figure is more than double at <a href="http://www-wds.worldbank.org/external/default/WDSContentServer/WDSP/IB/2014/03/24/000456286_20140324170149/Rendered/PDF/862020BRI0WB0R00Box382165B00PUBLIC0.pdf">350</a> people for every 100 000. In South Africa, the prevalence is <a href="http://www-wds.worldbank.org/external/default/WDSContentServer/WDSP/IB/2014/03/24/000456286_20140324170149/Rendered/PDF/862020BRI0WB0R00Box382165B00PUBLIC0.pdf">948</a> cases for every 100 000 people. </p>
<p>In some mines this rate is reported to be up to between <a href="http://www-wds.worldbank.org/external/default/WDSContentServer/WDSP/IB/2014/03/24/000456286_20140324170149/Rendered/PDF/862020BRI0WB0R00Box382165B00PUBLIC0.pdf">2500 and 3000</a> cases for every 100 000 people. This is 10 times the emergency <a href="http://www.who.int/tb/features_archive/tb_emergency_declaration/en/">threshold</a> set by the World Health Organisation.</p>
<p><strong>How important are mining houses in providing health care?</strong></p>
<p>Some mining houses provide a high standard of health care for their employees through on-site 24-hour primary health clinics, which are linked to secondary or tertiary hospitals. </p>
<p>These clinics provide a full package of health care services including anti-retroviral treatment, TB treatment and monitoring and treatment for chronic diseases like hypertension and high blood pressure. The service is available to all employees including migrant labourers from <a href="http://www.health-e.org.za/2014/03/26/sadc-harmonise-tb-treatment-cross-border-referrals/">neighbouring countries</a> such as Lesotho, Swaziland and Mozambique. About <a href="http://mg.co.za/article/2013-09-13-00-marikana-was-not-just-about-migrant-labour">30%</a> of mine workers in South Africa are migrant labourers.</p>
<p>But in some instances mine workers are totally dependent on local Department of Health facilities. Mine workers who require services access these facilities in their own time using often limited resources. </p>
<p><strong>How vulnerable are people to mine closures? Will they lose treatment?</strong> </p>
<p>Many will be vulnerable to treatment being interrupted or discontinued. Robust referral systems within South Africa and across borders are missing. Issues of stigma and disclosure to families may pose additional barriers to continued treatment for TB and HIV once miners return home. In addition, mine workers may come from areas with poor access to comprehensive medical care. This would restrict their options for HIV and TB screening, diagnosis and treatment.</p>
<p>Governments and mining houses in the region have recognised some of the challenges around poor access to care. There has been a commitment from governments to adopt a coordinated response to managing TB in the mining sector. In 2012, heads of state signed the SADC Declaration on TB in the Mining <a href="http://www.stoptb.org/assets/documents/news/Declaration%20on%20Tuberculosis%20in%20the%20Mining%20Sector2012English.pdf">Sector</a>. This was followed by a <a href="http://www.health-e.org.za/wp-content/uploads/2014/04/Hamonization-report.pdf">framework</a> to manage TB and a Code of <a href="http://www.hivsharespace.net/system/files/MSH%20Fact%20Sheet%20TB%20in%20Mining%20Sector%20March%202015%20web.pdf">Conduct</a> on TB in the mining sector. More recently the Global Fund against TB and malaria has awarded a grant for TB in the mining sector in Southern Africa <a href="https://TIMSSA.co.za">Programme</a>. </p>
<p>A multi-sectoral response is required to adequately respond to the challenges. This will need to include mining companies, health departments, labour departments and civil society.</p><img src="https://counter.theconversation.com/content/52384/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Liesl Page-Shipp does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The closure of several mines in South Africa and production cuts could have a detrimental impact on the health of miners who rely on in-house HIV and TB treatment programmes.Liesl Page-Shipp, Director: Health Programmes in Special Populations, Aurum InstituteLicensed as Creative Commons – attribution, no derivatives.