{"id":1017,"date":"2016-04-12T15:22:26","date_gmt":"2016-04-12T15:22:26","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1017"},"modified":"2017-08-21T10:57:45","modified_gmt":"2017-08-21T10:57:45","slug":"primary-care-corner-with-geoffrey-modest-md-urine-based-rapid-tb-test","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/04\/12\/primary-care-corner-with-geoffrey-modest-md-urine-based-rapid-tb-test\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Urine-Based Rapid TB Test"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest <\/strong><\/p>\n<p>The lancet just reported a study looking at a rapid, low-cost urine test to guide TB treatment in HIV-positive individuals in areas with high TB prevalence\u00a0(see\u00a0Lancet 2016; 387: 1187).<\/p>\n<p>Background:<\/p>\n<ul>\n<li>TB is the leading cause of death in people\u00a0with\u00a0HIV, accounting for 360K deaths in 2013; post-mortem analysis in resource-limited countries find that TB is the cause of death in about 40% of HIV-infected people,\u00a0in 85% of cases it\u00a0is disseminated, and\u00a0half are\u00a0undiagnosed at the time of death<\/li>\n<li>Those with HIV have a higher case-fatality rate when co-infected with\u00a0TB: increased disseminated extra-pulmonary TB, more severe TB as immunocompromise increases.<\/li>\n<li>It is harder to diagnose TB in those with advanced immunosuppression, since they often have low bacillary loads in their bodily fluids, reducing the sensitivity of smears and cultures<\/li>\n<li>\u200bThere is a urine test\u00a0detecting\u00a0the lipoarabinomannan Ag (LAM), a glycolipid antigen\u00a0of the M tuberculosis cell wall, which reflects\u00a0hematogenously disseminated TB. It requires 60 ml of urine, takes 25 minutes to get a result, and costs $2.66\/test.\u00a0It has a specificity of approx 94% and a sensitivity of around 56% in a meta-analysis. but, compared to sputum-smear microscopy, it\u00a0does identify patients with the most severe illness<\/li>\n<\/ul>\n<p>Details of study:<\/p>\n<ul>\n<li>2659 patients (median age 37, 51% female, CD4\u00a0of 84, 48% on antiretroviral therapy (ART) at time of hospitalization, 73% on\u00a0ART by 8-week follow-up)\u00a0in 10 hospitals in Africa (South Africa, Tanzania, Zambia, Zimbabwe) were randomly assigned to urinary LAM testing, with 2528 ultimately in the modified intention-to-treat analysis<\/li>\n<li>8-week mortality was\u00a0578 (23%)\n<ul>\n<li>261 (21%) in the LAM group and\u00a0317 (25%) in the\u00a0no LAM group, an absolute reduction of 4% (1-7%) and relative risk reduction of 17% [RR\u00a00.83 (0.73-0.96, p=0.012]<\/li>\n<\/ul>\n<\/li>\n<li>Overall sensitivity\u00a0of LAM was 45.6%, specificity was 88.7%, positive likelihood ratio of\u00a04.03, negative likelihood ratio of 0.61<\/li>\n<li>But for those with CD4\u00a0\u226450,\u00a0sensitivity\u00a0of\u00a0LAM was 63.7%, specificity was 83.2%, positive likelihood ratio of 3.80, negative likelihood ratio of 0.44; and 46% of the deaths happened in those with CD4\u00a0\u226450<\/li>\n<li>The overall % of patients begun on antiTB therapy was much higher in the LAM group (55% on day 1 and up to 91% on day 8) vs those without LAM (40% on day 1 and up to 89% on day 8), p=0.024 for difference.<\/li>\n<li>In the subgroup of patients with CD4\u00a0\u2264\u200b50, LAM reduced mortality by 29%<\/li>\n<li>The\u00a0attending clinicians delayed TB therapy in the no LAM group because\u00a0they favored a different diagnosis (e.g. bacterial pneumonia), or they were waiting for the results of diagnostic investigations.<\/li>\n<\/ul>\n<p>Of note,\u00a0a recent concern\u00a0has developed with the spread of MDR-TB (multiply drug-resistant) in Daru Island in\u00a0New Guinea, with a commentary in Lancet Respiratory Medicine (see\u00a0<a href=\"http:\/\/www.thelancet.com\/pdfs\/journals\/lanres\/PIIS2213-2600(16)00101-6.pdf\">http:\/\/www.thelancet.com\/pdfs\/journals\/lanres\/PIIS2213-2600(16)00101-6.pdf<\/a>\u00a0). The spread of TB, especially resistant TB, is referred to as a &#8220;time bomb&#8221;. And, of rather concerning note, TB is not so common in Daru\u00a0and most patients with MDR have never taken TB meds (i.e., they did not develop resistance by taking meds, but were infected with a very difficult-to-treat TB infection), and lots of people there got infected (200 people in this 6 km<sup>2<\/sup>\u00a0island\u00a0with only 15,000 individuals,\u00a0i.e., about 1% of the population). This scary outbreak &#8220;will almost certainly eclipse those of both the Ebola and the recent Zika virus outbreaks, deemed a global public health emergency, combined&#8221;, per the Lancet commentary.<\/p>\n<p>So, I bring up this LAM\u00a0study for several reasons:<\/p>\n<ul>\n<li>It seems pretty likely to me that TB really is a ticking time-bomb, and reading this article on LAM is\u00a0a reality check on this<\/li>\n<li>TB tends to have the highest morbidity and mortality in resource-poor countries, which have to deal with an array of very expensive and urgent other issues (little things like famine, war, etc.). A\u00a0couple of days ago the NY Times ran a\u00a0very concerning article\u00a0on Vietnam\u00a0(see\u00a0<a href=\"http:\/\/www.nytimes.com\/2016\/03\/29\/health\/vietnam-tuberculosis.html\">http:\/\/www.nytimes.com\/2016\/03\/29\/health\/vietnam-tuberculosis.html<\/a>\u200b ),\u00a0a country with a remarkably effective TB program (90% cure rate for uncomplicated TB, 75% in drug-resistant cases &#8212; with a global average is 50%), where improving outcomes further is getting more expensive (needing to\u00a0do more outreach into rural areas, finding\/treating\u00a0those addicted to heroin&#8230;), but their hospital wards are packed (with more potential to lead to spread of MDR) and\u00a0their &#8220;money is close to running out&#8221;<\/li>\n<li>TB has the potential to develop highly virulent strains, and the above article on New Guinea is shocking at how virulent a multi-drug resistant TB can be (and MDR, of course, is associated with much more cost to control as well as an inherently higher mortality). And the risk of worldwide spread of a virulent and less-treatable\u00a0TB is much increased as travel becomes easier and more frequent<\/li>\n<li>We are continually dealing with outbreaks of\u00a0newer, potentially devastating diseases (e.g., Zika, Chikungunya, Ebola,&#8230;) which divert attention and resources from staid old TB<\/li>\n<li>And LAM\u00a0really may be a huge benefit in resource-limited\u00a0countries, where AIDS-related deaths are still very high (i.e., AIDS has not evolved into a chronic disease requiring taking one pill to control, as in the\u00a0US and many resource-rich countries), and LAM is a cheap and easy test to identify and treat\u00a0those with likely imminent death<\/li>\n<li>But even in the US, TB infection in HIV has been increasing, with increasing numbers of observed vs expected cases (see <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3122491\/\">http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3122491\/<\/a>\u200b ), noting that the increase in cases in US cities is both from reactivation of latent TB by HIV-related immunocompromise, but that 41% were due to recent transmission<\/li>\n<li>Now,\u00a0one might argue that there should just be empiric anti-TB therapy in all HIV-infected patients in TB-endemic areas, given the high prevalence and mortality of HIV-TB coinfection, at least in those with more severe immunocompromise. But,\u00a0empiric treatment is more complicated, more expensive, and\u00a0more toxic, especially\u00a0in areas of MDR, which reinforces the potential benefit of LAM as a test\u00a0in those co-infected with HIV and even only a remote possibility of hematogenous TB.\u00a0And, with the very real possibility of TB spreading outside of the currently endemic areas (as now shown in\u00a0New Guinea), and co-infecting those with HIV, LAM may become a reasonable test in more and more\u00a0countries around the world.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Urine-Based Rapid TB Test [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/04\/12\/primary-care-corner-with-geoffrey-modest-md-urine-based-rapid-tb-test\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1017","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1017","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1017"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1017\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1017"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1017"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1017"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}