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<meta name="description" content="Despite 90 years of vaccination and 60 years of chemotherapy, tuberculosis (TB) remains the world’s leading cause of death from an infectious agent, exceeding human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) for the first time (WHO 2015b, 2016a). The World Health Organizat …"><meta name="keywords" content="pmid:30212088, NBK525174, doi:10.1596/978-1-4648-0524-0_ch11, Review, Barry R Bloom, Rifat Atun, Prashant Yadav, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Tuberculosis - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/30212088/"><meta property="og:description" content="Despite 90 years of vaccination and 60 years of chemotherapy, tuberculosis (TB) remains the world’s leading cause of death from an infectious agent, exceeding human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) for the first time (WHO 2015b, 2016a). The World Health Organizat …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Tuberculosis - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/30212088/"><meta name="twitter:description" content="Despite 90 years of vaccination and 60 years of chemotherapy, tuberculosis (TB) remains the world’s leading cause of death from an infectious agent, exceeding human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) for the first time (WHO 2015b, 2016a). The World Health Organizat …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="GhL6qMFn2OviOFZCK95AHEMAbQfh81X0X4vb3C8JCpiMI65snsICbMieJUXt1Cvk">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="GhL6qMFn2OviOFZCK95AHEMAbQfh81X0X4vb3C8JCpiMI65snsICbMieJUXt1Cvk">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="GhL6qMFn2OviOFZCK95AHEMAbQfh81X0X4vb3C8JCpiMI65snsICbMieJUXt1Cvk">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="GhL6qMFn2OviOFZCK95AHEMAbQfh81X0X4vb3C8JCpiMI65snsICbMieJUXt1Cvk">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="GhL6qMFn2OviOFZCK95AHEMAbQfh81X0X4vb3C8JCpiMI65snsICbMieJUXt1Cvk">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="30212088">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
book
dialog-focus"
href="https://www.ncbi.nlm.nih.gov/books/NBK525174"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3057&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=30212088&amp;db=pubmed"
title="See full text options at NCBI Bookshelf"
data-ga-category="full_text"
data-ga-action="NCBI Bookshelf"
data-ga-label="30212088"
><img class="book-icon" src="https://cdn.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-dcp3v6.png" alt="book cover photo"><div class="book-icon-label"><div class="book-icon-label-subtitle">Chapter 11</div><div class="book-icon-label-title">Major Infectious Diseases</div></div><span class="text">
NCBI Bookshelf
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/30212088/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/30212088/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="30212088" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F30212088%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="GhL6qMFn2OviOFZCK95AHEMAbQfh81X0X4vb3C8JCpiMI65snsICbMieJUXt1Cvk"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="collections_button"
data-ga-action="select_collection"
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="add">
Add
</button><button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="cancel">
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<p>
Despite 90 years of vaccination and 60 years of chemotherapy, tuberculosis (TB) remains the world’s leading cause of death from an infectious agent, exceeding human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) for the first time (WHO 2015b, 2016a). The World Health Organization (WHO) estimates that there are about 10.4 million new cases and 1.8 million deaths from TB each year. One-third of these new cases (about 3 million) remain unknown to the health system, and many are not receiving proper treatment.
</p>
<p>
Tuberculosis is an infectious bacterial disease caused by <i>Mycobacterium tuberculosis</i> (Mtb), which is transmitted between humans through the respiratory route and most commonly affects the lungs, but can damage any tissue. Only about 10 percent of individuals infected with Mtb progress to active TB disease within their lifetime; the remainder of persons infected successfully contain their infection. One of the challenges of TB is that the pathogen persists in many infected individuals in a latent state for many years and can be reactivated to cause disease. The risk of progression to TB disease after infection is highest soon after the initial infection and increases dramatically for persons co-infected with HIV/AIDS or other immune-compromising conditions.
</p>
<p>
Treatment of TB disease requires multiple drugs for many months. These long drug regimens are challenging for both patients and health care systems, especially in low- and middle-income countries (LMICs), where the disease burden often far outstrips local resources. In some areas, the incidence of drug-resistant TB, requiring even longer treatment regimens with drugs that are more expensive and difficult to tolerate, is increasing.
</p>
<p>
Diagnosis in LMICs is made primarily by microscopic examination of stained smears of sputum of suspected patients; however, smear microscopy is capable of detecting only 50–60 percent of all cases (smear-positive). More sensitive methods of diagnosing TB and detecting resistance to drugs have recently become available, although they are more expensive. The time between the onset of disease and when diagnosis is made and treatment is initiated is often protracted, and such delays allow the transmission of disease. Although bacille Calmette–Guérin (BCG) remains the world’s most widely used vaccine, its effectiveness is geographically highly variable and incomplete. Modeling suggests that more effective vaccines will likely be needed to drive tuberculosis toward elimination in high-incidence settings.
</p>
<p>
The basic strategy to combat TB has been, for 40 years, to provide diagnosis and treatment to individuals who are ill and who seek care at a health facility. The premise is that, if patients with active disease are cured, mortality will disappear, prevalence of disease will decline, transmission will decline, and therefore incidence should decline. The reality in many countries is more complex, and overall the decline in incidence (only about 1.5 percent per year) has been unacceptably slow.
</p>
<p>
Chemotherapy for TB is one of the most cost-effective of all health interventions (McKee and Atun 2006). This evidence has been central to the global promotion of the WHO and Stop TB Partnership policy of directly observed therapy, short course (DOTS) strategy, the package of measures combining best practices in the diagnosis and care of patients with TB (UN General Assembly 2000). The DOTS strategy to control tuberculosis promotes standardized treatment, with supervision and patient support that may include, but is far broader than, direct observation of therapy (DOT), where a health care worker personally observes the patient taking the medication (WHO 2013a).
</p>
<p>
Thanks in part to these efforts and national and international investments, much progress has been made in TB control over the past several decades. Between 1990 and 2010, absolute global mortality from TB declined 18.7 percent, from 1.47 million to 1.20 million (Lozano and others 2012) and by 22 percent between 2000 and 2015 (WHO 2016a). By 2015, an estimated 49 million lives had been saved (WHO 2016a). The internationally agreed targets for TB, embraced in the United Nations (UN) Millennium Development Goals (MDGs), sought “to halt and reverse the expanding incidence of tuberculosis by 2015,” and this target has been met to some extent in all six WHO regions and in most, but not all, of the world’s 22 high-burden countries (WHO 2014c).
</p>
<p>
Despite progress, major gaps persist. Although the Sustainable Development Goals (SDGs) seek to end the tuberculosis epidemic altogether (WHO 2015a, 2015c), the decline in incidence has been disappointing. One of every three TB patients remains “unknown to the health system,” many are undiagnosed and untreated, and case detection and treatment success rates remain too low in the high-burden countries. Ominously, rates of multidrug-resistant (MDR) TB—defined as resistance to the two major TB drugs, isoniazid and rifampicin—are rising globally (WHO 2011a) with the emergence of extensively drug-resistant (XDR) TB, resistant to many second-line drugs, as well as strains resistant to all current drugs (Dheda and others 2014; Udwadia and others 2012; Uplekar and others 2015). These are now primarily the result of transmission rather than inadequate treatment (Shah and others 2017).
</p>
<p>
Moreover, the TB problem has become more pressing because of co-infection with HIV/AIDS. While globally HIV/AIDS and TB co-infection represents only 11 percent of the total TB burden, in some areas of Sub-Saharan Africa with a high burden of TB, as many as three-quarters of TB patients are co-infected with HIV/AIDS. In those countries, efforts to control TB are overwhelmed by the rising number of TB cases occurring in parallel with the HIV/AIDS epidemic. And after decades of steady decline, the incidence of TB is also increasing in some high-income countries (HICs), mainly as the result of outbreaks in vulnerable groups (WHO 2015b).
</p>
<p>
If the ultimate goal of controlling an infectious disease is to interrupt transmission, turning the tide on TB will require early and accurate case detection, rapid commencement of and adherence to effective treatment that prevents transmission, and, where possible, preventive treatment of latent TB. It is universally understood that new strategies and more effective tools and interventions will be required to reach post-2015 targets (Bloom and Atun 2016; WHO 2015a). These interventions must be not only cost-effective, but also affordable and capable of having an impact on a very large scale.
</p>
<p>
TB control will need three new advances—development of new point-of-care diagnostics, more effective drug regimens to combat drug-susceptible and drug-resistant TB, and more effective vaccines. As argued in this chapter, these require new strategies and tools that include moving away from the traditional DOTS passive case finding and toward more active case finding in high-burden regions; service delivery that is targeted to the most vulnerable populations and integrated with other services, especially HIV/AIDS services; and care that is based at the primary health care and community levels. Specifically, in high-burden countries, many individuals with TB are asymptomatic, such that waiting for patients to become sick enough to seek care has not been sufficient to reduce transmission and incidence markedly (Bates and others 2012; Mao and others 2014; Willingham and others 2001; Wood and others 2007). A more active and aggressive approach is needed that tackles health system barriers to effective TB control.
</p>
<p>
The strategies for controlling TB recommended by the WHO have evolved significantly over time. In the early formulations, the central tenets of the global TB control strategy were clinical and programmatic in nature, focusing principally on the delivery of standardized drug regimens; the underlying assumption was that the problem could be solved largely by existing biomedical tools (Atun, McKee, and others 2005; Schouten and others 2011). Yet, in many LMICs, health system weaknesses in governance, financing, health workforce, procurement and supply chain management, and information systems have impeded TB control (Elzinga, Raviglione, and Maher 2004; Marais and others 2010; Travis and others 2004) and not been adequately addressed by TB control efforts. The current global TB strategy, formulated as the End TB Strategy, is the most comprehensive ever, with three major pillars:
</p>
<p>
<ol xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one" style="list-style-type:disc"><li><p>Integrated, patient-centered care and prevention</p></li><li><p>Social and political action to address determinants of disease</p></li><li><p>Recognition of the urgent need for research to provide new tools (WHO 2015a).</p></li></ol>
</p>
<p>
Health systems are important and need to be strengthened. As with other health interventions, the success of tuberculosis treatment and control in a country is often determined by the strength of its health system (McKee and Atun 2006; WHO 2003). A health system can be defined in many ways, perhaps best as “all the activities whose primary purpose is to promote, restore, or maintain health” (WHO 2000, 5).
</p>
<p>
In a sense, the major risk factor for acquiring TB is breathing. Thus, people of all social and economic statuses are at risk. While TB disproportionately affects the poor, the narrative that TB is a disease only of the poor is misleading and counterproductive, if it leads either to further stigmatization of the disease or to the view that middle- and high-income countries need not worry about the disease. In the case of co-infection with HIV/AIDS, evidence suggests that HIV/AIDS is often more prevalent in better-off populations in Africa that suffer high rates of TB.
</p>
<p>
The analytical framework underlying this chapter defines key functions of the health system, ultimate goals, and contextual factors that affect the health system (figure 11.1). It builds on the WHO framework (WHO 2000) as well as health system frameworks developed by Frenk (1994), Hsiao and Heller (2007), and Roberts and others (2004), and national accounts (OECD, Eurostat, and WHO 2011). It also draws on earlier studies by Atun (2012); Atun and Coker (2008); Atun, Samyshkin, and others (2006); Samb and others (2009); and Swanson and others (2012).
</p>
<p>
The four key health system functions represented in the framework are as follows:
</p>
<p>
<ol xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one" style="list-style-type:disc"><li><p><i>Governance and organization.</i> The policy and regulatory environment; stewardship and regulatory functions of the ministry of health and its relation to other levels of the health system; and structural arrangements for insurers and purchasers, health care providers, and market regulators</p></li><li><p><i>Financing.</i> The way funds are collected, funds and risks are pooled, finances are allocated, and health care providers are remunerated</p></li><li><p><i>Resource management.</i> The way resources—physical, human, and intellectual—are generated and allocated, including their geographic and needs-based allocation</p></li><li><p><i>Service delivery.</i> Both population- and individual-level public health interventions and health care services provided in community, primary health care, hospitals, and other health institutions.</p></li></ol>
</p>
<p>
Each of these functions is influenced by the economic, demographic, legal, cultural, and political context.
</p>
<p>
As the framework suggests, health system goals include better health, financial protection, and user satisfaction. Personal health services and public health interventions should be organized to achieve an appropriate balance of equity (including reducing out-of-pocket [OOP] expenditures and impoverishment of individuals and families), efficiency, effectiveness (that is, the extent to which interventions are evidence based and safe), responsiveness, equity, and client satisfaction (as perceived by the users of services).
</p>
<p>
This chapter is organized as follows. First, we provide a detailed discussion of the global burden of disease and clinical context, followed by a review of approaches to diagnosis, treatment, and prevention. The aim throughout is to approach TB through a health system lens and, in the latter part of the chapter, to provide recommendations for improving delivery strategies and strengthening health systems, including care, supply chain, and information systems. Because the current tools for combating TB are seriously inadequate, we conclude with sections on critical research and development and economic analyses of new interventions for diagnosis, treatment, and vaccines. Throughout, emphasis is placed on data or modeling of the economic costs and benefits, where available, of current or possible future interventions to combat this disease.
</p>
<p>
The chapter recommends moving toward active case finding in high-burden countries; greater investments in health systems; community-based rather than hospital-based service delivery; and greater support for research on new tools—that is, developing better diagnostics, treatment regimens, and vaccines. Most of these approaches were included in earlier WHO policies, but were not emphasized. They are now part of the WHO’s End TB Strategy, with which this report is fully consistent (WHO 2015a, 2015c).
</p>
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© 2017 International Bank for Reconstruction and Development / The World Bank.
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<div class="book-sections" id="book-sections">
<h2 class="title">
Sections
</h2>
<ul>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec1" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Overview
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec2" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Historical Trends, Current Burden, and Global Response
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec3" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Infection and Disease in Individuals and Populations
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec4" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
TB Diagnosis and Screening
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec5" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
TB Treatment
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec6" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
TB Prevention
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec7" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Turning the Tide Against TB
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec8" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Research and Development
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec9" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Financing for TB Programs
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec10" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Economic Analyses and Cost-Effectiveness
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec11" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Extended Cost-Effectiveness Analysis of Universal Public Financing of TB Treatment
</a>
</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.sec12" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Summary and Recommendations
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<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.fn-group1" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Notes
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</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK525174/#ch11.ref-list1" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
References
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