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<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<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="rSIy5GWpqcQmeBznsyOLk7gD8Qkqw5F0IFsDIwpL0NDQ82Fd5RrNOfMhGU2CpGdk">
<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="rSIy5GWpqcQmeBznsyOLk7gD8Qkqw5F0IFsDIwpL0NDQ82Fd5RrNOfMhGU2CpGdk">
<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="rSIy5GWpqcQmeBznsyOLk7gD8Qkqw5F0IFsDIwpL0NDQ82Fd5RrNOfMhGU2CpGdk">
<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="rSIy5GWpqcQmeBznsyOLk7gD8Qkqw5F0IFsDIwpL0NDQ82Fd5RrNOfMhGU2CpGdk">
<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="rSIy5GWpqcQmeBznsyOLk7gD8Qkqw5F0IFsDIwpL0NDQ82Fd5RrNOfMhGU2CpGdk">
<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="29281988">
<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
dialog-focus"
href="https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-017-2924-5"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3196&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=29281988&amp;db=pubmed&amp;nlmid=100968551"
title="See full text options at BioMed Central"
data-ga-category="full_text"
data-ga-action="BioMed Central"
data-ga-label="29281988"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--s3-service-broker-live-ddda94b7-dbb0-4917-917d-776dae91ebba.s3.amazonaws.com-bmc-linkout-fulltext.png" alt="BioMed Central full text link"><span class="text">
BioMed Central
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/29281988/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=29281988&amp;db=pubmed&amp;nlmid=100968551"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="29281988"
><span class="text">
Free PMC article
</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="/29281988/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/29281988/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="29281988" 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%2F29281988%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="rSIy5GWpqcQmeBznsyOLk7gD8Qkqw5F0IFsDIwpL0NDQ82Fd5RrNOfMhGU2CpGdk"><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"
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<h1 class="heading-title">
Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial
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1
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Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial
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Authors
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<span class="authors-list-item "><a class="full-name"
href="/?term=Byakika-Kibwika+P&amp;cauthor_id=29281988"
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data-ga-label="Pauline Byakika-Kibwika">Pauline Byakika-Kibwika</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medicine, College of Health Sciences, Makerere University, P. O. Box, 7072, Kampala, Uganda. pbyakika@gmail.com." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Infectious Diseases Institute, Kampala, Uganda. pbyakika@gmail.com." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Achan+J&amp;cauthor_id=29281988"
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data-ga-label="Jane Achan">Jane Achan</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Medical Research Council Unit, Serekunda, The Gambia." href="#short-view-affiliation-3" ref="linksrc=author_aff">
3
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Lamorde+M&amp;cauthor_id=29281988"
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data-ga-label="Mohammed Lamorde">Mohammed Lamorde</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Infectious Diseases Institute, Kampala, Uganda." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Karera-Gonahasa+C&amp;cauthor_id=29281988"
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data-ga-label="Carine Karera-Gonahasa">Carine Karera-Gonahasa</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Infectious Diseases Institute, Kampala, Uganda." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Kiragga+AN&amp;cauthor_id=29281988"
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data-ga-label="Agnes N Kiragga">Agnes N Kiragga</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Infectious Diseases Institute, Kampala, Uganda." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Harriet Mayanja-Kizza">Harriet Mayanja-Kizza</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medicine, College of Health Sciences, Makerere University, P. O. Box, 7072, Kampala, Uganda." href="#short-view-affiliation-5" ref="linksrc=author_aff">
5
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Noah Kiwanuka">Noah Kiwanuka</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="School of Public Health, Makerere University, Kampala, Uganda." href="#short-view-affiliation-6" ref="linksrc=author_aff">
6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Sam Nsobya">Sam Nsobya</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Makerere University, Kampala, Uganda." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Ambrose O Talisuna">Ambrose O Talisuna</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="University of Oxford-KEMRI-Wellcome Trust Programme, Nairobi, Kenya." href="#short-view-affiliation-8" ref="linksrc=author_aff">
8
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Concepta Merry">Concepta Merry</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Infectious Diseases Institute, Kampala, Uganda." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Trinity College Dublin, Dublin, Ireland." href="#short-view-affiliation-9" ref="linksrc=author_aff">
9
</a></sup></span>
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Affiliations
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<li data-affiliation-id="short-view-affiliation-1"
id="short-view-affiliation-1"
><sup class="key">1</sup> Department of Medicine, College of Health Sciences, Makerere University, P. O. Box, 7072, Kampala, Uganda. pbyakika@gmail.com.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> Infectious Diseases Institute, Kampala, Uganda. pbyakika@gmail.com.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> Medical Research Council Unit, Serekunda, The Gambia.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Infectious Diseases Institute, Kampala, Uganda.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> Department of Medicine, College of Health Sciences, Makerere University, P. O. Box, 7072, Kampala, Uganda.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> School of Public Health, Makerere University, Kampala, Uganda.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> Department of Pathology, Makerere University, Kampala, Uganda.</li>
<li data-affiliation-id="short-view-affiliation-8"
id="short-view-affiliation-8"
><sup class="key">8</sup> University of Oxford-KEMRI-Wellcome Trust Programme, Nairobi, Kenya.</li>
<li data-affiliation-id="short-view-affiliation-9"
id="short-view-affiliation-9"
><sup class="key">9</sup> Trinity College Dublin, Dublin, Ireland.</li>
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<strong class="current-id" title="PubMed ID">29281988</strong>
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Abstract
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<p>
<strong class="sub-title">
Background:
</strong>
Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence.
</p>
<p>
<strong class="sub-title">
Methods:
</strong>
In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda.
</p>
<p>
<strong class="sub-title">
Results:
</strong>
We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1-2) vs 3 (2-3), P &lt; 0.001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms.
</p>
<p>
<strong class="sub-title">
Conclusion:
</strong>
In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed.
</p>
<p>
<strong class="sub-title">
Trial registration:
</strong>
The study was registered with the Pan African Clinical Trial Registry ( PACTR201110000321348 ).
</p>
</div>
<p>
<strong class="sub-title">
Keywords:
</strong>
Artemisinin combination therapy; Artesunate; Quinine; Re-infection; Severe malaria.
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Conflict of interest statement
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<h5 class="coi-sec-title">Ethics approval and consent to participate</h5>
<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The study was approved by Makerere University School of Medicine Research and Ethics Committee (REC REF 2011175), Uganda National Drug Authority (369/ESR/NDA/DID-12/2011), Uganda National Council for Science and Technology (HS 1031) and registered with the Pan African Clinical Trial Registry (PACTR201110000321348). All study procedures were conducted according to Good Clinical Practice standards. Patients and parents or guardians of participants provided written informed consent prior to enrollment. Study related information was provided in the participants local languages. The dataset supporting the conclusions of this article is included in the submission as an additional file.</p>
<h5 class="coi-sec-title">Consent for publication</h5>
<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">“Not applicable” in this section.</p>
<h5 class="coi-sec-title">Competing interests</h5>
<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors declare that they have no competing interests.</p>
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p>
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<p> Fig. 1 </p>
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<div class="figure-caption-contents"><p> Schematic Diagram of the Trial… </p></div>
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<div class="figure-caption-contents"><p> Schematic Diagram of the Trial Profile </p></div>
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<div class="figure-caption-contents"><p> Kaplan-Meier survival curves of the… </p></div>
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<div class="figure-caption-contents"><p> Kaplan-Meier survival curves of the risk of unadjusted treatment failure categorized by ACT… </p></div>
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Fig. 2
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<div class="figure-caption-contents">Kaplan-Meier survival curves of the risk of unadjusted treatment failure categorized by ACT arm over 42 days of follow-up compared using the Log Rank test</div>
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<div class="figure-caption-contents"><p> Kaplan-Meier survival curves of the… </p></div>
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<p> Fig. 3 </p>
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<div class="figure-caption-contents"><p> Kaplan-Meier survival curves of the risk of adjusted treatment failure categorized by ACT… </p></div>
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Fig. 3
</strong>
<div class="figure-caption-contents">Kaplan-Meier survival curves of the risk of adjusted treatment failure categorized by ACT arm over 42 days of follow-up compared using the Log Rank test</div>
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