ChloroquineV1, Istex, Corpus, bibRecord, 000A58

Misattribution of Central Nervous System Dysfunction to Artesunate

Identifieur interne : 000A58 ( Istex/Corpus ); précédent : 000A57; suivant : 000A59

Misattribution of Central Nervous System Dysfunction to Artesunate

Auteurs : Paul N. Newton ; Nicholas P. J. Day ; Nicholas J. White

Source :

Clinical Infectious Diseases [ 1058-4838 ] ; 2005.

RBID : ISTEX:C3833A2D3B299072BCBA8FE2180230A7D419D128
Url:

https://api.istex.fr/ark:/67375/HXZ-SM4WX53G-7/fulltext.pdf

DOI: 10.1086/498033

Links to Exploration step

ISTEX:C3833A2D3B299072BCBA8FE2180230A7D419D128

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<p>S<sc>IR</sc>
—Franco-Paredes et al. [<xref rid="ref1" ref-type="bibr">1</xref>
] describe a 39-year-old man who returned from Sierra Leone with probable extrapyramidal syndrome that was self-limiting. He had had an undetermined febrile illness for which he had received inappropriately long and repeated courses of both artesunate and chloroquine. Franco-Paredes et al. concluded that the patient's condition “suggests neurotoxicity due to multiple courses of artesunate therapy, perhaps compounded by chloroquine therapy” [<xref rid="ref1" ref-type="bibr">1</xref>
, p. 1710]. However, there is no previous evidence, despite extensive investigation, that artesunate causes neurotoxicity in humans—although this is a well-recognized effect of chloroquine therapy—and, indeed, the presentation described is consistent with previous descriptions of reversible chloroquine-induced CNS dysfunction.</p>

<p>Pathological changes in the brain stem have been documented in mammals that have been given large doses of artemisinin derivatives [<xref rid="ref2" ref-type="bibr">2</xref>
, <xref rid="ref3" ref-type="bibr">3</xref>
]. Neurotoxicity in mammals has been associated particularly with the use of intramuscular artemether or artemotil, which results in sustained blood concentrations, rather than oral administration of the same drugs, which are absorbed and eliminated rapidly by this route. The pattern of irreversible neuropathological damage in mammals is unusual; selective damage is done to certain brain stem nuclei, particularly to those associated with hearing and balance. In experimental mammal models, water-soluble artesunate given orally or parenterally is considerably less neurotoxic than is oil-soluble artemether. These findings stimulated detailed prospective studies in humans—none of which have led to findings of neurotoxicity. These include case-control neurophysiological studies [<xref rid="ref4" ref-type="bibr">4</xref>
, <xref rid="ref5" ref-type="bibr">5</xref>
], human brain pathology studies [<xref rid="ref6" ref-type="bibr">6</xref>
], and a prospective clinical examination of a large series of patients with malaria who were treated with artemisinin derivatives [<xref rid="ref7" ref-type="bibr">7</xref>
]. Indeed, there have now been more trials reported with these drugs than with any other antimalarial therapy. In contrast, reversible neurological side effects, including extrapyramidal and psychiatric syndromes and tremor, have been very well documented after treatment with chloroquine [<xref rid="ref3" ref-type="bibr">3</xref>
, <xref rid="ref8" ref-type="bibr">8</xref>
-<xref rid="ref14" ref-type="bibr">14</xref>
].</p>

<p>Because chloroquine is known to cause adverse neurological events in humans and artesunate is not, we suggest that the patient described by Franco-Paredes et al. [<xref rid="ref1" ref-type="bibr">1</xref>
] was most likely suffering from the adverse effects of excessive chloroquine.</p>

</body>

<back>

<ack>

<title>Acknowledgments</title>

<p><bold><italic>Financial support</italic>
</bold>
. Wellcome Trust of Great Britain.</p>

<p><bold><italic>Potential conflicts of interest</italic>
</bold>
. All authors: no conflicts.</p>

</ack>

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<affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos</affiliation>
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<affiliation>Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</affiliation>
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<affiliation>Reprints or correspondence: Prof. Nicholas J. White, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand (nickw@tropmedres.ac).</affiliation>
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