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On the potential for discontinuing atovaquone-proguanil (AP) ad-hoc post-exposure and other abbreviated AP-regimens: Pharmacology, pharmacokinetics and perspectives


Schnyder, Jenny L; de Jong, Hanna K; Bache, Emmanuel B; van Hest, Reinier M; Schlagenhauf, Patricia; Borrmann, Steffen; Hanscheid, Thomas; Grobusch, Martin P (2022). On the potential for discontinuing atovaquone-proguanil (AP) ad-hoc post-exposure and other abbreviated AP-regimens: Pharmacology, pharmacokinetics and perspectives. Travel Medicine and Infectious Disease, 52:102520.

Abstract

According to current guidelines, atovaquone-proguanil (AP) malaria chemoprophylaxis should be taken once daily starting one day before travel and continued for seven days post-exposure. However, drug-sparing regimens, including discontinuing AP after leaving malaria-endemic areas are cost-saving and probably more attractive to travelers, and may thus enhance adherence. AP has causal prophylactic effects, killing malaria parasites during the hepatic stage. If early hepatic stages were already targeted by AP, AP could possibly be discontinued upon return. Pharmacokinetic data and studies on drug-sparing AP regimens suggest this to be the case. Nevertheless, the evidence is weak and considered insufficient to modify current recommendations. Field trials require large numbers of travelers and inherently suffer from the lack of a control group. Safely-designed controlled human malaria infection trials could significantly reduce study participant numbers and safely establish an effective AP abbreviated regimen which we propose as the optimal trial design to test this concept.

Abstract

According to current guidelines, atovaquone-proguanil (AP) malaria chemoprophylaxis should be taken once daily starting one day before travel and continued for seven days post-exposure. However, drug-sparing regimens, including discontinuing AP after leaving malaria-endemic areas are cost-saving and probably more attractive to travelers, and may thus enhance adherence. AP has causal prophylactic effects, killing malaria parasites during the hepatic stage. If early hepatic stages were already targeted by AP, AP could possibly be discontinued upon return. Pharmacokinetic data and studies on drug-sparing AP regimens suggest this to be the case. Nevertheless, the evidence is weak and considered insufficient to modify current recommendations. Field trials require large numbers of travelers and inherently suffer from the lack of a control group. Safely-designed controlled human malaria infection trials could significantly reduce study participant numbers and safely establish an effective AP abbreviated regimen which we propose as the optimal trial design to test this concept.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Public Health, Environmental and Occupational Health
Health Sciences > Infectious Diseases
Language:English
Date:14 December 2022
Deposited On:18 Jan 2023 16:19
Last Modified:28 Jun 2024 01:39
Publisher:Elsevier
ISSN:1477-8939
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.tmaid.2022.102520
PubMed ID:36526126
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)