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Title: Intermittent Preventive Treatment (IPT): Its Role in Averting Disease-Induced Mortality in Children and in Promoting the Spread of Antimalarial Drug Resistance

Abstract

Here, we develop an age-structured ODE model to investigate the role of intermittent preventive treatment (IPT) in averting malaria-induced mortality in children, and its related cost in promoting the spread of antimalarial drug resistance. IPT, a malaria control strategy in which a full curative dose of an antimalarial medication is administered to vulnerable asymptomatic individuals at specified intervals, has been shown to reduce malaria transmission and deaths in children and pregnant women. However, it can also promote drug resistance spread. Our mathematical model is used to explore IPT effects on drug resistance and deaths averted in holoendemic malaria regions. The model includes drug-sensitive and drug-resistant strains as well as human hosts and mosquitoes. The basic reproduction, and invasion reproduction numbers for both strains are derived. Numerical simulations show the individual and combined effects of IPT and treatment of symptomatic infections on the prevalence of both strains and the number of lives saved. Our results suggest that while IPT can indeed save lives, particularly in high transmission regions, certain combinations of drugs used for IPT and to treat symptomatic infection may result in more deaths when resistant parasite strains are circulating. Moreover, the half-lives of the treatment and IPT drugs usedmore » play an important role in the extent to which IPT may influence spread of the resistant strain. A sensitivity analysis indicates the model outcomes are most sensitive to the reduction factor of transmission for the resistant strain, rate of immunity loss, and the natural clearance rate of sensitive infections.« less

Authors:
ORCiD logo [1];  [2];  [3];  [4];  [5];  [6]
  1. Los Alamos National Lab. (LANL), and New Mexico Consortium, Los Alamos, NM (United States)
  2. Lehigh Univ., Bethlehem, PA (United States)
  3. Univ. of Kentucky, Lexington, KY (United States)
  4. Texas Tech Univ., Lubbock, TX (United States)
  5. Howard Univ., Washington, D.C. (United States)
  6. Purdue Univ., West Lafayette, IN (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1481971
Report Number(s):
LA-UR-17-20425
Journal ID: ISSN 0092-8240
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Bulletin of Mathematical Biology
Additional Journal Information:
Journal Volume: 81; Journal Issue: 1; Conference: SIAM Annual Conference, Pittsburgh, PA (United States), 10 Jul 2017; Journal ID: ISSN 0092-8240
Publisher:
Society for Mathematical Biology - Springer
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Biological Science; Mathematics; Age structure; Malaria-induced deaths; Plasmodium falciparum; Intermittent preventative treatment; Holoendemic Immunity

Citation Formats

Manore, Carrie A., Teboh-Ewungkem, Miranda I., Prosper, Olivia, Peace, Angela, Gurski, Katharine, and Feng, Zhilan. Intermittent Preventive Treatment (IPT): Its Role in Averting Disease-Induced Mortality in Children and in Promoting the Spread of Antimalarial Drug Resistance. United States: N. p., 2018. Web. doi:10.1007/s11538-018-0524-1.
Manore, Carrie A., Teboh-Ewungkem, Miranda I., Prosper, Olivia, Peace, Angela, Gurski, Katharine, & Feng, Zhilan. Intermittent Preventive Treatment (IPT): Its Role in Averting Disease-Induced Mortality in Children and in Promoting the Spread of Antimalarial Drug Resistance. United States. doi:10.1007/s11538-018-0524-1.
Manore, Carrie A., Teboh-Ewungkem, Miranda I., Prosper, Olivia, Peace, Angela, Gurski, Katharine, and Feng, Zhilan. Wed . "Intermittent Preventive Treatment (IPT): Its Role in Averting Disease-Induced Mortality in Children and in Promoting the Spread of Antimalarial Drug Resistance". United States. doi:10.1007/s11538-018-0524-1. https://www.osti.gov/servlets/purl/1481971.
@article{osti_1481971,
title = {Intermittent Preventive Treatment (IPT): Its Role in Averting Disease-Induced Mortality in Children and in Promoting the Spread of Antimalarial Drug Resistance},
author = {Manore, Carrie A. and Teboh-Ewungkem, Miranda I. and Prosper, Olivia and Peace, Angela and Gurski, Katharine and Feng, Zhilan},
abstractNote = {Here, we develop an age-structured ODE model to investigate the role of intermittent preventive treatment (IPT) in averting malaria-induced mortality in children, and its related cost in promoting the spread of antimalarial drug resistance. IPT, a malaria control strategy in which a full curative dose of an antimalarial medication is administered to vulnerable asymptomatic individuals at specified intervals, has been shown to reduce malaria transmission and deaths in children and pregnant women. However, it can also promote drug resistance spread. Our mathematical model is used to explore IPT effects on drug resistance and deaths averted in holoendemic malaria regions. The model includes drug-sensitive and drug-resistant strains as well as human hosts and mosquitoes. The basic reproduction, and invasion reproduction numbers for both strains are derived. Numerical simulations show the individual and combined effects of IPT and treatment of symptomatic infections on the prevalence of both strains and the number of lives saved. Our results suggest that while IPT can indeed save lives, particularly in high transmission regions, certain combinations of drugs used for IPT and to treat symptomatic infection may result in more deaths when resistant parasite strains are circulating. Moreover, the half-lives of the treatment and IPT drugs used play an important role in the extent to which IPT may influence spread of the resistant strain. A sensitivity analysis indicates the model outcomes are most sensitive to the reduction factor of transmission for the resistant strain, rate of immunity loss, and the natural clearance rate of sensitive infections.},
doi = {10.1007/s11538-018-0524-1},
journal = {Bulletin of Mathematical Biology},
issn = {0092-8240},
number = 1,
volume = 81,
place = {United States},
year = {2018},
month = {10}
}

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