Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance
Abstract Background Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-lin...
Published in: | Malaria Journal |
---|---|
Main Authors: | , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2009
|
Subjects: | |
Online Access: | https://doi.org/10.1186/1475-2875-8-253 https://doaj.org/article/21d1e12a94244d11b40b72d9bd26b446 |
id |
ftdoajarticles:oai:doaj.org/article:21d1e12a94244d11b40b72d9bd26b446 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:21d1e12a94244d11b40b72d9bd26b446 2023-05-15T15:12:59+02:00 Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance Lee Sue J Stepniewska Kasia Aguas Ricardo Saralamba Sompob Maude Richard J Pongtavornpinyo Wirichada White Nicholas J Dondorp Arjen M White Lisa J Day Nicholas PJ 2009-11-01T00:00:00Z https://doi.org/10.1186/1475-2875-8-253 https://doaj.org/article/21d1e12a94244d11b40b72d9bd26b446 EN eng BMC http://www.malariajournal.com/content/8/1/253 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-253 1475-2875 https://doaj.org/article/21d1e12a94244d11b40b72d9bd26b446 Malaria Journal, Vol 8, Iss 1, p 253 (2009) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2009 ftdoajarticles https://doi.org/10.1186/1475-2875-8-253 2022-12-31T00:42:17Z Abstract Background Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce "satisfactory" results. Methods The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed. Results Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission. Conclusion Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women). Patients with hyperparasitaemia who receive outpatient treatments provide the ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 8 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Lee Sue J Stepniewska Kasia Aguas Ricardo Saralamba Sompob Maude Richard J Pongtavornpinyo Wirichada White Nicholas J Dondorp Arjen M White Lisa J Day Nicholas PJ Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce "satisfactory" results. Methods The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed. Results Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission. Conclusion Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women). Patients with hyperparasitaemia who receive outpatient treatments provide the ... |
format |
Article in Journal/Newspaper |
author |
Lee Sue J Stepniewska Kasia Aguas Ricardo Saralamba Sompob Maude Richard J Pongtavornpinyo Wirichada White Nicholas J Dondorp Arjen M White Lisa J Day Nicholas PJ |
author_facet |
Lee Sue J Stepniewska Kasia Aguas Ricardo Saralamba Sompob Maude Richard J Pongtavornpinyo Wirichada White Nicholas J Dondorp Arjen M White Lisa J Day Nicholas PJ |
author_sort |
Lee Sue J |
title |
Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance |
title_short |
Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance |
title_full |
Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance |
title_fullStr |
Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance |
title_full_unstemmed |
Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance |
title_sort |
hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance |
publisher |
BMC |
publishDate |
2009 |
url |
https://doi.org/10.1186/1475-2875-8-253 https://doaj.org/article/21d1e12a94244d11b40b72d9bd26b446 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 8, Iss 1, p 253 (2009) |
op_relation |
http://www.malariajournal.com/content/8/1/253 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-253 1475-2875 https://doaj.org/article/21d1e12a94244d11b40b72d9bd26b446 |
op_doi |
https://doi.org/10.1186/1475-2875-8-253 |
container_title |
Malaria Journal |
container_volume |
8 |
container_issue |
1 |
_version_ |
1766343591077085184 |