Methylene blue inhibits lumefantrine-resistant Plasmodium berghei

Introduction: Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The large-scale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is nee...

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Main Authors: Victor Irungu Mwangi, Ruth Mwende Mumo, Daniel Muthui Kiboi, Sabah Ahmed Omar, Zipporah Waithera Ng'ang'a, Hastings Suba Ozwara
Format: Article
Language:English
Published: The Journal of Infection in Developing Countries 2016-06-01
Series:Journal of Infection in Developing Countries
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Online Access:https://jidc.org/index.php/journal/article/view/7556
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author Victor Irungu Mwangi
Ruth Mwende Mumo
Daniel Muthui Kiboi
Sabah Ahmed Omar
Zipporah Waithera Ng'ang'a
Hastings Suba Ozwara
author_facet Victor Irungu Mwangi
Ruth Mwende Mumo
Daniel Muthui Kiboi
Sabah Ahmed Omar
Zipporah Waithera Ng'ang'a
Hastings Suba Ozwara
author_sort Victor Irungu Mwangi
collection DOAJ
description Introduction: Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The large-scale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is need to identify drugs that can be used as substitutes to lumefantrine for use in combination therapy. Methylene blue, a synthetic anti-methemoglobinemia drug, has been shown to contain antimalarial properties, making it a candidate for drug repurposing. The present study sought to determine antiplasmodial effects of methylene blue against lumefantrine- and pyrimethamine-resistant strains of P. berghei. Methodology: Activity of methylene blue was assessed using the classical four-day test on mice infected with lumefantrine-resistant and pyrimethamine-resistant P. berghei. A dose of 45 mg/kg/day was effective for testing ED90. Parasitemia and mice survival was determined. Results: At 45 mg/kg/day, methylene blue sustained significant parasite inhibition, over 99%, for at least 6 days post-treatment against lumefantrine-resistant and pyrimethamine-resistant P. berghei (p = 0.0086 and p = 0.0191, respectively). No serious adverse effects were observed. Conclusions: Our results indicate that methylene blue at a concentration of 45 mg/kg/day confers over 99% inhibition against lumefantrine- and pyrimethamine-resistant P. berghei for six days. This shows the potential use methylene blue in the development of antimalarials against lumefantrine- and pyrimethamine-resistant parasites.
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spelling doaj-art-aec2ae6932144320a880a5d182c23bf82025-08-20T03:52:43ZengThe Journal of Infection in Developing CountriesJournal of Infection in Developing Countries1972-26802016-06-01100610.3855/jidc.7556Methylene blue inhibits lumefantrine-resistant Plasmodium bergheiVictor Irungu Mwangi0Ruth Mwende Mumo1Daniel Muthui Kiboi2Sabah Ahmed Omar3Zipporah Waithera Ng'ang'a4Hastings Suba Ozwara5Institute of Primate Research, Nairobi, KenyaInstitute of Primate Research, Nairobi, KenyaKenya Medical Research Institute (KEMRI), Nairobi, KenyaKenya Medical Research Institute, Kilifi, KenyaJomo Kenyatta University of Agriculture and Technology, Juja, KenyaInstitute of Primate Research, Nairobi, KenyaIntroduction: Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The large-scale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is need to identify drugs that can be used as substitutes to lumefantrine for use in combination therapy. Methylene blue, a synthetic anti-methemoglobinemia drug, has been shown to contain antimalarial properties, making it a candidate for drug repurposing. The present study sought to determine antiplasmodial effects of methylene blue against lumefantrine- and pyrimethamine-resistant strains of P. berghei. Methodology: Activity of methylene blue was assessed using the classical four-day test on mice infected with lumefantrine-resistant and pyrimethamine-resistant P. berghei. A dose of 45 mg/kg/day was effective for testing ED90. Parasitemia and mice survival was determined. Results: At 45 mg/kg/day, methylene blue sustained significant parasite inhibition, over 99%, for at least 6 days post-treatment against lumefantrine-resistant and pyrimethamine-resistant P. berghei (p = 0.0086 and p = 0.0191, respectively). No serious adverse effects were observed. Conclusions: Our results indicate that methylene blue at a concentration of 45 mg/kg/day confers over 99% inhibition against lumefantrine- and pyrimethamine-resistant P. berghei for six days. This shows the potential use methylene blue in the development of antimalarials against lumefantrine- and pyrimethamine-resistant parasites. https://jidc.org/index.php/journal/article/view/7556methylene bluelumefantrinepyrimethaminePlasmodium bergheiresistantparasitaemia
spellingShingle Victor Irungu Mwangi
Ruth Mwende Mumo
Daniel Muthui Kiboi
Sabah Ahmed Omar
Zipporah Waithera Ng'ang'a
Hastings Suba Ozwara
Methylene blue inhibits lumefantrine-resistant Plasmodium berghei
Journal of Infection in Developing Countries
methylene blue
lumefantrine
pyrimethamine
Plasmodium berghei
resistant
parasitaemia
title Methylene blue inhibits lumefantrine-resistant Plasmodium berghei
title_full Methylene blue inhibits lumefantrine-resistant Plasmodium berghei
title_fullStr Methylene blue inhibits lumefantrine-resistant Plasmodium berghei
title_full_unstemmed Methylene blue inhibits lumefantrine-resistant Plasmodium berghei
title_short Methylene blue inhibits lumefantrine-resistant Plasmodium berghei
title_sort methylene blue inhibits lumefantrine resistant plasmodium berghei
topic methylene blue
lumefantrine
pyrimethamine
Plasmodium berghei
resistant
parasitaemia
url https://jidc.org/index.php/journal/article/view/7556
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