Methylene blue inhibits lumefantrine-resistant Plasmodium berghei

  • Victor Irungu Mwangi Institute of Primate Research, Nairobi, Kenya
  • Ruth Mwende Mumo Institute of Primate Research, Nairobi, Kenya
  • Daniel Muthui Kiboi Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
  • Sabah Ahmed Omar Kenya Medical Research Institute, Kilifi, Kenya
  • Zipporah Waithera Ng'ang'a Jomo Kenyatta University of Agriculture and Technology, Juja, Kenya
  • Hastings Suba Ozwara Institute of Primate Research, Nairobi, Kenya
Keywords: methylene blue, lumefantrine, pyrimethamine, Plasmodium berghei, resistant, parasitaemia

Abstract

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.

Author Biographies

Victor Irungu Mwangi, Institute of Primate Research, Nairobi, Kenya

MSc Molecular Medicine student

(Istitute of Tropical Medicine and Infectious Diseases, College of Health Sciences - Jomo Kenyatta Universtity of Agriculture and Technology)

Research intern (Department of Tropical and Infectious Diseases - Institute of Primate Research)

Ruth Mwende Mumo, Institute of Primate Research, Nairobi, Kenya
Research Assistant (Department of Tropical and Infectious Diseases - Institute of Primate Research)
Daniel Muthui Kiboi, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya

Research Officer, KEMRI

 

Sabah Ahmed Omar, Kenya Medical Research Institute, Kilifi, Kenya

 

Senior Scientist, Malaria Research, KEMRI

Zipporah Waithera Ng'ang'a, Jomo Kenyatta University of Agriculture and Technology, Juja, Kenya
Professoor, ITROMID (College of Health Sciences)
Hastings Suba Ozwara, Institute of Primate Research, Nairobi, Kenya

Director, IPR

Senior Scientist, Dept. of Tropical and Infectious Diseases, IPR

Published
2016-06-30
How to Cite
1.
Mwangi VI, Mumo RM, Kiboi DM, Omar SA, Ng’ang’a ZW, Ozwara HS (2016) Methylene blue inhibits lumefantrine-resistant Plasmodium berghei. J Infect Dev Ctries 10:635-642. doi: 10.3855/jidc.7556
Section
Original Articles