Generic placeholder image

Infectious Disorders - Drug Targets


ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Research Article

Promising New Antimalarial Combination Drugs: Garlic and Arteether in Pregnant Mice Infected with Plasmodium berghei

Author(s): Vathsala Palakkod Govindan* and Krishna Murthy Purushothama

Volume 22, Issue 4, 2022

Published on: 05 April, 2022

Article ID: e100122200124 Pages: 10

DOI: 10.2174/1871526522666220110163945

Price: $65


Background: Antimalarial prescription remains a challenge in pregnant women because of maternal and fetal complications. Recently, garlic and α-β-arteether combination treatment in malariainfected mice conferred protection. The purpose of this study is to evaluate the efficacy of these drugs during malaria in pregnancy and its safety measures.

Objective: The study evaluates the efficacy of arteether and garlic combination drugs in protection against malaria-infected pregnant mice.

Methods: Plasmodium berghei-infected pregnant mouse model was used to assess the combination drug efficacy and the outcome of abnormalities of the disease after drug treatment. After optimizing the dose and gestation period, maternal protection was confirmed by parasite clearance in smear and mortality observation. In addition, maternal hematological parameters, different organ histopathology, and IgG levels were documented along with the fetal and infant outcomes.

Results: Arteether monotherapy resulted in spontaneous fetal abortion or resorption, while dosage optimization and garlic combination resulted in pregnancy completion and malaria protection. The derangements observed in the histoarchitecture of organs and hematological parameters caused by malaria infection revealed improvement after drug treatment, and the smear observation confirms the clearance of malaria parasite in the peripheral blood, but IgG level was maintained at the same higher level as in malaria-infected mice.

Conclusion: The first report of an arteether and garlic combination demonstrating high efficacy in protecting against malaria-infected pregnant mice establishes its safety as a viable possible treatment for pregnancy-associated malaria.

Keywords: Malaria in pregnancy, antimalarial, garlic, arteether, combination drug therapy, Plasmodium berghei, arteether monotherapy.

Graphical Abstract
WHO, 2019. World Malaria Report 2019. Geneva, Switzerland: World Health Organization. 2019. Available from:. https://www.who. int/publications-detail/world-malaria-report
Dellicour S, Tatem AJ, Guerra CA, Snow RW, ter Kuile FO. Quantifying the number of pregnancies at risk of malaria in 2007: a demographic study. PLoS Med 2010; 7(1): e1000221.
[] [PMID: 20126256]
WHO. Global malaria programme: Pregnant women and infants. Geneva, World Health Organization. 2009. Available from: html
Desai M, ter Kuile FO, Nosten F, et al. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis 2007; 7(2): 93-104.
Prevention and Control of Malaria in Pregnancy. Reference Manual, 2018 Update. 3rd ed. Baltimore, Maryland, USA: Jhpiego Corporation 2018.
Loutan L. Malaria: Still a threat to travellers. Int J Antimicrob Agents 2003; 21(2): 158-63.
Tatem AJ, Jia P, Ordanovich D, et al. The geography of imported malaria to non-endemic countries: A meta-analysis of nationally reported statistics. Lancet Infect Dis 2017; 17: 98-107.
Angelo KM, Libman M, Caumes E, Hamer DH, Kain KC, Leder K, et al. Malaria after international travel: A GeoSentinel analysis, 2003–2016. Malar J 2017; 16: 293-302.
WHO. Global technical strategy for malaria, 2016-2030. Available from:. http://www.who. int/malaria/areas/global_technical_strategy/en/
Arévalo-Herrera M, Lopez-Perez M, Medina L, et al. Clinical profile of Plasmodium falciparum and Plasmodium vivax infections in low and unstable malaria transmission settings of Colombia. Malar J 2015; 14: 154.
Umbers AJ, Aitken EH, Rogerson SJ. Malaria in pregnancy: Small babies, big problem. Trends Parasitol 2011; 2: 168-75.
Rogerson SJ, Desai M, Mayor A, Sicuri E, Taylor SM, van Eijk AM. Burden, pathology, and costs of malaria in pregnancy: New developments for an old problem. Lancet Infect Dis 2018; 18: e107-18.
WHO. WHO guidelines for the treatment of malaria; World Health Organization: Geneva, Switzerland 2006. Available from:.
Kovacs SD, van Eijk AM, Sevene E, et al. The safety of artemisinin derivatives for the treatment of malaria in the 2nd or 3rd trimester of pregnancy: a systematic review and meta-analysis. PLoS One 2016; 11(11): e0164963.
Manyando C, Kayentao K, D’Alessandro U, Okafor HU, Juma E, Hamed K. A systematic review of the safety and efficacy of artemether–lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy. Malar J 2012; 11: 141.
Dellicour S, Sevene E, McGready R, et al. First-trimester artemisinin derivatives and quinine treatments and the risk of adverse pregnancy outcomes in Africa and Asia: A meta-analysis of observational studies. PLoS Med 2017; 14: e1002290.
WHO. World Malaria Report. Geneva: World Health Organization 2010.
Björkman A, Shakely D, Ali AS, et al. From high to low malaria transmission in Zanzibar-challenges and opportunities to achieve elimination. BMC Med 2019; 17(1): 14.
[] [PMID: 30665398]
Berrevoets MA, Sprong T, Meis JF, Dofferhoff AS. Plasmodium falciparum malaria recrudescence occurring 2.5 years after leaving an endemic country. Neth J Med 2013; 71(8): 426-8.
[PMID: 24127503]
Neres R, Marinho CR, Gonçalves LA, Catarino MB, Penha-Gonçalves C. Pregnancy outcome and placenta pathology in Plasmodium berghei ANKA infected mice reproduce the pathogenesis of severe malaria in pregnant women. PLoS One 2008; 3(2): e1608.
[] [PMID: 18270595]
Rodrigues C, Susan S. Immunomodulatory effects of glutathione, garlic derivatives, and hydrogen sulfide. Nutrients 2019; 11(2): 295.
[] [PMID: 30704060]
Coppi A, Cabinian M, Mirelman D, Sinnis P. Antimalarial activity of allicin, a biologically active compound from garlic cloves. Antimicrob Agents Chemother 2006; 50(5): 1731-7.
[] [PMID: 16641443]
Arreola R, Quintero-Fabián S, López-Roa RI, et al. Immunomodulation and anti-inflammatory effects of garlic compounds. J Immunol Res 2015; 2015: 401630.
[] [PMID: 25961060]
Vathsala PG, Panduranga AN, Krishna Murthy P. Assessment of in vivo antimalarial activity of arteether and garlic oil combination therapy. Biochem Biophys Rep 2016; 5: 359-64.
[] [PMID: 28955843]
Vathsala PG, Krishna Murthy P. Immunomodulatory and antiparasitic effects of garlic–arteether combination via nitric oxide pathway in Plasmodium berghei-infected mice. J Parasit Dis 2019; 44(1): 49-61.
[] [PMID: 32174705]
Mader SL, Libal NL, Kathleen PC, Yang R, Murphy SJ. Refining timed pregnancies in two strains of genetically engineered mice. Lab Anim (NY) 2009; 38(9): 305-10.
[] [PMID: 19701181]
Wilson DD. McGraw-Hill’s manual of laboratory and diagnostic tests. New York: McGraw-Hill Companies, Inc. 2008; p. 149.
Ang KK, Holmes MJ, Kara UA. Immune-mediated parasite clearance in mice infected with Plasmodium berghei following treatment with manzamine A. Parasitol Res 2001; 87(9): 715-21.
[] [PMID: 11570556]
Chung MK, Yu WJ, Lee JS, Lee JH. Embryotoxicity and toxicokinetics of the antimalarial artesunate in rats. Toxicol Res 2013; 29(1): 27-34.
[] [PMID: 24278626]
Bashawri LA, Mandil AA, Bahnassy AA, Ahmed MA. Malaria: Hematological aspects. Ann Saudi Med 2002; 22: 372-6.
[] [PMID: 17146269]
Aitken EH, Alemu A, Rogerson SJ. Neutrophils and malaria. Front Immunol 2018; 9: 3005.
[] [PMID: 30619354]
Kotepui M, Phunphuech B, Phiwklam N, Chupeerach C, Duangmano S. Effect of malarial infection on haematological parameters in population near Thailand-Myanmar border. Malar J 2014; 13: 218.
[] [PMID: 24898891]
Morrell CN. Understanding platelets in malaria infection. Curr Opin Hematol 2014; 21(5): 445-9.
[] [PMID: 25054909]
Simister NE. Placental transport of immunoglobulin G. Vaccine 2003; 21(24): 3365-9.
[] [PMID: 12850341]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy