Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-28T11:39:30.408Z Has data issue: false hasContentIssue false

Efficacy of artemisinin–naphthoquine phosphate against Schistosoma haematobium adult flukes: dose–effect relationship and tegumental alterations

Published online by Cambridge University Press:  21 May 2018

S.N. El-Beshbishi*
Affiliation:
Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura 35516-Egypt
S. El Bardicy
Affiliation:
Department of Medical Malacology, Theodor Bilharz Research Institute, Warrak El Hadar, Imbaba, Giza, Egypt
M. Tadros
Affiliation:
Department of Medical Malacology, Theodor Bilharz Research Institute, Warrak El Hadar, Imbaba, Giza, Egypt
M. Ayoub
Affiliation:
Department of Medical Malacology, Theodor Bilharz Research Institute, Warrak El Hadar, Imbaba, Giza, Egypt
A. Taman
Affiliation:
Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura 35516-Egypt
*
Author for correspondence: S.N. El-Beshbishi, Fax.: +2 02 22755108, E-mail: [email protected]

Abstract

Schistosoma haematobium and Schistosoma mansoni infections have broadly overlapping geographical distributions. Praziquantel is the only treatment for human schistosomiasis, so drug tolerance and/or resistance are major concerns. Artemisinin–naphthoquine phosphate (CO-ArNp), an artemisinin-based combination therapy endorsed by the World Health Organization as a gold standard therapy for malaria, has also been identified as a promising treatment for S. mansoni. In this in vitro study, we tested the effect of 1–40 μg/ml CO-ArNp on S. haematobium worms, and inspected tegumental changes by using scanning electron microscopy (SEM), aiming to determine if this combination therapy has a broad-spectrum antischistosomal activity. Incubation of S. haematobium adults with 20 or 30 μg/ml CO-ArNp caused 100% mortality of worms within 72 or 48 h, respectively. SEM examination showed extensive tegumental alterations such as oedema, constriction, shortening and loss of spines, fissuring, sloughing and perforation, resulting in exposure of the underlying basal lamina, mainly in treated male schistosomes. Besides the well-established potent efficacy, bioavailability, tolerability and safety of the antimalarial artemisinin–naphthoquine phosphate combined therapy, these results may also suggest its possible utilization as a new broad-spectrum antischistosomal agent.

Type
Short Communication
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Benjamin, J, Moore, B, Lee, ST et al. (2012) Artemisinin–naphthoquine combination therapy for uncomplicated pediatric malaria: a tolerability, safety, and preliminary efficacy study. Antimicrobial Agents and Chemotherapy 56, 24652471.Google Scholar
Boulanger, D, Dieng, Y, Cisse, B et al. (2007) Antischistosomal efficacy of artesunate combination therapies administered as curative treatments for malaria attacks. Transactions of the Royal Society of Tropical Medicine and Hygiene 101, 113116.Google Scholar
Camacho, M and Agnew, A (1995) Schistosoma: rate of glucose import is altered by acetylcholine interaction with tegumental acetylcholine receptors and acetyl cholinesterase. Experimental Parasitology 81, 584591.Google Scholar
Corrêa Soares, JB, Menezes, D, Vannier-Santos, MA et al. (2009) Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. PLoS Neglected Tropical Diseases 3, e477.Google Scholar
Doenhoff, MJ, Hagan, P, Cioli, D et al. (2009) Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs. Parasitology 136, 18251835.Google Scholar
Duvall, RH and DeWitt, WB (1967) An improved perfusion technique for recovering adult schistosomes from laboratory animals. American Journal of Tropical Medicine and Hygiene 16, 483486.Google Scholar
Eissa, MM, El Bardicy, S and Tadros, M (2011) Bioactivity of miltefosine against aquatic stages of Schistosoma mansoni and Schistosoma haematobium and their snail hosts, supported by scanning electron microscopy. Parasites & Vectors 4, 73.Google Scholar
El-Beshbishi, SN, Taman, A, El-Malky, MA, Azab, MS, El-Hawary, AK and El-Tantawy, DA (2013) First insight into the effect of single oral dose therapy with artemisinin–naphthoquine phosphate combination in a mouse model of Schistosoma mansoni infection. International Journal of Parasitology 43, 521530.Google Scholar
El-Beshbishi, SN, El Bardicy, S, Tadros, M, Ayoub, M and Taman, A (2015) Spotlight on the in vitro effect of artemisinin–naphthoquine phosphate on Schistosoma mansoni and its snail host Biomphalaria alexandrina. Acta Tropica 141, 3745.Google Scholar
Eraky, MA, Aly, NSM, Selem, RF, El-Kholy, AAE and Rashed, GAE (2016) In vitro schistosomicidal activity of phytol and tegumental alterations induced in juvenile and adult stages of Schistosoma haematobium. Korean Journal of Parasitology 54, 477484.Google Scholar
Keiser, J, N'Guessan, NA, Adoubryn, KD, Silue, KD, Vounatsou, P, Hatz, C, Utzinger, J and N'Goran, EK (2010) Efficacy and safety of mefloquine, artesunate, mefloquine–artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial. Clinical Infectious Diseases 50, 12051213.Google Scholar
King, CH (2010) Parasites and poverty: the case of schistosomiasis. Acta Tropica 113, 95104.Google Scholar
Mohamed, AA, Mahgoub, HM, Magzoub, M, Gasim, GI, Eldein, WN, Ahmed, AA and Adam, I (2009) Artesunate plus sulfadoxine/pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni in eastern Sudan. Transactions of the Royal Society of Tropical Medicine and Hygiene 103, 10621064.Google Scholar
Moraes, J, Nascimento, C, Lopes, PO, Nakano, E, Yamaguchi, LF, Kato, MJ and Kawano, T (2011) Schistosoma mansoni: in vitro schistosomicidal activity of piplartine. Experimental Parasitology 127, 357364.Google Scholar
Oliveira, MF, Kycia, SW, Gomez, A et al. (2005) Structural and morphological characterization of hemozoin produced by Schistosoma mansoni and Rhodnius prolixus. FEBS Letters 579, 60106016.Google Scholar
Pica-Mattoccia, L, Novi, A and Cioli, D (1997) Enzymatic basis for the lack of oxamniquine activity in Schistosoma haematobium infections. Parasitology Research 83, 687689.Google Scholar
Portela, J, Boissier, J, Gourbal, B, Pradines, V, Collière, V, Coslédan, F, Meunier, B and Robert, A (2012) Antischistosomal activity of trioxaquines: in vivo efficacy and mechanism of action on Schistosoma mansoni. PLoS Neglected Tropical Diseases 6(2), e1474.Google Scholar
Ramirez, B, Bickle, Q, Yousif, F, Mouries, MA and Nwaka, S (2007) Schistosoma challenge in compound screening. Expert Opinion on Drug Discovery 2, 19.Google Scholar
Rinaldi, G, Okatcha, TI, Popratiloff, A et al. (2011) Genetic manipulation of Schistosoma haematobium, the neglected schistosome. PLoS Neglected Tropical Diseases 5(10), e1348.Google Scholar
Shaw, MK and Erasmus, DA (1987) Schistosoma mansoni: structural damage and tegumental repair after in vivo treatment with praziquantel. Parasitology 94, 243254.Google Scholar
Shiff, C, Naples, JM, Isharwal, S, Bosompem, KM and Veltri, RW (2010) Non-invasive methods to detect schistosome-based bladder cancer: is the association sufficient for epidemiological use? Transactions of the Royal Society of Tropical Medicine and Hygiene 104, 35.Google Scholar
Skelly, PJ and Wilson, RA (2014) Making sense of the schistosome surface. Advances in Parasitology 65, 185284.Google Scholar
Soliman, MF and Ibrahim, MM (2005) Antischistosomal action of atorvastatin alone and concurrently with medroxyprogesterone acetate on Schistosoma haematobium harboured in hamster: surface ultrastructure and parasitological study. Acta Tropica 93, 19.Google Scholar
Terer, CC, Bustinduy, AL, Magtanong, RV, Muhoho, N, Mungai, PL, Muchiri, EM, Kitron, U, King, CH and Mutuku, FM (2013) Evaluation of the health-related quality of life of children in Schistosoma haematobium-endemic communities in Kenya: a cross-sectional study. PLoS Neglected Tropical Diseases 7(3), e2106.Google Scholar
Utzinger, J, N'Goran, EK, Caffrey, CR and Keiser, J (2011) From innovation to application: social–ecological context, diagnostics, drugs and integrated control of schistosomiasis. Acta Tropica 120(Suppl 1), S121S137.Google Scholar
Utzinger, J, Xiao, SH, Tanner, M and Keiser, J (2007) Artemisinins for schistosomiasis and beyond. Current Opinion in Investigational Drugs 8, 105116.Google Scholar
WHO (World Health Organization) (2016) Overview of malaria treatment. Available at http:// www.who.int/malaria/areas/treatment/overview/en (accessed 18 March 2016).Google Scholar
WHO (World Health Organization) (2017) Schistosomiasis. Available at http://www.who.int/mediacentre/factsheets/fs115/en/ (accessed October 2017).Google Scholar
Xiao, SH, Chollet, J, Utzinger, J, Matile, H, Mei, JY and Tanner, M (2001) Artemether administered together with haemin damages schistosomes in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 95, 6771.Google Scholar
Xiao, SH, Mei, JY and Jiao, PY (2011) Effect of mefloquine administered orally at single, multiple, or combined with artemether, artesunate, or praziquantel in treatment of mice infected with Schistosoma japonicum. Parasitology Research 108, 399406.Google Scholar
Xiao, S, Shen, B, Chollet, J, Utzinger, J and Tanner, M (2000) Tegumental changes in adult Schistosoma mansoni harbored in mice treated with artemether. Journal of Parasitology 86, 11251132.Google Scholar