Parasite Drug Resistance
Forum: Ask Microbe Detectives
I realize that some people are seeking help from their practitioners. When medication is given, it is expected to work, but not in all cases as I had learned. If you have a resistance issue, it might be worth printing off the below for your doctor to consider. They need to be informed that a problem could possibly exist and that it isn't your "imagination". The only way that this will be understood more is when there is documentation -- if you have a resistance issue it should be documented and reported. Also, it might be a good idea to look at a posting that I did with parasitologists regarding the matter and concerns.
There are several publications on helminth infections questioning and reviewing resistance in humans. The first link is rather extensive following the Abstract with a study -- worth the read. The following are Abstracts which are cited below.
Clin Microbiol Rev. 2000 April; 13(2): 207–222. PMCID: PMC100151
Copyright © 2000, American Society for Microbiology
Drug Resistance in Human Helminths: Current Situation and Lessons from Livestock
In this review the available reports on drug resistance in human helminths, particularly hookworms and schistosomes, are critically analyzed. The experiences with helminths of livestock are then reviewed, in particular the factors contributing to the development of anthelmintic resistance, the mechanisms and genetics of resistance to various anthelmintic classes, and the methods available for detection. These experiences appear to be worryingly similar and relevant to the potential development of drug resistance in human helminths. Recommendations to reduce its risks are suggested.
Trends in Parasitology
Volume 19, Issue 11, November 2003, Pages 527-531
Human gastrointestinal helminth infections: are they now neglected diseases?
Department of Pharmacology and Therapeutics, University of Liverpool, Ashton Street, Liverpool, L69 3GE, UK
Available online 26 September 2003.
Although over half the world's population might be infected by gastrointestinal (GI) helminths, their importance as therapeutic targets has been much underrated. GI helminths have only been recognized as causing considerable damage to individuals and to communities in the past 20 years, and global recognition of the problem only occurred within the past few years. As we move into the 21st century, there is a desire to undertake the challenging task of global control of GI helminths, while problems of drug resistance are discussed in the same breath. Today, we have tools that are effective for the task ahead, but these might only be available for a short time. Because of their effectiveness (both for control and as treatments for individuals), their simplicity of use and their excellent tolerability, there has been no incentive to develop new options. Unless there is a sustained effort in drug research and development, we might have to face a world without effective anthelmintics.
Pharmacology & Therapeutics
Volume 60, Issue 2, 1993, Pages 331-336
Molecular aspects of drug resistance in parasitic helminths
Marleen H. RoosCorresponding Author Contact Information, Marcel S. G. Kwa, Jetty G. Veenstra, Frans N. J. Kooyman and Jaap H. Boersema
Department of Parasitology and Tropical Veterinary Medicine, Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.165, 3508 TD, Utrecht, The Netherlands
Available online 14 November 2002.
Parasitic helminths (worms) cause serious infectious diseases in humans and animals. As control of these infections relies mostly on chemotherapeutics, the anthelmintics, resistance has developed against most of these drugs in several parasite species. These resistant parasites are being used to elucidate the molecular mechanism of drug action.
Author Keywords: Haemonchus contortus; drug resistance; benzimidazoles; beta-tubulin; anthelmintics
Abbreviations: BZ, benzimidazoles; BZ-R, benzimidazole resistant; BZ-S, benzimadazole susceptible
International Journal for Parasitology
Volume 31, Issue 4, April 2001, Pages 336-345
The biochemical basis of anthelmintic action and resistance
Peter KöhlerCorresponding Author Contact Information, E-mail The Corresponding Author
Institute of Parasitology, University of Zürich, Winterthurerstrasse 266a, 8057 Zürich, Switzerland
Received 1 February 2001;
revised 2 February 2001;
accepted 2 February 2001
Available online 9 April 2001.
The most commonly used modern anthelmintics include the benzimidazoles, the nicotinic agonists, praziquantel, triclabendazole and the macrocyclic lactones. These drugs interfere with target sites that are either unique to the parasite or differ in their structural features from those of the homologous counterpart present in the vertebrate host. The benzimidazoles exert their effect by binding selectively and with high affinity to the β-subunit of helminth microtubule protein. The target site of the nicotinic agonists (e.g. levamisole, tetrahydropyrimidines) is a pharmacologically distinct nicotinic acetylcholine receptor channel in nematodes. The macrocyclic lactones (e.g. ivermectin, moxidectin) act as agonists of a family of invertebrate-specific inhibitory chloride channels that are activated by glutamic acid. The primary mode of action of other important anthelmintics (e.g. praziquantel, triclabendazole) is unknown. Anthelmintic resistance is wide-spread and a serious threat to effective control of helminth infections, especially in the veterinary area. The biochemical and genetic mechanisms underlying anthelmintic resistance are not well understood, but appear to be complex and vary among different helminth species and even isolates. The major mechanisms helminths use to acquire drug resistance appear to be through receptor loss or decrease of the target site affinity for the drug. Knowledge on the mechanisms of drug action and resistance may be exploitable for the development of new drugs and may provide information on ways to overcome parasite resistance, respectively.
Author Keywords: Anthelmintics; Benzimidazoles; Drug resistance; Ivermectin; Levamisole; Macrocyclic lactones; Nictonitic agonists; Praziquantel; Oxamniquine
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