Animal models have indicated conclusively that Th2 responses instil protective immunity against both L3 infective larvae and the microfilaria stage but that parasites are generally able to avoid these responses.
This indicates that development of an effective vaccine may be possible, once a more comprehensive understanding of the process has been established. Soon after its use became widespread in animal health, ivermectin resistance began to appear, at first in small ruminants but also, more significantly in cattle parasites, especially Cooperia spp.
More importantly, despite some 22 years of constant monotherapy in humans, no convincing evidence of resistance in Onchocerca volvulus has yet been found, although there are indications that resistance may be starting to develop and that resistant parasites are being selected. Ivermectin has continually proved to be astonishingly safe for human use.
Indeed, it is such a safe drug, with minimal side effects, that it can be administered by non-medical staff and even illiterate individuals in remote rural communities, provided that they have had some very basic, appropriate training. This fact has helped contribute to the unsurpassed beneficial impact that the drug has had on human health and welfare around the globe, especially with regard to the campaign to fight Onchocerciasis.
Today, ivermectin is being increasingly used worldwide to combat other diseases in humans, such as Strongyloidiasis which infects some 35 million each year , scabies which causes million cases annually , Pediculosis, Gnathostomiasis and Myiasis—and new and promising properties and uses for ivermectin and other avermectin derivatives are continuing to be found.
Studies of long-term treatment with ivermectin to control Onchocerciasis have shown that use of the drug is additionally associated with significant reduction in the prevalence of infection with any soil-transmitted helminth parasites including Ascaris, Trichuris and hookworm , most or all of which are deemed to be major causes of the morbidity arising from poor childhood nutrition and growth.
In many underprivileged communities throughout the tropics, intestinal worms and parasitic skin diseases are extremely common and associated with significant morbidity. They usually co-exist, with many individuals infected with both ecto- and endoparasites.
A recent study in Brazil, using locally produced ivermectin, looked at the impact on internal helminthes and parasitic skin diseases. In reality, the renewed interest in fighting tropical diseases, including the involvement of the pharmaceutical industry, which has become increasingly evident over the past three decades, and which has saved lives and improved the welfare of billions of people, notably the poor and disadvantaged in the topics, can be traced back to the introduction of ivermectin for use in humans.
Since the inception of the Mectizan Donation Programme, Merck has donated well over 2. A further million total treatments have been approved for lymphatic filariasis, with around 90 million treatments being administered annually Fig. At present 33 countries are receiving ivermectin for Onchocerciasis and 15 for Lymphatic filariasis.
In , Ecuador became the second country in the Americas to halt River Blindness transmission. It is hoped that transmission of the disease in the Western hemisphere will be stopped by —a goal that will have been achieved thanks to twice-yearly MDA with ivermectin. Lymphatic filariasis is targeted for global elimination by , and, if all goes well, Onchocerciasis may well be eliminated from Africa soon thereafter.
Fortunately, and contrary to the position seen with most antibiotics, despite several decades of monotherapy and occasional suboptimal responses observed in some individuals, there is no conclusive evidence that drug resistance is developing in human Onchocercal parasites.
In response, the Kitasato Institute has initiated a global collaboration to investigate all properties and potential of a range of ivermectin analogues, both individually and in combination, particularly with a view to having a ready-made alternative should resistance to current ivermectin monotherapy ever threaten ongoing disease elimination campaigns.
We would like to thank Prof. Campbell for his valuable, long-term collaboration, including his critical reading of a draft of this paper and for his constructive comments. He was born in and received his Ph. He served as President of The Kitasato Institute from to His research interests are the discovery of useful compounds from microorganisms, the biosynthesis and hybrid biosynthesis of new macrolide antibiotics, the breeding, genetic analysis, and mapping of Streptomyces avermectinius , the synthesis of novel semisynthetic macrolides, and the organic synthesis of new compounds.
His work has led to the discovery of well over new chemicals, several of which have become leading drugs that have improved the lives and welfare of billions of people worldwide.
His initial biological research work in the USA focussed on cold-tolerance and supercooling in insects, funded by the National Science Foundation as part of an investigation of the feasibility of freezing and reviving humans for possible space flight. This was followed by teaching and Environmental Impact Assessment work in the USA, and several years as a Research Biologist at Imperial College, London working on a UK government-supported project investigating the behaviour and biocontrol of tsetse flies.
Since then, he has travelled, observed and reported, living and working in several countries in Europe, North America, Africa, Asia and the Pacific Islands.
During his career, he has devoted over 30 years toward developing expertise in all aspects of communications and Information Design, with a particular interest in visual and cultural literacy. An accomplished author and producer, his work in communications, especially in the science and health fields, is wide-ranging and diverse. He has also undertaken photojournalism presentations, exhibitions, and various electronic publishing activities including video, television, CD-ROM and website projects.
He relocated to Tokyo in and has been involved with the Kitasato Institute and Kitasato University ever since. National Center for Biotechnology Information , U. Author information Article notes Copyright and License information Disclaimer. Received Oct 1; Accepted Dec This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This article has been cited by other articles in PMC. Abstract Discovered in the lates, the pioneering drug ivermectin, a dihydro derivative of avermectin—originating solely from a single microorganism isolated at the Kitasato Intitute, Tokyo, Japan from Japanese soil—has had an immeasurably beneficial impact in improving the lives and welfare of billions of people throughout the world. Keywords: avermectin, ivermectin, mode of action, onchocerciasis, lymphatic filariasis, drug resistance.
Open in a separate window. Figure 1. Molecular diagrams of avermectin and the di-hydro derivative, ivermectin. Onchocerciasis The origins of ivermectin as a human drug are inextricably linked with Onchocerciasis or River Blindness , a chronic human filarial disease caused by infection with Onchocerca volvulus worms.
Figure 2. Drug donation For over a decade, OCP operations were exclusively based on the spraying of insecticides by helicopters and aircraft over the breeding sites of vector blackflies in order to kill their larvae. Development of ivermectin for human use In the mids, the global community mobilized itself to address the major problems of neglected tropical diseases. Figure 3. Advantages of ivermectin for treating Onchocerciasis Ivermectin proved to be virtually purpose-built to combat Onchocerciasis, which has two main manifestations, dermal damage resulting from microfilariae in the skin and ocular damage arising from microfilariae in the eye.
Figure 4. Figure 5. Effect of ivermectin and diethylcarbamazine DEC on microfilariae in the skin. Do not miss any doses. The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing. It is important that your doctor check your progress at regular visits.
This is to help make sure that the infection is cleared up completely. In addition, if you have river blindness onchocerciasis , your doctor may want you to have your eyes checked by an ophthalmologist eye doctor. If you have a certain type of diarrhea strongyloidiasis , your doctor may want to examine three stool samples.
This should be done over the 3-month period following treatment. This medicine may cause some people to become lightheaded. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are lightheaded. If these reactions occur, check with your doctor. Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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