New Developments regarding Ivermectin.  (not to be confused with "Avermectin". https://www.healio.com/news/primary-care/20201208/this-was-a-gift-to-us-iver... In a press conference, researchers said that ivermectin is an FDA-approved anti-parasitic drug that has been available for approximately 40 years and previously earned researchers a Nobel Prize. | | | | | | | | | | | Both ivermectin, permethrin yield high clearance rates in scabies In scabies treatment, oral ivermectin at 200 µg/kg may be associated with slightly lower rates of complete clear... | | | Ivermectin is a key factor in the alliance’s I-MASK+ protocol for prophylaxis and early treatment of outpatients with COVID-19. In the protocol, those at high risk for COVID-19 infection receive ivermectin at 0.2 mg/kg on day 1 and day 3, and weekly for 4 weeks; those who were exposed to COVID-19 receive the same dose at day 1 and day 3; and both groups receive daily doses of vitamin D3, vitamin C, quercetin, zinc and melatonin. For early outpatients with COVID-19, the protocol calls for one dose of ivermectin at 0.2 mg/kg at day 1 and day 3, along with the same daily vitamins and 325 mg per day of aspirin. During the press conference, Marik said that much of the data available on ivermectin in the treatment and prevention of COVID-19 has been published since August, which was the last time the NIH updated its recommendations for the novel coronavirus. Thus far, Marik said, studies have indicated that ivermectin has demonstrated efficacy in preventing COVID-19 infection prior to and after exposure to COVID-19. He also said that it has been shown to effectively treat the virus in the early symptomatic stages and among patients hospitalized with COVID-19. | | | | | | | | | | | New trial evaluates potential COVID-19 treatments in high-risk patients Researchers from the University of Kentucky are conducting a clinical trial to evaluate the effectiveness of azi... | | | On Friday, April 3, 2020, 06:28:51 PM PDT, jim bell wrote: Anti-parasitic drug kills coronavirus cell cultures in just 48 hours A team of Australian researchers at Monash University in Melbourne have found that Ivermectin — an FDA-approved anti-parasitic drug that has been used to effectively fight viruses including HIV, Influenza, and Zika — was able to stop the SARS-CoV-2 virus from growing in cell cultures. While promising, the drug has yet to be shown to have the same effect inside the human body, because the Australian research was conducted “in vitro,” meaning it was in a Petri dish at a lab. The researchers are still trying to nail down funding for pre-clinical testing and clinical trials, after which they’d have to start the long approval process for the trials themselves. The results, though, are promising. In just 48 hours, the scientists say, all genetic material of the virus was eradicated. “We found that even a single dose could essentially remove all viral RNA by 48 hours and that even at 24 hours there was a really significant reduction in it,” Kylie Wagstaff, lead researcher and co-author of the study published today in Antiviral Research, said in a statement. “Ivermectin is very widely used and seen as a safe drug,” Wagstaff said. “We need to figure out now whether the dosage you can use it at in humans will be effective — that’s the next step.” “As the virologist who was part of the team who were first to isolate and share SARS-COV2 outside of China in January 2020, I am excited about the prospect of Ivermectin being used as a potential drug against COVID-19,” Leon Caly, senior medical scientist at the Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute, said. A vaccine for COVID-19 is likely still at least a year out, despite research teams across the world fast tracking work on potential vaccines. But that doesn’t mean we’re doomed. “In times when we’re having a global pandemic and there isn’t an approved treatment, if we had a compound that was already available around the world then that might help people sooner,” Wagstaff said in the statement. “Realistically it’s going to be a while before a vaccine is broadly available.” ----------------------------------- https://www.poison.org/articles/ivermectin-your-dogs-heartworm-medicine-173 The Full Story Sometimes new drugs are found in unusual places. The antiparasitic drug ivermectin was discovered in the 1970s in bacteria isolated from the soil on a Japanese golf course. Ivermectin was called the first "endectocide" since it was active against both endoparasites (parasites that live inside the host) and ectoparasites (parasites that live on the outside of the host). Ivermectin was initially developed as a veterinary antiparasitic drug. Of particular importance today is ivermectin's ability to prevent heartworm infections in dogs with monthly dosing (e.g., Heartgard). Ivermectin has also protected hundreds of millions of livestock from a variety of parasites. Ivermectin lotion is approved by the FDA for the treatment of head lice. Unlike many other treatments for head lice, ivermectin lotion only needs to be applied once. When given orally, ivermectin can be used for treating head or pubic lice and scabies (an itchy, highly contagious skin disease caused by mites burrowing in the skin). Oral ivermectin is useful to control outbreaks of scabies in nursing homes where whole-body application of topical agents is difficult. Ivermectin's greatest impact on human health has been in Africa. Since 1987, in addition to its use for other parasitic infestations, ivermectin has been used extensively to control onchocerciasis with 1.4 billion treatments so far. Onchocerciasis is also called "river blindness" because the blackfly that transmits the disease breeds in fast-moving streams and rivers. Once within the body, the adult female worm produces thousands of juvenile worms that migrate to the skin and eyes and can produce severe itching and eye injury that can lead to blindness. Ivermectin kills the juvenile worms, but not the adult females. The effectiveness of the drug lasts up to 12 months, but mature female worms produce offspring for 15 years, so ivermectin has to be taken once a year for that long. Over 300 million people take ivermectin each year. To date, ivermectin has been shown to be a safe and well-tolerated drug. Most adverse reactions are mild and temporary, such as loss of appetite, headache, muscle aches, lack of energy, and fever. There have been a small number of severe adverse events and even some deaths in humans treated with ivermectin in onchocerciasis-control programs. The reason for these events is unknown, but they might be linked to the presence of large numbers of other parasites that are killed off in treated patients. If you suspect someone has swallowed ivermectin, do not make the person vomit. Immediately check the webPOISONCONTROL® online tool for help or call Poison Control at 1-800-222-1222. When ivermectin gets in the eyes, minor irritation and redness can occur. Serious eye injury is not likely, but the eyes should be rinsed immediately. Remove contact lenses and use lots of room temperature water. For children, pour water onto the bridge of the nose and let it gently run into the eyes. Encourage blinking. After rinsing, call Poison Control or use the webPOISONCONTROL tool for help. Mary Elizabeth May, RN, BA, MPH Certified Specialist in Poison Information  ========================================================= On Friday, April 3, 2020, 04:12:39 PM PDT, jim bell wrote: https://www.dailymail.co.uk/health/article-8184997/Doctors-worldwide-say-mal... Doctors around the globe report that the malaria drug hydroxychloroquine seems the most effective treatment they've tried for coronavirus patients - but less than half as many doctors are prescribing it in the US as in other hard-hit countries like Spain.  A survey of 6,200 doctors around the globe reveals that while few corners of the world are untouched by the virus, the pandemic is being handled very differently from country-to-country.  And in some measures, the US continues to fall behind other nations' responses.  For example, an American waits an average of four to five days to get results back after being tested for COVID-19. Half of doctors in Europe and most in China get the test results back within 24-hours.  Dr Murali Doraiswamy, an adviser to Sermo, urged that countries should take note of what is working for doctors and governments elsewhere and move quickly to adopt practices that are saving lives.     Hydroxychloroquine (pictured) was deemed the most effective coronavirus treatment comared to other options by more doctors worldwide than any other in a global survey  =========================================================== On Sat, Feb 8, 2020 at 9:18 PM jim bell wrote: jim bell [chloroquine is an old-line drug typically used against malaria] [partial quote follows] https://www.asbmb.org/asbmb-today/science/020620/could-an-old-malaria-drug-h... ASBMB Today Science Could an old malaria drug help fight the new coronavirus? Could an old malaria drug help fight the new coronavirus? By John Arnst February 06, 2020 Chloroquine might be getting new life as an antiviral treatment for the novel coronavirus that emerged in Wuhan, China in late 2019 and has infected some 25,000 people in more than 25 countries. For decades, the drug was a front-line treatment and prophylactic for malaria. In a three-page paper published Tuesday in Cell Research, scientists at the Wuhan Institute of Virology’s State Key Laboratory of Virology write that both chloroquine and the antiviral remdesivir were, individually, “highly effective” at inhibiting replication of the novel coronavirus in cell culture. Their drug screen evaluated five other drugs that were not effective. The authors could not be reached for comment. Though the paper is brief, John Lednicky, a professor at the University of Florida’s Emerging Pathogens Institute, found its results intriguing. “It’s interesting in that it really lacks a lot of details but, nevertheless, if you look at the data as presented, at least in vitro, it seems like chloroquine can be used as an early-stage drug,” he said. “It would be very good if these types of experiments were repeated by more laboratories to see whether the same results occur across the board.” Chloroquine is a synthetic form of quinine, a compound found in the bark of cinchona trees native to Peru and used for centuries to treat malaria. Chloroquine was an essential element of mass drug administration campaigns to combat malaria throughout the second half of the 20th century, and remains one of the World Health Organization’s essential medicines. However, after the malaria parasites Plasmodium falciparum and Plasmodium vivax began exhibiting resistance to the drug in the 1960s and 1980s, respectively, it was replaced by similar antimalarial compounds and combination therapies. Chloroquine is still widely used against the three other species of plasmodium and to treat autoimmune disorders and some cases of amebiasis, an intestinal infection caused by the amoeba Entamoeba histolytica. Chloroquine’s antiviral properties were explored in the mid-1990s against HIV and in the following decade against severe acute respiratory syndrome, or SARS, which is closely related to the novel coronavirus. In 2004, researchers in Belgium found that chloroquine inhibited replication of SARS in cell culture. The following year, however, another team at Utah State University and the Chinese University of Hong Kong evaluated a gamut of compounds against SARS replication in mice infected with the virus, finding that chloroquine was only effective as an anti-inflammatory agent. They recommended that it could be used in combination with compounds that prevent replication. Nevertheless, in 2009, the Belgian group found that lethal infections of human coronavirus OC43, a relative of SARS, could be averted in newborn mice by administering chloroquine through the mother’s milk. [end of partial quote] Also: https://www.nature.com/articles/s41422-020-0282-0 Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Manli Wang, Ruiyuan Cao, Leike Zhang, Xinglou Yang, Jia Liu, Mingyue Xu, Zhengli Shi, Zhihong Hu, Wu Zhong & Gengfu Xiao  Cell Research (2020)Cite this article 171k Accesses 1108 Altmetric Metrics details Dear Editor, In December 2019, a novel pneumonia caused by a previously unknown pathogen emerged in Wuhan, a city of 11 million people in central China. The initial cases were linked to exposures in a seafood market in Wuhan.1 As of January 27, 2020, the Chinese authorities reported 2835 confirmed cases in mainland China, including 81 deaths. Additionally, 19 confirmed cases were identified in Hong Kong, Macao and Taiwan, and 39 imported cases were identified in Thailand, Japan, South Korea, United States, Vietnam, Singapore, Nepal, France, Australia and Canada. The pathogen was soon identified as a novel coronavirus (2019-nCoV), which is closely related to sever acute respiratory syndrome CoV (SARS-CoV).2 Currently, there is no specific treatment against the new virus. Therefore, identifying effective antiviral agents to combat the disease is urgently needed. An efficient approach to drug discovery is to test whether the existing antiviral drugs are effective in treating related viral infections. The 2019-nCoV belongs to Betacoronavirus which also contains SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Several drugs, such as ribavirin, interferon, lopinavir-ritonavir, corticosteroids, have been used in patients with SARS or MERS, although the efficacy of some drugs remains controversial.3 In this study, we evaluated the antiviral efficiency of five FAD-approved drugs including ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine and two well-known broad-spectrum antiviral drugs remdesivir (GS-5734) and favipiravir (T-705) against a clinical isolate of 2019-nCoV in vitro. Standard assays were carried out to measure the effects of these compounds on the cytotoxicity, virus yield and infection rates of 2019-nCoVs. Firstly, the cytotoxicity of the candidate compounds in Vero E6 cells (ATCC-1586) was determined by the CCK8 assay. Then, Vero E6 cells were infected with nCoV-2019BetaCoV/Wuhan/WIV04/20192 at a multiplicity of infection (MOI) of 0.05 in the presence of varying concentrations of the test drugs. DMSO was used in the controls. Efficacies were evaluated by quantification of viral copy numbers in the cell supernatant via quantitative real-time RT-PCR (qRT-PCR) and confirmed with visualization of virus nucleoprotein (NP) expression through immunofluorescence microscopy at 48 h post infection (p.i.) (cytopathic effect was not obvious at this time point of infection). Among the seven tested drugs, high concentrations of three nucleoside analogs including ribavirin (half-maximal effective concentration (EC50) = 109.50 μM, half-cytotoxic concentration (CC50) > 400 μM, selectivity index (SI) > 3.65), penciclovir (EC50 = 95.96 μM, CC50 > 400 μM, SI > 4.17) and favipiravir (EC50 = 61.88 μM, CC50 > 400 μM, SI > 6.46) were required to reduce the viral infection (Fig. 1a and Supplementary information, Fig. S1). However, favipiravir has been shown to be 100% effective in protecting mice against Ebola virus challenge, although its EC50 value in Vero E6 cells was as high as 67 μM,4 suggesting further in vivo studies are recommended to evaluate this antiviral nucleoside. Nafamostat, a potent inhibitor of MERS-CoV, which prevents membrane fusion, was inhibitive against the 2019-nCoV infection (EC50 = 22.50 μM, CC50 > 100 μM, SI > 4.44). Nitazoxanide, a commercial antiprotozoal agent with an antiviral potential against a broad range of viruses including human and animal coronaviruses, inhibited the 2019-nCoV at a low-micromolar concentration (EC50 = 2.12 μM; CC50 > 35.53 μM; SI > 16.76). Further in vivo evaluation of this drug against 2019-nCoV infection is recommended. Notably, two compounds remdesivir (EC50 = 0.77 μM; CC50 > 100 μM; SI > 129.87) and chloroquine (EC50 = 1.13 μM; CC50 > 100 μM, SI > 88.50) potently blocked virus infection at low-micromolar concentration and showed high SI (Fig. 1a, b). | | | | | | | | | | | Anti-parasitic drug kills coronavirus cell cultures in just 48 hours "If we had a compound that was already available around the world then that might help people sooner." | | |

On Tue, Dec 15, 2020 at 04:31:44PM +0000, coderman wrote:

‐‐‐‐‐‐‐ Original Message ‐‐‐‐‐‐‐ On Monday, December 14, 2020 6:36 AM, jim bell wrote:

...

New Developments regarding Ivermectin. (not to be confused with "Avermectin".

https://www.healio.com/news/primary-care/20201208/this-was-a-gift-to-us-iver...

i've de-wormed horses with this :P

Does it also work against rats?

glad to know i can head to the feed store in a covid pinch...

best regards,

On Wed, Dec 16, 2020 at 07:58:54PM +0000, jim bell wrote:

On Tuesday, December 15, 2020, 08:31:59 AM PST, coderman wrote:

‐‐‐‐‐‐‐ Original Message ‐‐‐‐‐‐‐ On Monday, December 14, 2020 6:36 AM, jim bell wrote:

...

...

New Developments regarding Ivermectin.  (not to be confused with "Avermectin".

...

...

https://www.healio.com/news/primary-care/20201208/this-was-a-gift-to-us-iver...

...

i've de-wormed horses with this :P

...

glad to know i can head to the feed store in a covid pinch...

Yes, I first became aware of Ivermectin in maybe 2014, when I saw that it was the main ingredient in 'ant-bait', ant-killer.   So, I noticed it when many months ago, they started talking about it against COVID-19.   I just bought a dozen tubes from Amazon, in a form intended as a horse-de-wormer.   It says it tastes like apples!  Yum! https://www.amazon.com/Durvet-Duramectin-Equine-Wormer-Paste/dp/B01EP4TPPC/ref=sr_1_20?dchild=1&keywords=ivermectin&qid=1608148501&sr=8-20

Would I take anything else?   I say, "Nay!!!"   (Neigh!!!)           Jim Bell

Hasn't worked well around here - still got this butt ugly rat running round the carpet - it seems to have very raw and bloody knees and refuses any soothing vaseline whatsoever. Strange critter.

Even more information on Ivermectin: https://rebelem.com/covid-19-update-ivermectin/ Suggested treatment: - - If you believe the evidence thus far, which are severely flawed: Dosing of Ivermectin Used in Trials - Prophylaxis: 0.2 mg/kg on day 1 and day 3 followed by one dose/month - Treatment 0.2mg/kg o day 1 and day 3 followed by Days 6 and 8 if not recovered - Suggested Dosing of Ivermectin Based on Weight [1] [end of partial quote] On Friday, December 18, 2020, 11:17:08 PM PST, jim bell wrote: On Wednesday, December 16, 2020, 11:59:30 AM PST, jim bell wrote:

Yes, I first became aware of Ivermectin in maybe 2014, when I saw that it was the main ingredient in 'ant-bait', ant-killer.   So, I noticed it when many months ago, they started talking about it against COVID-19.   I just bought a dozen tubes from Amazon, in a form intended as a horse-de-wormer.   It says it tastes like apples!  Yum! https://www.amazon.com/Durvet-Duramectin-Equine-Wormer-Paste/dp/B01EP4TPPC/ref=sr_1_20?dchild=1&keywords=ivermectin&qid=1608148501&sr=8-20

Would I take anything else?   I say, "Nay!!!"   (Neigh!!!)   >      Jim Bell

More information on Ivermectin: | | Jim b | | 11:07 PM (4 minutes ago) | | =============================I recently sent a reference that says to prevent COVID-19, a person should take about 0.2 mg of Ivermectin per kilogram of body weight weekly, after a couple of quick treatments  This is probably a different cite:     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043740/#:~:text=The%20half%2Dl... Partial quote follows: .Proc Jpn Acad Ser B Phys Biol Sci. 2011 Feb 10; 87(2): 13–28.doi: 10.2183/pjab.87.13PMCID: PMC3043740PMID: 21321478 Ivermectin, ‘Wonder drug’ from Japan: the human use perspective Andy CRUMP*1 and Satoshi ŌMURA*1†Editor: Satoshi ŌMURAAuthor information Article notes Copyright and License information DisclaimerThis article has been cited by other articles in PMC.Go to: Introduction There are few drugs that can seriously lay claim to the title of ‘Wonder drug’, penicillin and aspirin being two that have perhaps had greatest beneficial impact on the health and wellbeing of Mankind. But ivermectin can also be considered alongside those worthy contenders, based on its versatility, safety and the beneficial impact that it has had, and continues to have, worldwide—especially on hundreds of millions of the world’s poorest people. Several extensive reports, including reviews authored by us, have been published detailing the events behind the discovery, development and commercialization of the avermectins and ivermectin (22,23-dihydroavermectin B), as well as the donation of ivermectin and its use in combating Onchocerciasis and lymphatic filariasis.1–6) However, none have concentrated in detail on the interacting sequence of events involved in the passage of the drug into human use. When it first appeared in the late-1970s, ivermectin, a derivative of avermectin (Fig. (Fig.1 )1 ) was a truly revolutionary drug, unprecedented in many ways. It was the world’s first endectocide, forerunner of a completely new class of antiparasitic agents, potently active against a wide range of internal and external nematodes and arthropods. In the early-1970s, a novel international Public Sector–Private Sector partnership was initiated by one of us (Ōmura, then head of the Antibiotics Research Group at Tokyo’s Kitasato Institute), forming a collaboration with the US-based Merck, Sharp and Dohme (MSD) pharmaceutical company. Under the terms of the research agreement, researchers at the Kitasato Institute isolated organisms from soil samples and carried out preliminary in vitro evaluation of their bioactivity. Promising bioactive samples were then sent to the MSD laboratories for further in vivo testing where a potent and promising novel bioactivity was found, subsequently identified as being caused by a new compound, which was named ‘avermectin’.7) Despite decades of searching around the world, the Japanese microorganism remains the only source of avermectin ever found.1) Originating from a single Japanese soil sample and the outcome of the innovative, international collaborative research partnership to find new antiparasitics, the extremely safe and more effective avermectin derivative, ivermectin, was initially introduced as a commercial product for Animal Health in 1981. It is effective against a wide range of parasites, including gastrointestinal roundworms, lungworms, mites, lice and hornflies.7–12) Ivermectin is also highly effective against ticks, for example, the ixodid tick Rhipicephalus (Boophilus) microplus, one of the most important cattle parasites in the tropics and subtropics, which causes enormous economic damage. Indicative of the impact, in Brazil, where some 80% of the bovine herd is infested, losses total about $2 billion annually.13) Today, ivermectin is being used to treat billions of livestock and pets around the world, helping to boost production of food and leather products, as well as keep billions of companion animals, particularly dogs and horses, healthy. The ‘Blockbuster’ drug in the Animal Health sector, meaning that it achieved annual sales in excess of over US$1 billion, maintained that status for over 20 years. It is so useful and adaptable that it is also being used off-label, sometimes, illegally, for example to treat fish lice in the aquaculture industry, where it can have a negative impact on non-target organisms. It also has extensive uses in agriculture.2) Figure 1. Molecular diagrams of avermectin and the di-hydro derivative, ivermectin. Ivermectin proved to be even more of a ‘Wonder drug’ in human health, improving the nutrition, general health and wellbeing of billions of people worldwide ever since it was first used to treat Onchocerciasis in humans in 1988. It proved ideal in many ways, being highly effective and broad-spectrum, safe, well tolerated and could be easily administered (a single, annual oral dose). It is used to treat a variety of internal nematode infections, including Onchocerciasis, Strongyloidiasis, Ascariasis, cutaneous larva migrans, filariases, Gnathostomiasis and Trichuriasis, as well as for oral treatment of ectoparasitic infections, such as Pediculosis (lice infestation) and scabies (mite infestation).14) Ivermectin is the essential mainstay of two global disease elimination campaigns that should soon rid the world of two of its most disfiguring and devastating diseases, Onchocerciasis and Lymphatic filariasis, which blight the lives of billions of the poor and disadvantaged throughout the tropics. It is likely that, throughout the next decade, well over 200 million people will be taking the drug annually or semi-annually, via innovative globally-coordinated Mass Drug Administration (MDA) programmes. Indeed, the discovery, development and deployment of ivermectin, produced by an unprecedented partnership between the Private Sector pharmaceutical multinational Merck & Co. Inc., and the Public Sector Kitasato Institute in Tokyo, aided by an extraordinary coalition of multidisciplinary international partners and disease-affected communities, has been recognized by many experts and observers as one of the greatest medical accomplishments of the 20th century.15) In referring to the international efforts to tackle Onchocerciasis in which ivermectin is now the sole control tool, the UNESCO World Science Report concluded, “the progress that has been made in combating the disease represents one of the most triumphant public health campaigns ever waged in the developing world”.16) Go to: 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. The parasites are transmitted via the bite of infected blackflies of the genus Simulium, which breed in highly-oxygenated, fast-flowing rivers and watercourses. In the human body, immature larval forms of the parasite create nodules in subcutaneous tissue, where they mature into adult worms. After mating, female worms can release up to 1000 microfilariae a day for some 10–14 years. These move through the body, and when they die they cause a variety of conditions, including skin rashes, lesions, intense itching, oedema and skin depigmentation (Fig. (Fig.2 ).2 ). Microfilariae also invade the eye, causing visual impairment and loss of vision, onchocerciasis being the second leading cause of blindness caused by an infectious disease.17) The disease causes visual damage for some 1–2 million people, around half of who will become blind.18) Open in a separate windowFigure 2. Mali: an old man, blinded by onchocerciasis, with leopard skin on his legs and nodules on his abdomen. Credit line: WHO/TDR/Crump. In the early-1970s, the disease was endemic in 34 countries: 27 in Africa; 6 in the Americas; and 1 in the Arabian Peninsula. The World Health Organization (WHO) later estimated that 17.7 million people were infected worldwide, of whom some 270,000 were blind, and another 500,000 severely visually disabled. The burden of onchocerciasis was particularly extreme in the hyper-endemic belt across sub-Saharan Africa. Communities in these areas exhibited high rates of visual disability caused by Onchocerciasis, up to 40% in some areas, which caused immeasurable negative impact on individual and community health, reducing economic capacity and productivity, and leading to the abandonment of fertile agricultural lands.19) By 1973, Onchocerciasis had been recognised by the then head of the World Bank, Robert McNamara, as a major disease of massive health and socioeconomic importance and one in dire need of combating in West Africa, and he became the key agent for change. In 1974, following international recognition of the dramatic consequences of disabling and disfiguring Onchocerciasis in Africa, four United Nations agencies, including the World Bank, launched the Onchocerciasis Control Programme in West Africa (OCP). The programme covered 1.2 million km2, protecting 30 million people in 11 countries from River Blindness. Go to: 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. Following the registration of ivermectin (produced under the brand name Mectizan®) for human use in 1987, in a hitherto unprecedented move and with unheralded commitment, Mectizan® was donated by the manufacturing company, Merck & Co. Inc., to treat onchocerciasis in all endemic countries for as long as it was needed. The resultant drug donation programme was the first, largest, longest running and most successful of all—and proved a model for all others that have followed. Ivermectin began to be distributed in 1988, with operations being organized through the independent Mectizan Donation Program (MDP) established and funded by Merck. Thereafter, OCP control operations changed from exclusive vector control to larviciding combined with ivermectin treatment or, in some areas, to ivermectin treatment alone. Ivermectin swiftly became the drug of choice for the treatment of Onchocerciasis due to its unique and potent microfilaricidal effects, the absence of severe side effects and its excellent safety. It is now the sole tool being used in disease elimination campaigns in the 16 other African countries where the disease exists, orchestrated by the African Programme for Onchocerciasis Control (APOC), which commenced operations in 1996. A single annual dose of 150 µg/kg of ivermectin, given orally, can reduce the level of skin microfilariae to zero and, by interfering with worm embryogenesis, can delay the build-up of new microfilariae for a period of up to two years. OCP was closed in December 2002 after virtually stopping disease transmission in all target nations except Sierra Leone where operations were hampered by civil war. The process, from the discovery of ivermectin’s activity against onchocercal microfilariae to the successful distribution programme from 1988 onward, was neither an easy or direct path. Success was achieved through groundbreaking and innovative partnerships. The journey was a complex undertaking, incorporating scientific uncertainty, conflicting views, ambiguity, frustration, individual innovation and unexpected twists and turns. The actual discovery of ivermectin was an international team effort involving a unique, pioneering Public Sector/Private Sector partnership and the commitment and vision of several key individuals. Ivermectin’s development into a drug for human use also involved a number of organizational, individual and pharmacological variables—together with a large slice of luck, educated insight and personal commitment. Go to: Development of ivermectin for human use In the mid-1970s, the global community mobilized itself to address the major problems of neglected tropical diseases. Following the setting up of the OCP in 1974, the UN-based Special Programme for Research & Training in Tropical Diseases (TDR) was established in 1975.20) Onchocerciasis, one of two filarial infections among TDR’s eight target diseases, was at that time a major public health problem affecting 20–40 million people in endemic areas. At exactly this time, a specialized novel anthelmintic mouse screening model in Merck’s research laboratories was identifying the avermectins in the microbial sample sent by the Kitasato Institute, of which ivermectin would become the most successful derivative. At the time, there were no safe and acceptable drugs available to treat Onchocerciasis, which had plagued Africa for centuries, effectively leading to the creation of the OCP and its vector control focus. TDR quickly found that, despite many pharmaceutical companies, such as Bayer, Hoffman-LaRoche, CIBA-Geigy and Rhône-Poulenc, carrying out routing screening for filaricidal compounds, no companies were interested in developing suitable anti-Onchocerca drugs, as there was no apparent commercial market. Worse still, Onchocerca species would not develop to maturity in any rodents, making it impossible to screen compounds in an animal model against the target organism.21) It had been shown that O. volvulus could infect chimpanzees (Pan troglodites) but it was deemed unethical to use these animals for the necessary large-scale research, even though some testing of compounds was undertaken.22,23) Consequently, the OCP opted to devote operations to aerial larviciding via helicopters and small fixed-wing planes. It was a very ‘vertical’ programme, mainly coordinated through the World Bank and other UN agencies, with multimillion dollar contracts given to a US-based helicopter company and to an American chemical company for the insecticides. Meanwhile, with respect to research needs, TDR had identified six specific areas that required special attention, with the discovery of effective and safe chemotherapeutic agents considered to be the highest priority. In 1975, only two drugs were available for the treatment of onchocerciasis: diethylcarbamazine (DEC) and suramin. The use of both was highly unsatisfactory. DEC, which was known to kill microfilariae, caused violent and even dangerous hypersensitivity reactions in the human host. Suramin, developed 50 years previously for treatment of Sleeping Sickness, was the only drug considered for killing adult worms but was highly toxic, often causing severe and occasionally fatal reactions. Moreover, parasitological cure of patients using DEC and suramin required lengthy and expensive treatment given under medical supervision. Therefore, the TDR Scientific Working Group (SWG), composed of leading independent scientists in the field from around the globe, including industry, decided that the priority was a new and non-toxic macrofilaricide (to kill adult worms), a macrofilaricide being determined to be substantially preferable to a microfilaricide (which would target immature worms).24) At the first meeting of TDR’s Filariasis Scientific Steering Committee in 1976, it was reported that Programme staff had visited 16 major pharmaceutical companies but had found none actively working on onchocerciasis. Nor was there any validated model for screening. The Committee agreed that the high cost of maintaining screening facilities for drugs against tropical diseases was a significant deterrent to industrial involvement.25) TDR acted to rectify this situation and thereby engage industry in the search for a new drug. Unfortunately, O. volvulus parasites can only develop fully in humans and a few primates. Fortunately, the closest relative to the human parasite is O. ochengi, found in cattle, which is restricted to Africa and which is also transmitted by the same vector. The O. ochengi cattle model thus facilitated experimental studies, in the field and laboratory-based, that were not possible in humans, leading to detailed knowledge of the parasite’s life cycle (Fig. (Fig.3 ).3 ). From 1977 on, TDR provided technical and financial support to establish a comprehensive screening system for Onchocercal filaricides. The Programme identified five academic and private research institutions with technical capacities and facilities for primary and secondary screens: the University of Georgia (USA), University of Giessen (Germany), the Wellcome Foundation (UK), the London School of Hygiene and Tropical Medicine (UK) and the University of Tokyo (Japan). TDR provided some US$2.25 million to these Public Sector institutions for primary and secondary screening of compounds, while pressing pharmaceutical companies to donate compounds for testing with the promise of full confidentiality. Additionally, TDR established a unique tertiary screen, using cattle, for compounds showing positive results in any secondary screen. Based at the James Cook University of North Queensland, Australia, the screen, costing almost US$435,000, was the best predictor of what a compound would do in humans. Some 10,000 compounds, many supplied by leading pharmaceutical companies as coded samples, passed through the screening network, including several from Merck.26) | | | | | | | | | | | Ivermectin, ‘Wonder drug’ from Japan: the human use perspective Discovered in the late-1970s, the pioneering drug ivermectin, a dihydro derivative of avermectin—originating sol... | | | | | | | | | | | | | | Ivermectin, ‘Wonder drug’ from Japan: the human use perspective Discovered in the late-1970s, the pioneering drug ivermectin, a dihydro derivative of avermectin—originating sol... | | | [partial quote ends]