Proguanil Hydrochloride

Researchers looking to develop a long-acting, injectable malaria preventive using atovaquone have shown in a new study that resistance may not be the challenge scientists thought it was, particularly when using atovaquone as a malaria preventive. Malaria parasites in infected patients being treated with atovaquone tend to develop a resistance to the drug. Because of this, atovaquone by itself is not used as a malaria treatment nor has not been seen as a strong candidate for use as a preventive.  Johns Hopkins researchers looking to develop a long-acting, injectable malaria preventive using atovaquone have shown in a new study that resistance may not be the challenge scientists thought it was, particularly when using atovaquone as a malaria preventive. Malaria parasites in infected patients being treated with atovaquone tend to develop a resistance to the drug. Because of this, atovaquone by itself is not used as a malaria treatment nor has not been seen as a strong candidate for use as a preventive. The study, led by a team of researchers at the Johns Hopkins Malaria Research Institute and the Johns Hopkins University School of Medicine, in conjunction with colleagues at the University of Liverpool, was published online October 12 in Nature Communications. The Malaria Research Institute is based at the Johns Hopkins Bloomberg School of Public Health. In their study, the researchers found that the same genetic mutation that renders malaria parasites resistant to atovaquone in patients also destroys the parasite's ability to live within mosquito hosts -- meaning atovaquone-resistant malaria parasites would not be transmissible. The researchers concluded that atovaquone, despite concerns over resistance, holds promise as a long-acting, injectable "chemical vaccine" that could prevent infection in malaria-endemic areas. "These findings should reduce concerns about the transmission of atovaquone resistance with atovaquone therapy, particularly when it is used as a chemical vaccine," says study senior author Theresa Shapiro, MD, PhD, professor of Clinical Pharmacology in the Johns Hopkins University School of Medicine and professor in the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Bloomberg School. Malaria continues to be a major global health burden. According to the World Health Organization, the mosquito-borne parasitic disease afflicted nearly a quarter of a billion people in 2021, killing more than 600,000. Researchers generally agree that, despite the impact of insecticides and other malaria control measures, and the recent development of a malaria vaccine, new approaches against this deadly parasitic pathogen are needed. One new approach, described by Shapiro and colleagues at the University of Liverpool in a 2018 preclinical study, would use an injectable, slow-release formulation of atovaquone to provide vaccine-like protection for weeks at a time. Atovaquone is generally considered safe for long-term use even at higher doses, and has the further advantage that it interrupts the malaria life-cycle in human hosts even at the pre-symptomatic stage, when the parasite is developing in liver cells. However, when atovaquone is used not as a preventive but as a treatment for symptomatic malaria infection, it often fails due to the emergence of genetically acquired resistance. Shapiro notes that by the time an infection is symptomatic, it involves billions of individual malaria organisms, and in this vast population it is likely that a resistance mutation will appear, if only by random genetic variation. Under atovaquone treatment, parasites with this mutation will come to dominate the infection. Because of the resistance problem, atovaquone is used to treat malaria only in combination with another antimalarial called proguanil. Resistance should be much less likely when using atovaquone as a preventive in people who are malaria-free, Shapiro says. The drug in such cases would be acting against a far smaller number of individual parasites that are only in the early, liver-infection stage. "In fact, there are no reported cases of atovaquone resistance when the drug has been given prophylactically," she says. Nevertheless, fear of resistance has left a cloud over the drug's use even as a preventive. Indeed, there have been concerns that the mutation, once it emerged -- for example, in a large population treated prophylactically with atovaquone -- could spread via human-to-mosquito-to-human transmission. In the study, Shapiro's team examined the resistance problem, focusing on a key resistance mutation, cytochrome-b Y268S, that has been found in clinical investigations involving the major malaria parasite of concern, Plasmodium falciparum. The researchers confirmed that P. falciparum parasites carrying this mutation are thousands of times less susceptible to atovaquone, compared to unmutated parasites. However, the scientists also found that the Y268S mutation, while it enables P. falciparum to survive in human hosts being treated with atovaquone, essentially destroys its ability to live within its Anophelesmosquito hosts. This means that atovaquone-resistant mutant parasites cannot spread via transmission from humans to mosquitoes and back again -- as the researchers demonstrated using mosquitoes and a P. falciparum-infectable mouse model. For the study, the mice were engrafted with human liver cells and human red blood cells. "Testing the mutant parasites for their ability to infect humanized mice is the best in vivo assay we have short of using humans, and strongly supports the inability of drug-resistant parasites to be transmitted by mosquitoes," says Photini Sinnis, MD, deputy director at the Johns Hopkins Malaria Research Institute and one of the paper's senior authors. The findings suggest that a "chemical vaccine" strategy for protecting people from malaria with atovaquone remains viable and should continue to be investigated. Shapiro and colleagues are collaborating with Andrew Owen, PhD, a professor at the University of Liverpool, and his team to complete preclinical studies and launch a Phase I trial. Owen is principal investigator for LONGEVITY, an international project funded by Unitaid that aims to translate long-acting medicines for malaria and other diseases that disproportionately affect people in low- and middle-income countries. "Many advances in malaria medicines that have started at small scale for the protection of travelers, later see wider use in endemic areas where they are most needed -- and this may be the path atovaquone takes as a chemical vaccine," Shapiro says. The study's first author was Victoria Balta, PhD, a graduate student working with coauthor David Sullivan, MD, a professor in the Bloomberg School's Department of Molecular Microbiology and Immunology.

Increase in incidence of malaria, rise in healthcare expenditure worldwide, and presence of large number of pipeline products fuel the growth of the global antimalarial drugs market. According to the report published by Allied Market Research, the global antimalarial drugs market was estimated at $711,360 thousand in 2018 and is expected to hit at $1,019,396 thousand by 2026, registering a CAGR of 4.6% from 2019 to 2026. Rise in prevalence of malaria, increase in healthcare expenditure worldwide and presence of large number of pipeline products propel the growth of the global antimalarial drugs market. Conversely, poor demand in underdeveloped countries curtails down the growth to some extent. Nevertheless, development in emerging economies is expected to create lucrative opportunities in the near future. Request Sample Report at: Covid-19 Scenarios- However, certain studies showed that the use of antimalarial drugs on some patients has increased the risks of hazardous disturbances. The demand and manufacturing of antimalarial drugs have been dramatically increased during the initial phase of Covid-19, as antimalarial drugs were believed to be effective in treating novel coronavirus. Malaria is a deadly infectious disease, which is transmitted through the bite of female Anopheles mosquito. The infection spreads to liver cells where the parasites multiply at a fast rate to invade red blood cells. These parasites further grow and mature in red blood cells to form merozoites, which are released upon the rupture of red blood cells to invade other blood cells. This leads to fever, tiredness, vomiting, headaches, impaired consciousness, multiple convulsions, and abnormal bleeding. Hence, the drugs which are employed in the treatment of malarial infection are called as antimalarial drugs. There are different types of antimalarial drugs such as quinine, chloroquine, proguanil, mefloquine, pyrimethamine, and others available in the market. The global antimalarial drugs market is segmented on the basis of drug class, distribution channel, and region. Based on drug class, the quinine segment contributed to more than one-fifth of the global antimalarial drugs market revenue in 2018. In addition the segment is expected to maintain its dominance by the end of 2026. The same segment would also portray the fastest CAGR of 4.7% during the study period. This is attributed to the fact that quinine is widely used for malaria treatment. Based on distribution channel, the retail pharmacy segment held the major share in 2018, garnering more than three-fifths of the global antimalarial drugs market. This is owing to the strong presence of retail pharmacies around the globe and convenience offered by them. However, the e-commerce websites and online drug stores segment would grow at the fastest CAGR of 5.9% throughout the forecast period. This is due to rise in preference for online purchasing of drugs over the traditional methods, increase in awareness of online pharmacy, and rise in number of internet users. Based on region, LAMEA accounted for 94% of the total market revenue in 2018, and is projected to maintain the lion’s share till 2026. Simultaneously, the Asia-Pacific region would manifest the fastest CAGR of 5.6% from 2019 to 2026. The other provinces analyzed in the market report take in Europe and North America. Access Full Report: The Major Key Players Are: Alvizia Healthcare Pvt. Ltd., Bayer AG, F. Hoffmann-La Roche Ltd, GlaxoSmithKline Plc, Ipca Laboratories Ltd., Merck & Co., Inc, Novartis AG, Pfizer Inc., Sun Pharmaceutical Industries Ltd. (Ranbaxy Laboratories), and Zydus Cadila. 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