- Email: [email protected]
Newer Antiparasitic Agents
Journal of Patient Safety & Infection Control 1 (2013) 27–28
Journal of Patient Safety & Infection Control
Review Article
Newer Antiparasitic Agents Namita Jaggi1,*
Head-Lab Services, Senior Consultant Microbiology and Chair-Infection Control, Artemis Hospital, Gurgaon
K E Y W O R D S
A B S T R A C T
Parasitic infections, leishmaniasis, malaria.
Development of drug resistance, insecticide resistance and appearance of newer antiparasitic strains are some of the current challenges being faced by healthcare professionals in the field of parasitology. Highlighting the opportunities for antiparasitic drug discovered and the progress in recent years is the main objective of this review. Very few antiparasitic drugs have been discovered in the recent past, as compared to the other drugs of the pharmaceutical industry. Public-private partnerships have proven beneficial in providing funds to some parasite-focused projects. Some countries, especially the poor, undeveloped still have a problem due to the neglect of certain parasitic diseases which are unique to their epidemiology. There is a need to change prescribing patterns of clinicians, promote research in anti-parasitic drugs, and increase awareness of infection prevention and control in order to minimize the spread of parasitic diseases especially as newer anti-parasitic agents are scarce on the horizon. Copyright © 2013, Hospital Infection Society–India. All rights reserved.
There are approximately 5 billion people across the World living with parasitic infections. Majority them live in countries where the prospects of any financial return on investment are too low to support market-driven drug discovery and development of new drugs for these diseases. Development of drug resistance, insecticide resistance, appearance of new parasitic strains, emerging and re-emerging parasitic infections and animal parasites gaining importance as human pathogens are few of the challenges for health professionals for ultimate control of these diseases.1 The clinical effects of parasitic infections are aggravated by concurrent disease, poor sanitation, and impaired immune system and make it a challenge to treat/remove infection without harming the host. In this article, challenges and opportunities for antiparasitic drug discovery are considered, highlighting some of the progress that has been made in recent years, partly through scientific advances, but also by more effective partnership between the public and private sectors. The present scenario of antiparasitic drugs consists of Thiabendazole, Pyrantel pamoate, Mebendazole, Praziquantel, Niclosamide, Bithionol, Oxamniquine, Metrifonate,
*Corresponding author: Tel: +91 (0) 9716822224 E-mail address: [email protected] (Namita Jaggi) ISSN: 2214–207X Copyright © 2013. Hospital Infection Society–India. All rights reserved.
Ivermectin, Albendazole, Benznidazole, Nifurtimox, Nitroimidazole etc.2 We are lagging far behind in discovery of antiparasitic drugs as compared to other antimicrobial drugs as only 3 new anti-malarial drugs were discovered in past 20 years. On the contrary, over 1,200 new drugs approved by FDA in that timeframe. Moreover, of more than 1,300 new drugs introduced for all indications between 1975 and 1999, only 13 were for Tropical diseases. In 2000, only about 0.1% of global investment in health research was devoted to drug discovery for selected tropical diseases (malaria, leishmaniasis and trypanosomiasis) and tuberculosis, which together contribute about 5% of the global disease burden. Four antiparasitic drugs: Atovaquone/proguanil (Malarone) and artemether (malaria), Eflornithine and nifurtimox (trypanosomiasis) were discovered in last two decades. Metronidazole, Nitazoxanide (giardiasis) and Secnidazole (trichomoniasis), Sodium stibogluconate (SSG) (leishmaniasis).3–5 The other new drug discoveries include Nitazoxanide and Ivermectin as broad spectrum antiparasitic agents. Nitazoxanide is effective against giardiasis, intestinal helminthes, tape worms, Cryptosporidium parvum as well as chronic fascioliasis producing low side effects.6 Ivermectin (belongs to class of anthelmintics) is used to treat onchocerciasis, strongyloidiasis, ascariasis, trichuriasis,
28
Namita Jaggi / Journal of Patient Safety & Infection Control (2013) 27–28
filariasis and enterobiasis. Changing scenario of various parasitic diseases, especially in view of the problem of drug resistance in leishmaniasis and malaria have been studied at length. Against leishmaniasis, single-dosage administrations of liposomal amphotericin B have been shown to be effective, and oral formulations are currently under development to increase access and facilitate distribution of the efficacious drug in the field. Recent clinical trials of miltefosin and paromycin for the treatment of leishmaniasis are expected to overcome the public health problem in the state of Bihar, West Bengal and eastern Uttar Pradesh. The need for the development of malaria vaccine is emphasized as Plasmodium falciparum is showing resistance to all the drugs presently available for the treatment of malaria and no new drugs are likely to be available in near future. Several welcome developments during the past few years have given new impetus to antiparasitic drug discovery. These include the publiclyfunded sequencing of the genomes of parasites and the establishment of new public–private partnerships (PPPs) whose focus is specifically on tropical diseases counteracting, to some extent, the withdrawal of many large pharmaceutical companies from direct involvement in antiparasitic drug discovery.7 The injection of new funds into the area of antiparasite research, particularly by the Bill and Melinda Gates Foundation, is also having a significant impact. Some PPPs currently involved in antiparasite drug discovery are the Medicines for Malaria Venture (MMV), the Drugs for Neglected Diseases initiative (DNDi) and the Institute for One World Health (IOWH). Most areas that still have problems with parasites are the poor, underdeveloped countries where not much research is going on for the development of new drugs because pharmaceutical companies would not make a profit on drugs, much less break even. Strategies for combating this problem are to develop drugs that have both commercial markets in the
west, as well as applications against a neglected parasite disease in poorer areas and to develop new drugs at academic institutions. Most of the anti-parasitic drugs work by blocking critical metabolic pathways like Krebs cycle whereas few are parasite specific. New drugs are needed as effective vaccines are unavailable, drugs are often toxic and resistance is mounting. The potential for misuse of drugs include prescribing antimalarials for fevers due to inappropriate diagnosis leads to mass prescribing of antiprotozoals.8 This misuse of drugs needs to be prevented as it may lead to resistance and toxicity. The road ahead is to change prescribing patterns of clinicians, promote research in antiparasitic drugs and increase awareness of infection prevention and control.
REFERENCES 1.
2. 3.
4.
5.
6. 7. 8.
Pérez JL, Carranza C, Mateos F. Antiparasitic drugs. Review of the useful drugs in the treatment of classic and emergent parasitic diseases. Rev Esp Quimioter 2009;22:93–105. Liu LX, Weller PF. Antiparasitic drugs. N Engl J Med 1996;334:1178–84. Antimalarial Drug Combination Therapy. Report of a WHO Technical Consultation. World Health Organization, Geneva WHO, 2001. Nègre E, Chance ML, Hanboula SY, et al. Antileishmanial drug targeting through glycosylated polymers specifically internalized by macrophage membrane lectins. Antimicrob Agents Chemother 1992;36:2228–32. Siqueira-Neto JL, Song O-R, Oh H, Sohn J-H, et al. Antileishmanial high-throughput drug screening reveals drug candidates with new scaffolds. PLoS Negl Trop Dis 2010;4:e675. White AC, Jr. Nitazoxanide: a new broad spectrum antiparasitic drug. Expert Rev Anti-Infect Ther 2004;2:43–50. Geary TC, Thompson DP. Development of antiparasitic drugs in the 21st century. Veterinary Parasitology 2003;115:167–84. Pink R, Hudson A, Mouriès M-A, et al. Opportunities and challenges in antiparasitic drug discovery. Nature Reviews Drug Discovery 2005;4:727–40.
Journal of Patient Safety & Infection Control
Review Article
Newer Antiparasitic Agents Namita Jaggi1,*
Head-Lab Services, Senior Consultant Microbiology and Chair-Infection Control, Artemis Hospital, Gurgaon
K E Y W O R D S
A B S T R A C T
Parasitic infections, leishmaniasis, malaria.
Development of drug resistance, insecticide resistance and appearance of newer antiparasitic strains are some of the current challenges being faced by healthcare professionals in the field of parasitology. Highlighting the opportunities for antiparasitic drug discovered and the progress in recent years is the main objective of this review. Very few antiparasitic drugs have been discovered in the recent past, as compared to the other drugs of the pharmaceutical industry. Public-private partnerships have proven beneficial in providing funds to some parasite-focused projects. Some countries, especially the poor, undeveloped still have a problem due to the neglect of certain parasitic diseases which are unique to their epidemiology. There is a need to change prescribing patterns of clinicians, promote research in anti-parasitic drugs, and increase awareness of infection prevention and control in order to minimize the spread of parasitic diseases especially as newer anti-parasitic agents are scarce on the horizon. Copyright © 2013, Hospital Infection Society–India. All rights reserved.
There are approximately 5 billion people across the World living with parasitic infections. Majority them live in countries where the prospects of any financial return on investment are too low to support market-driven drug discovery and development of new drugs for these diseases. Development of drug resistance, insecticide resistance, appearance of new parasitic strains, emerging and re-emerging parasitic infections and animal parasites gaining importance as human pathogens are few of the challenges for health professionals for ultimate control of these diseases.1 The clinical effects of parasitic infections are aggravated by concurrent disease, poor sanitation, and impaired immune system and make it a challenge to treat/remove infection without harming the host. In this article, challenges and opportunities for antiparasitic drug discovery are considered, highlighting some of the progress that has been made in recent years, partly through scientific advances, but also by more effective partnership between the public and private sectors. The present scenario of antiparasitic drugs consists of Thiabendazole, Pyrantel pamoate, Mebendazole, Praziquantel, Niclosamide, Bithionol, Oxamniquine, Metrifonate,
*Corresponding author: Tel: +91 (0) 9716822224 E-mail address: [email protected] (Namita Jaggi) ISSN: 2214–207X Copyright © 2013. Hospital Infection Society–India. All rights reserved.
Ivermectin, Albendazole, Benznidazole, Nifurtimox, Nitroimidazole etc.2 We are lagging far behind in discovery of antiparasitic drugs as compared to other antimicrobial drugs as only 3 new anti-malarial drugs were discovered in past 20 years. On the contrary, over 1,200 new drugs approved by FDA in that timeframe. Moreover, of more than 1,300 new drugs introduced for all indications between 1975 and 1999, only 13 were for Tropical diseases. In 2000, only about 0.1% of global investment in health research was devoted to drug discovery for selected tropical diseases (malaria, leishmaniasis and trypanosomiasis) and tuberculosis, which together contribute about 5% of the global disease burden. Four antiparasitic drugs: Atovaquone/proguanil (Malarone) and artemether (malaria), Eflornithine and nifurtimox (trypanosomiasis) were discovered in last two decades. Metronidazole, Nitazoxanide (giardiasis) and Secnidazole (trichomoniasis), Sodium stibogluconate (SSG) (leishmaniasis).3–5 The other new drug discoveries include Nitazoxanide and Ivermectin as broad spectrum antiparasitic agents. Nitazoxanide is effective against giardiasis, intestinal helminthes, tape worms, Cryptosporidium parvum as well as chronic fascioliasis producing low side effects.6 Ivermectin (belongs to class of anthelmintics) is used to treat onchocerciasis, strongyloidiasis, ascariasis, trichuriasis,
28
Namita Jaggi / Journal of Patient Safety & Infection Control (2013) 27–28
filariasis and enterobiasis. Changing scenario of various parasitic diseases, especially in view of the problem of drug resistance in leishmaniasis and malaria have been studied at length. Against leishmaniasis, single-dosage administrations of liposomal amphotericin B have been shown to be effective, and oral formulations are currently under development to increase access and facilitate distribution of the efficacious drug in the field. Recent clinical trials of miltefosin and paromycin for the treatment of leishmaniasis are expected to overcome the public health problem in the state of Bihar, West Bengal and eastern Uttar Pradesh. The need for the development of malaria vaccine is emphasized as Plasmodium falciparum is showing resistance to all the drugs presently available for the treatment of malaria and no new drugs are likely to be available in near future. Several welcome developments during the past few years have given new impetus to antiparasitic drug discovery. These include the publiclyfunded sequencing of the genomes of parasites and the establishment of new public–private partnerships (PPPs) whose focus is specifically on tropical diseases counteracting, to some extent, the withdrawal of many large pharmaceutical companies from direct involvement in antiparasitic drug discovery.7 The injection of new funds into the area of antiparasite research, particularly by the Bill and Melinda Gates Foundation, is also having a significant impact. Some PPPs currently involved in antiparasite drug discovery are the Medicines for Malaria Venture (MMV), the Drugs for Neglected Diseases initiative (DNDi) and the Institute for One World Health (IOWH). Most areas that still have problems with parasites are the poor, underdeveloped countries where not much research is going on for the development of new drugs because pharmaceutical companies would not make a profit on drugs, much less break even. Strategies for combating this problem are to develop drugs that have both commercial markets in the
west, as well as applications against a neglected parasite disease in poorer areas and to develop new drugs at academic institutions. Most of the anti-parasitic drugs work by blocking critical metabolic pathways like Krebs cycle whereas few are parasite specific. New drugs are needed as effective vaccines are unavailable, drugs are often toxic and resistance is mounting. The potential for misuse of drugs include prescribing antimalarials for fevers due to inappropriate diagnosis leads to mass prescribing of antiprotozoals.8 This misuse of drugs needs to be prevented as it may lead to resistance and toxicity. The road ahead is to change prescribing patterns of clinicians, promote research in antiparasitic drugs and increase awareness of infection prevention and control.
REFERENCES 1.
2. 3.
4.
5.
6. 7. 8.
Pérez JL, Carranza C, Mateos F. Antiparasitic drugs. Review of the useful drugs in the treatment of classic and emergent parasitic diseases. Rev Esp Quimioter 2009;22:93–105. Liu LX, Weller PF. Antiparasitic drugs. N Engl J Med 1996;334:1178–84. Antimalarial Drug Combination Therapy. Report of a WHO Technical Consultation. World Health Organization, Geneva WHO, 2001. Nègre E, Chance ML, Hanboula SY, et al. Antileishmanial drug targeting through glycosylated polymers specifically internalized by macrophage membrane lectins. Antimicrob Agents Chemother 1992;36:2228–32. Siqueira-Neto JL, Song O-R, Oh H, Sohn J-H, et al. Antileishmanial high-throughput drug screening reveals drug candidates with new scaffolds. PLoS Negl Trop Dis 2010;4:e675. White AC, Jr. Nitazoxanide: a new broad spectrum antiparasitic drug. Expert Rev Anti-Infect Ther 2004;2:43–50. Geary TC, Thompson DP. Development of antiparasitic drugs in the 21st century. Veterinary Parasitology 2003;115:167–84. Pink R, Hudson A, Mouriès M-A, et al. Opportunities and challenges in antiparasitic drug discovery. Nature Reviews Drug Discovery 2005;4:727–40.