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Principal Investigator: JOHN M HAWDON
Organization: GEORGE WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $201,652
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract: Parasitic nematode (PN) infections remain a major threat to human health globally. More than 1.5
billion people are infected with PNs, with children, pregnant women, and the elderly especially susceptible to
morbidity from nematode infection. Control strategies are restricted to periodic de-worming of infected
individuals, which is limited by rapid re-infection rates and the inevitable development of drug resistant worm
populations. There are currently no vaccines available for human PN infections. Therefore, there is a clear and
pressing need for new drugs to treat PN infections to forestall the emergence of resistant isolates. Of the PNs
infecting humans, hookworms are arguably the most important due to their voracious blood feeding activities.
The Center for Disease Control and Prevention estimates that hookworm currently infects 576-740 million
people worldwide. Infection may cause anemia and protein deficiency, causing gastrointestinal health
problems generally and retarded growth and cognitive development in children. The bitter melon Momordica
charantia is widely grown in areas where hookworm is endemic, and has been used as a traditional medicine
for parasitic infections and other disease in developing countries. Aqueous extracts of M. charantia (MCE)
have been shown to inhibit feeding of infective hookworm larvae (L3) and to kill adult and L4 hookworm in
vitro, as well as several other nematodes. Chemical identification and characterization of the biologically active
component(s) may lead to development of a drug to treat hookworm and other PN infections. Here we propose
to isolate the active anthelmintic compound(s) from M. charantia using mortality of the hookworm
Ancylostoma ceylanicum to screen fractions. In Aim 1, we will use natural product chemistry to separate the
active component(s) from the rest of the plant material and a bioassay to identify the active anthelmintic
compund(s) within MCE. In Aim 2, we will determine if the isolated anthelmintic can successfully treat
hookworm infections in vivo. Identifying the active components of MCE that are responsible for the plant’s
remarkable anthelmintic activity and confirming its in vivo activity may lead to the development of a new
anthelmintic for the treatment of hookworm and other PNs.
Terms: <0-11 years old><21+ years old><Adult><Adult Human><Albendazole><Ancylostoma><Ancylostoma (genus)><Ancylostoma caninum><Ancylostomatidae><Anemia><Anthelmintics><Antihelminthic Agent><Antihelminthic Drugs><Area><Assay><Bioassay><Biological Assay><Bitter Gourd><Bleeding><Blood><Blood Reticuloendothelial System><Botanical medicine><C elegans><C. elegans><C.elegans><Caenorhabditis elegans><Canine Species><Canis familiaris><Centers for Disease Control><Centers for Disease Control and Prevention><Centers for Disease Control and Prevention (U.S.)><Cessation of life><Chemical Structure><Chemicals><Child><Child Youth><Children (0-21)><Communicable Diseases><Cricetinae><Data><Death><Developing Countries><Developing Nations><Development><Disease><Disorder><Dogs><Dogs Mammals><Dose><Drug resistance><Drugs><Elderly><Ensure><Esophagus><Exhibits><Exposure to><Farm Animal><Food><Future><Goals><Growth and Development><Growth and Development function><Haiti><Hamsters><Hamsters Mammals><Health><Health Benefit><Hemorrhage><Hookworm Infections><Hookworms><Human><In Vitro><Individual><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Ingestion><Intestinal><Intestines><Iron deficiency anemia><Jamaica><Karela><Larva><Lead><Less-Developed Countries><Less-Developed Nations><Livestock><M Components><Measures><Medication><Medicinal Plants><Medicine><Melons><Modern Man><Momordica charantia><Morbidity><Morbidity - disease rate><Myeloma Proteins><Natural Products Chemistry><Nematoda><Nematode infections><Nematodes><Oral Administration><Oral Drug Administration><Parasitic infection><Parasitic nematode><Pb element><Periodicals><Persons><Pharmaceutical Preparations><Phytomedicines><Phytotherapeutics><Plant Extracts><Plant Leaves><Plants><Population><Predisposition><Pregnant Women><Proliferating><Protein Deficiency><Pump><Resistance><Rest><Safety><Source><Spectrometry><Susceptibility><Tea><Techniques><Testing><Third-World Countries><Third-World Nations><Toxic effect><Toxicities><Traditional Medicine><Under-Developed Countries><Under-Developed Nations><United States Centers for Disease Control><United States Centers for Disease Control and Prevention><Vermifuges><access to vaccination><access to vaccines><adulthood><advanced age><antihelminthic><aqueous><blood loss><bowel><canine><cognitive development><deficiency of protein><developing country><developing nation><developmental><domestic dog><drug development><drug resistant><drug/agent><expectant mother><expecting mother><feeding><gastrointestinal><geriatric><global health><heavy metal Pb><heavy metal lead><high reward><high risk><in vivo><infection rate><ingest><intraoral drug delivery><kids><leaf><mortality><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><parasite infection><parasitic roundworm><periodic><periodical><pregnant mothers><programs><rate of infection><resistance to Drug><resistant><resistant to Drug><roundworm><roundworm infection><senior citizen><tool><vaccination access><vaccination availability><vaccine access><vaccine availability><youngster>