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UIC PCOL 425 - Anthelminthic and antifungal Agents

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EpidemiologyPhysiology & Clinical ManifestationsDiagnosisEpidemiologyPhysiology & Clinical ManifestationsDiagnosisPhysiology & Clinical ManifestationsPhysiology & Clinical ManifestationsPhysiology & Clinical ManifestationsPCOL425 Medical Pharmacology Lecture (Part II)Anthelminthic and Antifungal AgentsBy Prof. A.H. ChishtiPhone: 312-355-1293E-mail: [email protected]: COMRB 5097Recognize clinically important helminths, with particular emphasis on epidemiology, physiology, clinical manifestations, and diagnosis.HELMINTHS (WORMS)(1) Nematodes (round worms)(2) Cestodes (tapeworms)(3) Trematodes (flukes)(1) Nematodes: (round worms)Enterobius vermicularis (pinworm)Ascaris lumbricoidesTrichuris trichiura (whipworm)Ancylostoma duodenale and Necator americanus (hookworms)Strongyloides stercoralisTrichinella spiralis• Enterobius vermicularis (pinworm)EpidemiologyE. vermicularis occurs worldwide but is most common in the temperate regions, where person-to-person spread is greatest in crowded conditions such as day-care centers, schools, and mental institutions. It is the most common helminthic infection in the U.S.Physiology & Clinical ManifestationsInfection is initiated by ingestion of embryonated eggs. Larvae hatch in the small intestine and migrate to the large intestine, where they mature into adults (small, white worm, 8-13 mm long) in 2 to 6 weeks. Fertilization of the female by the male produces the characteristic asymmetrical eggs. The eggs are laid in the perianal folds. As many as 20,000 eggs are deposited on the perianal skin. The eggs rapidly mature and are infectious within hours. Many children and adults have no symptoms and serve only as carriers. Patients who are allergic to the secretions of the migrating worms experience severe pruritus, loss of sleep, and fatigue. The pruritis may cause repeated scratching of the irritated area and lead to secondary bacterial infection.DiagnosisThe diagnosis of enterobiasis is usually suggested by the clinical manifestations and confirmed by detectionof the characteristic eggs on the anal mucosa. The method of choice for diagnosis is the “Scotch tape” test. The sticky side of a piece of transparent tape is pressed on the perianal skin. The tape is applied to a glassslide and examined under a microscope for the characteristically shaped eggs. The ova measure approximately 30 x 50 um in size and have a thin, smooth, transparent shell, are oval in outline, asymmetric, with one side flattened. Yield is greatest if the test is performed early in the morning when worm migration is maximal.• Ascaris lumbricoidesEpidemiologyAscaris lumbricoides is prevalent in areas where sanitation is poor and human feces are used as fertilizer. Ascaris is the most common helminth worldwide, with an estimated 1 billion people infected.Physiology & Clinical ManifestationsAscaris lumbricoides are large (20 to 35 cm in length), pink worms. The ingested infective egg releases a larval worm that penetrates the duodenal wall, enters the bloodstream, is carried to the liver and heart, and then enters the pulmonary circulation. The larvae break free in the alveoli of the lungs, where they grow and molt. In about 3 weeks, the larvae pass from the respiratory system to be coughed up, swallowed, and returned to the small intestine. As male and female worms mature in the small intestine, fertilization of the female by the male initiates egg production, which may amount to 200,000 eggs per day for as long as a year. Eggs are found in the feces 60-75 days after the initial infection. Fertilized eggs become infectious after 2 weeks in the soil.Infections caused by the ingestion of only a few eggs may produce no symptoms. After infection with manylarvae, migration of worms to the lungs may produce pneumonitis resembling an asthmatic attack. Also, a tangled bolus of mature worms in the intestine can results in obstruction, perforation, and occlusion of the appendix. Migration into the bile duct, gallbladder, and liver can produce severe tissue damage. Patients with many larvae may also experience abdominal tenderness, fever, distention, and vomiting. Eosinophilia is common.DiagnosisExamination of stool reveals the knobby-coated, bile-stained, fertilized or unfertilized eggs. Eggs are oval, 55-75 um long and 50 um wide. The thick-walled outer shell can be partially removed (decorticated egg). Decorticated eggs have had prolonged exposure to pancreatic secretions that remove the outer coat.• Strongyloides stercoralisEpidemiologyS. stercoralis prefers warm temperatures and moisture, but has a geographic distribution that includes both the northern and southern parts of the U.S. Physiology & Clinical ManifestationsLike hookworms, S. stercoralis larvae penetrate the skin and enter the circulation and follow the pulmonarycourse. It is coughed up and swallowed, and adults develop in the small intestine. Adult females burrow into the mucosa of the duodenum and reproduce parthenogenetically. Each female produces about a dozen eggs each day, which hatch within the mucosa and release rhabditiform larvae into the lumen of the bowel. The rhabditiform larvae are distinguished from the larvae of hookworms by their short buccal capsule and large genital primordium. The rhabditiform larvae are passed in the stool and my either continue the direct cycle by developing into infective filariform larvae or develop into free-living adult worms.Clinical symdromes include pneumonitis from migrating larvae. The intestinal infection is usually asymptomatic. Heavy worm loads may involve the biliary and pancreatic ducts, the entire small bowel, and the colon, causing inflammation and ulceration leading to epigastric pain and tenderness, vomiting, diarrhea, and malabsorption. Symptoms mimicking peptic ulcer disease coupled with peripheral eosinophilia should strongly suggest the diagnosis of strongyloidiasis.DiagnosisDiagnosis is by identification of the larvae as eggs are generally not seen in the stool.• Trichinella spiralisEpidemiologyIt is estimated that more than 1.5 million Americans carry live Trichinella cysts in their musculature and that 150,000 to 300,000 acquire new infection annually. It is one of the few tissue parasitic diseases seen in the United States.Physiology & Clinical ManifestationsT. spiralis is the etiologic agent of trichinosis. The infection begins when meat (pork) that contains encystedlarvae is digested. The larvae leave the meat in the small intestine and


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UIC PCOL 425 - Anthelminthic and antifungal Agents

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