PCOL425 Medical Pharmacology Lecture Part II Anthelminthic and Antifungal Agents By Prof A H Chishti Phone 312 355 1293 E mail chishti uic edu Room COMRB 5097 Recognize 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 lumbricoides Trichuris trichiura whipworm Ancylostoma duodenale and Necator americanus hookworms Strongyloides stercoralis Trichinella spiralis Enterobius vermicularis pinworm Epidemiology E 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 Manifestations Infection 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 Diagnosis The diagnosis of enterobiasis is usually suggested by the clinical manifestations and confirmed by detection of 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 glass slide 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 lumbricoides Epidemiology Ascaris 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 Manifestations Ascaris 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 many larvae 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 Diagnosis Examination 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 stercoralis Epidemiology S 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 Manifestations Like hookworms S stercoralis larvae penetrate the skin and enter the circulation and follow the pulmonary course 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 Diagnosis Diagnosis is by identification of the larvae as eggs are generally not seen in the stool Trichinella spiralis Epidemiology It 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 Manifestations T spiralis is the etiologic agent of trichinosis The infection begins when meat pork that contains encysted larvae is digested The larvae leave the meat in the small intestine and within 2 days develop into adult worms A single fertilized female produces more than 1500 larvae in 1 to 3 months The larvae move from the intestinal mucosa into the bloodstream and are carried in the circulation to various muscle sites throughout the body where they coil in striated muscle fibers and encysted Most patients have no or minimal symptoms In
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