PHARMACOTHERAPY III PHCY 510 University of Nizwa College of Pharmacy and Nursing School of Pharmacy PHARMACOTHERAPY III PHCY 510 Lecture 11 Infectious Diseases “Parasitic Infections” Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy, CPN University of Nizwa

Course Outcome Upon completion of this lecture the students will be able to Describe etiology, clinical presentations and treatment options of Parasitic infections, Individualize the antiparasitic treatments.

Major parasitic infections such as protozoal infections (malaria, cryptosporidiosis, giardiasis), helminthic infections (ascariasis, enterobiasis), and ectoparasites (lice, scabies). Parasitic infections are significant threat to international travelers. MALARIA Plasmodium species responsible for human malaria include P. falciparum, P. vivax, P. malariae, and P. Ovale. Plasmodium species are spread by Anopheles mosquitoes, endemic in tropical areas such as sub-Saharan Africa, Asia, Central America, South America, and portions of Turkey, Greece, and the Middle East.

Pathophysiology Infection acquired from female Anopheles mosquito when saliva containing sporozoites is injected during a blood meal. Sporozoites spread to liver, resulting in development of exoerythrocytic forms (tissue schizonts, hypnozoites) within hepatocytes. Merozoites are released from tissue schizonts into the circulation approximately 1 to 2 weeks later, leading to invasion of erythrocytes. Rupture of schizont-infected red cells occurs after 48 hours, releasing merozoites that continue erythrocytic invasion. Ingestion of gametocyte-infected red blood cells by Anopheles mosquitoes leads to fertilization of male and female forms within the mosquito gut and development of sporozoites that migrate to the mosquito’s salivary glands, completing the infectious cycle.

Clinical Presentation Nonspecific includes fever, malaise, headache, rigors, and diaphoresis in over 80% of patients. Splenomegaly and hepatomegaly can develop as the disease progresses. Falciparum malaria can rapidly become life-threatening. Acute renal failure, symmetrical encephalopathy (cerebral malaria) manifesting as seizures and coma, and pulmonary edema may occur. Severe anemia secondary to hemolysis and decreased hematopoiesis along with thrombocytopenia and hypoglycemia are common.

Uncomplicated P. vivax, P. malariae, P Uncomplicated P. vivax, P. malariae, P. ovale, and chloroquine-sensitive P. falciparum infections should be treated with oral chloroquine. A loading dose of chloroquine base 600 mg (10 mg base/kg for children) followed by 300 mg (5 mg base/kg for children) at 6, 24, and 48 hours. Primaquine should not be used in patients with severe G6PD deficiency (hemolytic anemia) or during pregnancy. Patients with suspected chloroquine-resistant falciparum malaria should receive oral quinine in combination with a second agent. Quinine sulfate 650 mg every 8 hrs (25–30 mg/ kg/day in three divided doses for children) for 3 days in conjunction with doxycycline 100 mg twice daily (2–4 mg/kg/day divided twice daily for children) for 7 days is recommended.

Cinchonism (tinnitus, nausea, headache, blurred vision) and corrected QT (QTc) interval prolongation can occur with quinine. For pregnant women or children less than 8 years old, quinine should be used in combination with clindamycin 900 mg three times daily (20 to 40 mg/kg/day in three divided doses) for 5 to 7 days. Single-dose sulfadoxine/ pyrimethamine can be used if clindamycin is not tolerated and should be administered on the last day of quinine. Artemisinin and its derivatives (e.g., artesunate, artemether) are widely used as alternatives to quinine for drug resistant falciparum malaria.

Combination therapy with a second agent (e. g Combination therapy with a second agent (e.g., mefloquine) for 3 to 5 days is typically necessary in multidrug-resistant areas to prevent relapse because of the short half-life of artemisinin compounds. In areas where chloroquine resistant P. falciparum exists, mefloquine, doxycycline, or atovaquone/proguanil can be used. Neuropsychiatric effects are the primary reason for discontinuation of mefloquine therapy and are more common in women. Prophylaxis with primaquine for 14 days on departure from a malarious region endemic for P. ovale or P. vivax should be considered for individuals with extended stays.

Giardiasis Giardia lamblia (also known as G. duodenalis or intestinalis) is a flagellated, intestinal protozoan that is a common cause of diarrheal illness worldwide. Infection occurs through ingestion of fecally contaminated food or water or by fecal-oral contact. Stools are typically greasy and foul smelling but may be watery and profuse at symptom onset. Significant weight loss (10 lb) occurs in over half of patients. Malaise, nausea, abdominal cramping, bloating, and flatulence are also common.

Gastric infection may develop in patients with achlorhydria. Oral metronidazole 250 mg three times daily for 5 to 7 days in adults or 5 mg per kilogram three times daily for 7 days in children is the treatment of choice for Giardia. Side effects include metallic taste, nausea, dizziness, headache, and a disulfuram reaction when taken with alcohol. Reversible neutropenia may occur rarely. Furazolidone 100 mg four times daily for 7 to 10 days in adults. Side effects include nausea, vomiting, brown discoloration of the urine, and mild hemolysis in G6PD-deficient patients.

Helminthic Diseases Helminthic parasites consist of the nematodes (roundworms; e.g., Ascaris, Enterobius, Trichuris), trematodes (flukeworms; e.g., Schistosoma), and cestodes (tapeworms; e.g., Taenia). Fecal-oral spread is the predominant means of transmission for intestinal nematodes and cestode larvae. Infection with adult cestodes (e.g., Taenia) and tissue nematodes (e.g., Trichinella) is acquired by eating raw or undercooked meat.

Trematode infection (e. g Trematode infection (e.g., Schistosoma) occurs by contact with fresh water inhabited by larval forms. Abdominal cramping, vomiting, and diarrhea caused by intestinal or biliary obstruction can occur with heavy Ascaris or T. saginata infections. Eosinophilia is more commonly observed with ascariasis, hookworm, strongyloidiasis, and occasionally taeniasis. Seizures, hydrocephalus, coma, and death can result from cysticerci in the brain (neurocysticercosis). Mebendazole 100 mg twice daily for 3 days or a single 500 mg dose (for mass treatment programs) is used for trichuriasis, ascariasis, and hookworm. Expulsion of worms through the nose and mouth can occur with heavy Ascaris infections.

Mebendazole 100 mg twice daily for 3 days or a single 500 mg dose (for mass treatment programs) is used for trichuriasis, ascariasis, and hookworm. Expulsion of worms through the nose and mouth can occur with heavy Ascaris infections. Albendazole (400 mg daily for 3 days) is 80% curative for trichuriasis. A single 400 mg dose is as effective as mebendazole for ascariasis, more effective against hookworm. Albendazole serum concentrations can be increased fivefold when taken with a fatty meal. Mebendazole and albendazole come in100 mg and 200 mg chewable tablets, respectively. tablets may be chewed, crushed and mixed with food, or swallowed whole.