Antiparasitics #2 -- Not Malaria Flashcards
Definitive host of toxoplasma gondii
Cat
Transmission of toxoplasma gondii
Eating Raw Meat
Cat feces
Descri e the life cycle of T gondii
Sexual development in cat
Cysts develop in other mammals
Ca get infected from oocysts spread by cats OR by eating raw meat containing cysts.
Who gets toxoplasmosis?
HIV/AIDS patients
Organ Transplants
Chemo patients
What happens when a pregnant woman gets infected with toxoplasma gondii for the first time
Congenital toxoplasmosis
Drug treatment for Toxoplasma gondii
Pyrimethamine + Sulfadiazine
Alt – Atavaquone or Pentamidine
Top three parasitic infections associated with HIV in the US
Penumocystis jirovecii – Pneumonia
Toxoplasma gondii – Encephalitis
Cryptosporidium – Cryptosporidiosis
Top three parasitic infection associated with HIV globally
Malaria
Leishmania
Trypanosoma cruzi (Chagas Disease)
What is Pentamidine?
An aromatic diamidine used as a first line agent for West African Trypanosomiasis
Alt. treatment for visceral leishmania and pneumocystosis
How is Pentamidine administered?
Parenterally
Side effects of Pentamidine?
Highly Toxic
50% have side effects
hypo- or rarely hyper glycemia
Anerobic protozoa include what three major infections
Entamoeba histolytica (Amebiasis) Giardia lamblia (Giardiasis) Trichamonas vaginalis
Mechanism of entamoeba histolytica infection
Ingestion of cysts Formation of trophozoites Penetration of and multiplication within intestinal wall Systemic invasion Cysts let out in feces
Symptoms of entamoeba histolytica infection
Flatulence, Diarrhea, Abdominal Cramps and ulcers of the lining of the intestine
In some cases, liver abscesses
How to kill entamoeba histolytica in water
Boiling
Chlorination won’t do it
Entamoeba histolytica spread is promoted by….
Poor sanitation
Fecal contamination of food and water
Most common intestinal parasitic disease in the US
Giardia lamblia
Treatment for Giardia lamblia?
Metronidazole
Nitazoxanide
Symptoms of Giardia lamblia infection?
Range from asymptomatic to severe diarrhea and malabsorption
Most frequent cause of recreational water-related disease outbreaks?
Cryptosporidium
Symptoms of Cryptosporidium?
The most common – Watery Diarrhea
Also – Stomach Cramps, Pain, Dehydration, Nausea, Vomming, Fever, Weight Loss
How to treat Cryptosporidium?
Nitazoxanide
Where does Trichomonas reside?
Female lower genital tract and male urethra/prostate
Symptoms by gender
Female – Vaginitis w/ purulent discharge, Vulvar and cervical lesions, abdominal pain, dysuria, and dyspareunia
Male – Aysmptomatic
Treatment for anaerobic protazoa (Entamoeba histolytica, giardia lamblia, trichamonas vaginalis)
Metronidazole (kill trophozoites, but not cysts)
Follow with luminal drug to eliminate asymptomatic infection
Drug like Metronidazole, but less toxic
Tinidazole
Why shouldn’t you drink alcohol while taking Metronidazole?
Metronidazole is an inhibitor of Acetalhehyde dehydrogenase. With this enzyme blocked, any alcohol that enters the system will be stuck as acetaldehyde.
What symptoms are caused by build up of acetaldehyde
Hypotension, Nausea, Vomiting, Discomfort
Drugs for intestinal forms of Entamoeba histolytica
Paromycin and Iodoquinol
Paromycin can treat Entamoeba histolytica and ______
Cryptosporidium
Iodoquinol is typically combined with
Metronidazole
How does Nitazoxanide work?
Metabolized to active form – tizoxanide
Mechanism uncertain, but interferes with pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction and inhibits anaerobic metabolism
What do you use Nitazoxanide for?
Inhibits the growth of sporozoites and oocysts of Cryptosporidium parvum and trophozoites of Giardia lamblia
The Kinetoplastid parasites include…
Leishmania
African Trypanosomes
American Trypanosomes (Cruzi)
African Trypanosomes include…
brucei gambiense – W. African, 95% of cases - Tetse Fly
brucei rhodesiense – E. African
Common features of Kinetoplastid parasites
Kinoplast, Glycosome
Distinct mechanisms of gene expression
How to treat Leishmaniasis
Sodium stibogluconate or Amphotericin B
Alt – Pentamidine or Miltefosine
How to treat African Trypanosomiasis in early stage
Pentamidine (West) or Suramin (East)
How to treat African Trypanosomiasis in late stage
Melarsoprol (Both) or Eflornithine (West)
How to treat American trypanosomiasis
Nifurtimox or Benznidazole
Anti-parasitic use of Miltefosine
Visceral leishmaniasis
first oral drug
Most commonly used drugs for T. cruzi
Nifurtimox and Benznidazole
How do Nifurtimox and Benznidazole work?
Mechanism unknown. Activated by a NADH-dependent mitochondrial nitroreductase. This causes the generation of nitro radical anions
Pros of Nifurtimox and Benznidazole for T. cruzi
Reduces severity of the Acute phase
Orally available
Cons of Nifurtimox and Benznidazole for T. cruzi
Toxicity common – hypersensitivity, GI complications
What makes worm biology unique from other parasites
Multiply outside their definitive host
Top five most common helminth infections in the world
Ascaris Hookworms Trichuris Filarias Enterobius
Three types of helminths
Cestodes (Tapeworms)
Trematodes (Flukes)
Nematodes (Roundworms)
Four most common cestodes
Diphyllobothrium latum (broad fish tapeworm) Echinococcus granulosus (dog tapeworm) Taenia saginata (Beef Tapeworm) Tania solium (Pork Tapeworm)
Top Five Flukes
Clonorchis sinensis (Oriental Liver Fluke) Paragonimus westermani (Lung Fluke) Schistosoma mansoni (Blood Fluke) Schistosoma haematobium (Blood Fluke) Schistosoma japonicum (Blood Fluke)
Seven types of intestinal nematode infection
Ancylostoma duodenale Necator americanus Ascaris lumbricoides (giant roundworms) Enterobius vermicularis (Pinworm) Strongyloides stercoralis (Threadworm) Trichinella spiralis Trichuris Trichiura (Whipworm)
Six types of tissue nematodes
Brugia malayi Dracunculus medinensis (Guenia worm) Loa Loa (Filarial worm, african eye worm) Onchocerca volvulus (Filarial worm) Toxicara canis (Dog Worm) Wuchereria bancrofti (Filarial worm)
Echinococcosis. Cause? Symptoms? Transmission? Diagnosis? Treatment?
Echinococcus granulosus (dog tapeworm)
Large hyatid cysts in liver, lung, and brain. Anaphylaxis with cyst rupture.
Ingestion of eggs in dog feces, sheep as intermediate host
Treatment with Albendazole and cyst excision
Taeniasis. (Pork) Cause? Symptoms? Transmission? Diagnosis? Treatment?
Taenia solium.
Intestines are the primary site of infection –> diarrhea.
Transmitted by undercooked pork
Diagnosed by finding proglottids in the stool.
Treated with niciosamide.
Cysticercosis. Cause? Symptoms? Transmission? Diagnosis? Treatment?
Taenia solium larvae infection produces cysticerci in the brain. Seizures, headache, and vomiting. Follows ingestion of eggs from human feces.
Treat with praziquantel, albendazole, and/or surgery.
Taeniasis. (Beef) Cause? Symptoms? Transmission? Diagnosis? Treatment?
Taenia saginata. Transmitted by larvae in undercooked or raw beef. Taeniasis diagnosied by proglottids in the stool and treated with niciosamide.
Diphyllobothriasis. Cause? Symptoms? Transmission? Diagnosis? Treatment?
Diphylloborthrium latum. Transmitted by larvae in raw or undercooked fish. Diagnosed by detection of eggs in stool. Treat with Nicosamide
Cause of cysticercosis
Autoinfection by ingesting eggs produced by T. solium
What happens in cysticercosis infection
Oncospheres hatch in the intestine, invade the intestinal wall, and migrate to striated muscles (+brain, liver, other). There, they hatch into cysticerci that can cause serious brain damage.
Enterobiasis. What shit did the packet say?
Enterobius vermicularis. Most common helminth infection in US.
Pruritis ani w/ white worms visible in stools or perianal region. Transmitted by ingesting organisms eggs.
Scotch Tape test
Mebendazole or pyrantel pamoate
Ascariasis. What shit did the packet say?
Ascaris lumbricoices. Trans. by ingestion of soil containing the oranisms eggs. Larvae grow in intestine == can cause obstruction. Can pass to the blood throught he lungs.
Diagnosed by eggs in the stool.
Treat with pamoate or mabendazole
Trichuriasis. What shit did the packet say?
Trichuris trichura. Abdominal pain, diarrhea, flatulence, rectal prolapse. Transmitted by eating soil with eggs in it. ID’d by eggs in the stool. Treat with mebendazole.
Hookworm disease. What shit did the packet say?
Ancylostoma duodenale and Necator americanus.
Worm latches onto intestine –> anorexia, ulcer-like symptoms, chronic intestinal blood loss/ anemia. Transmitted through direct skin penetration by larvae in soil. ID’d by eggs in stool. Treat with pyrantel pamoate or mebendazole.
Strongyloidiasis (threadworm disease). What shit did the packet say?
Strongyloides stercoralis. In IC patients, can disseminate into the CNS or other deep organs. Trans through driect skin penetration by larvae found in the soil. Diagnosed by IDing larvae in stool.
Treat with Thiabendazole, lbendazole, or ivermectin.
Onchocerciasis (River Blindness) What shit did the packet say?
Onchocerca volvulus. Subcutaneous nodules, puruitic rash, and ocular lesions causing blindiness. Transmitted by blackfly. Diagnoses by microfilariae in skin biopsy.
Treat with ivermectin and/or surgery.
Visceral larva migrans. What shit did the packet say?
Toxocara canis. Mostly little kids. Larval form matures in the intestines then migrates to liver, brain, eyes. Trans. by eating eggs from dog feces. ID’d by finding larvae in tissue.
Treat with mabendazole or thiabendazole.
Filariasis (elephantitis) What shit did the packet say?
Wuchereria bencrofti and Brugia malayi. These filarial worms block lymph flow, causing edematouch arms, legs, and scrotum. Transmitted by infected mosquito bite. ID’d by microfilariaw in blood.
Treat with Combination diethylcarbamazine and albendazole.
Loiasis. What shit did the packet say?
Loa loa. Larvae crawl under the skin, leaving characteristic tracks. Can enter the eye, where adult worms are visible. Transmitted by deer flies. Treat with diethylcarbamazine.
Dracunculiasis. What shit did the packet say?
This disease is caused by dracunculus medinensis. Adults cause skin inflam and ulceration. Transmitted by water contaminated with intermediate host copepods with larvae. ID’d with head of worm in skin lesion or larvae released from lesion after H2O contact. Treat with surgical removal.
Trichinosis. What shit did the packet say?
Trichinella spiralis. Eating encysted larvae in undercooked pork. Trichinosis diagnoses by locating coiled encysted larvae in musc. biopsy. Treat with thibendazole.
Three types of Benzimidazoles on the market
Mebendazole (1st place)
Thiabendazoe (Kinda Toxic)
Albendazole (Useful for both GI and tissue)
Mechanism of benzimidazole action.
Binds to tubulin, inhibiting the formation of microtubules. Cap blocks addition to the plus end, while the minus end continues to be shortened.
Albendazole is the drug of choice for…
Cysticercosis
Also used for pinworms, hookworms, ascariasis, trichuriasis, and strongyloidiasis.
Mabendazole is used for…
Pinworms, Hookworms, Ascariasis, and trichuriasis
Thiabendazole is used for…
Pretty much nothing. Toxic and potential teratogen.
Praziquantel is used to treat…
Cestodes and trematodes
How does praziquantel work at low concentrations
At low concentrations, increased muscular activity –> contraction and spastic paralysis, worms detach from BV walls, migration from the mesenteric veins to the liver.
How does praziquantel work at high concentrations.
Tegumental damage exposes a number of tegumental antigens.
May also disrupt Ca homeostasis.
Praziquantel is the drug of choice for what specific class of diseases.
All forms of Schistosomiasis
What is Ivermectin? What is it used to treat?
Semisynthetic macrocyclic lactone
Strongyloidiasis and Onchocerciasis + dog heartworm
How does Ivermectin work?
Paralyzes microfilariae. Binds to glutamate-activated, GABA-gated, and other Cl- channels in nematode nerve/muscle cells, causing hyperpolarization.
This helps host cytotoxic cells adhere. This won’t kill the adults, but blocks progeny release.
Ivermectin is primarily seen in mass treatment programs for…
Onchocerciasis
What is Pyrantel pamoate used to treat?
Pinworms and Ascaris
Less effective against Hookworms
Hits the adults and immature worms, but not the migratory or ova
How does Pyrantel pamoate work?
Depolarizing neuromuscular blocking agent that causes the releast of acetylcholine and inhibition of cholinesterase. This will paralyze worms and allow for their expulsion.
Scabies. What shit did the packet say?
Sarcoptes scabei.
Itching dermatosis caused by shit left behind after female mites burrowing under stratum corneum
Scabies treatment?
Permethrin cream (5%) Give 6% Salicyclic Acid if crusted over
How to treat if live lice detected.
10-minute application of 1% permethrin/pyrethrins
2nd application 10 days later
How to treat a chronic lice infection
0.5% malathion
Newer pediculicides contain…
benzyl alcohol or spinosad
