Week 9 Flashcards
Parasites
either protozoa or helminth that lives on or in a host and gets its food from or at the expense of its host
Protozoa - 4 kinds
unicellular eukaryotes
1) Amoebas
2) Sporozoans
3) Flagellates
4) Ciliates
Amoebas (3)
motility?
pseudopod mobility
1) Entamoeba histolytica
2) Naegleria fowleri
3) Acanthamoeba
Entamoeba histolytica
Transmission
fecal-oral
Cysts ingested and differentiate in ileum to trophozoites → invade colon epithelium → local necrosis, hematogenous spread → intestinal/extraintestinal amebiasis
INVASIVE + HEMATOGENOUS SPREAD
Entamoeba histolytica
Trophozoite stage vs. Infective cyst stage
Trophozoite stage: pseudopods allow organism to move along intestinal wall and take up nutrients
Infective cyst stage: cysts ingested and cause infection
Entamoeba histolytica
Presentation (3 possibilities)
1) Asymptomatic carrier (most common)
2) Intestinal amebiasis
3) Liver abscess
Entamoeba histolytica
asymptomatic carrier
(most common) - cysts in stool → highly contagious, cysts can survive outside host
Entamoeba histolytica
Intestinal amebiasis
subacute onset over weeks
Bloody diarrhea**, INVASIVE
Abdominal pain, nausea, vomiting
Entamoeba histolytica
Liver abscess
“anchovy paste” liver abscess
Dull RUQ pain, elevated LFTs
Entamoeba histolytica
Diagnosis - 2 characteristic findings
antigen testing + parasite in stool or extraintestinal sites, asymptomatic carriers will have cysts in stool
***FLASK SHAPED ULCERS on biopsy - colonic lesions with mucosal ulceration and submucosal invasion
**TROPHOZOITES with INGESTED RBCs
Entamoeba histolytica
Treatment (3)
metronidazole (invasive colitis) + paromomycin, iodoquinol
Naegleria fowleri
Transmission
enter through nose from water sources, ascends olfactory nerve through cribriform plate → into frontal lobe
Typically infection in summer months (warmer water)
Naegleria fowleri
Presentation
causes rapidly fatal meningoencephalitis
Severe headache, fever, vomiting
SX 5-8 days after contact
Nearly 100% lethal
Affects healthy young adults and children with recent exposure to warm freshwater
Naegleria fowleri
Diagnosis
organisms in CSF samples
Naegleria fowleri
TX
amphotericin B (rarely effective) - always fatal
Acanthamoeba
Transmission
nasopharyngeal route (similar to Naegleria fowleri), or breaks in skin
Acanthamoeba
Presentation (2)
1) granulomatous amebic encephalitis (especially IMMUNOCOMPROMISED)
- Headache, nausea, vomiting, etc.
2) Keratitis (associated with CONTACT LENSES)
**Can cause death
Sporozoans include what amoebas? (3)
motility?
no pseudopod, flagellar, or ciliary motility
1) Cryptosporidium
2) Toxoplasma gondii
3) Plasmodium spp
Cryptosporidium
Transmission
fecal-oral transmission
Oocytes ingested → sporozoites released in small intestine and differentiate into trophozoites
Trophozoites attach to intestinal wall → oocysts passed out of GI tract
INTRACELLULAR replication within intestinal wall
Cryptosporidium
Risks for infection
drinking water supplies, swimming pools, recreational water facilities
Cryptosporidium
Presentation?
Self-limiting WATERY diarrhea
Immunocompromised → protracted, severe watery diarrhea
Cryptosporidium
Diagnosis
stool samples with ACID-FAST oocysts
Cryptosporidium
TX (3)
**supportive
Nitazoxanide (children)
Antiretroviral therapy (HIV) (CD4 > 100)
Toxoplasma gondii
Transmission (3)
Cysts in undercooked meat
Oocysts in cat feces
Transplacentally to fetus
**Obligate INTRACELLULAR parasitic protozoa
Toxoplasma gondii
Risks for infection
common infection in US
Change litter box daily (don’t do it if you’re pregnant)
Uncooked meat (high incidence in France)
Toxoplasma gondii
Presentation (4)
1) Asymptomatic
2) Mononucleosis-like illness (sore throat, fever, swollen lymph nodes)
3) TOXOPLASMOSIS
4) Congenital toxoplasmosis
Toxoplasma gondii
TOXOPLASMOSIS
Immunocompromised → cysts rupture and release tachyzoites = TOXOPLASMOSIS
**TRIAD = Chorioretinitis, encephalitis, pneumonitis
Most common cause of encephalitis in HIV patients
Toxoplasma gondii
Congenital Toxoplasmosis
Pregnant woman infected WITHOUT previous exposure → can cross placenta causing congenital toxoplasmosis
**chorioretinitis, HYDROCEPHALUS, intracranial calcifications (MULTIPLE ring-enhancing lesions in cortex and basal ganglia on head CT)
Blueberry muffin rash, hepato- splenomegaly, hyperbilirubinemia, lymphadenopathy
Toxoplasma gondii
Treatment
pyrimethamine, Sulfadiazine, Leucovorin
Prophylaxis: TMP/SMX
Plasmodium spp
hematologic infection - parasites in blood cells (Infects RBCs)
> 0.5 million deaths/year, ½ children under age of 5 in Africa
Plasmodium spp
Transmission
Anopheles mosquito
Mosquito bite release sporozoites into bloodstream → LIVER, infects hepatocytes → sporocytes divide into merozoites and released from hepatocytes
→ infect RBCs → merozoites develop into trophozoites → infected RBCs less flexible → destroyed in spleen (splenomegaly) or RBCs burst and release parasite
Plasmodium spp
Presentation
Malaria
Anemia, fever, chills
P. malariae presentation? infects what type of RBCs?
cyclical symptoms (every 3 days), only infect mature RBCs
P. vivax and P. ovale presentation? infects what type of RBCs?
“relapsing infection” (every 2 days) and infects only reticulocytes (immature RBCs)
Schuffner dots unique to P. vivax/ovale - brick red dots in host erythrocytes
P. falciparum
presentation? infects what type of RBCs?
most severe, infects ALL RBCs
Make RBCs stick to capillary and venule walls → occlusion, hemorrhage
- Brain (cerebral malaria)
- Kidneys (renal failure)
- Lung (pulmonary edema)
Sickle cell trait, thalassemia, and glucose-6-phosphate dehydrogenase deficiency confers protection
P. Malaria has what trophozoite and what gametocyte shape?
Trophozoite → band or rectangular
Gametocyte shapes → round
P. vivax and P. ovale have what trophozoite and what gametocyte shape?
Trophozoite → large, irregular rings
Gametocyte shapes → round
P. falciparum has what trophozoite and what gametocyte shape?
Trophozoites → small rings
Gametocytes → banana-like
Flagellates include what amoebas? (5)
Motility?
whip-like flagella motility
1) Giardia Lamblia
2) Trichomonas vaginalis
3) Leishmania spp
4) Trypanosoma cruzi
5) Trypanosoma brucei
Giardia Lamblia
Transmission
fecal-oral
10-25 cysts required for infection
Cysts ingested → become trophozoites in duodenum that attach to duodenal villi
Giardia Lamblia
Risks for infection
travelers, daycares, homosexual men, hikers, campers - chlorination NOT effective, only boiling/iodine
Giardia Lamblia
Presentation
Diarrhea - foul smelling, fatty stools
Malabsorption AND hypersecretion
Most common cause of nonbacterial diarrhea in USA
NONINVASIVE destruction of villi
Can cause lactase deficiency
Giardia Lamblia
Diagnosis
tear shaped cysts in stool, owl eye nuclei (two nuclei) and four flagella or antigen testing
Giardia Lamblia
TX
metronidazole
Trichomonas vaginalis
Transmission
*Sexually transmitted
Lacks cyst form, rarely leaves host
Trichomonas vaginalis
Presentation (3)
1) Asymptomatic carrier
2) Acute vaginitis
3) Urethritis (men)
Trichomonas vaginalis
Acute vaginitis - symptoms?
- burning, itching, dysuria, frequency)
- STRAWBERRY CERVIX
- GREEN, foul-smelling vaginal discharge
- Vaginal pH > 4.5
Trichomonas vaginalis
Diagnosis
vaginal wet mount shows motile pear-shaped flagellated trophozoites (corkscrew motility)
Trichomonas vaginalis
TX
Metronidazole
Leishmania spp
Transmission
intra or extracellular?
blood sucking bite of female sandfly
Intracellular parasites in macrophages
Leishmania spp
Presentation (3)
1) Visceral leishmaniasis = Black Fever
2) Cutaneous leishmaniasis
3) Mucocutaneous leishmaniasis
Visceral leishmaniasis = Black Fever
Intermittent/spiking fever
Splenomegaly
Pancytopenia
Skin hyperpigmentation (“black fever”)
Cutaneous leishmaniasis
Erythematous papule at sandfly bite which expands and ulcerates
Mucocutaneous leishmaniasis
Lesions confined to skin, mucous membranes, and cartilage
Leishmania spp
Diagnosis
tissue biopsy with macrophages containing amastigotes (non motile, non flagellated form)
Outside of macrophages, Leishmania spp. Flagellated
Leishmania - Treatment?
sodium stibogluconate, liposomal amphotericin B
Trypanosoma cruzi
Transmission
painless bite and defecation of Reduviid bug (“kissing bug”)
Trypanosoma cruzi
Presentation: Acute
Chagoma = inflammation at bite site
Romana’s sign = swelling/inflammation around eyelids when organisms enter conjunctiva
Trypanosoma cruzi
Presentation: Chronic
Dilated cardiomyopathy with apical atrophy Cardiac arrhythmias Megacolon Megaesophagus Achalasia
Trypanosoma cruzi
Diagnosis
flagellated trypomastigotes on blood smear (acute) or non flagellated amastigotes within cells on biopsy
Chronic infection → parasitemia below detectable levels
Trypanosoma cruzi
TX
benznidazole and nifurtimox
Chronic = supportive care
Trypanosoma brucei
Transmission
painful bite of infected tsetse fly
Found in Sub-Saharan Africa
Trypanosoma brucei
Presentation: Early vs. Late
causes African sleeping sickness
Early: intermittent fever, malaise, and headache
Late: CNS involvement, daytime somnolence, nighttime insomnia, persistent headaches
Trypanosoma brucei
Diagnosis
mobile trypanosomes on blood smear
Trypanosoma brucei
TX
suramin (early), melarsoprol (late, CNS)
Primary host
host in which parasite reaches maturity and sexually reproduces within
Secondary host/Intermediate host
host that harbors parasite only for a short transition period
Reservoir host
host in which parasite can live indefinitely with no harmful effects
Dead-end/Incidental host
intermediate host that does not allow transmission to definitive host → prevent parasite from completing its development
Helminths
parasitic worms
1) Platyhelminthes (flatworms)
2) Nematodes (roundworms)
Platyhelminthes (flatworms)
include what 2 classes of wormies?
1) Cestodes (tapeworms)
2) Trematodes (flukes)
Cestodes (tapeworms) include what?
Platyhelminthes (flatworms)
1) Taenia solium (pork tapeworm)
2) Taenia saginata (beef tapeworm)
3) Echinococcus (dog tapeworm)
4) Diphyllobothrium (fish tapeworm)
Trematodes (flukes) include what?
Platyhelminthes (flatworms)
1) Schistosoma (blood flukes) = Schistosomiasis
2) Clonorchis sinensis (Asian liver fluke)
3) Paragonimus westermani (lung fluke)
Nematodes (roundworms)
include what worms?
6 intestinal roundworms
2 tissue roundworms
Intestinal roundworms:
1) Enterobius vermicularis (pinworm)
2) Ascaris lumbricoides: giant roundworm
3) Trichinella spiralis
4) Trichuris trichiura: whipworm
5) Strongyloides stercoralis
6) Necator americanus (hookworm)
Tissue roundworms:
1) Onchocerca volvulus = River blindness
2) Wuchereria bancrofti
Taenia solium (pork tapeworm)
Transmission - two main routes?
Intestinal infection: ingestion from undercooked pork → mature into adults in small intestine, consume food ingested by host
Tissue infection: ingested as eggs from feces → eggs hatch in SI, penetrate intestinal wall → travel to other tissues (brain, skeletal muscle, eye)
Taenia solium (pork tapeworm)
Appearance
4 suckers + circle of hooklets
Taenia solium (pork tapeworm)
Presentation
1) Intestinal infection
2) Tissue infection: cysts grow slowly and can cause seizures, neurological deficits and blindness
Taenia solium (pork tapeworm)
Diagnosis
proglottids and eggs in stool or calcified cysticerci in muscle or brain on imaging
Taenia solium (pork tapeworm)
Treatment
praziquantel, albendazole + corticosteroids
Taenia saginata (beef tapeworm)
Transmission
ingestion via undercooked beef → intestinal infection, attachment to small intestine wall → eggs passed in feces
Taenia saginata (beef tapeworm)
Presentation
Typically asymptomatic**
Malnutrition
Abdominal discomfort
Taenia saginata (beef tapeworm)
Appearance
4 suckers + NO hooklets
Taenia saginata (beef tapeworm)
Diagnosis
identification of proglottids and eggs in stool
Taenia saginata (beef tapeworm)
TX
praziquantel
Echinococcus (dog tapeworm)
Transmission
ingestion of eggs found in dog feces
Eggs → hatch into larvae → small intestine → penetrate and travel to other tissues
Echinococcus (dog tapeworm)
Presentation
tissue infection
HYDATID CYSTS in liver, lung, brain
- Cysts grow and cause organ displacement/ dysfunction
- “EGGSHELL” calcification (typically liver)
- Release of cyst contents can cause severe ANAPHYLAXIS and spread of infection
Common in sheepherders
Echinococcus (dog tapeworm)
Treatment
albendazole
Inject larvicidal solution into cysts during surgery
Diphyllobothrium (fish tapeworm)
Transmission
ingestion of undercooked freshwater fish → larvae mature into adults in SI → consume food/B12
Diphyllobothrium (fish tapeworm)
Presentation
Usually asymptomatic
Malnutrition
Megaloblastic anemia (B12 deficiency)
Diphyllobothrium (fish tapeworm)
Diagnosis
proglottids and eggs in stool
Diphyllobothrium (fish tapeworm)
TX
praziquantel
Schistosoma (blood flukes) = Schistosomiasis
Life cycle
Trematodes (flukes)
humans and snails
Snails excrete cercariae into fresh water that then PENETRATE human SKIN and enter blood → LIVER → mature into adults
Adults migrate against portal flow to venous plexuses - release eggs
EGGS CAUSE PATHOLOGY → cause acute inflammatory response, passed into feces or urine, etc.
Evade immune system via molecular mimicry
Schistosoma (blood flukes)
Presentation (6)
1) Cercarial dermatitis (swimmer’s itch)
2) Acute schistosomiasis
3) Chronic schistosomiasis (months to years after infection)
4) Intestinal schistosomiasis
5) Hepatosplenic schistosomiasis
6) GU Schistosomiasis
Schistosoma (blood flukes)
Cercarial dermatitis (swimmer’s itch)
within days of infection due to cercariae penetrating skin - **can be seen in USA
Schistosoma (blood flukes)
Acute schistosomiasis
1-2 months after infection - serum sickness-like disease
Cough, fever, chills, abdominal pain, dysentery, lymphadenopathy
Schistosoma (blood flukes)
Intestinal schistosomiasis
chronic/intermittent abdominal pain, poor appetite, diarrhea, intestinal bleeding and iron deficiency
Schistosoma (blood flukes)
Hepatosplenic schistosomiasis
hepatomegaly, splenomegaly, periportal fibrosis, portal HTN
Schistosoma (blood flukes)
GU Schistosomiasis
hematuria, eggs excreted in urine, dysuria, urinary frequency
Can lead to squamous cell carcinoma of bladder
Schistosoma (blood flukes) - DX
eggs or stool in urine, clinical presentation
Enterobius vermicularis
(pinworm)
Intestinal round worm
-Most common helminth in the US
Symptoms: perianal itching
Enterobius vermicularis (pinworm)
Transmission
fecal-oral
Ingest eggs → hatch in duodenum/jejunum → mature in ileum and large intestine
Adults mate in colon, at night, females migrate out of rectum to perianal skin and lay eggs
Enterobius vermicularis (pinworm)
Diagnosis
“Scotch tape” test for eggs
Eggs NOT found in stool
Enterobius vermicularis (pinworm)
TX
benzimidazoles, pyrantel pamoate
Ascaris lumbricoides
giant roundworm
intestinal roundworm
One of most common helminthic infections worldwide, highest prevalence in tropical countries
Ascaris lumbricoides: giant roundworm
Transmission
Fecal-oral transmission
Ingestion of ova → hatch in SI → release larvae that penetrate intestinal wall and migrate hematogenously or via lymphatics to lungs
Larvae mature in alveoli and ascend bronchial tree and are swallowed → back in SI → mature into adult worms
Ascaris lumbricoides: giant roundworm
Symptoms (5)
1) Asymptomatic (most)
2) Respiratory symptoms
3) Nutritional deficiencies
4) Obstruction of bowel lumen
5) If in biliary tree → biliary colic, cholecystitis, ascending cholangitis, obstructive jaundice
Ascaris lumbricoides: giant roundworm
Respiratory symptoms
Loeffler’s syndrome (hypersensitive eosinophilic pneumonitis)
Dry cough, burning/substernal discomfort, dyspnea, fever, wheezing
Ascaris lumbricoides: giant roundworm
Diagnosis
stool microscopy with identification of eggs
Ascaris lumbricoides: giant roundworm
TX
benzimidazoles, ivermectin
Trichinella spiralis
Transmission
Caused by ingestion of undercooked meat containing larvae of T. spiralis from animal
Gastric acid/pepsin in stomach causes larvae to be released from cysts → small bowel mucosa
Adults in SI migrate to striated muscles
Trichinella spiralis
Domestic vs. Sylvatic cycle
Domestic cycle: involves pigs, rodents
Sylvatic cycle: involves many animals (bears, moose, wild boars)
Trichinella spiralis
Symptoms (3)
1) Trichinosis
2) Intestinal phase
3) Invasive phase
Trichinella spiralis
Trichinosis
associated with consumption of raw or undercooked meat (especially PIGS)
Trichinella spiralis
Intestinal phase
diarrhea, abdominal pain, nausea (occurs within 1 week of inoculation)
Trichinella spiralis
Invasive phase
myalgia, periorbital edema, eosinophilia, splinter hemorrhages, fever (occurs within 4 weeks)
Trichinella spiralis
Diagnosis
clinical symptoms + serology or larvae on muscle biopsy
Trichinella spiralis
TX
benzimidazoles
Trichuris trichiura
whipworm
Intestinal parasite associated with poor hygiene in tropical climates
Trichuris trichiura (whipworm)
Transmission
fecal-oral
Unembryoated eggs passed in stool → become infective → ingest via food or hands contaminated with soil
→ eggs hatch and release mature larvae → mature into adult worms → establish in COLON
Trichuris trichiura (whipworm)
Symptoms
Asymptomatic (most)
Stools may contain mucus and blood
Nocturnal bowel movements
Rectal prolapse
Trichuris trichiura (whipworm)
Diagnosis
stool examination for eggs (FOOTBALL/barrel shape)
Trichuris trichiura (whipworm)
TX
Benzimidazoles
Strongyloides stercoralis
Transmission
fecal-cutaneous
Penetrate skin of feet → local itching → enter bloodstream and lungs (pneumonia)
Swallowed → mature into adults in SI → invade mucosa and lay eggs
Larvae hatch from eggs embed within intestinal wall → inflammation and pain (diarrhea)
Can have autoinfection by penetrating intestinal wall to re-enter bloodstream
Strongyloides stercoralis
Symptoms
pneumonia + gastroenteritis
Strongyloides stercoralis
DX
LARVAE seen in stool (not eggs) + eosinophilia
Strongyloides stercoralis
TX
benzimidazoles, ivermectin
Necator americanus (hookworm)
Symptoms
Pneumonia
Gastroenteritis
Anemia (secretion of anticoagulant + consumption of blood by worm)
Necator americanus (hookworm)
Transmission
fecal-cutaneous
Infective larvae penetrate skin of FEET → local itching, eventually enter bloodstream → transported to LUNGS → enter alveoli
Cause respiratory tract inflammation (pneumonia) → SWALLOW larvae → mature into adults in SMALL INTESTINE and attach to mucosa via cutting plates of teeth
Adults mate in lumen of intestine → eggs shed in feces
Necator americanus (hookworm)
Diagnosis
detection of EGGS (not larvae) in stool + eosinophilia
Onchocerca volvulus
Transmission
Human = only definitive host
Female black fly bite release onchocerca volvulus larvae → mature into adult form in subcutaneous tissue
Adults mate and release microfilariae
Onchocerca volvulus
Symptoms (3)
- Fibrosis around adult worms
- Inflammation due to microfilariae → thick, scaling, hyperpigmented pruritic rash (“lizard skin”)
-River blindness: when microfilariae reach eye
MAJOR cause of blindness
Onchocerca volvulus
Diagnosis
skin biopsy with microfilariae
Onchocerca volvulus
TX
ivermectin
Wuchereria bancrofti
Symptoms
1) Lymphatic filariasis
2) Tropical pulmonary eosinophilia
Wuchereria bancrofti
Lymphatic filariasis
lymphedema and elephantiasis (scrotum, arms, breast)
ONLY adult worms causes elephantiasis (not microfilariae)
Wuchereria bancrofti
Tropical pulmonary eosinophilia
caused by microfilariae in lung → immediate hypersensitivity reaction, increased IgE, eosinophilia, coughing, wheezing at night
Wuchereria bancrofti
Transmission
female mosquito deposits larvae in skin → enter lymph nodes → after 1 year larvae mature into adult worms and trigger inflammation, fever, lymphadenopathy → obstruction of lymphatics
Mosquito transmission
Wuchereria bancrofti
Diagnosis
blood with microfilariae
Wuchereria bancrofti TX
diethylcarbamazine
Nitroimidazoles - Metronidazole
Therapeutic use
GET GAP on the Metro
Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (bacteroides, C. diff - BELOW the diaphragm), H. Pylori
Nitroimidazoles - Metronidazole
Mechanism of action
pro-drug targets enzyme unique to parasite
Generates free radicals → cytotoxic intermediates that inhibit DNA synthesis
Nitroimidazoles - Metronidazole
Toxicity
disulfiram-like reactions, metallic taste, headache, nausea
Nitazoxanide
used for what?
Cryptosporidiosis in non-AIDS patients
Tinidazole
longer half life, better tolerated than Metronidazole
Paromomycin
Mechanism?
aminoglycoside abx
Mechanism of action: binds A site of 30S ribosome, inhibits protein synthesis (bactericidal) - concentrates in gut
Paromomycin - uses?
entamoeba histolytica, leishmania donovani, giardia
minimal toxicity
Pentamidine - used for…
used for treatment/prophylaxis of P. jirovecii infection in patients with sulfa allergies
Minimal side effects
Pyrimethamine - mechanism and use?
antifolate that acts synergistically to target enzymes involved in folate synthesis → impair parasite DNA synthesis
Use: Malaria
Benzimidazoles - use?
Mebendazole, Albendazole
NEMATODES - Ascaris, Necator (hookworm), Enterobius (pinworm), Trichuriasis (whipworm)
Mebendazole
poor absorption, concentrates in GI tract, excreted in bile
Used to treat nematode infections isolated to GI tract
Albendazole
better absorption, distributed into tissues
Benzimidazoles
Mechanism?
inhibit microtubule assemble by binding interface of alpha-beta tubulin dimer
Selectively bind to parasite tubulin
Widespread resistance exists
Pyrantel Pamoate
Therapeutic use
NEMATODES - Ascariasis (roundworm), Enterobiasis (pinworm), Hookworm
Pyrantel Pamoate
Mechanism of action
ACh receptor agonist → spastic paralysis of worm
Praziquantel
Use?
Cysticercosis (pork tapeworm, Taenia solium) Cystic hydatid disease (echinococcus
Praziquantel
Mechanism?
Ca2+ ionophore→induce paralysis, detachment, excretion
Induces tegmental damage - activates host immune system
**DO NOT use if neurocysticercosis - can cause permanent damage
Quinolones
Mechanism?
act against erythrocytic stage of infection, block detoxification of heme into hemozoin → heme accumulates and is toxic to plasmodium
Chloroquine
used for all except falciparum (widespread resistance)
Toxicity: retinopathy, pruritus, hepatotoxicity, cardiac disorders
MUST exclude G-6-PD deficiency
Primaquine
used for P. ovale or P. vivax - activity against hypnozoites which can remain dormant in liver for months to years
MUST exclude G-6-PD deficiency
Mefloquine
treatment or prophylaxis for P. falciparum or P. vivax
Used for prophylaxis during pregnancy
Rarely used due to psychotic disturbances as side effects
Quinine - use and mechanism
treatment and cure of erythrocytic stages of chloroquine resistant and MDR P. falciparum malaria
Mechanism: inhibit parasite feeding mechanism, generate oxidative stress
Quinine - toxicity
Cinchonism - visual dysfunction, tinnitus, nausea, vomiting Stimulates pancreatic B-cells Hypotension MUST exclude G-6-PD deficiency CONTRAINDICATED in pregnancy
Atovaquone with Proguanil
Use?
Mechanism?
Use: drug resistant P. falciparum, PCP pneumonia
Mechanism:
- Atovaquone → block electron transport chain of P. falciparum
- Proguanil → inhibit parasite dihydrofolate reductase and potentiate mitochondrial toxicity of atovaquone
Artemisinin
Mechanism and use?
Mechanism: bind iron, break down peroxide bridges → generate free radicals
Use: Fastest parasite clearance times of any antimalarial and act rapidly killing blood stages of ALL Plasmodium species
-Often combined with other drugs to prevent resistance
