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PARASITOLOGY
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Infection Number infected Annual deaths
Amebiasis 10% of world 40-110,000 population
Malaria >300 million 1 million
Americantrypanosomiasis 24 million 60,000
Leishmaniasis 1.2 million (not available)
Shistosomiasis 200 million 0.5-2 million
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Intestinal and Urogenital Protozoa
Amoebae Abdominal pain & crampingFlagellates Giardia Diarrhea, abdominal cramps Trichomonas VaginitisCoccidia Cryptosporidium Enterocolitis (watery diarrhea) Cyclospora Nausea, anorexia, crampingMicrosporidia Diarrhea, ocular pain, hepatitis
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Entamoeba histolytica
trophozoite12-60 m
cyst10-20 m
Cytotoxin andphospholipase A2
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Life cycle ofEntamoebahistolytica
Ingested cysts release the pathogenic trophozoites in the duodenum local necrosis in the large intestine
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Entamoebahistolytica
Trophozoites can spread to the peritoneal cavity, liver, lungs, brain and heart
Fever, chills and leukocytosis
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Entamoebahistolytica
Treatment: Metronidazole, followed by iodoquinol
Prevention:Boil waterClean fruitsand vegetables
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FlagellatesGiardia lamblia
trophozoite9-12 m long
cyst8-12 m long
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Giardia lamblia
The releasedtrophozoites canattach to theintestinal villi,causinginflammation
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Giardia lamblia
In streams and lakes
Acquired by drinkinginadequately treatedcontaminated water,ingestion of contaminated,uncooked vegetables or fruits,or person to person bythe fecal-oral route
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Giardia lamblia
Clinical syndromes: Asymptomatic in ~ 50% of infected peopleMild diarrhea to severe maladsorption syndrome Abdominal cramps
Treatment:Quinacrine or metronidazole
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How does metronidazoleact?
Active under anaerobicconditions
Nitro group reduced by bacterial or protozoalferredoxins or their equivalents
cytotoxic compound that binds to parasite guanine and cytosine causes DNA breakage
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How does metronidazoleact?
Inhibits the metabolism of glucose
Interferes with mitochondrial function
Originally introduced for the treatment of Trichomonas vaginitis
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Flagellates Trichomonas vaginalis
trophozoite7-23 m wide
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Trichomonas vaginalis
Urogenital infections
Transmitted sexually
Prevalence in developed countries:5-20% in women2-10% in men
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Trichomonas vaginalis
Clinical syndromes: Asymptomatic in most women Vaginal dischargeItching, burning and painful urination (extensive inflammation and erosion of the epithelial lining)Associated with pelvic inflammatory disease in HIV-seropositive women
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Trichomonas vaginalis
Treatment:Metronidazole
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Coccidia Cryptosporidium
Acid-fast stained oocysts 5-7 m
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Cryptosporidium
Attach to the brush border of intestinal epithelium
Zoonotic spread from animal reservoirs
Person to person spread by the fecal-oral route
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Cryptosporidium
Infects mammals, reptilesand fish
Milwaukee outbreak(300,000 people)linked to contaminated water supply
Resistant to usual water-purificationprocedures, including chlorine andozone
Many outbreaks in daycare centers
Cryptosporidium
Giardia
Oocysts
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Cryptosporidium
Clinical syndromes: Watery diarrhea Spontaneous resolution in ~ 10 days
Immunocompromised or AIDS patients: Extensive fluid loss (50 or more stools per day)
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Cryptosporidium
Treatment:No broadly effective treatment
Prevention:Avoidance of contaminated water supplies, and high-risk sexual activities
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Microsporidia
Obligate intracellular
Primitive eukaryotic cellslack mitochondriaperoxosimes, Golgi
Spores extrude infective sporoplasm into host cellsin the small intestines
Disseminated infection in immunocompromised patientsfever, vomiting, diarrhea and malabsorption
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Microsporidia
Some species causechronic diarrhea inpatients with AIDS
Ocular pain, loss of vision
Hepatitis
No known effective treatment
Metronidazole effects temporary improvement
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Medically important blood and tissue protozoa
Plasmodium MalariaBabesia Hemolytic anemia, renal failureToxoplasma Lung, heart, CNS infectionSarcocystis Muscle infectionAcanthamoeba Encephalitis, eye and skin infectionBalamuthia EncephalitisNaegleria MeningoencephalitisLeishmania LeishmaniasisTrypanosoma Sleeping sickness, Chagas disease
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Malaria kills an African child every 30 seconds (WHO)
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Each year malaria is estimated to cause
More than 1 million deaths
Up to 500 million attacks of acute illness
Up to 50,000 cases of neurological damage
Up to 400,000 cases of severe anemia in pregnancy
Up to 300,000 low-birth-weight babies
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UN campaign to“Roll Back Malaria”
UNICEF$3.7M for obsolete drugs$17.3M for bednets & insecticides
USAID$8.4M to a private company to sell bednets
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The exact number of malaria sufferers in Africa is hard to quantify
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Plasmodium
Requires two hosts:
Sexual reproductionin the mosquito
Asexual reproductionin humans and otheranimals
Can be transmitted viatransfusion, needle sharing and congenitally
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Humans are infected by the bite of an Anopheles mosquito
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Exoerythrocytic cycle: Sporozoites in the bloodstream enter the parenchymal cells of the liver
Erythrocytic cycle:Hepatocytes rupture to release merozoites which then enter erythrocytes
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Following reproduction, up to 24 merozoites are relased from theerythrocytes
Some merozoites develop into male and female gametocytes
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Plasmodium merozoites burst out of erythrocytes
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Nature OUTLOOK Vol 430 (2004)
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Plasmodium vivax Benign tertian malariaAttacks of fever, chills and malarial rigors every 48 hours
Plasmodium malariae causes quartan or malarial malaria, with fever patterns of 72 hours
Plasmodium ovaleBenign tertian or ovale malaria
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Ring forms of Plasmodium falciparum in erythrocytes
Plasmodium falciparum causes malignant tertian malaria
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Mature gametocyte of Plasmodium falciparum
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Plasmodium falciparum causes malignant tertian malaria
The most likely Plasmodium species to cause death if left untreated
Severe nausea, vomiting anddiarrhea
Destroyed red cells adhereto the vascular endothelium
Capillaries can be plugged by red cells, platelets, leukocytes and malarial pigment
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Cerebral malariaComa and death
Blackwater feverKidney damage (hemoglobinuria)Acute renal failureTubular necrosis and death
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Treatment: Chloroquine or parenteral quinine if the patient is not from a chloroquine-resistant area
Chloroquine accumulates preferentially in parasitized red blood cells
Interferes with DNA replication
Binds ferriprotoporphyrin released from hemoglobin to form a toxic complex
Raises the pH of the parasite's intracellular vesicles, interfering with its ability to degrade hemoglobin
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Other antimalarials:
Malarone (atovaquone+proguanil)
Mefloquine + artesunate
Fansidar (pyrimethamine-sulfadoxine)
Doxycycline
Phenanthrene methanols (Halofantrine, Lumafantrine)
Artemisinins (Artemether, Artesunate)
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Toxoplasma gondii
Intracellular parasite whose essential reservoir host is the cat
Human infection is ubiquitous
Severe manifestations in the immuno-compromised
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Cyst of Toxoplasma gondii in mouse brain maycontain hundreds of organisms
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Toxoplasma gondii
Can infect cells in the lungs, heart, lymphoid organs, and the CNS including the eye
Cell destructionReproductionEventual cyst formation
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Clinical syndromes:Chills, fever, headaches,myalgia, lymphadenitis,and fatigue, occasionallyresembling infectiousmononucleosis
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Toxoplasma gondii
Treatment: In immuno-compromised patients, pyrimethamine plus sulfadiazine
Prevention: Avoid uncooked meat and exposure to cat fecesPregnant women should avoid Toxoplasma infection
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Leishmania donovaniamastigotes in bonemarrow
Leishmania
Flagellated protozoa
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Leishmania
Transmitted via sandflies
Promastigote stage infects the skin
Transforms into the amastigote stage
L. donovani invades reticuloendothelial cells
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Leishmania donovani
Clinical syndromes: Causes "kala-azar," "dum dum fever,” or visceral leishmaniasisChills and sweating resembling malariaEnlargement of liver and spleenWeight loss and emaciation Kidney damageIf untreated, it can lead to death
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Leishmania donovani
Treatment: Pentavalent antimonial compounds (stibogluconate)Inhibit glycolytic and Krebs cycle enzymesToxic to the hostTherapeutic value due to enhanced uptake by the parasite and intense metabolic activity of the parasite
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Leishmania tropica
Cutaneous leishmaniasis
Leishmania braziliensis
Mucocutaneous leishmaniasis
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Cutaneous leishmaniasis
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Trypanosomes
Trypanosoma brucei gambiense Causes African trypanosomiasis, or sleeping sickness
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Trypanosomes
Trypanosoma brucei gambiense
Transmitted by tsetse flies
Lethargy, tremors, meningoencephalitis, general deterioration
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Trypanosoma brucei gambiense
Treatment: At the early stages of the diseases, suramin and pentamidine(inhibits topoisomerase II; does not penetrate CNS)
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Trypanosomes
Trypanosoma cruzi causes American trypanosomiasis or Chagas' disease
Transmitted by the reduviid bug ("kissing bug")
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Trypanosomes
Trypanosoma cruzi
Erthematous area “chagoma” around the bite, rash and edema around the eyes and face, and CNS involvement
Amastigote stage ofTrypanosoma cruzi
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Trypanosomes
Organisms proliferate in the heart, liver, spleen, brain and lymph nodes
Treatment: nifurtimox, allopurinol (inhibits enzymes in purine metabolism) and benzimidazole (inhibits fumarate reductase, glucose transport and microtubule function)
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Trematodes
Also called flukes
Members of the Platyhelminthes
Flat, fleshy, leaf-shaped worms
The first intermediate hosts are mollusks (snails and clams)
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Shistosoma mansoniS. japonicumS. haematobium
Cause shistosomiasis (bilharziasis, "snail fever”)
Infective forms: ciliated, free-swimming cercaria
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Shistosoma mansoni, S. japonicum andS. haematobium
Mature in intrahepatic portal blood
They coat themselves with host substances; thus there is little protective response against schistosomes
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The male and female adult worms pair up and migrate to their final destinations, where egg production takes place
The eggs hatch in fresh water and release motile miracidia, which then infect the snail host
115-175 m long
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Resides in the small branches of the inferior mesenteric vein near the lower colon and causes intestinal schistosomiasis
Widespread in Africa, Saudi Arabia, Brazil, Surinam, Venezuela, parts of the West Indies and Puerto Rico
Cases originating in these areas occur in the U.S.
Shistosoma mansoni
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Clinical syndromes:Dermatitis, with allergic reactions and edemaHepatitis, tenderness of the liverFever, malaiseAbdominal pain, diarrhea, and blood in the stool
due to inflammation when the eggs are deposited in the bowel mucosa
The eggs can migrate to the liver, where inflammation causes "periportal fibrosis," which can be lethal
Shistosoma mansoni
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Treatment: PraziquantelCalcium influx -> muscle contraction -> exposure of new epitopes -> vulnerable to immune system
OxamniquineAlkylates DNA, inhibits DNA, RNA and protein synthesis
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Nematodes
Dracunculus medinensis (“little dragon of Medina”)
Infection via ingestion of water containing infective Cyclops species harboring the larvae of the nematode
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Life cycle of Dracunculus medinensis (Guinea worm)
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Painful blister induced bythe female Guinea worm
After rupture of the blisterthe worm emerges as a white filament
Dracunculiasis
Complications include abscess formation and secondary bacterial infection, leading to further tissue destruction
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Treatment and Control
Surgical removalRemoving emerging worm by wrapping around a twigNiridazole, metronidazole, thiabendazole
Boiling or chemical treatment of waterSimple filtration
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The Carter Center has helped to eliminate Guinea worm infection from 3 million people in Africa
Here, while Jimmy and Rosalind Carter look on, a local woman is demonstrating the use of a simple filtration device to obtain Guinea worm-free water
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