PARASITOLOGY

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

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

Entamoeba histolytica

trophozoite12-60 m

cyst10-20 m

Cytotoxin andphospholipase A2

Life cycle ofEntamoebahistolytica

Ingested cysts release the pathogenic trophozoites in the duodenum local necrosis in the large intestine

Entamoebahistolytica

Trophozoites can spread to the peritoneal cavity, liver, lungs, brain and heart

Fever, chills and leukocytosis

Entamoebahistolytica

Treatment: Metronidazole, followed by iodoquinol

Prevention:Boil waterClean fruitsand vegetables

FlagellatesGiardia lamblia

trophozoite9-12 m long

cyst8-12 m long

Giardia lamblia

The releasedtrophozoites canattach to theintestinal villi,causinginflammation

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

Giardia lamblia

Clinical syndromes: Asymptomatic in ~ 50% of infected peopleMild diarrhea to severe maladsorption syndrome Abdominal cramps

Treatment:Quinacrine or metronidazole

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

How does metronidazoleact?

Inhibits the metabolism of glucose

Interferes with mitochondrial function

Originally introduced for the treatment of Trichomonas vaginitis

Flagellates Trichomonas vaginalis

trophozoite7-23 m wide

Trichomonas vaginalis

Urogenital infections

Transmitted sexually

Prevalence in developed countries:5-20% in women2-10% in men

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

Trichomonas vaginalis

Treatment:Metronidazole

Coccidia Cryptosporidium

Acid-fast stained oocysts 5-7 m

Cryptosporidium

Attach to the brush border of intestinal epithelium

Zoonotic spread from animal reservoirs

Person to person spread by the fecal-oral route

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

Cryptosporidium

Clinical syndromes: Watery diarrhea Spontaneous resolution in ~ 10 days

Immunocompromised or AIDS patients: Extensive fluid loss (50 or more stools per day)

Cryptosporidium

Treatment:No broadly effective treatment

Prevention:Avoidance of contaminated water supplies, and high-risk sexual activities

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

Microsporidia

Some species causechronic diarrhea inpatients with AIDS

Ocular pain, loss of vision

Hepatitis

No known effective treatment

Metronidazole effects temporary improvement

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

Malaria kills an African child every 30 seconds (WHO)

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

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

The exact number of malaria sufferers in Africa is hard to quantify

Plasmodium

Requires two hosts:

Sexual reproductionin the mosquito

Asexual reproductionin humans and otheranimals

Can be transmitted viatransfusion, needle sharing and congenitally

Humans are infected by the bite of an Anopheles mosquito

Exoerythrocytic cycle: Sporozoites in the bloodstream enter the parenchymal cells of the liver

Erythrocytic cycle:Hepatocytes rupture to release merozoites which then enter erythrocytes

Following reproduction, up to 24 merozoites are relased from theerythrocytes

Some merozoites develop into male and female gametocytes

Plasmodium merozoites burst out of erythrocytes

Nature OUTLOOK Vol 430 (2004)

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

Ring forms of Plasmodium falciparum in erythrocytes

Plasmodium falciparum causes malignant tertian malaria

Mature gametocyte of Plasmodium falciparum

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

Cerebral malariaComa and death

Blackwater feverKidney damage (hemoglobinuria)Acute renal failureTubular necrosis and death

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

Other antimalarials:

Malarone (atovaquone+proguanil)

Mefloquine + artesunate

Fansidar (pyrimethamine-sulfadoxine)

Doxycycline

Phenanthrene methanols (Halofantrine, Lumafantrine)

Artemisinins (Artemether, Artesunate)

Toxoplasma gondii

Intracellular parasite whose essential reservoir host is the cat

Human infection is ubiquitous

Severe manifestations in the immuno-compromised

Cyst of Toxoplasma gondii in mouse brain maycontain hundreds of organisms

Toxoplasma gondii

Can infect cells in the lungs, heart, lymphoid organs, and the CNS including the eye

Cell destructionReproductionEventual cyst formation

Clinical syndromes:Chills, fever, headaches,myalgia, lymphadenitis,and fatigue, occasionallyresembling infectiousmononucleosis

Toxoplasma gondii

Treatment: In immuno-compromised patients, pyrimethamine plus sulfadiazine

Prevention: Avoid uncooked meat and exposure to cat fecesPregnant women should avoid Toxoplasma infection

Leishmania donovaniamastigotes in bonemarrow

Leishmania

Flagellated protozoa

Leishmania

Transmitted via sandflies

Promastigote stage infects the skin

Transforms into the amastigote stage

L. donovani invades reticuloendothelial cells

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

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

Leishmania tropica

Cutaneous leishmaniasis

Leishmania braziliensis

Mucocutaneous leishmaniasis

Cutaneous leishmaniasis

Trypanosomes

Trypanosoma brucei gambiense Causes African trypanosomiasis, or sleeping sickness

Trypanosomes

Trypanosoma brucei gambiense

Transmitted by tsetse flies

Lethargy, tremors, meningoencephalitis, general deterioration

Trypanosoma brucei gambiense

Treatment: At the early stages of the diseases, suramin and pentamidine(inhibits topoisomerase II; does not penetrate CNS)

Trypanosomes

Trypanosoma cruzi causes American trypanosomiasis or Chagas' disease

Transmitted by the reduviid bug ("kissing bug")

Trypanosomes

Trypanosoma cruzi

Erthematous area “chagoma” around the bite, rash and edema around the eyes and face, and CNS involvement

Amastigote stage ofTrypanosoma cruzi

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)

Trematodes

Also called flukes

Members of the Platyhelminthes

Flat, fleshy, leaf-shaped worms

The first intermediate hosts are mollusks (snails and clams)

Shistosoma mansoniS. japonicumS. haematobium

Cause shistosomiasis (bilharziasis, "snail fever”)

Infective forms: ciliated, free-swimming cercaria

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

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

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

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

Treatment: PraziquantelCalcium influx -> muscle contraction -> exposure of new epitopes -> vulnerable to immune system

OxamniquineAlkylates DNA, inhibits DNA, RNA and protein synthesis

Nematodes

Dracunculus medinensis (“little dragon of Medina”)

Infection via ingestion of water containing infective Cyclops species harboring the larvae of the nematode

Life cycle of Dracunculus medinensis (Guinea worm)

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

Treatment and Control

Surgical removalRemoving emerging worm by wrapping around a twigNiridazole, metronidazole, thiabendazole

Boiling or chemical treatment of waterSimple filtration

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