BIOL 2421 Microbiology         Lecture Notes: Protozoans        Dr. Weis

Protozoa means “first animal” and are a diverse group of eukaryotic single celled cells that have different modes of mobility and can still be categorized based on those modes.

    Amoebas

These protozoans move by extending blunt like projections of the cytoplasm called pseudopods. This group is characterized by a feeding and dividing trophozoite stage that can form a temporary resistant cyst stage.

   Flagellates

These protozoans have a whip-like structure (flagella) that allows them to be pulled through the medium. The flagellum is present in the trophozoite stage and infection arises from the ingestion of cysts. Some produce toxins.

   Ciliates

These protozoans possess cilia, which are tiny hair like structures that beat in a rhythmic fashion and are found in rows covering the surface of the cell.

    Sporazoans

The sporozoans do not have structures for movement.


Life Cycle

Protozoa exist as a motile feeding stage called a trophozoite. Many protozoans convert into a cyst, a dehydrated, protective form of the organism when they encounter harsh environmental conditions.  In a cyst form, the organism is able to survive a wide variety of environments and thus allows the organism to spread more easily. Reproduction may be through asexual means: binary fission or schizogony or sexual reproduction involving the fusion of gametes. Cysts rupture releasing the trophozoite that is the more motile, feeding, and replicating stage. Cysts are formed and passed in the environment.


New groupings have been based on sequencing RNA rather than motility.

A. Alveolates

  1. Ciliates: 2 nuclei
  2. Apicomplexans: all pathogenic; infective stage has intracellular organelles in an apical complex
  3. Dinoflagellates: photosynthetic, plankton; some produce neurotoxins

B. Amoebae

C. Euglenozoa

  1. Euglenoids: Characteristics of plants and animals

2. Kinetoplastids: mitochondrial DNA = kinetoplast

D. Archaezoa

  1. Diplomonadida

2. Parabasala



Taxonomy:

Kingdom Protista

            Phylum Sarcomastigophora [the protozoa]

                        Subphylum Mastigophora [Flagellates]

                                    Order Trichomonadida (Archaezoa)

                                                Genera: Trichomonas

                                    Order Diplomanadida (Archaezoa)

                                                Genera: Giardia; Microsporidium

                                    Order Kinetoplastida (Euglenoid)

                                                Genera: Trypanosoma

                                                Genera: Leishmania

                        Subphylum Sarcodina [Amoebae]

                                    Genera: Entamoeba, Naegleria, Acanthoamoeba

            Phylum Apicomplexa (Apicomplexans)

                            Subclass Coccidia

                                 Order Eucoccidiorida

                                       Suborder Eimeriina

                                           Family Eimeriina

                                                Genus: Isospora

                                                Genus: Eimeria

                                          Family Sarcocystidae

                                                Genus: Toxoplasma

                                          Family Cryptosporidiidae

                                                Genus: Cryptosporidium

                                      Suborder Haemosporoina

                                                Genus: Plasmodium

                           Subclass Piroplasmasina

                                          Family Babesiidae

                                                Genus: Babesia

            Phylum Ciliophora (Ciliates)

                        Class Litostomatea

                                 Order Vestibuliferida

                                                Genera: Balantidium


Ecological Niches in the Human Body:

            Skin: Leishmania

            Eye: Acanthamoeba

            GI: Giardia, Entamoeba, Cryptosporidium, Isospora, Balantidium, Leishmania

            Urinary: Trachomonas

            Circulatory: Plasmodium, Trypanosoma

            Lymphatic: Leishmania

            Muscle: Trypanosoma cruzi

            CNS: Trypanosoma, Naegleria, Toxoplasma, Plasmodium


AMOEBA

            Entamoeba histolytica

Causative agent of amoebic dysentery which can spread to the liver causing abscesses.

The organism is characterized by a trophozoite and cyst stage.  Humans are the definitive host. These amoeba have a pathogenic phase and a non pathogenic phase.

Ingestion of cysts in sewage contaminated water or unwashed vegetables / fruits. Excystation occurs in the distal small intestine and colon.  Trophozoites feed and multiply several times to cause disruption [ulcer , necrosis] of the lining. Trophozoites move by extending a finger like pseudopodium and pulling the rest of the organism forward.  Amoeba may be carried to the liver via the hepatic portal vien. Cysts pass out with the feces and can be in the environment for 2-5 weeks.

DX: Id cysts or trophozoites in feces or tissues

TX: Metronidizole

Prevention: clean water

            Acanthoamoeba castellanii, A. culbertsoni

Free living amoeba causing opportunistic infection.  Amoeba causes corneal ulcers. Occasional death through invasion of the CNS.

            Naegleria fowleri

Free living amoeba. Opportunistic infection. Enters the nasal passages from water.

Invasion of the CNS causes fatal meningitis.


CILIATE

            Balantidium coli

Similar lifecycle to E. histolytica with transmissions by cysts. Zoonotic infection acquired from pigs. Also spread by infected food and water. May invade and cause ulceration of the colon resulting in severe diarrhea since trophozoites will invade the intestinal epithelium. Cysts can remain in intestinal wall and cause chronic disease.

DX: Id organism in feces

TX: Metronidizole

Prevention: Hygiene


FLAGELLATES

            Giardia lamblia

Single celled protozoan that moves with the aid of 5 flagella.  It is the most frequent non-bacterial cause of diarrhea in the U.S. within in 1 week of infection.  Illness normally lasts for 1-2 weeks, but there are cases of chronic infections lasting months to years. Transmission: Infection of cysts in contaminated water. Ingested cysts pass through the stomach and excystation takes place in the duodenum with possible toxin production.  Flagellar activity begins within 5-10 minutes flowing exposure to acid and the trophozoite emerges through a break in the cyst wall.  The trophozoite will undergo several cell divisions to create binuclear trophozoites that possess 4 flagella to create a erratic twisting motion as they move.  The trophozoite state an also attach to the epithelial cells of the small intestine by an adhesive sucker disk.  The trophozoite absorbs nutrients from the intestinal lumen via pinocytosis.

Children are most often infected along with HIV individuals who will exhibit chronicity.

 Life long immunity post infection in normal individuals.

Clinical Syndromes

            Asymptomatic

            Acute, self limiting diarrhea with nausea and upper abdominal discomfort, cramps

            Chronic: Damage to upper small intestinal wall that can lead to malabsorption syndrome resulting in diarrhea that can last for several weeks and weight loss.

DX: Id organism in stool (multiple samples) looking for cysts or trophozoite state

         ELISA detects excretory products of the organism

            IFA

TX: Metronidizole

Prevention: Clean water sources

            Trichomonas vaginalis

STD affecting the vagina in females and urethra, prostate, epididymis in males and causes a white purulent discharge with burning /itching.

Life cycle consists only of a trophozoite stage which is transmitted by direct contact during sexual contact. Trophozoites live closely associated to the epithelium of the urogenital tract, where they replicate by binary fission. Organisms have four flagella and a single nucleus.

DX: Demonstration of trophozoites in secretions

            Culture organism if not seen in secretions

TX: Metronidizole

Prevention: Safe sex

            Trypanosma brucei gambiense and T. brucei rhodesciense

Causative agent of African sleeping sickness. The disease is an arthropod (insect) born infection that is spread by the bite of the tsetse fly found in rural Africa. Zoonotic infection as animals can act as reservoir hosts of the disease. The Glossina fly takes up a trypanosome with bloodmeal.  These trypanosomes multiply and undergo a developmental cycle first in the gut and then in the salivary glands of the fly.  Infective forms (metacyclics) develop here and pass out in the saliva during feeding.  In the host, the first stage is multiplication of the trypanosomes at the site of the bite causing a chancre.  The trypanosomes gain access to the blood causing fever and malaise.  The final stage is invasion of the CNS causing a comatose state and the classical sleeping sickness syndrome.

            Trypanosoma cruzi

Causative agent of Chagas disease. Zoonosis as animals can act as a reservoir.

The intermediate host in this case are triatomid bugs that feed off the blood man.

Bug takes a blood meal that takes up the trypanosome.  Multiplication occurs in the midgut and moves down the GI tract of the bug until metacyclic forms are in the rectum. Infection results from the inoculation of the bug’s feces that contains the organism in the bite wound. The organism circulates in the blood and then invade cells.  Individuals who survive the acute stage of the disease are frequently left with chronic and progressive neuronal and muscle lesions in the heart and GI tract due to amastigote forms that multiply in these areas and form a pseudocyst. Trypanosome form will occur if the cyst ruptures and the trypanosome form will circulate in the blood to continue the cycle.  Human Clinical syndromes include: Megaesophagus, megacolon, arrhythmia, cardiac dialation, sudden death.

            Leishmania species:  L. donoviani, L. tropica, L.mexicana, L. braziliensis

Causative agent of visceral and cutaneous leishmaniasis. Zoonotic infections due to the reservoir in dogs and rodents. The disease is spread to vertebrate hosts by the bite of sandflies. In man, the promastigotes are inoculated when a sandfly bites. These promastigotes are ingested by macrophages and multiply within the WBC to become amastigotes which are released and ingested by further macrophages.  Amastigotes are picked up in circulation by the fly and will multiply asexually in the gut of the vector to create promastigota and migrate forward to be reinoculated at the next bite.

Cutaneous leishmania will occur as a localized open sore in the dermis. If it spreads, it can occur in the nose, mouth and palate causing destruction and called mucocutaneous leishmaniasis.

Visceral leishmania can produce systemic disease. Affected macrophages can be in the liver, spleen, bone marrow and other organs. The parasites continue to multiply in macrophages and if the disease is untreated, it is usually fatal.


APICOMPLEXA

            Cryptosporidium parvum

Small coccidian organism.  Zoonotic potential as it is enzootic in young calves and is passed to main in fecal contaminated water containing oocysts of the organism. Oocysts are ingested and hatch in the instestine into sporozoites.  These invade intestinal cells and undergo 2 asexual reproduction cycles to form gametes, an oocyst containing 4 sporozoitesOocyts then pass out with the feces. Organism causes a self limiting diarrhea in infants, small children.  In AIDS patients it can cause severe and life-threatening diarrhea.

DX: Oocysts in feces

TX: antiprotozoal drugs

Prevention: Sanitation, especially in agricultural “run off” areas

            Plasmodium species: P. falciparum, P. vivax, P. malariae, P.ovale

Cauative agent of malaria. The disease is spread by mosquitoes inhabiting fould, stagnant water. Humans are the definitive host.

In the stomach of the female anopheline mosquito, the male and female gametocytes of the parasite to form a zygote.  This in turn forms a motile ookinete that penetrates the midgut wall and develops into an oocyst within which are many thousands of sporozoites. When mature, the sporozoites rupture and the oocyst penetrates the salivary glands. The female mosquito inoculates sporozoites during feeding. These sporozoites first invade human hepatocytes to form pre-erythrocytic schizonts which create daughter cells called merozoites.  These merozoites enter the RBCs to start the asexual intraerythrocytic cycle (schizogony) to form new gametocytes. The asexual red cell stages (invasion, rupture, and reinvasion) are responsible for the pathological changes that occur in malaria: fever, chills, anemia, hepatomegaly, encephalitis, renal damage and death. The new male (micro) and female (macro) gametocytes are taken up by the mosquito to continue the life cycle.

DX: clinical symptoms and microscopic examination of a blood smear.

TX: antimalarial drugs

Prevention: Mosquito control

            Toxoplasmosis gondii

A coccidian organism which is the causative agent of toxoplasmosis. The domestic cat is the definitive host from which man and other mammals can become infected. Cats are exposed by ingesting paratenic (intermediate) hosts such as mice, birds, or acquire disease transplacentally. The life cycle includes two phases called the intestinal (enteroepithelial) and extraintestinal phases. The intestinal phase occurs in casts only and produces “oocysts.”

Infection commonly arises from the consumption of cysts either through contamination with cat feces or arises from the consumption of bradyzoites under cooked meat. Cysts rupture in the intestine, releasing sporozoites which penetrate gut epithelial cells.  After several cycles of multiplication (endodygeny), tachyzoites enter circulation and infect various nucleated cell types in the extraintestinal phase.

Finally tissue cysts are formed in brain and muscle, which contain many slowly dividing bradyzoites and lasts for years.

 In the healthy adult is usually asymptomatic.  Infectin is problematic in the fetus or AIDS patients. The most devastating form of toxoplasmosis is seen in congenital infection when a pregnant mother passes the organism to the fetus.  This can result in severe abnormalities at birth such as miscarriage, stillbirth, or severely handicapped child, both mentally and physically.

In AIDS patients, cysts can develop in the brain.

Other signs: rash, high fever, chills, trouble breathing, and fatigue.  Inflammation of organs a can cause heptatitis, pneumonitis, mycarditis, meningoencephalitis.

Three main life forms of T. gondii occur

            a) Oocyst produced from the sexual cycle that occurs in the GI tract of cats

                        oocysts contain sporozoites

            b) Tachyzoite is produced from the asexual cycle found in the secondary host

            c) Tissue cyst contains bradyzoites.

DX: Ab titer; CT/MRI ; biopsy

TX: Antibiotic {TMPS}

Prevention: Freeze or thoroughly cook meats

                   Pregnant women should not clean out litter boxes

            Coccidiosis

Two genera (Eimeria and Isospora) are referred to as the “coccidia,” which after infecting a number of species can have a variety of disease syndromes. Life cycles for both are similar.

The host is infected when it ingests an oocyts that have been passed in the feces of another host.  The oocyst then excysts in the new host’s small intestine and the sporozoites contained within the oocyst are liberated. The sporozoites penetrate the cells lining the intestine and reproduce asexually for several generations, each time producing multiple merozoites.  The merozoites are released from the infected cell and are now able to reinfect other cells, resulting in massive tissue distruction that will eventually result in the death of the host organism. Some merozoites that enter the host’s cells transform into gametocytes à gametes à fuseà zygote à oocyst.  The unsporulated oocyst escapes from the host’s cells and is passed in the host’s feces. The unsporulated oocyst will continue its development cycle in the environment to sporulate and produce sporozoites inside to become the infective stage.

DX: Oocysts in the feces of the host (sporulated oocysts allows for Genera Id)

TX: Ab [Sulfa drugs]

Prevention: Sanitation

                   Disease is self limiting as parasite stops dividing after several generations

            Babesia bigemina

Piroplasm organism that have two host life cycles involving ticks and mammals. Infection of red blood cells transmitted by a hard tick [Boophilus sp].  Babesia lives inside RBCs (usually in pairs) that eventually destroys the RBCs, producing fever, headache, and muscle aches.  Anemia may result from the breakdown of red blood cells as the organism undergoes asexual reproduction results in red urine (due to hemoglobin).

People are rarely infected, unless their spleen has been removed, and then the risk of death is high. Clinical signs resemble malaria and include: high fever, anemia, jaundice, dark urine, and kidney failure.

DX: Id organism in RBC blood smear

TX: Ab [Clindamycin, Azithromycin]

Prevention: Tick control


OTHER Organisms

            Pneumocystis jiroveci [Formally P. carinii]

Debate as to whether this pathogenic organism is a fungus or protozoan.

RNA analysis indicates that this organism is related to yeasts / fungi.

Source: Found in Human respiratory system in the lining of the alveoli

Transmission: Respiratory droplet as early as 2 years of age.

Clinical Course:

Thick walled cyst in the alveolar lining that contains 8 intracystic bodies created via sexual reproduction. Cyst ruptures releasing the 8 bodies that develop into trophozoites.

Trophozoites reproduce asexually by fission or sexually as an encysted stage.

Susceptible individuals: immunocompromised [HIV, cancer, transplant patients]

Dz: Pneumonia, alveoli fill with frothy exudate, can be fatal

DX: Id cysts found in sputum

            PCR

TX: Ab [TMPS]

Prevention: Prophylaxis treatment in susceptible patients.


NOTE: See chapter table in book for overall comparision of pathogenic protozoa.