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Dr Abdul Ghaffar 
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University of South Carolina


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bab1.jpg (15702 bytes)  
Figure 21A  
Babesia microti infection, Giemsa-stained thin smear. The organisms resemble Plasmodium falciparum; however Babesia parasites present several distinguishing features: they vary more in shape and in size; and they do not produce pigment. A 67 year old woman, status post-splenectomy, infection probably acquired in Long island (New York) 

Babesiosis, like malaria, is an infection of erythrocytes. It is spread by ticks.

Babesia microti is the most important member of the genus that infects man, although a few cases of infection by Babesia sp. have been detected.

In the United States, infections are usually seen in the northeast and the upper mid-west (figure 21E) during the summer months (figure 21F)  when ticks are more likely to come in contact with humans. In 2012, there were 911 reported cases of babeosis (figure 21G). Patients had a median age of 62 (figure 21H) and two thirds were male, probably reflecting the fact that men are more likely to come in contact with Ixodid ticks.

The trophozoite is very similar to the ring form of the Plasmodium species (figure 21A and B).

bab2.jpg (16356 bytes)   Figure 21B  
Infection with Babesia. Giemsa-stained thin smears. Note  the tetrad (left side of the image), a dividing form pathognomonic for Babesia.  A 6 year old girl, status post splenectomy for hereditary spherocytosis, infection acquired in the US.


Babesiamicroti-label.jpg (13972 bytes)  Figure 21C
Thin blood film of B. microti ring forms with a typical Maltese Cross (four rings in cross formation).

© MicrobeLibrary and Lynne Garcia, LSG & Associates

Life cycle
The organism (sporozoite) is transmitted by a tick (Ixodes scapularis) and enters the red cell where it undergoes mitosis and the organisms (merozoite) are released to infect other red cells. Ticks acquire the organism during feeding on an infected individual. In the tick, the organism divides sexually in the gut and migrates into the salivary gland (figure 21D).

Babesiosis has also be spread by blood transfusion and from other to fetus.

Infections are often asymptomatic and in others there are flu-like symptoms:

  • fever

  • malaise

  • chills sweats

  • general aches and pains

However, the destruction of erythrocytes can lead to:

  • hemolytic anemia

  • jaundice

  • hepatomegaly

These occur usually 1 to 2 weeks after infection.  Although usually not severe, babeosis can be life-threatening as a result of additional complications including thrombocytopenia, low blood pressure, disseminated intravascular coagulation (consumptive coagulopathy) leading to thromboses, and organ collapse. This can be fatal, especially in immunosuppressed patients, the elderly and those that have undergone splenectomy.

Diagnosis is based on symptoms, patient history and detection of intraerythrocytic parasite in the blood (figure 21B,D) or transfer of blood in normal hamsters which can be heavily parasitized.

Treatment and Control
Drugs of choice are clindamycin combined with quinine or atovaquone combined with azithromycin.

The patient may recover spontaneously. One should avoid tick exposure and, if bitten, remove the tick from the skin immediately.




Babesia-lc.gif (31039 bytes)  Figure 21D

The Babesia microti life cycle involves two hosts, which includes a rodent, primarily the white-footed mouse, Peromyscus leucopus.  During a blood meal, a Babesia-infected tick introduces sporozoites into the mouse host  .  Sporozoites enter erythrocytes and undergo asexual reproduction (budding)  .  In the blood, some parasites differentiate into male and female gametes although these cannot be distinguished at the light microscope level  .  The definitive host is a tick, in this case the deer tick, Ixodes dammini (I. scapularis).  Once ingested by an appropriate tick  , gametes unite and undergo a sporogonic cycle resulting in sporozoites  .  Transovarial transmission (also known as vertical, or hereditary, transmission) has been documented for “large” Babesia spp. but not for the “small” babesiae, such as B. microti  .  Humans enter the cycle when bitten by infected ticks.  During a blood meal, a Babesia-infected tick introduces sporozoites into the human host  .  Sporozoites enter erythrocytes  and undergo asexual replication (budding)  .  Multiplication of the blood stage parasites is responsible for the clinical manifestations of the disease.  Humans are, for all practical purposes, dead-end hosts and there is probably little, if any, subsequent transmission that occurs from ticks feeding on infected persons.  However, human to human transmission is well recognized to occur through blood transfusions  .
Note: Deer are the hosts upon which the adult ticks feed and are indirectly part of the Babesia cycle as they influence the tick population.  When deer populations increase, the tick population also increases, thus heightening the potential for transmission. 
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Figure 21E
Number of reported cases of babesiosis, by county of residence — 27 states, 2013

Figure 21F
Number of reported cases of babesiosis, by month of symptom onset — 2013

Figure 21G
Number of reported cases of babesiosis, by year

Figure 21H
 Number of reported cases of babesiosis, by age group — 2013

Toxoplasma-lc.gif (18764 bytes)  
Figure 22  Members of the cat family (Felidae) are the only known definitive hosts for the sexual stages of T. gondii and thus are the main reservoirs of infection.  Cats become infected with T. gondii by carnivorism (1).  After tissue cysts or oocysts are ingested by the cat, viable organisms are released and invade epithelial cells of the small intestine where they undergo an asexual followed by a sexual cycle and then form oocysts, which are then excreted.  The unsporulated oocyst takes 1 to 5 days after excretion to sporulate (become infective).  Although cats shed oocysts for only 1 to 2 weeks, large numbers may be shed.  Oocysts can survive in the environment for several months and are remarkably resistant to disinfectants, freezing, and drying, but are killed by heating to 70°C for 10 minutes.
Human infection may be acquired in several ways: A) ingestion of undercooked infected meat containing Toxoplasma cysts (2); B) ingestion of the oocyst from fecally contaminated hands or food (3); C) organ transplantation or blood transfusion; D) transplacental transmission; E) accidental inoculation of tachyzoites.  The parasites form tissue cysts, most commonly in skeletal muscle, myocardium, and brain; these cysts may remain throughout the life of the host.

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Toxoplasma gondii is the organism responsible for toxoplasmosis

Toxoplasma has worldwide distribution and 20%-75% of the population is seropositive without any symptomatic episode. In the United States, 22.5% of the population is seropositive. However, the infection poses a serious threat in immunosuppressed individuals and pregnant females.

The most common routes for human infection are:

  • Food, resulting from

    • consumption of contaminated, undercooked meat, especially pork, lamb and venison

    • ingestion after handling contaminated meat

    • using contaminated utensils

  • Zoonotic transmission via

    • cat feces in a litter box

    • contact with something that has contacted cat feces

    • contaminated soil (especially sand covered play areas where a cat may have defecated

    • contaminated water

Toxoplasma may also be spread congenitally (from a mother with no symptoms)  and rarely via blood transfusions and organ transplants.

The intracellular parasites (tachyzoite) are 3x6 microns, pear-shaped organisms that are enclosed in a parasite membrane to form a cyst measuring 10-100 microns in size. Cysts in cat feces (oocysts) are 10-13 microns in diameter (figure 22).

Life cycle
The natural life cycle of T. gondii occurs in cats and small rodents, although the parasite can grow in the organs (brain, eye, skeletal muscle, etc.) of any mammal or birds (Figure 22). Cats gets infected by ingestion of cysts in flesh. Decystation occurs in the small intestine, and the organisms penetrate the submucosal epithelial cells where they undergo several generations of mitosis, finally resulting in the development of micro- (male) and macro- (female) gametocytes. Fertilized macro-gametocytes develop into oocysts that are discharged into the gut lumen and excreted. Oocysts sporulate in the warm environment and are infectious to a variety of animals including rodents and man. Sporozoites released from the oocyst in the small intestine penetrate the intestinal mucosa and find their way into macrophages where they divide very rapidly (hence the name tachyzoites) (figure 23) and form a cyst which may occupy the whole cell. The infected cells ultimately burst and release the tachyzoites to enter other cells, including muscle and nerve cells, where they are protected from the host immune system and multiply slowly (bradyzoites). These cysts are infectious to carnivores (including man). Unless man is eaten by a cat, it is a dead-end host.

Although Toxoplasma infection is common, it rarely produces symptoms in normal individuals and when symptoms do occur, they are flu-like and sometimes associated with lymphadenopathy. Serious consequences are limited to pregnant women and immunodeficient hosts.

Congenital infections
These occur in about 1 to 5 per 1000 pregnancies of which 5 to 10% result in miscarriage and 8 to 10% result in serious brain and eye damage to the fetus. 10 to 13% of the babies will have visual handicaps. Although 58 to 70% of infected women will give birth to a normal offspring, a small proportion of babies will develop active retino-chorditis or mental retardation in childhood or young adulthood. Eye lesions are often not identified at birth but are found in 20 to 80% of infected patients by adulthood. In the United States fewer than 2% of patients develop eye lesions.

Immunocompromized patients
In immunocompromized individuals, infection results in generalized parasitemia involvement of brain, liver lung and other organs, and often death.

Both humoral and cell mediated immune responses are stimulated in normal individuals. Cell-mediated immunity is protective and humoral response is of diagnostic value.

Suspected toxoplasmosis can be confirmed by isolation of the organism from tonsil or lymph gland biopsy and by serologic testing.

Acute infections benefit from pyrimethamine or sulphadiazine. Spiramycin is a successful alternative. Pregnant women are advised to avoid cat litter and to handle uncooked and undercooked meat carefully.



Figure 23    

tox2.jpg (58169 bytes)  Figure 23A  
Toxoplasma gondii in the bronchoalveolar lavage (BAL) material from an HIV infected patient. Numerous trophozoites (tachyzoites) can be seen, which are typically crescent shaped with a prominent, centrally placed nucleus. Most of the tachyzoites are free, some are still associated with bronchopulmonary cells. 


 tox3.jpg (28393 bytes)  Figure 23B 
Toxoplasma gondii in tissue from a cat.


Figure 23C
Toxoplasma gondii in mouse ascitic fluid. Smear



Pneumocystis jiroveci (formerly known as Pneumocystis carinii)

Pneumocystis jiroveci was formerly thought to be a protozoan but is now known to be a fungus. It is included here because pneumocystis pneumonia is often described as an opportunistic parasitic disease. 

Pneumocystis pneumonia is an infection of immunosuppressed individuals and is particularly seen in AIDS patients. In the United States, about 10% of AIDS patients and about 1% of solid organ transplant recipients are infected.

The organism is pleomorphic, exhibiting, at various stages of its life cycle: 1-2 micron sporozoites, 4-5 micron trophozoites and 6-8 micron cysts. It spreads from person to person in cough droplets. Infection in immunosuppressed individuals results in interstitial pneumonia characterized by thickened alveolar septum infiltrated with lymphocytes and plasma cells. Pneumonia is associated with fever, tachypnea, hypoxia, cyanosis and asphyxia. Diagnosis is based on isolation of organisms from affected lungs.

Trimethoprim-sulphamethoxazole is the treatment of choice (figure 24). The mortality rate for P. jiroveci infections is 5 to 40% when treated and near 100% when untreated.




pneu1.jpg (23306 bytes)  Figure 24A  
Pneumocystis jiroveci trophozoites in broncho-alveolar lavage (BAL) material. Giemsa stain. The trophozoite are small (size: 1-5 µm), and only their nuclei, stained purple, are visible (arrows). AIDS patient seen in Atlanta, Georgia 

pneu2.jpg (21610 bytes)   pneu3.jpg (37595 bytes)  Figure 24 B and C
Pneumocystis jiroveci cysts
B. 3 cysts in bronchoalveolar material, Giemsa stain; the rounded cysts (size 4-7 µm) contain 6-8 intracystic bodies, whose nuclei are stained by Giemsa; the walls of the cysts are not stained; note the presence of several smaller, isolated trophozoites.
C. cysts in lung tissue, silver stain; the walls of the cysts are stained black; the intracystic bodies are not visible with this stain; baby who died with pneumonia in California.

Pneumocystis-lc.gif (29633 bytes)  Figure 24D
This is a generalized life cycle proposed by John J. Ruffolo, Ph.D. (Cushion, MT, 1988) for the various species of Pneumocystis.  These fungi are found in the lungs of mammals where they reside without causing overt infection until the host's immune system becomes debilitated.  Then, an oftentimes lethal pneumonia can result.  Asexual phase: trophic forms  replicate by mitosis  to  .  Sexual phase: haploid trophic forms conjugate  and produce a zygote or sporocyte (early cyst)  .  The zygote undergoes meiosis and subsequent mitosis to produce eight haploid nuclei (late phase cyst)  .  Spores exhibit different shapes (such as, spherical and elongated forms).   It is postulated that elongation of the spores precedes release from the spore case.  It is believed that the release occurs through a rent in the cell wall.  After release, the empty spore case usually collapses, but retains some residual cytoplasm  .  A trophic stage, where the organisms probably multiply by binary fission is also recognized to exist.  The organism causes disease in immunosuppressed individuals.  

stages were reproduced from a drawing by Dr. John J. Ruffolo, South Dakota State University, USA.  Reproduced by permission of Arnold and Dr. Ruffolo. Thanks to Dr. Melanie T. Cushion for her comments on the life cycle text. References:
Ruffolo JJ. Pneumocystis carinii Cell Structure. In: Walzer, PD, editor. Pneumocystis carinii Pneumonia. 2nd ed. Marcel Dekker; 1994. p. 25-43. 
Cushion MT, Ruffolo JJ, Walzer PD. Analysis of the developmental stages of Pneumocystis carinii in vitro. Lab Invest 1988;58:324-331.
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These are free-living amebae that occasionally cause serious human disease. They are of particular significance in immunocompromised hosts.

Naegleria fowleri

This organism causes a rare disease. It is a flagellate that may inhabit warm waters (spas, warm springs, heated swimming pools, etc.) and gain access via the nasal passage to the brain and cause primary amebic meningoencephalitis which is almost always fatal (figure 25). Only three people out of 132 have survived primary amebic meningoencephalitis in the last 50 years.

Naegleria fowleri is sometimes call "the brain eating ameba". Although Naegleria can be found in contaminated tap water, human infection does not result from drinking the water.

In the United States, infections are rare with only 34 cases between 2004 and 2013. These resulted from

  • Contaminated recreational water (3o cases)

  • Nasal irrigation with contaminated tap water (3 cases)

  • Contaminated tap water on a backyard slide (1 case)

One to seven days after nasal exposure, the patient suffers:

  • Sever headache

  • Nausea/vomiting

  • Fever

As the meningoencephalitis develops, patients then experience:

  • Stiff neck

  • Seizures

  • Hallucinations

  • Coma

  • They usually die 1 to 12 days after experiencing symptoms

There is an investigational drug, miltefosine, that may show promise. In 2013, two children survived an infection. One started treatment 36 hours after onset of treatment. She was treated with therapeutic hypothermia and miltefosine. She made a complete recovery. Another child did not receive hypothermia and was treated later after the onset of symptoms. He did receive miltefosine. He suffered permanent brain damage.



nae1.jpg (15553 bytes)  Figure 25 A  
Naegleria fowleri trophozoites, cultured from cerebrospinal fluid. These cells have characteristically large nuclei, with a large, dark staining karyosome. The amebae are very active and extend and retract pseudopods. Trichrome stain. From a patient who died from primary amebic meningoencephalitis in Virginia.


nae2.jpg (37751 bytes)   Figure 25B  
Naegleria fowleri trophozoite in spinal fluid. Trichrome stain. Note the typically large karyosome and the monopodial locomotion. Image contributed by Texas SHD.


nae3.jpg (84476 bytes)  Figure 25C   
Histopathology of amebic meningoencephalitis due to Naegleria fowleri. Direct fluorescent antibody stain. 

CDC/Dr. Govinda S. Visvesvara  gsv1@cdc.gov 

 nae4.jpg (115371 bytes)  Figure 25D   
Histopathology of Naegleria infection of brain.


FreeLivAmb-lc.gif (41826 bytes)  Figure 25E   
Free-living amebae belonging to the genera Acanthamoeba, Balamuthia, and Naegleria are important causes of disease in humans and animals.  Naegleria fowleri produces an acute, and usually lethal, central nervous system (CNS) disease called primary amebic meingoencephalitis (PAM).  N. fowleri has three stages, cysts  , trophozoites  , and flagellated forms  , in its life cycle.  The trophozoites replicate by promitosis (nuclear membrane remains intact)  Naegleria fowleri is found in fresh water, soil, thermal discharges of power plants, heated swimming pools, hydrotherapy and medicinal pools, aquariums, and sewage.  Trophozoites can turn into temporary flagellated forms which usually revert back to the trophozoite stage.  Trophozoites infect humans or animals by entering the olfactory neuroepithelium  and reaching the brain.  N. fowleri trophozoites are found in cerebrospinal fluid (CSF) and tissue, while flagellated forms are found in CSF.
Acanthamoeba spp. and Balamuthia mandrillaris are opportunistic free-living amebae capable of causing granulomatous amebic encephalitis (GAE) in individuals with compromised immune systems.  Acanthamoeba spp. have been found in soil; fresh, brackish, and sea water; sewage; swimming pools; contact lens equipment; medicinal pools; dental treatment units; dialysis machines; heating, ventilating, and air conditioning systems; mammalian cell cultures; vegetables; human nostrils and throats; and human and animal brain, skin, and lung tissues.  B. mandrillaris however, has not been isolated from the environment but has been isolated from autopsy specimens of infected humans and animals.  Unlike N. fowleri, Acanthamoeba and Balamuthia have only two stages, cysts  and trophozoites  , in their life cycle.  No flagellated stage exists as part of the life cycle.  The trophozoites replicate by mitosis (nuclear membrane does not remain intact)  .  The trophozoites are the infective forms and are believed to gain entry into the body through the lower respiratory tract, ulcerated or broken skin and invade the central nervous system by hematogenous dissemination  Acanthamoeba spp. and Balamuthia mandrillaris cysts and trophozoites are found in tissue.  

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A aca1.jpg (42684 bytes)  

aca2.jpg (24719 bytes)  
Figure 26 Acanthamoeba sp. keratitis. A: Biopsy showing a cyst; B: cyst, at a larger magnification, with a characteristic shape, in corneal scraping. CDC


Several species of free-living Acanthameba are pathogenic to man. They normally reside in soil and can infect children who swallow dirt while playing on the ground. In normal individuals, the infection may cause mild disease (pharyngitis) or remain asymptomatic, but in immunodeficient individuals, the organism may penetrate the esophageal mucosa and reach the brain where it causes Granulomatous Amebic Encephalitis (figure 26).

Granulomatous Amebic Encephalitis
This is a rare infection that can affect the brain and disseminate to the rest of the body. It can affect healthy people but is normally associated with immunocompromized individuals (organ transplants, lymphocyte disorders) and patients with diabetes, cancer, liver cirrhosis, lupus and people who have used antibiotics and steroids excessively.

Most cases are fatal. The use of miltefosine is recommended by CDC.

Acanthameba Keratitis
Most cases of this disease in the United States occur in contact lens users (1 to 33 cases per million). It results from improper storage and cleaning of lenses in tap water.

Summary of blood and tissue protozoa






Trypanosoma brucei

Tsetse fly. Sleeping sickness; cardiac failure. Hemoflagellate in blood or lymph node. Blood stage: Suramin or petamidine isethionate;
T. cruzi Reduvid (kissing) bug.

Chagas disease: megacolon, cardiac failure.

Hemoflagellate in blood or tissue. CNS: melarsoprol
Nifurtimox and Benzonidazole.
Leishmania donovani Sand fly Visceral leish-maniasis, granulo-matous skin lesions.

Intracellular (macrophages) leishmanial bodies.

Pentosam; Pentamidine isethionate.
L. tropica Sand fly. Cutaneous lesions. As for L. donovani. As for L. donovani.
L. braziliensis Sand fly Mucocutaneous lesions. As for L. donovani. As for L. donovani.
Plasmodium falciparum

P. ovale, P. malariae and P. vivax

Female anopheline mosquito.

Malarial paroxysm: chills, fever, headache, nausea cycles.

Plasmodia in rbc, typical of the species involved. Quinine derivatives


Babesia microti

Tick Hemolytic anemia, Jaundice and fever Typical organism (Maltese cross) in rbc. None; self resolving.
Toxoplasma gondii

Oral from cat fecal material;

or meat

Adult: flu like;

congenital: abortion, neonatal blindness and neuropathies.

Intracellular (in macrophages) tachyzoites.

Sulphonamides, pyemethamine, possibly spiramycin (non-FDA).

Pneumocystis jiroveci

Cough droplets


Pneumocystis in sputum.

Trimethoprim and sulphamethoxazole.





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