Protozoa are a subset of protists which are eukaryotes that are not classified as animals, plants, or fungi.

Protozoa constitute a large genus (some 12,000 species) that although single-celled, have a great deal of complexity with respect ot movement, feeding and behavior. Although most members are harmless, free living inhabitants of water and soil, a few species are pathogens which are collectively responsible for hundreds of millions of infections of humans each year. Protozoa are called “trophozoites” when they are in their motile feeding stage. A large number of species are also capable of entering into a dormant, resting stage called a “cyst” when conditions in the environment become unfavorable for growth and feeding. Cycsts can be dispersed by air currents and may even be important factor in the spread of diseases such as amoebic dysentery. If provided with moisture and nutrients, a cyst breaks opena dn releases the active trophozoite.

Protozoan parasites were the most frequently identified etiologic agents in waterborne disease outbreak from 1991 to 1994. The waterborne parasites Giardia lamblia, Naegleria fowleri, Acanthamoeba spp., Entamoeba histolytica, Cryptosporidium parvum, Cyclospora cayetanesis, Isospora belli. See Sterling

Affecting Blood, the Cardiovascular and Lymphatic System

Babesiosis: Babesia is a protozoan that infectes red blood cells. It is carreid by ticks and found in the upper Great Lakes region as well as in the northeast U.S. It is often diagnosed via a blood smear; the protozoan is visible inside red blood cells. A combined therapy of either atovaquone (an antiprotozoal) plus azithromycin or clindamycin plus quinine (another antiprotozoal) is recommended.

Chagas Disease (the American trypanosomiasis”): Chagas disease is named after the Brazilian physician Carlos Chagas, who discovered the disease in 1909. It is caused by the flagellated protozoan Trypanosoma cruzi, which is transmitted to animals and people by insect vectors (triatomine bug) and is found only in the Americas (mainly, in rural areas of Latin America where poverty is widespread). The bug is found in dwellings constructed form materials such as mud, adobe and straw. The insect bites the host and while feeding on its blood deposits feces. The parasite can then enter the body of the host from the insect’s feces when the host scratches and breaks the skin, or transfers the parasite to a mucous membrane. The disease can also be passed from mother to child during childbirth, during blood transfusions, and from organ transplants. Chagas disease can lead to severe cardiac and digestive problems in humans and domestic animals, but it appears to be tolerated in wild mammals. Tsetse fly-transmitted trypanosomes have evolved an elaborate genetic mechanism for repeatdly changing the antigenic nature of their protetive glycoprotein coat. Only a single gene out of some 1000 variable surface glyoprotein genes is expressed at a time. The variable surface glyscoprotein is usually duplicated and moved to 1-20 expression sites enar the end of the chromosome where it is transcribed. In the guts of the flies that spread them, trypanosomes are noninfective. When they are ready to transfer to the skin or bloodstream of their host, trypanosomes migrate to the salivary glands and acquire the thick coat of glycoprotein antigens that protect them form the host’s antibodies. Later, when they are taken up by a tsetse fly, the trypanosomes again shed their coats. The producitoh of vaccines against such a system is accordingly complex. Rleasing sterilzied flies to iimpede the rproduction of populations is another technique. Traps made of dark cloth and scented like cows but poisoned with insecticides have likewise proved effective.

A different trypanosome, T. brucei causes sleeping sickness on the African continent. It has a long incubation time and is very difficult to cure. Once the trypanosomes are transmitted by a group of insects called the triatomines, they multiply in muscle and blood cells. From time to time, the blood cells rupture and large numbers of trypanosomes are released into the bloodstream. The disease manifestations are divided into acute and chronic phases. In the acute phase, symptoms are nondescript and range form mild to severe fever, nausea and fatigue. A swelling called a “chagoma” at the site of the bug bite may be present. If the bug bite is close to the eyes, a distinct condition called Romana’s sign, swelling of the eyelids, may appear. The acute phase lasts for weeks or months after which the condition becomes chronic, which is virtually asymptomatic for a period of years or indefinitely. Eventually the trypanosomes are found in numerous sites around the body and in later years may lead to inflammation and disruption of function in organs such as the heart, the brain and the intestinal tract. Estimates put the prevalence at 8 million, 300,000 of whom live in the U.S. Chagas disease is a neglected parasitic infection in the U.S. Drugs for treatment are only available through the CDC. Recently, the U.S. begain screening all donated blood for Chagas Disease. See CDC

Plasmodium are blood and tissue protozoa. These parasites require two hosts; (1) a mosquito for sexual reproduction and (2) animals for asexual reproduction. Infection is by bite of the anopheles mosquito. Human pathogens include the following:

–Malaria:

—-Signs and Symptoms: after a 10-16 day incubation period, the first symptoms are malaise, fatigue, vaue aches and nausea with or without diarrhea, followed by bouts of chills, fever and sweating. These syptomes occur at 48-72 hour intervals, as a result of the synchronized rupturing of red blood cells.

Patients with falciparum malaria, the most virulent type, often display persistent fever, cough and weekenss for weeks without relief. Complications of malaria are hemoytic anemia from lysed blood cells and organ enlargement and rupture due to cellular debris that accumulates in the spleen, liver and kidneys. A serius complication of falciparum malaria is “cerebral malaria” where small blood vessels in the brain become obstructed due to the increased ability of red blood cells to adhere to veseel walls. The resulting decrease in oxxygen in brain tissue can result in coma and death.  See Mayo Clinic  See CDC

—-causative agent: 

Five species of over 200 species of the genus Plasmodium are known to commonly infect humans. They are P. malariae, P. vivx, P, knowleski, P. ovale and P. falciparum.  The five species show variations in the pattern and severity of disease. For example, P. falciparum is responsible for the vast majority of deaths.

—-Pathogenesis and Virulence factors:

The invasion of the merozoites into RBCs leads to the release of fever inducing chemicals into the bloodstream. Plasmodium also metabolizes glucose at a high rate, leading to hypoglycemia. The damage ot RBCs results in anemia.

—-Transmission:

All forms of malaria are spread primarly by the female Anopheles mosquito. About 200 million new cases are reported each year, about 90% in Africa. The most frequent vitims are children and young adults, of whom between 500k to 1 million die annually.

—-Diagnosis:

Malaria can be diagnosed defininitevely by the discovery of a typical stage of Plasmodium in stained blood smears. Newer serological proecdures are available. Other indications are knowledge of the patient’s residence or travel in endemic areas and symptoms such as recurring chills, fever, and sweating.

—-Prevention:

Abatement includes elimination of standing water that can serve as a breeding site and spraying of insecticides to reduce populations of adult mosquitoes, especially in or near human dwellings.

Serile male mosequitos have also been introduced into endemic areas.

One can reduce their risk of infections considerably by using netting, screens and repellants, by remaining indoors at night and by taking weekly doses of prophylactic drugs.

A vaccine callaed “RTS.S, is effective against P. faciparum (the most deadly and most common strain in Africa) in children.

—-Treatment:

——Quinine with chloroquine being the least toxic type is used in nonresistant forms of Malaria. By 1820, the active ingredient in the bark of Cinchona trees, quinine, had been identified. In the 19th century, British soldiers in India used quinine-containing tonic water to fight malaria. In 1944, American chemists synthesized quinine. Qyinine can affect DNA replication and also, when P. falciparum breaks down hemoglobin from red blood cells in the digestive vacuole, an intermediary toxic form of heme is released. Quinine may itnerfer with the subsequent polymerization of these hemes, leading to a buildup of toxic hemes that poison the parasite. Now several other synthetic drugs are available to treat maleria. 

A drug called “artemisinin, derived from a plant, is recommended in many situations.

Affecting the Reproductive Tract

Vaginitis: is an inflammation of the vagina.

–signs and sumptoms: in clude some degree of vaginal itching, depending ont he etiologic agent. Sumptoms may also include burning and sometimes a discharge.

–Causative agents: While a varienty of bacteria and even protozoa can cause vaginitis, the must well known agent is the fugus Candida albicans. C albicans is a dimorphic fungus that is noraml biota in the majority of humans, living in low numbers on many mucosal surfaces such as the mouth, gastrointestinal tract and vagina. In otherwise healthy people, the fugus is not invasisive.

—-Trichomonas vaginglis: Another possible cause of vaginitis is Trichomonas which are small, pear-shaped protozoa. Trichomonas is a common sexually transmitted infeciton. Because it does not form cysts, it is more delicate and must be transmitted by intimate contact between sexual parrtners. see CDC

–Transmission and epidemilogy: Vaginal infections are nearly always opporutnistics. Disruptions of the normal bacterial biota or even minor damage to the mucosal epithelium in the vagina canlead to overgrowth by this fungus. Disruptions may be mechanical such as trauma to the vagina or they may be chemical as wehn broad spectrum antibiotics taken for some other purpose temperarily diminish the vaginal bacterial population.

–Prevention and treatment: no vaccine is available for C. albicans. Topical and oral azole drugs are used to treat vaginal candidiasis and many of them are available over hte counter.

Affecting the Gastrointestinal Track

Amoebiasis is the second leading cause of death from parasitic disease worldwide. The causative protozoan parasite, Entamoeba histolytica, is a potent pathogen. Secreting proteinases that dissolve host tissues, killing host cells on contact, and engulfing red blood cells, E histolytica trophozoites invade the intestinal mucosa, causing amoebic colitis. In some cases amoebas breach the mucosal barrier and travel through the portal circulation to the liver, where they cause abscesses consisting of a few E histolytica trophozoites surrounding dead and dying hepatocytes and liquefied cellular debris. See Stanley  Amoebiasis is a common infection of the human gastro-intestinal tract.  Amoebiasis is more closely related to poor sanitation and socioeconomic status than to climate. It has worldwide distribution. It is a major health problem in China, South East and West Asia and Latin America, especially Mexico. Only about 10% to 20% of people who are infected with E. histolytica become sick from the infection. The clinical spectrum ranges from asymptomatic infection, diarrhoea and dysentery to fulminant colitis and peritonitis as well as extra-intestinal amoebiasis. Acute amoebiasis can present as diarrhoea or dysentery with frequent, small and often bloody stools. Chronic amoebiasis can present with gastrointestinal symptoms plus fatigue, weight loss and occasional fever. Extra-intestinal amoebiasis can occur if the parasite spreads to other organs, most commonly the liver where it causes amoebic liver abscess. Amoebic liver abscess presents with fever and right upper quadrant abdominal pain. Other organs can also be involved, including pleuropulmonary, cardiac, cerebral, renal, genitourinary, peritoneal, and cutaneous sites. In developed countries, amebiasis primarily affects migrants from and travellers to endemic regions, men who have sex with men, and immunosuppressed or institutionalized individuals. The use of night soil for agricultural purposes favours the spread of the disease. Epidemic/ outbreaks (occurrence of more cases of a disease than would be expected in a community or region during a given time period) are usually associated with sewage seepage into the water supply. See AIMU

Balantidium coli: is an intestinal protozoan parasite that causes the infection “balantidiasis”. It is most prevalent in tropical and subtropical regions. It is rare in the U.S. It is transmitted by the fecal-oral route. Humans can become infected by eats fruits and vegetables that have come into contact with fecal matter from an infected animal, as well as drinking and washing food with contaminated matter. Most people experience no symptoms. It infects the large intestine of humans and the cysts are then passed into the feces. It can be serious for immunocompromised people. Symptoms in these people include persistent diarrhea, weight loss, nausea and vomiting. It is treated with tetracycline, metronidazole, and iodoquinol. See CDC website

Cryptosporidium: is an intestinal protozoan that infects a vareity of mammals, birds and reptiles. For many eyars, it was considered an intestinal ailment exclusive to calves, pigs, chickens and other puoltry but it is ceraly a zoonosis as well. Humans accidentally ingest the oocysts with water or food that has been contaminated by feces form infected animals. The organism penetrates the intestinal cells and lives intracellularly in them. It undergoes asexual and sexual reproduction in these cells, produces more oocysts which are released into the gut lumen, excreted form the host and after a short time become infective again. The oocysts are highly infectious and extremely resistant to treatment with chlorine and other disnfectants. Half of the outbreaks of diarrhea associated with swimming pools are casued by Crytosporidium. Because chlorination is not entirely successful in eradicating the cysts, most treatment plants use filtraiton to remove them, but even this method can fail. Treatment is not usually required for otherwise healthy patietns. Antidiarrheal agents (antimotility drugs) may be used. Although no curative antimicrobial agent exists for Cryptosporidium, physicians will often try nitazoxanide, which can be effective agaisnt protozoa in immunocompetent patients. See K-State (outlines many potential treatments) for Cryptosporidium parvum)

Cystoisosporiasis is an intestinal disease caused by the microscopic parasite Cystoisospora belli. This is the same parasite that used to be called Isospora belli. The parasite can be spread by ingesting food or water that was contaminated with feces (stool) from an infected person. People become infected by swallowing mature parasites, for example, by ingesting contaminated food or water. Infected people shed the immature form of the parasite in their feces. The parasite usually needs about 1 or 2 days in the environment (outside of people) to mature enough to infect someone else. In some settings, the parasite might mature in less than a day. Cystoisospora usually is spread indirectly, such as through contaminated food or water. This is because the parasite needs time to mature. However, oral-anal contact with an infected person might pose a risk for transmission. The infection is treated with prescription antibiotics. The usual treatment is with trimethoprim-sulfamethoxazole, which is also known as Bactrim*, Septra*, or Cotrim*. People who have diarrhea should also rest and drink plenty of fluids. See CDC

Giardiasis: Giardiasis is a diarrheal disease caused by the microscopic parasite Giardia. A parasite is an organism that feeds off of another to survive. Once a person or animal (for example, cats, dogs, cattle, deer, and beavers) has been infected with Giardia, the parasite lives in the intestines and is passed in feces (poop). Once outside the body, Giardia can sometimes survive for weeks or months. Giardia can be found within every region of the U.S. and around the world. See CDC

Giardia lamblia (syn.Giardia intestinalis, Giardia duodenalis) is a flagellated unicellular eukaryotic microorganism that commonly causes diarrheal disease throughout the world. It is the most common cause of waterborne outbreaks of diarrhea in the United States . It is occasionally seen as a cause of food-borne diarrhea. In certain areas of the world, water contaminated with G. lamblia cysts commonly causes travel-related giardiasis in tourists. Giardia species have two major stages in the life cycle. Infection of a host is initiated when the cyst is ingested with contaminated water or, less commonly, food or through direct fecal-oral contact. The cyst is relatively inert, allowing prolonged survival in a variety of environmental conditions. After exposure to the acidic environment of the stomach, cysts excyst into trophozoites in the proximal small intestine. The trophozoite is the vegetative form and replicates in the small intestine, where it causes symptoms of diarrhea and malabsorption. After exposure to biliary fluid, some of the trophozoites form cysts in the jejunum and are passed in the feces, allowing completion of the transmission cycle by infecting a new host. See Adam

The greatest clinical experience is with the nitroimidazole drugs, i.e., metronidazole, tinidazole, and ornidazole, which are highly effective. A 5- to 7-day course of metronidazole can be expected to cure over 90% of individuals, and a single dose of tinidazole or ornidazole will cure a similar number. Quinacrine, which is no longer produced in the United States, has excellent efficacy but may be poorly tolerated, especially in children. Furazolidone is an effective alternative but must be administered four times a day for 7 to 10 days. Paromomycin may be used during early pregnancy, because it is not systematically absorbed, but it is not always effective. Patients who have resistant infection can usually be cured by a prolonged course of treatment with a combination of a nitroimidazole with quinacrine. See Gardner

 Affecting the Nervous System

Amoebas:

Amoebae are unicellular microorganisms which are trophozoites in that they have 2 stages; an active motile feeding stage that is non infectious and a cyst stage that is infectious. Important amoebae include the following:

–Naegleria fowleri:

Naegleria fowleri is an ameboflagellate found in freshwater lakes and ponds and is the casative agent of primary amebic meningoencephalitis, a rapidly fatal disease of the central nervous system. The determinants of virulence for this ameba are unkown, but resitance to complement lysis appears to play a major role in its pathogenicity. While both pathogenic and nonpathonic Naegleria species activate AP, pathogenic N. fowleri amebae are resistance to the lytic effect of complement. Fritzinger (Infection and Immunity, 2006, 74 (2) pp. 1189-1195) demonstrate a CD59-like protein which could bind human C9 on the surface of pathogenic N. fowleri amebae and that the ability of a pathogenic species of Naegleria to synthesize a protein which protects the amebae from lytic molecules, such as MAC of complement (C5b-C9), may serve as an important virulence factor.

Naegleria fowleri occurs in people who have been swimming in warm, natural bodies of freshwater. Infection can begin when amoebas are forced into human nasal passages as a result of swimming, diving, or other aquatic activities. Once the amoeba is inoculated into the favorable habitat of the nasal mucosa, it burrows in, multiples and uses the olfactory nerve to migrate into the brain and surrounding structures. The result in primary ameibic meningo-encephalitis is a rapid massive destruction of brain and spinal tissue that causes hemorrhage and coma and invariable ends in death within a week or so. Early therapy with amphotericin B, sulfadiazine or tetracyline in some cominbation can be of some benefit. Becasue of the wide distribution of the amoeba and its hardiness, no general method of control exists. Public swimming pools and baths must be adequately chlorinated and checked periodically for the amoeba.

–Acanthamoeba: differs from Naegleria below in its portal of entry. It invades broken skin, the conjunctiva, and occasionally the lungs and urogentical epithelia. It causes a meningoencephalitis somewhat similar to that of Naegleria. The course of infection is lenghthier but nearly as deadly with only a 2-3% survival rate. At special risk for infection rare people with traumatic eye injuries, contact lens wearers and AIDS patients exposed to contaminated water.

—acanthamoebae are a potential pathogen in ocular keratitis. Improper contact lense maintenance can result in infection. Incubation time is longer than naegleria.

—Giardia lambia is a flagellate. Symptoms can be mild to severe (particularly for those with immunocompetency like AIDS patients).

—Balantidium coil is the only member of the ciliate group which is pathogenic for humans, particularly for AIDS patients.

—cryptosporidium typically caues watery diarrhea with abdominal pain that lasts for 1-4 weeks or more. Children, the elderly and immunosuppresed are particularly susceptible to severe or protracted disease. It can be spread when the feces of an infected animal is deposited in the water supply. One of the largest breakouts occurred in Milwaukee in 1992. Crytosporidium can be particularly severe in  patients. Crytosporidium belongs to the group coccidia.

—isospora belli also belong to the coccidia. It reproduces in the intestinal epithelium and results in tissue damage.

—enterocytozoan is a species of the microsporidia and causes chronic diarrhea in AIDS patients. 

—pneumocystis carinii is an important cause of pneumonia in immunocompromised people and is transmitted by inhalation (but not from person to person). Untreated P. carinii mortality is almost 100%.

—entamoeabae histolytica: have a highest infection rate in tropical and sub-tropical (which includes Florida and Southern California) area. 

—naegleria:  The genus Naegleria consists of a group of free living ameboflagellates found in diverse habitats through the world. Naelgeria have been isolated from freshwater lakes, ponds, domestic water supplies, swimming pools, thermal pools, soil and dust Although over 30 species of Naegleria have been isolated, only Naegleria fowleri has been isolated from humans. (Marciano-Cabral, “The immune response to Naegleria fowleri amebae and pathogensis of infection”. FEMS Immunol. Med Microbiol 51 (2007) 243-259.)

Toxoplasma gondii: is a protozoal infection in the fetus and in immmunodeficient people, espcially those with AIDS. It is severe and often fatal. In otehrs, most cases of toxoplasmosis are asymptomatic or marked by mild symptoms such as sore throat, lumph node enlgargemetn,a nd low grade fever. Toxoplasma is an obligate intravellular parasite, making its ability to invade host cells an important factor for virulence. T. gondii is a very successful parasite iwth so little host specificity that it can attack at least 200 species of birds and mammals. However, the parasite udnergoes a sexual phase in the intestine of cats and is then released in feces, wehre it becomes an infective oocyst that survives in moist soil for several months. These forms eventually enter an asexula cyst state in tissues, called a psuedocyte. Most of the time, the parasite does not cycle in cats alone and is spread by oocysts to intermediate hosts, including rodents and birds. The cycle returns to cats when they eat these infected prey animals. Cattle and sheep can also be infected. Humans appear to be constantly exposed to the pathogen. The rate of infection can be as high as 90% in some populations. Many cases are casued by ingesting pseudocysts in undercooked contaminated meat, and other source s include contact with other mammals or even dirt and dust contamated with oocysts. In view of the fact that the oocysts are so widespread and resistant, hygiene is of paramount importance in controlling toxoplasmosis. Adequate cooking or freezing below -20C destroys both oocysts and tissue cysts. Oocysts can also be aovided by washing the ahnds after handling cats or soil possible contaimianted with cat feces, especially sandboxes and litter boxes.