Protozoan Parasites

After completing the article, the reader should be able to:Parasitic infections continue to have a substantial socioeconomic impact and are associated with high morbidity and mortality globally, despite recent advances in prevention and treatment. The need for improved epidemiologic surveillance, more accurate diagnostic tools, newer medications to combat resistance, and faster vaccine development continues to be considerable.In the United States, the Centers for Disease Control and Prevention (CDC) identified five “neglected parasitic infections” (NPIs) affecting a substantial number of individuals. (1) Commonalities among these infections include underrecognition due to a lack of clinical awareness and optimal diagnostic tests and limited means for therapy and prevention. This article focuses on six protozoan parasitic infections, highlighting new diagnostic tests and reviewing epidemiology and management: cryptosporidiosis, giardiasis, amebiasis, malaria, toxoplasmosis, and trichomoniasis.Cryptosporidiosis and giardiasis are endemic infections in the United States, predominantly seen in children in northern states during warm months in association with recreational water use. (4)(5)(6) Cryptosporidium sp, Giardia lamblia, and Entamoeba histolytica (amebiasis) are all intestinal parasites transmitted feco-orally via consumption of contaminated food and water and sexual activity. All three enteric parasites have a small infective dose and have been associated with outbreaks. (7) Newer tests with better sensitivity and specificity than stool microscopy are now available to aid in the diagnosis of these infections.In the United States, immigrants and travelers from endemic areas are the most likely population to have amebiasis or malaria. (8)(9) Malaria, caused by Plasmodium sp, continues to claim the lives of 1300 children every day, despite a 42% decline in the global mortality rate since 2000. (10) In nonendemic areas, 15% of imported cases are seen in children, and malaria continues to pose a challenge to clinicians caring for travelers, with delays in diagnosis of up to 2 weeks. (11)Toxoplasmosis and trichomoniasis are two of the five NPIs. (The other three parasitic infections of Chagas disease, cysticercosis, and toxocariasis are not discussed in this article.) (1) Both diseases disproportionately affect low-income populations and ethnic minorities. (2)(3) Toxoplasmosis can cause significant debilitation among affected infants and is the second most common cause of foodborne illness resulting in death. (12) Trichomoniasis is “more common than chlamydia, gonorrhea and syphilis infections combined,” but control efforts have been insufficient. (3)Cryptosporidium sp are a well-known cause of diarrhea worldwide. Two species cause most of the infections in humans: C hominis infects humans only, while C parvum also affects bovines and other mammals.In the United States, where cryptosporidiosis is a nationally notifiable illness, 7000 to 9000 (2.5 to 2.9 per 100,000 population) cases were reported for 2009 and 2010, with most cases occurring in children 1 to 9 years of age. (4) The incidence of infection was highest in the northern states and peaked in the summer and fall, mirroring increased communal and recreational water use.Transmission of infection is via the fecal-oral route. Numerous oocytes are shed in the stool, but as few as 10 ingested oocysts can result in infection. Furthermore, oocysts remain infectious in the environment for months. Outbreaks have been reported in recreational water facilities, child care centers, and in association with contaminated drinking water systems. (7)The incubation period for cryptosporidiosis is 1 to 4 weeks, with an average of 7 days. Although asymptomatic infections occur, affected patients generally experience voluminous, nonbloody, and watery diarrhea. The clinical presentation may vary, depending on the infecting species. C hominis is associated with malaise, vomiting and nausea, and increased oocyst shedding and duration; C parvum is associated with diarrhea only. (13)For most immunocompetent patients, cryptosporidiosis is self-limited and symptoms usually last 1 to 2 weeks. However, malnourished children or those with T-cell immunodeficiency may have a severe and protracted course that lasts for weeks to months, resulting in dehydration and death.Atypical and extraintestinal manifestations may be seen among patients with acquired immune deficiency syndrome (AIDS). (14) Pneumatosis cystoides intestinalis, which are multiple gas-filled sacs in the intestinal wall, can lead to pneumoperitoneum. Cholecystitis, pancreatitis, and respiratory disease may also been seen.The diagnosis of cryptosporidiosis can be established by: 1) microscopic examination of stool for oocysts using modified acid-fast stain, direct immunofluorescence, or auramine phenol stain; 2) stool antigen detection via enzyme immune assay (EIA) or immunochromatography; and 3) stool molecular testing via polymerase chain reaction (PCR). Visualization is highly specific, but sensitivity is low. Antigen detection, especially with EIA, has better sensitivity and high specificity (80%–100%), is commercially available, and does not require a skilled technician, unlike oocyst visualization. PCR has both high sensitivity and specificity as well as the ability to differentiate species. However, PCR is expensive to perform.Therapy is usually not required among immunocompetent patients in whom the symptoms are self-limited in 1 to 2 weeks. For patients with depressed immune function, therapy may be necessary.Nitazoxanide is the only drug for cryptosporidiosis approved by the U.S. Food and Drug Administration (FDA). It is approved for use among children at least 12 months of age; the dosing recommendations are listed in Table 1. Treatment with nitazoxanide results in decreased duration of diarrhea; most cases resolve within 3 days of therapy, and oocysts become undetectable in stools within 7 to 10 days after start of treatment. (15)Human immunodeficiency virus (HIV)-infected patients with CD4 counts less than 200 cells/μL or immunocompromising conditions with equivalent degrees of T-cell function are at highest risk for severe and prolonged infection. Nitazoxanide may be ineffective in this population. (14) Restoration of immune status with use of antiretroviral therapy or withdrawal of immunosuppressing medications is necessary for treatment.Regulatory changes leading to enhanced treatment of surface water supplies and prevention of transmission through drinking water were made following the cryptosporidiosis outbreak in Wisconsin in 1993. Ground water supplies are also required to have additional treatment and filtration. (4)Travelers to high-risk areas or those who intend to drink untreated water sources (eg, hikers, campers) are advised to boil water for at least 1 minute or use water filters certified by the National Safety Foundation (Table 2).Cryptosporidium sp are resistant to chlorination. Avoidance of swallowing water when in swimming pools, river, or lakes is advised. Those who have been recently infected with cryptosporidiosis should not swim in recreational water for at least 2 weeks after the resolution of diarrhea.Other preventive measures include washing of hands and raw foods, barrier protection during oral-anal sex, and avoidance of contact with human and animal feces.G lamblia, also known as G intestinalis or G duodenalis, causes giardiasis and is one of the common parasitic enteropathogens worldwide. In the United States, it is the most common intestinal parasitic infection, with 19,000 cases reported annually. The highest number of cases occurs in the northeast states among children ages 1 to 9 years during the summer. (5)Ingestion of as few as 10 cysts can result in infection. Infected humans and animals may contaminate water and food products with fecal matter. Outbreaks have occurred in child care settings and in association with contaminated water supplies. (7)Infected individuals may remain asymptomatic or may exhibit acute or chronic symptoms. The incubation period is 1 to 4 weeks. An infected individual presents with acute watery, nonbloody, foul-smelling, and greasy diarrhea; abdominal distention; and anorexia with or without fever. Symptoms usually last 1 week, but infective cysts may be shed for months. Occasionally, symptoms become chronic, resulting in bouts of diarrhea for months to years and resulting malabsorption and failure to thrive.Extraintestinal and postinfectious complications with giardiasis have been described and include cholecystitis, ocular pathologies, allergies, reactive arthritis, myopathy, and irritable bowel syndrome. (16)Visualization of cysts or trophozoites in the stool with trichrome stain has a sensitivity of 70%. To improve sensitivity, the test may be repeated thrice on separate days in a week. Medications (eg, antibiotics, antacids, laxatives, enema) that may alter the morphology of the parasites should be withheld for 3 days.Stool antigen testing with either immunofluorescence assay or EIA has sensitivity and specificity of 85% to 100% and is available commercially.When the stool test results are negative and suspicion for giardiasis remains high, string test, duodenal aspiration, or duodenal biopsy may be employed.Therapy is not routinely administered to asymptomatic individuals. For those who are symptomatic, metronidazole administered for 5 to 7 days or a single dose of tinidazole has a cure rate of greater than 85%. Nitazoxanide is administered for 3 days. Although metronidazole is often used, only tinidazole and nitazoxanide are approved by the FDA for this indication (Table 1).In cases of relapse, the recommendation is to repeat administration of the same drug. Patients with frequent infections should be evaluated for repeated exposures and immunodeficiency (hypogammaglobulinemia and combined variable immunodeficiency).In addition to sanitation and proper hygiene, children should be excluded from child care until asymptomatic and refrain from swimming for 1 week. Boiling, filtration, or treatment of water is recommended for campers and hikers. Barrier protection during oral-anal sex is recommended. Specific recommendations for prevention of infection are available at the CDC website (Table 2).E histolytica and E dispar are morphologically similar but genetically different species. E histolytica is considered invasive and pathogenic while E dispar is not. This distinction was recognized in the 1990s and has implications for diagnosis and management.As with giardiasis and cryptosporidiosis, feco-oral transmission of E histolytica occurs with ingestion of contaminated food and water or via sexual activity. Ingested cysts undergo excystation to become trophozoites, which then multiply by binary fission to produce more cysts. Trophozoites may colonize the large bowel or may invade tissue and induce cell destruction. Cysts survive in the environment for weeks to months and are responsible for transmission. As few as 10 cysts (or less) can cause infection.Amebiasis accounts for an estimated 100,000 annual deaths worldwide. It is considered endemic in Central and South America, Africa, and Asia. In the United States, immigrants and travelers from endemic areas, institutionalized persons with poor sanitary conditions, and men who have sex with men are considered at high risk for amebiasis. (8)Most infected people remain asymptomatic; only 10% manifest symptoms within 2 to 4 weeks, although some may take years to become ill after ingestion of cysts. Asymptomatic infected individuals may excrete cysts intermittently for years.Intestinal and extraintestinal diseases may be seen among symptomatic patients (Table 3). Intestinal disease can range from diarrhea to a more severe and complicated presentation, including amebomas. An ameboma, also called an amebic granuloma, is a mass that develops from inflammation of the colon and can be mistaken for a tumor. Patients with amebic colitis usually present with gradual progression over several weeks of diarrhea (bloody in 70% of patients) and abdominal pain; only 10% may develop fever. (8)The most common extraintestinal manifestation is hepatic abscess, 90% of which are located in the right lobe. Affected patients present with fever (>85%), abdominal pain (>84%), and hepatomegaly (>30%). (8) Hepatic abscesses may rupture in about 20% of cases, leading to pleural, peritoneal, or pericardial involvement with associated high mortality. Patients with amebic colitis and neurologic symptoms may have brain abscess from hematogenous spread. Cutaneous amebiasis may result from prolonged exposure to the tissue-invasive trophozoites excreted in the feces, extension of a ruptured appendiceal or liver abscess, or through direct infection of the stool examination for cysts and trophozoites has been for However, stool examination is to differentiate Entamoeba sp dispar and E from E In sensitivity is of The recommendation is to use the commercially available E antigen test on stool to differentiate E histolytica from E molecular and have better specificity but are not to E by EIA, are present in more than 70% of patients with colitis and extraintestinal diseases as well as 10% of patients with asymptomatic infection. The of does not differentiate or acute infection. In acute cases where amebiasis is highly testing should be repeated in 1 to 2 weeks to for Visualization of trophozoites on tissue is considered the for for Entamoeba on the species and of involvement (Table 3). Asymptomatic intestinal with E dispar does not require treatment. In with E histolytica treatment due to the high risk for invasive illness and transmission (Table are with the metronidazole or to tinidazole is better and administered for a duration (Table 3). are well after administration and are ineffective for of as of patients may have despite therapy with these be following therapy with to and transmission. for therapy include and (Table 3). are from the and high is not available commercially in the United therapy for invasive illness may include of especially is clinical after of of or of patients with amebiasis is as is treatment of asymptomatic Barrier protection during sexual is also to endemic areas should boil drinking water for at least 1 As with cryptosporidiosis, use of a water with an of 1 or is recommended. should be and sp known to cause malaria in humans include and The outbreak in and of human infections to of a The these in Africa, is considered the most of all parasites is in and South America, while is most common in malaria has and can be in Africa, South America, and Asia. is in Asia. In to the other Plasmodium sp, and cause severe estimated people are at risk for malaria. continues to be one of the leading causes of in In were malaria (10) of the deaths occurred in and were caused by the United States, efforts in the to the of malaria. However, sp are in the the of of malaria. In the United States, to cases are annually. are with occurring in United who have a of recent to endemic areas and in of other of cases occurred in children than In by may Plasmodium sp to humans in and in nonendemic areas, resulting in a known as malaria. of are and a most individuals become symptomatic within 1 to 4 weeks. diagnosis has been seen in patients who and in patients infected with and Both and have a in the with occurring months to years symptoms of malaria are and include symptoms of and As the disease to the of the from the may be every for and and every for and may also be can be as either or Disease on the Plasmodium sp, and immune status of the illness is associated with and The clinical and for severe illness (Table to children with severe malaria are more likely to have duration of illness 7 neurologic and invasive infection. with and is the for the diagnosis and is a of of infection and to treatment. of the greater of has better sensitivity in infection, especially in while is for tests should be repeated every 12 to for three to The for these tests is the need for skilled diagnostic test in was approved by the FDA in This test, which malaria has the ability to infections due to and and on limited and malaria as may not be able to infection when is of the result or should be by with tests are especially in the but these tests are not of to Plasmodium exposure but not on disease the ability to drug resistance, and species. cases can be on an with Patients with severe disease should be for administration of and The CDC for patients with greater than 10% or this therapy results in in those and those not who are to medications or those who have severe malaria are with or therapy is until patients can with may result in and patients are to care for frequent In the United States, is the only for treatment of severe malaria. However, which is now the for severe malaria, can be from the CDC an new drug is the drug of for patients able to who have infection acquired from Those from areas with may be 1) 2) 3) or or infections caused by or should be administered with the to in the Patients should be for deficiency administration of on drug and duration is available at the CDC website (Table to endemic areas should take to through avoidance of use of as and and use of of is on drug in the and to The CDC on malaria per and the recommended per (Table is caused by the This in three and a in transmission. The trophozoites invade during infection, the are present in tissue cysts and and the are present in are the with one of to including and become after ingestion of the oocysts and in tissue cysts. and have a of infection due to to contaminated and infected infection by ingestion of oocysts through contaminated food or water or by consumption of raw in tissue cysts. with and is one of the three causes of foodborne illness resulting in death. (12) of infection include transmission to the and of or from infected among with the highest seen in South and some of In the United States, the has been with of of infected with The is to be to multiple including improved in cysts in on proper of and of use of to to improve and and to that the tissue and increased use of also the The highest is seen among and those from low-income patients who become infected are generally may have illness or develop Symptoms are usually over or can lead to and may as a result of infection or acquired infection. Affected individuals may be of have develop in or have or patients, as those with infection, a acquired or infection may result in and in these patients is usually and has a poor despite treatment. patients with a CD4 less than cells/μL have a of who the infection during are usually infection acquired during an risk of transmission to the of of infection with the risk of transmission to the when infection is acquired at weeks of to at weeks and at weeks. occurring at an results in a more affected presentation in the affected and may range from asymptomatic infection to death. The of and is highly of manifestations include and complications include and infected patients may have years as a result of of infection with conditions as and has been but a has to be is by or in acute or infection, has is during infection, but it can remain up to 2 of of infection In of results can be as high as in tests by test result should be through a and may also be during acute infection and can last for weeks to about 1 to 2 weeks after infection and for the risk for To the of infection may be The of of to the antigen develops over following infection. the of that infection occurred more than 5 months the of infection is who infection during are at risk of transmission and may from treatment. In those who acquired the infection are less likely to it and not require may also be via PCR in or of the via of or tissue acute is on the of to a patients with asymptomatic infection or symptoms as or illness are usually not the symptoms are severe or for is on of inflammation and the and the or immunocompetent patients, resolution occurs within 1 to 2 months. patients with are usually with and for 4 to weeks after resolution of by or until has to are treatment is recommended for who have acute infection during to transmission or to the of therapy on the and transmission has is usually is less than weeks and is of infection PCR and of on therapy with and is administered for or is of infection. is considered an drug in the United and is available through the FDA new drug who are infected are and for 1 to associated with for are often associated with that can of therapy more and may with is administered to and diarrhea may with should exposure to The should be oocysts require 1 to 5 days to and become In other as for among is to treatment during is not in the United should include washing of and and avoidance of consumption of raw or products at is recommended (Table with or and is to patients with CD4 counts less than caused by the protozoan is the most common transmitted infection in the with an estimated new cases annually. the United States, new cases affecting and Although most infections are asymptomatic and not with trichomoniasis are now and may have been increased risk of and other transmitted infections, increased risk of and and The poor and are disproportionately with trichomoniasis are may have or or the may be and a of infected men may have with or in children can with sexual or in following transmission during of with trichomoniasis may have the parasites are to survive in the environment of the resolution of occurs over several weeks without disease has been reported in both and examination of may the of However, this test has a sensitivity of only to 70%. of or is considered the and is highly may not be available for up to 1 week, and the test and available tests use newer for enzyme test, and tests have faster to a few with improved sensitivity while specificity at to this these tests are only for use in from test may but it is not recommended as a of poor are the only for treatment of single dose of either metronidazole or tinidazole is therapy is and has use of metronidazole a for 7 days is recommended. In cases of treatment a to course of tinidazole or metronidazole may be is not recommended due to poor therapy is recommended for patients with reaction to the is should be and and patients and should from sex until both are and are of also infection.