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Home , Axostyle, Balamuthia mandrillaris, Emetine, Entamoeba histolytica, Giardiasis, Monsters Inside Me

Readings- pt. 1 • Ch. 8 (p. 163 [table 8.2] Lecture 7: Emerging Parasitic • Ch. 11 (pp. 272-74, 275-76, 286) Protozoa part 1 (Intro, Intestinal Protozoa (non-Apicomplexan), FLA, Microsporidia

Presented by Matt Tucker, M.S., MSPH [email protected]

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Monsters Inside Me Learning objectives: Protozoans

• Primary amebic ( fowleri, free living ) • Describe basic characteristics of protozoa Background: http://animal.discovery.com/invertebrates/monsters-inside-me/brain-eating- amoeba-naegleria/ • Know basic life cycle and developmental stages Video: http://animal.discovery.com/videos/monsters-inside-me-the-brain-eating-amoeba.html • Required hosts keratitis (Acanthamoeba spp., free living amoeba) – strategy – Background: http://animal.discovery.com/invertebrates/monsters-inside-me/acanthamoeba- Infective and diagnostic stages keratitis/ – Unique character of Videos: http://animal.discovery.com/videos/monsters-inside-me-acanthamoeba-keratitis.html • Know the common characteristics of each group http://animal.discovery.com/videos/monsters-inside-me-acanthamoeba-keratitis- – Be able to contrast and compare parasite.html • Diseases, high-risk groups • Diagnostic methods, treatment • Know important parasite survival strategies

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Protozoa (boring biology?) Taxonomic Overview

• Unicelluar • – Cilia, Flagella, Amoeboid, Gliding • Sarcomastigophora – (Trypanosoma, Leishmania, , ) – Amoebae ( spp., Naegleria, Acanthamoeba) • Phylum Ciliophora (Balantidium) • Phylum Microsporidia (encompasses many genera) • Phylum ‐sporozoa (Cyclospora, , Toxoplasma, , Babesia) • Usually range from 10–50μm

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1 Parasitic Protozoa

• Infect a variety of hosts • Multiplication within hosts, enabling huge numbers in short periods • 50,000 species of protozoa, of which a fifth are parasitic • Life cycles – Usually less complex than helminths – Many examples of direct and indirect – Cyst form offers protection against harsh conditions, allowing to survive extreme temperatures or harmful chemicals or lack of , water, or oxygen

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On the Menu: Lecture 7

Intestinal Protozoa Other Important Protozoa • Amoebae • Free-living amoebae • – Microsporidia • Flagellates – Giardia lamblia – • – Balantidium coli

Another nice review slide

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Entamoeba histolytica E. histolytica Life Cycle

• Cosmopolitan distribution • Infects 500 million people worldwide- causes Amebiasis • 100,000 deaths per year have been attributed to complications of amebiasis, notably – Second in terms of deaths from parasitic protozoa • More prevalent and more severe in tropical/subtropical locations • Risk groups – Crowded conditions: orphanages, prisons, mental institutions may exacerbate transmission of disease. • 1-5% infected in U.S. • Highly pathogenic • Humans=definitive host • Fecal-oral transmission

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2 trophozoites and cysts Symptoms and Pathology

• Asymptomatic ("luminal amebiasis") • Invasive intestinal amebiasis (, colitis, appendicitis, toxic megacolon)

• Invasive extraintestinal amebiasis (liver abscess, peritonitis, pleuropulmonary abscess, cutaneous and genital amebic lesions).

• Death and illness due to dysentery and liver abcess. • Typical flask-shaped lesions in the large intestines

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Amebiasis caused by Entamoeba histolytica Diagnosis

• Microscopic identification of cysts and trophozoites in the stool – Characteristics: bulls-eye nucleus, ingested red blood cells, chromatin bar • Differentiation from other amoebae based on morphologic characteristics of the cysts and trophozoites. – Entamoeba dispar (non-pathogenic) vs. E. histolytica, based on isoenzymatic, immunologic, or molecular analysis.

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Treatment Prevention

• Asymptomatic- only carry cysts • Safety of drinking water supplies – (Flagyl) – Iodoquinol – Cysts are fairly resistant to chlorination of – furoate (Furamide) if passing cysts (not in U.S.) drinking water – • Symptomatic • Environmentally stable cysts – Acute amebic dysentery – Heat water above 50°F . Emetine HCL – Liver abscess – Freezing kills cysts . Flagyl . or Omidazole (not in US) • Traveler precautions – Followed by treatment with iodoquinol, paromomycin, or diloxanide furoate

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3 Outbreaks Giardia lamblia

• Obligate parasite that infects numerous Flagellated with ventral sucker disk • World’s Fair, Chicago (1933) mammalian hosts (for attachment) – >1400 cases, 100 deaths • Fecal-oral transmission through food and • Los Angeles, CA. (1983) water – 38 patients over the course of 3 months were diagnosed, in • Distributed worldwide, more prevalent in comparison to a previous frequency of about 1 case per warm climates, and in children. month. – Up to 2 million cases in U.S. per year • Tbilisi, republic of Georgia (1998) – Prevalence 3-7% in developed countries – A case-control study indentified 177 cases, but outbreak was – Average prevalence of 20% in widespread may have affected 84,000–225,000 people. undeveloped countries • The most frequent cause of non- • Emerging in Japan bacterial in U.S. – Male homosexuals and mentally handicapped persons in • Risk groups in the US: travelers, institutions. children in day care, homosexual men . 500–600 cases of amebiasis reported annually, with 3-4 deaths

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Giardia Life Cycle

• Acute disease develops after an incubation period of 1-14 days (average of 7 days) and usually lasts 1-3 weeks. • Symptoms – Diarrhea, , bloating, ,vomiting, (fatty diarrhea). – In chronic giardiasis, the symptoms are recurrent and and debilitation may occur. • Suction force may damage microvilli. • Large number of parasites may interfere mechanically with digestion. • Symptoms may result from inflammation of the mucosal cells of the . • Asymptomatic carriage • Antigenic Switching occurs during differentiation to cyst stage when a parasite is transmitted from one host to another. – Enhances the probability of parasite being transmitted to reservoir animals that are partially immune to other variants.

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Diagnosis and Treatment Prevention

• Identification of cysts or trophozoites • Proper and disposal of waste (monkey-face morphology) in the • Avoid drinking water from sources associated with outbreaks • Samples of duodenal fluid or • Avoid swallowing water while swimming in public pools, duodenal biopsy may demonstrate water parks trophozoites. • Avoid livestock and exotic pets, zoonotic transmission • Antigen detection tests by enzyme • In day care centers: wash hands and proper disposing of immunoassays, and detection of diapers parasites by immunofluorescence. • Hikers and backpackers: boil, filter, chemically treat water • Water filtration (moderate Chlorine resistance) • Treatment: Metronidazole, http://www.cdc.gov/healthywater/pdf/swimming/resources Tinidazole, in children. /giardia-factsheet.pdf

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4 Major Outbreaks Trichomonas vaginalis

• Europe • Causes the most prevalent non-viral sexually Characteristic mutiple flagella transmitted disease worldwide at top and on side – Sweden 1986- >1400 cases • Only known host is humans • Worldwide prevalence, but higher prevalence – Norway 1994- >1300 cases among persons with multiple sexual partners or other venereal diseases • U.S. • No cyst stage; sexual transmission of trophozoites – Colorado (Vail-1978): 5,000 cases during intercourse • Found in vagina and urethra of women and – Rome, N.Y. (1974-1975): 4800-5300 cases prostate, seminal vesicles, urethra of men – Bradford, PA. (1979): 3500 cases • Other non-pathogenic species: T. hominis, T. tenax • Over 180 million infected each year globally, up to 8 – Berlin, N.H. (1977): 7000 cases million in U.S – Trichomonas is the most common parasitic infection – (1996): 77 cases in the U.S., accounting for an estimated 7.4 million cases per year.

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Life Cycle-T. vaginalis : Clinical Features

• Women Trichomonas vaginalis – More persistent infection resides in the female – Vaginitis with a pus-like discharge (leukorrhea) is the prominent lower genital tract and the symptom, and can be accompanied by vulvar and cervical lesions, male urethra and prostate, abdominal pain, dysuria and dyspareunia. where it replicates by – Predisposes to HIV infection- erosion of vaginal wall-blood into vagina binary . The – Pelvic Inflammatory Disease- damage the fallopian tubes and tissues parasite does not appear in and near the uterus and ovaries. to have a cyst form, and – Increased risk of cervical cancer, association with preterm birth and does not survive well in premature rupture of membrane and low birth weight infants the external • Males usually asymptomatic; occasionally infects prostate and environment. seminal vesicles. – Increased HIV transmission, infectivity – Common cause of nongonococcal urethritis – Male infertility- decrease sperm motility and viability

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Trichomoniasis: Diagnosis/Rx Prevention

• Clinical presentation: discharge, strawberry cervix • In men, anterior urethral or prostatic secretions • Abstain from sexual contact, or to be in a long-term should be examined. mutually monogamous relationship with a partner • Microscopic examination of vaginal and urethral secretions can establish the diagnosis by detecting who has been tested and is known to be uninfected. actively motile organisms. • Condom use for as long as both partners are • Direct immunofluorescent antibody staining is more sensitive than wet mounts, but technically more infected complex. • Any genital symptom such as discharge or burning • PCR assays Treatment during urination or an unusual sore or rash=consult • Metronidazole and tinidazole; therapy is usually a health care provider immediately. highly successful. • • Strains of Trichomonas vaginalis resistant to both Possible transmission via contaminated towels, drugs have been reported. washcloths, clothing

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5 Comparing, Giardia, Trichomonas and E. Histolytica Balantidium coli

G. lamblia E. histolytica T. vaginalis Morphology Ameba Flagellate/Ameba • Largest protozoan and only infecting humans – Trophozoites: 50x35 µm and 100x70 µm, Cysts: 50-70 µm Life form s Trophozoite Trophozoite Trophozoite only Resistant Cyst Resistant Cyst No Cyst form • invasive in large intestines: causes dysentery • Extraintestinal spread (e.g. lungs, liver) Host Many mammals Humans Only Humans Only including humans • Pigs implicated as reservoir host Transmission Ingestion of Cyst Ingestion of Cyst Sexual – Other potential animal reservoirs include rodents and Intercourse nonhuman primates. Disease Diarrhea/ Diarrhea/ Vaginitis • Worldwide distribution Manifestation s Dysentery Dysentery • Periodic outbreaks in institutionalized populations

Review, anyone?

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Free-living amoebae

• Usually found in warm bodies • Species of Acanthamoeba, Balamuthia, Naegleria and are important causes of of water such as ponds, disease in humans and animals. irrigation ditches, lakes, coastal – 9 species of Acanthamoeba implicated in human waters, and hot springs, well disease. water • Naegleria fowleri and Acanthamoeba spp. – Water temp. between 77–95:F commonly found in lakes, swimming pools, tap water, soil, and heating and air conditioning units. Attack of the……. • Can cause primary amebic • , is morphologically similar to Acanthamoeba and causes human disease. • Other species are non- • While infrequent, occur worldwide. pathogenic to humans – Can be isolated from all types of fresh water and soil habitats

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Naegleria fowleri life cycle Naegleria fowleri in the USA

• In U.S., has caused infections in 15 southern tier states – 121 deaths in the U.S. from 1937 through 2007. – From 1998 to 2007, 33 infections were reported in the U.S., all but one died – 6 documented deaths in 2007, all in warmer regions (Arizona, Texas, Florida)

• Florida – Prior to 2008, primary amebic meningoencephalitis was not a reportable disease in Florida. . 30 cases have been documented from 1962 through 2007. Of the 30 cases, 19 were from Central Florida, (3 in Orange County in 2007) – Other counties: Baker, Brevard, Broward, Citrus, Lee, Miami-Dade, Orange, Pasco, Pinellas, Polk, Putnam, Seminole and 3 unknown counties. All cases resulted in death.

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6 Primary Amebic Meningoencephalitis

• Acute and usually lethal, central nervous system (CNS) disease • The ameoba enters the nasal passages, 3 deaths in Summer penetrates the nasopharyngeal mucosa, and 2007 around migrates to the olfactory nerves, eventually Orlando area invading the brain through the cribriform plate. • The initial symptoms of PAM start 1-14 days after infection. – Headache, fever, nausea, vomiting, and stiff neck. • As the amoeba causes more extensive destruction of brain tissue this leads to confusion, lack of attention to people and surroundings, loss of balance and bodily control, , and hallucinations. • Progresses rapidly (<10 days) and frequently to coma and death.

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Diagnosis and Treatment Naegleria Prevention

• In Naegleria infections, the diagnosis can be • Avoid swimming or jumping into made by microscopic examination of cerebrospinal fluid (CSF). bodies of warm freshwater, hot springs and thermally polluted water • A wet mount may detect motile trophozoites, and a Giemsa-stained smear such as water around power plants. will show trophozoites with typical – Water above 80:F- use caution morphology. • Avoid swimming or jumping into • Often diagnosed post-mortem freshwater during periods of high • Can be found by MRI and treated with temperature and low water volume. if found early enough • Hold the nose shut or use nose clips • is effective against N. fowleri when jumping or diving into bodies in vitro of warm fresh water such as lakes, • After progression to PAM, less than 1% rivers or hot springs. survival

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Acanthamoeba spp., Balamuthia Life cycles

• Both are opportunistic protozoan that rarely causes disease in humans. • Acanthamoeba spp. – Approximately 400 cases have been reported worldwide with a survival rate of 2-3%. – No flagella and can’t tolerate water as hot as Naegleria can – Usually skin infections, but serious disease in immunocompromised • Balamuthia mandrillaris – Approximately 100 published and unpublished cases of Balamuthia amebic encephalitis (BAE) have been reported; most were fatal. Acanthamoeba spp. Balamuthia mandrillaris – Extremely rare, mostly in immunocompromised

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7 Diseases Diagnosis and Tx

• Both can cause granulomatous amebic encephalitis (GAE) in individuals • In Acanthamoeba infections, the dx from microscopic with compromised immune systems. examination of stained smears of biopsy specimens (brain tissue, skin, cornea) or of corneal scrapings • Acanthamoeba crosses the blood brain barrier and invades • Confocal microscopy or cultivation of the causal connective tissue, induction of pro-inflammatory responses leads to organism, and its identification by direct neuronal damage which can be fatal within days. immunofluorescent antibody, may also prove useful. – Subacute symptoms including altered mental status, headaches, fever, • Post-mortem biopsy reveals severe oedema and neck stiffness, seizures, other neuropathies leading to coma and death hemorrhagic necrosis. – Also, granulomatous skin lesions and keratitis, corneal ulcers following corneal trauma or contaminated contact lens use. Treatment • Balamuthia-induced GAE can cause focal paralysis, seizures, and • The misdiagnosis of bacterial encephalitis often leads to brainstem symptoms such as facial paralysis, difficulty swallowing, erroneous treatment that is ineffective. and double vision. • In the case that Acanthamoeba is diagnosed correctly, – Also causes a variety of non-neurological symptoms, and often causes amphotericin-B, , trimethroprim- skin lesions, through which the amoeba may enter the bloodstream sulfamethoxazole, ketokonazole, fluconazole, and migrate to the brain. sulfadiazine, are only tentatively successful.

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Prevention

• Encephalitis diseases: similar to Naegleria • IC careful in environment-soil, water • – Wear and replace contact lenses according to the schedule prescribed by your eye care provider. – Remove contact lenses before any activity involving contact with water, including showering, using a hot tub, or swimming. – Wash hands with soap and water and dry before handling contact lenses. • MRSA can infect and replicate inside of Acanthamoeba polyphaga; Since A. polyphaga can form cysts, cysts infected with MRSA can act as a mode of airborne dispersal for MRSA. – that emerge from amoeba are more resistant to antibiotics and more virulent?

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Microsporidian species Clinical manifestation/location Comments Keratoconjunctivitis, skin and deep muscle Brachiola algerae infection Microsporidia Global, in 6-30% of al AIDS patients with Diarrhea, acalculous cholecystitis small and chronic diarrhea. Most common Enterocytozoon bieneusi* large intestine, gall bladder, bile duct, lung, microsporidian in immunocompetent • One general phylum nasal . Systemic disease people.

• Obligate, spore-forming, intracellular Brain, kidney, liver; parasites that invade vertebrates and Encephalitozoon cuniculi Keratoconjunctivitis, infection of respiratory Global, Very rare, HIV+; invertebrates. and genitourinary tract, disseminated infection systemic spread to nose, eye , lung, kidney, etc. • Polar tube or polar filament found in the Keratoconjunctivitis, infection of respiratory may be transmitted via sputum, urine, nasal spore used to infiltrate host cells. Encephalitozoon hellem and genitourinary tract, disseminated infection aerosol, known only from HIV+ • More than 1,200 species belonging to 143 genera have been described as parasites Infection of the GI tract causing diarrhea, and Encephalitozoon intestinalis (syn. Septata Found in about 2% of all AIDS patients with infecting a wide range of vertebrate and dissemination to ocular, genitourinary and intestinalis) chronic diarrhea invertebrate host. respiratory tracts Microsporidium (M. ceylonensis and M. • First human case was described in 1959 in Infection of the cornea Sri Lanka, Botswana a Japanese child. africanum) • Transmission route is unclear Nosema sp. (N. ocularum), Ocular infection; USA, HIV+

• Since 1985, microsporidia have been Brachiola connori striated and smooth muscle Immunocompromised infant (athymic) identified as a cause of opportunistic infections associated with persistent Pleistophora sp. Muscular infection, striated muscle USA, two cases immunocomp, HIV pos and neg diarrhea and in persons with Trachipleistophora anthropophthera Disseminated infection Muscular infection, stromal keratitis, (probably AIDS Trachipleistophora hominis disseminated infection) 47 HSC4933. Emerging Infectious Diseases Vittaforma corneae (syn. Nosema corneum) Ocular infection,

8 Wide range of disease Diagnosis and Treatment

• Occurs mainly, but not exclusively, in severely • DX: Microscopic ID-light and TEM, IFA, PCR immunocompromised patients with AIDS. • Ocular microsporidiosis-oral albendazole plus • Chronic diarrhea and wasting are the most common symptoms topical . of microsporidiosis – Corneal infections with V. corneae often do • Disseminated infection is characterized by symptoms of not respond to chemotherapy and may cholecystitis (inflammation of the gallbladder), renal failure, require keratoplasty. respiratory infection, headache, nasal congestion, ocular pain and • Oral fumagillin has been effective to treat sinus involvement. Enterocytozoon bieneusi infections, but it has • Respiratory infection may cause cough, dyspnea (labored been associated with thrombocytopenia. breathing) and wheezing. • Albendazole for caused • With ocular infection, symptoms range from foreign body by Encephalitozoon intestinalis and to treat sensations, eye pain, light sensitivity, redness, excessive tearing or disseminated microsporidiosis (various blurred vision. species) and skin and deep muscle infection (Brachiola algerae). • Finally, infections of the brain or other nervous tissue cause seizures, headache and other symptoms depending the precise area of infection.

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Prevention

• Transmission is still unclear, but possibly by inhalation, ingestion. • Contaminated food and water sources? • Highly resistant spores can survive outside host for up to several years • Proper disinfection, sterilization in health care settings

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