Toxoplasmosis & Cryptosporidiosis PDF

TOXOPLASMOSIS & CRYPTOSPORIDIOSIS Dr. NANTHA KUMAR JEYAPRAKASAM, PhD Center for Toxicology and Health Risk Studies (CORE) Faculty of Health Science (FSK) Universiti Kebangsaan Malaysia (UKM)  TAXONOMY...

TOXOPLASMOSIS & CRYPTOSPORIDIOSIS Dr. NANTHA KUMAR JEYAPRAKASAM, PhD Center for Toxicology and Health Risk Studies (CORE) Faculty of Health Science (FSK) Universiti Kebangsaan Malaysia (UKM)  TAXONOMY CLASSIFICATIONS Phylum Apicomplexa Order Eucoccidiorida Order Haemosporida Family Family Family Family Eimeriidae Sarcocystidae Plasmodiidae Crytosporidiidae Genus Genus Genus Genus Eimeria Toxoplasma Plasmodium Cryptosporidium Isospora Sarcocystis Haemoproteus Tyzzeria Coccidia are single-celled obligate intracellular protozoan parasites in the class Conoidasida within the phylum Apicomplexa.  LECTURE OUTLINE (TOXOPLASMOSIS) General introduction Epidemiology Morphology Lifecycle Pathogenesis & Clinical features Diagnosis Treatments Prevention & control measures  GENERAL INTRODUCTION Toxoplasmosis Infection by Toxoplasma gondii an obligate intracellular coccidian parasite Toxoplasma gondii Parasite of human and animal. Discovered in small North American rodent called gundi (Ctenodactylus gundi) The name Toxoplasma is derived from the Greek word Toxon meaning arc or brow referring to the curved shape of the trophozoite.  EPIDEMIOLOGY 1/3 of world population have been exposed/infected with toxoplasmosis. Chronic asymptomatic infection (latent) is common, and the prevalence increases with age - continuous exposure to the source of infection. Cosmopolitan in distribution The widest range of hosts ranging from birds and warm- blooded animals including human. Cats (family Felidae) act as the definitive host. Toxoplasmosis, is most serious in: congenital infection, immunocompromised patients eg.AIDS. Zoonotic disease ▪ Many animals can be the intermediate host Eating habit ▪ Eating improperly cooked meat (eg. steak, barbeque) The distribution is related to the cat distribution in the world. In Malaysia, prevalence highest among Malays (37.7%) followed by Indian (29.9%) and Chinese (20.8%) - Related to keeping cat as pet  MORPHOLOGY An obligate intracellular coccidian parasite and it occurs in 3 forms: All 3 forms occur in cat which is the 1. Trophozoite (Tachyzoite) definitive host. 2. Tissue cyst (Bradyzoite) 3. Oocyst Tachyzoites and tissue cysts are present in the intermediate hosts Intracellular parasite & all nucleated cells (other animals including humans). may be infected esp. the reticuloendothelial system, nerve, brain, eye and muscle. All the 3 forms are infectious to human. Does not infect RBC.  MORPHOLOGY: 3 FORMS Tachyzoites Bradyzoites Oocysts  MORPHOL OGY: TROPHOZOITES (TACHYZOITES) Cresent shaped and measures 3 x 7 um. One end is rounded but the other is sharp. The nucleus is ovoid and is situated at the blunt end of the parasite. Multiplies rapidly & cause tissue damage Can invade any nucleated cell and replicate within cytoplasmic vacuoles by a process called endodyogeny (internal budding) Toxoplasma gondii tachyzoites, stained with Giemsa  MORPHOL OGY: TISSUE CYST (BRADYZOITES ) In the tissue, the parasites form a thick wall around them when the host immune system is activated - called tissue cyst. The parasites divide slowly and becomes bradyzoites in tissue cyst - Resting/dormant form of the parasite. Found during chronic stage of the infection in the brain (most common site), eye, skeletal muscles & other organs. Round or oval, 10-20 μm in size & contains numerous bradyzoites. Remain viable in tissue for several years - When the host immunity goes down, bradyzoites changes into tachyzoites and come out from the tissue cyst to start new attack. Resistant - when raw or undercooked meat containing the Stained (Left) & unstained (Right) cyst of T. gondii. Cysts are usually spherical in the brain but more elongated in cardiac and skeletal cysts is ingested, infection occurs - Cysts are susceptible to muscles. freezing & thawing and heat above 60 °C. Tissue cyst stained with hematoxylin and eosin Tissue cyst in muscle  MORPHOL OGY: OOCY T S Only in intestine of CATS & other felines (definitive hosts) - NOT in humans - Cats shed millions of oocysts per day in feces for about 2 weeks during the primary infection. Oval in shape, 10-12 µm in diameter - surrounded by a A. Unsporulated oocyst; thick resistant wall. B. Sporulated oocyst Formed by sexual reproduction (gametogony). The freshly passed oocysts are not infectious - The sporulated oocyst is infective. They undergone sporulation in the soil with formation of Sporozoites 2 sporocysts, each containing 4 sporozoites. 2 sporocysts Need external maturation (3-4 days) before becoming infective. Very resistant to environmental conditions - Can remain infective in soil for about a year. When the infective oocyst is ingested → releases sporozoites in the intestine → initiates infection. LIFE CYCLE  HUMAN INFECTION OCCURS : by ingestion of the oocysts, through contaminated water or food by consuming improperly cooked meat containing the cyst congenital infection organ transplantation blood transfusion accidents in the laboratory when handling the tachyzoites  PATHOGENESIS AND CLINICAL FEATURES Toxoplasma gondii is an opportunistic parasite. Most human infections are asymptomatic. Clinical toxoplasmosis may be congenital or acquired Clinical manifestations depend on the immune status of the infected person. Toxoplasmosis may cause fatal complications in AIDS patients.  PATHOGENESIS AND CLINICAL FEATURES Acquired toxoplasmosis Congenital toxoplasmosis Toxoplasmosis in immunodeficient host i. Acquired toxoplasmosis Usually asymptomatic or mild infection - 80% of primary infection are asymptomatic- rarely serious Most common manifestations of acute acquired toxoplasmosis are: ▪ Cervical lymphadenopathy, fever, headache, myalgia and splenomegaly. ▪ The illness may resemble viral infection and is self-limiting. Rarely but some may present with pneumonitis, myocarditis and meningoencephalitis which can be fatal. Sometime involving the eye causing ocular toxoplasmosis Present as uveitis, choroiditis, or chorioretinitis. Some cases may be so severe that they require enucleation. A classical well-demarcated circular atrophic pigmented scar of inactive toxoplasmosis ii. Congenital toxoplasmosis Transmitted transplacentally from mother with primary Toxoplasma infection to foetus Risk of foetal infection ↑with the progress of pregnancy Infection in 1st trimester of pregnancy: Severity of foetal damage is highest - May cause abortion or stillbirth or born with various defects Most infected newborns are asymptomatic at birth and may remain so throughout. Some develop clinical manifestations of toxoplasmosis weeks, months and even years after birth. iii. Toxoplasmosis in immunocompromised patients May be due to reactivation of chronic or latent infection. ▪ AIDS patients, lymphoma, or other cancer and those undergoing prolonged immunosuppressive therapy as in organ transplant recipient. Involvement of the brain is most common, causing toxoplasmic encephalitis. Symptoms may include headache, confusion, ataxia, hemiparesis and seizures. Toxoplasmic Encephalitis in Patient with Acquired Immunodeficiency Syndrome DIAGNOSIS For congenital infections: The presence of IgM in the baby’s serum is diagnostic because a high IgG titre may come from the mother as IgG can pass through the placenta but not IgM.  TREATMENTS Symptomatic cases Pyrimethamine + sulfadiazine with folinic acid for 1 month to prevent bone marrow suppression for Pregnant mother (1st trimester) Spiramycin (as Pyrimethamine is teratogenic) Congenital toxoplasmosis Pyrimethamine + sulfadiazine with folinic acid for 1 year Systemic corticosteroid may be added to reduce chorioretinitis AIDS patients (CD4+ T lymphocyte count below 1010) in single host Small size of the oocyst (4–6 μm) Resistant to the available drugs and disinfectants Large animal and human reservoir Lack of appropriate immune response Poor sanitary conditions Travel to underdeveloped countries Zoonotic contact Peak age of infection: Infants and children. MORPHOLOGY Oocyst Infective form Diagnostic to man form (in feces) Morphology: Oocyst Round, small, 4–6 μm in size, surrounded by a cyst wall and bears four sporozoites Each sporozoite is crescentic shaped with pointed anterior end, blunt posterior end and a nucleus located posteriorly Extremely resistant to routine chlorination, heat and other disinfectants. LIFE CYCLE Only needs 1 host (homoxenus) Unlike Toxoplasma or Sarcocystis, where intermediate hosts are also needed (heteroxenus) C. parvum completes its life cycle (both sexual and asexual stages) in single host (man or other animals). Infective stage: Sporulated oocyst is the infective form of the parasite. Thick-walled oocyst is infectious to other persons, whereas the thin-walled oocysts can cause autoinfection (through contaminated fingers). PATHOGENESIS & CLINICAL FEATURES Very much depends on the immunity status of patients. Cryptosporidium is an opportunistic organism CLINICAL FEATURES Cryptosporidiosis in Immunocompetent Hosts Usually, the infection is asymptomatic Some develop to self-limiting watery non-bloody diarrhea Other features like abdominal pain, nausea, anorexia, fever, and/or weight loss may be present. Symptoms develop after an incubation period of 1 week and subside within 1–2 weeks. C. parvum accounts for 2–6% of cases of traveler’s diarrhea. CLINICAL FEATURES Cryptosporidiosis in Immunocompromised Hosts Severe Diarrhea, dehydration and can be fatal. May also involve other organs, pharynx, stomach, large intestine and respiratory tract is quite common in HIV positive patients Can also cause cholecystitis, hepatitis, & pancreatitis (Many AIDS patients develop these). LABORATORY DIAGNOSIS LABORATORY DIAGNOSIS 1. Faecal examination identification of oocyst Modified Ziehl-Neelsen (Acid-fast staining) Direct fluorescent antibody staining (IFAT) using fluorescent labelled monoclonal Ab directed against cyst wall antigens (more sensitive & specific than acid-fast staining). ( best to repeat 3x because oocysts are intermittently passed out ) LABORATORY DIAGNOSIS TREATMENT PREVENTIONS Requires minimizing exposure to infectious oocysts in human or animal feces Proper hand washing Use of submicron water filters Drink only boiled water Improved personal hygiene Health education  Dr. NANTHA KUMAR JEYAPRAKASAM, PhD Center for Toxicology and Health Risk Studies (CORE) Faculty of Health Science (FSK) Universiti Kebangsaan Malaysia (UKM)