Blood &Tissue Protozoa

Rhodesian sleeping sickness (East ASS)

Acute phase occurs very rapidly-fever, rigors, myalgia Lymphadenopathy Progresses to a fulminating, rapidly fatal illness CNS invasion early (within few wks)-lethargy, anorexia, mental disturbance, neurological problems Kidney damage, myocarditis and death

Morphology of Naegleria fowleri

Amoeba - protozoan, exists as Cyst (only in the environment, not in human body) Trophozote (have pseudopodia, reproductive stage) Flagellated form

Trypanosoma cruzi Life Cycle

An infected triatomine insect vector (or "kissing" bug) takes a blood meal and releases trypomastigotes in its feces near the site of the bite wound. Trypomastigotes enter the host through the wound or through intact mucosal membranes, such as the conjunctiva. Common triatomine vector species for trypanosomiasis belong to the genera Triatoma, Rhodnius, and Panstrongylus. Inside the host, the trypomastigotes invade cells near the site of inoculation, where they differentiate into intracellular amastigotes . The amastigotes multiply by binary fission and differentiate into trypomastigotes, and then are released into the circulation as bloodstream trypomastigotes . Trypomastigotes infect cells from a variety of tissues and transform into intracellular amastigotes in new infection sites. Clinical manifestations can result from this infective cycle. The bloodstream trypomastigotes do not replicate (different from the African trypanosomes). Replication resumes only when the parasites enter another cell or are ingested by another vector. The "kissing" bug becomes infected by feeding on human or animal blood that contains circulating parasites . The ingested trypomastigotes transform into epimastigotes in the vector's midgut . The parasites multiply in the midgut and differentiate into infective metacyclic trypomastigotes in the hindgut . Trypanosoma cruzi can also be transmitted through blood transfusions, organ transplantation, transplacentally, and also by laboratory accidents.

Treatment of Malaria

Antimalarial drugs Chloroquine or quinine; For chloroquine resistant cases: mefloquine± artesunate, artemether-lumafantrine, atovaquone-proguanil Prevention and Control Chemoprophylaxis for traveler to endemic areas: Chloroquine (P. falciparum sensitive areas) Mefloquine or doxycycline (chloroquine resist. P. falciparum endemic areas) Eradications of infections Vector control: control of mosquito breeding Protection of individuals by screening/window screening, netting, protective clothing and insect repellants

Romana's sign

Associated with the acute stage of Chagas' disease. It is unilateral painless periorbital/lymphoid swelling which occurs when the T. cruzi enters through the conjunctiva. Not to be confused with a chagoma (A chagoma is an inflammatory nodule at the bite site of the reduviid bug)

Microscopy of Malaria

Blood smear (thick/thin) examination after Giemsa staining-infected red blood cells, ring form, and gametocyte form. P. falciparum, can be differentiated from the others by multiple ring form per cell and crescent shaped gametocyte Thick films contain 10 to 20 times more blood than thin films, correspondingly providing increased sensitivity for malaria screening

Plasmodium spp.

Causes Malaria Five species of medical importance P. falciparum (most serious form of malaria) P. vivax P. malariae P. ovale P. knowlesi: Infects primarily long-tailed & pig-tailed macaques human cases in Malaysia & other South east Asian countries)

Diagnosis of Naegleria fowleri

Demonstration of organism in sterile tissue or fluid (CSF, nasal discharge) Detection of trophozoite by: Wet mount: live motile trophozoites Staining: Giemsa-staining, H & E staining or Florescent staining PCR Culture in a plate covered in bacteria, at 420 C The amoebae can be grown in culture to increase the likelihood of detection

Diagnosis of Acanthamoeba castellani

Demonstration of parasite in corneal scraping/CSF/biopsy from Sinus (H&E stain) Culture: Xenic and axenic culture Treatment: miltefosine Prevention & Control Proper care of eye lenses Steps to prevent GAE: unclear

Diagnosis of Toxoplasma gondii

Demonstration of the organism as trophozoites/ cysts in tissues and body fluids: definitive method of diagnosis A. Trophozoite (Tachyzoite) stage: typically crescent shaped with a prominent, centrally placed nucleus B: Toxoplasma gondii cyst (Bradyzoites) in brain tissue stained with hematoxylin and eosin (100×). C: Zoom of Image B, T. gondii cyst Serology: Toxoplasma gondii Serologic profile (TSP): measure IgM, IgG, IgA and IgE To diagnose congenital toxoplasmosis Amniotic fluid (obtained by Amniocentesis): PCR- test of choice during prenatal (before birth) diagnosis Detection of IgM and IgA antibodies in new born

Diagnosis of T. Brucei

Demonstration of trypomastigotes in body fluids From primary lesion, blood, CSF

Plasmodium Species Differentiation

Done on Thin Films P. falciparum: infects RBC of all ages P. vivax and P. ovale: young RBCs P. malariae: old RBcs P. falciparum demonstrates no selectivity in host erythrocytes and invades any red blood cell (RBC) at any stage in its existence. Also, multiple merozoites can infect a single erythrocyte. Thus three or even four small rings may be seen in an infected cell. P. falciparum is often seen in the host cell at the very edge or periphery of the cell membrane, appearing almost as if it were "stuck" on the outside of the cell. This is called the appliqué or accolé position and is distinctive for this species (Murrary)

Treatment of Leishmaniasis

Drug of choice for all forms-sodium stibogluconate (Antimonial/heavy metal) Alternatives For Visceral : Amphotericin B (liposome formulation), oral miltefosine, paromomycin, sitamaquine Cutaneous: Miltefosine plus fluconazole, Amphotericin B Muco-cutaneous: Amphotericin B Prevention and control Prompt treatment of cases Control of vector and reservoir host Use screening and insect repellents Vaccination under trial

T. brucei (African Trypanosoma): Life cycle

During a blood meal on the mammalian host, an infected tsetse fly (genus Glossina) injects metacyclic trypomastigotes into skin tissue. The parasites enter the lymphatic system and pass into the bloodstream. Inside the host, they transform into bloodstream trypomastigotes , are carried to other sites throughout the body, reach other blood fluids (e.g., lymph, spinal fluid), and continue the replication by binary fission . The entire life cycle of African Trypanosomes is represented by extracellular stages. The tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host. In the fly's midgut, the parasites transform into procyclic trypomastigotes, multiply by binary fission , leave the midgut, and transform into epimastigotes . The epimastigotes reach the fly's salivary glands and continue multiplication by binary fission, producing metacyclic trypomastigotes . The cycle in the fly takes approximately 3 weeks. Humans are the main reservoir for Trypanosoma brucei gambiense, but this species can also be found in animals. Wild game animals are the main reservoir of T. b. rhodesiense.

Pathogenesis of Toxoplasma gondii

Intracellular parasite: infect macrophages, muscle cells, epithelial cells - in different tissues Toxoplasmosis: affect many organs Clinical manifestations based on type of infection: I. Acquired infection: Immunocompetent Immunocompromised: severe II. Congenital infection:

Malarial Infection of RBC

During the erythrocytic stage of the parasite's life cycle, it uses intracellular hemoglobin as a food source. The protein is broken down into peptides, and the heme group is released and detoxified in the form of hemozoin Maurer clefts/dots: finely granular precipitates or irregular cytoplasmic particles that usually occur diffusely in red blood cells infectedwith the trophozoites of Plasmodium falciparum. They are membrane-limited vacuoles or sack-like structures in the cytosol of the erythrocyte, formed early after invasion by the parasite, visible as blue dots in Giemsa-stained blood smears. Their origin and functions remain still unclear.

Babesia microti

Epidemiology: Found where Borrelia burgdorferi (Lyme disease) is found, North east US. Reservoir: Rodents; deer, cattle transmitted by tick (Ixodes dammini); or by blood transfusion Morphology: Sporozoan Exists in different forms - sexual and asexual reproduction. Pathogenesis: Infective form: Sporozoites (pyriform bodies) Infect and lyse RBC Clinical disease: Malaria like syndrome Incubation Period: 1-4 wks, General malaise, Fever without periodicity, headache, chills, sweating, fatigue, hemolytic anemia; hepatosplenomegaly in severe case

T. brucei (african sleeping sickness)

Epidemiology: Transmitted by Glossina (Tsetse fly) - T. b. gambiense: humans as the main host (vector prefers shaded stream banks proximity to human dwellings)-98% infection T. b. rhodesiense : human and cattle, and antelopes (Vector prefers brush land rather than stream banks)-2% infection Morphology: flagellate

Naegleria fowleri

Epidemiology: Ubiquitous in nature Reservoir: Warm water bodies such as heated swimming pools, hot tubs, hydrotherapy and medicinal pools, aquariums and sewage Transmission: Acquired during warm summer months from contaminated lakes - or in hot tubs, via the olfactory mucosa and nasal tissues Risk Factors/High Risk Populations: Mostly young children

Toxoplasma gondii

Epidemiology: World wide, two hosts - definitive host - cat family, intermediate host: man, cattle, rodents. Transmitted by: a) oral route: fecal (cat feces)-oral; or consumption of meat with cyst; b) blood transfusion or organ transplantation; and c) Transplacental route Morphology and life cycle: Sporozoan; 3 important forms: Oocyst, Tachyzoites and Bradyzoites; undergo sexual (Intestinal) and asexual (extra-intestinal) reproduction

Trypanosoma cruzi (Chagas Disease/ American trypanosomiasis)

Epidemiology: infects human, domestic cats, dogs, wild rats, raccoon and even armadillo and opossums Transmitted: by insect vector Reduviid bugs (Triatomine bugs/kissing bugs); across the placenta (congenital); and by blood transfusion/organ transplantation Geographic distribution: Rural areas of South and Central America: endemic Migrants in the USA, Europe, Australia, Japan Morphology: exists as a flagellate and non flagellate

Acanthamoeba castellani

Epidemiology: ubiquitous in nature; water bodies, warm climate, hot tub Transmission: by contaminated water/soil through damaged skin, corneal abrasion; inhalation Risk factors: improper contact lens care and contact with nonsterile water during wear. Rare disease; incidence in developed countries: approx. 1 to 33 cases per million contact lens wearers Morphology: free living Amoeba (Protozoan), exists in two stages, cysts and trophozoite

Morphology of leishmania

Exist as flagellate (promastigote) and non flagellate form (amastigote form) Kinetoplast: a mass of mitochondrial DNA lying close to the nucleus

Pathogenesis of Trypanosomiasis

Extracellular - multiply in body fluids Programmed gene rearrangement (Antigenic variation)/ about 1000 gene varieties Lesion at the site of insect bite (Chancre) Gambian sleeping sickness (West ASS): IP-few days to weeks, can progress to chronic disease-fatal Early (hemolymphatic phage): Fever (intermittent/weekly), myalgia, arthralgia and lymphadenopathy (Posterior cervical lymphadenopathy-Winterbottom's sign), Rash Chronic (Neurologic phage): CNS involvement (usually after 1-2 year )-lethargy, daytime sleepiness with night sleep disturbance, tremors, meningoencephalitis, mental retardation, convulsions, hemiplegia, coma and death

Maurer dots

Finely granular precipitates or irregular cytoplasmic particles that usuallyoccur diffusely in red blood cells infected with the trophozoites of Plasmodium falciparum. They are membrane-limited vacuoles or sack-like structures in the cytosol of the erythrocyte, formed early after invasion by the parasite, visible as blue dots in Giemsa-stained blood smears. Their origin and functions remain still unclear.

Acanthamoeba castellani Life Cycle

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. Unlike N. fowleri, Acanthamoeba has only two stages: cysts and trophozoites , in its life cycle. No flagellated stage exists as part of the life cycle. The trophozoites replicate by mitosis. The trophozoites are the infective forms, although both cysts and trophozoites gain entry into the body through various means. Entry can occur through the eye , the nasal passages to the lower respiratory tract , or ulcerated or broken skin . When Acanthamoeba spp. enters the eye it can cause severe keratitis in otherwise healthy individuals, particularly contact lens users . When it enters the respiratory system or through the skin, it can invade the central nervous system by hematogenous dissemination causing granulomatous amebic encephalitis (GAE) or disseminated disease , or skin lesions in individuals with compromised immune systems. Both cysts and trophozoites of Acanthamoeba spp are found in tissue

Leishmania spp.

Four species L. donovani : causes kala-azar (visceral leishmaniasis) L. tropica L. mexicana L. braziliensis: mucocutaneous Leishmaniasis Epidemiology : World wide with restricted distribution. Favor arid, dry warm environment. Also infects animals (dogs and rodents). Transmitted by Sand fly, Phlebotomus spp. The second-largest parasitic killer in the world (after malaria) An estimated 1.3 million new cases and 20 000 to 30 000 deaths occur annually (WHO).

Pathogenesis of Chagas Disease

Invade and multiply inside: smooth muscle and ganglion cells in organs such as heart, walls of GIT; skeletal muscle cells or cells of RES Clinical symptoms: can be divided into: Acute phase: nodular lesion (chagoma) at the site of bite, Romana's sign, may include fever, lymphadenopathy Latent phase - asymptomatic, may last for many years Chronic phase - many years later; muscular degeneration and denervation of heart & GIT heart rhythm abnormalities that can cause sudden death; megaesophagus, megastomach, and megacolon

Naegleria fowleri life cycle

Has 3 stages in its life cycle: , ameboid trophozoites , flagellates, and cysts. The only infective stage of the ameba is the ameboid trophozoite. Trophozoites are 10-35 µm long with a granular appearance and a single nucleus. The trophozoites replicate by binary division . Trophozoites infect humans or animals by penetrating the nasal tissue and migrating to the brain via the olfactory nerves causing primary amebic meningoencephalitis (PAM). Trophozoites can turn into a temporary, non-feeding, flagellated stage (10-16 µm in length) when stimulated by adverse environmental changes such as a reduced food source. They revert back to the trophozoite stage when favorable conditions return. Naegleria fowleri trophozoites are found in cerebrospinal fluid (CSF) and tissue, while flagellated forms are occasionally found in CSF. Cysts are not seen in brain tissue. If the environment is not conducive to continued feeding and growth (like cold temperatures, food becomes scarce) the ameba or flagellate will form a cyst. The cyst form is spherical and about 7-15 µm in diameter. It has a smooth, single-layered wall with a single nucleus. Cysts are environmentally resistant in order to increase the chances of survival until better environmental conditions occur.

Acquired Toxoplasma gondii

IP: 5-23 days A. Immunocompetent persons Cervical lymphadenopathy: most common Single or multiple, usually non tender Fever [usually <40°C] Headache, malaise, fatigue, myalgia, sore throat B. Immunocompromised patients: rapidly fatal if untreated -CNS: Principal opportunistic infection of the CNS in persons with AIDS meningoencephalitis, and mass lesions. -Lungs: Toxoplasma pneumonia (dyspnea, fever and non productive cough) -Heart: usually asymptomatic, but may progress to heart failure

Cytoadherence

In P. falciparum infections, membrane protuberances appear on the erythrocyte's surface 12-15 h after the cell's invasion. These "knobs" extrude a high-molecular-weight, antigenically variant, strain-specific erythrocyte membrane adhesive protein (PfEMP1) that mediates attachment to receptors on venular and capillary endothelium—an event termed cytoadherence.

Treatment of T. Brucei

Indicated for all persons diagnosed Pentamidine for first stage T. b. gambiense infection is widely available in US Other drugs (suramin, melarsoprol, eflornithine, and nifurtimox) to treat Afr. Tryp. are available in the U.S. only from the CDC Prevention and Control Wearing long-sleeved clothes Inspection of vehicles before entering Avoiding bushes. Use of insect repellent

Toxoplasma gondii congenital infection

Infection during pregnancy may lead to abortion, still birth, blindness and congenital defects of the fetus: Ocular: Chorioretinitis- blurred vision, photophobia, and eye pain Neurologic: Intracerebral calcification, hydrocephaly/ microcephaly, convulsions, mental retardation Cardiac: Cardiomegaly Intracerebral calcification. If a woman is infected for the first time during pregnancy the parasite can cross the placenta and cause fetal disease. Both the probability and severity of the disease depend on when the infection takes place during pregnancy. Early: low transmission, but severe disease Late: high transmission, more benign symptoms. Hydrocephaly.

Pathogenesis of Plasmodium

Intracellular parasite, infects red blood cells and hepatocytes, dormancy in hepatocytes (except P. falciparum) P. falciparum: The processes of cytoadherence, rosetting, and agglutination are central to the pathogenesis of falciparum malaria Sequestration of RBCs containing mature forms of the parasite in vital organs (particularly the brain) interfere with microcirculatory flow and metabolism Clinical disease: Malaria : Incubation period: approx. 2 wks after bite. Fever, chills and sweating, shows periodic cycle. Febrile paroxysm synchronizes with erythrocytic schizogony, Types of fever: A. Tertian fever (with 48 hr cycle): recurs every 3rd d B. Quartan fever (with 72 hr cycle): recurs every 4th d C. Quotidian fever: recurs every 24 hrs Hepatosplenomegaly and anemia.

Leishmania spp. Life Cycle

Is transmitted by the bite of infected female phlebotomine sandflies. The sandflies inject the infective stage (i.e., promastigotes) from their proboscis during blood meals . Promastigotes that reach the puncture wound are phagocytized by macrophages and other types of mononuclear phagocytic cells. Progmastigotes transform in these cells into the tissue stage of the parasite (i.e., amastigotes) , which multiply by simple division and proceed to infect other mononuclear phagocytic cells . Parasite, host, and other factors affect whether the infection becomes symptomatic and whether cutaneous or visceral leishmaniasis results. Sandflies become infected by ingesting infected cells during blood meals. In sandflies, amastigotes transform into promastigotes, develop in the midgut, and migrate to the proboscis

Pathogenesis of Acanthamoeba castellani

Keratitis: associated with contact lens or eye trauma, Granulomatous amoebic encephalitis (GAE), plus Disseminated cutaneous and subcutaneous infections in HIV/immunocompromised patients

Treatment of Naegleria fowleri

Largely ineffective, early diagnosis critical Amphotericin B, New drug: Miltefosine Amphotericin B - considered investigational for this purpose Miltefosine is an experimental drug, which was initially developed for breast cancer but had shown some amoeba-killing capabilities in the lab. Amphotericin B is effective against N. fowleri in vitro, but the prognosis remains bleak for those who contract PAM, and survival remains less than 1% Therapeutic hypothermia: cooling the body below normal body temperature Only three known survivors Prevention: Avoid exposure to contaminated water: nose clip

Plasmodium: Life Cycle

Life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host . Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . (Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later). After this initial replication in the liver (exo-erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony) . Merozoites infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites . Some parasites differentiate into sexual erythrocytic stages (gametocytes) . Blood stage parasites are responsible for the clinical manifestations of the disease. The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal . The parasites' multiplication in the mosquito is known as the sporogonic cycle . While in the mosquito's stomach, the microgametes penetrate the macrogametes generating zygotes . The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts . The oocysts grow, rupture, and release sporozoites , which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle.

Black water fever (dark urine)

Manifestation of falciparum malaria in previously infected subjects. Intra vascular hemolysis, fever, hemoglobinuria, Can result in acute renal failure and death In majority cases, parasites not detected in periph. blood.

Relapse of Malaria

May result from Recrudenscence: due to persistence of blood infection in which surviving population of erythrocytic forms are increased. Is a feature of P. falciparum infection Recurrence or true relapse: Persistence of exoerythrocytic forms in the liver in which erythrocytic schizogony commences again Is a feature of P. vivax, P. ovale and P. malariae infections

Blood &Tissue Protozoa

Medically Important: Plasmodium spp. Babesia microti Toxoplasma gondii Leishmania spp. Trypanosoma spp. Naegleria fowleri Acanthamoeba castellani

Pathogenesis of Leishmaniasis

Multiply inside macrophages and other cells. Kala-azar (Visceral form)/Black fever/Dumdum fever: asymptomatic to rapidly fatal disease affects organs of the reticuloendothelial system (RES) Liver, spleen and bone marrow IP: several wks to a year Gradual onset of fever, chills, sweating, diarrhea, anemia Hyperpigmentation of skin Persistence results in Post-Kala-azar dermal leishmaniasis: hypopigmented/nodular lesions Cutaneous and muco-cutaneous forms: pruritic lesions enlarge and ulcerate

Diagnosis of Leishmaniasis

Microscopic examination Of bone marrow, spleen, liver or lymph node biopsy, Of scrapings from margin of lesions demonstrate parasites inside macrophages Serology: Direct Agglutination Test (DAT) rK39 test: Serologic test using the cloned antigen rK39 instead of whole Leishmania parasites. The rK39 antigen, which consists of 39 amino acid repeats of a kinesin-like gene found in L. chagasi, is used in an enzyme-linked immunosorbent assay (ELISA) format and rapid diagnostics Novy-MacNeal-Nicolle (NNN) medium is used to grow Leishmania. It consists of 0.6% sodium chloride (NaCl) added to a simple blood agar slope. NNN can also be used to grow Trypanosoma cruzi. leishmanin test (Also called as Montenegro test) is a delayed hypersensitivity test for cutaneous leishmaniasis, In this test, killed Leishmania antigens are injected intradermally. A positive reaction is indicated by the appearance of a palpable nodule in 48 to 72 hours

Diagnosis of Chagas Disease

Microscopy Blood - flagellate form only during acute form, Tissue biopsy: amastigote form Culture: Cell culture/culture in NNN medium Animal inoculation -intra-peritoneal inoculation, mice Serology Xenodiagnosis: Reduviid bug is allowed to feed on a patient, then parasites are detected in the bugs

Diagnosis of Malaria

Microscospy: Examination of thick & thin blood films Gold standard Demonstration of infected red blood cells; ring form, schizont and gametocyte form of parasite. Antigen detection by rapid diagnostic test (RDT): Aldolase enzyme (all Plasmodium) Lactate dehydrogenase (all Plasmodium & also specific to P. falciparum) Histidine rich protein-2 (specific to P. falciparum) Molecular: PCR based test

Trypanosoma cruzi in non-endemic countries

Migration routes from Latin America and estimation of the total number of infected individuals in non-endemic countries.

Treatment of Babesia microti

Mild to moderate case: Atovaquine + Azithromycin Severe: Clindamycin+ quinine/Exchange transfusion Prevention and Control Use of protective clothing and insect repellants Prompt removal of ticks, minimize exposure time The Ixodes nymphs that typically spread B. microti are so small (about the size of a poppy seed) that they are easily overlooked. But they usually must stay attached to a person for more than 36-48 hours to be able to transmit the parasite.

Treatment of Toxoplasma gondii

Most infections in immunocompetent: resolve spontaneously Disseminated infection: Pyrimethamine plus sulfadiazine, Alternative: clindamycin plus pyrimethamine Cerebral edema and ocular infection: corticosteroid added Prevention and control Routine serologic screening for patients before organ transplantation and early in HIV infection (For sero+, Trimethoprim-sulphamethoxazole) Screening of Pregnant women (a part of 'TORCH' screening) Pregnant women and immunocompromised: avoiding raw or undercooked food, avoiding exposure to cat feces

Cerebral malaria

Most severe neurological complication of infection with Plasmodium falciparum malaria; Coma; Only young ring forms and occasionally gametocytes peripheral blood Mortality high, surviving patients sustain brain injury- long-term neuro-cognitive impairments.

Treatment of Chagas Disease

Nifurtimox and benznidazole (FDA not approved) In the U.S., drugs available only through CDC Prevention and Control Improved housing and spraying insecticide inside housing to eliminate triatomine bugs Screening for Chagas disease during blood donations Early detection and treatment of new cases

Pathogenesis of Naegleria fowleri

Rare but fatal. Primary Amebic Meningoencephalitis (PAM). It starts with flu like symptoms, severe headache followed by Meningeal signs: high fever, stiff neck, vomiting; Olfactory hallucinations, focal neurologic deficits, and progresses rapidly (<10 days); and Coma and death.

Morphology of Plasmodium spp.

Sporozoan, exists in different forms (sexual and asexual reproduction). Sporozoites : infective to liver cells Trophozoites: early stages in liver/RBC Schizont - mature malarial parasite, contains many merozoites. Merozoites: infective to RBC Gametocyte: inside RBC

Babesia: Life cycle

The Babesia microti life cycle involves two hosts, which include a rodent, primarily the white-footed mouse and a tick in the genus Ixodes. During a blood meal, a Babesia-infected tick introduces sporozoites into the mouse host . Sporozoites (pyriform bodies) enter erythrocytes and undergo asexual reproduction (budding) . In the blood, some parasites differentiate into male and female gametes, although these cannot be distinguished by light microscopy . The definitive host is the tick. Once ingested by an appropriate tick , gametes unite and undergo a sporogonic (sexual) cycle resulting in sporozoites . Transovarial transmission (also known as vertical, or hereditary, transmission) has been documented for "large" Babesia species but not for the "small" Babesia, 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 usually are dead-end hosts. However, human-to-human transmission is well recognized to occur via contaminated blood transfusions

Toxoplasma gondii life cycle

The oocyst/cyst is rapidly digested by the acidic-pH gastric secretions. Bradyzoites or sporozoites are released, enter the small-intestinal epithelium, and transform into rapidly dividing tachyzoites. The tachyzoites can infect and replicate in all mammalian cells except red blood cells. Once attached to the host cell, the parasite penetrates the cell and forms a parasitophorous vacuole within which it divides. Parasite replication continues until the number of parasites within the cell approaches a critical mass and the cell ruptures, releasing parasites that infect adjoining cells. Most tachyzoites are eliminated by the host's humoral and cell-mediated immune responses. Tissue cysts containing many bradyzoites develop 7-10 days after systemic tachyzoite infection. These tissue cysts occur in various host organs but persist principally within the central nervous system (CNS) and muscle. The development of this chronic stage completes the nonfeline portion of the life cycle. Active infection in the immunocompromised host is most likely to be due to the spontaneous release of encysted parasites that undergo rapid transformation into tachyzoites within the CNS. The principal (feline) stage in the life cycle takes place in the cat (the definitive host) and its prey. The parasite's sexual phase is defined by the formation of oocysts within the feline host. This enteroepithelial cycle begins with the ingestion of the bradyzoite tissue cysts and culminates (after several intermediate stages) in the production of gametes. Gamete fusion produces a zygote, which envelops itself in a rigid wall and is secreted in the feces as an unsporulated oocyst. After 2-3 days of exposure to air at ambient temperature, the noninfectious oocyst sporulates to produce eight (from 2 sporocysts, each with 4 sporozoites) sporozoite progeny. The sporulated oocyst can be ingested by an intermediate host, such as a person emptying a cat's litter box or a pig rummaging in a barnyard. It is in the intermediate host that T. gondii completes its life cycle.

Diagnosis of Babesia microti

Thin Smear: "Maltese cross" - intra-erythrocytic ring-shaped parasites in a thin blood smear. Inoculation of blood sample to hamsters Serology - IFA Detects Antibodies PCR

Epidemiology of Malaria

Tropical and subtropical, human to human via a vector- mosquito (Anopheles spp), by blood transfusions/organ transplant, also by IV drug use Malaria is one of the most severe public health problems worldwide. It is a leading cause of death and disease in many developing countries 1-5 billion febrile episodes and 1-3 million deaths annually. Approx. 1,500-2,000 cases every year in US Airport malaria: In Palm Beach County, Florida, during the summer of 2003, a cluster of eight cases of malaria was detected

Trypanosoma

Trypanosoma brucei 2 subclasses Trypanosoma brucei gambiense Trypanosoma brucei rhodesiense African Sleeping sickness Trypanosoma cruzi --American trypanosomiasis, Chagas disease

Reduviid bugs (Triatomine bugs/kissing bugs)

Trypanosoma cruzi vector, feeding and defecating on the wound after taking a blood meal. The bug excretes the trypomastigote form along its feces while feeding. It enters the bite site or eye while the persons rub the site of infection and the eye.

Detection of Plasmodium antigens

pLDH (parasite lactate dehydrogenase) Rapid diagnostic test (RDT) is based on rapid immunochromtatographic lateral flow principle. Dye-labeled antibody, specific for target antigen, is present on the lower end of nitrocellulose strip or in a plastic well provided with the strip. Antibody, also specific for the target antigen, is bound to the strip in a thin (test) line, and either antibody specific for the labeled antibody, or antigen, is bound at the control line. Blood and buffer, which have been placed on strip or in the well, are mixed with labeled antibody and are drawn up strip across the lines of bound antibody. If antigen is present, some labeled antibody will be trapped on the test line. Excess-labeled antibody is trapped on the control line. The accumulation of microscopic dye particles on the thin band produces a visible line if sufficient antigen-labeled antibody complex is present.