Parasitology Review

PARASITOLOGY REVIEW

Types of Life Cycle • Direct life cycle  – Only one animal (human) host needed for entire life cycle. Pinworm, hookworm, head lice  – •

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Indirect life cycle  – More than one animal host required for complete life cycle beef tapeworm (human + ox)  –  – fluke (human + snail) filariasis (human + mosquito/fly)  – malaria (human + anopheline mosquito)  – Vectors Animals, usually arthropods (insects/ticks/mites) that transmit infection

Types of host in indirect life cycles Definitive host •  – Host where sexually mature adult forms.  – Malaria (mosquito); Toxoplasma (cat) • Intermediate host  – host(s) in which larvae form Reservoir Hosts Wild or domestic animals that maintain parasite life cycle. I.e. stage of life cycle is not restricted to humans with animals and humans acting as alternative hosts

Many wild animal hosts Water buffalo Dogs

: Trypanosoma brucei  (African trypanosomiasis) : Schistosoma japonicum (Borneo) : Leishmania infantum

LIVER PHASE OF MALARAIA Sporozoites invade hepatocytes  – Multiply greatly (1 sporozoite gives rise to several thousand merozoites) Merozoites released in 1-2 weeks (depends on species)  – These will infect RBCs

Dormant forms hypnozoites derived from sporozoites (Gr . hypno = sleep). These activate and grow in hepatocytes at various times after original mosquito bite to give relapse Reactivation  –  –  –

P. vivax  and P. ovale ~5 years reactivation due to hypnozoites P. malariae > 20 years due to reactivation of persistently infected RBCs P. falciparum does NOT have hypnozoites and cause relapse

Red cell phase RBC infection to cell lysis ~48 h (tertian malaria) except for P . malariae • •  falciparum. capillaries in CNS (cerebral malaria) and GI (diarrhea).  – Potentially deadly. Infected RBCs become sticky and block capillaries Liver phase (hepatocyes). Persons with sickle cell trait (HbA+S) resistant • vivax  Persons who are Duffy-negative are resistant  – • ovale

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malariae fever every 4 day

Damage due to P. falciparum Blocking of capillaries • Anemia (of inflammation + some red cell lysis: 5% RBCs can be infected) • Fever • Treatment • AFRICAN TRYPANOSOMIASIS TRYPANOSOMIASIS Extracellular blood protozoan that divides longitudinally • Transmitted by tsetse fly • Wild animals provide major reservoir •

Surface coating has antigenic antigenic VSG (variable surface glycoprotein). glycoprotein). Different VSGs are expressed by organisms organisms within a population. This allows a replacement population to be generated generated after an effective antibody response against the dominant VSG. This enables evasion of host response Infection occurs in 3 stages. • chancre may develop at inoculation site. hemolymphatic stage • fever, lymphadenopathy, and pruritus. meningoencephalitic stage invasion of the central nervous system cau sing headaches, somnolence, abnormal behavior, and leading to loss of  consciousness and coma. •

Chagas’ Disease - Trypanosoma cruzi  South American (and Central Central American) trypanosoma. Transmitted by reduviid bugs bugs that pick up flagellated form from • blood In addition to blood form, amastigotes (no flagella) are produced and these live intracellularly • Major cause of  cardiomyopathy . Also megaesophagus with or without megacolon following destruction of myenteric • plexus. Other sites may may be involved too LEISHMANIASIS Old World and New World diseases caused by different species • Infective form is flagellated is released into skin by a sandfly and is phagocytosed to form the intracellular amastigote. • The amastigotes lack flagella and divide divide within macrophages. macrophages. This is the diagnostic form • Transmitted to sandflies ingesting blood containing amastigotes within monocytes •

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Visceral disease (most serious) affects all organs where grows in fixed macrophages or macrophages that enter enter organ Cutaneous disease (chronic sore). Several species: differ in Old and New World Mucocutaneous disease in South and Central America. Single species that has potential to eat away face Controlled by Th1 activity (IFN-g activation of macrophages)

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Visceral Leishmaniasis Human main source for L. donovani  Dogs, main source for L. infantum

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TOXOPLASMOSIS Definitive hosts are felines (cats etc) where T. gondii  grows within the gut epithelium. When infected, these release oocysts • in their feces for about 3 weeks. weeks. It takes about 3 days for oocysts to become infective (embryonate) Embryonated oocysts ingested by mammalian intermediate host • Oocyst wall digested in small intestine. Parasites penetrate intestinal wall and are picked up by macrophages, then spread • throughout body via blood. •

The tachyzoite stage in macrophages divides extensively, when released can infect other macrophages or almost any nucleated cell

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Progressive disease controlled by T-cell mediated immunity (Th1) which prevents spread of infection in organ. Area where infection occurred and somewhat controlled is a pseudocyst (especially brain but the other sites) If pseudocysts are eaten, infectious toxoplasma can cause infection in humans (mainly associated with not fully cooked meat) Humans infected by eating: oocysts (from cat feces)  – ppseudocysts (uncooked flesh of an intermediated host)  – Congenital disease serious Can occur if mother is not immune and becomes infected shortly before or during pregnancy (Torch syndrome).  – Chorioretinitis often seen.  – Keep cats indoor and don’t handle cat feces AIDS reactivation of pseudocysts can occur. Toxoplasma is the most common reason for ring-enhancing lesion in brain  – seen in contrast enhanced CT or MRI scan Diagnosis: serology (IgG in absence of I gM antibody suggests immunity and no ongoing infection)  –

GIARDIASIS In USA, most common protozoal pathogen reported causing GI infection • Acquired by ingesting cysts (usually in water or other fecal-oral). • Cysts are present in feces (human and several animals including beaver) • Infection causes diarrhea and can lead to chronic malabsorption syndrome. syndrome. Giardia attaches to upper small small bowel • IgA deficient people very susceptible • Diagnosis; detection of trophozoites and/or cysts in f eces (specific antibody-based stains a vailable for trophozoites) •

CRYPTOSPORIDIOSIS persons typically recover very fast. It grows within the GI tract, • Cryptosporidium parvum is a common cause of diarrhea but persons hardly ever disseminates Incidencem of diarrhea increases with communal bathing a t swimming pools during summer months • In AIDS, C. parvum can cause a chronic, potentially lethal, diarrhea. • Infection from ingesting oocysts (1 oocyst is enough to establish infection) • Diagnosis via microscopy for oocysts in feces ( C. parvum oocysts are acid fast). Antibody-based stains are available • ENTAMOEBA HISTOLYTICA Infects ~ ½ billion people • Causes intestinal and extraintestinal infection • Infection is fecal-oral  – cysts transmit disease. Almost all infectionis human-human • ~90-95% infectiuons asymptomatic • Colitis most common disease (flask shaped ulcers in colon mucosa) • If invade portal venous system, can cause liver abscess. Abscess also can form elsewhere such as lung and brain • Entamoeba histolytica types of disease and diagnosis Colitis – Colitis – diagnose using feces or mucosa biopsy (Serology c an help but is not positive all teh time) • • Extraintestinal diseases (e.g. liver abscess) – abscess)  – visible by imaging. (could be hydatid cyst, tumor or Entamoeba )

For differential, serology is needed since finding E. histolytica in intestine does not prove it is causing an extraintestinal abscess (antibody and antigen tests available)

Material drained from abscess is just necrotic cells. You cannot see Entamoeba in it since the live amebae are penetrating and attacking the surrounding liver tissue Typical therapy is metronidazole then paromomycin • TRICHOMONIASIS Major STD. Often asymptomatic in men, can be asymptomatic asymptomatic in women • Infection in women characterized by vaginal discharge + soreness. • Diagnosis made by from wet mount with motile protozoan seen. Also with various stains including antibody-based stains •

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Metronidazole is usual treatment

DRUGS FOR MALARIA • Chloroquine Oral. Used as prophylaxis and for acute attacks  – all types of malaria. Kills schizonts in blood, not in liver liver  – BUT much P. falciparum is now resistant so rarely able to be first choice for prophylaxis or treatment of falciparum  – malaria • Mefloquine Oral. First line prophylaxis where where chloroquine resistance is present. Resistance to mefloquine is emerging emerging in SE  – Asia. Used for acute malaria (as alternative to quinine) Primaquine • Kills schizonts in tissues but not in blood  – (good for eradicating liver stages of  vivax and ovale)  – • Quinine Oral for active disease (can be i.v. in severe disease). Fairly toxic. Usually used with doxycycline or clindamycin clindamycin to  – reduce time of use. Kills schizonts in blood- not in liver. Problems in G6PDH deficiency. Can cause intravascular hemolysis (Blackwater fever) Antifolates • Doxycycline (can be used as prophylaxis in areas with resistance to mefloquine and chloroquine)  – A variety of other drugs available with varying effectiveness and side effects • DRUGS FOR OTHER PROTOZOA Metronidazole (oral) • Amebiasis, giardiasis, trichomoniasis  –  – Bacteroides fragilis, Clostridium difficile Free radicals produced during its metabolism. metabolism. Requires high redox potential (not found in non-anaerobic  – microbes) Reported effective in cutaneous forms of leishmaniasis  –  – Paromomycin Aminoglycoside that can be used for luminal amebiasis  – ? ? Some efficacy for cryptosporidioisis in AIDS  – Being investigated and looks effective as cheap alternative for visceral leishmaniasis (r eplacing liposomal  – amphotericin B or sodium stibogluconate which is toxic and tends to prolong cardiac QT interval) DRUGS FOR TOXOPLASMOSIS AND TRYPANOSOMIASIS Toxoplasmosis •  – Antifolates Pyrimethamine + sulfadiazine • Pyrimethamine + clindamycin • Given with folinic acid (=leucovorin) to offset offset hematologic toxicity. Folinic acid is converted to • tetrahydrofolate directly (not requiring dihydrofolate reductase) • Trypansomiasis blood stages of African trypanosomiasis. Also used for Pneumocystis  – Pentamidine - only the blood  – Melasoprol - CNS stages of african trypanosomiasis mucocutaneous leishmaniasis).  – Nifurtimox - Both Chagas and African trypanosomiasis (+ mucocutaneous Highly toxic TAPEWORMS Adult in intestinal lumen has a scolex that attaches to intestine wall, followed by the neck region and strobila composed of  proglottids. immature near neck • mature, • gravid (with fertile eggs) • Eggs (+ proglottids) in feces give diagnosis

Larval forms derived from eggs that are ingested

In correct host, eggs hatch within small intestine and larva penetrates through intestinal wall and migrates into tissues where it forms a mature infective larva. This is the damaging form of tapeworm disease The infective larva, larva, when eaten by a definitive host, develops into the adult tapeworm within the intestine Adult Tapeworms • Site in human Source Diagnosis Beef  intestine larva in beef eggs(+proglottids) in feces T. saginata intestine larva in pork eggs(+proglottids) in feces Pork T. solium These have humans as their sole definitive host Fish intestine larva in fish eggs(+proglottids) in feces D. latum May absorb beaucoup vitamin B12 and, if enough, cause megaloblastic anemia (rare) Has a number of wild animals as reservoir definitive hosts Human Larval tapeworm disease • Acquired from ingesting eggs from feces • i.e. fecal oral • Controlled by good sanitation • Hydatid cyst. Many intermediate hosts including humans. (Dogs are definitive hosts) • Cysticercosis Pigs and humans can both be intermediate intermediate hosts infected via via eatings Taenia solium eggs released in human • feces Cysticercosis • Taenia solium eggs release larvae in small intestine Larvae penetrate intestinal wall and spread to multiple sites including muscle, liver and CNS • Muscle infection  – myalgias, see calcifications by X-ray • Brain infection - seizures etc. Especially after a few years when aging cysticercus cysticercus begins to swell swell • Fairly common in parts of Mexico where incidence of pork tapeworm is high and hygiene may be low • Larval disease caused by Echinococcus granulosus (hydatid cyst) Many animals, including humans, can act as intermediate hosts. • Herding animals with dogs associated as an occupational risk • Larva forms a large ball like structure filled with fluid and protoscolices (hydatid sand). On rupture of the cyst, protoscolices protoscolices • can form new cysts. Antigens in fluid may also cause anaphylaxis leading to death. When protoscolices eaten by dog, adult tapeworm forms in dog intestine • Diagnosed by imaging and serology • FLUKES • • • • • •

All flukes have a mollusc (a water snail) as an intermediate host. Therefore all show an indirect life cycle. Eggs released from humans hatch in water and release a larva that infects the snail. In the snail, the organism divides a nd the numbers of larvae increase substantially The larval form released from the snail is motile and named a cercaria Humans are either infected via ingestion of encysted cercaria (liver fluke and lung fluke) or the cercariae may infect directly through the skin (i.e. for schistosomes) After infection larvae enter human circulation by penetrating small intestine wall (lung and liver flukes) or after some time as a schistosomulum in the skin and migrate through tissues before arriving arriving at target site and becoming adults (eosinophilia seen)

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Liver flukes (bile duct), Lung flukes (lungs), Schistosomes (blood vessels in mesentery or a round bladder) Liver fluke (Fasciola) Lung fluke  – Paragonimus westermani 

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Schistosoma mansoni  Water snail host of certain sc histosome species (limited snail species are hosts)

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Schistosomes Contact with water leads to infection through skin by cercaria

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The cercaria then undergoes transition to a schistosomulum 5 min: schistosomule penetrated penetrated surface of epidermis epidermis o 10 min: broken through basement membrane membrane of epidermis o o 20 min: migration in dermis. Search for blood vessel and time for antigen coating (2 days) o

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transition to schistosomulum hyaluronidase helps in skin penetration • • cercaria loses tail • fresh water to salt water organism physiology glycolysis switch to fermentation • tegument takes up host components including RBC antigens, HLA, Ig • Once complete (~2 days) schistosomulum migrates from skin via lung to liver

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3 main species. species. Mate, produce eggs S. mansoni : mesenteric veins • • S. japonicum : mesenteric veins • S. haematobium : veins around bladder Eggs released (100s - 1000s a day) migrate into intestinal lumen or bladder. Eggs produce proteases allowing migration • through host tissue. ~50% eggs die within host tissue. • The dead eggs induce inflammation and that eventually causes tissue damage • Schistosoma haematobium hematuria in early disease • (school urines: East Africa who/tdr/crump) o evential fibrosis of bladder and obstructive uropathy • renal failure and hydronephrosis can occur. • Bladder carcinoma also found •

Diagnosis  –

Eggs are characteristic

Main species • and Central America, Caribbean) Caribbean) Lateral spine S. mansoni (Tropical Africa, S. and • S. japonicum (Asia) eggs in feces • S. haematobium (Tropical Africa, Near East) eggs in urine, and some in feces Terminal spine. (Additional 2 less common species with more localized distributions) Control (~200 million million persons affected) affected) Specificity for snail host prev ents spread outside snail’s geographical range Sanitation (avoiding excretion into open water where snails live)  –  – Snail reduction (also control irrigation projects that allow snail spread) • Reduction in carriage in population by using medication. But S. mansoni  also in some rodents  –  – Immunity Main target is schistosomulum and enzymes involved in skin penetration. • Low worm load may give minimal disease but stimulate some (not total) resistance to further infection - (Concomitant • immunity) Macrophages, eosinophils, neutrophils all involved in resistance. • IgE receptors on macrophages and activated eosinphils. • Cercarial dermatitis Infection of skin by cercariae that are not a dapted to humans (e.g. in ducks, these mature into adult schistosomes) • cercariae penetrate skin (pin prick) • fail to form functional schistosomulum and die • inflammatory reaction in skin (treatable with antinflammatory drugs • serious problem locally for swimmers in ponds, quarries etc •

PARASITIC HELMINTHS Basic Life Cycle Tapeworms, Flukes, Nematodes Egg • Larval stage(s) • Adult • INTESTINAL NEMATODES adults live in GI tract, maturing usually in small intestine or colon. • some species get to intestine after larval migration via internal organs (e.g. lung) • usually direct infection by eggs or larvae • (but hookworms & Strongyloides infect through skin)  – Almost all intestinal worms have direct life cycle Most cannot replicate without without humans • Pinworm (Enterobius) Extremely common, most notable in young children • 400,000,000 worldwide • Direct life cycle • Female 8-13 mm • Male 2-5 mm • Eggs ingested Larvae hatch in small intestine (2 molts) and migrate to colon Mature and mate Females (containing ~10,000 eggs) migrate out of anus and lay eggs on anal skin after explosive evagination of uterus Eggs become infective (embryonate) after 6 h INTENSE ANAL ITCHING – ITCHING  – main symptom! but many persons with low level carriage are asymptomatic Diagnosis: characteristic eggs on anal skin - detected using using clear sticky tape (Scotch tape test). Sometimes worms seen in feces Whipworm - Trichuris Similar life cycle to pinworm except adults live in colon and females release ~5000 eggs/day directly into feces. • Eggs take ~3-4 weeks to become infectious (embryonate) in soil • Infection by ingesting embryonated eggs • Often coinfecting with hookworm and Ascaris •  – 1 billion persons Extremely heavy infections  – can cause rectal prolapse  –  Ascaris lumbricoides Worldwide 1.5 billion • (in USA, mainly in South) • Direct life cycle • Adults are large • 8-14 inch female (200,000 eggs/day)  – 6-12 inch male  – Infection after ingestion of embryonated eggs • Eggs released in feces require 2-4 wk. incubation in soil to become embryonated. embryonated. Widely spread when human feces used • as fertilizer  Ascaris lumbricoides - A long journey journey home

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Infection via oral route: embryonated eggs Larvae hatch in small intestine (pH bile) and enter lamina propria and mesenteric capillaries Migrate via liver, heart to lung Enter alveoli and then migrate up bronchioles, bronchi and trachea to epiglottis and then swallowed Larval migration and molt in lung induces IgG antibody and eosinophilia After entry to small intestine, intestine, larvae mature (2 molts) into adults. adults. Mating occurs with 6 weeks Adults feed on digested food in intestine

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Problems Larval migration: (no effective drug). Large number can cause pneumonitis & liver enlargement  – worms: rarely problem. If many, can cause intestinal intestinal blockage.  – Adult worms: Aberrant migration known.  – Bile duct, liver, • penetrate intestinal wall  – peritonitis • Diagnosis  – Eggs in feces characteristic Occasionally whole worms expelled  – Many carriers asymptomatic  – Control:  – Sanitation Eggs resist disinfectants and sewage treatment  – Treatment: • mebendazole, albendazole  – also pyrantel pamoate, ivermectin, tribendimine •

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Trichinosis - Trichinella spiralis Infection after ingestion of larvae in meat. • Several million humans were infected in USA most usually due to T. spiralis in pork (16.1% population in 1943; 4.2% in • 1970) Main source now is wild animals. 72 cases reported to CDC (1997-2001) • In most environments kept in in circulation by rodents being being eaten by carnivores • In Arctic animals, variety of parasite survives deep freezing • Adults are very small and have short short life (~7 days) in intestine. Not usually seen. • Female releases larvae that penetrate intestinal wall • Released larvae enter lamina propria, then blood/lymph, and migrate around body. • Penetrate into cells • • In skeletal muscle “encysted” in a Nurse cell and survive many years. In other tissues, larvae die. Signs and Symptoms Intestinal - First week Nausea, vomiting, cramps, diarrhea (sometimes bloody) Extraintestinal – Extraintestinal – Second week Muscle invasion (myalgia, weakness, malaise) Other organs may be invaded, may see petechiae Myocarditis (uncommon) is potentially fatal CNS invasion can cause fits, paralysis, coma etc. rd By 3 week, larvae begin to encyst nd rd Eosinophilia in 2 week peaking in 3 week Serum creatinine phophokinase and LDH levels Diagnosis No eggs are passed!! Serology for antibody and muscle biopsy to see larvae • Hookworm • 2 species - Widespread in tropics and important important cause of anemia. 1.3 billion infected, 12% morbidity.  – 65,000 die, 0.005% Adults (~1 cm) in intestine live 4-5 years •  –  Ancylostoma - 0.1-0.2 ml blood per day

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Necator - 0.01- 0.02 ml blood per day Heavy infections can have >1000 worms

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Adults in small intestine Females release 10,000-30,000 eggs/day Eggs hatch within 2 days on warm sandly soil Larvae feed on debris and molt twice Filariform larvae climb on vegetation (grass etc)  –

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On contact with bare bare skin, filariform larvae PENETRATE PENETRATE skin, usually usually entering via hair follicle. Enter capillaries. Migrate via lung, bronchi and trachea to epiglottis and are swallowed (as for  Ascaris)

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Migratory phase  – Eosinophilia Diagnosis distinguish hookworm species  – Characteristic eggs: do not distinguish Prevention good sanitation  – (avoid feces on soil- privies are adequate) • wearing shoes.  –

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Strongyloides • Tropical: Seen in Indochina and and other areas of the world Similar to hookworm but differs by: • Non-human reservoir hosts (monkey, dogs)  – Eggs released but hatch within human intestine  – rhabditiform larvae in feces (diagnostic).  – Filariform larvae penetrate human skin (as in hookworm)  –

Autoinfection possible rhabditiform larvae molt in intestine (constipation)  – resultant filariform larvae can directly reinfect via colon mucosa or via skin  – Large build up in immunosuppressed patients  –  – Strongyloides • Diagnosis Rhabditiform larvae in feces.  – Eggs NOT found in feces  –  – String test ELISA  – Long term survival of infection means screening must be done before immunosuppression for transplant, cancer  – etc. • Nematode Parasites in Wrong Host • Larvae wander in tissues in absence of sensing sensing correct signals for migration. Intense inflammation and irritation. irritation. Eventual death Dog hookworm and other nematodes • Cutaneous larva migrans  –  – Dog ascaris and other species. Infection after ingesting eggs  – Visceral larva migrans (eye, brain are possible)  – Many different species known to cause these  – diseases including a nematode of raccoons Wandering larvae • Tissue nematodes  – vector transmitted • Prevalence Lymphatic filariasis (elephantiasis) 120 million Onchocerciasis (river blindness) 37 million Loiasis (African eye worm) 13 million Dracunculiasis (Guinea worm) 1 million •

(a deep tissue nematode: not truly a filarial species) Many species of filarial nematodes contain essential bacterial endosymbionts: potential treatment target Lymphatic filariasis • Wuchereria bancrofti  and other species Wuchereria bancrofti  Detection of filariasis in humans • Detection of microfilariae in blood. Requires testing at time mosquitoes were biting (often middle of night). Still needed • when not Wuchereria infections Most easy method now for detecting Wuchereria is via antigen in blood  – can be done at any time of day/night •

Onchocerciasis – River blindness Major cause of blindness following continual inflammation of eye • Larvae transmitted by bites from Simulium blackflies that live on rocks with fast moving water • Adults live in subcutaneous nodules and release microfilariae that mainly are found in skin and connective tissues. • Inflammation follows their death Severe itching of skin • Adult Onchocerca volvulus in nodules • Guinea worm ( Dracunculus) Removing the Guinea Worm • Treatments (main drugs) for helminths • Not all of them Nematodes •  – Ivermectin intensifies GABA-mediated neurotransmission  – Mebendazole inhibits microtubule synthesis  – Albendazole  – Pyrantyl pamoate Others (antibacterials being investigated investigated for filariasis)  – Flukes and Adult Tapeworms • ++  – Praziquantel for most acts on Ca uptake  – Oxamniquine ( Schistosoma mansoni  only) Larval tapeworms •  – Albendazole Tick paralysis (fairly rare) Toxin produced by female ticks: several genera • Affects motor nerve conduction • Ascending paralysis • Tick typically attaches at back of neck. • Treatment: Remove tick and support patient • SCABIES Mite (itch mite, Sarcoptes scabiei ) • Forms tunnels in epidermis • After mating in skin pits, fema le mite tunnels within epidermis, leaving feces and eggs behind • Irritation associated with immune inflammatory inflammatory response. More rapid if already sensitized on previous occasion. • Only short term survival off body • In typical case