Intro to Parasitic Infections Flashcards Preview

Skin MS: Week 4 > Intro to Parasitic Infections > Flashcards

Flashcards in Intro to Parasitic Infections Deck (72):


River Blindness (Robles disease in Latin America)


Onchocerca volvulus lifecycle

Blackfly takes blood meal (L3 larvae enter bite wound)
Go to subcutaneous tissues - adults in subQ, sexually reproduce to produce unsheathed microfilariae typically found in skin and lymphatics of CT, blackfly takes meal here, microfilariae penetrate blackfly's midgut and migrate to thoracic muscles --> L1 larvae --> L3 larve --> migrate to head and blackfly's proboscis


Drugs for onchocerciasis and what effective against

Ivermectin - effective against microfilariae (not adults)


Epidemiology of onchocerciasis

sub-Saharan Africa, tropical climates of the Americas, Yemen, Middle EAst
Transmitted by blackfly (near rivers and streams)


Onchocerciasis causative agent

nematode (roundworm) = Onchocerca volvulus


Sxs of onchocercaisis

Eye and skin disease
Nodules under skin (adults growing in SubQ)
Hyperpigmented skin (post-inflamm)
Severe itching, eye lesions, skin lesiosn (migration and inflammation by microfilariae, release of symbiont bacteria)
Destruction of elastic fibers --> skin looks thin


dx of onchocerciasis

skin snip method


symbiont bacteria of onchocerca volvulus

Wolbackia pipientis (causes inflammation when released by dead worms)


Onchocerciasis prevention

No vaccine. Aerial applications of larvicides to control blackflies and DEET application to prevent bites.


Onchocerciasis tx

Ivermectin (to avoid blindness, longterm damage to skin, continued transmission)
Well absorbed, affective against microfilariae. Retreatment required.
Doxy as co-tx for Wolbackia pipientis


Ivermectin mechanism

binds to and blocks glutamate-gated chloride channels that are present on invertebrate muscle and nerve cells


Leishmania life cycle

Sandfly takes blood meal - injects promastigote stage into skin (flagellar) - promastigotes phagocytized by macrophages and other types of mononuclear phagocytic cells - promastigotes transform into amastigotes - amastigotes multiply in cells of various tissues and infect other cells - sandlfy takes blood meal (ingests macrophages w/ amastigotes) - ingestion of parasitized cell - amastigotes transform into promastigote stage in gut of fly - diving in the gut and migrate to proboscis

** Requires uptake by phagocytic cell to achieve mammalian life cycle state - replicated in phagolysosome.


Leishmaniasis causative agent

Caused by the protozoan parasite Leishmania transmitted by the sand fly.


Leishmaniasis epidemiology

Leishmaniasis is found in East Africa, Asia, and Latin America and has multiple forms


Cutaneous leishmaniasis

leishmaniasis is most common, found in Old World (Asia, the Middle East, Africa) and New World (Latin America).
Symptoms: One or more skin sores. sores can change in size and appearance over time. Often volcano-like, with raised edge and central crater. sores can be painless or painful. Some people have swollen glands near the sores (for example, in the armpit if the sores are on the arm or hand).


Mucocutaneous leishmaniasis

very rare but results from a metastasis of an untreated case of cutaneous leishmaniasis


Visceral leishmaniasis

occurs mostly in Bangladesh, Brazil, Ethiopia, India, South Sudan and Sudan. Also called kala-azar. Life threatening!!!
Symptoms: weight loss, and an enlarged spleen and liver (usually the spleen is bigger than the liver). Some patients have swollen glands. Patients usually have low blood counts, including a low red blood cell count (anemia), low white blood cell count, and low platelet count. An emerging HIV opportunistic pathogen.


Leishmaniasis prevention

No vaccines or prevention (limit sandfly)


Dx leishmaniasis

Definitive diagnosis in laboratory : CDC will need to be involved. Usually still involves microscopic detection of the organism in a blood or tissue sample.
Serological tests will only be positive in the case of visceral leishmaniasis (same with tests that detect antigen directly).


Leishmaniasis - should be treated?

Should be treated. While cutaneous sores often heal on their own, they can leave disfiguring scars and possibly lead to mucocutaneous form even years later.


Leishmaniasis tx options

Pharmacology: Need drugs that can get into the macrophage, and furthermore, into the phagolysosome
Organic antimonials: Sodium stibogluconate and Meglumine antimoniate. Competing theories for mechanism of action. Incidence of treatment failures is increasing and resistance occurs. Must be administered intramuscularly.
Miltefosine. Mechanism not well understood. good alternative for drug-resistant leishmaniasis. Highly bioavailable and absorbed well.
Liposomal Amphotericin B. Only for visceral leishmaniasis. Only liposomal formulation of this anti-fungal is shown to be effective (injection necessary). Binds to ergosterol to form pores in membranes.


Romana's sign

swelling of child's eyelid - marker of acute chaga's disease
d/t bug feces into eye or bite wound on same side of face as swelling


Chagas disease - causative agent

flagellated protozoan parasite Trypanosoma cruzi


T. cruzi lifecycle

Triatomine bug takes blood meal and passes metacyclic trypomastigotes in feces/enter bite wound or mucosal membrane --> metacyclic trypomastigotes penetrate various cells at bite wound site - inside cells, transform into amastigotes - amastigotes multiply by binary fission in cells of infected tissues --> intracellular amastigotes transform into trypomastigotes then burst out and enter blood stream (and can infect other cells) --> triatomine takes blood meal - multiply in midgut - passed through feces


Acute Chagas

symptoms are often asymptomatic but often mild, typical innate immune response to an infection. Often acquired early in life. Occasionally severe.
Without treatment at the acute stage, individuals do not entirely clear the parasite, go on to the chronic stage.


Chronic Chagas

T. cruzi replicates intracellularly (immune evasion), but does exit cell in an additional life stage to find a new cell. The presence of parasites and a continuous low-grade immune response (inflammatory) is what is thought to contribute to the following:
Also, symptoms can reappear in chronic indeterminate individuals if they become immunocompromised


Dx Chagas

Identification of parasites in blood (acute or recurring infection only). Chronic infection is usually diagnosed with more than one serological test.


Should treat chagas ds?

Yes! Drugs are effective in acute stages, use and effectiveness in chronic stages where cardiomyopathy has developed is controversial. Permanent damage.


Chagas tx

nitroaromatics: Nifurtimox & Benznidazole are well absorbed from GI tract, no IV administration necessary.
Nifurtimox induces oxidative stress due to inhibition by NAD(P)H-dependent dehydrogenases with subsequent impairment of mitochondria membrane potential, Benznidazole has similar mechanism



Chagas disease (T. cruzi)
well absorbed from GI tract, no IV administration necessary.
Nifurtimox induces oxidative stress due to inhibition by NAD(P)H-dependent dehydrogenases with subsequent impairment of mitochondria membrane potential, Benznidazole has similar mechanism


Nifurtimox/Benznidazole specificity

This drug class requires a bacterial-like Type I nitroreductase to turn it from a prodrug to the active form. Trypanosomes have one, typical eukaryotic cells do not.


African Sleeping Sickness Causative agent

Trypanosoma brucei


T. brucei lifecycle

1. Tsetse fly takes blood meal - injects metacyclic trypomastigotes --> injected metacyclic trypomastigotes transform into blood stream trypomastigotes which are carried to other sites --> multiply by binary fission in various body fluids --> trypomastigotes in blood taked up by tsetse fly again --> transform into procyclic trypomastigotes in midgut - multiply --> leave midgut and transform into epimastigotes - multiply in salivary gland = metacyclic trypomastigotes


Tsetse Fly transmits two subspecies of Trypanosoma brucei that infect humans:

Trypanosoma brucei gambiense, West Africa
Less severe, longer lasting
African Sleeping Sickness

Trypanosoma brucei rhodesiense, East Africa
More acute illness


First Stage ASS

First stage: possible chancre at site of bite, fever, headache, swollen lymph nodes, muscle and joint aches, possibly rash or itchiness


Second Stage ASS

Second stage: CNS involvement, neurological symptoms include Somnolence (extreme sleepiness, esp. at inappropriate times), altered gait, tremors, cranial neuropathies, urinary incontinence, personality changes


Time scale ASS:

gambiense: CNS involvement after 1-2 yrs, death usually in 3 if not treated
rhodesiense: CNS involvement after a few weeks, death in a few months if not treated


T. b. gambiense antigenic variation

“Waves” of parasitemia are a major challenge to the immune system.
Not intracellular so immune system should find - organisms switch surface proteins/antigens to proliferate and evade immune system



Positive diagnosis is finding organisms in blood (special labs do this test), and in CSF if in second stage



The earlier the better! Sleeping sickness is Invariably fatal unless treated (waves of parasitemia)


ASS prevention

No vaccine or preventative is available


ASS meds

Suramin: Has an inhibitory effect on enzymes of the pentose phosphate and glycolytic pathways. Selectively accumulates in trypanosomes.

Pentamidine: Possible mechanism: interference with DNA replication of its unique mitochondrial genome. Selectively accumulates in trypanosomes.

Eflornithine: inhibits ornithine decarboxylase, which turns over faster in human cells than in trypanosomes

Melarsoprol: Unknown mechanism, may relate to metabolism


Nitrofurtimox and ASS

Has good absorption from GI tract (other don't - give IV) but can't cross BBB to CSF (co-treat with eflornithine)


Lymphatic filariasis (elephantitis) causative agent

tissue nematode Wuchereria bancrofti
transmitted by female mosquito


Wuchereria bancrofit lifecycle

Mosquito takes blood meal - L3 larvae enter skin --> adults into lymphatics - sexually reproduce to produce sheathed microfilaraie that migrate into lymph and blood channels --> mosquito takes blood meal and microfilariae --> shed sheaths, penetrate mosquito's midgut and migrate to thoracic muscles --> L1 larvae --> L3 larvae --> migrate to head and proboscis


Lymphatic filariasis epidemiology

Endemic to tropical areas in Asia, Africa, the Western Pacific, and parts of the Caribbean and South America.


Lymphatic filariasis shortened lifecycle

Larvae enters skin and gains access to the lymphatic system where it matures to adult worms. The adult worms only live in the human lymph system


Lymphatic filariasis clinical presentation

lymphedema and elephantiasis and in men, swelling of the scrotum, called hydrocele. Lymphatic filariasis is a leading cause of permanent disability worldwide.
Most individuals infected never develop clinical symptoms, or if they do, these symptoms appear years after initial infection. However, it may impact functioning of the lymphatic system, which in turn means the individual cannot fight bacterial infections as effectively.


Lymphatic filariasis dx

most typical is blood smear. Microfilariae that cause lymphatic filariasis circulate in the blood at night. Blood collection should be done at night to coincide with the appearance of the microfilariae. Alternately, elevated levels of antifilarial IgG4 in the blood can be detected with a serological assay.


LF prevention

No vaccines or preventatives, but MDA have been successful at wiping out the disease in certain foci, also important is mosquito control.


Tx LF?

Depends on whether infection in active or not
Lymphedema and elephantiasis are not indications for DEC treatment because most people with lymphedema are not actively infected with the filarial parasite. Hygiene assistance suggested. The treatment for hydrocele is surgery


LF tx

Diethylcarbamazine (DEC) administered orally, kills microfilaria and some adult worms. No longer FDA approved. Mechanism of action is on the arachidonic acid metabolic pathway in microfilaria. Generally well tolerated; however, DEC should not be administered to patients who may also have onchocerciasis as  DEC can worsen onchocercal eye disease.  In patients with loiasis, DEC can cause serious adverse reactions, including encephalopathy and death. Doxycycline????


Toxoplasmosis causative agent

Caused by Toxoplasma gondii parasite


Spread of toxoplasma gondii parasite

ingested as a tissue cyst (uncooked meat) or an Oocycst from unwashed produce or cat feces.
Also, in its life cycle, it forms muscle tissue cysts in its non-definitive hosts, which is one of the ways it is transmitted to humans.


Toxoplasma is a ________ parasite
Intracellular encystment is in host _____ and ______ cells

muscle and brain cells


Toxoplasmosis is opportunistic (2 populations?)

Immunocompromised- cerebral abscesses, fever, confusion, HA, seizures, nausea, poor coordination
Ocular toxoplasmosis (headlight in fog lesion)

A fetus if the mother is first infected during that pregnancy -->
Stillbirth or miscarriage
Abnormal head size (small or large)
May seem normal at birth but later develop:
vision loss, mental disability, and seizures

The earlier in pregnancy the infection occurs, the more severe the symptoms


Ocular toxoplasmosis

most common: red, painful, photophobic eye, with some decrease in visual acuity."headlight in the fog" lesion with multiple surrounding healed chorioretinal scars in one eye (need not be immunocompromised to get ocular toxoplasmosis, but more likely)


Toxoplasmosis dx

Serological testing is possible, but diagnosis requires some estimate of time of infection


Toxoplasmosis prevention

Vaccines are not available


Toxoplasmosis tx?

Not for most patients. Most will recover w/out tx, asymptomatic anyway
Pregnant women, newborns, and infants will need to be treated but note the caveats
Patients with ocular toxoplasmosis if the size, location, or characteristics of the lesion (actively growing) warrant it should be treated
The immunocompromised should be treated, until they have improvements in their condition
AIDS patients may require lifelong treatment as long as they remain immunosuppressed



Toxoplasma, babesia, malaria


Toxoplasmosis tx options

Some antimalarial combos also work on Toxoplasma and Babesia (apicomplexans)
High concentration in tissues over long times is desired -

Folate antagonist combo****
Sulfadiazine (Fundamentals) and Pyrimethamine (anti-malarial)
Folinic acid often co-administered
Specificity…T. gondii cannot utilize presynthesized folinic acid

Pregnant women shouldn’t use these drugs unless extreme circumstances warrant its use, instead, the experimental spiramycin could be obtained from the FDA. Does not cross placenta. A macrolide - prevent peptidyltransferase from adding the growing peptide attached to tRNA to the next amino acid, inhibiting ribosomal translation, premature dissociation of the peptidyl-tRNA from the ribosome.



- inhibitory effect on enzymes of PPP and Glycolytic pathways, trypanosomes (ASS)



- interference w/ DNA replicatoin of unique mitochondrial genome (ASS)



- inhibits ornithine decarboxylase, which turns over faster in human cells than trypanosomes (ASS)



- unknown MOA (ASS)


African Sleeping Sickness Hallmarks

T. brucei
Enters into bloodstream
Bloodstream CNS


Chagas hallmarks

T. cruzi
Enters mucosal tissue/dermal cells
bloodstream, cardiac, GI


Leishmaniasis hallmarks

Leishmania spp
Enters via skin macrophage
Skin, systemic


Toxoplasmosis hallmarks

Toxoplasma gondii
Enters via GI tract
GI, brain tissue, fetus, eyes


Onchocerciasis hallmarks

Onchocerca volvulus
Enters via SubQ
Skin and Eyes


Lymphatic filariasis

Wucheria bancrofti
Enters via skin
Lymphatic tissue