Toxoplasmosis: Amoebic Meningitis Flashcards
Aetiology:
Toxoplasma gondii - A _______ _______
usually (asymptomatic or symptomatic?) infection in humans
tissue sporozoan
asymptomatic
Toxoplasmosis
Significant disease in _____________________,__________ patients and occasionally in ____________ individuals.
congenitally infected infants, immunodeficient
immunocompetent
Epidemiology of toxoplasmosis
T. gondii infection is a worldwide ______.
The organism infects ______,_______ and _________ animals, including ______.
zoonosis
herbivorous, omnivorous, and carnivorous
birds
Epidemiology of Toxoplasmosis
Mode of transmission:
Infection in humans most commonly occurs through
•the ________ of _______________ that contains _______
•the ________ of _________ contaminated with _______
•____________(________) transmission from a mother who acquired her infection during gestation
ingestion of raw or undercooked meat
tissue cysts
ingestion of water or food ; oocysts
transplacental (congenital)
Epidemiology of Toxoplasmosis
Less common transmission are:
– by _______ of _____________
–____________ of ___________
–___________ with contaminated needles
-exposing _________ or _____ surfaces to the parasite
transplantation of an infected organ
transfusion of contaminated blood cells.
Needle stick injury
open lesions or mucosal
Toxoplasmosis
The normal final hosts are strictly _____ and members of the family ______.
They play a significant role as powerful ______ of the infection in nature because the ______-producing (sexual or asexual?) stage of Toxoplasma develops in their ________.
cats; Felidae
amplifiers
oocyst; sexual
intestine
Life cycle of Toxoplasmosis
Organisms (either ________ from ________ or ________ from ________ cysts) invade the ________ cells of the ____________________, where they form ________ or ________________
After sexual fusion of the gametes, ________ develop, exit from the ________ into the ________ of the cat, and pass out via the ________.
In about __________, the environmentally (sensitive or resistant?) ______ are infective
When _______ are ingested by the cat, the parasites _______________. If oocysts are ingested by intermediate hosts such as certain birds, rodents, or mammals, including _______, the parasites can ____________ but reproduce only _________.
sporozoites ; oocysts
bradyzoites ; tissue
mucosal cells ;cat’s small intestine
schizonts ; gametocytes.
oocysts ;host cell
gut lumen ; the feces
48 hours; resistant ; oocysts
Oocysts; repeat their asexual and sexual cycle
humans; establish an infection
asexually.
Only members of the ____ family shed oocysts
cat
Life cycle of Toxoplasmosis
The oocyst opens in the human’s or animal’s ________ and releases the _______, which pass through the ______, circulate in the body, and invade various cells, especially _________, where they form ____________.
________ multiply, break out, and spread the infection to ________ and other organs.
duodenum ; sporozoites
gut wall; macrophages; trophozoites
Trophozoites ; lymph nodes
Trophozoites of toxoplasmosis
_________ are the actively proliferating trophozoites, which are observed during the (acute or chronic?) stage of infection
Tachyzoites
Acute
Life cycle of toxoplasmosis
The trophozites (rapidly multiplying _________ cells called ________ ) initiate the (acute or chronic?) stage of disease.
Subsequently, they penetrate _____ cells, especially of the _____ and _______, where they multiply (slowly or rapidly?) (as ______) to form ________ ——- cysts, initiating the (acute or chronic?) stage of disease.
The tissue cysts are infective when _________ (resulting in the intestinal ______ stage and _______ production); when they are eaten by other animals, more _________ are produced (_______).
crescentic ;tachyzoites
acute ; nerve
brain and eye
slowly ;bradyzoites
quiescent tissue ; chronic
ingested by cats ; sexual ; oocyst production
tissue cysts ;asexually
Tissue cysts of toxoplasmosis are found most commonly in the _____ and in __________________________ muscle but can occur in ______ organ
brain
skeletal and cardiac muscle
any organ
Pathogenesis of Toxoplasmosis 1
The tachyzoite directly ________ and has a predilection for ________ cells and those of the _______________ system.
Humans are relatively (resistant or sensitive?) , but a (low or high?) -grade _______ infection resembling _____________ may occur.
When a _______ ruptures, releasing numerous _______, a local _______ may cause _______, _______ of blood vessels, and cell death near the ___________.
destroys cells ;parenchymal cells
reticuloendothelial system ; resistant
low; lymph node
infectious mononucleosis
tissue cyst ; bradyzoites
hypersensitivity reaction ; inflammation
blockage; damaged cyst.
Pathogenesis Of toxoplasmosis 2
Presence of ________ is the hallmark of active infection
They reside and multiply within ______ in their host’s cells, can infect virtually all __________ and _________ cell types, and multiply approximately every ______ to form __________.
Continuous multiplication leads to cell disruption and release of organisms that go on to invade nearby cells or are transported to other areas of the body by _______ and _______.
Tachyzoites; vacuoles
phagocytic and nonphagocytic cell types
6 to 8 hours ; rosettes.
blood and lymph.
Tachyzoites appear to (actively or passively?) and (slowly or rapidly?) migrate across epithelial cells and may traffic to distant sites while ____cellular.
Actively ; rapidly
extra
Pathogenesis Of Toxoplasmosis 3
T. gondii multiplies ______cellularly at the site of invasion (the _________ is the major route for and the initial site of infection in nature)
________ released from tissue cysts or ______ released from oocysts penetrate, differentiate to _______, rapidly multiply within __________ cells.
Organisms may spread first to the ______ lymph nodes and then to distant organs by invasion of ________ and _______
T. gondii tachyzoites infect virtually all cell types, and cell invasion occurs as a/an (active or passive?) process.
intra; gastrointestinal tract
bradyzoites ;sporozoites
tachyzoites; intestinal epithelial
mesenteric ; lymphatics and blood.
active
Pathogenesis Of Toxoplasmosis 4
Survival of tachyzoite is due to the formation of a ____________ that lacks _______ necessary for ______________
Active invasion of ______ by ______ does not trigger ________ mechanisms.
With the appearance of humoral and cellular immunity, only those parasites protected by ________ habitat or within ________ shall survive.
An effective immune response significantly reduces the number of _________ in ____ tissues
after the initial acute stages, _________ are (often or rarely?) demonstrable histologically in tissues of infected immunocompetent humans.
parasitophorous vacuole
host proteins ; fusion with lysosomes
macrophages ; tachyzoites
oxidative killing; intracellular habitat
tissue cysts; tachyzoites ; all
tachyzoites ; rarely
Clinical Features of Humans toxoplasmosis:
(Asymptomatic or Symptomatic?) in most immunocompetent humans
Congenital infection develops only when ___________ mothers are infected during pregnancy, is usually of (little or great?) severity
postnatal toxoplasmosis is usually much (more or less?) severe
Asymptomatic
nonimmune; great
Less
Clinical Features of Humans toxoplasmosis:
fulminating fatal infections may develop in patients with ______, presumably by alteration of a _____ infection to an ______ one.
Varying degrees of disease may occur in immunosuppressed individuals, resulting in _________ or ________ , _______ ,___________ , or various other conditions.
AIDS; chronic ; acute
retinitis or chorioretinitis
encephalitis, pneumonitis
Clinical features of toxoplasmosis
The major features of (acute or chronic ?) acquired _______ toxoplasmosis are those of meningoencephalitis, myocarditis, pneumonitis, lymphadenitis, rash, and occasionally ______
In rare instances in immunocompromised hosts ,———— may be a prominent clinical manifestation resembling _________
Marked ______,__________,_________, and __________s occur in such patients.
acute; disseminated ; hepatitis
polymyositis ; autoimmune polymyositis.
Marked myalgias, muscle weakness and swelling, and fasciculations
Clinical features of toxoplasmosis
Muscle biopsy specimens show ______ with destruction of muscle fibers, and _________ of Toxoplasma gondii can be found in areas of muscle that are __________
interstitial myositis
pseudocysts
free of inflammatory reaction
Clinical features of Toxoplasmosis
Congenital infection leads to ________, _________, _________ calcifications, _______ disturbances, and _________ or ________
Major cause of _______ and other congenital defects.
Infection during the first trimester generally results in _________ or ________
Second- and third-trimester infections induce (more or less?) severe ______ damage
stillbirths, chorioretinitis
intracerebral; psychomotor
hydrocephaly or microcephaly
stillbirth or major CNS anomalies.
Less; neurologic
Clinical features of Toxoplasmosis
Clinical manifestations of these infections may be delayed until _____, even beyond ______.
_______ problems or ______ difficulties may be caused by the long-delayed effects of late prenatal toxoplasmosis.
long after birth
childhood
Neurologic; learning
Diagnosis of Toxoplasmosis
Direct detection of the organism is by
– ___________ assay,
– histopathology with immunoperoxidase staining,
-__________
–______ inoculation.
polymerase chain reaction (PCR)
tissue culture
mouse
Diagnosis of Toxoplasmosis
Serologic assays
can help distinguish ______ from _______ infection and can identify patients at risk for __________
.
acute from chronic
reactivation
Treatment of toxoplasmosis
Immunocompetent asymptomatic patients:____-
Immunocompromised patients: The therapy:
____________ plus ____________ plus ____________
OR
____________ plus ____________ plus either ____________ or ____________
OR
____________ ____________
no therapy
pyrimethamine plus sulfadiazine plus leucovorin
Pyrimethamine plus leucovorin plus either clindamycin or atovaquone
Trimethoprim sulfamethoxazole
Treatment of Toxoplasmosis
______ are given only for clinically significant edema or mass effect, and _______ are given only after a seizure.
Corticosteroids
anticonvulsants
Treatment of Toxoplasmosis
In pregnancy
less than 18 weeks: _______
Greater than 18weeks: ________+ ________
Congenital infection: ___________
spiramycin
pyremethamine + Folinic acid
pyremethamine
Prevention of Toxoplasmosis
Avoidance of contact with _______ particularly for pregnant women with negative serologic tests.
pregnant women should avoid all contact with _____, particularly _____
daily changing of ______ and its safe disposal, since oocysts usually take ______ to become infective,
cat feces
cats; kittens
cat litter; 48 hours
Prevention of Toxoplasmosis
Meat should be cooked very well to kill _______
Freezing meat at _____°C for ____ hours or heating to ___°C for _____ minutes will kill the organism.
tissue cysts
−20; 48hrs
50; 4-6mins
Prevention of Toxoplasmosis
Kitchen cleanliness, ______ after touching raw meat .
Periodic serologic screening for ____________ antibodies to Toxoplasma is recommended.
Do not allow cats to eat __________ and ________
Wash hands thoroughly after outdoor activities
handwashing
immunoglobulin (Ig) G and IgM
wild rodents and birds
prophylaxis of Toxoplasmosis
Immunocompromised patients: –_____-_____
–_______ + _______
TMP-SMX
dapsone; pyrimethamine
Free-living amebae (FLAs) are (aerobic or anaerobic?) , __karyotic ____ that comprise several genera.
Aerobic
eukaryotic protists
Free-living amebae (FLAs)
have ____ known insect vectors
Have ____ human carrier states of epidemiologic importance,
No
No
Free-living amebae (FLAs)
(Little or Major?) relationship between poor sanitation and their transmission
Infection of humans with FLAs is an (frequent or infrequent?) but often _____ occurrence in both normal and immunocompromised individuals.
Little ; infrequent
fatal
Free-living amebae (FLAs)
Central nervous system (CNS) invasion by __________,_________,__________ has been reported in hundreds of patients worldwide, with thousands of ____________________ cases described.
Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris
Acanthamoeba keratitis
Four distinct clinical syndromes are caused by the FLAs that infect humans
•_________________________(PAM)
•_____________________(GAE)
•_________________ disease
•______________ (AK).
primary amebic meningoencephalitis (PAM)
•granulomatous amebic encephalitis (GAE)
•disseminated granulomatous amebic disease
•Amebic keratitis (AK).
Microbiology and Epidemiology of Free-living amoeba
The trophozoite stages of these organisms feed on _______ and ___________
Naegleria fowleri is widely distributed globally and has been isolated from _______, most commonly in (warm or cold?) environments.
bacteria and debris in the environment.
fresh water; warm
Microbiology and Epidemiology of Free-living Amoeba
Acanthamoeba spp. are ubiquitous members of the environment and are found worldwide in ______ and ________.
Balamuthia mandrillaris is widely distributed and has been isolated from ____
soil and fresh water
soil.
Clinical Manifestations and Diagnosis
N. fowleri typically causes a __________ ————- in healthy, immunocompetent young patients, in association with ______ in _______ water.
fulminant meningoencephalitis
swimming; warm fresh
N. fowleri
The disease is nearly always fatal.
T/F
T
Clinical Manifestations and Diagnosis
N. fowleri
The cerebrospinal fluid (CSF) profile of patients with N. fowleri primary amebic meningoencephalitis (PAM) is similar to that seen in ______ meningitis (____ white blood cell count, ____ glucose, ___ protein), but with a ____ Gram stain and culture.
(Motile or Non-motile?) trophozoites can sometimes be seen on wet mount of the CSF.
bacterial; high
Low; high ; negative
Motile
Clinical Manifestations and Diagnosis
Neuroimaging studies in patients with PAM are usually (specific or nonspecific?).
nonspecific.
Clinical Manifestations and Diagnosis
Acanthamoeba spp. and B. mandrillaris cause the ______ onset of focal neurologic deficits
mental status changes (_______________) are related to central nervous system ___________.
subacute
granulomatous amebic encephalitis [GAE]
mass lesions
Clinical Manifestations and Diagnosis
Acanthamoeba is mostly seen in _________ and _________ individuals
Balamuthia occurs in _____________________ patients.
The case-fatality rate for these infections is also (low or high?).
immunocompromised and debilitated
both immunocompromised and immunocompetent
High
Clinical Manifestations and Diagnosis
CSF studies of patients with GAE are usually (specific or nonspecific?) , and it is (common or rare ?) to isolate organisms from the CSF.
Neuroimaging studies generally reveal multiple _________ lesions in the brain, with or without contrast enhancement.
Biopsy of involved tissues (skin, brain, etc.) can be diagnostic, usually via histopathologic examination/immunohistochemical staining or polymerase chain reaction (PCR).
nonspecific; rare
space-occupying
Clinical Manifestations and Diagnosis
Acanthamoeba spp. and B. mandrillaris can involve other sites ( _____,_______,_______, and skin).
Acanthamoeba spp. also cause _____ threatening ______ in otherwise healthy individuals in association with ______ use.
lungs, sinuses, adrenals
sight; keratitis; contact lens
Diagnosis of free living amoeba
Diagnosis depends on a __________, in conjunction with IN VIVO ____ microscopy
Demonstration of Acanthamoeba in _____________
biopsy specimens by histopathologic examination, culture, or PCR.
high clinical suspicion
confocal
corneal scrapings
Therapy for FLA
Therapeutic regimens for free-living amebic infections of humans are well defined
T/F
F
not well defined.
Therapy for FLA
Treatment for N. fowleri PAM should include high-dose ______ amphotericin products; _______ amphotericin may also provide some benefit, and the addition of azoles, rifampin, miltefosine, or other antimicrobials should be considered.
Acanthamoeba keratitis should be treated with _______ _______ or ———- ————
adjunctive surgical therapy may also be necessary.
intravenous; intrathecal
topical chlorhexidine or polyhexamethylene biguanide
Acanthamoeba GAE should be treated with ___________ regimens, possibly including ______,_______,________,_______, and ______.
However, the most efficacious regimen is _________________
Combination antimicrobial
pentamidine, an azole, a sulfonamide, miltefosine, and flucytosine
not currently known.
B. mandrillaris GAE should be treated with ________ regimens, possibly including pentamidine, flucytosine, a sulfonamide, albendazole, an azole, a macrolide, amphotericin, and/or miltefosine.
However, the most efficacious regimen is _______________
combination antimicrobial
not currently known.
_________________ may play an adjunctive role in the management of both forms of GAE( __________ and __________)
Surgical débridement
Acanthamoeba GAE
B. mandrillaris GAE
