**acronym for grp of infectious diseases that can cause illness in "pregnant woman" and may cause "birth defects in newborns."
- sporozoan - tissue coccidia (invades tissue)
- widespread in humans, domestic/wild animals (i.e. cats)
- asymptomatic or mild infection
- serious congenital (existing from birth) and ocular (eye) infections
- severe infections in immunocompromised patiens (HIV, Bone Marrow Transplant, elderly, etc)
- ***PARASITIC INFECTION (only one of TORCH organisms)
infection with the parasite Toxoplasma gondii, transmitted to humans by consumption of insufficiently cooked meat containing the parasite or by contact with contaminated cats or their feces: the illness produced is usually mild, but in pregnant women may damage the fetus.
Toxoplasmosis (life cycle)
1. sexual stage in intestinal epithelium of cats/feline hosts
2. immature oocysts (eggs) passed in feces (pregnant women should not clean litter boxes!)
3. mature to infective stage in the environment in 2-21 days
-- ingestion of these sporocysts may lead to infection--the trophozoites (tachyzoites) infect nucleated cells.
- most infections asymptomatic
- may be fever and lymphadenopathy (chronic swollen lymph nodes)
- resempling Inf Mono
- **most signif. infection = Congenital (existing from birth)w/ variable symptoms (depends on time during preg.)
- Immunosuppressed = CNS symptoms, affect any organs, immunosupp. due to reactivation of a latent infec.
- causes blindness, psychomotor retardation, convulsive disorders
- 1st half: intrauterine death, microcephaly (small head), or hydrocephaly (water in the brain)
- 2nd half: asymptomatic at birth, ppossibly fever, hepatosplenomegaly (enlarged liver & spleen), jaundice at birth, chorioretinistis (inf. in back of eye) or CNS manifestation
Lab Testing (Direct examination)
- exam tissue via H&E stain (hematoxylin and eosin)
- smear & imprints via Giemsa stain
- immunoflorescence w/ anti-P30 monoclonal Ab (P30=Ag)
- smears: tachyzoites--spindle to oval shape 3x7 um; Cysts - 30 um
Lab Testing (Serology)
- "most common" way to estab. diag. (ELISA/EIA)
- Ab appear in 1-2 weeks
- titer peaks @ 6-8 weeks
- IFA or EIA "detect IgM" = congenital & accute infecions
***IgM used to diag. acute, primary infections
- EIA elev. for 4-8 mnths
- IFA fall by 2-4 mnths
***LOW TITERS not significant, since asymptomatic infect. are common.
Rubella - aka "Three day measles" or "German Measles" (3 names)
- first described in Germany, called Rotheln
- 30s viral agent transmitted to man and monkeys
- virus isolated in 1962
***single-stranded RNA virus
***member of Togaviridae
- highly contagious
- transmitted via respiratory secretion
- causes severe Congenital abnormalities if inf. in 1st tri
- epidemics in school-aged child until attenuated vaccine (proof of immu thru "Positive" Sero. screening test)
- now "more common" in older child & adolescents
- college/univ camp. susceptible to rubella inf.
- transmitted via inhalation of inf. droplets
- highly communicable
- incubation: 2-3 weeks
- contagious period: week before to week after onset of rash
- congental birth defects varies w/ time of maternal inf.
- risk of fetal malformations:
1st month of preg. = 50-80%
2nd month = 25%
3rd month = 17%
Note: cong. inf. infants declines w/ age but can still excrete virus up to 3yrs = reservoirs of inf.
Rubella (clinical aspects)
- mild generalized lymphadenophathy (ch.swollen lymph nodes), followed by macular rash (usu. last 3 days)
- malaise (body weak/discomfort), headache, fever
- few complicatoin include post-inf. encephalitits (inflam. subst. of brain), thrombocytopenia, arthritis, arthralgia (sev. joint pain)
**Congenital rubella (aka "Rubella Syndrome")
- ton of problems. Not a good thing!!
Important Rubella Lab Diag notes
***IgM found in fetus = Congenial rubella syndorome
***for current infection, paired sample is needed to observe IgM and IgG
***virus found in oropharynx and feces provides a reservoir for infection of others.
Lab Diag (Rubella)
Postnatally acq infection
- incubation: 10-21 days
- inf. peeps contagious for 12-15 days (5-7 days prior to rash)
Virus isolated from feces, urine, placental/fetal tissue of abortuses
Virus grown in rat kidney, rabbit cornea, and green monkey kidney cell line---microfoci of CPE
***remember Rubella virus produces microfoci CPE (cytopathic effect), so if CPE is absent in inoculated tube, virus possibly present.
***CPE virus will cause cells to change or die.
Lab Diag (Rubella) cont.
- absolute id req. "neutralization" of interference w/ rubella anti-serum
- Rubella titer of 8 or greater = immune
- titer of 16, 64, 512 or greater = acute and past infection
- Paired sera should always be examined simultaneously
- presence of titer in absence of disease = prev. infect. & hence immunity to re-infection
- re-exposure = rise in Ab titer, w/o viremia - fetus little risk
Hemagglutination inhibition test
principle: virus agglut. ckn RBCs.
- Patient sera comb. w/ Rubella Ag, if pt has Ab to rubella Ag then Ag-Ab forms not allowing the Ag to agglut. the "indicator" ckn RBCs.
--Note: NO Agglutination = +
- Live, attenuated rubella vacc
- Give alone @ 12 mnths old or @ 15 mnths old in MMR vacc
- ubiquitous (everywhere) human viral pathogen
- member of "herpes" family virus
- large enveloped "DNA" virus
- spread from cell to cell, via intracellular bridges, in presence of Abin extracellular phase
***not a problem for someone healthy.
- cell appearance of an "owl's eye" or alien
- replication found in WBCs
- long incubation period; slow replicative cycle in tissue
- local or systemic infectoins either active or latent
- endemic worldwide
- high prevalence in "young children" living in under developed, crowded, intimate conditions
- most often acq. peri- or postnatally; may be congenital
- transmitted via organ transplants or transufsion of blood; req. intimate contact of secretion or excretions
- nearly 100% of adults have Ab by age 35
CMV (Congenital infection)
***most common cause of congenital infections in humans.
- transmission from mother to fetus poorly defined
- maternal CMV infections subject to recurrence; genital tract
- asymptomatic or mild hepatomegaly (enlarge liver)
- symptoms vary
- Congenitally infected infants excrete extreme high titer
CMV (acq. infection or reactivation)
- same or diff strain excrete titers as high as 10^6
- infect others via oral, sexual, or parenterally by organ or blood trans.
- clinical manifestations: liver, spleen, heatopoitic syst, kidney, lungs
- can cause negative mono. like syndrom w/ fever
- CMV neg. blood = donors test neg for Ab to CMV
CMV (lab diag)
- culture method of choice
- often recovered from urine (during active phase)
- treatment = Ganciclovir
***most common manifestation = common cold sore, or fever blister.
- 2 types:
1. HSV-1 (herpes simplex virus type 1)
2. HSV-2 (type 2)
5 distinct herpes virus
3. Varicella-zoster virus (aka Chicken Pox)
4. Epstein Barr virus
- widespread, **man only!! host
- incubation: 2-12 days
- Serologic evidence: by age 25 = 70-80% of individuals, by age 45 = nearly 100% in some populations
- transmission by close contact: hand to mouth, kissing, sexual
- **most common manifest. of HSV-1 is "gingivostomatitis" = sores on the mouth and gums
- Adult: acute upper resp. illness pharyngitis and tonsillitis
- Neonatal: thru infected birth canal; asymptomatic mothers; organs affected--lungs, liver, adrenals, brain, retina, skin
Herpes (lab diag)
- isolated from vesicular fluid, ulcer scraping, throat swap, saliva, cervical secretions, CSF, etc.
- **virus grows rapidly in vitrow/ CPE - often in 24hrs (human diploid fibroblast and primary rabbit kidney tissue culture syst of choice)
- **HSV produce specific pattern of CPE - "balloon" cells
- Direct detection of Ag - prep by IF or EIA
- IF or Immunoperoxidase methods to type HSV isolates
- Serology: tool for determining prevalenc of exposure to HSV
- EIA - determine "Ig" class of Ab responce
caused by Treponema pallidum
destroyed by heat, cold, and drying out
transmission: sexual contact, kissing open lesions, rarely blood
incubation: usually 3 weeks; ranges 10-90 days
congenital infections occur after 18th week of preg.
primary stage of syphilis
painless chancre appears 2-3 weeks after infection
persist for 1-5 weeks & spont. heal (disappear but you still have it)
one week after chancre appear, lymph nodes enlarge
Ab are produced 1-4 weeks after chancre appears
Dark-field analysis of lesion demos spirochetes
T. pallidum once entered in circulatory syst is then carried to every organ in body
secondary stage of syphilis
1-2 mnths after chancres (more severe)
dissemination of organism (travels thru blood stream); involves CNS, eyes, bones, or liver
develop flat lesions resembling warts in moist areas
resolves w/i 2-6 weeks w/o treatment
Latent stage of syphilis
lack of clinical symptoms
noninfectious stage (Ab present; not Ag)
both nontrep and trep test are +
diagnosis can only be made serologically at this stage
occurs 2-40yrs after primary infection
gummas (syphillic lesions) appear in areas of bones, skin, or subq tissue
10% untreated = cardio probs
8% untreated = CNS probs
caused by maternal spirochetemia
if mother recvs treatment (PCN or Doxy) during first 4 mnths of preg, ocngenital syphilis can be avoided
associated w/ Congenital syphilis
- short notched incisor teeth
- interstitial keratitis (blindness)
- nerve deafness
Syphalis (lab diag)
organism cannot be cultured
long intervals of manifestation
T cells and macrophage moderatley increase
Ab destroy organism via damaging cell membraine enhances phagocytosis
nontreponemal sero tests
"think screening test"
nonspecif Ab are called "reagin ab"--produced by infected patient against comp of their own or other mamm cells.
Ab found in cardiolipin--cholesterol and lecithin
i.e. tests = VDRL (veneral disease research lab) and RPR (rapid plasma reagin)
treponemal sero tests
***don't do these unless onntrep sero tests are +
specific for spoirochetes or T. pallidum (syphalis)
- TPI, FTA-ABS (fluorescent), Hemaagglutination: MHA-TP (TP-PA)
Note: used to "confirm" RPR & VDRL results
TP-PA has replaced MHA-TP but folow the same princip.
VDRL and RPR (nontreponemal)
- Flocculation tests: soluble Ag particl coalesce to form large particles as clumps when aggregated by Ab
- Results reported as reactiv or nonreacti or weak reactive (why not + or - ? b/c these are "screening" tests)
used to monitor adequacy of treatment (quart. for 1yr)
- Ag = buffer salin susp of cardiolipin (lecithin-cholesterol)
- patient serum or CSF
- rotate 4 min
- read microscopically for agglut
- inactivate via heating to avoid activating compliment
Ag = modified VDRL Ag containing choline & charcoal (to help see it)
unheated serum (not CSF) added to RPR Ag
rotate for 8 min
**ART - automated reagin test (to test units of blood)
+ show flocc. of charcoal particles
more sensitive than VDRL
Ag killed susp of T. pallidum (syphalis)
Treponemes fixed on glass slide
fluorescent Ab tagging!
Test is specific!
SRBCs coated w/ Treponemal Ag
(+) forms flat, smooth mat accross bottom of well
(-) compact button formed by the settling of nonagglutinated cells
Treponema pallidum - particle agglutination
uses gelatin particle coated w/ treponemal Ag instead of sRBCs
allows longer storage and stability of test
cross reacting Ab's are elimin.
Syphalis (lab results)
greatest elevation of IgG in secondary syphilis
higher titers indicative of active disease
low titers < 8 suggest latent infection, prev treatment, or late syphilis
treatment: long acting inj of PCN