W3P2 Flashcards
What makes a successful STI?
Attachment to the mucosal cell surface
eg. using pili (gonorrhea)
Local invasion and proliferation while evading the host immune system
eg. by replicating intracellularly in epithelial cells and neutrophils (gonorrhea)
+/- Systemic dissemination
Some hosts are infected without symptoms
What is the Organism and Description for
a. Gonorrhea “the clap”
b. Chlamydia
a. Gonorrhea “the clap”
Neisseria gonorrhoeae -Gram-negative diplococcus
Bacteria
b. Chlamydia
Chlamydia trachomatis - Intracellular; lack normal cell wall (no peptidoglycan)
Bacteria
What is the Organism and Description for
a. Syphilis
b. Herpes
a. Syphilis
Treponema pallidum - Small, spiral-shaped organism
Bacteria/Spirochete
b. Herpes
Herpes Simplex Virus (HSV 1 + 2)- DNA virus, Herpes viridae family
Virus
What is the Organism and Description for
a. HPV, genital warts
b. Tichomonas “Trich”
a. HPV, genital warts
Human Papilloma Virus (HPV; many different types)- DNA virus
b. Tichomonas “Trich”
Trichomonas vaginalis- Flagellated, motile eukaryote
Which organisms cause Urethritis/ cervicitis
- Neisseria gonorrhoeae
- Chlamydia trachomatis
- Trichomonas vaginalis
Which organisms cause Genital Ulcer Disease
- Herpes Simplex Virus
- Treponema pallidum
- (Chlamydia trachomatis, certain serovars-> LGV)
Which organism causes genital warts?
Human Papilloma Virus
Presentation of Urethritis, Cervicitis, Procitits?
“ It hurts when I pee” = Urethritis
“ I have vaginal discharge” = Cervicitis
anal irritation, hurts when poo = proctitis
Differential diagnosis for Urethritis, Cervicitis, Procitis?
Neisseria gonorrhoeae
Chlamydia trachomatis
Trichomonas vaginalis
Transmission of Neisseria Gonorrhoeae
Gram-negative diplococci
Transmission via sexual contact
genital /anal
oral
Gonorrhea is easily treated, so what’s the big deal?*
Complications of N. gonorrhoeae:
- Epididymitis: swelling of scrotum
- Pelvic Inflammatory Disease: Chronic inflammation → adhesions within genital tract → infertility
- Perihepatitis = Fitz-Hugh Curtis Syndrome (abdominal pain)
all these result from leaving it untreated. sometimes people are asymptomatic and don’t know something is wrong
Which is the most common STI
Chlamydia
What is a emphasized site of infection for N.gonorrhoeae
ARTHRITIS
Is a common extragenital complication of gonorrhea
I.e. wrist pain
it can still, but rarely can affect heart, brain, Gut etc.
Disseminated Gonnococcal infection
Triad of:
1) polyarthralgia/arthritis
2) dermatitis
3) tenosynovitis
How to diagnose Gonorrhea
NAATs (nucleic acid amplification test)
approved for urine/urethral/vaginal/cervical specimens (but used also for rectal, pharyngeal specimens)
- commonly used^
culture: hard
Gram stain: from purulent urethritis in men
Treatment for Gonorrhea
First there was penicillin→ resistance
….then there were fluoroquinolones
→ resistance (~28% in Canada, 2014)
Now, for acute urethritis:
Combination therapy recommended
Ceftriaxone (intra-muscular) x 1 dose, or
Cefixime (by mouth) x 1 dose
Plus Azithromycin x 1 dose
Chlamydia trachomatis
- gram stain, description
- mechanism
- symptoms
Small Gr – rods with no peptidoglycan layer in cell wall
Intracellular; infects epithelial cells
Different life cycle than other bacteriae
Chlamydia trachomatis serovars D-K
Majority of people infected: asymptomatic
Clinical Manifestations of Chlamydia
Females vs Males
Females: Asymptomatic Cervicitis Vaginal discharge Dysuria Lower abdominal pain Dyspareunia Proctitis Pelvic inflammatory disease Perihepatitis
Males: Asymptomatic Urethral discharge Urethral itch Dysuria Testicular pain Proctitits
Diagnosis of C. trachomatis
Chlamydia
- very hard to culture (not done routinely)
- Thus : NAATs (nucleic acid amplification tests) is the go to
high Sn and Sp (higher Sn than culture)
use for urine, urethral or cervical specimens (and sometimes vaginal, rectal, pharyngeal specimens)
Treatment for Chlamydia
Adults with genital disease:
Azithromycin (oral) x 1 dose, OR
Doxycycline (oral) for 7 days
Trichomonas vaginalis
- organism
The last one that drips^
- Urogenital protozoa
parasite
- flagella
Trichomonas vaginalis
- Clinical presentations
Vaginal discharge Erythema of vulva and cervix Itch Dysuria 10-50% asymptomatic; most who have symptoms are women (many men asymptomatic)
Typical “strawberry” appearance of cervix
is associated with which infection?
Trichomonas Vaginalis
Diagnosis of Trichomonas Vaginalis
Microscopy of vaginal/urethral discharge for characteristic trophozoites
Antigen detection kits
NAAT
Treatment for Trichomonas Vaginalis
Metronidazole
aka flagyl, used for parasites
Genital Ulcer Disease
- patient descriptions
- DDX
“ I can see something down there…”
“ I have a rash”
DDx: HSV 1, 2 Treponema pallidum Lymphogranuloma venereum (= serovars L1, L2, L3 of Chlamydia trachomatis)
Herpes Simplex Virus 1&2
- organism type
- most transmission happens when?
- timeline of infection
- how long does the infection last
Herpesviridae family (DNA viruses)
Very common (seroprevalence studies: 15-50% positive)
Classically: HSV-1 = orolabial disease, HSV-2= genital: not true any more
Most transmission is during asymptomatic shedding
Establishes latent infection in the sacral sensory ganglia → periodic reactivation
Infection is for life
Clinical Manifestation of Herpes
Cluster of vesicles on an erythematous base: painful
Lesions anywhere in ‘boxer short’ area
Primary genital herpes Sometimes extensive vesiculo-ulcerative lesions: lesions are PAINFUL! Systemic symptoms (fever, muscle aches) Tender lymphadenopathy Meningitis (rare)
Diagnosis of HSV
Culture [not anymore]
PCR
Direct fluorescent Antibody (DFA) staining
Treatment of HSV
It is NOT curable
Medical treatment for clinically important first episodes and recurrences with either Acyclovir, Famciclovir or Valacyclovir
Can consider daily suppressive therapy for people with frequent recurrences (this also decreases transmission to partners)
Syphilis epidemiology
- mode of transmission
Least common of the 3 provincially reportable bacterial STIs
Incidence rising
Transmission via vaginal, anal, and oral sexual contact
Syphilis can be more complicated to recognize and diagnose than other STIs. Why?
different stages of disease (primary, secondary, latent, tertiary, etc). Can live in body and cause problems for decades!
different clinical manifestations at each stage of disease (“the great masquerader”), because it can spread to many organs in body
diagnosis can be complicated (no culture, PCR not widely used)
Stages of Disease of Syphilis
Transmission: sexual, congenital
+
Primary Syphilis
Secondary Syphilis: disseminated in skin, lymph nodes, etc commonly and classically found on the palms and soles
Latents syphilis is ASYMPTOMATIC
Early latent [within 1 year]: no symptoms
Late latent [over 1 year] low transmissibility, no symptoms
Tertiary Syphilis [years later] = aortitis, neurosyphilis
Chancres are found in what stage of syphilus
Primary Syphilis
this is a PAINLESS ulcer
What stage of syphilius would you see Gumma
Teriary Syphilis
- Serpiginous Gummata of forearm
like full mouth bite mark shape
Syphilis Diagnostics
Mostly based on serology
Dark field microscopy of chancres
2 algorithms for Syphilis Serology
- Screen with non-treponemal test (VDRL, RPR) and confirm with treponemal test
- Screen with treponemal test (EIA), then perform non-treponemal test, then confirm with another treponemal test
Non-Treponemal Tests
measure antibodies in patients serum to cardiolipin antigen
- Venereal Disease Research Lab test (VDRL)
- Rapid Plasma Reagin (RPR)
Aggregation of Cardiolipin antigen in presence of antibody = positive test result for syphilis
this type of test is NON specific, so you get a lot of false positives*
Treponemal Tests
Syphilis Serology
measure antibodies against specific T. pallidum antigens
These tests are very SPECIFIC for T. pallidum
Enzyme-linked Immuno-Assay (EIA)
agglutination tests eg. Treponema Pallidum Particle Agglutination assay (TPPA)
Line immunoassay (LIA)
Syphilis Serology Interpretation
RPR or VDRL: Positive
TPPA: Positive
Interpretation:
Syphilis (any stage)
Previously treated disease (soon after trtmnt)
Syphilis Serology Interpretation
RPR or VDRL: Positive
TPPA: Negative
False Positive
Syphilis Serology Interpretation
RPR or VDRL: Negative
TPPA: Negative
No syphilis
Very early disease (need to repeat VDRL in 2-4 weeks)
Syphilis Serology Interpretation
RPR or VDRL: Negative
TPPA: Positive
Some cases of late stage disease
Previously treated disease (late after trtmnt)
Syphilis Serology First Algorithm
- Start with non-treponemal test (RPR, VDRL) then confirm positives with treponemal test
Syphilis Serology 2nd algorithim
Start with treponemal test (EIA), then if positive perform non-treponemal test.
(If discordant, confirm with a second treponemal test)
Treatment of Syphilis if:
Primary, Secondary, or early latent
Late Latent, tertiary
Neurosyphilis
Penicillin is the treatment, dosage changes/increases
Primary, Secondary, or early latent: Penicillin IM x 1
Late Latent, tertiary: Penicillin IM weekly x 3 doses
Neurosyphilis: Penicillin IV for 10-14 days
LGV: Lymphogranuloma Venereum
- Clinical Presentation
Chlamydia trachomatis serovars L1, L2 and L3
Relatively rare
Outbreaks starting in 2003 (risk factor: MSM)
Clinical Presentation;
genital warts
often single painless papule
weeks later: tender adenopathy
HPV: Human Papilloma Virus
- prevalence
- which types cause warts
- which cause precancerous lesions
- prevention?
Very common (~70% adults have at least 1 HPV genital infx)
[More than 130 HPV types]
Types 6 and 11 commonly cause condyloma acuminata (genital warts)
Types 16 and 18 commonly cause (pre)cancerous lesions: cervical CA, anal CA
Vaccine now given in all provinces in grades 4-7
Treatment for HPV
Cryotherapy
Topical agents
Cervix: Colposcopy +/- excision procedures for pre-malignant/malignant lesions
Endovascular Infection includes:
- Direct infection of blood and its components
Bacteremia, viremia, fungemia
Ehrlichia/Anaplasma
Plasmodium, Babesia, Trypanosoma, Leishmania - Infection of endovascular device
Prosthetic cardiac valve, PPM, ICD, CVL, AV fistula/mesh, vascular graft, LVADs, mechanical heart - Direct infection of vasculature and structures
Suppurative thrombophlebitis
Endarteritis
Endocarditis
Acute Infective Endocarditis
Abrupt toxic course lasting days to weeks
Subacute infective Endocarditis
Indolent protracted course featuring systemic symptoms often lasting longer than weeks
Shifting Age Distribution for Infective Endocarditis
Change in the nature of underlying heart diseases: rheumatic → DEGENERATIVE
Population is aging, aged with heart disease survive longer
Aged with heart disease benefitting from PROSTHETIC VALVE replacement surgeries
“health-care associated” IE due to increased uses of endovascular technologies
- IV catheters, hyperalimentation lines, dialysis lines/shunts,
- PPMs/ICDs
Biofilm formation
Predisposing factors to Infective Endocarditis
- Native Valve (i.e the valves with which you are born)
Rheumatic heart disease
Congenital heart disease (some but not all)
Degenerative heart disease
Mitral valve prolapse
- Uncontrolled bacteremia and/or history of prior endocarditis - Prosthetic Valve (i.e the synthetic valve placed during cardiac surgery)
- Endovascular device utilization
Intravenous access: long standing CVAD»_space;» peripheral IV
Implanted devices, surgical materials - IVDU
intravenous drug use
Pathogenesis of Infective Endocarditis
Adherence -> Colonization [bcterial division, fibrin deposition, platelet aggregation, extracellular proteases, protection from neutrophils]
-> Mature vegetation
Many things can lead to adherence:
trauma, turbulence, metabolic changes
Bacteriocins, IgA protease, bacterial adhereance
Which area of the heart is MOST affected by Infective Endocarditis
Mitral Valve: 30-45%
Aortic: 5-35%
other two quite rare
Transient Bacteremia
When heavily colonized mucosal surfaces are traumatized
Degree of bacteremia is proportional to the burden of colonization and degree of trauma
Typically “low grade” and “transient”
- ≤ 10 CFUs/ml
- Blood stream sterilized within 30 minutes
- Function of “serum susceptibility” of the organism
Sufficient to infect a NBTE valvular lesion
Virulence Factor Dextran:
Complex extracellular polysaccharide, “glycocalyx”
Role in dental caries (S. mutans)
Prominent among certain Streptococcus spp.
Promotes adherence to platelet-fibrin matrix (NBTE)
Virulence FActor: Adhesion to markers of Damaged Endothelium
Fibronectin
- S. aureus binding and uptake into “normal” endothelium, followed by triggered apoptosis
- Clumping factor, coagulase
Virulence Factor: Bacteria-platelet-aggregates in circulating blood
- Staphylococcus spp. (surface receptor-fibrinogen-platelet receptor, or via vWF system)
- Streptococcus spp. (surface Antigens-IgG-platelet FcR)
↓ rate of removal of organism
↑ adherence and aggregation on vegetations
Virulence Factor Disruption
Utility of prophylactic antibiotics
- Even sub-inhibitory (prophylactic) antibiotics may prevent IE by
a. Decreasing expression of adhesion virulent factors
b. Direct cell killing
Describe within the Vegetation of Infective Endocarditis
Minimal phagocyte infiltration
Protected from circulating immune factors
Environment for major proliferation
Deeper dormant/inert bacterial forms (may represent up to 90% of bacterial burden)
Microbiology of IE for a Native Valve
Native Valve
Community acquired
- Staphylococcus aureus / viridans Streptococcus spp.
- Lesser extent Enterococcus spp.
Nosocomial
- Staphylococcus aureus
- Lesser extent Enterococcus spp.
IVDU
- Staphylococcus aureus
- Lesser extent other bacteria
Microbiology of IE for a prosthetic Valve
Early post surgical, intermediate Post surgical (2-12 months)
coagulase NEGATIVE STAPH > staph aureus
HACEK
Considered in microbiology of culture negative endocartitis
HACEK
- Gram negative organisms with unusual growth charcteristics
- Not truly “culture negative” using modern techniques
HACEK is an acronym for a group of organisms that are small, fastidious gram-negative bacilli. 1. The HACEK organisms include Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae.
Clinical presentation of Infective Endocarditis
symptoms vs signs
FEVER 80%
Chills
Weakness
Dyspnea
SIGNS:
fever 90%
heart murmur 85%
* important to do cardiac Auscultation
Diagnostic test for Infective Endocarditis
Most important diagnostic test is BLOOD CULTURE
When bacteremia present, first two cultures yield agent > 90% of the time
Can be altered if ABX are given prior to culturing
Recommended
3 sets, only 2 bottles per stick in first 24 hours
At least 10 ml of blood in each bottle
May need prolonged incubation
Role of Echocardiogram in Diagnosing IE
TTE- transthroacic echo?
Utility in all patients suspected of having endocarditis (usually by agent and syndrome)
May be technically inadequate in up to 20% of individuals
Variable sensitivity
Negative study cannot R/O IE
Highest in right sided IE due to positioning of the heart
False positive studies are rare
TEE- trans esophageal echo?
Invasive
More sensitive than TTE (65% vs 95%)
Should be considered in suspected cases where TTE was negative
Especially useful for prosthetic heart valves, intracrdiac abscesses and fistulae
Negative results do not exclude IE
May repeat TEE in 7-10 days
What is the modified Duke Criteria
Used to diagnose Definite vs Possible IE
Definite IE:
Pathologic Criteria
Microorganisms: demonstrated by culture or histology in a vegetation, OR in a vegetation that has embolized, OR in an intracardiac abscess, OR
Pathologic lesions: vegetation or intracardiac abscess present, confirmed by histology showing active endocarditis
Clinical criteria
2 major OR 1 major and 3 minor OR 5 minor
Possible IE:
- 1 major and 1 minor or 3 minor
Rejected:
Firm alternative diagnosis, OR
Resolution of manifestation of IE with ABX for 4 days or less, OR
No pathologic evidence of IE at surgery or autopsy, after ABX therapy for 4 days or less
Does not meet criteria for possible IE
Major IE criteria
- Blood culture positive for IE (at least one of:)
a. Typical microorganisms consistent with IE from 2 separate blood cultures:
- Viridans streptococci, S. bovis, HACEK group, S. aureus
- Community acquired enterococci, without primary focus
b. Microorganisms consistent with IE from persistently positive blood cultures
Evidence of Endocardial Involvement
a. Echocardiogram positive for IE
(TEE recommended in patient with prosthetic valves, rated at “possible IE” by clinical criteria, or complicated IE/paravalvular abscess)
b. New valvular regurgitation (worsening or changing of pre-existing murmur not sufficient)
Minor Criteria
a. Predisposition: predisposing heart condition or injection drug use
b. Fever: T>38C
c. Vascular phenomenon: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions
d. Immunologic phenomenon: GN, Osler nodes, Roth spots, and positive RF
e. Microbiological evidence: positive blood culture but does not meet a major criterion as noted above, or serological evidence of active infection with organism consistent with IE
Echocradiographic minor criteria eliminated
Pathologic changes to the heart from IE
- Destruction of underlying heart valve
- Healing by fibrosis and calcification - Acute IE
Vegetation is larger, softer, more friable
Associated with more suppuration, more necrosis
Less healing
Valve perforation
Rupture of chordae tendonae, interventricular septum, papillary muscle
Perivalvular abscess
Fistula into pericardium, myocardium
Myocarditis, myocardial infarction, and pericarditis - Involvement of conduction system
Pathologic Changes, EXTRA CARDIC of IE
1. Embolic phenomenon 15-35% of cases have clinical events 70-95% of cases had clinical events in pre-antibiotic era Kidney, spleen, coronaries, brain Immune phenomenon
- Immune complex deposition
Complement activation
Autoimmune process activated by increased circulating antibodies
Pathologic Changes in IE in the Kidney
During active IE, all biopsies are found to have abnormal architecture
- Abscess
- Infarction
- GN
Pathologic Changes in IE: Vascular
Mycotic aneurysm
- Can be prominent clinical presentation, or discovered at autopsy years later
- More common with viridans Streptococcus
Mechanism
- Direct invasion of arterial wall, abscess and/or rupture
- (Septic) emboli occluding vasa vasorum
- IC deposition and injury to the vascular wall
Tend to occur at bifurcation points
Pathologic Changes of IE: CNS
Cerebral emboli
Most common neurologic event in IE – 20%
MCA and branches most commonly involved
Hemorrhagic transformation of ischemic event is leading CNS related cause of death in IE
Other (non-exhaustive list)
Purulent meningitis – S. pneumoniae
Microabscesses – S. aureus
Pathologic Changes IE: Spleen
Enlargement
Immune stimulation, follicle engorgement
Infarction
44% of autopsies, usually clinically silent
Abscess
Surgical indication, or percutaneous drainage
Spontaneous Rupture
Pathologic Changes IE: Lung
Typically associated with right sided IE (right heart supplies to lungs)
- PE (septic or “bland”) ± infarction
- Acute pneumonia
- Pleural effusion
- Empyema
Pathologic Changes IE: Skin
- Petechiae – 20-40%
- Osler nodes (Immunologically mediated)
IC deposition in blood vessel
- arteriollar intimal proliferation with extension to venules and capillaries, may be accompanied by thrombosis or necrosis
- Tender, at pulp of fingers - Janeway lesions (Vascular event)
Septic emboli
- feature subcutaneuous abscesses
- Non-tender, palms and soles
Pathologic Changes IE: Eye
- Roth Spots
- Lymphocytes, edema and hemorrhage in nerve fibre layer of the retina - Conjunctival petechiae/hemorrhage
- Flame hemorrhages
Special Immunological Problems of the Fetus and Neonate
- Protective factors
All components of immune system are deficient c/w immune system of older children/adults
Degree of deficiency is inversely related to gestational age and birth weight, but even term are deficient
Protection
Placenta, filters microorganisms
Maternal Ab, but mostly transferred in 3rd trim
Breast milk, contains secretory IgA
Determinants of Fetal Infection
- The three types of effects
Most important is the time during gestation that the transmission of infection occurs
- During 1st trimester, while the fetus is being formed, the most devasting effects occur
Three types of effects:
- Interference with normal development
- Inflammatory reaction to the infection
- Placental insufficiency leading to poor growth
Diagnosis of fetal infection depends on…
THE MOTHER
Recognizing exposure of a pregnant woman
- Most of the time the pregnant woman are not symptomatic
- Detection of specific IgM Ab to an offending agent or rising titre of IgG are helpful in assessing risk
- Baseline immunity will help to exclude dx
I.e. was the mother already immune to Rubella, CMV, parvo, etc…
diagnosis based on the Infant
IgG crosses placenta, so not helpful
- Would be measuring mother’s Ab
Presence of specific IgM or rising IgG titre indicates fetal infection
Isolation of offending agents if possible
- Viral cultures of urine and other body secretions for CMV, Rubella, HSV
- PCR amplification if possible, ie. Toxo
- Pathology of placenta
- Darkfield microscopy from lesions for T. pallidum (syphillis)
Treatment for Fetal Infections
Limited number of treatable infections. Don’t want to miss these: Toxoplasmosis Syphillis HSV HIV CMV
No effective treatment
Rubella
Prevention for Toxo Rubella CMV Syphilis Listeria
Toxoplasmosis
Avoid cat litter boxes, gardening, eating raw or undercooked meat
Rubella
Prenatal vaccination, or if non immune post delivery to protect future offspring
CMV
Meticulous handwashing
Syphillis
Serologic testing early on, and repeated if at risk for exposure. Of course treat pregnant mother to prevent infection in the fetus
Listeria (gram+)
Avoid Deli meats
The following tests were ordered for a 19yrs old with hepatomegaly to r/out congenital defect… but would you order them?
CBC: yees has look for abnormalities (i.e. platelets are low)
Blood culture/Urine culture: bacterial infections would present acutely and this is not an acute presentation
CSF culture^
Torch screen: misconception, not effective THERE IS NO SUCH THING**
Immunoglobulins, specifically IgM (it doesn’t cross the placenta)
TORCH SCREEN
TORCH: Toxo, Other, Rubella, CMV, Herpes
^ just an acronym for screening general stuff
The common misconception
There is no ONE test that will screen for congenital infections
Congenital infections of different causes have many clinical similarities
The acronym “TORCH” should be expanded. “O”ther now includes
Syphillis, TB, Listeria, leptospirosis, Hepatitis B, enteroviruses, Varicella, Parvovirus, HIV…and most recently ZIKA!!
Nothing replaces a good clinical accumen and directed specific testing
What is better than TORCH
Go by your index of suspicion!
Always start with your clinical history, and getting the OB/GYN report
- Ultrasounds, serologies AND when they were done. You will save a lot of time, effort and cost
A full work up should always include and ophthamology assessment
Suspected Toxoplasma (T in TORCH) - the classic triad
Classic Triad: Hydrocephaly, diffuse intracranial calcifications, chorioretinitis (inflammation in the eye)
Do maternal serology (IgG)
NEG: excludes Congenital Toxoplasmosis, mom was never infected.
POS: Titre and Avidity help us with timing
Only infection while pregnant will affect the baby
Do Toxo IgM, but stays positive for 6-18 months
NEG: Does not totally exclude, but unlikley
POS: Increases the likelihood, but + for >6 months
Diagnosing Toxoplasmosis in child vs mom
CHILD
Ophthamology: assess for chorioretinitis
Head imaging: CT vs Ultrasound vs Xray
PCR on whole blood, and CSF
MOM
Toxoplasmosis suspected during pregnancy
Seroconversion documented
Work up to assess if baby infected/affected
PCR on amniotic fluid
Serial ultrasounds, looking for ventricular dilatation
Placental histology
If work up indicates infection, then important to treat mom, which will also treat the fetus
Baby will need to continue treatment once born
Suspected Rubella (R in TORCH)
Once the baby is born:
Check Mom’s rubella status PRIOR to the current pregnancy
POSITIVE: excludes Rubella
NEGATIVE/ or unknown
- Check Rubella IgG on Mom and/or baby
If negative: excludes Rubella, immunize Mom
If Positive: Do Rubella IgM on both Mom and baby
If IgM Positive: Congenital Rubella
If Negative: Do Rubella Viral Cultures
Isolation of the virus in the baby is proof positive
Cytomegalovirus (C in TORCH)
Once the baby is born:
Urine viral culture/PCR for CMV
POSITIVE: If done within first 2-3 weeks of birth, then can diagnose Congenital CMV
NEGATIVE: excludes CMV
While mother is still pregnant:
Serology IgG not helpful as most women have antibody (60-80%), indicating infection at some point during her life.
Complicated and controversial on how to diagnose in mother, but includes IgM and PCR
Suspected Herpes (H in TORCH)
- 3 distinctive syndromes
- Diagnosis
3 distinctive syndromes in the baby: Majority of infections start during delivery with incubation of 2 days to 6 weeks
- Skin, eye, mucous membrane “SEM”
- Encephalitis
- Disseminated
If there are skin lesions: test the lesion (special stain, or PCR, or viral culture)
POSITIVE: Confirms Diagnosis
If there are no lesions:
- Culture mouth, eye, urine, rectum
- CSF and Blood for HSV PCR
Suspected O in TORCH
SYPHILIS
Check maternal serology, and recheck at time of delivery, or thereafter
NEGATIVE: exclude
POSITIVE: Review history, prior treatment
This is not something you want to miss, as this plus congenital Toxo, HIV, HSV, CMV are really the only treatable causes!
Congenital CMV
Maternal primary CMV in pregnancy
43-58% transmit to fetus
15-20% of infected newborns are symptomatic
- Mortality: 20-30%
- Sequelae: 90% of survivors
- Severe psychomotor delay 50-60%
- Hearing loss 30-60%
80-85% are asymptomatic at birth
12-15% hearing loss, behavior or learning problems
Maternal CMV reactivation in pregnancy
17% of seropositive pregnant women shed virus at some point during the pregnancy
0.8-3.4% transmit to fetus
Symptoms and severe sequelae: extremely rare
Hearing loss: 5% (unilateral or mild)
Although congenital CMV can cause the hearing loss, finding it in the urine at 8 months of age is not helpful… WHY?
Baby may have become infected at time of delivery or anytime afterwards. Only infection during pregnancy causes the hearing problems.
Therefore must find the virus when the baby is a newborn to say that this happened.
Parovirus
if exposed to this virus, must tell pregnant women:
About 30-60% of adults are immune
So if she was immune, there is no risk to the baby
In pregnancy: ?spontaneous abortion in 1st trimester; fetal anemia and hydrops in 2nd and 3rd trimester; ? Stillbirth
Causes bone marrow aplasia, resulting in severe anemia in the baby, and congestive heart failure
- Hydrops fetalis: abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema.
Other infectious causes of nonimmune hydrops:
Toxoplasmosis, rubella, CMV, syphilis
Diagnosis of Parovirus in pregnant women
Diagnosis: Serology on mom at time of exposure
If IgG positive: She is immune, and baby not at risk
If IgG negative, check and follow IgM, IgG
If there is seroconversion, then need to follow fetus, and can do fetal blood transfusions if necessary
Pregnany women from Eastern Europe, we know nothing of her antenatal serology, but she tells you that she has chronic hepatitis
What are the risks to the baby?
What should you do?
Hepatitis B
If mother is sAg and eAg positive:
70-95% transmission, and 90% of infants will become chronic carriers
THEREFORE GIVE HBIG to the baby (HepB immuneglobulin), AND FIRST DOSE OF VACCINE AT BIRTH (then at 1, 6 months) protective in 85-95%
VACCINE ALONE protective in 70-80%
Hep C
Perinatal tranmission
Less than 5%
Increased if co-infected with HIV (18-20%)
Diagnosis in infant?
Follow serology at 6, 12, 18 months
?PCR
Herpes Simplex Virus, congenital infections
Highest risk of transmission if
First episode of maternal infection in pregnancy
- 40-50% transmission, versus 0-5% if recurrent
Multiple cervical lesions
Rupture of membranes > 6 hours
Instrumentation, scalp electrodes
Prematurity, no maternal antibody
Clinical presentation:
- Skin-eye-mucous membrane (SEM)
- Encephalitis
- Disseminated
20 % HAVE NO SKIN LESIONS!!
Pregnant women exposed to child with chicken pox.. what is your advice
Varicella Zoster Infection
VZV embryopathy: - Limb scarring and atrophy - Bony defects - CNS abnormalities - Eye, chorioretinitis Development of Zoster early in life Congenital varicella syndrome: 1-2%
Unlikely that VZIG (varicella immuneglobulin) is protective to fetus
Give VZIG to newborn if maternal varicella 5 days before, to 2 days after delivery
- Severe disease in newborn: mortality of 5 %
Frequency of UTIs
Up to 20% of women experience by age 30 >50% have at least 1 in a lifetime 10% of women have recurrent infections Up to 20% chance of the cause of fever in feverish newborns - High if uncircumcised male (20%) - Approx 7% otherwise
UTI definitions
- general
- Cystitis
- Pyelonephritis
- Renal Abscess
- Bacterial Prostatitis
Infections at any site:
Bladder, kidney or protate
Cystitis
Infection at level of bladder
Pyelonephritis
Infection involving renal parenchyma (kidney)
Renal abscess
Pus collection with severe pyelo or spread from blood stream
Bacterial Prostatitis
Infection of the Prostate gland
Pathogenesis of Gut Flora as source for UTI
Higher incidence in females because of shorter distance from urethra to bladder
- Most of the time bacteria is “flushed out” with the next void
- Transport from bladder to kidney can result in pyelonephritis
Ascent to kidney facilitated by: Pili of the bacteria (E. coli) Obstruction Neurologic disease leading to a poorly functioning bladder Pregnancy Reflux (urine going up the ureters)
Microbiology of UTI
- most common organism
E.coli accounts for 85% (due to pathogenic factors)
- P Fimbriae/pili allow for bacteria to attach
Staph. Saprophyticus isolated in 5-15% of young women with UTIs
Other Enterobacteriaceae, enterococcus, yeast, Group B strep, account for the minority
Urea splitting organsims may form struvite stones
- Proteus, Morganella and Providencia
All bets are off in there is indwelling plastic, such as catheters
- Biofilm forms and traps unusual organisms
Host factors that decrease risk vs factors that increase risk
Most important is periodic, complete and normal voiding
Washes out bacteria, and cells to which they are attached
Behavioral risks
Sexual intercourse
Mechanically allows bacteria to ascend. Occurs 30% of encounters, but voiding clears the bacteria
Patients with structural or functional abnormalities of the Urinary tract that compromise voiding.
- Obstruction to flow
- Increased access (catheters)
- Pregnancy (urinary stasis)
Clinical Presentation of UTI
- lower vs
- upper tract symptoms
- unlikely if it presents ____
Uncomplicated Cystitis or Pyelonephritis Lower tract symptoms Dysuria (pain on voiding) Frequency (frequent urination) Urgency (“I need to go NOW!) Discomfort in suprapubic or lower back area Gross hematuria Upper tract or Pyelonephritis High fever CVA (costo-vertebral angle) tenderness Unlikely UTI if symptoms are in between voids and if there are vaginal symptoms
UTI presentation in kids who can’t describe their symptoms
Young infants cannot complain of the typical symptoms
Fever, irritablility
Afebrile, but poor feeding; vomiting; diarrhea; jaundice; poor weight gain
What is meant by a positive urinalysis (urine dipstick)?
Leukocyte esterase: detectsesterase, an enzyme released by white blood cells. Most sensitive
94% when UTI suspected
Specificity: 64-92% (due to other infection/inflammation of tract, urethera, vaginitis..)
Nitrite: Bacteria that cause a UTI make an enzyme that changes urinary nitrates to nitrites.
Sensitivity: 16-82%
Specificity: 95-100%, good to Rule-In
[Blood and/or protein
Poor sensitivity and specificity]
THE BEST UTI diagnostic measure include
Microscopy: Technologist dependant
#WBC/HPF: Sensitivity: 32-100%; Specificity: 45-97%
Bacteria: Sensitivity: 15-96%; Specificity: 11-100%
If analyzed > 3 hours after collection: The sensitivity drops by 35%
How to maximize diagnostic sens and specificity for UTI?
Combination of tests maximize the Sensitivity and the Specificity
LE or nitrite +: Sens: 83-100%; Spec: 68-98%
Microscopy for WBC and bacteria:
- Sensitivity: 99%
Anything positive on dip/microscopy
- Sensitivity of 100%; Specificity poor
If dip/microscopy all negative
- Negative Predictive Value: 100%
General Principles of treatment for UTI
Empiric therapy may need to be modified based on susceptibility testing
Antimicrobials excreted in urine are preferred
For cystitis, only urinary antibacterial activity is necessary
For Pyelonephritis, need adequate drug level in urine and tissue, and possible blood level
Cystitis Treatment
Usually treated empircally based on symptoms and dipstick result, and often cultures are not sent (adult medicine)
It takes 2-3 days to get urine culture results,and many treat for only 3 days
Send a culture if symptoms are uncertain, history of frequent relapse, or if pregnant
Most use TMP/SMX (Septra) for 3 days
Alternatives: Quinolone (Cipro) also for 3 days, or Nitrofurnatoin (local bacteriostatic) for 7 days
Treatment of Pyelonephritis
Can have bloodstream extension, so blood and urine cultures are indicated before treatment
Empiric therapy is based on severity, i.e oral vs. initial IV then oral or all IV.
Usually start with Ampicillin (to cover possible enterococcus) and aminoglycoside (To cover gram negatives: Genta/Tobra), and tailor based on urine C&S
For oral treatment, many use Septra or quinolone
Because both are extremely well absorbed (bioavailable)
If no improvement by day 3, consider a complicated infection (obstruction, abscess
Treatment for Asymptomatic Bacteriuria
Should not be treated except
- Pregnancy: Can go onto pyelonephritis, which can precipitate premature labor
- About to have a urological procedure: compromise of the mucosa can lead to the complication of spread to the bloodstream
Treatment for Prophylaxis vs. recurrent uncomplicated UTIs (adults)
2 episodes every 6 months, or 3 every year
Some refer to it as “Honeymoon cystitis”
Can try daily or alternate day low dose TMP/SXT, or following intercourse
- Reduces gram negative flora in periurethral area, but increase incidence of resistant UTIs
Nitrofurantoin has less of an impact on colonizing flora, but can intermittently sterilize the urine through high urinary antimicrobial levels
What is considered Pediatric UTI
UTIs under 3 months
- quite common!
- higher if infant is febrile
- uncircumsized males = higher
infant, male vs female UTI prevalence
Incidence decreases in boys and increases in females during the first 6 months, and by age 1 females outnumber boys 3-10:1.
UTI in Children vs Adults
WORSE IN CHILDREN
May have no symptoms attributable to the urinary tract
Higher likelihood of having blood spread, and complications as meningitis (neonates)
Higher likelihood of having some malformation of the urinary tract
Therefore needs more extensive workup initially and in follow-up
Signs and Symptoms in Neonates as opposed to Adults with UTIs
Neonates have lower grade fever or afebrile
Fever is of shorter duration, and disappears more promptly on treatment
May just have poor feeding, lethargy, grunting, poor weight gain and no fever OR fulminant sepsis
Asymptomatic other than jaundice
Pathogenesis of UTI for infants
Ascending vs Hematogenous
- not sure which comes first, chicken vs egg situation
A substantial proportion of newborns with UTI have bacteremia
Main treatment for Cystitis and Pyelonephritis
Septra and Quinolone
Infants with UTI: Traditional management
If under 6-8 weeks of age: all have a septic workup including a lumbar puncture
Treated all IV if under 1 month
All newborns should have an ultrasound to rule out congenital malformations of the urinary tract
Consider radiographic work up with VCUG to detect reflux from bladder up the ureter, if the UTI is considered “atypical”
- Recurrent; Non E.coli; abnormal ultrasound; bacteremia
May require prophylaxis if there is high grade reflux, at least until the time they are toilet trained
Grade rating for Infant UTI
Higher the grade, higher up the infection = worse
Role of Ultrasound in infant UTI
To detect dilatation, obstruction, anomalies
If a late prenatal ultrasound has been done, is this still a necessary test?
NEJM: Jan.16,2003 Hoberman et al
Ultrasound did not change management, nor did it differentiate those with or without reflux
There is no role for an U/S for every repeat UTI if the anatomy is known, and there is no unexpected response to treatment
