Infectious Disease And Immunology Flashcards
Encapsulated organisms
SHiNS Salmonella H. Influenzae Neisseria S. Pneumo
Which serotype of GBS is most often associated with late onset sepsis?
Type 3
Disorders associated with congenital asplenia
Ivemark
Pearson
Smith-Meyers-Fineman
Stormorken
Early onset sepsis preterm infants
Gram-negative organisms more likely
Early onset sepsis in term infants
Gram-positive organisms more likely
What can cause early pneumonia in a neonate?
Aspiration of infected amniotic fluid
Transplacental transmission (syphilis, listeria, TB)
MCC GBS
What can cause late pneumonia in a neonate?
Ventilator associated pneumonia (ET tube in place)
Previous bacteremia
Usually colonized with bad bugs - pneumococcus, S. aureus, S. pyogenes, H. influenzae, Enterobacter, pseudomonas
How do you diagnose pneumonia In a neonate?
Very difficult
Worsening respiratory status
Chest x-ray is not pathognomonic
Tracheal aspirates do not really change management
Diagnosis of meningitis in a neonate
Abnormal CSF count with neutrophy predominance, increase protein, low glucose
Enteric gram neg 30-40%
What percent of infants with GBS bacteremia also have meningitis?
5-10%
What percent of neonates with listeria bacteremia also have meningitis?
5-20%
What complication do you worry about if a neonate has Citrobacter meningitis?
Brain abscess
Are UTIs more common in male or female neonates?
Males
Pathogenesis of UTIs in neonates
Urinary tract abnormality 20-50%
Ascending or hematogenous from bacteremia
E. coli causes 80%
How long after infection are the bony changes associated with osteomyelitis typically detectable by x-ray?
7-10 days
Pathogenesis of osteomyelitis in neonates
Majority via hematogenous spread
Typically in the metaphyses of long bones (reduced rate of blood flow)
Caused by S. aureus**, E. coli, GBS (majority S. aureus)
What symptoms would make you suspect osteomyelitis in a neonate?
Pain with passive positional changes
Lack of extremity use
Joint/limb swelling
How do you treat osteomyelitis?
Vancomycin + Aminoglycoside or 3rd gen cephalosporin
4-6 weeks and resolution of inflammatory markers
Complications of osteomyelitis in neonates?
Growth plate damage
Avascular necrosis
Limb length discrepancies
Angular joint deformities
What type of conjunctivitis does erythromycin prophylaxis reduce?
Gonococcal not chlamydial
What special media is needed to isolate gonorrhea?
Thayer-Martin media
Sheeps blood +4 antibiotics
Gonococcal ophthalmia neonatorum
2-5 days of life
Profuse bilateral purulent discharge
Ophthalmic emergency - can lead to corneal ulceration/perforation
Treatment with IV ceftriaxone
 Chlamydial conjunctivitis
5-14 days of life
Begins as clear discharge and progresses to perulant
Treatment with 14 days of oral erythromycin
When does Chlamydia pneumonia Present?
2-8 weeks of life
Cough/congestion without fever
What percentage of neonates develop gonorrhea conjunctivitis if mother is infected?
30-40%
What percentage of neonates will develop chlamydial conjunctivitis if mother is infected?
20%
Which organism causing conjunctivitis is an obligate intracellular bacteria?
Chlamydia trachomatis
Which organism causing neonatal conjunctivitis is a gram-negative intracellular diplococcus?
Neisseria gonorrhea
What are symptoms of omphalitis?
Cellulitis - periumbilical erythema/induration, tenderness
Purulent drainage from umbilical stump
Pathogenesis of omphalitis
Dirty cord
Aggressive cord care disrupts barrier
S. Aureus, GAS, GBS, GN bacilli
Which serotype of group B strep causes meningitis?
Type 3
IAP prevents which type of GBS infection?
Early onset
No change in late onset
What Percentage of staph aureus infections in the NICU are methicillin-resistant?
25%
What kind of infections does S. Aureus cause in the NICU
Osteomyelitis Septic arthritis Pneumonia Bacteremia/meningitis Skin and soft tissue infections (SSTIs)
What is the most frequent single organism isolated in late onset sepsis?
Coag negative staph
How does CONS infection present in neonates?
Non-specific all the way to frank sepsis Embolic phenomena Line infections Thrombi Rarely meningitis
Which strain Of E. coli causes majority of meningitis?
K1 strain (80%) 40% of sepsis
What bacteria can cause noma neonatorium?
Pseudomonas
Erosion of the gum/tongue, life-threatening
Which pathogens are primarily transmitted transplacentally?
Treponema pallidum
Mycobacterium tuberculosis
Listeria monocytogenes
What percentage of neonates will acquire syphilis if mother has untreated primary syphilis during pregnancy?
70-100%
In utero transmission of toxoplasmosis
Transmission increases with gestation
Disease is more severe at earlier gestational ages
In utero transmission of syphilis
Transmission can occur at any time during pregnancy
Disease is more severe at older gestational ages
In utero transmission of rubella
Transmission to fetus is most likely in early and late pregnancy (U-shaped distribution)
Disease is more severe at younger gestational ages
In utero transmission of CMV
Transmission can occur anytime during pregnancy
Disease is more severe at younger gestational ages
What is the most frequent presentation of late onset sepsis with listeria?
Meningitis
What is the most frequent presentation of early onset sepsis with listeria?
Pneumonia and sepsis
Immunoglobulin concentrations with age
Conjunctivitis in first 24 hours
Chemical following prophylaxis
Spontaneously resolves within 48 hours
Conjunctivitis at 24-48 hrs. of age
S aureus - Golden crust around eyelids, MCC GBS H. influenzae - dacryocystitis S. pneumo - dacryocystitis Pseudomonas
Most frequent viral etiology of conjunctivitis?
HSV
Ocular complications of HSV
Conjunctivitis
Keratitis
Chorioretinitis
Retinal dysplasia
When does HSV conjunctivitis occur?
4 days to 3 weeks
Presumptive exclusion of HIV infection in neonates
- 2 neg HIV RNA/DNA from separate specimens both >2 weeks of age and 1 at least >4 weeks of age
- 1 neg HIV RNA/DNA >8 weeks of age
- 1 neg HIV antibody test >6 months of age
How to definitively rule out HIV infection in a neonate?
- 2 neg HIV RNA/DNA from separate specimens, both >1 month of age, 1 >4 months of age
- 2 negative HIV antibody tests from separate specimens >6 months of age
How can congenital tuberculosis infection occur?
Hematogenous spread across infected placenta
Aspiration of infected amniotic fluid
Ingestion of infected amniotic fluid
Treatment of congenital TB infection
Isoniazid
Rifampin
Pyrazinamide
Aminoglycoside
Initial drug of choice for neonatal candidal infections?
Amphotericin B
Why is liposomal amphotericin B not used in neonates?
Less penetrance into brain and kidney
Increased liver toxicity
Differences in neutrophils between neonates and adults
Neonatal neutrophils adhere poorly to endothelium
Neonatal neutrophils have impaired chemotactic response
Preterm neutrophils have a developmental defect in phagocytosis that corrects at term
Granule contents and degranulation response are similar to those in adults
Preterm infants have ____ B-lymphocyte numbers compared to term infants
Significantly lower
At birth the proportion of B cells is ____ to adults, but the absolute number of B cells is ____
Similar
Significantly higher
Which type of HSV is responsible for the majority of neonatal infections?
HSV 2
What is the most common route of HSV transmission during pregnancy?
Intrapartum 85%
Multinucled giant cells on Tzanck smear
HSV
Which form of congenital HSV is most common in neonates?
SEM 45%
Cluster of grapes on erythematous base
HSV
Ideal timing to perform HSV swabs after birth?
12-24 hrs
Can maternal RSV infection transmit to fetus?
No because There is no maternal viremia
What kind of virus is RSV?
ssRNA
What kind of virus is HSV?
dsDNA
Viruses causing severe/fulminant hepatitis
Enterovirus > Adenovirus > HSV > CMV
What kind of virus is hepatitis B?
dsDNA
Which antigen associated with HBV increases the risk of transmission?
HBeAG
Timing of hepatitis B immunoglobulin
<2kg HBIG in 12 hrs
>2kg HBIG in 7 days
What type of virus is hepatitis C virus?
ssRNA
Risk of maternal fetal transmission of HCV?
5% if mom positive for hepatitis C at delivery
10-20% if HIV coninfected and HCV positive at delivery
Diagnosis of neonatal HCV
PCR for HCV RNA at 1-2 months of life
Antibodies after 18 months
What kind of virus is hepatitis A?
ssRNA
What kind of virus is parvovirus B19?
ssDNA
When is parvovirus B19 infectious?
Before rash onset
Non-infectious after rash appears
When does maternal IgG appear during parvovirus infection?
Day two of rash, persist for life
What kind of virus is varicella zoster?
dsDNA
When is varicella contagious?
1-2 days before rash until all lesions crusted
Congenital VZV
<1%
VZV infected mother during first 20 weeks of gestation
Microcephaly, chorioretinitis, intracranial calcification, scarred skin (cicatricial lesions)
Perinatal VZV
Five days before and two days after delivery greatest risk
30% mortality rate due to disseminated varicella
Not enough time for antibodies to cross to fetus
When to give VZIG or IVIG if VZV +
Premature <28 weeks regardless of maternal history
When mother develops disease 5d before - 2d after delivery
>28 weeks and mother has exposure without h/o disease
What kind of virus is rubella?
ssRNA
Precautions for congenital rubella syndrome
Droplet until seven days after onset of rash
Contact until one-year-old or 2 cultures obtained 1 month apart after 3 months of age are negative
What type of virus is CMV?
dsDNA
Intranuclear giant cells
CMV histology
Treatment for symptomatic congenital CMV
Valganciclovir for 6 months (start before 1 month of age)
Improves developmental/auditory outcomes
When are neonates tested for HIV?
If mother HIV +
48 hours, 14-21 days, 1-2 months, 4-6 months
What type of virus is enterovirus?
ssRNA
Examples of enteroviruses
Echovirus - sepsis-like, hepatic necrosis
Coxsackievirus - myocarditis (B)
Polio virus - IUFD
What type of virus is influenza?
ssRNA
Symptoms of congenital cutaneous candidiasis
Diffusely erythematous papular rash at birth
Can develop vesicles and bullae or look like a burn
Risk factors for invasive candidiasis
Extreme prematurity >2 wks of age Prolonged antibacterial treatment NICU site Empiric 3rd gen cephalosporin (x2 risk) Central lines Gut injury H2 blockers, dexamethasone, ET tube
Evaluation of babies with candidemia
LP and culture UA and culture Neuroimaging Eye exam Ultrasound kidney/spleen/liver Echo
Most common species of Candida?
C. Albicans
Most pathogenic
Sensitive to Ampho B and fluconazole
Second most common cause of candida?
C. Parapsilosis
20 to 35%
Decrease sensitivity to ampho B
What percentage of neonates with invasive candidiasis have Meningoencephalitis?
More than 15%
When to use fluconazole prophylaxis?
Facilities were risk of invasive candidiasis is >5% in VLBWs
What maternal exposures lead to toxoplasmosis?
New kittens
Poorly cooked meat
Treatment of congenital toxoplasmosis
Pyrimethamine
Sulfadiazine
Folinic acid
What drug do you avoid in cases of botulism?
Aminoglycosides
Can increase neuromuscular blockade
What can lead to neonatal tetanus?
Contamination of the umbilical cord
Symptoms of neonatal tetanus
Stiffness, rigidity, spasms
Symptoms of botulism
Symmetric, descending, flaccid paralysis
Spore forming gram-positive rods that grow anaerobically
Clostridium tetani
Clostridium botulinum
What does the tetanus toxin do?
Binds at neuromuscular junction and blocks GABA release
Timing of neonatal tetanus infection
3-12 days of life
Timing of botulism infection
3 weeks - 6 months
Treatment of neonatal tetanus
Penicillin or metronidazole
You can give neuromuscular blocking agents
What is granulomatosis Infantiseptica associated with?
Listeria infection
 What type of bacteria is listeria?
Nonspore forming gram-positive rod
What maternal exposures can lead to listeria infection?
Soft/raw cheese
Undercooked meats (bears, goat)
Salads
Low ANC + high I/T ratio
Infection, autoimmune destruction
Increased production of immature forms with ongoing destruction of mature forms (not matched)
Low ANC + low I/T ratio
Infection, PIH, SGA
Suppression of production with/without associated consumption
Normal ANC + high I/T ratio
Infection, autoimmune state
Increase production of immature forms but ongoing destruction of mature forms (matched)
Normal ANC + low I/T ratio
Normal
What is the innate immune system
Performs nonspecific immune response
Acts within minutes of exposure
Includes barriers, inflammatory response factors, and cells
Barriers of the innate immune system
Skin
G.I. and respiratory mucosa
How does pathogen recognition occur?
Pathogen recognition receptors aka Toll-like receptors (TLRs)
What inflammatory response mediators lead to vasodilation?
Histamine
Prostaglandin
Nitric oxide
Bradykinin
What inflammatory response mediators lead to increased vascular permeability?
Histamine Complement Bradykinin Leukotrienes Nitric oxide
What inflammatory response mediators lead to leukocyte adhesion?
Cytokines
Complement
Eicosanoids (prostaglandins, leukotrienes)
Selectins
What inflammatory response to mediators lead to chemotaxis?
Chemokines
Complement
Eicosanoids
What inflammatory response mediators lead to fever?
IL-1
TNF-a
Prostaglandins
What inflammatory response mediators lead to tissue necrosis?
Neutrophil granules
Free radicals
What inflammatory response mediators lead to platelet aggregation?
Eicosanoids
What are eicosanoids?
Prostaglandins
Leukotrienes
What happens in the classical complement pathway?
Antigen antibody complexes are formed leading to complement activation
What happens in the MB-lectin complement pathway?
Lectin binding to pathogen surfaces leading to complement activation
What happens in the alternative complement pathway?
Complement binds directly to pathogen surfaces leading to complement activation
Outcomes of complement activation
Recruitment of inflammatory cells
Opsonization of pathogens
Killing of pathogens
Does complement cross the placenta?
No
When do adult level/function of complement system develop?
6-18 months of age
Genetics of chronic granulomatous disease
X-linked recessive Xp21.1 gp91phox 65-70% of cases Deficient or absent function of NADPH oxidase
Symptoms of chronic granulomatous disease
Severe, recurrent infections with catalase positive bacteria or fungi
Negative nitroblue tetrazolium test (remains colorless)
Chediak-Higashi Syndrome
Abnormal degranulation
Albinism
Recurrent infections
Giant intracellular granules
Monocytes in newborns
Poor cytokine production and antigen presentation in first year of life
Decreased migration
Macrophages in neonates
Poor response to IFN-g
Decreased activation and migration
What is the function of B cells?
Produce antibodies
Sometimes need T cell co-stimulation
Neonatal B cells differentiate into predominantly IgM secreting cells
Immunoglobulin levels with age
What is the only source of IgA initially in newborns?
Colostrum
What are the functions of CD4 T cells?
Helper cells- coordinate immune system
Secrete cytokines
Stimulate besels to make IG
Activate macrophages
What are CD4 T cells stimulated by?
Cytokines
Antigen presenting cells
What do CD8 T cells do?
Release preforins, degradative enzymes, cytokines
Cytotoxic activity is limited in neonates
When do Predominant antibody defects become more apparent?
After six months of age
X-linked agammaglobulinemia
Profoundly diminished immunoglobulin levels
Tyrosine kinase mutation -> B cells can’t become mature
No plasma cells in G.I. tract
Normal T cell numbers
Hyper IgM syndrome
Low/absent IgG, IgA, IgE Normal to elevated levels of IgM Neutropenia Perirectal abscesses Oral ulcers Infection with PCP, cryptosporidium, salmonella Associated with congenital rubella 70% X-linked
What antibodies are low in turner syndrome?
IgG and IgM
What antibodies are low in trisomy 21 and trisomy 8?
IgG, IgM, and IgA
Syndromes associated with defects in cell mediated immunity
DiGeorge Wiskott-Aldrich syndrome Perinatal HIV infection SCID Ataxia telangiectasia IPEX syndrome
Symptoms of cell mediated immune disorders
Opportunistic infections
Macular erythematous rash
Hepatitis
Chronic diarrhea
Symptoms of Wiskott-Aldrich syndrome
Eczema, thrombocytopenia, increased infections
Platelets small, defective, abnormally shaped
Decreased lymphocytes
Abnormal T cell function
Elevated IgA and IgE
Decreased IgM
Normal IgG
Genetics of Wiskott-Aldrich syndrome
X-linked recessive
Xp11.23
WAS gene
Genetics of SCID
X-linked -> due to defects in cellular signal transduction
Abnormal purine salvage pathway -> adenosine deaminase deficiency
Omenn syndrome (RAG1/2)
Symptoms of SCID
Deficient antibodies and cell-mediated immunity
Diarrhea, pneumonia, otitis, sepsis, cutaneous infections
Eosinophilia
Graft versus host disease following blood transfusion
Levels of T regulatory cells in neonates
High, especially in premature neonates
Decrease to adult levels by 3-6 years of age
Metabolic disorders with neutropenia
Isovaleric acidemia Propionic acidemia Methylmalonic acidemia Glycogen storage disease 1B Orotic aciduria Hyperglycemia
Syndromes causing congenital neutropenia
Kostmann Pure white cell aplasia Reticular dysgenesis Cartilage-hair hypoplasia Hyper IgM syndrome Shwachman-Diamond Dyskeratosis congenita
Genetics of IPEX syndrome
X linked
Forkhead box protein three mutation
Symptoms of IPEX syndrome
Immunodysregulation, polyendocrinopathy, enteropathy (IPEX)
Impaired Treg suppressor function
Decreased IL-2 and IFN-g production
Severe watery diarrhea, FTT, dermatitis, type 1 DM
Increased IgE levels
Eosinophilia
Electrolyte abnormalities with amphotericin B
Hypomagnesemia
Hypokalemia
Placental findings with listeria infection?
Microabscesses
Where are B cells produced in utero?
Start in liver at 8 weeks gestation
By 30 weeks solely produced in bone marrow
Immune deficiency in patients with DiGeorge syndrome
Thymic hypoplasia and mild to moderate peripheral lymphopenia (CD3 cells especially)
Leukocyte adhesion deficiency
Recurrent bacterial infections
Delete separation of umbilical cord
Neutrophilia
What can be done to breastmilk to reduce CMV transmission?
Freezing
Pasteurization
