Micro 3 Flashcards
Herpes Simplex
- Herpes labialis (cold sores) (HSV-1)
a. Incubation 2-12/7. Severe painful ulceration,
tendency to coalesce, erythematous base
b. Fever + submandibular lymphadenopathy.
Differential – Herpangina (Coxsackie A) - Genital ulceration (HSV-2)
a. Incubation 4-7/7. Fever, dysuria, malaise, Inguinal lymphadenopathy, Pain++, vesicular rash
b. Herpes meningitis 1-2/52 later in 4-8% of 1o genital herpes. SACRAL RADICULOMYELTIS – urinary retention (self limiting)
Aciclovir: guanosine analogue
- Competitively inhibits viral DNA polymerase by acting as an analogue to deoxyguanosine triphosphate (dGTP).
- Incorporation of aciclovir triphosphate into DNA results in chain termination
- Absence of a 3’ hydroxyl group prevents the attachment of additional nucleosides
OR Valaciclovir
HSE in immunocompromised
In immuncompromised:
- Cutaneous dissemination
- Oesophagitis – pain on swallowing
- Hepatitis
- Viraemia
Congenital HSE
Congenital infection (85% perinatal):
- Neurological: Microcephaly, encephalomalacia, hydranencephaly
- Skin: scarring, active lesions, hypo- and hyperpigmentation
- Eyes: microphthalmia, retinal dysplasia, optic atrophy, and/or chorioretinitis
VZV- what is it? what does it cause?
Enveloped, dsDNA genome
Lies latent in sensory neurons; hence dermatomal distribution when it is reactivated
Chicken pox: Fever, malaise, headache followed by characteristic crops of rash (dew on a rose petal). Lesions scab after 1/52 (no longer contagious).
In the immunocompromised it causes:
- pneumonitis
- encephalitis
- hepatitis
- Purpura fulminans in the neonate
- More rarely: eye manifestations (PORN - progressive outer retinal necrosis and ARN - acute retinal necrosis) and vasculopathy (any organ)
- Secondary infection (shingles) is earlier, more servere and multi-dermatomal
Congenital infection and Neonate VZV
Congenital infection: 1. Eyes: chorioretinitis, cataracts 2. Neurological: microcephaly, cortical atrophy 3. MSK/skin: limb hypoplasia, cutaneous scarring Neonate 1. Purpura fulminans 2. Visceral infection 3. Pneumonitis
VZV Mx
Acyclovir 800mg PO TDS 7/7 or ValAciclovir 1g TDS
- Indications: (both mx and prophylaxis) All adults with chickenpox (at risk of complications), Neonates, Immunocompromised prophylaxis, Eye involvement, All pts presenting with pain
Post-exposure prophylaxis: VZIG (Immunocompromised, Pregnant women)
Live vaccine against varicella – Attenuated Oka strain (Contraindicated in pregnancy)
Rx of shingles – Symptomatic children OR (If <24hrs of rash) Healthy Adult smokers, Chronic lung disease, >20/40 gravid
- Aciclovir 800mg PO 5x daily OR Famciclovir 250 mg PO TDS OR Valaciclovir 1000mg PO TDS
- Topical eye drops plus oral for ophthalmic
- PEP 7-9/7 for Immunocompromised
VZV Ix
Diagnosis
• Exam – vesicles (?HSV)
• Cytology – scrapings for multinucleated giant cells (Tzanck cells)
• Immunofluorescence cytology – cells from vesicles
• PCR – especially if rash is old, CNS and ocular disease
CMV Presentation
In immuocompetent can be A/S or can develop infection mononucleosis style.
In immunocompromised patients:
Encephalitis
Retinitis (in HIV)
Colitis (in transplant pts)
NB the risk in immunocompromised pts is determined by their pretransplant serostatus and whether its an organ or SCT.
If its an organ: D+/R- carries greatest risk of re@.
If its SCT (and you’re hoping that the donor immune system will take over): D-/R+ carries greatest risk of re@.
CMV Tx
- 1st line Ganciclovir (IV)/valganciclovir (oral): guanosine analogue chain terminator
- 2nd line Foscarnet (IV): Non- competitive inhibitor of viral DNA polymerase
- 3rd line Cidofovir (IV): cytidine analogue chain terminator
o Often used in treatment of non-herpes viral infections in the opportunistic post-transplant setting:
o Eg:BKvirusforBK nephropathy/BK cystitis/Adenovirus/PML (JC virus)
IVIg (adjunct in pneumonitis)
EBV in immunocomrpomised
Post-transplant lymphoproliferative disease (Predisposes to lymphoma. Treatment – reduce immunosuppression + give Rituxumab (anti-CD20 monoclonal Ab))
Don’t need to treat EBV in immunocompetent patients and make sure you avoid penicllins due to rash (nfectious mononucleosis exanthema)
Where do alll the herpes viridae lie latent?
EBV - latent in B cells
VZV - sensory neurones
HSV - sensory neurones
CMV - monocytes and dendritic cells
HHV8 - what is it? how does it present? mx?
Kaposi’s sarcoma (Pathognomonic for HIV)
• Primary effusion lymphoma (assoc with EBV
coinfection)
• Castleman’s disease (non-cancerous growth in the
LNs).
Mx Chemotherapy, surgical excision or initiation of anti-retroviral therapy
Polyomaviridae- what are these?
These are uneveloped viruses (unlike the herpes) but are dsDNA (alike the herpes)
JC virus and BK virus
JC Virus:
In immunocompromised (especially AIDS that isn’t on ART, but also in monoclonal antibody use such as natalizumab for MS):
1. Progressive multifocal leukoencephalopathy PML
(demyelination of white matter) Mx is ART
2. Rapidly demyelinating disease + neurological deficits
BK:
In immunocompromised (especially transplant):
1. BK haemorrhagic cystitis in post transplant pts
2. BK nephropathy in renal pts
Respiratory Virus: influenza virus and adenovirus? PC, iX,mx
Influenza virus
URTI; systemic features include muscle aches.
Increased risk of pneumonitis.
Mx: Oseltamivir for 5 days for influenza A or B (Tamiflu)- inhibits NA, blocks virion release
Zanamivir for influneza A due to high risk of resistance
Adenovirus, unenveloped, in immunocompromised (especially post-transplant): Manifests usually as a fever. Test stool of fever patients in case of these manifestations:
1. Encephalitis
2. Pneumonitis
3. Colitis
Usually self-limiting, so supportive care in ITU or HDU setting
In multi-organ involvement:
Cidofovir; IVIG
Rubella
Togaviridae
No longer taken blood for screening during pregnancy
Really really really rare, eliminated in 2015.
CRS - Congenital Rubella Syndrome - completely completely fucks you up.
CRS
Can’t see - cataracts, glaucoma retinopathy
Cant hear -sensorineural deafness
Cardaic - PDA
Microcephaly
Hepatosplenomegaly
First trimester is worst -> 20% die, 90% CRS
Second trimester -> CNS development (deafness retinoopathy)
3rd trimester -> IUGR
Rubella diagnosis and presentation and mangement
PCR
Vaccine
Mx - none.
CMV in pregnancy
Most common cause of viral congenital infection (dark horse) and deafness
50% of people are not immune
Diagnosis: PCR and serology
Pre-natal amniotic fluid at 21 weeks, if post natal needs to be diagnosed within 21 days to be called congenital CMV
CMV disease in baby
Deafness without cataracts but still have very similar
Outcomes if mum is infected
Primary maternal infection -> 30/40%* congenital infection -> 10% abnormalities at birth (most of which have CNS involvement)-> 90% A/S at birth and 10% have disease on follow up such as hearing loss.
- Rates for re@ is lowered to 1-2% (adaptive response in place)
- Overall 0.3% get congenital CMV
CMV Mx
Cant treat in pregnancy
Valganciclovir and ganciclovir
HSV maternal viral infections
- Worse transmission if primary infection (57% vs 25%)
- WITHIN 6 WEEKS OF BIRTH DATE -> C SECTION as 85% are transmitted during birth
Why is it so bad? Neonatal Disease (and why we want to avoid it)
1/3 - CNS
1/4 - Disseminated infection: liver, meningoencephalitis
NB Infection risk control on the neonatal ward
Other features: presents widespread blistering rash
NOTE - this is much more an acute and severe issue than intrauterine infection
Mx - still poor prognosis with antiretroviral disease
Up to a month post natally you can still present with HSE
HSV Diagnosis
PCR
HSV Diagnosis
PCR
VZV
Spread by resp droplets and direct contact and can cause skin rash
Forms of VZV:
Intrauterine - Congenital Varicella Syndrome
(very generic - cataracts, microcephaly, etc) Risk increases with gestation (opposite of rubella) First trimester - 0.5, 3rd 2%
SHINGLES HAS NOT RISK TO FOETUS
Neonatal Varicella - peri/intrapartum
Herpes Zoster in early childhood -
Neonatal Varicella infection
7d before and after birth (no time for passive transfer VZV)
Manifestation:
Skin or can disseminated infection
20% Mortality
Cx: Pneumonitis, encephalitis, also don’t forget bacterial SUPER infection (spanish flu)
B19 Parovirus
SLAPPED CHEEK in normal
Foetl anaemia , hydrops fetalis
Virus also directly infects and injured myocardial
Intrauterine infection
20 weeks cut off (before as higher percentage)
Ix: PCR (both maternal and if +ve consider fetal)
Mx: Blood transfusion
Measles
Rare
No congenital abnormalities to fetus
Zika
Congenital Zika Syndrome
What do we test pregnant women for?
Hep B
HIV
Syphillis
(No longer blood screened for rubella)
Listeria in pregnancy
Mother often has a flu like illness or is asymptomatic. If early > miscarriage. If later -> pre term labour
• Gram-positive rods
• Can cause sepsis in both the mother and baby
• This can be catastrophic
Chlamydia Trachomatis in pregnancy
- Infection transmitted during delivery
- Mother may be A/S
- Causes neonatal conjunctivitis or pneumonia (RARE)
- Treated with erythromycin
Neonatal infection/sepsis classification
Early-onset - within 48 hrs of birth - Some say 3-5 days
• Group B Streptococcus
• Escherichia coli
• Listeria monocytogenes
Late-Onset Sepsis - After 48-72 hours • Coagulase-negative Staphylococci (CoNS) • Group B Streptococcus • Escherichia coli • Listeria monocytogenes • Staphylococcus aureus • Enterococcus sp. Gram-negatives - Klebsiella, Enterobacter, Pseudomonas aeruginosa, Citrobacter koseri • Candida species
GBS
• Gram-positive coccus • Catalase-negative • Beta-haemolytic • 1/3 of women are colonised in their vagina • In neonates, can cause: • Bacteraemia (1-2wks abx) • Meningitis (6 wks abx) • Disseminated infection Mx benzylpenicillin
Late onset sepsis
organisms
Coagulase negative Staph (CoNS) (skin organisms crawl in through catheter in etc after they've had a few days) LEG S aureus G-ves: Kleb, Pseudomonas, Enterobacter Candida sp
Late onset sepsis features
Bradycardia Apnoea Poor feeding Irritability Convulsions
Late onset sepsis mx
1st line - cetax + vanco
2nd line -meropenem
Treat early but if cultures are negative stop after 36 hrs. f there is an element of sepsis stop after 5d.
What do you need to be careful of after VZV infection?
Secondary bacterial infection e.g. iGAS (invasive group a strep)
What investigations can you do for childhood investigations?
FBC CRP Blood culture Urine suprapubic catheter Sputum (children can't cough so you need to get gastric aspirates)
main cause of meningitis
Men B in UK due to vaccination schedule
Strep pneumoniae is highest cause of morbidity and mortality especially in < 2 years
Describt he bacteria e.g. g+/- etc that cause meningitis in the neonatal period
Strep pneumoniae: Gram-positive diplococcus, Alpha-haemolytic
Hib -Gram-negative rod
Streptococcus agalactiae (also known as group B streptococcus or GBS) is a gram-positive coccus (round bacterium) with a tendency to form chains (as reflected by the genus name Streptococcus). It is a beta-hemolytic, catalase-negative, and facultative anaerobe
Respiratory tract infections in kids
Respiratory Tract Infections
•1/3 of all childhood illnesses
•Mostly upper respiratory tract infections
•Mostly viral
•Age is important
•Sputum is difficult to obtain
•Often need to give empirical antibiotics
•Streptococcus pneumoniae is the most important bacterial cause. Most UK strains of pneumococcus remain sensitive to amoxicillin or penicillin
•Mycoplasma pneumoniae tends to affect older children (> 4 years)
oTreated with macrolides (azithromycin)
oPerson-to-person droplet infection
oIncubation period of 2-3 weeks
oEpidemics occur every 3-4 years
If a respiratory tract infection fails to respond to treatment, consider:
o Whooping cough (Bordatella pertussis)
o TB
Mycoplasma Pneumoniae (presentations)
Classical Presentation • Fever • Headache • Myalgia • Pharyngitis • Dry cough Extrapulmonary Manifestations • Haemolysis - IgM ab to the I antigen on erythrocytes. Cold agglutinins in 60% • Neurological: • Encephalitis • Aseptic meningitis • Peripheral neuropathy • Transverse myelitis • Cerebellar ataxia • Cardiac • Polyarthralgia, myalgia, arthritis • Otitis media • Bullous myringitis (vesicles on the tympanic membrane - pathognomonic of mycoplasma disease) - learn this
UTI in kids
• COMMON
• Diagnosis
oSymptoms - if child can give a history
oPure growth of > 105 CFU/mL
oPyuria - pus on urine microscopy
•Obtain sample before starting treatment
Organisms:
Escherichia coli - MAIN ORGANISM
o Other coliforms (Proteus, Klebsiella, Enterococcus sp.)
o Coagulase-negative Staphylococcus (Staphylococcus saprophyticus)
• Early diagnosis and antibiotic treatment is important
• Renal tract imaging may be required to check for congenital anomalies
• Antibiotic prophylaxis may be given after treatment of the infection
Who is susceptible to candida?
Premature infants
ITU pts
Immunocompromised pts
How do we diagnose candida?
o Swabs
o Blood cultures for candidaemia
• Candida is often outcompeted in cultures because bacteria grow more quickly
• So, a selective agar plate that is impregnated with antibiotics is usually used (Sabouraud agar)
• Therefore, if you are suspicious that someone has a Candida infection then you should say so when you send the sample
• Grows in about 48 hours
o Beta-D Glucan assay (serology)
• Sometimes used to look for evidence of invasive Candida infection
o Imaging (e.g. for hepatosplenic candidiasis)
What is Cryptococcus neoformans var. gatii?
It is a species of cryptococcus that causes meningitis in immunoCOMPTENT people in SE Asia and australia
High incidec of SOL in lungs
Resistance to amphotericin B
Cryptococcus investigation
o Cryptococcus has a very distinct capsule around the yeast
o India ink is used to stain for Cryptococcus
o The ink will stain everything black except for the capsule around the yeast
o The capsule is NOT always present (if the organism is not under any form of stress it will not need the capsule (e.g. in blood cultures))
o India ink is not used very frequently anymore
o Instead, an enzyme immunoassay (EIA) to look for components of the capsule are used now
o Cryptococcus can grow in culture but the antigen test is much quicker
Aspergillosis ix
o Blood test
o Serology (look for IgE - check for an allergic response (i.e. in ABPA))
• Antigen detection (galactomannan)
• This can also be detected in BAL fluid
o PCR
o Histology
Classes of antifungals
Azoles
Echinocandin
Ampotericin B
Flucytosine
Azoles
Inhibit ergosterol production > accumulation of toxic steroids in the cell membrane which will result in cell death
• They do this by inhibiting cytochrome P450
( some cross-reactivity with mammalian CYP450 enzymes > drug interactions and impairment of steroidogenesis (ketoconazole, itraconazole))
Types of Azoles
o Water-Soluble Triazoles
Fluconazole (good against Candida and Cryptococcus)
Voriconazole (similar to fluconazole but has improved activity against Aspergillus)
o Lipophilic Triazoles
Itraconazole (useful against dermatophytes)
Posaconazole (has activity against mucor)
Echinocandin Antifungals
Examples: Caspofungin, Micafungin, Anidulafungin
IMPORTANT: Cryptococcus is inherently RESISTANT to echinicandins
MoA: Inhibit Beta-(1,3) D-glucan synthase> inhibits the production of Beta-D glucan which is a component of the fungal cell wall. This results in osmotic fragility
o Candida species (including non-albicans isolates that are resistant to fluconazole)
o Aspergillus species (but NOT other moulds e.g. Fusarium, Zygomycosis)
o NO coverage for Cryptococcus neoformans
Polyene antifungals
• Main polyene is Amphotericin B
- Ambisome has amphotericin within a phospholipid bilayer
- Amphotericin B is a fermentation product of Streptomyces nodusus
MoA: It binds to ergosterol in the fungal cell membrane. This creates transmembrane channels leading to electrolyte leakage. This leads to fungal cell death
Active against MOST FUNGI except:
o Aspergillus terreus
o Scedosporium spp.
NB The original formulation of amphotericin B is amphotericin B deoxycholate (Fungizone) but this has serious toxic side-effects (e.g. nephrotoxicity)
Renovascular and tubular mechanisms
• Vascular - decrease in renal blood flow leading to a drop in GFR (azotaemia)
• Tubular - distal tubular ischaemia, wasting of sodium, potassium and magnesium
o Enhanced in patients who are volume-depleted or who are on concomitant nephrotoxic agents
Flucytosine
• Restricted spectrum of activity
• Inhibits DNA in the fungal cells
• Resistance is due to:
o Decreased uptake (permease activity)
o Altered 5-FC metabolism (cytosine deaminase or UMP pyrophosphorylase activity)
• Clinical Uses
o Monotherapy is now limited
o Candidiasis and Cryptococcosis (in combination with amphotericin B or fluconazole)
• Side Effects
o Infrequent (D&V, changes in LFTs, blood disorders)
o Blood concentrations need monitoring when used in conjunction with amphotericin B
