Microbiology Flashcards

Question

Vaccine indications for Hep A

Answer 1

Travel to endemic country Chronic liver disease Chronic hepatitis B/C Haemophilia People who inject drugs ‘PWID’ MSM Occupational risk: lab, residential facilities, sewage work

Answer 2

Family: Hepadnaviridae, dsDNA virus 8 genotypes Transmission: Parenteral Sexual Vertical Incubation period: 2-6 months Notifiable

Answer 3

<5 years old: Asymptomatic 90% progress to chronic hepatitis B virus infection Adults: 20-40% symptomatic 10% progress to chronic hepatitis B virus infection

Answer 4

Mostly asymptomatic Complications: Cirrhosis Hepatocellular carcinoma Extra-hepatic manifestations

Answer 5

HBsAg = surface antigen --> current infection HBeAg = E antigen --> high viral replication/infectivity HBcIgM = core IgM antibody --> acute infection AntiHBc = total/IgG core antibody --> exposure to HBV infection past or present AntiHBe = E antibody --> immune control: imminent or already achieved eAg clearance AntiHBs = surface antibody --> Immunity Natural (past infection) or Induced (vaccination)

Answer 6

Cirrhosis: Clinical: Child-Pugh score Radiological: coarse echotexture, nodularity, portal HTN – splenomegaly Transient elastography: >12.5 kPa Histopathological: gold std Hepatocellular carcinoma: Alpha-fetoprotein Imaging

Answer 7

Pegylated IFN-apha: Strategy: induce long term immune control: eAg, sAg loss s.c. injections 48 weeks low tolerability, lots of contraindications Nucleotide analogues: Strategy: inhibit viral replication by inhibiting viral DNA polymerase Entecavir Tenofovir long-term oral treatment (until HBsAg loss)

Answer 8

Vaccine: routine imms in UK since 2017: 2, 3, 4 months Screening in pregnancy: HBsAg positive, eAg negative --> vaccine at birth + routine schedule, HBsAg positive, eAg positive --> vaccine at birth PLUS HBIG within 48 hours Blood screening

Answer 9

Family: Flaviviridae ssRNA virus 6 genotypes (type 1 and 3 most common) Transmission: Mainly blood products Sharing of needles Sharing banknotes to insufflate (snort) recreational drugs Incubation period: 2 weeks-6 months Notifiable

Answer 10

Mostly asymptomatic 20-40% will spontaneously clear the infection 40-60% progress to chronicity

Answer 11

Incidental finding Complications: CLD/cirrhosis Hepatocellular carcinoma

Answer 12

Clinical + raised ALT AntiHCV Ab becomes reactive >4 weeks after infection HCV RNA should be requested if acute infection is suspected

Answer 13

Direct acting antivirals (DAA) have revolutionized treatment Hepatitis C is now considered a curable disease Every patient should be considered for treatment 12-week treatment course with a daily pill Very good results against all genotypes ‘-previr’ e.g. bocepravir ‘-asvir’ e.g. velpatasvir ‘-buvir’ e.g. sofosbuvir

Answer 14

no vaccine screening of blood, organs, tissue products Needle exchange programs & similar risk-reduction strategies

Answer 15

Delta is a defective virus – small genome of ss RNA Can only exist WITH hepatitis B virus uses machinery of Hep B to destroy liver cells (makes Hep B hepatotoxic)

Answer 16

severe acute disease with very high ALT, possibly leading to hepatic failure unlikely to become chronic serology: HDV RNA, IgM anti-HDV, HBsAg

Answer 17

usually leads to chronic infection with very high risk of severe liver disease Serology: ALT, total anti-HDV, IgM anti-HDV, HDV RNA and HbsAg

Answer 18

prevent Hep B infection: Vaccination Post-exposure prophylaxis Educate patients with HBV re: risky behaviours (parenteral/sexual)

Answer 19

pegylated IFN-alpha New agent: Bivalirutide

Answer 20

Family: Hepeviridae RNA virus 4 genotypes infect humans: GT 1 and 2: Natural host: human Transmission: faecal-oral 30% mortality in pregnant women GT 3 and 4: Natural host: pig/wild boar Transmission: Zoonotic – undercooked meat Organ transplantation Blood transfusion asymptomatic in 95% adults, tends to affect older males Incubation period: 2-8 weeks Chronic infection rare and only occurs in severely immunocompromised

Answer 21

Immunocompetent: HEV IgM and IgG Immunocompromised: HEV RNA (Ab often undetectable) ‘Chronic infection’ = HEV RNA positive > 3 months HEV RNA becomes detectable in stool and serum during the incubation period Subsequent appearance of the IgM and IgG anti-HEV antibodies. The level of IgM antibody peaks early and becomes undetectable during recovery, whereas the level of the IgG antibody continues to increase and persists in the long term. Clinical symptoms (fatigue, nausea, and jaundice) begin shortly after elevations in serum alanine aminotransferase (ALT) levels. HEV RNA disappears from serum with recovery, whereas detectable virus usually persists longer in stool (arrows).

Answer 22

Haematological: thrombocytopenia red cell aplasia Neurological: encephalitis ataxia brachial neuritis GBS Muscular: proximal myopathy necrotising myositis Renal: membranoproliferative glomerulonephritis IgA nephropathy

Answer 23

Treatment: Supportive Acute, severe hepatitis – consider ribavirin Chronic hepatitis in immunocompromise: 3/12 Rx course Vaccination: Vaccine has been developed, only licensed in China Screen blood products Avoid undercooked meat (pork, wild boar, venison)

Answer 24

(a) beta-lactam antibiotics (penicillins, cephalosporins and carbapenems) - safe in pregnancy - broad-spec - can cross damaged BBB and be used in meningitis - need to clarify penicillin allergies (b) Glycopeptides (Vancomycin and Teicoplanin) - used for MRSA

Answer 25

Gram-positive have cytoplasmic membrane and thick peptidoglycan layer Gram-negative have cytoplasmic membrane and thin peptidoglycan layer then a thick outer membrane so harder to get into Both have peptidoglycan layer so can be targeted with beta-lactams and glycopeptides

Answer 26

Inactivate the enzymes that are involved in the terminal stages of cell wall synthesis (transpeptidases also known as penicillin binding proteins) – β-lactam is a structural analogue of the enzyme substrate Bactericidal - weakened cell wall causes cell lysis Active against rapidly-dividing bacteria only Ineffective against bacteria that lack peptidoglycan cell walls (e.g. Mycoplasma or Chlamydia)

Answer 27

penicillin - Gram positive organisms, Streptococci, Clostridia; broken down by an enzyme (β-lactamase) produced by S. aureus amoxicillin – Broad spectrum penicillin, extends coverage to Enterococci and Gram negative organisms ; broken down by β-lactamase produced by S. aureus and many Gram negative organisms flucloxacillin- Similar to penicillin although less active. Stable to β-lactamase produced by S. aureus. piperacillin – similar to amoxicillin, extends coverage to Pseudomonas and other non-enteric Gram negatives; broken down by β-lactamase produced by S. aureus and many Gram negative organisms clavulanic acid and tazobactam – β-lactamase inhibitors. Protect penicillins from enzymatic breakdown and increase coverage to include S. aureus, Gram negatives and anaerobes

Answer 28

1st, 2nd, 3rd Increasing generation = increasing activity against gram-negative bacilli examples: 1st - cephalexin 2nd - cefuroxime 3rd - ceftriaxone, cefotaxime, ceftazidime

Answer 29

cefuroxime – Stable to many β-lactamases produced by Gram negatives. Similar cover to co-amoxiclav but less active against anaerobes ceftriaxone – 3rd generation cephalosporin. Associated with C. difficile ceftazidime – anti-Pseudomonas Extended Spectrum β-lactamase (ESBL) producing organisms are resistant to all cephalosporins regardless of in vitro results

Answer 30

Stable to Extended Spectrum β-lactamase (ESBL) enzymes Meropenem, Imipenem, Ertapenem Carbapenemase enzymes becoming more widespread. Multi drug resistant Acinetobacter and Klebsiella species.

Answer 31

Relatively non-toxic Renally excreted (so ↓dose if renal impairment) Short half life Will not cross intact blood-brain barrier Cross-allergenic (penicillins approx 10% cross-reactivity with cephalosporins or carbapenems)

Answer 32

Large molecules, unable to penetrate Gram –ve outer cell wall Active against Gram +ve organisms Inhibit cell wall synthesis Important for treating serious MRSA infections (iv only) Oral vancomycin can be used to treat serious C. difficile infection Vancomycin and Teicoplanin are examples of glycopeptides Slowly bactericidal Nephrotoxic – hence important to monitor drug levels to prevent accumulation

Answer 33

Aminoglycosides (e.g. gentamicin, amikacin,tobramycin) Tetracyclines Macrolides (e.g. erythromycin) / Lincosamides (clindamycin) / Streptogramins (Synercid) – The MSL group Chloramphenicol Oxazolidinones (e.g. Linezolid) all bind to ribosome or different parts of ribosome

Answer 34

Bind to amino-acyl site of the 30S ribosomal subunit Rapid, concentration-dependent bactericidal action Require specific transport mechanisms to enter cells (accounts for some intrinsic R) Ototoxic & nephrotoxic, therefore must monitor levels Gentamicin & tobramycin particularly active vs. Ps. aeruginosa Synergistic combination with beta-lactams (used in endocarditis) No activity vs. anaerobes

Answer 35

Prevent elongation of the polypeptide chain Cause misreading of the codons along the mRNA

Answer 36

Broad-spectrum agents with activity against intracellular pathogens (e.g. chlamydiae, rickettsiae & mycoplasmas) as well as most conventional bacteria Bacteriostatic (not good for bacteraemias/sepsis) Widespread resistance limits usefulness to certain defined situations Do not give to children or pregnant women (stain teeth and deposit in bone) Light-sensitive rash Uses: soft-tissue infections, returner's diarrhoea etc.

Answer 37

Reversibly bind to the ribosomal 30S subunit Prevent binding of aminoacyl-tRNA to the ribosomal acceptor site, so inhibiting protein synthesis.

Answer 38

Bacteriostatic Minimal activity against Gram –ve bacteria Useful for diarrhoea in a returning traveller, shigella and salmonella Useful agent for treating mild Staphylococcal or Streptococcal infections in penicillin-allergic patients Also active against Campylobacter sp and Legionella. Pneumophila, mycoplasmas, chlamydia Newer agents include clarithromycin & azithromycin with improved pharmacological properties Used for cellulitis in penicillin-allergic patients

Answer 39

binds to 50S subunit of ribosome: 1. interfere with translocation 2. stimulate dissociation of peptidyl-tRNA

Answer 40

Bacteriostatic Very broad antibacterial activity Rarely used (apart from eye preparations and special indications) because risk of aplastic anaemia (1/25,000 – 1/45,000 patients) and grey baby syndrome in neonates because of an inability to metabolise the drug used in meningococcal meningitis if penicillin-allergic

Answer 41

binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation

Answer 42

Binds to the 23S component of the 50S subunit to prevent the formation of a functional 70S initiation complex (required for the translation process to occur). Highly active against Gram positive organisms, including MRSA and VRE. Not active against most Gram negatives. May cause thrombocytopenia and optic neuritis and should be used only with Infectious Diseases approval

Answer 43

Quinolones e.g. Ciprofloxacin, Levofloxacin, Moxifloxacin - associated with c diff and severe side effects (esp. tendonitis), lower threshold for seizures - levo used sometimes in penicillin-allergy Nitroimidazoles e.g. Metronidazole & Tinidazole - used for amoebas

Answer 44

Act on alpha-subunit of DNA gyrase predominantly, but, together with other antibacterial actions, are essentially bactericidal Broad antibacterial activity, especially vs Gram –ve organisms, including Pseudomonas aeruginosa Newer agents (e.g. levofloxacin, moxifloxacin) high activity vs G +ves and intracellular bacteria, e.g. Chlamydia spp Well absorbed following oral administration Use for UTIs, pneumonia, atypical pneumonia & bacterial gastroenteritis

Answer 45

Include the antimicrobial agents metronidazole & tinidazole Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage Rapidly bactericidal Active against anaerobic bacteria and protozoa (e.g. Giardia) Nitrofurans are related compounds: nitrofurantoin is useful for treating simple UTIs (not pyelonephritis) - should be taken after emptying bladder

Answer 46

Rifamycins, e.g. rifampicin & rifabutin - mainly used for TB - can be used post-joint surgeries - resistance can develop very quickly so should only be used in combination

Answer 47

Inhibits protein synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation Bactericidal Active against certain bacteria, including Mycobacteria & Chlamydiae Monitor LFTs Beware of interactions with other drugs that are metabolised in the liver (e.g oral contraceptives) May turn urine (& contact lenses) orange Except for short-term prophylaxis (vs. meningococcal infection) you should NEVER use as single agent because resistance develops rapidly Resistance is due to chromosomal mutation. This causes a single amino acid change in the ß subunit of RNA polymerase which then fails to bind Rifampicin.

Answer 48

Daptomycin – a cyclic lipopeptide with activity limited to G+ve pathogens. It is a recently-licenced antibiotic likely to be used for treating MRSA and VRE infections as an alternative to linezolid and Synercid Colistin – a polymyxin antibiotic that is active against Gram negative organisms, including Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella. pneumoniae. It is not absorbed by mouth. It is nephrotoxic and should be reserved for use against multi-resistant organisms

Answer 49

Sulfonamides Diaminopyrimidines (e.g. trimethoprim)

Answer 50

Act indirectly on DNA through interference with folic acid metabolism Synergistic action between the two drug classes because they act on sequential stages in the same pathway Sulphonamide resistance is common, but the combination of sulphamethoxazole+trimethoprim (Co-trimoxazole) is a valuable antimicrobial in certain situations (e.g. Treating Pneumocystis jiroveci pneumonia) Trimethoprim is used for Rx community-acquired UTIs

Answer 51

Chemical modification or inactivation of the antibiotic Modification or replacement of target Reduced antibiotic accumulation 1) Impaired uptake 2)Enhanced efflux Bypass antibiotic sensitive step

Answer 52

ß Lactamases are a major mechanism of resistance to ß Lactam antibiotics in Staphylococcus aureus and Gram Negative Bacilli (Coliforms). NOT the mechanism of resistance in penicillin resistant Pneumococci and MRSA. Penicillin resistance not reported in Group A (S. pyogenes), B, C, or G ß haemolytic Streptococci.

Answer 53

Methicillin Resistant Staphylococcus aureus (MRSA): mecA gene encodes a novel PBP (2a). Low affinity for binding ß Lactams. Substitutes for the essential functions of high affinity PBPs at otherwise lethal concentrations of antibiotic. Streptococcus pneumoniae: Penicillin resistance is the result of the acquisition of a series of stepwise mutations in PBP genes. Lower level resistance can be overcome by increasing the dose of penicillin used. (for meningitis: add vancomycin)

Answer 54

Able to break down cephalosporins (cefotaxime, ceftazidime, cefuroxime) Becoming more common in E. coli and Klebsiella species. Treatment failures reported with ß Lactam/ ß Lactamase inhibitor combinations (eg. Augmentin/Tazocin).

Answer 55

N. meningitidis meningitis: 7 days Acute osteomyelitis (adult): 6 weeks Bacterial endocarditis: 4-6 weeks Group A strep pharyngitis: 10 days Simple cystitis (women): 3 days

Answer 56

TB is spread person to person through the air via droplet nuclei M. tuberculosis may be expelled when an infectious person: Coughs Sneezes Speaks Sings Transmission occurs when another person inhales droplet nuclei Whether TB will be transmitted depends on: Infectiousness of person with TB disease Environment in which exposure occurred Length of exposure Virulence (strength) of the tubercle bacilli The best way to stop transmission is to: Isolate infectious persons Provide effective treatment to infectious persons as soon as possible requires around 8 hours of exposure

Answer 57

About ¼ to 1/3 of world’s population estimated to have a latent TB infection, So risk of developing active TB disease Post TB infection, 10% lifetime risk for active TB =dogma; 30-50% active TB if HIV positive Latent infection: prevent active TB = diagnosis +chemoprophylaxis Fever+Wt loss+Night sweats+cough (2-3 wks), haemoptysis (rare, very advanced disease) Disease can occur decades later but rare Diagnosis: Mantoux with PPD or Interferon gamma release assays (IGRA)

Answer 58

Isoniazid, Rifampicin, Pyrazinamide +/- Ethambutol for 2 months Then Rifampicin and Isoniazid for 4 months (95% cure rate) Daily therapy (or 3 x weekly), orally Total 6 months 12 months for TB meningitis Baseline checks incl CXR, LFT, FBC, U&E, CRP

Answer 59

Microscopy ZN stain (quickest) Microscopy auramine stain Xpert MTB/RIF assay MGIT (liquid culture) Solid culture (best)

Answer 60

Molecular line probe assays: DNA extraction from cultures and clinical specimens (sputum); PCR amplification of fragments of genes associated with drug resistance; Hybridization with the DNA probes on membranes; Development, reading and interpretation of results

Answer 61

Hep E: maternal infection Measles: miscarriage/stillbirth Zika: teratogenicity CMV: IUGR/Prematurity Parvovirus: congenital disease HBV: vertical transmission

Answer 62

Vesicular: VZV HSV enterovirus (monkey pox) Maculopapular: Parvovirus B19 Measles Rubella (Dengue/Zika/Yellow Fever, HIV)

Answer 63

HSV VZV CMV EBV These are DNA viruses Once exposed they will cause lifelong infection (often latent) Have the capacity to reactivate under stress/ immunosuppression etc

Answer 64

Transmission: respiratory (isolate!) 70% infection rate in those who are susceptible Incubation: 7-13 days (mean 14 days) Rash will be precipitated by prodromal illness

Answer 65

Neurological – intellectual disability, microcephaly , hydrocephalus, seizures, Horner’s syndrome Occular abnormalities – optic nerve atrophy, cataracts, chorioretinities, micropthalmost, nystagmus Limb abnormalities – hypoplasia , atrophy, paresis GI – GORD, atretic or stenotic bowel Skin scarring

Answer 66

MATERNAL VARICELLA 10-20% of women of childbearing age are susceptible 10-20% of pregnant women with varicella will have varicella pneumonia. Encephalitis is rare but mortality is 5-10% CONGENITAL (foetal) VARICELLA SYNDROME 0.4% if maternal infection weeks 0-12 2% if weeks12-20

Answer 67

Ask if previous exposure to VZV If had previous chickenpox/shingles infection or had the vaccine: sufficient evidence of immunity If no previous exposure: Urgent antibody testing on recent blood sample If VZV IgG <100 mIU/ml offer PEP - aciclovir (start 7 days after exposure due to replication cycle)

Answer 68

Transmission : via close contact Incubation: Oropharyngeal/ oro-facial 2-12 days Genital infection 4-7 days Latency: established in nerve cells Symptoms: Asymptomatic Painful vesicular rash Lymphadenopathy Fever Diagnosis: Viral detection – lesion swab for PCR Serology

Answer 69

Foetal infection: ascending infection in PROM (premature rupture of membranes) Neonatal infection Direct contact with infected maternal secretions during delivery (usually C-section recommended) Oral herpes : kissing baby Non familial transmission: other relatives, hospital staff etc VERTICAL TRANSMISSION Greatest risk of transmission is primary genital infection in the 3rd trimester If active HSV in final 6 weeks before delivery then C-section is recommended IN UTERO INFECTION (rare but severe) Primary infection only Miscarriage Congenital abnormalities ( ventriculomegaly, CNS abnormalities) Preterm birth IUGR Non-primary and recurrent have antibodies that can pass onto neonate

Answer 70

GUM clinic referral Aciclvoir HSV anti-body testing Consider planned C-section if within 6 weeks before delivery If gets recurrent outbreaks: May not treat recurrence Consider suppressive therapy from 36 weeks Maternal antibody will offer some protection (but may not prevent transmission) Avoid prolonged rupture of membranes / invasive foetal monitoring

Answer 71

Untreated -> mortality >80% and severe neurological involvement is common Skin, Eye, Mouth: 45% of cases Initially benign High risk of progression to CNS MUST be treated Usually first 14 days Up to 6 weeks CNS involvement: 30% of cases Weeks 2-3 of life (up to 6) Seizures Lethargy Irritability Poor feeding Fevers Need CSF! Disseminated: Presents like sepsis Often in 1st week of life Multi-organ involvement (liver, lungs, CNS, heart, GI tract, renal tract, bone marrow) Treat with aciclovir

Answer 72

Rubella is a Togavirus – RNA virus . AKA German measles Transmission: respiratory (isolate!) Incubation 12-21 days Symptoms 20-50% are subclinical May be a prodrome (more likely in adult infection) – coryza, sore throat , cough, headache (1-5 days pre rash) Fine, macular rash. Mildly pruritic. Starts on face and spreads to trunk / limbs (within hours) Lymphadenopathy – tender, postauricular/ cervical/ suboccipital Diagnosis: Viral detection (PCR) Serology

Answer 73

In well vaccinated countries immigrants form the burden of CRS (congenital rubella syndrome) Risk of this rising with vaccine avoidance CRS can be catastrophic Greatest risk is in the 1st trimester If infection before 8 weeks -> 20% spont abortion If infection before 10 weeks 90% incidence of fetal defects If infection after 18-18 weeks -> hearing defects and retinopathy If infection after 20 weeks risk is much lower

Answer 74

Rash starts at hairline / behind ears and spreads cephalocaudally over 3 days Paramyxovirus – RNA virus Transmission: respiratory (isolate!) , conjunctiva Incubation 7-18 days (mean 10 days) Symptoms Prodrome 2-4 days Conjunctivitis Koplick spots Rash Complications for mother: Secondary bacterial infection Otitis media / pneumonia / gastrointestinal Encephalitis

Answer 75

Manifest in infancy: bone lesions microcephaly cataracts retinopathy meningioencephalitis cardiac (PDA, PS) purpura hepatosplenomegaly later manifestation: panencephalitis hearing loss intellectual disability diabetes mellitus thyroid dysfunction

Answer 76

foetal loss preterm delivery no congenital abnormalities SSPE – subacute sclerosing panencephalitis – fatal, progressive degenerative disease of CNS. Occcurs 7-10 years after natural infection.

Answer 77

DNA virus 30-60% of adults have antibodies Transmission: Respiratory, blood products Incubation: 6-8 days Symptoms Mostly asymptomatic Erythema infectiosum/ slapped cheek/5ths disease Polyarthropathy Transient aplastic crisis Diagnosis Virus detection (PCR) Serology Infectious: 6 days post exposure – 1 week. You are infectious before symptoms commence

Answer 78

Before 20 weeks Transmission 33% 9% risk of infection 3% hydrops fetalis if infection) 1% fetal anomalies 7% fetal loss (refer to foetal medicine for monitoring, may need intrauterine blood transfusions) Fetal hydrops Cytotoxic to fetal red blood precursor cells -> anaemia -> accumulation of fluid in soft tissues and serous cavities. -> can rapidly cause fetal death (acites, pleural effusion, skin edema, hydopic placenta, pericardial effusion, cardiomegaly, polyhydramnos, oligohydramnos RX: intrauterine transfusion 50% of fetal infections result in interuterine death) After 20 weeks: no documented risk

Answer 79

Transmission: respiratory +/- faecal Incubation: 2-40 days Symptoms: Hand, foot and mouth disease Rash Encephalitis Myocarditis Not generally associated with severe outcomes Coxsakie virus presents main risk Perinatal newborn infection can occur in last week of pregnancy Neonates are at risk of myocarditis, fulminant hepatitis , encephalitis , bleeding and multi-organ failure.

Answer 80

Common early childhood infection 2-6% of infants infected by 6 months, 40% by 16yrs. Transmission: salvia/ resp secretions/ urine Incubation: 4-8 weeks Virus persists lifelong Symptoms Mostly asymptomatic Maculopapular rash, infectious mononucleosis-like illness Test: PCR of urine/ saliva / amniotic fluid/ tissue Serology

Answer 81

If maternal CMV infection is suspected then check serology (compare booking to repeat sample) Is seroconversion suspected (aka infection during pregnancy) then refer to fetal medicine unit for USS +/- amniocentesis No treatment available Neonates are investigated – urine and saliva CMV PCR within 1st 21 days. Foetus: microcephaly encephalitis ventriculomegaly choriorenitis hepatosplenomegaly thrombocytopenia jaundice

Answer 82

mosquito vector no vaccine incubation period: 5-7 days in pregnancy: microcephaly visual and hearing problems seizures feeding problems movement problems

Answer 83

Current advice: All travellers – bite avoidance Pregnant women – avoid travel to areas with current transmission Avoid conception for 2 – 6 months after travel (prolonged viral shedding in semen) Testing only if symptomatic or abnormalities identified on antenatal USS

Answer 84

pt monitored through hepatology HBV can be transmitted from infected mothers (perinatal transmission) - increased risk of becoming chronically infected with the virus vaccination at birth can prevent 90% perinatal transmission neonate given extra vaccine dose +/- immunoglobulin Normal vaccination schedule: 8,12,16 weeks If mother is HBV infected then given additional doses: 24 hours, 4 weeks, 1 year

Answer 85

birth plan managed through MDT viral load cervicovaginal vertical transmission of HIV review plasma viral load at 36 weeks - c-section> - intrapartum IV infusion of cART viral load implications for duration of neonatal treatment

Answer 86

HSV infection progressive encephalopathy anaemia frequent nose bleeds thrush pnuemonia pneumocystis, TB diarrhoea bruising enlarged parotids lymphadenopathy suppurative infections hepatosplenomegaly clubbing nappy rash (severe) failure to thrive

Answer 87

Staph.aureus (MSSA and MRSA) E.coli Pseudomonas aeruginosa

Answer 88

If surgical site is contaminated with > 10 5 microorganisms per gram of tissue, risk of SSI is increased. The dose of contaminating bacteria required to cause infection is much lower if there is foreign material present e.g silk suture

Answer 89

Superficial incisional- affect skin and subcutaneous tissue Deep incisional- affect fascial and muscle layers Organ/space infection- any part of anatomy other than incision

Answer 90

Age ; over 75 in hip replacement ASA score of 3 or more Diabetes – two to three fold increased risk. Association with post-op hyperglycaemia. Control blood glucose. HbA1C < 7 Radiotherapy and steroid use. Taper steroids Rheumatoid arthritis. Stop disease modifying agents for 4 weeks before and 8 weeks post-op. Obesity 2-7 increased risk if BMI> 35 Smoking- delayed wound healing and vasoconstrictive effect

Answer 91

Rheumatoid arthritis , osteoarthritis, crystal induced arthritis Joint prosthesis Intravenous drug abuse Diabetes, chronic renal disease, chronic liver disease Immunosuppression- steroids Trauma- intra-articular injection, penetrating injury

Answer 92

Organisms adhere to the synovial membrane, bacterial proliferation in the synovial fluid with generation of host inflammatory response. Joint damage leads to exposure of host derived proteins such as fibronectin to which bacteria adhere BACTERIAL FACTORS S.aureus has receptors such as fibronectin binding protein that recognise selected host proteins. Kingella kingae synovial adherence is via bacterial pili Some strains produce the cytotoxin PVL ( Panton-Valentine Leucocidin) which have been associated with fulminant infections. HOST FACTORS Leucocyte derived proteases and cytokines can lead to cartilage degradation and bone loss. Raised intra-articular pressure can hamper capillary blood flow and lead to cartilage and bone ischaemia and necrosis. Genetic variation in expression of cytokines may lead to differential susceptibility to septic arthritis.

Answer 93

Staph. aureus 46% - Coagulase negative staphylococci 4% Streptococci 22% Streptococcus pyogenes Streptococcus pneumoniae Streptococcus agalactiae Gram negative organisms -E.coli - Haemophilus influezae - Neisseria gonorrhoeae - Salmonella Rare- Lyme, brucellosis, mycobacteria, fungi

Answer 94

1-2 week history of red, painful, swollen restricted joint Monoarticular in 90% Knee is involved in 50% Patients with rheumatoid arthritis may show more subtle signs of joint infection

Answer 95

Blood culture before antibiotics are given Synovial fluid aspiration for microscopy and culture ESR,CRP -Traditionally a synovial count> 50,000 cells/mm3 used to suggest septic arthritis (Negative culture result does not exclude septic arthritis) US- confirm effusion and guide needle aspiration MRI- joint effusion, articular cartilage destruction, abscess, contiguous osteomyelitis

Answer 96

Arthroscopic washout Antibiotics- iv Cephalosporin or Flucloxacillin - may need to add vancomycin if at high risk of MRSA Intravenous antibiotics for 2 weeks and review; then upto four weeks orally

Answer 97

S.aureus- 48.3% CNS- 6.7% GNR- 23.1% Strep- 43.1% cervical- 10.6% cervico-thoraco- 0.4% lumbar 43.1%

Answer 98

Back pain Fever Neuro impairment

Answer 99

MRI: 90% sensitive Blood cultures CT/ open biopsy

Answer 100

Six weeks of treatment (IV & PO Abx) Longer treatment if undrained abscesses/implant associated Surgery if there is spinal cord compression

Answer 101

Pain Patient complains that the joint was ‘never right’ Early failure Sinus tract

Answer 102

Gram positive cocci -coagulase negative staphylococci -staphylococus aureus Streptococci sp Enterococci sp Aerobic gram negative bacilli Enterobacteriaceae Pseudomonas aeruginosa Anaerobes Polymicrobial Culture negative Fungi

Answer 103

Symptoms CRP Synovial fluid analysis: Leukocytes, PMN, alpha defensin Aspiration fluid culture Intraoperative tissue culture Histology Nuclear imaging

Answer 104

Tissue specimens from at least 5 sites around the implant Histopathology – infection defined as >5 neutrophils per high power field. If 3 or more specimens yield identical organisms, this is highly predictive of infection (sensitivity 65%, specificity 99%)

Answer 105

Single stage revision: Remove all foreign material and dead bone Change gloves, drapes etc Re-implant new prosthesis with antibiotic impregnated cement and give iv antibiotics Two stage revision: Remove prosthesis Take samples for microbiology and histology Period of iv antibiotics (6weeks). Stop antibiotics for 2 weeks Re-debride and sample at second stage Re-implantation with antibiotic impregnated cement No further antibiotics if samples clear OPAT

Answer 106

= debridement, antibiotics and implant retention Within 3 weeks of operation Tissue sampling Radical debridement Exchange of modular components Antibiotics

Answer 107

Gram positive diplococci 30-50% of CAP Acute onset Severe pneumonia Fever, rigors Lobar consolidation Almost always penicillin sensitive (increasing resistance in southern europe so important to obtain travel history and to check sensitivities)

Answer 108

Inflammation of the lung alveoli Patients are sick- mortality 5-10%, 20-40% admitted to hospital Presentation Fever Cough Pleuritic chest pain Shortness of breath Often localising signs and abnormal CXR Classification: - community acquired - hospital acquired

Answer 109

No microbiological ID made in most cases Main organisms: - Streptococcus pneumoniae - Haemophilus influenzae - Moraxella catarrhalis - Staphylococcus aureus - Klebsiella pneumoniae

Answer 110

0-1 mths- E.coli, GBS, Listeria 1-6mths- Chlamydia trachomatis, S aureus, RSV 6mths-5yrs- Mycolpasma, Influenza 16-30yrs-M pneumoniae, S pneumoniae

Answer 111

SOB Cough +/- sputum Fever Rigors Pleuritic chest pain Malaise, nausea & vomiting Pyrexia Tachycardia Tachypnoea Cyanosis Dullness to percussion, tactile vocal fremitus Bronchial breathing Crackles

Answer 112

used to assess severity of pneumonia score 2-5 = manage as severe Confusion Urea >7 mmol/l RR >30 BP <90 systolic <60 diastolic >65 years

Answer 113

Inflammation of medium sized airways. Mainly in smokers Cough, fever, increased sputum production, increased shortness of breath. CXR: normal Organisms: viruses S. pneumoniae H. influenzae M. catarrhalis Bronchodilation; Physiotherapy +/- Abx

Answer 114

Gram –ve coccobacillus 15-35% of CAP More common with pre-existing lung disease (older individuals) May produce β-lactamase

Answer 115

Inhalation of infected water droplets Can cause mild disease upto multi-organ failure Requires special culture: buffered charcoal yeast extract Aerosol spread Environmental outbreaks Associated with confusion, abdo pain, diarrhoea Lymphopenia, hyponatremia Dx by antigen in urine/serum Sensitive to macrolides

Answer 116

Pneumonia caused by organisms without a cell wall - Mycoplasma - Legionella - Chlamydia - Coxiella Cell-wall active antibiotics e.g. penicillins don't work Need agents that work on protein synthesis - Macrolides (clarithromycin / erythromycin) - Tetracyclines (doxycycline) Extrapulmonary features – e.g. hepatitis; low sodium ~20% of CAP Flu-like prodrome before fever & pneumonia

Answer 117

Common in domestic/farm animals Transmitted by aerosol or milk Dx by serology Sensitive to macrolides

Answer 118

Spread from birds by inhalation Dx by serology Sensitive to macrolides

Answer 119

Empyema / abscess Proximal obstruction (tumour) Resistant organism (incl. Tb) Not receiving / absorbing Abx Immunosuppression Other diagnosis Lung cancer Cryptogenic organising pneumonia

Answer 120

influenza A influenza B RSV SARS-CoV-2 everyone admitted usually gets one

Answer 121

(mycobacterium tb) “The white plague” Must always be considered in differential. (great mimic - doesn't always present with resp symptoms due to extrapulmon features) Clues: - Ethnicity - Prolonged prodrome - Fevers - Weight loss - Haemoptysis CXR: Classically upper lobe cavitation (but can vary considerably) Auramine and ZN stain TB culture

Answer 122

> 48 hours in hospital. Often previous antibiotics; +/- ventilator Infectious vs Non-infectious causes of abnormal CXR / lung function. Bronchial lavage desirable to differentiate upper respiratory from lower respiratory flora

Answer 123

Staphylococcus aureus 19% Enterobacteriaciae 31% Pseudomonas spp 17% Acinetobacter baumanii 6% Fungi (Candida sp.) 7%

Answer 124

Protozoan Ubiquitous in environment Insidious onset Dry cough, weight loss, SOB, malaise CXR “bat’s wing” Dx Immunofluorescence on BAL/PCR, silver stain (cytology lab) desaturation on walking up and down corridor Rx Septrin (Co-trimoxazole) Prophylaxis Septrin (usually seen in pts with HIV, or immunosuppressed due to medications)

Answer 125

Allergic bronchopulmonary aspergillosis - Chronic wheeze, eosinophilia - Bronchiectasis Aspergilloma - Fungal ball often in pre-existing cavity - May cause haemoptysis Invasive aspergillosis - Immunocompromised - Rx Amphotericin B

Answer 126

HIV: PCP, TB, atypical mycobacteria Neutropenia: fungi e.g. Aspergillus spp Bone marrow transplant: CMV Splenectomy: encapsulated organisms e.g. S. pneumoniae, H. influenzae

Answer 127

Each hospital has its own guideline Mild-moderate: - Amoxicillin - Or erthromycin / clarithromycin Moderate-severe: - Needing hospital admission: Augmentin (co-amoxiclav) AND clarithromycin. - Allergic: Cefuroxime AND clarithromycin.

Answer 128

First line: Ceftazidime/Ciprofloxacin +/- vancomycin. Second line/ITU: Piperacillin/tazobactam AND vancomycin Specific therapy: MRSA: Vancomycin. Pseudomonas: Piperacillin/tazobactam or Ciprofloxacin +/- gentamicin.

Answer 129

Petersdorf 1961 Fever >38.3C Lasting > 3 weeks Uncertain diagnosis after 7 days in hospital Durack 1991 Prescriptive set of mandatory investigations 3 days of hospital investigation or 3 OP visits Knockaert 2003 Pragmatic 3 days of Hospital investigation with no diagnosis

Answer 130

Infection Inflammation Malignancy Other

Answer 131

B-symptoms, localising symptoms Medications - doses and initiation date Contact history, pets / animal exposures Injecting drug use, sexual history Foreign travel

Answer 132

True multisystem diseases Fundoscopy – roth spots (endocarditis) ENT – sinusitis, OM, or oropharyngeal candidiasis - ?HIV SSTI – OM, ticks - annular lesions (lyme disease), erythema migrans Neuro and spinal exam

Answer 133

Routine admission tests: FBC U&E LFT CRP CXR Blood cultures Urine dip PUO initial tests: 2 x more blood cultures Urine culture Stool cultures + OCP CMV /EBV serology HIV/HBV/HCV CK Ferritin LDH ANA ANCA RhF TFT FDG-PET CT scan Echocardiogram Biopsies Lumbar puncture Bone marrow aspirate

Answer 134

IgM = pentamer in acute phase IgG = dimer after IgM production has stopped (chronic phase) - during clearance of infection

Answer 135

Fluoro-D-Glucose accumulates in cells with an increased rate of glycolysis All activated leukocytes demonstrate increased FDG uptake Allows metabolic correlation to anatomical scan Useful in endocarditis and vascular infections / inflammation Caution in those with poor glucose control Ensure patient fasted appropriately

Answer 136

Viral CMV / EBV HIV Hepatitis A,B,C,D,E Parasites Malaria Amoebic liver abscess Schistosomiasis Toxoplasmosis Trypanosomiasis Fungal Cryptococcosis Histoplasmosis Coccidioides Bacterial Q-Fever, Bartonella, Brucella. Mycobacteria TB/NTM Enteric fevers Zoonoses

Answer 137

Connective tissue diseases: Adult onset stills diseases (rule out using ferritin, salmon pink rash) SLE Polymyalgia rheumatica RA Sjogrens Vasculitis syndromes: Giant cell arteritis (rule out using ESR) Wegener disease Polyarteritis nodosa

Answer 138

Age >50 Headache - Not needed for diagnosis – but should raise suspicion Jaw claudication ESR > 45 - need to adjust for age - Not raised in 7-20% in case series - CRP adds sensitivity 50% will have change if vision on presentation - Often minor / fluctuating High risk of sight impairment / stroke Temporal biopsy gold standard PET CT useful Treat immediately – involve rheumatologist.

Answer 139

Lymphoma – especially non-Hodgkin’s Often advanced disease with aggressive subtype Raised LDH, weight loss, lymph nodes Leukaemia Bone marrow biopsy Renal Cell Carcinoma 20% of cases present with fever, haematuria can occur Hepatocellular carcinoma or other tumours metastatic to the liver Often identified on axial imaging

Answer 140

Subacute thyroiditis Addison's Dressler syndrome PE Habitual hyperthermia Drugs Factitious fever

Answer 141

Infective endocarditis Disseminated TB CNS TB GCA Clinical signs of sepsis

Answer 142

Diseases that pass between people and animals. >70% of emerging human infectious diseases come from animals. Examples of new emerging infectious diseases: VHF respiratory diseases novel influenza viruses

Answer 143

Every day contact with animals - Scratches or bites By-products (feces/urine) - Contaminated soil - Litter Foodstuffs - Carcass processing - Milk and milking - Raw/undercooked meats

Answer 144

Farm/wild: Campylobacter Salmonella Brucella Coxiella Rabies VHF Companion: Bartonella Toxoplasmosis Ringworm Psitticosis Rabies Tick-borne diseases Spirilum minus

Answer 145

Reservoir: poultry cattle Transmission: contaminated food (80% from raw chicken) also found in: red meat, unpasteurised milk and untreated water Clinical presentation: Diarrhoea Bloating Cramps Ix: stool culture Mx: supportive

Answer 146

Reservoir: poultry reptiles/amphibians Transmission: contaminated food poor hand hygiene Presentation: Diarrhoea Vomiting Fever Ix: stool culture Mx: Supportive (Ciprofloxacin, azithromycin)

Answer 147

= slightly curved gram neg rod Reservoir: kittens > cats Transmission: Scratches Bites Licks of open wounds Fleas Causes two diseases: Cat Scratch Disease Bacillary angiomatosis

Answer 148

Presentation: Macule at site of innoculation Becomes pustular Regional adenopathy Systemic symptoms Ix: serology Mx: Erythromycin doxycycline

Answer 149

Presentation: Occurs in immunocompromised Skin papules Disseminated multi-organ and vasculature involvement Ix: Histopathology Serology Mx: erythromycin doxycycline PLUS rifampicin

Answer 150

Reservoir: cats sheep Transmission: infected meat faecal contamination Presentation: Fever Adenopathy Still-birth Progressive visual, hearing, motor, & cognitive issues Seizures Neuropathies Ix: Serology Mx: spiramycin pyrimethamine plus sulfadiazine

Answer 151

Reservoir: cattle goats Transmission: Unpasteurised milk Undercooked meat Mucosal splash Aerosolisation/inhalation Presentation: Fever chills, headache, myalgia, arthralgia, anorexia, fatigue, lymphadenopathy and splenomagaly Back pain Orchitis Focal abscesses (Psoas, liver etc) Ix: blood/pus culture serology Mx: doxycycline PLUS gentamicin or rifampicin Incubation period- usually 30 days but can be up to 5 months (often presents like TB)

Answer 152

Reservoir: goats sheep cattle Transmission: Aerosolisation/inhalation of secretions, waste, or milk of infected animals Unpasteurised milk Presentation: Fever ‘Flu-like illness Pneumonia Hepatitis Endocarditis Focal abscesses (Para-vertebral/discitis etc) Ix: serology Mx: doxycycline (hydroxychloroquine)

Answer 153

Reservoir: dogs cats bats Transmission: bites scratches contact with infected fluid Presentation: Seizures Excessive salivation Agitation Confusion Fever Headache Ix: serology brain biopsy (USA saliva PCR) Mx: (too late if neuro symptoms) Ig Vaccine

Answer 154

Reservoir: rats Transmission: bites contact with infected urine or droppings Responsible agents either: Streptobacillus moniliformis or Spirillum minus Presentation: Fevers Polyarthralgia Maculopapular progressing to purpuric rash Can progress to endocarditis Ix: Joint fluid microscopy & culture blood culture Mx: penicillins

Answer 155

Reservoir: Deer mouse; Sin Nombre virus White footed mouse; Sin Nombre virus Cotton rat; Black canal virus Rice rat; Bayou virus Transmission: contact with infected urine or droppings aerosolisation Presentation: Fever Myalgia ‘Flu-like illness Respiratory failure Bleeding Renal failure Ix: serology PCR Mx: supportive

Answer 156

Reservoir: Ebola - ? Bats Marburg - ? Bats Lassa – Rats CCHF - ticks Transmission: contact with fluids of infected Viruses: Lassa, Marburg, Ebola, and Congo-Crimean Hemorrhagic Fever Presentation: Fever Myalgia ‘Flulike illness Bleeding Ix: serology PCR Mx: supportive

Answer 157

Baltimore: depends on replicative life cycle All viruses produce a positive sense messenger RNA to generate proteins for their replication. The nature of their genomes means different classes achieve this through differing mechanisms. This has implications for their life cycle, diagnosis and treatment

Answer 158

An infection caused by an organism that does not normally cause disease …Or symptomatology may be altered in the immunocompromised compared to immunocompetent May be “endogenous” Latent viruses that reactivate in the absence of a normal immune system Acquired in the past prior to immune suppression – eg Varicella Zoster (VZV) May be “exogenous” Viruses which are acquired from the environment Increased severity in the immunocompromised – eg influenza, SARS-CoV-2.. Or even primary acquisition of VZV

Answer 159

Candidiasis of the esophagus, bronchi, trachea, or lungs Cervical cancer, invasive Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal (greater than one month's duration) Cytomegalovirus disease (other than liver, spleen, or nodes) Cytomegalovirus retinitis (with loss of vision) Encephalopathy, HIV related Herpes simplex: chronic ulcer(s) (more than 1 month in duration); or bronchitis, pneumonitis, or esophagitis Histoplasmosis, disseminated or extrapulmonary Isosporiasis, chronic intestinal (more than 1 month in duration) Kaposi sarcoma Lymphoma, Burkitt's (or equivalent term) Lymphoma, immunoblastic (or equivalent term) Lymphoma, primary, of brain Mycobacterium avium complex or M kansasii, disseminated or extrapulmonary Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary Pneumocystis jiroveci pneumonia Pneumonia, recurrent Progressive multifocal leukoencephalopathy Salmonella septicemia, recurrent Toxoplasmosis of brain Wasting syndrome due to HIV

Answer 160

Viruses are challenging to grow – they require human cells + dangerous Therefore, we look for indirect or direct evidence of their presence Indirect detection: Useful to see whether you have ever had the infection Response of the immune system to the virus (IgM and IgG) Direct detection: Useful to see whether you currently have the infection Viral proteins (lateral flow/antigen tests) Viral genetic material (virus genetic material is present with patient sample) Polymerase Chain Reaction, PCR used in immunosuppressed as cannot detect immune response in these people

Answer 161

(Indirect activation) Measure levels of antibody in patients serum +++ IgM indicate Active or Resolving infection +++ IgG indicates past infection > 6 weeks ago Antibody levels ↓↓↓ reduced in Immunosuppressed Serological course may differ depending upon virus

Answer 162

(direct detection) Polymerase chain reaction Detect viral genome in samples via amplification Highly sensitive and specific Performed on many different sample types Viral load can be used to monitor infection May remain positive after infection resolved (lingering DNA)

Answer 163

Immune system = non functional → Serology useless 1.Screen prior to immunosuppression Identify previous viral exposure that may reactivate Guide the use of antiviral prophylaxis 2.Monitor using PCR Identify viral reactivation promptly → Rx Detect infection

Answer 164

Serological screening (before): HIV Ag/Ab HBV surface antigen HBV core antibody HBV surface antibody HCV antibody EBV antibody CMV antibody HSV antibody VZV antibody HTLV antibody Monitoring (during): CMV monitoring PCR or prophylaxis EBV monitoring PCR BK monitoring PCR (Renal & BMT) Adenovirus monitoring PCR (Paediatric BMT) HSV prophylaxis if indicated

Answer 165

(increasing to decreasing risk) Allogeneic stem cell transplant Advanced HIV infection (CD4 dep) Solid organ transplant Various monoclonal antibody therapies Cytotoxic chemotherapy DMARDs and steroids

Answer 166

Stem cells: Before: conditioning regime (eg. total body irradiation or cyclophosphamide) Engraftment During: ongoing immunosuppression and graft vs host prophylaxis Solid organ: Before: induction immunosuppression During: maintenance immunosuppression

Answer 167

Viruses acquired from graft eg. HBV Viral reactivation from host eg. HSV Novel infection from infected individual eg. VZV

Answer 168

Therapeutically challenging Pre-emptive treatment Prophylaxis Increased doses Longer duration Combination therapy ↑ Opportunity antiviral resistance ↑ Toxicity of antivirals

Answer 169

Present differently Disseminated Different organs More severe Oncogenic Lack of immune mediated symptoms

Answer 170

Increased frequency Increased severity /risk of dissemination More organs can be involved (pneumonitis, eosophagitis, hepatitis); NB: not enceph! Increased risk of acyclovir resistance Management: HIV/AIDS CD4 <200 Prophylaxis: Test for HSV IgG Bone marrow - 1 month (until engraftment) Solid organ - 3-6 months - And if treated for rejection

Answer 171

Varicella: Pneumonitis Encephalitis Hepatitis Purpura fulminans in neonate Zoster (shingles): Multi-dermatomal / disseminated Often a late presenting immunosuppression

Answer 172

Prevention: Prophylaxis (prolonged if post-bone marrow) PEP Vaccination Treatment: Varicella Anti-viral for 7-10 days IV until no new lesions; PO until all crusted Zoster Anti-viral (IV if disseminated) + analgesia If Ramsay-Hunt: add steroids If HZO (ophthalmic): add topical steroids

Answer 173

Issues: Oncogenesis - B cell latency, high turn-over - T-cells monitor/control this B-cell lymphomas PTLD (post-transplant lympho-proliferative disorder Post-transplant lymphoproliferative disease (PTLD) : Latently infected B cells – polyclonal activation Predisposes to lymphoma Occurs in solid organ or allogenic haematopoietic cell transplants Related to the level of immunosuppression Suspicion on rising EBV viral load (> 105 c/ml) and CT scan Confirmation with biopsy of lymph nodes Management: Monitor EBV levels (proactive monitoring) Ix for lymphoma as needed Rx: ?Rituximab Rx: reduce immunosuppression (if possible)

Answer 174

HIV/AIDS: CD4 <50 - Ocular (retinitis) - Polyradiculopathy - Pneumonitis - GI tract SOT - Allograft disease (function of transplant organ reduced) - GI tract (i.e. renal) Histology: inclusion bodies Management: Prophylaxis (i.e. lung transplant) Pre-emptive treatment (i.e. renal transplant / HSCT) Treat if disease (HIV/AIDS) Rx: Ganciclovir / Valganciclovir (pro-drug) Rx: Reduce immunosuppression (if possible)

Answer 175

SOT: Donor + / Recipient – Immunosuppressed patient gets given some CMV for the first time (reactivation from donor) HSCT: Donor - / Recipient + Patient with CMV has immune system replaced with one that hasn’t seen CMV

Answer 176

HSCT: CMV viral load measured twice weekly, treat if virus reactivated until suppressed (pre-emptive therapy) SOT: valganciclovir prophylaxis for 100 days

Answer 177

Ganciclovir (IV): bone marrow suppression Valganciclovir: oral Foscarnet (IV) (nephrotoxicity) Cidofovir (nephrotoxicity) IVIg (with another drug for pneumonitis)

Answer 178

JC virus is a polyomavirus Progressive multifocal leukoencephalopathy Effective antiretroviral therapy has drastically reduced PML incidence in HIV+ve patient PML can be seen in other types of immunosuppressed - humanised monoclonal antibodies - Natalizumab (for treatment of multiple sclerosis)

Answer 179

Cognitive disturbance, personality change, motor deficits other focal neurological signs Demyelination of white matter → neurological deficits Diagnosis: MRI and PCR on CSF

Answer 180

Polyomavirus Double stranded DNA BK cystitis post SCT BK nephropathy post Renal Tx

Answer 181

Increased risk of complications (pneumonitis) and high mortality associated particularly with: Influenza A and B Parainfluenza 1, 2, 3 and 4 Respiratory Syncytial Virus (RSV) Adenovirus SARS-CoV-2 Influenza A and B → Oseltamivir (oral drug) for 5 days If resistance/severe/immunosuppressed → zanamivir (inhalation or IV) SARS-CoV-2 Paxlovid Rituximab

Answer 182

Hep A: more severe, vaccinate Hep B: re-activation, vaccinate/prophylaxis Hep C: ?increased fibrosis, Rx direct-acting antiviral Hep E: chronic infection, reduce immunosuppression

Answer 183

Two things can happen: 1. Carriers may have flare of disease. 2. Those who have had past infection can reactivate Reactivation ↑ B-cell depleting therapies (i.e Rituximab) - IL-6 inhibitor COVID also a risk Prevention: Nucleoside (lamivudine) nucleotide (tenofovir, entecavir) Prophylaxis HIV makes control more difficult

Answer 184

* Eukaryotic organisms - Possess chitinous cell walls, plasma membranes containing ergosterol, 80S RNA Can be divided into 2: * Yeasts – single celled, reproduce by budding – Candida – Cryptococcus – Histoplasma (dimorphic) * Moulds – multicellular hyphae, grow by branching and extension – Dermatophytes – Aspergillus – Agents of mucormycoses Dimorphic fungi: exist as moulds at lower temperatures and yeasts at higher temperatures Both positive on gram stain

Answer 185

* A yeast and the commonest fungal infection * > 150 Candida spp., but < 10 are human pathogens * Clinical manifestations – Acute, subacute, chronic, episodic – Superficial or systemic/invasive

Answer 186

* Oral thrush * Candida oesophagitis * Vulvovaginitis * Cutaneous – Localised or generalised very common treatment: * Topical – Oral thrush: nystatin – Vulvovaginitis: cotrimazole – Localised cutaneous: cotrimazole * Oral – Vulvovaginitis: fluconazole – Oesophagitis: fluconazole

Answer 187

RFs – Malignancies, esp haematological – Burns patients – Complicated post-op courses (eg Tx or GIT Sx) – Long lines Management * Look for source and signs of dissemination – Imaging – Serology for beta-D-glucan – ECHO – Fundoscopy * Antifungals for at least 2/52 (from date of first –ve BC) – Echinocandin (broad spec cover) eg anidulafungin (whilst a/w identification and susceptibilities) * BC every 48 hours * REMOVE ANY LINES/PROSTHETIC MATERIAL

Answer 188

* Candidaemia * CNS – Dissemination, trauma, Sx * Rx: Ambisome/voriconazole * Endocarditis – Abnormal valves/prosthetic valves, long lines, IVDU * Rx: Ambisome/voriconazole, Sx * Urinary tract – Vulvovaginits, catheters * Rx: Fluconazole * Bone and joint – Dissemination. Trauma * Rx: Ambisome/voriconazle, Sx * Intra-abdominal – Peritoneal dialysis, Sx, perforation * Rx: Echinocandin/Fluconazole

Answer 189

* Encapsulated yeast – Serotypes A&D = C neoformans (immunodeficient) – Serotypes B&C = C gattii (immunocompetent) * Transmission by inhalation of aerosolised organisms * Chronic, subacute to acute pulmonary, meningitic or systemic disease associated with pigeons

Answer 190

* Impaired T-cell immunity – E.g patients with HIV, who have reduced CD4 helper T-cell numbers (typically less than 200/ml) * Patients taking T-cell immunosuppressants for solid organ transplant also have a 6% lifetime risk

Answer 191

* Causes a meningitis in apparently immunocompetent individuals in tropical latitudes, esp. SE Asia and Australia * Outbreak in Vancouver Island 2004 * High incidence of space-occupying lesions in brain and lung * Increased resistance to amphotericin B clinically

Answer 192

* Typical clinical history/features – Immunosuppressed host * Imaging * India ink staining of CSF * Serum/CSF cryptococcal Ag (CRAG) * Can culture from blood/body fluids

Answer 193

* Induction: – Amphotericin B + flucytosine (at least 2/52) * Consolidation: – High dose fluconazole (at least 8/52) * Maintenance: – Low dose fluconazole (at least 1 year) * Repeat LP for pressure management * Pulmonary disease: – If mild, fluconazole alone

Answer 194

* A mould with worldwide distribution * Causes a spectrum of disease in helath and immunocompromised patients – Mycotoxicosis - ingestion of contaminated foods – Allergy and sequelae - presence of conidia/transient growth of the organism in body orifices – Colonization - in preformed cavities and debilitated tissues – invasive, inflammatory, granulomatous, necrotizing disease of lungs, and other organs – systemic and fatal disseminated disease * type of disease and severity depends upon the physiologic state of the host and the species

Answer 195

Dx * Imaging * Sputum/BAL – MC&S, Ag testing * Aspergillus Abs (precipitans) * Galactomannan (surface antigens) * Bx – histology, MC&S Mx * Voriconazole * Ambisome * Duration based on host/radiological/mycological factors – At least 6/52 Complications: - aspergillomas - invasive fungal disease

Answer 196

* Ubiquitous in the environment and distributed worldwide * Lacks ergosterol in it’s cell wall * Acquisition by airborne route – Pneumonia – Extrapulmonary disease = rare * RFs – Immunodeficiency – Immunosuppressive drugs – Debilitated infants – Severe protein malnutrition

Answer 197

* Dx – Microscopy – PCR – Beta-D-glucan * Mx – High dose cotrimoxazole 2-3/52 – Alternatives: atovaquone, clindamycin + primaquine – Steroids if hypoxia present

Answer 198

* Clinical syndrome caused by a number of fungal species belonging to the order Mucorales eg Rhizopus, Rhizomucor, Mucor * Inoculation via inhalation of spores or primary cutaneous inoculation * Favours immunosuppressed/diabetic patients Clinical features * Rhinocerebral => CNS – Cellulitis of the orbit and face progress with discharge of black pus from the palate and nose. – Retro-orbital extension produces proptosis, chemosis, ophthalmoplegias and blindness. – As the brain is involved, there are decreasing levels of consciousness. * Pulmonary * Cutaneous

Answer 199

* Dx – Isolation from tissue Bx * Mx – Ambisome/Posaconazole – Sx – Rx guided by response

Answer 200

* A group of fungi capable of ivading dead keratin of skin, hair and nails * Classified by site infected e.g tinea capitis * Spread via contact with desquamated skin scales * RFs – Moisture – Deficiencies in cell mediated immunity – Genetic predisposition tinea pedis: foot tinea capitis: scalp tinea cruris: groin tinea corporis: abdomen

Answer 201

* Dx – Skin scrapings, nail specimens and plucked hairs - MC&S * Mx – Topical eg clotrimazole, ketoconazole – Oral eg griseofulvin, terbinafine, itraconazole

Answer 202

Azoles: abnormal LFTs Polyenes: nephrotoxicity Echinocandins: relatively innocuous Pyrimidine analogues: blood disorders

Answer 203

Cell membrane: Fungi use principally ergosterol instead of cholesterol Cell Wall: Unlike mammalian cells, fungi have a cell wall DNA Synthesis: Some compounds may be selectively activated by fungi, arresting DNA synthesis

Answer 204

* Polyene antibiotics - Amphotericin B, lipid formulations - Nystatin (topical) * Azole antifungals - Ketoconazole - Itraconazole - Fluconazole - Voriconazole - Miconazole, clotrimazole (and other topicals)

Answer 205

* In fungi, the cytochrome P450-enzyme lanosterol 14-a demethylase is responsible for the conversion of lanosterol to ergosterol * Azoles bind to lanosterol 14a-demethylase inhibiting the production of ergosterol – Some cross-reactivity is seen with mammalian cytochrome p450 enzymes * Drug Interactions * Impairment of steroidneogenesis (ketoconazole, itraconazole)

Answer 206

* Polyene antibiotic * Fermentation product of Streptomyces nodusus * Binds sterols in fungal cell membrane * Creates transmembrane channel and electrolyte leakage * Active against most fungi except Aspergillus terreus, Scedosporium spp. Nephrotoxicity * Most significant delayed toxicity * Renovascular and tubular mechanisms – Vascular-decrease in renal blood flow leading to drop in GFR, azotemia – Tubular-distal tubular ischemia, wasting of potassium, sodium, and magnesium * Enhanced in patients who are volume depleted or who are on concomitant nephrotoxic agents * Less toxic preparations: 1) Liposomal amphotericin B 2) Amphotericin B colloidal dispersion 3) Amphotericin B lipid complex

Answer 207

* Echinocandins -Caspofungin acetate (Cancidas)

Answer 208

* Cyclic lipopeptide antibiotics that interfere with fungal cell wall synthesis by inhibition of ß-(1,3) D-glucan synthase * Loss of cell wall glucan results in osmotic fragility * Spectrum: – Candida species including non-albicans isolates resistant to fluconazole – Aspergillus spp. but not activity against other moulds (Fusarium, Zygomycosis) – No coverage of Cryptococcus neoformans

Answer 209

* Pyrimidine analogues - Flucytosine

Answer 210

* Restricted spectrum of activity * Acquired Resistance – result of monotherapy – rapid onset * Due to: – Decreased uptake (permease activity) – Altered 5-FC metabolism (cytosine deaminase or UMP pyrophosphorylase activity) Uses and side effects * Limited – Candida and cryptococcosis * In combination with Ambisome/fluconazole * Ses – Infrequent – include D&V, alterations in liver function tests and blood disorders. * Blood concentrations need monitoring when used in conjunction with Amphotericin B

Answer 211

Influenza SARS-CoV-2 Nipah West Nile virus Dengue Zika

Answer 212

No fever and no white blood cells in stool --> secretory diarrhoea (cholera, E coli) Fever and white blood cells in stool sample (neutrophils) --> inflammatory diarrhoea (campylobacter, shigella, salmonella) Fever and mononuclear cells in stool sample --> enteric fever (typhoidal salmonella, yersinia, brucells)

Answer 213

Campylobacter: 1-10 days incubation, duration 2-20 days, poultry E coli 0157: 1-5 days incubation, 1-4 days duration Shigella, Salmonella, Vibro 2-3 days incubation period Staph aureus 2-6 hours incubation period

Answer 214

superantigen binding directly to T-cell receptors and MHC molecules (outside peptide binding site) causes massive cytokine release (systemic toxicity)

Answer 215

excess inflammatory response and bacteraemia can be managed in immunocompetent but immune suppressed will have enteric picture

Answer 216

spread by skin lesions on food handlers catalase and coagulase positive produces enterotoxin, causes prominent vomiting and watery (non-bloody) diarrhoea self-limiting

Answer 217

reheated rice gram positive rod-spores has heat stable emetic toxin (not destroyed by reheating) heat labile diarrhoeal toxin (food not cooked to high enough temp) watery, non-bloody diarrhoea self-limiting rare cause of bacteraemia in vulnerable population can cause cerebral abscesses

Answer 218

gram-positive anaerobe C. botulinum: botulism source in canned or vacuum-packed food (honey in infants) ingestion of preformed toxin (inactivated by cooking) blocks ACh release from peripheral nerve synapses (present with paralysis) treatment: antitoxin C. pefringens: food poisoning Source: reheated food (meat) normal flora of colon but not small bowel is where enterotoxin acts (superantigen) Incubation: 8-16 hours watery diarrhoea, cramps, little vomiting lasting 24 hrs C difficile: pseudomembranous colitis HAI children and >65s carry it in gut so don't commonly test for it in these groups antibiotic related colitis (any but mainly cephalosporins, cipro, clindamycin etc.) Infection control Mx: PO metronidazole, vancomycin (stop Abx where possible)

Answer 219

outbreaks of febrile gastroenteritis beta-haemolytic, aesculin positive with tumbling motility Source: refrigerated food, unpasteurised dairy, vegetables grows at 4 degrees Watery diarrhoea, cramps, headache, fever, little vomiting perinatal infection (can cause miscarriage), immunocompromised patient Mx: ampicillin

Answer 220

facultative anaerobes, glucose/lactose fermenters, oxidase negative E. coli: traveller's diarrhoea source: food/water contaminated with human faeces Enterotoxins: - heat labile stimulate adenyl cyclase and cAMP - heat stable stimulates guanylate cyclase - act on the jejunum and ileum, not colon

Answer 221

ETEC: toxigenic, main cause of traveller's diarrhoea EPEC: pathogenic, infantile diarrhoea EIEC: invasive, dysentery EHEC: haemorrhagic, 0157:H7 EHEC: shiga-like verocytotoxin causes HUS (avoid antibiotics - could exacerbate)

Answer 222

non-lactose fermenters H2S producers TSI agar and XLD agar, selenite F broth Antigens: - cell wall O (groups A-I) - flagellar H - capsular Vi (virulence, antiphagocytic) 3 species: - S. typhi (and paratyphi) - S. enteritidis - S. cholerasuis Sources: poultry and meat, pets (reptiles)

Answer 223

Enterocolitis transmitted from poultry, eggs, meat invasion of epi- and sub-epithelial tissue of small and large bowel fever and bacteraemia infrequent self-limited non-bloody diarrhoea usually no treatment stool positivity

Answer 224

Typhoid (enteric) fever) transmitted only by humans multiples in Payer's patches spreads via endoreticular system (ERS) --> bacteraemia (sickle cell and prosthetic materials increase risk) slow onset, fever and constipation, splenomegaly, rose spots anaemia and leucopenia bradycardia, haemorrhage, perforation blood culture positive Mx: ceftriaxone

Answer 225

non-lactose fermenters non H2S producers non motile Antigens: - cell wall O antigens - polysaccharide (groups A-D): S. sonnei, S. dysenteriae, S. flexneri (MSM) most effective enteric pathogen (low ID 50) no animal reservoir no carrier state Dysentery: invading cells of mucosa of distal ileum and colon, producting enterotoxin (shiga) usually self-limiting avoid Abx (ciprofloxacin if required)

Answer 226

curved, comma shaped, late lactose fermenters, oxidase positive Vibrio cholerae Vibrio parahaemolyticus Vibrio vulnificus

Answer 227

- O1 group: epidemics - Non O1 group: sporadic or non pathogens - transmitted by contamination of water and food from human feaces - colonisation of small bowel and secretion of enterotoxin with A and B subunit, causing persistent stimulation of adenylate cyclase causes massive diarrhoea (rice water stool) without inflammatory cells treat the losses (fluid resus)

Answer 228

ingestion of raw or undercooked seafood major cause of diarrhoea in Japan or when cruising in Carribean self-limiting: 3 days grows in salty 8.5% NaCl treat with doxycycline

Answer 229

cellulitis in shellfish handlers fatal septicaemia with D+V in HIV patients treat with doxycycline

Answer 230

curved, comma or S shaped Microaerophilic C. jejuni at 42 degrees oxidase positive, motile self-limiting but symptom can last for weeks (20 days) only treat if immunocompromised (macrolides) transmitted via contaminated food and water with animal faeces (poultry, meat, unpasteurised milk) Enterotoxin --> watery diarrhoea Invasion --> bacteraemia watery, foul-smelling diarrhoea, bloody stool, fever and severe abdo pain treat with erythromycin or cipro if in first 4-5 days (otherwise self-limiting) can cause guillan-barre, reactive arthritis and Reiter's

Answer 231

non-lactose fermenter, prefers 4 degrees transmitted via contaminated food with domestic animals excreta (farms) enterocolitis or mesenteric adenitis associated with reactive arthritis and Reiter's

Answer 232

(tuberculosis, avium, intracellulare) will appear as gram variable always think of TB

Answer 233

(protozoa) motile trophozoite in diarrhoea non-motile cyst in non-diarrhoeal illness killed by boiling, removed by water filters 4 nuclei no animal reservoir ingestion of cysts --> trophos in ileum --> colonise caecum, colon --> flask-shaped ulcer dysentery, flatulence, tenesmus chronic: weight loss +/- diarrhoea liver abscess Diagnosis: stool micro (wet mount, iodine and trichrome) serology in invasive disease Mx: metronidazole and paromomycin in luminal disease

Answer 234

(protozoa) trophozoite pear-shaped 2 nuclei 4 flagellas and a suction disk (attachment) ingestion of cyst from faecally contaminated water and food excystation at duodenum tropho attaches no invasion malabsorption of protein and fat travellers, hikers, day care, mental hospitals, MSM foul smelling, non-bloody diarrhoea cramps, flatulence, no fever Diagnosis: stool micro, ELISA, string test Mx: metronidazole

Answer 235

(protozoa) infects the jejunum severe diarrhoea in immunocompromised oocysts seen in stool by modified Kinyoun acid fast stain Mx: reconstitution of immune system (self-limiting)

Answer 236

outbreaks low infectious dose (18-1000 viral particles) environmental resilience (0-60 degrees) no long-term immunity GII.4 currently predominant strain

Answer 237

dsRNA wheel-like virus replicates in mucosa of small intestine secretory diarrhoea, no inflammation can get watery diarrhoea by stimulation of enteric nervous system by age 6, most children have antibodies to at least one type exposure twice confers lifelong immunity

Answer 238

Types 40 and 42 cause non-bloody diarrhoea (<2yrs of age) any type in immunocompromised diagnosis: stool EM, antigen detection, PCR

Answer 239

polio entero hepatitis A

Answer 240

Cholera: inactivated whole cell or live attenuated (if travelling to endemic area) Campylobacter: military, infants, travellers ETEC: inactivated and live vaccines in trials Salmonella typhi: Vi capsular PS (IM) and live (PO) Rotavirus: 3 types, age 6-12 weeks NB: all gastroenteritis is notifiable

Answer 241

Protein-only infectious agent Rapidly infect existing prions in cells and cause them to switch to abnormal isoforms which triggers neurodegeneration Rare transmissable spongiform encephalopathies in humans + animals Rapid neuro-degeneration (max survival from first symptom to death is 6 months) Currently untreatable

Answer 242

normal prion protein gene on chromosome 20 - thought to be involved in copper metabolism and binding Codon 129 polymorphism: MM, MV, VV (MM predisposes to prion disease)

Answer 243

PrP: Alpha-helical configuration Protease sensitive PrPsc: Beta-sheet configuration Protease/radiation resistant (abnormal isoform)

Answer 244

Seed of PrPSc acts as a template which promotes irreversible conversion of PrP to insoluble PrPSc ie. conformational change in PrP The trigger for this process remains unclear in sporadic cases

Answer 245

Sporadic Creutzfeldt-Jakob Disease (80%) Acquired (<5%): - Kuru (cannibalism) - variant CJD (mad cow epidemic, young people) - iatrogenic CJD: *GH *Blood *Surgery Genetic (15%): - PRNP mutations eg. Gerstmann-Straussler-Sheinker syndrome Familial Fatal Insomnia

Answer 246

Rapid dementia with: - myoclonus - cortical blindness - akinetic mutism - LMN signs (anterior horn cells --> signs consistent with MND) Mean age onset 65 yrs (range 45-75 yrs) Incidence 1/million/year Death within 6/12 Cause uncertain ? somatic PRNP mutation ? spontaneous conversion of PrPc to PrPsc ?? Environmental exposure to prions

Answer 247

EEG (electroencephalography) - periodic, triphasic complexes (non-specific: can also be caused by hepatic encephalopathy and lithium use but would be able to rule this out using history and blood tests) - 2/3 abnormal MRI - basal ganglia – increased signal - cortical/striatal signal change on DWI MRI CSF  14-3-3 protein, S100 Neurogenetics to r/o genetic cause Tonsillar biopsy NOT useful Brain biopsy (cannot reuse equipment): spongiform vacuolation(water) (basal ganglia and cortical structures), amyloid plaques Autopsy – by experienced pathologist

Answer 248

Younger age of onset (median age 26 yrs) Median survival time 14 months Psychiatric onset: - dysphoria, anxiety, paranoia, hallucinations Then neurological: - peripheral sensory symptoms - ataxia - myoclonus - chorea - dementia First appeared during BSE (mad cow disease) epidemic due to poor practices in food chain

Answer 249

MRI brain - positive pulvinar sign (high signal in posterior thalamus aka putamen) EEG – non-specific slow waves CSF – 14.3.3, S100 not useful (usually normal) Neurogenetics (almost 100% are MM at codon 129 so far) Tonsil biopsy 100% sensitive and specific (prions find way into lymphoid tissue) (Brain biopsy) - no need if tonsil biopsy positive Autopsy PrPSc type 4t detectable in CNS + most lympo-reticular tissues

Answer 250

100% sensitivity and specificity for vCJD Early clinical diagnosis Eliminates need for further investigation (e.g. brain biopsy to exclude other treatable causes) Important for therapeutic trials and early treatment May be positive during incubation period before clinical onset (sheep scrapie, mouse models) Histology: florid plaques and areas of vacuolation

Answer 251

Human cadaveric growth hormone (in past) Corneal transplants Neurosurgical procedures eg. dural grafts, pre-1991 Blood transfusions, other blood products Other surgical procedures ? appendicectomy and tonsillectomy in vCJD

Answer 252

Progressive ataxia initially Dementia and myoclonus later stages Speed of progression depends on route of inoculation (CNS inoculation fastest)

Answer 253

3 Aspects: - Codon 129 polymorphism Methionine – Methionine (MM) Methionine – Valine (MV) Valine – Valine (VV) - Specific PRNP mutations (~30 so far) - Consider other neuro-genetic conditions eg. Huntington’s, spinocerebellar ataxia prion protein mutations are all autosomal dominant

Answer 254

(GSS, FFI, CJD) F.H. crucial: Dementia “MS” Ataxia Psychiatric EEG – non-specific MRI – basal ganglia: sometimes high signal Neurogenetics crucial If negative: SCA / Huntington’s Autopsy

Answer 255

Slowly progressive ataxia Diminished reflexes Dementia Onset age 30-70 years Survival 2-10 years PRNP P102L, but several other mutations

Answer 256

Untreatable insomnia Dysautonomia Ataxia (thalamic degeneration) PRNP D178N +/-pyramidal/extrapyramidal signs late cognitive decline

Answer 257

(Papua New Guinea) Foré tribes – Papua New Guinea highlands Epidemic 1950’s / 1960’s - Women - Children Last endo-cannibalistic feast 1957 Longest incubation: up to 45 years No MM’s left Progressive cerebellar syndrome: - death within 2 years Dementia late or absent

Answer 258

Symptomatic: clonazepam – myoclonus (valproate, levetiracetam, piracetam) Delaying prion conversion: quinacrine pentosan (intra-ventricular administration) tetracycline Anti-prion antibody (prevents peripheral prion replication and blocks progression to disease in infected mice but does not get into CNS) Depletion of neuronal cellular prion protein (prevents onset of disease in mice and blocks neuronal cell loss + reverses early spongiosis)