Microbiology Med Ed

1. Microbiology Med Ed By Dr. Stuart Taylor Infectious Diseases AFP

2. introduction • When I went to a few MedEd lectures back in 5th year, I thought people tried to cover too much in too short a time. • I will focus on certain topics which are harder to understand, rather than trying to cover everything in no depth at all. • Failing that, we will try and cover interesting topics and hope to inspire you to do ID/microbiology in the future.

3. Updates from last year • More SBAs/EMQs! • Candida auris • Less niche stuff

4. Lecture Overview • Fungal Infections • Antifungals • PUO • Fever in the Returning Traveller • Herpes infections • Zoonoses • Viral Hepatitis

5. INTRODUCTION TO MYCOLOGY • A fungus is any member of the group of eukaryotic organisms that includes unicellular microorganisms such as yeasts and molds • Most fungi grow as hyphae, which are cylindrical, thread-like structures 2–10 µm in diameter and up to several centimeters in length. A fungi that grows like this is called a mould. • Organisms that grow as single cells are yeasts • Have a chitin and glucan containingcell wall!

6. Who are the Big Names on culture?

7. Candida - yeast • The main organism responsible for infection is Candida albicans • Candida can cause opportunistic infections (mucosa – thrush, hair, nails) but also disseminated disease e.g. candidiasis in immunocompromised hosts. • Dx: swabs, blood cultures, PAS staining. • Rx: oral candidiasis nystatin 100,000 units QDS or oral fluconazole • Rx: Organ disease: At least 2 weeks of antifungals. Fluconazole for C. albicans. Echinicandin (caspofungin) for non-albicans candida. Ambisome, Fluconazole or Viroconazole for organ-based disease

8. Candida auris • Emerging HAI associated with invasive infections in patients with immunocompromise or indwelling lines. • Often multidrug resistant • Has been associated with outbreaks on 5 continents • Difficult to identify with standard laboratory measures

9. Cryptococcosis - yeast • Main agent: cryptococcusneoformans • Can cause acute->chronic pulmonary, systemic or meningitic disease. • Large cause of death in immunocompromised patients e.g. HIV or those with T-cell dysfunction (think transplant drugs) • Dx: India ink staining of CSF or cryptococcal antigen in blood. Can be cultured • Rx: 3/52 Amphotericin B +/- flucytosine. Repeat LP for pressure management. Secondary suppression with fluconazole

11. Cryptococcus gattii growing on water agar from Eucalyptus leaves

12. Aspergillosis - mold • Many diseases/disease states associated with aspergillus infections. • Presentations: Allergic BronchopulmonaryAspergillosis (ABPA), aspergilloma (fungal ball within old lung cavity), sinusitis, systemic infections. • Rarely aspergillusflavus -> aflatoxin A1 -> liver/biliary cancer. • Dx: culture, methenamine silver staining of tissue, serology. • Rx: voriconazole, amphotericin B, caspofungin. ABPA can be rx with steroids and itraconazole. • A. fumigatus is intrinsically resistant to fluconazole.

14. mannoproteins b1,3 b1,6 glucans Cell membrane b1,3 glucan synthase chitin ergosterol The Fungal Cell Wall

16. EMQ 1 • Some of these are relatively tricky. MRCP level! So smash it out!

17. A: Invasive candidiasis B: Mucosal candidiasis C: Cryptococcosis D: Tuberculosis E: Histioplasmosis F: Invasive aspergillosis G: Allergic bronchopulmonary aspergillosis H: Pneumocystis jirovecii I: Sarcoidosis J: Neisseria meningitidis 1. 30yr old man presents with male partner to Brighton A+E complaining of 2 day Hx of drowsiness, confusion and headache. Examination reveals cachexia, widespread lymphadenopathy and photophobia with meningitis. CSF analysis reveals lymphocytosis and low glucose. 2. 50 yr old diabetic man who has had recent course of antibiotic complains of difficulty swallowing and change in taste. Examination reveals white exudate on tongue. 3. 72yr old lady with panhypogammaglobulinaemia presents with increased oxygen requirement on background of recent treatment for PCP. CXR shows rapidly enlarging masses in R + L lung with positive galactomannan. 4. 50yr old Pennsylvanian man presents 5 days after a recent hiking trip with increased breathlessness and tender nodules on his legs. CXR shows nodular opacities. He makes a full recovery with no targeted intervention.

18. Pyrexia of unknown origin • Definition: Fever higher than 38.3C on several occasions, persisting without diagnosis for at least 3 weeksin spite of at least 1 weeks investigation in hospital (1961) • Aetiology • Infection - 27% - if someone is spiking persistent fevers think about an abscess and find it! • Neoplasm - 13% • Connective tissue - 17% vasculitis, lupus etc. • Undiagnosed - 23% • Miscellaneous - 21%

19. PUO- History • Travel? Where did they go? For how long? When did they get back? • Animal exposure? Brucellosis (milk), rabies, cats (toxoplasmosis) • Food exposure? Salmonella, E. coli, Hep A+E. • Sex? HIV, syphilis, shigella, Hep B and C • Recreational activities: watersports (leptospirosis or schistosomiasis), lyme disease • Unwell contacts: viruses, TB etc.

20. PUO- examination • Skin and nails – splinter haemorrhages, ulcers (TB, sarcoid, leprosy), rashes! • Fundi – Roth spots • Heart- murmurs of IE • Abdomen- HSP (leishmania and lymphoma) • Lymph nodes? Lymphoma or TB • Back – spinal abscess/discitis can be hard to pick up

21. Investigations • Urine dip: may indicate endocarditis or glomerulonephritis from AI disease e.g. lupus. Consider urinary legionella antigen. Urinary bence Jones for myeloma. • Bloods: FBC (anaemia with AI disease or HUS), high WCC (infection/lymphoma), high eosinophils (parasitic infection), U+Es (could indicate HUS if bad), LFTs (hepatitis/AI disease), ESR (raised in AI disease). At least 3x blood cultures and swab anything that looks funky. HIV test.Thick and thin films for malaria if ANY doubt. Auto-antibodies: anti-dsDNA, Ro, La, Sm, ENA, RF. • Imaging: CXR could show up Ca, hilar lymphadenopathy, TB, atypical pneumonia e.g. mycoplasma, legionella or fibrosis with AI disease. If on surgical firm and you are impatient CTAP to look for intrabdominal source/collection. If on medicine and you have ran out of ideas: CT CAP looking for Cancer or any incidentaloma.

22. Infective endocarditis • Infection of heart valves typically by bacteria. • Acute endocarditis: pathogenic bacteria affecting normal valves. • Subacute endocarditis: opportunistic bacteria affecting damaged valves. • Risk factors: • Acute: injecting Staph into your bloodstream (IVDU), dialysis lines. • Subacute: rheumatic fever when child, poor dentition, replaced valve • Symptoms: fevers, chills, weakness, dyspnoea • Signs: fever, murmur, embolic lesions, splenomegaly, haematuria, clubbing

24. IE continued • IVDU: often affects tricuspid valve (as venous system will drain here first). Often caused by Staph aureus. • Non-IVDU: Viridans strep, enterococci and staph aureus are top 3 causes. Coag negative staph can cause infections in prosthetic valve endocarditis (can form biofims).

25. Duke Criteria for endocarditis • Dx can be made with two major, one major and 3 minor or 5 minor criteria. • Major: • Positive blood culture: typical organism or persistently positive culture • Evidence of endocardial involvement: mass on valve, abscess, new regurgitation • Minor • Predisposing heart condition • Fever >38 • Vascular phenomenon: arterial emboli, septic infarcts • Immunological phenomena: glomerulonephritis, oslers nodes, janewaylesiuons • Microbiological evidence: +ve culture not meeting major criteria • Echo findings not meeting major criteria.

26. Treatment of IE • Medical: • Likely will need PICC line for extended IV abx. • Strep viridans: benzylpen and gentamicin • Staph aureus: fluclox for 4-6 weeks. • MRSA: vanc and gentamicin. • Surgical • May require if significant valve dysfunction, lack of response or serious sequelae. • What on an ECG might indicate aortic root abscess development?

27. Fever in the returning traveller

28. Incubation periods • Long >3 weeks • Hepatitis, HIV • Typhoid, TB • Malaria, schistosoma, amoebic liver abscess, filaria • Medium 10-21 days • Malaria, enteric fever, rickettsia, brucella, leptospirosis, VHF if endemic area • Short <10 days • Enteric fever, dengue, chikungunya, influenza, typhus, VHF, malaria also

29. Malaria • Caused by parasitic infections transmitted by anopheles mosquitos • 5 types: • P. falciparum: can cause severe malaria, • P. ovale • P. vivax • P. malariae • P. knowelsi: found in Malaysian Borneo, has a short life cycle so can be rapidly fatal. • Predominantly found in Africa but also found in SE Asia and South America.

31. Clinical features • May be minimal symptoms • 7 days to 3 months post exposure. • Fevers, myalgia, headache, shivers/rigors, GI tract problems. Haemolytic anaemia -> jaundice. • Diagnose with thick and thin films (thick for detection, thin for species identification) • Antigen test and PCR may also be used.

32. Falciparum and severity • Mild • Parasitaemia <2%, no schizonts • Temp <39°C • No complications • Severe • Parasitaemia >2%, or schizonts on film • Non-ambulant • Complications: shock, renal failure, ARDS -> pulmonary oedema, severe anaemia (Hb < 80 g / L), DIC, hypoglycaemia, coma, convulsions (cerebral malaria), acidosis (pH < 7.3)

33. Treatment of malaria • Nowadays IV artesunate is used for severe falciparum. • Milder cases of falciparum can be treated with Riamet (artemether and lumefantrin) for 3 days. • NB quinine which was classically used is arrhthymogenic and causes hypoglycaemia. • Non-falciparum malaria can be treated with chloroquine and primaquine (to eradicate hypnozoites in the liver) • Need to do G6PD test before giving primaquine.

34. S. typhi • Infection is called typhoid or enteric fever • Prevalent in South East Asia. • Invades regional lymphatics and multiplies in Payer’s patches • Phagocytosed by monocytes but can survive intracellularly. • Spreads via endothelial-reticular system – will come back to this!

35. S+S of typhoid • Slow onset – 7-14 days after exposure • Fever • Abdo pain and constipation • Splenomegaly • Rose spots • Leucopaenia • Bradycardia • Intestinal perforation.

37. Complications of typhoid • Chronic infection: cholecystectomy may help • Sepsis • Osteomyelitis, again think Sickle Cell – encapsulated. • Endocarditis + mycotic aneurysm formation. • NB: treat with ceftriaxone + gentamicin if shocked.

38. Dengue • Arboviral infection transmitted by Aedes mosquitoes. • As opposed to malaria mosquitoes bite in day and in urban areas. • Clinical features: • Myalgia, breakbone fever, retro-orbital pain • Sunburn like rash. • Develop 4-7 days post exposure

39. Complications include: • Leucopenia, thrombocytopenia • Haemorrhage • Plasma leakage • Organ impairment e.g. impaired liver function or reduced consciousness.

40. Dengue haemorrhagic fever • Usually occurs after 2nd infection with different serotype. • Previously generated antibodies make the infection worse and can lead to dengue haemorrhagic fever. • Diagnosis can be difficult as there is crossover of IgG between other flaviviruses e.g. yellow fever, Japanese encephalitis. • Treatment is with supportive care.

41. EMQ 2!

42. A: Plasmodium vivax B: Plasmodium falciparum C: Coag negative Staph D: Dengue E: E. coli F: Salmonella typhi G: Acute lymphoma H: Staph aureus I: Yellow fever J: G6PDD • 35yr old man complains of fever and rigors one week after returning from India. He mentions that he had one episode of diarrhoea while there. Examination reveals HR 56 but nil else specific. Bloods show WBC 3. You are rang by the microbiology registrar two days into admission with G- rods in his blood cultures. They advise swapping antibiotics from Co-amoxiclav to a cephalosporin. • A 23yr old injecting drug user is admitted with fever and feeling generally unwell. Examination shows prominent JVP waveforms and a PSM over L. sternal edge. He self-discharges before further investigation. Blood cultures reveal Gram positive cocci in clusters. • A 35yr Italian businessman who was recently treated for P. Vivax represents with jaundice and SOB. Bloods show Hb 60, MCV 110, unconjugated bilirubin 90 and raised LDH. • A 45yr old lady presents comatose on a b/g of 3 days of fever after returning from Africa. She took malaria prophylaxis. VBG shows glucose 2.8 and metabolic acidosis. Formal bloods reveal AKI and low platelets. Urine dip is +++ for blood.

44. HERPES INFECTIONS • Herpesviridae is a family of viruses that contains many important disease causing viruses

45. HSV 1 + 2 • DNA viruses that multiply in mucosal surfaces producing vesicles or ulcers. • Latent infection occurs when the virus enters the sensory ganglion and can reactivate and replicate. • Primary infection: sensory nerve tingling, vesicles then shallow ulcers. Occasionally fever, malaise, lymphadenopathy. Heals in 8-12 days.

46. Anatomy of infection

47. Herpes encephalitis • Encephalitis presents as fever, headache, confusion, drowsiness +/- seizures. • Predominantly caused by HSV I • Diagnosis by LP and viral PCR of CSF • Rx: IV aciclovir • 70% mortality in untreated disease

48. Varicella zoster virus • Respiratory droplet transmission, incubation period of 14-21 days. • Infections are more severe/dangerous in adults! • Chickenpox: • Prodrome of 1-2 days then fever, malaise, rash. • Rash development: pruritic, erythematous macules -> vesicles then crust in 48 hours. • Infectious 1-2 days pre and up to 5 days post rash (scabbed) • Shingles • Painful, hypersensitive area then macular -> vesicular rash in dermatomal distribution.

49. Rare complications of VZV • Chickenpox • Pneumonitis, • Encephalitis, • Transverse myelitis, • Pericarditis • Shingles • Ramsay hunt syndrome • Post-herpetic neuralgia

50. Treatment/prevention of infection • Can give oral aciclovir/valaciclovir for VZV infection in adults. • IV aciclovir if disseminated disease or pregnant. • Vaccine for VZV is given at 70 to prevent reactivation of shingles. • VZV Ig is given to non-immune pregnant/immunocompromised patients if they come into contact with the infection.