Opportunistic Infections

Question 1

Definition: what patients?, opportunistic vs non-opportunistic

Answer 1

Infections that occur in patients with weakened immune system
- opportunistic = micro-organisms that are usually harmless and may exist as commensals could lead to potentially lethal consequences

• non-opportunistic = normal pathogens with atypical presentations (occur more often and with higher severity)
  e. g. TB: extra pulmonary manifestations
  e. g. Syphilis: multiple primary chancres and rapid progression to secondary syphilis

Question 2

Causes of Immunosuppression (5)

Answer 2

Congenital
- primary immunodeficiency e.g. SCID, CGD, Autoantibody against IFN-gamma

Acquired

• infections e.g. HIV
• transplants (disease and immunosuppressive therapy)
• medications e.g. glucocorticoids, cyclosporine, methotrexate, azathioprine, biologics
• splenectomy (surgical or functional)

Question 3

**Immune component defect and related infections (5)

Answer 3

Neutropenia (defective phagocytes)

• pyogenic organisms e.g. gram +ve cocci and gram -ve bacilli
• abscess with granuloma, deep seated infections
• test: neutrophils, nitroblue tetrazolium test

Impaired cellular immunity (T cells)

• virus e.g. HSV, CMV, HPV, BK
• fungi e.g. PCP, aspergillus, cryptococci
• parasites e.g. toxoplasma
• bacteria e.g. MTB, nocardia, listeria
• test: lymphocytes, T cell subsets

Impaired humoral immunity (B cells)

• sinupulmonary infections
• serious and fatal infections e.g. severe CMV, PML, reactivation of HBV
• also encapsulated bacteria?
• test: total Ig, Ig subclass

Splenectomy
- encapsulated bacteria e.g. s. pneumoniae, h. influenza, n. meningitides

(Complements - bacterial infection and neisseria; test total complements)

Question 4

HIV recap: natural clinical course, diagnostic algorithm, criteria for AIDS, principals of treatment

Answer 4

enveloped +ssRNA
HIV-1 (majority) and HIV-2

Natural history of HIV and AIDS

• acute infection similar to IM syndrome with fever, LN and sorethroat (difficult to differentiate from CMV, EBV, viral flu-like)
• CD4 T cells prone to infection by HIV –> continuously decrease in number and function (correlate with viral load increase)
• dendritic cells and macrophages as reservoirs of virus

Diagnostic algorithm
- 4th gen ELISA for HIV-1/2 –> if +ve, HIV-1/2 antibody differentiation immunoassay –> if indeterminate or -ve, HIV RNA

Criteria for AIDS
- lab confirmed HIV
AND
- CD4 <200 cells/microL or CD4 <14%
OR
- AIDS defining conditions

Principles for starting anti-retroviral treatment

• start Tx for all patients regardless of CD4 count
• check HIV genotype resistance test before starting
• 2 NRTI + 1 NNRTI/PI/INSTI
• influenced by resistance pattern, pregnancy, co-morbidity e.g. dysplipidaemia, co-infection e.g. HBV

Question 5

**Opportunistic infections in HIV: CD4 200-350

Answer 5

Common pathogens occur more frequently (need prophylaxis and screening like in elderly healthy patients)

Bacteria:

• S. pneumonia –> PCV13 and PPV23 vaccine
• Syphilis –> syphilis serology –> +ve, give benzathine pen G

MTB:

• check for latent TB –> treat if +ve, isoniazid 300mg 9/12
• pulmonary TB

Virus:

• HBV –> anti-HBs –> HBV vaccine if -ve
• HAV –> check IgG –> HAV vaccine if -ve
• Influenza A and B –> vaccination
• HPV (13-26 yrs old?) –> full 9-valent vaccine

Question 6

**Opportunistic infections in HIV: CD4 100-200

Answer 6

Increased risk of more serious infections e.g. PCP (most common) and oesophageal candidiasis

Fungi:

• candida
• pneumocystis jirovecii (PCP) –> Septrin DS prophylaxis or treatment

Virus:
- VZV/ HSV –> VZIG prophylaxis?

Bacteria:

• Extrapulmonary TB due to reactivation –> check for LTBI –> isoniazid 300mg 9/12 prophylaxis
• 2nd most common

Question 7

**Opportunistic infections in HIV: CD4 50-100

Answer 7

Toxoplasmosis –> check IgG –> if +ve, Septrin DS prophylaxis

Fungal infections (3rd most common)

• cryptococcosis –> Fluconazole PO as secondary prophlylaxis
• penicillosis –> Itraconazole PO as secondary prophylaxis

Question 8

**Opportunistic infections in HIV: CD4 <50

Answer 8

Non-tuberculous mycobacteria –> not on fully suppressive ART and active MAC disease ruled out –> azithromycin or clarithromycin prophylaxis

CMV/ EBV/ HHV-8/ JCV
- disseminated CMV esp. retinitis (and hepatitis, pneumonitis) –> valgancyclovir PO for secondary prophylaxis

Question 9

Prevention of HIV infection (5)

Answer 9

Interrupt transmission

• sexual – safe sex(especially in serology-discordant couples), male cirumcision
• pre-exposure prophylaxis
• blood transfusion and tissue transplant donor screening
• health care setting – PEP, prevention of needle stick injury and blood/body fluid exposure
• perinatal infection – antenatal screening and pre-natal antiretroviral treatment

Question 10

Solid organ tumour patients risk factors for infection

Answer 10

Risk factors:

• neutropenia (ANC <500) due to cytoreductive chemotherapy
• damage of anatomical barriers e.g. surgery, chemo, RT
• alternation of microbiota diversity e.g. antibiotics, PPI, chemo/RT
• indwelling device e.g. CVC, urine catheter
• biologics

Note: neutropenic fever is a medical emergency!

Question 11

*Management of fever in neutropenic patients (5 steps)

Answer 11

Fever within 6 weeks of chemotherapy
- fever defined as single temp >38.3 or >38.0 sustained for 1 hr

• assume bacterial infection, take pretreatment blood samples
• conduct hx and pe to assess most likely clinical and microbiological dx
• Ix by 2 sets of blood culture from different anatomical site, respiratory viral pathogen test, chest imaging
• empirical antibiotics within 1 hr – mono therapy with anti-pseudomonas coverage e.g. cefepime, carabapenem or tazocin

if clinically stable, candidate for outpatient management

• oral empirical therapy with fluoroquinolone and augmentin
• observe >4 hrs before discharge

if unstable, inpatient management

• frequent and regular monitoring
• further Ix e.g. any hidden source of infection, and review antibiotics if no response in 2 days e.g. add vancomycin if MRSA, empiral anti fungal therapy

Question 12

Solid organ transplantation risk factors for infection, infections in renal transplants (3), treatment and complications

Answer 12

Risk factors for infection

• infectious agents from donor
• surgery
• maintenance immunosuppressant

Infections related to renal transplantation:

CMV infection or reactivation

• retinitis, pneumonitis, colitis
• treat by decreasing immunosuppressant and gancyclovir antiviral agent
• complication: allograft lose, mortality

BK polyomavirus

• haemorrhagic cystitis
• treat by decreasing immunosuppressant
• complication: AKI, allograft lose

HBV reactivation
- hepatitis, liver failure

Question 13

**Haematopoietic stem cell transplant phases

Answer 13

Pre-engraftment (<30 days)

• from onset of conditioning therapy to transplant to 40 days after HCT
• engraftment = NAC >0.5 for 3 separate days (usually day 14-21)
• graft failure = no neutrophil recovery by day 42

Early postengraftment (days 30-100)
- begins with neutrophils recovery continues to day 100

Late postengraftment (>100 days)
- from day 100 til regaining of normal immunity, usually 18-36 months

Question 14

**Haematopoietic stem cell transplant infections: immune status and common infections

Answer 14

Pre-engraftment

• severely immunocompromised due to cytotoxic chemo, RT, catheters, disease itself
• neutropenia, mucositis, central catheter, acute GVHD
• –> pyogenic bacteria, candida and early aspergillus, HSV reactivation

Early postengraftment

• impaired cellular immunity, NK cells recover first, CD8 increasing but restricted
• bacterial infections less common
• –> CMV, PCP, aspergillus

Late postengraftment

• impaired cellular and humoral immunity
• B cells and CD4 recover slowly
• –> encapsulated bacteria, VZV, PCP

Question 15

Immunosuppressants: steroids, biologics

Answer 15

Glucocorticoids

• bind to intracellular receptors –> nucleus
• inhibit inflammatory cytokines
• dose-dependent inhibition on phagocytes
• prednisolone: high dose = >40mg/d e.g. in herpes zoster, TB, strongyloides stercoralis hyper infection syndrome

Biologics (always check infective complications)

• Anti CD20 monoclonal Ab affecting B cells – Rituximab
• Anti CD52 monoclonal Ab affecting T cells – Alemtuzumab
• JAK inhibitors e.g. Ruxolitinib
• TNF inhibitors e.g. Infliximab
• —> TB is the most common opportunistic infection caused by biologics