Opportunistic Infections Flashcards
Definition: what patients?, opportunistic vs non-opportunistic
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
Causes of Immunosuppression (5)
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)
**Immune component defect and related infections (5)
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)
HIV recap: natural clinical course, diagnostic algorithm, criteria for AIDS, principals of treatment
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
**Opportunistic infections in HIV: CD4 200-350
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
**Opportunistic infections in HIV: CD4 100-200
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
**Opportunistic infections in HIV: CD4 50-100
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
**Opportunistic infections in HIV: CD4 <50
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
Prevention of HIV infection (5)
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
Solid organ tumour patients risk factors for infection
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!
*Management of fever in neutropenic patients (5 steps)
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
Solid organ transplantation risk factors for infection, infections in renal transplants (3), treatment and complications
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
**Haematopoietic stem cell transplant phases
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
**Haematopoietic stem cell transplant infections: immune status and common infections
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
Immunosuppressants: steroids, biologics
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
