SPR L16 Infections in the Immunocompromised Host Flashcards
Learning Outcomes
- Host defence overview
- Factors that make a host compromised
- Microbes that infect the compromised host
Definitions
Define the following…
- Pathogen
- Primary Pathogen
- Opportunisitc Pathogen
- a micro-organism causing disease
- common cause of disease in healthy non-immune hosts e.g. S. aureus, S. pneumoniae
- rare cause of disease in healthy individuals, causes serious disease in compromised hosts e.g. Pseudomonas aeruginosa, Pneumocystis jirovecii,
Source of infection
Outline the following sources
- Endogenous
- Exogenous
- Micro-organisms originating from the patient’s own body which cause harm when they move to another body site
- Micro-organisms originating from an external source (e.g. other human) which are transmitted by a variety of possible mechanisms to the host, eg. Direct contact, airborne route etc.
Define a ‘compromised person’
A compromised person is one whose normal defenses against infection are defective
What can compromised patients be
infected with?
Pathogens capable of infecting immunocompetent individuals AND Opportunist pathogens
Host defence overview
What do the following involve?
- Innate immunity
- Adaptive immunity
- Defences against entry into the body→ physical & chemical factors & normal bacterial flora
Defenses once the microorganism penetrates the body - Soluble factors: lyzozymes- complement- acute phase proteins- IFN AND Cells of innate immunity: phagocytes- NK cells
- Antibody
T-lymphocytes
What may immunodeficiency involve?
The immunodeficiency may involve the innate or adaptive systems and may be primary or secondary
Primary immunodeficiencies
(defects in innate immunity)
Give examples
- Phagocytic cells defects eg. Chronic granulomatous disease (CGD) & Leukocyte Adhesion Deficiency (LAD) → recurrent bacterial & fungal infections
- Complement deficiencies => Deficiencies of terminal complement components => severe Neisseria infections
Primary immunodeficiencies
(defects in adaptive immunity)
Generally, outline the following
- T cell defects
- B cell defects
- Combined T & B cells deficiency (SCID)
- viral , fungal & protozoal infections
- pyogenic infections (pus forming)
- all kinds of infections
Secondary immunodeficiencies
(defects in innate immunity)
How can these arise?
-
Disruption of mechanical barriers
- Burns (Damage to mechanical barriers of the body, Abnormalities in neutrophil function, Highly nutritious surface for organisms)
- Trauma
- Major surgery
- Devices or procedures
- Foreign bodies
- Obstruction → interference with clearance mechanisms → infection
-
Malnutrition
- inadequate cell-mediated response
- Infections – immunosuppressive viruses (HIV→ AIDS), measles and many others
- Neoplasia → reduced immunoreactivity
- Splenectomy => phagocytosis of antibody coated bacteria
-
Drugs/treatment
- Cytotoxic agents
- Corticosteroids & antibiotics–Radiation therapy
Secondary immunodeficiencies
(defects in innate immunity)
What are the important pathogens involved?
- P aeruginosa : particular problem in these patients
- Staph aureus
- Fungi
- Others
Secondary immunodeficiency-
physical factors
Define how the following bring about immunodeficiency
- Traumatic injury & surgical wound infections
- In situ devices (prosthetic valves and joints, pacemakers)
- Compromised clearance mechanism
- Destroy integrity of body – make it vulnerable to infections, staph. aureus commonest cause of surgical wound infection
- Gain access during surgery or subsequent bacteremia. Staph. epidermidis is an important pathogen.
- Ciliary escalator damage, Obstruction of urine flow.
Secondary immunodeficiency-
physical factors
Splenectomy
- What are these patients susceptible to?
- What actions need to be taken?
- capsulate bacteria
- Prevention of infection
- vaccination (preferably before splenectomy)
- Prophylactic antibiotics against Streptococcus pneumoniae
Secondary immunodeficiency-
physical factors
Neutropenia
- What are the causes?
- Major problem infections with neutropenia are…?
- What is important to remember?
See picture - where pt drops and levels is unpredictable: important to monitor - daily white cell counts
- Iatrogenic (Post chemotherapy, Post BMT) Aplastic anaemia
- Bacterial : gram negative rods & gram positive
Fungal: if neutropenia > 21 days
-
infection or suspicion of infection in a neutropenic patient is an absolute clinical emergency
- Instead of source isolation, protective isolation
Secondary immunodeficiency
AIDS infections
- What does the clinical definition of AIDS include?
- What has led to a decline in the incidence of these infections in HIV-positive patients?
- the presence of one or more opportunistic infections
- The arrival of highly active antiretroviral therapy, or HAART
Opportunist infections & tumors in AIDS
Give examples of these…
- Viruses
- Bacteria
- Protozoa
- Fungi
- Tumors
see picture
TB
Salmonella - prolonged infections
Kaposi’s Sarcoma - common tumor in AIDs driven by HHV8).
Tumours have an infective origin. See these late. CD4+ count almost non-existent.
Secondary immunodeficiency
AIDS infections
Spectrum of infecting organisms relates to what?
to disease progression (CD4 count)*
- 0.5 X 109/l M. tuberculosis
- <0.2 X 109/l , P. jiroveci pneumonia, Toxoplasmosis
- <0.10 X 109/l CMV, MAI
- CD4 count boosted by HAART
- Rational prophylaxis offered for P. jiroveci pneumonia , Mycobacterium Avium-Intracellulare (MAI), CMV with falling counts
- (Normal Ratio of CD4:CD8 is 0.9-1.9)
Candida (yeast)
What may this cause?
What is candidiais?
site may depend on type of immunodeficiency
- vaginal and oral thrush
- skin infections
- endocarditis
Candidiais
- chronic mucotaneous
- oropharyngeal and esophageal
- gastrointestinal
Disseminated - through GI tract but also intravascular catheter related infections
Cryptococcus neoformans (yeast)
Who is this seen in? What does it result in?
- People with impaired cell-mediated immunity
- Lung infections and mengioencephalitis
- Sometimes bone and joints
Other Fungi
Outline the following…
- Histoplasma
- Aspergillius
- mainly tropical- ‘histo belt’ central USA, Ohio, Misissippi spores in soil – deposited in alveoli and germinate- fungi and spreads to lymph nodes and then other tissues
- lung infection but increasingly reported in profoundly neutropenic patients
What does Pneumocystis jirovecii
(formerly P carinii) cause?
- Atypical fungus
- Pneumonia
- Cell-mediated immune deficiences
- Hard to diagnose-symptoms resemble other infections or non-infectious diseases
Protozoa
Describe the following…
- Cryptosporidium
- Isopora Belli
- Protozoan, animal pathogen, severe chronic diahorrea in the immunocompromised
- similar organism- in AIDS patients
Protozoa-Toxoplasma gondii
- What is the host?
- What will it give rise to?
- Cat
- Ring-enhancing lesions on CT/MRI scan and
Toxoplasma- IgG antibody
Examples of opportunist infections & tumors associated with HIV infection
Give examples
A) Hairy cell leukoplakia (EBV)
(B) Extensive oral candidiasis.
(C) Kaposi’s sarcoma (HHV 8)
(human herpsesvirus 8)
Viruses
List the clinically important viruses in the immunosuppressed
- Herpesviruses - reactivate when immunosuppressed.
- CMV
- Prophylaxis given for CMV (can be own virus or e.g acquired from transplant).
- EBV- tumour development-non-Hodgkin’s lymphomas.
CMV in the transplant setting
CMV is an issue in both Solid organ and Bone marrow (Stem cell) transplants in the weeks or months post transplant
How does it present?
CMV infection post transplant:
- leukopenia (unexplained)
- shivery, fever, hepatitis
- occasionally retinitis
- very occasionally pneumonitis
CMV in the transplant setting
CMV is an issue in both Solid organ and Bone marrow (Stem cell) transplants in the weeks or months post transplant
- Which type of infection is associtated with more severe infections?
- What is tested?
- What is the most risky situation?
- Primary infection
- “CMV status” IgG positive or negative
- Approximately 50 % of the adult population are CMV positive (CMV status positive i.e. IgG positive). Infected at somestage at the past. Still latent because it is a herpesvirus. If an organ donor - CMV will be in the organ and will be transplanted in the organ.
- Once infected, virus is in all tissues for rest of life. And will be in any harvested organ.
- For solid organ transplants Donor positive Recipient negative is most risky situation => primary CMV infection via the graft.
Solid Organ vs Bone marrow
- What is the most severe situation now?
- Most severe situation is different
Solid organ = Donor CMV positive, Recipient CMV negative
Bone marrow transplant = Donor CMV negative, Recipient CMV positive
Need to think with respect to the immune system! => primary infection of a naïve bone marrow
Solid Organ vs Bone marrow
- What is the most severe situation now?
- Most severe situation is different
Solid organ = Donor CMV positive, Recipient CMV negative
Bone marrow transplant = Donor CMV negative, Recipient CMV positive
Need to think with respect to the immune system! => primary infection of a naïve bone marrow
Diagnosis of CMV disease post transplant
How is CMV diagnosed here?
CMV PCR (on blood sample)
- Quantitative (copies per ml or IU per ml)
- Measures amount of CMV DNA in blood
- Also used for monitoring – response to treatment
2 key tests:
“CMV Status” = CMV IgG – used to look at donor and recipient prior to transplant
CMV PCR – used to diagnose and monitor CMV infection post transplant
CMV in transplant setting
- How is it treated?
- What does prophylaxis involve?
- ganciclivir (IV) used to treat symptomatic CMV infection
- oral valganciclovir (can be given for 3 or 6 months post transplant in risky situations – donor recipient CMV mismatch)
- Aim is to delay the CMV infection and make it clinically less severe
What other Viruses are important in immunosuppressed patients?
Respiratory viruses
- RSV, parainfluenza, influenza, adenovirus, measles.
Polyomaviruses (BK, JC)- JC causes progressive multifocal leucoencephalopathy (PML). Slow progressive –multiple neurological signs.
Case presentation
An 8-year-old girl with sickle cell disease combined with ß-thalassemia received an allogeneic hematopoietic stem cell transplant. Cyclosporine and methotrexate were given as prophylaxis against graft-versus-host disease. A suspension of cotrimoxazole and amphotericin B was given as anti-infective prophylaxis. Seventeen days after transplant, patient developed persistent fever unresponsive to broad-spectrum antibacterial agents while the patient was still profoundly neutropenic (< 0.1 x 109/L) so intravenous amphotericin B (30 mg) was empirically added. Germ tube–producing organism was isolated from two sets of blood cultures drawn 6 hours apart from a peripheral vein and from two sets through the central venous catheter. Once the results of the positive blood cultures became known, 5-flucytosine (100 mg/kg) was added to the regimen.
- What is the likely diagnosis of this condition?
- How may the girl have become infected?
- Disseminated candidiasis
- Central Intravascular catheter
