Download Infections in the compromised host

Infections in the compromised
host
Learning Objectives
At the end of this lecture, the
student should be able to:
• list the main types of defects in immune
system
• List the most common microorganisms
associated with disease in each type of
immunodeficiency
• List the main laboratory methods for most of
the infections in immunocompromised
patients
Immune system
-the innate defense system (e.g. skin, mucous
membranes)
-the adaptive (cellular and humoral) immune
system
protects us from infection
The Immune system
• Immunocompetent host: intact
• Immunocompromised host:
– has defects in their body's natural defenses
– prone to severe and life-threatening infections !
The immunocompromised patient
• Defects , accidental or intentional, in the
body's innate defense mechanisms
• deficiencies in the adaptive immune response
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• Primary immunodeficiency
• Acquired immunodeficiency
• Primary immunodeficiency: rare
– inherited or
– occurs by exposure in utero to environmental
factors or by other unknown mechanisms
• Secondary or acquired immunodeficiency
– due to an underlying disease state or
– occurs as a result of treatment for a disease.
Immunocompromised patients
• increase in number due to:
– Therapy of many cancer types
– Organ transplantation
– HIV/AIDS
Innate immunity
• Primary defects:
– congenital defects in phagocytic cells or
complement synthesis
Extracellular infections
Innate immunity
• Secondary defects:
– disruption of the body's mechanical barriers:
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Burns
traumatic injury
major surgery
Devices such as intravascular and urinary catheter
procedures such as lumbar puncture or bone marrow
aspiration
• Foreign bodies such as prostheses
• Obstruction
Burn wound infections
• Burns damage :
– the body's mechanical barrier
– neutrophil function
– immune responses
– The major pathogens in burns are aerobic and
facultatively anaerobic bacteria and fungi
– Septicemia in patients with burns is often
polymicrobial.
The most important pathogens in
burn wounds are:
 Pseudomonas aeruginosa and other Gramnegative rods
 Staphylococcus aureus
 Streptococcus pyogenes
 other streptococci
 enterococci.
 Candida spp. and Aspergillus together account
for about 5% of infections. Anaerobes are rare
in burn wound infections.
Surgical wound infections
• Staphylococcus aureus: the most important
cause
– May be severe
– Invade the bloodstream
– seed other sites
• heart valves: causing endocarditis
• bones:osteomyelitis
– thereby further compromising the patient.
Urinary catheters
 Catheter-associated infection of the urinary
tract is common
 Especially if catheters are left in place for >48
h.
 The organisms involved are usually Gramnegative rods from the patient's own fecal or
periurethral flora
Intravenous and peritoneal
dialysis catheter infections
• Staphylococci :the most common
– coryneforms, Gram-negative rods and Candida
are also implicated.
Infections of plastic devices in situ
• Coagulase-negative staphylococci, particularly
Staphylococcus epidermidis, account for more
than 50% of the infections
• These opportunists are members of the
normal skin flora
• multiple antibiotic resistances, and agents
such as a glycopeptide (vancomycin or
teicoplanin) and rifampicin may be required
• Whenever possible the plastic device should
be removed.
Percentage of infections caused by
Staph. epidermidis in patients with
plastic devices in situ
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Infections caused by Staph. epidermidis
(%)
Prosthetic heart valve
Early (<2 months postoperatively) 30-70
Late (>2 months postoperatively) 20-30
Prosthetic hip
10-40
Cerebrospinal fluid shunt
30-65
Vascular grafts
5-20
Peritoneal dialysis related
30
Intravascular catheters
10-50
Infections due to compromised
clearance mechanisms
• Stasis: cystic fibrosis: Staph. aureus and
Haemophilus influenzae and later with P.
aeruginosa
• Obstruction and interruption of normal urine
flow: Gram-negative organisms from the
periurethral flora
– Septicemia is an important complication of urinary
tract infection superimposed on obstruction.
Adaptive immunity
• Primary defects:
– T-cell defects
– B-cell deficiencies
– severe combined immunodeficiency
Adaptive immunity
• Secondary defects:
malnutrition
infectious diseases
neoplasia
irradiation
chemotherapy
splenectomy
Adaptive immunity
• Secondary defects:
-The underlying immunodeficiency state
determines
-the nature
-severity of any associated infection,
and in some cases:
- infection is the presenting clinical feature
Infections that cause
immunosuppression
• Viral
• Measles
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Bacterial
Mycobacterium
tuberculosis
Mumps
Mycobacterium
leprae
Congenital rubella Brucella spp.
Epstein-Barr virus
Cytomegalovirus
HIV-1, HIV-2
Treatment of disease can also
cause immunosuppression
• Cytotoxic agents such as cyclophosphamide and
azathioprine cause leukopenia or deranged T- and Bcell function
• Corticosteroids reduce the number of circulating
leukocytes, monocytes and eosinophils and suppress
leukocyte accumulation at sites of inflammation
• Radiotherapy adversely affects the proliferation of
lymphoid cells.
Treatment for neoplastic disease
– patient becomes immunocompromised as a result of both
the disease and the treatment.
– Due to improvements in medical technology, many
immune defects, particularly immunosuppression resulting
from radiotherapy or cytotoxic drugs, are transient, and
patients who survive the period of immunosuppression
have a good chance of a complete recovery.
Hematologic malignancy and bone
marrow transplant infections
• A lack of circulating neutrophils following
bone marrow failure predisposes to infection
• Opportunistic pathogens in neutropenic
patients and organ transplant recipients:
– Bacteria
– Fungi
– Parasites
Toxoplasma gondii
Strongyloides stercoralis
Hematologic malignancy and bone
marrow transplant infections
–Viruses
Herpesviruses,
Hepatitis B
Hepatitis C
Polyomaviruses, e.g. BKV, JCV
Adenoviruses
Cytomegalovirus (CMV) infections:
associated with graft-versus-host disease as well as
immunosuppressive therapy.
Solid organ transplant infections
• Most infections occur within 3-4 months of
transplantation
• Suppression of a patient's cell-mediated
immunity is necessary to prevent rejection of
a grafted organ, and the cytotoxic regimens
used usually suppress humoral immunity to
some extent as well. In addition, high doses of
corticosteroids to suppress inflammatory
responses are required. The combination of
these factors results in a severely
compromised host
HIV/AIDS
 As the HIV-infected individual progresses to
AIDS ,
 organisms that are usually controlled by cellmediated immunity are able to reactivate to
cause disseminated infections not seen in the
immunologically normal individual.
Opportunistic pathogens
• Fungi
Candida spp.
Aspergillus spp.
Cryptococcus neoformans
Histoplasma capsulatum
Pneumocystis jiroveci
Downloaded from: StudentConsult (on 17 September 2009 05:51 PM)
© 2005 Elsevier
Downloaded from: StudentConsult (on 17 September 2009 05:51 PM)
© 2005 Elsevier
Pneumocystis jiroveci
• causes symptomatic disease in people whose
cellular immune mechanisms are deficient.
• high incidence of pneumonia
– in patients receiving immunosuppressive therapy
to prevent transplant rejection and
– in people with HIV.
Pneumocystis jiroveci
• the organism cannot be isolated in
expectorated sputum using conventional
culture methods
• invasive techniques such as bronchoalveolar
lavage or open lung biopsy are required.
• The organism can be demonstrated by silver
or immunofluorescent stains .
• DNA amplification by the polymerase chain
reaction improves the sensitivity of the
diagnostic tests.
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© 2005 Elsevier
Actinomycetes
• contain two pathogenic genera, Actinomyces
and Nocardia.
• The lung is usually the primary site, but
infection can spread to the skin, kidney or
central nervous system
• Mycobacterium avium-intracellulare disease
is often a terminal event in AIDS
Protozoa and helminths
• Cryptosporidium and Isospora belli infections
cause severe diarrhea in AIDS
• Strongyloides stercoralis
Certain virus infections
• both more common and more severe in
compromised patients, and regular
surveillance is critical
• Many of these represent reactivation of latent
infections.
• Pre-transplantation baseline serology is carried out
to determine both the donor and recipient status for
a number of virus infections, including HIV, hepatitis
B and C, CMV, EBV and HSV.
• CMV quantitative DNA monitoring is carried out on
blood samples on a regular basis posttransplantation to detect early infection and start
antiviral therapy (preemptive therapy)as soon as
possible.
• HSV, VZV may reactivate
• HHV-8 has been associated with the
development of Kaposi's sarcoma (KS) in
individuals with AIDS
• EBV infection can lead to tumor development
• Respiratory viruses
Polyoma viruses
• BK and JC virus can reactivate.
• can cause hemorrhagic cystitis and
progressive multifocal leukoencephalopathy
Compromised patients
• Infection may be due to:
– any of the pathogens capable of infecting immunocompetent
individuals.
– opportunist pathogens.
– The type of infection is related to the nature of the compromise
• Effective antimicrobial therapy is often difficult to achieve in
the absence of a functional immune response, even when the
pathogen is susceptible to the drug in vitro
• For microorganisms involved direct methods for detection
especially nucleic acid detection techniques are prefered.
Reference:
7th ed 2013