SNO201617 1

CL7: INFECTIONS IN THE

IMMUNOCOMPROMISED
BLOOD & LYMPH MODULE
YEAR 2, SEM 3 (2016/17)

Dr. Siti Norlia Othman

Dept. of Medical Microbiology & Immunology, FPUKM

1/9/2016
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OUTLINE
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What/who is immunocompromised?
Risk of infections
Types of infection & examples
Clinical features
Laboratory investigations
Principles of management

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What / who is immunocompromised?
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Compromised hosts = people

with one or more defects in
their bodys natural defense
against microbial invaders
Infections : more severe and life-

threatening
Risk of opportunistic infections
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Risk of infection
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Advanced treatment more patients with

cancers/organ transplant survived =
immunocompromised prone to infection
Due to:
Defects, accidental/intentional in bodys
innate defense mechanism
examples?
Deficiencies in adaptive immune system
examples?
Inherited vs acquired SNO201617 1/9/2016
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Causes of immunodeficiency
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Genetic - inherited genetic defects

Acquired - infections, such as HIV, and certain
cancers, including leukemia, lymphoma, or
multiple myleoma
Chronic diseases - such as end stage renal
disease and dialysis, diabetes, cirrhosis
Medications - such as steroids, chemotherapy,
radiation, immunosuppressive post-transplant
medications
Physical State e.g. pregnancy
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Factors affecting immune
systems
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Factors affecting innate systems

Primary Complement deficiencies, phagocyte cell
deficiencies
Secondary Burns, trauma, major surgery, catheterization,
foreign bodies (e.g shunts, prostheses),
obstruction
Factors affecting adaptive systems
Primary T-cell defects, B-cell deficiencies, severe
combined immunodeficiency
Secondary Malnutrition, infectious diseases, neoplasia,
irradiation, chemotherapy, splenectomy
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 Primary adaptive
immunodeficiencies
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Defect in lymphocyte
differentiation
Failure to produce B-cells
(Bruton-type
agammaglobulinaemia) or T-
cells (DiGeorge syndrome)
Severe combined immunodef
(SCID)
Antibody deficiency:
characterized by -
recurrent pyogenic
infections
Secondary adaptive
immunodeficiencies
Acquired
Malnutrition kwashiorkor,
marasmus
Infections eg HIV, measles,
mumps, congenital rubella,
CMV
Neoplasia of the lymphoid
system
Splenectomy impaired
humoral responses
Treatment e.g. cytotoxic
agents, corticosteroids,
radiotherapy
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 1) Infections of the host with deficient
innate immunity due to physical factors
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Burn wound infections

Traumatic injury and surgical wound
infections
Infections of plastic devices in situ
Infections due to compromised
clearance mechanisms

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2) Infections associated with secondary
adaptive immunodeficiency
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Underlying immunodeficiency state

determines the NATURE & SEVERITY of
infections
Can be a major cause of morbidity & mortality
Commonly in:
a) Haematologic malignancy & bone marrow
transplant patients
b) Solid organ transplant patients
c) AIDS patients

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 a) Haematologic malignancy and bone marrow
transplant infections
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Due to lack of circulating neutrophils following

bone marrow failure
Neutropenia (<0.5 x 109 neutrophils/L)
Infections -- duration of neutropenia
Presenting feature: septicaemia
Aetiological agents:
GNR e.g. E.coli, P.aeruginosa (fr owns bowel)
GPB e.g. Staph, Streptococci, Enterococci
Staph.epidermidis assoc with IVC
Fungi prolonged neutropenia (>21 days)
Viruses BMT, GVHD, immunosuppresive tx
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 b) Solid organ transplant infections
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Most infections occur within 3-4months of

transplantation (after that risk is reduced)
d/t suppression of cell-mediated immunity
as well as suppression of humoral immunity
High doses of corticosteroids reduce inflammation
Other factors:
The underlying medical condition
Patients previous immune status
Type of organ transplant
Immunosuppressive regimen
Exposure to the pathogens SNO201617 1/9/2016
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 c) HIV infection leading to AIDS
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Clinical definition of AIDS = presence of 1

opportunistic infections
Body failed to eradicate the organisms
Pathogens are intracellular (cell-mediated
immunity defects)
Reactivation of organisms causing
disseminated infections
Opportunistic infections does not infect
immunocompetent hosts

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 Examples of opportunistic
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pathogens
Bacteria Viruses
GPB Herpesviruses
Staph aureus Hepatitis B, C
Coagulase-negative staphylococci Polyomaviruses e.g. BKV, JCV
Streptococci Adenoviruses
Listeria spp. HIV
Nocardia asteroides Fungi
M. tuberculosis,
Mycobacterium avium-intracellulare Candida spp.
Aspergillus spp.
GNB Cryptococcus neoformans
Enterobacteriaceae Histoplasma capsulatum
Pseudomonas aeruginosa Pneumocystis jirovecii
Legionella spp. Parasites
Bacteroides spp. Toxoplasma gondii
Strongyloides stercoralis 13
 Important opportunistic pathogens & clinical
features
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FUNGI Gastrointestinal
1. Candida spp. candidiasis major
Mucocutaneous candidiasis gastric / abdo
rare, persistent, non- surgery, neoplastic
invasive disease. Blood
Oropharyngeal /
oesophageal candidiasis culture +ve if
HIV pts, DM, on antibx / dissemination
steroids Disseminated
candidiasis via
GIT, or IV cath-
related infections.
Leukaemia and
lymphoma patients
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are at risk 14
 2) Cryptococcus neoformans
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Impaired cell-mediated
immunity
Onset maybe slow
Lung infections or
meningoencephalitis
Also skin, bone, joints
infections
Diagnosis: Treatment: ampho B +
CSF
india ink encapsulated flucytosine (prophylaxis
yeast cells fluconazole)
Latex agglutination test
(antigen detection) Prognosis: depends on
culture
the underlying disease
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 3) Histoplasma capsulatum
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Highly infectious
Endemic in tropical
countries
Natural habitat : soil
Transmit by air-borne
Fungal spores deposited Dx: cultures of blood,
in alveoli spreads via bone marrow, sputum,
lymphatics regional CSF, skin lesions; biopsy
nodes & HPE (BM, liver, lymph
Causes skin lesions, nodes)
pulmonary infection, Thermally dimorphic
disseminated dzs fungi budding yeasts
Disseminated disease @37C and hyphae
after many years after @25C
initial exposure
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Tx: amphothericin 16
 4) Aspergillus spp.
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Invasive disease
High fatality rate
Usually in profoundly
neutropenic patients Dx: microscopy,
or those receiving culture, Ag detection,
high-dose PCR (specimen BAL,
corticosteroids lung biopsy)
Transmission: Tx: IV liposomal
airborne ampho B (prophylaxis
Site of infxn: lungs, caspofungin,
may disseminate to posaconazole,
other sites (eg CNS, voriconazole & early
heart 25% of patients) dx)
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 5) Pneumocystis jirovecii (P.carinii)
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Atypical fungus Dx: not easy, high index

of suspicion. Silver
Symptomatic disease in
staining of BAL, PCR
people with deficient
cellular immunity e.g. pts Tx: high-dose co-
on immunosuppressive trimoxazole
drugs, people with HIV
Usually causes
pneumonia, rarely in other
sites

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 Bacteria
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1. Nocardia asteroides Dx: on routine media,

Actinomycetes family but slow grower. Gram
positive branching,
Uncommon but
weak AFB
reported in
Tx: sulphonamides or
immunocompromised
co-trimoxazole
esp. renal transplant
pt
Primary site: lungs
spread to skin, kidney,
CNS (brain abscess)
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 2) Mycobacterium avium-intracellulare
(MAC)
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Commonly seen in AIDS

patients
Causing lung infections
Isolated fr blood culture
Atypical mycobacteria or
MOTT
Resembles M.tuberculosis
Dx: AFB, Runyon III, LJ
media
tx: macrolides +
ethambutol + rifamycins
(others
aminoglycosides)

= slow-growers, but
resistant to conventional
anti-TB drugs.
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 Culture & AFB (tissue)
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 Protozoa & helminths
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1. Cryptosporidium Dx: modified ZN stain

Protozoa (oocysts), direct IF,
Causes severe & ELISA Ag detection,
chronic diarrhoea in ppl PCR
with AIDS (CD4 TX: HAART improves
<100/mm3) the diarrhoea

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 2) Strongyloides stercoralis
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Parasitic roundworm
Dormant after initial
infection reactivated =
autoinfection
Most common sites: lungs,

liver, brain
Dx: identification of the
adult worms, larvae or
eggs
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 Viruses
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Viral infections are more

Pre-emptive/
common and more
prophylaxis treatment
severe
suppress the virus
Represent reactivation
before it causing
(latent infection) infections
Pre-transplant serologic
Specimens are sent
test baseline status for early detection
(both donor & recipient)

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 1. CMV
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Broad spectrum of Serologic determination

infections pneumonitis, pre-transplant
oesophagitis, colitis, Tx: prophylaxis /
hepatitis, encephalitis preemptive / treatment
Donor CMV IgG+ to ganciclovir
recipient CMV IgG- =
primary infection (within
4wks post-tx)
CMV IgG+ recipient =
reactivation / reinfection
(within 6-8wks post-
transplant)
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 2) HSV 3) VZV
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Herpetic lesions Reactivation within

persistent (lips,
oesophagus, GIT,
pneumonitis, hepatitis,
encephalitis)
Dx: culture, PCR (material
from the lesion)
Tx: acyclovir
few months post-
transplant
Affect skin dermatomes,
multidermatomes,
disseminated disease
Tx: acyclovir

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 4. EBV Risk factors: post-tx
primary CMV infections,
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mismatched D-R CMV
a/w development of Hodgkins,
status, CMV disease,
non-Hodgkins lymphoma (HIV
intensity/type of
pts), PTLD & smooth muscle
immunosuppression tx.
tumours (in
Primary EBV infection in
immunosuppressed children)
children & adolescents
EBV-associated PTLD = broad
incidence of PTLD higher
spectrum of clinical syndromes
in paeds pts
(infectious mono to
Tx: reducing
malignancies)
immunosuppression (for
Abnormal proliferation of EBV-
better host response to
infected B-cells (lack of T-cells
fight infection BUT risk of
(immunosuppression) to
graft rejection), rituximab,
contain B-cell replication)
chemotherapy
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 5. Respiratory viruses 6. Polyomaviruses
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At risk of pneumonia & BK or JC viruses

death Via respiratory tract
Prevention: latent in kidneys
immunization, BMT recipients
prophylaxis, early
BK viruria =
diagnosis
haemorrhagic cystitis
Treatment: antiviral
JC = reactivate &
(oseltamivir (influenza),
disseminate to cause
ribavirin (RSV))
CNS infections (PML)
in patient with AIDS
become less often d/t
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HAART
 Diagnosis & investigations
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Can be difficult
Aetiology can be ANYTHING

Aggressive approach to diagnosis

CT scan
BAL
biopsy
Presumptive treatment

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 Principle of management
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Prophylaxis vs Pre-emptive
therapy
Organism-targeted therapy

Screening (pre-transplant, post-

transplant)
High index of suspicion

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