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Medical treatment or hereditary deficiency of components of the
immune system may allow organisms with reduced virulence to
cause infection and normal pathogens to cause severe infection.
The origin of immune deficiency is often multifactorial; for
example patients undergoing bone marrow transplantation are
neutropenic, which reduces resistance to bacterial infection, whilst
intravenous cannulation provides a route for Staphylococcus epidermidis
Neutropenia most often arises as a result of acute leukaemia or its
treatment; infection risk depends on the duration and severity of
the neutropenia. Bacteraemia occurs in between 40 and 70% of
neutropenic patients with Enterobacteriaceae and Pseudomonas
invading following gut damage by antineoplastic agents or
irradiation. Gram-positive organisms (e.g. S. epidermidis
, Streptococcus oralis
, Enterococcus spp.
and Corynebacterium jeikeium
) are increasingly
important causes of sepsis.
With increasing duration of neutropenia, fungal infection may
develop due to Candia albicans
, Aspergillus spp.
and, rarely, Fusarium
, Pseudallescheria boydii
and Trichosporon beigelii
Treatment of fever in neutropenic patients
Empirical therapy includes tazobactam and an aminoglycoside,
with vancomycin being added if central-line infection is possible.
If fever persists, fungal pathogens are more likely and amphotericin
or itraconazole may be added.
Prevention of infection
Infection risk can be reduced by:
- source isolation (see Principles of infection control
- filtration of room air to remove fungal spores;
- antifungal prophylaxis (e.g. nystatin, either alone or in combination
with oral amphotericin, or fluconazole or itraconazole);
- antibiotic prophylaxis (e.g. fluoroquinolones are used in some
T-cell deficiency is an increasingly common problem, which may
follow HIV infection, cancer chemotherapy, corticosteroid therapy
or organ transplantation. Congenital T-cell deficiencies are rare
but may be purely linked to T-cell function or combined with
These are mainly the microorganisms that have an intracellular
location in the human host, such as:
- Toxoplasma gondii, Strongyloides stercoralis;
- Mycobacterium tuberculosis, Mycobacterium avium-
- Listeria monocytogenes, Cryptococcus neoformans, Pneumocystis
- herpes simplex, cytomegalovirus (CMV), varicella zoster virus
(VZV) and measles.
Measles infection, especially if complicated by giant cell pneumonia
or encephalitis, can be life-threatening.
Specific infections should be investigated appropriately. All patients should have at least two blood cultures
taken from different sites.
Patients with X-linked agammaglobulinaemia are at increased risk
of infection for the first 6 months of life; patients with common
variable immunodeficiency are at increased risk throughout life.
Functional hypogammaglobulinaemia develops in patients with
Patients suffer recurrent respiratory tract infections with Streptococcus pneumoniae
, the novel Mycoplasma amphoriforme and
non-capsulate Haemophilus influenzae, which lead to bronchiectasis.
be more persistent. Intravenous immunoglobulin reduces recurrent
Hereditary complement deficiencies are rare. Deficiency in the
later components of the complement cascade (C7-9) results in an
inability to lyse Gram-negative bacteria, and patients are susceptible
to recurrent Neisseria infection. Deficiency of the alternative
complement pathway leads to serious S. pneumoniae
including meningitis. Acquired complement deficiency occurs in
systemic lupus erythematosus.
A wide range of bacteria fungi, viruses and protozoa bind to
mannose-binding lectin and there are reports that infection with
these organisms are commoner or more severe with some deficiency
The incidence of serious sepsis following splenectomy is about 1% per
year; the rate is higher in infants and children. The highest mortality
is associated with splenectomy for lymphoma and thalassaemia.
Patients with sickle cell disease have functional asplenia. Although
the risk of sepsis diminishes with time, it never disappears.
is responsible for approximately twothirds
of infections; others H. influenzae
and Escherichia coli
Malaria may run a fulminant course. Splenectomy predisposes to
Capnocytophaga canimorsus infection, which usually arises after a
- Conjugate vaccines against S. pneumoniae meningococcus and
H. influenzae type b.
- Low-dose, oral antibiotic prophylaxis with penicillin V.
- Patient awareness of the urgency of treating respiratory infections
with antibiotics, which may be prescribed in advance to
avoid delay in initiation of treatment.
is a fungus causing infection in individuals
with severe T-cell dysfunction. Transmitted by the respiratory
route, P. jiroveci
adheres strongly to pneumocytes.
- Dyspnoea develops insidiously over days or weeks.
- Patients have an unproductive, dry cough.
- Pleuritic chest pain is uncommon.
- Patients are febrile but chest examination usually normal,
although fine basal crackles may be heard.
- Chest X-ray may appear normal initially then develop through
reticular shadowing until finally there is diffuse air-space
Specimens, obtained by bronchoalveolar lavage or sputum induction
may be examined by specific immunofluorescence, or nucleic
acid amplification test (NAAT).
Treatment is with oral co-trimoxazole in high dosage or intravenous
pentamidine. Alternatives include trimethoprim-dapsone,
pyrimethamine-clindamycin and atovaquone.
Toxoplasma infection persists inside the host cells for very long
periods. Falling immunity allows the reactivation of previously
dormant infection. A space-occupying lesion may develop in the
brain, which may be accompanied by encephalitis.
Toxoplasma encephalitis presents with fever and headaches.
Convulsions, coma and focal neurological signs may follow. A CT
scan may demonstrate multiple diagnostic focal lesions with ring
enhancement. Brain biopsy may yield material for tissue culture
or PCR. Toxoplasma encephalitis is treated with pyrimethamine-
sulfadiazine. Long-term suppressive treatment is required after