362
U N I T 4
Infection and Immunity
metabolism.
41
A deficiency in ADA leads to deoxy-
adenosine and its derivatives, which are toxic to imma-
ture lymphocytes, especially those of the T-cell lineage.
Hence there is a greater reduction in T lymphocytes
than B lymphocytes. Although the number of NK cells is
low, their function is normal. Other distinguishing fea-
tures of ADA deficiency include the presence of rib cage
deformity and numerous skeletal deformities.
Diagnosis and Treatment.
Severe combined immuno-
deficiency is a pediatric emergency. Because the disorder
is not apparent at birth and early recognition is essential
for lifesaving treatment, a recommendation to add SCID
and other severe T-cell defects to the routine newborn
screening panel was approved by the U.S. Department
of Health and Human Services in 2010.
42
All infants
who test positive on the newborn screening test should
receive rapid referral to an immunologist for a complete
immune evaluation.
Bone marrow transplant is the mainstay treatment
for all forms of SCID. Both HLA-identical and T-cell
depleted HLA-haploidentical hematopoietic stem cell
transplants have been very effective in reconstitution of
the immune system, especially if performed within the
first 3.5 months of life and without pretransplantation
chemotherapy or posttransplanation drugs for graft-
versus-host rejection prophylaxis.
35
Enzyme replace-
ment therapy also may be used in the management of
persons ADA-deficient SCID. However, it should not
be used if bone marrow transplantation is anticipated
because it can predispose to graft rejection.
35,40
Immune Deficiency withThrombocytopenia
and Eczema
Immune deficiency with thrombocytopenia and eczema
(Wiskott-Aldrich syndrome) is an X-linked recessive dis-
order characterized by thrombocytopenia, eczema, and
marked susceptibility to bacterial infections.
2,43
Bleeding
episodes or symptoms due to infection usually begin
within the first 6months of life. Abnormalities of humoral
immunity include decreased serum levels of IgM and
markedly elevated serum IgA and IgE concentrations.
T-cell dysfunction initially is mild but progressively dete-
riorates, and children with the disorder become increas-
ingly susceptible to the development of malignancies of
the mononuclear phagocytic system, including Hodgkin
lymphoma and leukemia. Children with Wiskott-Aldrich
syndrome typically are unable to produce antibody to
polysaccharide antigens and therefore are susceptible
to infections caused by encapsulated microorganisms,
including septicemia and meningitis. Varicella infection
can be lethal to children with this condition.
Management of children with Wiskott-Aldrich syn-
drome focuses on treatment of eczema, control of infec-
tions, and management of bleeding episodes. Bone
marrow transplantation has been successful in children
with Wiskott-Aldrich syndrome. Splenectomy, some-
times recommended for children with thrombocytope-
nia, effectively stops the bleeding episodes but increases
the risk of septicemia.
43
Acquired Immunodeficiency
Syndrome
Acquired immunodeficiency syndrome is a disease caused
by infection with human immunodeficiency virus (HIV)
and is characterized by profound immunosuppression
with associated opportunistic infections, malignancies,
wasting, and central nervous system degeneration. HIV
is a retrovirus that selectively attacks the CD4
+
T lym-
phocytes, the immune cells responsible for orchestrating
and coordinating the immune response to infection. As
a consequence, persons with HIV infection have a dete-
riorating immune system, and thus are more susceptible
to severe infections from ordinarily harmless organisms.
As a national and global epidemic, the degree of mor-
bidity and mortality caused by HIV, as well as its impact
on health care resources and the economy, is tremendous
and unrelenting. In 2011, it was estimated that there
were nearly 34 million people worldwide living with
HIV/AIDS and 1.7 million people died of HIV-related
causes.
44
During the same year, 2.5 million people were
newly infected with HIV. Because the reporting of cases
is not uniform throughout the world, many countries
may not be accurately represented in this number.
44
Transmission of HIV Infection
Human immunodeficiency virus is transmitted through
conditions that facilitate the exchange of blood or body
fluids that contain the virus or virus-infected cells,
the major routes being sexual contact; contaminated
blood, either through sharing needles or syringes used
for illicit drugs; or passage from infected mothers to
their newborns.
2,3,45,46
It is estimated that more than
90% of children living with HIV acquired the virus
in utero, during the birth process, or through breast-
feeding.
47
Human immunodeficiency virus is not trans-
mitted through casual contact. Several studies involving
more than 1000 uninfected, nonsexual household con-
tacts with persons with HIV infection (including sib-
lings, parents, and children) have shown no evidence of
casual transmission.
48
Sexual contact is the most frequent mode of HIV
transmission. There is a risk of transmitting HIV when
semen or vaginal fluids come in contact with a part of
the body that lets them enter the bloodstream. This can
include the vaginal mucosa, anal mucosa, and wounds or
sores on the skin. Thus, the risk of infection is increased
in the presence of ulcerative sexually transmitted infec-
tions (STIs) such as syphilis, herpes simplex virus infec-
tion, and chancroid; however, it is also increased with
nonulcerative STIs such as gonorrhea, chlamydial infec-
tion, and trichomoniasis.
46
Condoms are highly effective
in preventing the transmission of HIV. Unprotected sex
between men is still the main mode of transmission in
both Canada and the United States (48% of new HIV
cases in Canada in 2011
49
and 63% in the United States
in 2010.
50
) During the same years, 25% of newly diag-
nosed HIV/AIDS cases in the United States
50
and 30%
of newly diagnosed cases in Canada were attributable to
high-risk heterosexual intercourse.
49
