Porth's Essentials of Pathophysiology, 4e

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Infection and Immunity

U N I T 4

Acquired Immunodeficiency Syndrome

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 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