Book Text

Human Immunodeficiency Virus

With major improvements in the treatment and management of HIV, the incidence of new infections in children is decreasing in the United States and Western Europe. HIV in a young child is secondary to vertical transmission from a seropositive mother. Adolescents with HIV infection present in much the same way as an adult; therefore, this discussion is limited to HIV in younger children.

Perinatal HIV is the primary issue. A mother with untreated HIV infection has a 12% to 30% chance of infecting her child. Perinatal treatment of infected mothers with antiretroviral drugs has dramatically decreased these rates. Vertical transmission can occur in the intrauterine setting (30% to 40%), in the intrapartum setting by exposure to infected blood or cervicovaginal secretions (60% to 70%), or in the postpartum setting by breast-feeding (rare in industrialized nations). The diagnosis of perinatal infection is problematic in that most infants have passively acquired maternal IgG antibody, which prevents serodiagnosis. Nucleic acid-based detection methods are the preferred virologic assay in developed countries. Testing should be performed within the first 2 days of life to begin early initiation of anti-retroviral therapy, but false negatives can occur, and repeat testing through 4 to 6 months of age is recommended. The usual clinical manifestation in the very young includes failure to thrive, hepatosplenomegaly, and chronic interstitial pneumonitis. The toddler age group has a higher incidence of lymphadenopathy, recurrent bacterial infections, neurologic delay, and progressive encephalopathy. Some children may be asymptomatic for years.

Pneumocystis carinii pneumonia (PCP) is seen in all age groups, but it is more common and associated with higher mortality in children younger than 1 year. The mainstay

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**TABLE 76-19** -- Opportunistic infection in inherited and acquired disorders
Predisposing Causes: Inherited and Acquired Disorders of Inflammation or Immunity	Opportunistic Organism Isolated Most Frequently	Suggested Mechanisms
Chronic granulomatous disease	Staphylococcus, gram-negative enteric organisms, Serratia, Nocardia	Impaired production of H₂ O₂ with defective bactericidal function
Job's syndrome	Staphylococcus aureus	Unknown
Myeloperoxidase deficiency	Candida	Failure to kill Candida
Glucose-6-phosphate dehydrogenase deficiency	Staphylococcus, Serratia	Deficient cellular NADH and NADPH, deficient HMPS activity, decreased H₂ O₂ production, defect in bacterial killing
Chédiak-Higashi syndrome	Pyogenic infection	Defective bactericidal activity, impaired chemotaxis, neutropenia
Congenital neutropenia	Herellea, Serratia, Pseudomonas, Staphylococcus epidermidis	Insufficient number of neutrophils
Complement deficiencies (C3, C3 inactivator)	Pathogens (e.g., Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria meningitidis)	Defective chemotaxis, impaired opsonization
Splenic insufficiency	Streptococcus pneumoniae, Salmonella	Defective opsonization, defective clearing of organisms
Sickle cell disease and other hemoglobinopathies	Streptococcus pneumoniae, Salmonella, Edwardsiella	Reticuloendothelial blockade, defective opsonization
Humoral immunodeficiency syndrome (predominantly B-cell defects)	Bacterial pathogens, Pseudomonas	Reduced phagocytic efficiency, failure of lysis and agglutination of bacteria, inadequate neutralization of bacterial toxins
Cellular immunodeficiency syndromes (predominantly T-cell defects)	Mycobacterium, Listeria, Nocardia, cytomegalovirus, varicella, Cryptococcus, Candida, Pneumocystis	Absence of or impaired delayed hypersensitivity response, absent T-cell cooperation for B-cell synthesis of antibodies to T-cell-specific antigens
Severe combined immunodeficiency syndrome	Many bacteria, fungi, viruses, and Pneumocystis	Absence of T- and B-cell responses
Cancer	Pseudomonas, Klebsiella, Escherichia coli, Listeria, Cryptococcus, varicella-zoster, herpes simplex, Pneumocystis, Mycobacterium; incidence of infection with gram-negative organism increases in presence of neutropenia	Granulocytopenia, decreased neutrophil chemotaxis, decreased bactericidal activity of neutrophils, lymphopenia, defective cell-mediated immunity, impaired antigenic response to challenge
Immunosuppression	Pseudomonas, Klebsiella, Escherichia coli, Herellea, Serratia, herpes simplex, varicella-zoster, cytomegalovirus, Epstein-Barr virus, papovavirus, hepatitis virus, Candida, Aspergillus, Mucor, Cryptococcus	Dependent on agent used
Transplantation	Staphylococcus, Pseudomonas, Klebsiella, Candida, Aspergillus, Nocardia, Pneumocystis, cytomegalovirus, hepatitis viruses, herpes simplex, varicella-zoster	Probably related to use of immunosuppressive agents
Malnutrition	Measles, herpes simplex, varicella-zoster, Mycobacterium	Impaired T-cell function, reduction in complement activity, impaired migration of phagocytes, reduced bacterial activity
Cystic fibrosis	Staphylococcus, Pseudomonas	Presence of ciliary dyskinesia factor, impaired phagocytosis of Pseudomonas
Diabetes mellitus	Staphylococcus, Escherichia coli, Proteus, Clostridium, Actinomyces, Candida, Mucor, Torulopsis	Impaired phagocytic activity, decreased serum opsonizing capacity, decreased chemotaxis of neutrophils
Polyendocrinopathy	Candida	Unknown
Nephrotic syndrome	Streptococcus pneumoniae, enteric bacteria	Unknown
Uremia	Bacteroides, Serratia, Enterobacter, Staphylococcus, Candida, Mucor, herpes, varicella-zoster	Defects in early phases of inflammatory response, lymphopenia, impaired T-cell function
Exudative enteropathy	Streptococcus pneumoniae, enteric bacteria, Giardia lamblia	Low levels of IgG, depressed T-cell function in intestinal lymphangiectasia
Inflammatory bowel disease	Candida, Mucor, herpes, varicella-zoster	Probably not related to basic disease but rather to use of corticosteroids
Collagen diseases	Candida, Mucor, Aspergillus, Pneumocystis, diphtheroids, Listeria, Pseudomonas, Serratia, Staphylococcus, Nocardia, Aspergillus, cytomegalovirus, herpes, varicella-zoster	Probably related to use of immunosuppressive agents; may relate to involvement of reticuloendothelial system
HMPS, hexose monophosphate shunt; H₂ O₂ , hydrogen peroxide; NADH, reduced nicotinamide-adenine dinucleotide; NADPH, reduced NADH phosphate
From Feigin RD, Matson DO: Opportunistic infections: The compromised host. In Feigin RD, Cherry JD (eds): Textbook of Pediatric Infectious Diseases, vol 1, 2nd ed. Philadelphia, WB Saunders, 1987, p 1013.

of treatment remains trimethoprim-sulfamethoxazole and supportive care.

Lymphocytic interstitial pneumonitis is a slowly progressive interstitial disease characterized by chronic cough and slight to moderate hypoxemia; it is seen more commonly in children older than 1 year. The radiographic findings are small nodules and fine reticular densities. Treatment is supportive, but the efficacy of steroids remains uncertain.

Children with HIV infection are most commonly admitted to an ICU for pulmonary disease, usually PCP. At this time, aggressive care is provided in the absence of other organ system failure. Antibiotic prophylaxis and prevention have drastically decreased the incidence of disease, and survival after respiratory failure from PCP has improved.^[342]