591CHAPTER 52 Pneumonitis and Interstitial Disease Viral Pneumonitis Infection is the most common cause of pulmonary interstitial disease in children, and viral agents are the leading cause of lower r[.]
CHAPTER 52 Pneumonitis and Interstitial Disease TABLE Viral Agents Associated With Pediatric 52.4 Interstitial Lung Disease Agent Frequency Respiratory syncytial virus 11111 Parainfluenza virus 1111 Adenovirus 111 Influenza virus 111 Cytomegalovirus Enterovirus Rhinovirus Measles Viral Pneumonitis Infection is the most common cause of pulmonary interstitial disease in children, and viral agents are the leading cause of lower respiratory tract infection in infants and children The viral agents listed in Table 52.4 account for the greatest percentage of pediatric pulmonary disease Nearly 85% of all hospitalizations of children younger than 15 years occur during outbreaks of respiratory syncytial, parainfluenza, or influenza virus The diagnosis of viral pneumonia in children is frequently based on the clinical presentation, epidemiologic setting, and exclusion of bacterial pathogens by negative cultures A specific agent is identified in only approximately 50% of cases of presumed viral pneumonia Pediatric viral respiratory tract infections occur most commonly during the winter, with distinct peaks during midwinter and early spring in temperate climates Closed population groups provide for greater spread of respiratory viruses and increased recognition of viral pneumonias Pathophysiology The mechanism of infection for most respiratory viruses appears to be a progressive spread from the larger airways to the alveoli The respiratory epithelial cell is the major target of cytopathic effect The normal ciliated columnar epithelium may become markedly dysplastic with loss of the overlying cilia.50,51 Areas of ulceration then occur as segments of the mucosal surface desquamate into the bronchial lumen Impaired mucociliary clearance occurs, and altered stimulation of nerves mediating bronchial smooth muscle tone leads to increased airway resistance.52 Enhanced mucus formation along with mucosal debris may lead to obstruction of the bronchioles, luminal narrowing, distal air trapping, and hyperinflation of various lung segments In advanced disease with complete small airway obstruction, atelectasis results, causing hypoxemia as a result of intrapulmonary shunting and V/Q imbalance In persons with severe viral pneumonia, widespread parenchymal injury caused by a necrotizing alveolitis may develop Alveolar round cell infiltrates often occur, with subsequent hyaline membrane formation and intraalveolar hemorrhage, which produces extensive parenchymal destruction and diminished lung compliance, decreased lung volumes, and intrapulmonary shunting.53 591 Diagnosis Although the clinical presentations of illness by respiratory viruses overlap, presumptive diagnosis of the specific etiology is based on clinical presentation, setting, and, most importantly, epidemiologic information In the past, virus isolation or seroconversion was necessary for a definitive diagnosis Today many respiratory viral infections can be diagnosed using new techniques.54 Viral specimens should be obtained as early as possible during the period of greatest viral excretion Cultures may be negative in up to 40% of patients during acute viral respiratory tract disease; failure to isolate a virus is not definitive evidence against the diagnosis of viral pneumonia Serologic tests—including complement fixation, hemagglutination inhibition, enzyme-linked solid-phase assays (enzyme-linked immunosorbent assays), and antibody assays—have been used in the diagnosis of viral infection Histologic evidence of infection in biopsy or postmortem specimens may be helpful, particularly when intranuclear inclusions are documented Rapid diagnostic techniques focus on detection of the virus or its components in the sample These new techniques include refinements in the use of immunofluorescence, enzyme immunoassay, time-resolved fluoroimmunoassay, latex agglutination assays, and use of nucleic acid hybridization methods, such as DNA probes and PCR.55–58 Three major clinical syndromes are associated with lower respiratory tract viral illness: Bronchitis: Acute bronchitis is a febrile illness associated with a new productive cough Symptoms of upper respiratory tract infection may be present Acute bronchitis can adversely affect respiratory function, particularly in patients with chronic pulmonary impairment, leading to hospitalization of persons with marginal lung function Bronchiolitis: Symptoms result from airflow obstruction caused by localized inflammation of the terminal respiratory bronchioles The development of cough; tachypnea with intercostal retractions; fine, moist, inspiratory crackles; and expiratory wheezes are characteristic Hypoxemia and cyanosis are often present.59 Pneumonia: Primary viral pneumonia is frequently a mild illness characterized by a mild cough and one or more segmental infiltrates on chest radiograph Although usually a self-limited process, some patients may progress with extensive parenchymal injury, diffuse interstitial alveolar infiltrates, and severe hypoxemia Bacterial superinfection is heralded by increased temperature, change in sputum, and signs of localized consolidation several days after the initial onset of symptoms Radiographic Findings Differentiation of bacteria from viral pneumonia cannot be made solely on radiographic appearance Children with presumed viral pneumonia, however, may have several radiographic findings, including the following: Peribronchial thickening and perihilar linear densities Partial lobar or patchy involvement in multiple areas of the lung Shifting regional infiltrates Areas of hyperinflation and atelectasis Hilar adenopathy is usually absent Diffuse bilateral infiltrates similar to those reported in acute respiratory distress syndrome (ARDS) have been found in persons with severe influenza, adenovirus, and respiratory syncytial virus (RSV) pneumonias.60 Pleural effusions can occur in both adenovirus and parainfluenza 592 S E C T I O N V Pediatric Critical Care: Pulmonary pneumonias Pulmonary calcifications/nodules have been described in the convalescent phase of varicella and measles Specific Pathogens We review the most common viral pathogens that cause pneumonitis in children but have elected to exclude such viruses as hantavirus, which are beyond the scope of this chapter There continue to be viruses that are identified as pathogens in viral pneumonitis but as of yet not have effective chemoprophylaxis or therapy, such as the human metapneumovirus or the bocavirus Thus, their inclusion would not add to our discussion Consult up-to-date journal articles for specific pathogens of interest.25,61 Respiratory Syncytial Virus RSV is the most common cause of bronchiolitis and pneumonia in the United States in children between the ages of months and years The disease produced by RSV varies from upper respiratory tract infection to severe bronchiolitis and pneumonia with wheezing and respiratory failure.59 Higher mortality rates and greater severity with prolonged symptoms occur in infants and children younger than weeks of age and in those who have a history of prematurity, chronic lung disease, cardiopulmonary disease, congenital heart disease, pulmonary hypertension, or neuromuscular impairment, as well as in those receiving chemotherapy or immunosuppressive therapy.16,62–69 Signs of RSV pneumonia include wheezing, dyspnea, pulmonary infiltrates, and areas of atelectasis and hyperinflation on the chest radiograph RSV infection may result in increased airway reactivity and airway resistance that persists for months Significant respiratory tract shedding of virus continues for up to 21 days from the onset of illness Nosocomial spread of RSV infection is common; early diagnosis and appropriate isolation techniques are critical in hospitalized patients Methods for diagnosis of RSV include viral isolation in cell culture, immunofluorescence of exfoliated nasopharyngeal epithelial cells for detection of RSV antigens, and enzyme immunoassay for detection of RSV antigens in nasal secretions.70,71 PCR technology is also commonly used All hospitalized patients with bronchiolitis and RSV pneumonia should be monitored for hypoxia, hypercarbia, and the need for ventilatory assistance Supportive care includes the use of humidified oxygen, secretion clearance, and hydration.72,73 Mechanical ventilation for respiratory failure is usually well tolerated Extracorporeal membrane oxygenation has been used successfully in infants who not respond to conventional ventilation.74,75 The routine administration of bronchodilators and corticosteroids is not warranted; use should be individualized on the basis of clinical response.75,76 Passive immunoprophylaxis has proved useful in high-risk populations in preventing RSV infection, as has palivizumab, a humanized mouse monoclonal antibody.33,77–81 The incidence of bacterial superinfection in persons with RSV disease is low; therefore, prophylactic antibiotics are not recommended for RSV disease.62,82,83 It is not unusual for an infant with RSV to require hospitalization for to 10 days following the onset of illness Long-term complications of RSV infection may include persistent bronchial reactivity, with lower respiratory tract symptoms in more than 70% of infants in the year following hospitalization.84 Whether moderately severe RSV infection predisposes a person to asthma later in life remains controversial.85–89 Parainfluenza Virus Parainfluenza virus (types and 2) is more often associated with laryngotracheobronchitis and croup than with pneumonia (usually type 3) Parainfluenza is second only to RSV as an etiology of lower respiratory tract disease responsible for the hospitalization of children.90–96 The pneumonia associated with parainfluenza is typically mild; however, fatal cases with prolonged viral shedding have been reported in patients with severe combined immunodeficiency disease.97–100 Conferred immunity following infection is low; repeat infection occurs in nearly 50% of patients by age 30 months, although it results in progressively milder illness Parainfluenza virus, like RSV, has demonstrated the ability to elicit an immunoglobulin E–specific antibody response.93 Rapid identification of parainfluenza virus by either fluorescent or enzyme-linked immunologic techniques is possible, but results are variable depending on the viral type and antisera used A viral culture may take up to week PCR methods are available for detection and differentiation, with high sensitivity and specificity Treatment is supportive Adenovirus Adenoviruses are responsible for approximately 3% of the pneumonias occurring in children Clinical features are similar to other viral pneumonias except that the onset of illness is often gradual, occurring over several days Of the 51 serotypes, types 3, 4, and are the most common causes of lower respiratory tract disease in children Adenovirus type is most commonly associated with severe pneumonitis in infants and children and has a significant incidence of mortality and morbidity.41,101–105 In 2007, a new strain of adenovirus 14 was isolated in previously healthy infants and young adults in the United States in whom fatal pneumonia developed.106 A clinical presentation similar to that of bacterial pneumonia—with massive pleural effusion, rhabdomyolysis, and myoglobinuria—has been reported with adenovirus type 21.107 In many infants with documented adenovirus respiratory tract infection, chronic pulmonary disease develops, which manifests as persistent atelectasis, bronchiectasis, and recurrent pneumonitis with areas of hyperinflation and interstitial fibrosis Bronchiectasis and restrictive lung disease have been documented in children following acute adenovirus infection Adenovirus pneumonia is the most common cause of bronchiolitis obliterans in children, and unilateral hyperlucent lung syndrome has been reported.108–112 Disseminated adenovirus occurs and is usually associated with infection by serotype 3, 7, or 21 It occurs most frequently in infants younger than 18 months and usually involves the heart, pericardium, liver, pancreas, kidneys, CNS, and skin.113 Fatal cases of adenovirus and pneumonia can occur in previously healthy young individuals Diagnosis is made by cell culture and antigen and DNA detection by PCR Adenovirus typing is available from some reference and research laboratories Treatment is mainly supportive in immunocompetent patients, but cidofovir and intravenous immunoglobulins (IVIGs) have been used in some immunocompromised patients.114 Influenza Three antigenically distinct influenza viruses exist—types A, B, and C All three have hemagglutinin surface antigen, but only types A and B have neuraminidase surface antigen Antigenic drift for types A and B produces minor changes in the surface antigens, resulting in endemic illness Antigenic shift occurs only with influenza type A, resulting in a major change or new surface antigen CHAPTER 52 Pneumonitis and Interstitial Disease for which there may be low or no immunity in the population Influenza type A is subtyped by its surface antigens; currently, three influenza strains are circulating worldwide, including influenza A/H1N1, H1N2, and H3N2.33,115 Clinical signs of uncomplicated influenza pneumonia include coryzal symptoms followed by dyspnea, fever, cyanosis, cough, and wheezing Children with influenza typically have a more sudden onset of “toxic” signs than those with other viral diseases Infection is associated with myalgia, encephalopathy, and cardiac involvement Pathologically, influenza virus infection is similar to RSV in that the virus destroys ciliated respiratory epithelial cells with subsequent edema and an acute inflammatory response Influenza has been associated with Reye syndrome and significant bacterial suprainfections.116 In patients in whom bacterial infection develops, there often is a period of apparent improvement before a sudden worsening that is heralded by the production of purulent sputum, return of fever, and development of pulmonary consolidation.117 Fatal outcomes have been reported in previously healthy children as well as in high-risk groups Prevention of influenza disease is possible with either administration of multivalent influenza vaccine (influenza A/H1N1, A/H3N2, and B) or chemoprophylaxis with oseltamivir or inhaled zanamivir (influenza A, B, and A/H1N1) One study showed the efficacy of aerosolized ribavirin in the treatment of persons with influenza B.118,119 Diagnosis of influenza pneumonia may be made by a culture of the virus from respiratory secretions or with serologic techniques Rapid diagnosis by means of immunofluorescence of exfoliated nasopharyngeal cells may be helpful, as well as by PCR Treatment includes supportive care, monitoring of respiratory status, and administration of antiviral medications Measles Measles is a highly contagious disease that is preventable by vaccine; the incidence fell below the endemic threshold in the United States in 2000.120 Endemic outbreaks continue in developing countries and when international travelers import measles to nonimmunized persons in the United States.33,120 Typical disease manifests as high fever, cough, runny nose, and generalized rash Respiratory symptoms are nearly universal in this illness, making the prevalence of measles pneumonia difficult to determine Moist crackles develop in most children, and approximately 20% have expiratory wheezes and hypoxia In cases in which radiographs have been obtained, a fine reticular infiltrate was present, compared with the nodular infiltrates in children with atypical measles Although the clinical syndrome usually resolves over to weeks, both radiographic and pulmonary function abnormalities may persist for months Severe life-threatening tracheitis may occur during the course of measles or bacterial suprainfection.121–123 In fatal cases, severe respiratory and nervous system diseases are manifested, and lung tissue demonstrating interstitial pneumonitis with diffuse endothelial cells, pneumatocyte degeneration, and presence of multinucleated giant cells has been reported.124 Diagnosis is made by isolation of the virus, standard serology, or identification of viral ribonucleic acid by reverse transcription PCR All suspected cases should be reported to local and state health departments No antiviral agent is available; treatment is supportive Two doses of vitamin A (200,000 International Units on consecutive days) have been shown to reduce pulmonaryspecific and overall mortality rates in patients up to years of age.125 Administration of IVIG may be of benefit to high-risk or 593 immunosuppressed patients when it is started within days of exposure.33 Human Immunodeficiency Virus Human immunodeficiency virus (HIV) infection in children most commonly presents with recurrent bacterial infections The major causes of morbidity and mortality in pediatric AIDS patients are associated with lung disease, ranging from opportunistic infections such as Pneumocystis jiroveci pneumonia to entities such as chronic interstitial pneumonitis.126,127 Treatment for specific pulmonary pathogens is discussed throughout this chapter, but specific guidelines for HIV/AIDS treatment are lengthy, rapidly changing, and beyond the scope of this chapter Complications The actual mechanisms by which viruses predispose the lung to secondary bacterial infection are not precisely understood Viruses are capable of altering both cellular and noncellular defenses of the respiratory tract.52,53,128 Viral infection of the epithelial cells appears to predispose the upper respiratory tract mucosa to bacterial colonization by allowing bacterial pathogens to adhere to injured cells.51,52 Viral infection may cause significant impairment of both intracellular killing and ingestion of bacteria by the pulmonary macrophage Significant defects in polymorphonuclear leukocyte chemotaxis and phagolysosome fusion occur during acute viral infection The greatest impairment of macrophage function occurs week after the onset of viral infection, which correlates with the peak incidence of bacterial superinfection Thus, superinfection during the course of viral lower respiratory tract disease appears to be the result of a combination of the cytopathic effects of the virus on the respiratory mucosa and various alterations in host immune response Significant life-threatening complications of viral lower respiratory tract disease are noted in Table 52.5 Respiratory failure with viral pneumonitis resembling ARDS is frequently seen in patients in the pediatric critical care unit It is often associated with influenza or adenovirus but can occur with varicella, cytomegalovirus, and RSV.60 Diagnosis Several techniques are available for establishing a viral diagnosis In the critical care setting, the decision to undertake these diagnostic measures should be guided by how awareness of the specific viral illness will affect clinical management Potential benefits include (1) a guide to the selection of appropriate antiviral therapy and avoidance of unnecessary treatments with antibiotics and (2) initiation of appropriate infection control measures and the use of a vaccine or drug prophylaxis Direct isolation of viruses is a sensitive method of diagnosis early in the course of a disease when a large number of infectious particles are present in respiratory secretions Nasopharyngeal washings are the preferred specimens for viral cultures because large quantities of secretions for culture are easily available Unfortunately, viral isolation may require up to weeks for positive culture results Serologic testing or diagnosis depends on the demonstration of a rising antibody titer between acute and convalescent sera Although serologic data may provide a diagnosis, they are of little value in guiding therapeutic critical care interventions The more commonly used methods for viral diagnosis involve the detection of viral antigens present in respiratory secretions These antigen-detection techniques using 594 S E C T I O N V Pediatric Critical Care: Pulmonary TABLE Major Sequelae/Life-Threatening Complications 52.5 Associated With Viral Pneumonitis Sequelae/Complication Infectious Cause Subacute sclerosing panencephalitis Measles Guillain-Barré syndrome Influenza, varicella Reye syndrome Influenza, VZV Encephalitis Adenovirus, measles, RSV, CMV Seizures Influenza Bacterial superinfection Influenza, VZV, Epstein-Barr virus, measles Asthma RSV, parainfluenza, rhinovirus Apnea RSV, influenza Bronchiolitis obliterans Influenza, adenovirus, measles Chronic obstructive pulmonary disease RSV Fatal pneumonitis Influenza, measles, adenovirus, RSV, parainfluenza, CMV Tracheitis, life-threatening Measles, parainfluenza Appendicitis Adenovirus, measles Intussusception Adenovirus, CMV Hepatitis Adenovirus, influenza, measles, CMV Nephritis Adenovirus, influenza, measles Myocarditis Adenovirus, influenza, measles Pericarditis Adenovirus, influenza, measles Arthritis Adenovirus Deafness Adenovirus Keratoconjunctivitis Adenovirus Myositis Influenza Stevens-Johnson syndrome Measles Coagulopathy Measles Thrombocytopenia Measles, CMV CMV, Cytomegalovirus; RSV, respiratory syncytial virus; VZV, Varicella zoster virus radioimmune or enzyme-linked assays can detect all riboviruses and adenoviruses that commonly produce lower respiratory tract infections Antibody detection has also been used successfully in the diagnosis of lower respiratory tract viral disease (cytomegalovirus pneumonia).129 A major advantage of tests capable of detecting viral components is that these studies can be performed rapidly and the results made available to the critical care physician in hours, allowing timely management Prevention and Treatment Guidelines for influenza chemoprophylaxis and treatment are lengthy and rapidly changing Specific and current information regarding the use of antiviral drugs is available at www.aapredbook org/flu or www.cdc.gov/flu/professionals/antivirals/index.htm Vaccination Passive immunization is also available for some viruses that can be associated with pneumonitis, but recommendations are everchanging Check the Centers for Disease Control and Prevention (CDC) recommendations and see Table 52.3 Chemoprophylaxis Amantadine, rimantadine, oseltamivir, and zanamivir are approved for prophylaxis of viral respiratory tract infection caused by influenza Amantadine and rimantadine have been shown to be effective prophylaxis for influenza type A However, they are not active against influenza type A/H1N1 or influenza type B Therefore, they are no longer recommended for prophylaxis Oseltamivir and zanamivir have activity against influenza types A, B, and A/H1N1 Oseltamivir resistance has been reported among persons with influenza type A/H1N1 strains globally, but no significant resistance has been reported among persons with influenza type A/H1N1 strains circulating in the United States Oseltamivir and zanamivir are recommended for persons at high risk for serious influenza infection who have not been vaccinated or who have received the vaccine within weeks of the onset of an epidemic They are also recommended for persons in whom appropriate immune response may not develop following vaccination and for persons who cannot receive the influenza vaccine because of allergic reactions.33,130,131 Therapy Several antiviral agents inhibit the replication of respiratory viruses in vitro Some of these drugs have been used clinically in both experimental and naturally occurring respiratory infections (Table 52.6) Most influenza A and B virus strains are susceptible to oseltamivir and zanamivir.132,133 These neuraminidase inhibitors have been shown to reduce the severity and duration of illness.134–137 Resistance to oseltamivir has been reported in persons with influenza type A/H1N1 strains but not A/H3N2 or B strains.138–141 Zanamivir is effective against influenza types A, B, and A/H1N1, but it has not been approved for therapeutic use in children younger than years.33 Peramivir was approved to treat influenza infection in adults in December 2014 Peramivir is the first neuraminidase inhibitor approved in IV form Peramivir is a neuraminidase inhibitor and should not be administered if the patient has a severe allergy to oseltamivir, zanamivir, or one of their metabolite components.142 Oral baloxavir is effective against influenza types A and B but has a different mechanism of action than neuraminidase inhibitors Resistance patterns are perpetually changing; for the most up-to-date information regarding resistance patterns, see the CDC website at www.cdc.gov/flu/ professionals/antivirals/ Ribavirin is a synthetic nucleoside analog licensed for use in aerosol form for the treatment of persons with severe RSV infection This therapy may shorten the course of the illness and improve oxygenation in high-risk patients A few children with severe combined immune deficiency have been treated with ribavirin with resulting clinical improvement and decrease in viral shedding.65,143–153 Ribavirin aerosol may be effective in shortening the course of both influenza types A and B in infections in college students, and it is possible that parainfluenza and the measles virus can be treated with ribavirin.154 Various case reports of treatment in seriously ill adults with complicated viral infections suggest that ribavirin may be an effective treatment Overall, the documented therapeutic benefit of antiviral agents has been inconclusive Improvement is most apparent when the therapy was CHAPTER 52 Pneumonitis and Interstitial Disease 595 TABLE Antiviral Agents Used in Viral Pneumonia 52.6 Agent Indication Route Side Effects Acyclovir HSV, varicella Prophylaxis/treatment IV, PO Phlebitis, seizures, leukopenia, renal dysfunction Valacyclovir HSV, varicella Prophylaxis/treatment PO Bone marrow suppression, renal failure Ganciclovir CMV in immunocompromised host Prophylaxis/treatment IV, PO Renal failure, bone marrow suppression, seizure Valganciclovir CMV prophylaxis PO Same as ganciclovir Baloxavir Influenza types A and B Treatment PO None more common than placebo in clinical trials Zanamivir Influenza types A and B Treatment, prophylaxis under study Diskhaler Bronchospasm Oseltamivir Influenza types A and B Prophylaxis/treatment PO Nausea, vomiting, vertigo Peramivir Influenza type A and limited type B treatment IV Stevens-Johnson syndrome, erythema multiforme, neuropsychological events, and diarrhea RSV-IVIG RSV prophylaxis (high-risk population) IV Allergic, fluid overload, not approved for CCHD Palivizumab RSV prophylaxis IM Anaphylaxis Ribavirin RSV (parainfluenza, influenza types A and B, measles) Small-particle aerosol Conjunctival edema Foscarnet CMV retinitis, HSV resistant to acyclovir IV Renal dysfunction, nausea, bone marrow suppression Pleconaril (under investigation) Enterovirus and rhinovirus Prophylaxis/treatment PO Under investigation CCHD, cyanotic congenital heart disease; CMV, cytomegalovirus; HSV, herpes simplex virus; IM, intramuscular; IV, intravenous; IVIG, intravenous immunoglobulin; PO, by mouth; RSV, respiratory syncytial virus initiated early after the onset of infection Future investigations are necessary to define the optimum dose/route of antiviral agents for each respiratory virus/pneumonia and to clarify the ability of antiviral therapy to modify serious lower respiratory tract infection in high-risk infants and children In persons with varicella or zoster, acyclovir reduces the period of viral shedding and the time needed to heal skin lesions It can also prevent the dissemination of localized zoster in immunocompromised children Thus, the use of acyclovir in immunosuppressed patients can be justified by the low toxicity of the drug and the potential severity of the illness Ganciclovir is an antiviral drug with significant activity against cytomegalovirus.155 It has been used successfully in immunocompromised patients with disseminated cytomegalovirus and pneumonia.156 Symptomatic infection of the lower airway with herpes viruses is rare When it occurs, it usually does so in an immunosuppressed child Antiviral therapy for herpes viruses includes acyclovir, foscarnet, and adenine arabinoside.157,158 Fungal Pneumonitis Fungal infections are becoming increasingly important in the differential diagnosis of pulmonary infections, particularly in immunocompromised hosts The majority of pulmonary mycotic infections occur in two microbiologic and clinical groups (Box 52.2) In general, different patient groups are at risk for infection because of either opportunistic or pathogenic dimorphic pulmonary fungi • BOX 52.2 Major Pulmonary Mycoses Primary (Endemic; Pathogenic to Normal Children) Dimorphic Soil • • • • • Histoplasmosis Blastomycosis Coccidioidomycosis Paracoccidioidomycosis Sporotrichosis Nondimorphic Soil • Cryptococcosis Opportunistic (Ubiquitous; Abnormal Host) • Aspergillosis • Mucormycosis • Candidiasis Primary pulmonary mycotic infections generally infect healthy children exposed to the pathogen in a particular geographic or environmental setting, whereas the opportunistic mycoses occur in children whose immunity is compromised.159,160 The increase in opportunistic fungal infections can be attributed to numerous factors, including the following: Selection of fungal organisms as flora by the use of broadspectrum antibiotics Leukopenia secondary to use of cytotoxic agents ... pulmonary pathogens is discussed throughout this chapter, but specific guidelines for HIV/AIDS treatment are lengthy, rapidly changing, and beyond the scope of this chapter Complications The actual... high fever, cough, runny nose, and generalized rash Respiratory symptoms are nearly universal in this illness, making the prevalence of measles pneumonia difficult to determine Moist crackles develop... Administration of IVIG may be of benefit to high-risk or 593 immunosuppressed patients when it is started within days of exposure.33 Human Immunodeficiency Virus Human immunodeficiency virus (HIV) infection