CMV is a virus in the herpes group and a common cause of infection in patients with primary immune deficiency, HIV infection, an organ transplant, or who require cancer chemotherapy.
CMV can involve all organ systems; the organism is transmitted congenitally through an infected birth canal and postnatally by breast milk, saliva, and blood (via infected white cells).
CMV pneumonia is a major cause of morbidity and mortality.
Diagnosis can be established by serology, polymerase chain reaction (PCR), antigenemia, and viral culture.
Administration of antiviral drugs (ganciclovir, foscarnet) in immunocompromised hosts improves outcome.
Varicella Zoster Virus (VZV) Infection
VZV is a DNA virus that typically causes benign infections of the skin and mucous membranes.
VZV can lead to visceral dissemination and pneumonia in children with cancer, AIDS, congenital defects of cellmediated immunity, or those who have received organ transplantation.
Varicella can be diagnosed on the basis of physical findings, vesicle scrapings using direct fluorescent antibody, serology, or PCR.
The high-risk group, of susceptible individuals, exposed to varicella should be given immune globulin (either VZIG or IVIG up to 96 hours after exposure).
Immunocompromised patients should receive IV acyclovir.
Experience with efficacy of famciclovir and valacyclovir in children is limited.
Human Herpes Virus Type 6 (HHV-6)
HHV-6 is the most widespread among the human herpes viruses and causes exanthem subitum in immunocompetent children. HHV-6 is an emerging pathogen in immunocompromised hosts and experience is limited concerning clinical manifestations, diagnosis, and treatment.
HHV-6 has been associated with clinical disease (pneumonia, encephalopathy) in patients with HIV infection and who have received a hematopoietic stem cell or solid organ transplant.
Diagnostic tests for HHV-6 includes serology, culture, immunohistochemistry, and nucleic acid assays.
Treatment is not well established; antiviral drugs that can be used are ganciclovir, valganciclovir, acyclovir, valacyclovir, cidofovir, and foscarnet.
Candida Infections
Candida species are recognized as a leading contributor to morbidity and mortality in patients with oncohematologic malignancies, HIV infection, primary immunodeficiencies, prolonged neutropenia, diabetes, corticosteroid administration, broad-spectrum antibiotic treatment, IV hyperalimentation, or indwelling central venous lines.
The portals of entry are usually lesions of the gastrointestinal tract, oral mucosa, or skin puncture sites, and organisms can disseminate by the hematogenous route to one or more organs.
Common sites of infection in patients with disseminated candidiasis include lungs, kidneys, liver, spleen, and brain.
Diagnosis of Candida infections is based on clinical findings, examination of tissue, and body fluid culture.
First-line therapy includes amphotericin B, fluconazole, and voriconazole.
Caspofungin and Micafungin are indicated as a first-line treatment in adults and may be considered in pediatric patients.
Pneumocystis jiroveci
P. jiroveci (earlier known as P. carinii) is now classified as a fungus based on ribosomal RNA and other microbiologic characteristics.
Patients at higher risk for pneumocystis pneumonia (PCP) include infants with severe malnutrition, children with primary immunodeficiencies, hematologic malignancies, HIV infection, and recipients of solid organ or hematopoietic stem cell transplants.
PCP is diagnosed through direct identification of organisms from lung tissue or induced sputum specimens.
The first-line treatment for PCP is with TMP-SMZ, given either intravenously or orally, regardless of previous prophylactic regimen.
No randomized, controlled trials have been conducted to evaluate trimethoprim/dapsone combination, pyrimethamine/sulfadoxine combination, clindamycin, primaquine, or atovaquone in children.
Invasive Aspergillosis
Aspergillus is a group of ubiquitous fungal organisms found in soil and other settings that include the hospital environment. Aspergillus organisms enter the body via the respiratory route.
Susceptible hosts include recipients of lung, hematopoietic stem cell, and liver transplants; those who received treatment for malignancy, chronic granulomatous disease, or HIV infection; and those on immunosuppressive chemotherapy.
Invasive pulmonary aspergillosis is manifested most commonly as necrotizing bronchopneumonia.
Diagnosis is established by demonstration of organisms on body fluids or tissue.
Voriconazole is the treatment of choice for invasive aspergillosis.
Diagnosis is difficult, as imaging findings are nonspecific and noninvasive tests (galactomannan assay) are difficult to interpret in children.
Mucormycosis
Infections by members of the mucormycosis class of fungi occur in children with hematopoietic malignancies, organ transplantation, and diabetes.
Mucormycosis may involve lungs, brain, sinuses, kidneys, and skin.
The organism invades blood vessels and may disseminate to other sites. Sudden death may occur due to massive pulmonary hemorrhage, mediastinitis, or airway obstruction.
Isolation of fungi is difficult; diagnosis is established by histopathology and tissue culture.
Treatment consists of prompt management of the underlying medical condition, reduction of immunosuppression, antifungal therapy (lipid formulation amphotericin B), and surgical debridement.
A noninvasive method for diagnosis is not available.
Cryptococcus
C. neoformans, a yeast-like encapsulated fungus, causes disease in immunocompromised patients.
The disease primarily presents as subacute or chronic meningitis and may involve all organ systems in disseminated disease.
Diagnosis of cryptococcal pulmonary infection is suggested by characteristic clinical and radiographic findings, sputum culture, serologic assays for IgG and IgM, and serologic testing for cryptococcal polysaccharide antigen by latex agglutination.
Treatment consists of combination of amphotericin B and flucytosine.
Histoplasmosis
Histoplasmosis is a systemic disease caused by the dimorphic fungus H. capsulatum.
Histoplasmosis occurs more commonly in children with HIV infection.
Clinical manifestations include acute, progressive, lifethreatening infection that presents as unexplained fever, weight loss, respiratory complaints, abdominal pain, and diarrhea.
Diagnosis is made via culture, fungal stain, antigen detection, and serologic tests for antibodies.
Amphotericin B is the standard therapy for serious infections, followed by itraconazole for long-term suppressive therapy.
Nontuberculous Mycobacteria
Nontuberculous mycobacteria pathogens frequently cause opportunistic infections associated with AIDS and primary immune deficiency disorders.
Clinical manifestations of disseminated disease include lymphadenopathy and gastrointestinal tract involvement.
Treatment depends on the organism involved and site of infection. Commonly used drugs for pulmonary disease are clarithromycin and ethambutol, with other antituberculosis drugs used in disseminated disease.
Epidemiology, clinical features, and management protocols have not been well established.
Mycobacterium tuberculosis
HIV and tuberculosis (TB) form a lethal combination because each increases the other’s progress.
TB can occur in HIV-infected individuals at any CD4 count.
TB in HIV-infected children may be more severe, progresses very fast, and causes more extrapulmonary manifestations.
Diagnosis of TB in children is very difficult. No simple test exists for confirmation of diagnosis. Diagnosis is based on demonstration of acid-fast bacilli (AFB) in sputum or other body fluid. In the absence of AFB, a diagnosis of probable TB can be made on the basis of a history of contact with adults with TB, a positive tuberculin skin test, and compatible radiologic findings.
A newer test, the automated nucleic acid amplification test, performed on sputum or on gastric aspirates may give results within 2 hours for the presence of Mycobacterium tuberculosis and of its resistance to rifampicin.
Treatment for TB depends on the clinical syndrome and consists of anti-TB drugs for 6-12 months.
Toxoplasmosis
Disseminated T. gondii infection in immunocompromised patients has emerged as a potentially fatal pathogen.
Common presentations include fever, encephalitis, pneumonia, myocarditis, and bone marrow suppression.
Confirmation of the diagnosis is either through serologic methods (reserved for immunocompetent hosts) or molecular methods, such as PCR.
Treatment consists of administration of pyrimethamine, sulfadiazine, and folinic acid.
Cryptosporidium Infection
Cryptosporidium spp. causes severe diarrheal in children with HIV infection, primary immunodeficiencies, or acute leukemia on chemotherapy.
Diagnosis of cryptosporidium infection is made by examination of stool.
Treatment is not satisfactory. The current therapy includes supportive care with administration of nitazoxanide.
Opportunistic infections typically do not cause disease in a person with a healthy immune system but generally affect people with a poorly functioning or suppressed immune system because of immunodeficiency or immunosuppression.
These infections can be severe to fatal, but early recognition and treatment may improve outcomes. The diagnosis of infections in immunocompromised pediatric patients remains a difficult challenge as presenting clinical signs and symptoms may be atypical and serologic testing may be unreliable. Immunocompromised children include those with congenital defects of host defense and defects in cell-mediated or humoral immunity, but the major expansion of this population has occurred with increased hematopoietic stem cell and solid organ transplantation, successful treatment of childhood malignancies, and the use of immunomodulatory agents for chronic diseases such as Crohn disease and rheumatoid arthritis. These developments have significantly increased the population of children at risk for opportunistic infections, and the list of organisms that lead to infections in these groups has become extensive and continues to grow. Pediatric intensivists are likely to see increasing numbers of children survive with primary immunodeficiencies or receive immunosuppressive therapy for treatment of malignancies, autoimmune disorders, or transplantation. For this reason, it is critical that all practitioners are able to recognize signs and symptoms of infections in these patients.
TABLE 95.1 CONDITIONS PREDISPOSING AN INDIVIDUAL TO OPPORTUNISTIC INFECTIONS
▪ MAJOR DEFECTS IN IMMUNE SYSTEM
▪ CLINICAL CONDITIONS
▪ INFECTIONS/CLINICAL MANIFESTATIONS
B-cell defects (humoral deficiencies)
Agammaglobulinemia, hypogammaglobulinemia, selective IgA deficiency, IgG subclass deficiencies, common variable immune deficiency, hyper-IgM syndrome
Infections with S. aureus; encapsulated organisms, such as S. pneumoniae, H. influenzae; and gram-negative organisms, such as Pseudomonas species
Arthritis due to echoviruses, coxsackieviruses, adenoviruses, and U. urealyticum
Infections due to P. jiroveci (P. carinii) pneumonitis, and Cryptosporidium
Infections caused by bacteria, fungi, or viruses Chronic diarrhea, mucocutaneous or systemic candidiasis, P. jiroveci pneumonitis, and CMV early in life
Infections with S. pneumoniae or H. influenzae type b, P. jiroveci
Late-onset recurrent sinopulmonary infections from bacteria and respiratory viruses
Recurrent episodes of S. aureus abscesses of the skin, lungs, and musculoskeletal system
Recurrent pyogenic and fungal infections due to Pseudomonas, S. marcescens, and S. aureus, and fungi such as Aspergillus and Candida present as cellulitis, perirectal abscesses, or stomatitis
Pulmonary infection, suppurative adenitis, subcutaneous abscess, liver abscess, osteomyelitis, and sepsis due to fungi or bacteria (Staphylococcus)
Gastric outlet obstruction, urinary tract obstruction, and enteritis or colitis
History of delayed cord separation and recurrent infections of the skin, oral mucosa, and genital tract, Predisposed to development of ecthyma gangrenosum and pyoderma gangrenosum
Disorders of the complement system
Disorders involving any one of the complement components, asplenia, splenic dysfunction due to hemoglobinopathies, splenectomy
Infections due to Salmonella spp. and encapsulated bacteria including S. pneumoniae and H. influenzae. These agents can cause sepsis, pneumonia, meningitis, and osteomyelitis
Infections occurring with acquired immunodeficiencies
HIV and other virus infections, cancer chemotherapy, immunosuppressive therapy after organ transplant, diabetes mellitus, sickle cell disease, severe malnutrition
Similar to cell-mediated immune deficiency
Neutropenic patients: infections due to gram-positive cocci and gram-negative organisms, such as P. aeruginosa, E. coli, and Klebsiella
Fungal infections due to Candida and Aspergillus in prolonged neutropenia