• Infectious diseases range from minor upper respiratory tract
infection to lethal sepsis. • Occasionally, presumed noninfectious signs or symptoms are due to an infectious disease. Many nonspecific disease manifestations are presumed to be infectious. The foremost reason is the fear that an untreated minor infection may progress to a life-threatening illness if antibiotic treatment is not given. • Many infections can be treated relatively easily with antimicrobial agents; a good clinical response while receiving antibiotic treatment is taken as evidence that it is not necessary to pursue non-infectious diagnoses. • Nonetheless, many illnesses are short-lived and would resolve without antibiotics. The consequence is that many individuals are treated unnecessarily with antimicrobial agents. This unnecessary treatment has resulted in the serious problem of the development of antibiotic-resistant bacteria. Appropriate diagnosis of infectious and noninfectious diseases and providing specific treatment only as indicated would help reduce the unnecessary use of antibiotics. HISTORY A complete medical history is essential for assessment of infectious risk. • The principal symptom can suggest a primary infectious disease or infection that is secondary to another disease, such as immunodeficiency or cystic fibrosis. The history may provide many potential clues for diagnosis of infection. Family history, especially of unexpected deaths of male infants, may suggest familial immunodeficiency. PHYSICAL EXAMINATION A complete physical examination is essential to identify the signs of infection, which may be systemic, such as fever, or focal, such as localized signs of inflammation, including swelling, erythema, tenderness, and limitation of function. • Many infectious diseases have associated cutaneous signs, which require firsthand examination of the patient to characterize the lesions accurately. Accurate otolaryngologic examination is key to diagnosing upper respiratory tract infections and otitis media, the most common childhood infectious diseases in the U.S. COMMON MANIFESTATIONS Attention to the common manifestations of infectious diseases usually leads to an appropriate diagnosis. Infections often have signs and symptoms recognizable at respiratory and gastrointestinal mucosal surfaces, where microbes first interface with the host. Viral infections of the respiratory tract rarely are limited to one target site. Pharyngitis with coryza and conjunctivitis suggests a viral (adenovirus) upper respiratory infection; if there is also cough, the diagnosis may be viral bronchitis. If there are signs of respiratory distress and crackles, viral or bacterial pneumonia is likely. Alternatively, if the only manifestation is severe conjunctivitis, the diagnosis is more likely to be a bacterial conjunctivitis. The host immune response varies with age, and neonates are at risk for different types of infections and have different clinical manifestations than school-age children or adolescents. The clinical manifestations and consequences of the inflammatory response may be more deleterious than the injury directly attributed to the pathogen. Certain presentations of infections are medical emergencies. Severe gastroenteritis with extreme dehydration or sepsis with hypotension can lead to multiorgan damage and requires immediate fluid resuscitation and appropriate antibiotics. Infections of the airway, such as o croup, o epiglottitis, o retropharyngeal abscess, o peritonsillar abscess, or o tonsillitis with obstruction from severe Epstein-Barr infection, o can result in airway obstruction that may require emergent intubation or rarely tracheostomy. Fever, headache, vomiting, changes in sensorium, and signs of nuchal rigidity suggest bacterial meningitis and necessitate emergent lumbar puncture and examination of the CSF and a CT scan if indicated. DIFFERENTIAL DIAGNOSIS Fever does not always represent infection; children with overwhelming infection may be afebrile or hypothermic. • Rheumatologic disease, inflammatory bowel disease, Kawasaki disease, poisoning, and malignancy also may present with fever. • The varied manifestations of infectious diseases frequently mimic rheumatoid arthritis, lupus erythematosus, inflammatory bowel disease, leukemia, and lymphoma. Many manifestations of infectious diseases mimic noninfectious diseases. Symptoms such as bone pain or lymphadenopathy that suggest infection also are symptoms that could be due to leukemia, lymphoma, juvenile rheumatoid arthritis, or Kawasaki disease. Acute mental status changes or focal neurologic impairment could be due to infections, such as encephalitis, meningitis, or brain abscess; manifestations of brain or spinal tumors; inflammatory conditions, such as multiple sclerosis; postinfectious sequelae, such as acute demyelinating encephalomyelitis; or impairment owing to toxic ingestions or inhalants. • If the underlying cause is an infection, the presenting manifestation may be CNS infection of bacterial, viral, fungal, or parasitic origin. • Certain infections are more common in specific geographic areas; • parasitic infections are more common in tropical climates. • Diarrhea may be bacterial, viral, or parasitic in the tropics, but in temperate climates parasitic causes of diarrhea other than giardiasis are much less likely. • Certain fungal infections are common in specific geographic areas, such as coccidioidomycosis in the southwestern U.S., blastomycosis in the upper Midwest, and histoplasmosis in the central part of the U.S., especially in the states bordering the Mississippi and Ohio Rivers. In other areas, fungal pneumonias are rare except in immunocompromised persons. Some infections are prone to recurrence, especially if the treatment is suboptimal or for a shorter duration than is recommended. Recurrent, severe, or unusual (opportunistic) infections suggest the possibility of immunodeficiency. Many manifestations of mucosal allergy (rhinitis, diarrhea) may mimic an infectious disease. DISTINGUISHING FEATURES • Signs of inflammation, including fever, are routinely associated with infection, but inflammation is not specific and may reflect rheumatologic diseases, inflammatory bowel diseases, and cancer. • The absence of fever may suggest an allergic etiology, unless secondary infection (sinusitis) occurs. Initial complaints of infection may be nonspecific, especially in infants who present with fever, lethargy, irritability, excessive sleeping, or poor feeding. • Certain individual physical findings, such as unique rashes, may be diagnostic. • Because of the varied presentations of infectious diseases, it is important to investigate thoroughly every objective finding from the history and physical examination. INITIAL DIAGNOSTIC EVALUATION • The ability to diagnose specific infection accurately in pediatric patients begins with an understanding of: the epidemiology and risk factors associated with each infectious agent and the age-related susceptibility, which reflects the maturity of the immune system. Initial diagnostic evaluation requires accurately recognizing the site of the infection, recognizing all of the manifestations that are present, knowing all of the risk factors, recognizing exposure to potential infectious agents, and knowing the most likely organisms causing each infection and the usual host immune response to the infection. • Obtaining a thorough history identifies most of these risk factors (see Table 93-1). Antibiotics often are begun before a definitive diagnosis is established, which complicates the ability to rely on cultures for microbiologic diagnosis. • Although persistent or progressive symptoms despite antibiotic treatment may indicate the need to change the regimen, they more frequently indicate the need to stop all antibiotics to facilitate definitive diagnosis by obtaining appropriate cultures. Antibiotics should not be given before obtaining appropriate cultures, unless there is a life-threatening situation (e.g., septic shock). SCREENING TESTS • Laboratory diagnosis of infection includes: examination of bacterial morphology using Gram stain, various culture techniques, molecular microbiologic methods such as polymerase chain reaction (PCR), and assessment of the immune response with antibody titers or skin testing (e.g., tuberculosis). The acute phase response is the nonspecific metabolic and inflammatory response to infection, trauma, autoimmune disease, and some malignancies. Acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are commonly elevated during an infection, but are not specific for infection and do not identify any specific infection. These tests are often useful to show response to therapy (e.g., osteomyelitis). The complete blood count frequently is obtained to identify evidence of bone marrow response to infection. The initial response to infection, especially in children, is usually a leukocytosis, which is an increase in the number of circulating leukocytes, with a neutrophilic response to bacterial and viral infections. • With most viral infections, the initial neutrophilic response is transient and is followed quickly by the characteristic mononuclear response. In general, bacterial infections are associated with greater neutrophilia than are viral infections. • A shift to the left is an increase in the numbers of circulating immature cells of the neutrophil series, including band forms, metamyelocytes, and myelocytes. A shift to the left indicates the rapid release of cells from the bone marrow and characteristically is seen in the early stages of infection and with bacterial infections. Transient lymphopenia at the beginning of illness and lasting 24 to 48 hours has been described with many viral infections. Atypical lymphocytes are mature T lymphocytes with larger, eccentrically placed, and indented nuclei that classically are seen with infectious mononucleosis caused by Epstein-Barr virus (EBV). Other infections associated with atypical lymphocytosis include: cytomegalovirus (CMV) infection, toxoplasmosis, viral hepatitis, rubella, roseola, mumps, and some drug reactions. • Eosinophilia is characteristic of tissue-invasive multicellular parasites, such as the migration of the larval stages of the parasite through skin, connective tissue, and viscera. • High-grade eosinophilia (>30% eosinophils, or a total eosinophil count >3000/μL) frequently occurs during the muscle invasion phase of trichinellosis, the pulmonary phases of ascariasis and hookworm infection (eosinophilic pneumonia), and the hepatic and CNS phases of visceral larva migrans. • Other common screening tests include urinalysis for urinary tract infections (UTIs), transaminases for liver function, and lumbar puncture for evaluation of the CSF if there is concern for meningitis or encephalitis. A grouping of various tests may help distinguish viral versus bacterial infection, but definitive diagnosis requires culture or PCR. Cultures are the mainstay of diagnosis. • Blood cultures are sensitive and specific for bacteremia that may be primary or secondary to a focus (osteomyelitis, gastroenteritis, urinary tract, endocarditis). • Urine cultures confirm UTI, which may be occult in young infants. • CSF cultures should be obtained with any lumbar puncture. • Other cultures are determined by the presence of fluid collections or masses that are suspected to be infectious. • Tissue culture techniques help identify viruses and intracellular pathogens. Rapid tests are useful for preliminary diagnosis and are included in numerous bacterial, viral, fungal, and parasitic antigen detection tests. • Serologic tests, using enzyme-linked immunosorbent assay (ELISA) or Western blotting, showing an IgM response, high IgG, or seroconversion between acute and convalescent sera can be used for diagnosis. • Molecular detection methods, such as PCR for DNA or RNA, offer the specificity of culture, high sensitivity, and rapid results. • When an unusual infection is suspected, the laboratory must be notified before the sample is obtained. DIAGNOSTIC IMAGING • The choice of diagnostic imaging mode should be based on the location of the findings. • In the absence of localizing signs and an acute infection, imaging of the entire body is rarely productive. • There is often more than one suitable approach to diagnostic imaging of suspected infections. Plain x-rays are useful for the middle and lower respiratory tract, but they have been superseded by cross-sectional imaging techniques. Ultrasonography is a noninvasive, nonirradiating technique well suited to infants and children for solid organs, such as the kidneys, liver, pancreas, and spleen. It also is useful to identify soft tissue abscesses with lymphadenitis and to diagnose suppurative arthritis of the hip. • CT (with contrast enhancement) and MRI (with gadolinium enhancement) allow characterization of lesions and precise anatomic localization and are the modalities of choice for the brain. • CT shows greater bone detail, and MRI shows greater tissue detail. • High-resolution CT is useful for complicated chest infections. • Contrast studies (upper gastrointestinal series, barium enema) are used to identify mucosal lesions of the gastrointestinal tract, with CT or MRI for evaluation of appendicitis and intra- abdominal masses. • A voiding cystourethrogram (VCUG) is used to evaluate for ureteral reflux, which is a predisposing factor for upper UTIs. MRI is especially useful for diagnosis of osteomyelitis, myositis, and necrotizing fasciitis. • Radionuclide scans, such as technetium-99m for osteomyelitis and dimercaptosuccinic acid (DMSA) for acute pyelonephritis or chronic renal scarring, are often informative.
Contagious Diseases: The Science, History, and Future of Epidemics. From Ancient Plagues to Modern Pandemics, How to Stay Ahead of a Global Health Crisis