Intrathoracic tuberculosis (pulmonary parenchymal disease, intrathoracic lymphadenopathy, and pleural disease) and peripheral lymphadenopathy account for over 90% of all cases of childhood tuberculosis Most children with tuberculosis have negative acid-fast sputum smears and cultures; the diagnosis is instead based on a triad of findings: a positive TST or TB blood test (interferon gamma release assays [IGRAs]); compatible radiographic and clinical findings; and contact with a person known to have tuberculosis disease Preadolescent children with pulmonary tuberculosis without cavitary findings on radiography rarely are contagious; however, providers should utilize airborne precautions because in many instances, the child is brought to the ED by the person from whom they acquired tuberculosis, and that adult is by definition contagious Current Evidence The most common sites of infection are intrathoracic (pulmonary parenchymal, intrathoracic adenopathy, and/or pleural effusions) and peripheral lymphadenopathy Together, these account for over 90% of all childhood TB cases Meningeal tuberculosis comprises 1% to 2% of all childhood TB cases, and is most common in children in the first years of life Latent tuberculosis infection (LTBI) is defined as a positive TST ( e-Table 94.16 ) or IGRA in a child who lacks TB symptoms and has a normal chest radiograph and physical examination While LTBI will rarely be an ED-based diagnosis, clinicians may see children with LTBI for nontuberculosis concerns or for medication adverse events Children with LTBI are not contagious and have no specific infection control considerations As most tuberculosis medications are hepatically metabolized, the clinician should be aware of potential hepatotoxicity if a child receiving tuberculosis medication presents with abdominal pain, vomiting, anorexia, or icterus Isoniazid (INH) can also cause peripheral neuropathy and can cause benzodiazepine-refractory seizures in cases of overdose (the antidote is pyridoxine, administered as a gram-to-gram dose based on the estimates of the INH dose ingested) Goals of Treatment The goal of treatment is to recognize which children with pulmonary, meningeal, or lymphadenitis may have tuberculosis as opposed to other diagnoses Clinical Considerations Clinical recognition: Tuberculosis disease ( e-Table 94.17 ) should be included in the differential diagnosis of children with fever of unknown origin; pneumonia refractory to therapy for community-acquired pneumonia; cavitary pneumonia/lung abscesses; hilar or mediastinal adenopathy; miliary pattern on chest radiograph; freeflowing pleural effusions with or without consolidation; chronic nontender adenopathy; chronic otorrhea or chronic otitis media; and meningitis with an elevated CSF protein Children with pulmonary tuberculosis often have chest radiographs that look far worse than the child Weight loss in combination with pneumonia should lead the provider to broaden the differential diagnosis outside of the usual pathogens causing community-acquired pneumonia TB meningitis has an insidious onset, and in the early stages, children may have fever and constitutional symptoms alone Unexplained protracted vomiting (due to increased intracranial pressure) often is identified only in retrospect Given the nonspecific initial symptoms and the rarity of the diagnosis in industrialized nations, many children with TB meningitis have had multiple healthcare encounters prior to diagnosis Triage considerations: While prepubertal children with noncavitary chest radiographs rarely are contagious, the person bringing the child to medical attention may be the person who transmitted tuberculosis to the child As such, airborne precautions should be used more to protect healthcare workers and other patients from the caregivers, as opposed to from the patient him/herself Clinical assessment: The diagnosis of tuberculosis in a child infrequently is made based upon microbiologic confirmation Acid-fast cultures of respiratory secretions are positive in a minority of children; the highest culture yield occurs in children with peripheral lymphadenopathy or skeletal disease Instead, children usually are diagnosed based on a triad of findings: epidemiologic links to a person with known or suspected tuberculosis disease; a positive TST or IGRA; and compatible clinical or radiographic findings A chest radiograph should be performed in all children in whom TB is suspected; the most common findings include parenchymal infiltrates, intrathoracic lymphadenopathy, and pleural effusions; miliary disease is more common in infants and immunocompromised children The majority of children with extrapulmonary disease (especially those with meningitis) will have abnormal chest radiographs CT of the brain should be obtained in children with suspected TB meningitis, as leptomeningeal enhancement, hydrocephalus, infarcts in watershed areas (e.g., putamen, caudate, basal ganglia), and tuberculomas (mass-occupying lesions) may be present and hydrocephaly may require shunting All infants in whom TB disease is suspected should undergo LP for routine studies, acid-fast culture, and M tuberculosis PCR CSF profiles show a lymphocytic pleocytosis, high CSF protein, and low CSF glucose While TSTs and IGRAs are helpful when positive, negative tests not rule out TB All children in whom TB disease is suspected should be screened for HIV and have a baseline CBC and hepatic transaminases performed Management: Initiation of multidrug tuberculosis therapy should be performed in consultation with ID specialists The management of children with drug-resistant tuberculosis is outside the scope of this chapter Airborne precautions should be used Typhoid CLINICAL PEARLS Typhoid fever is caused by the bacteria Salmonella enterica serotype typhi It is a human pathogen transmitted via the fecal–oral route and can cause local (diarrheal) or invasive disease (bacteremia, meningitis, bowel perforation, osteomyelitis) For many children fever alone is the only presenting symptom Typhoid fever is more common in the pediatric and immunocompromised hosts of any age and should be suspected in any febrile child who has returned from Asia, Africa, or Latin America in the preceding month Current Evidence Typhoid fever is endemic in sub-Saharan Africa, the Indian subcontinent, Southeast Asia, East Asia, the Middle East, and central and South America with an estimated incidence of 27 million/yr It is most prevalent in impoverished areas where sanitary conditions are poor Approximately 350 returned travelers to the United States are diagnosed with typhoid fever every year In the United States, 67% of imported cases were from South Central Asia, 10% from Southeast Asia, and 10% from sub-Saharan Africa Increasing rates of antibiotic resistance to cephalosporins, fluoroquinolones, and macrolides have been seen in recent years In Southeast Asia, reduced susceptibility to fluoroquinolones has complicated empiric therapy Goals of treatment: The goal of treatment is the rapid recognition that fever in a returned traveler could represent typhoid fever, and for the PEM clinician to be cognizant of drug-resistance patterns globally that may impact empiric antibiotic selection Clinical Considerations Clinical recognition: Many patients infected with S enterica subtype typhi are either asymptomatic or have mild symptoms; 60% to 90% not seek medical attention or are treated on in the outpatient setting Patients with typhoid fever have an insidious onset of fever and development of symptoms over a period of to 21 days after the ingestion of contaminated food or water A majority of patients develop anorexia, abdominal pain, chills, in addition to malaise, tender splenomegaly, marked headache, relative bradycardia (given the degree of pyrexia), and a nonproductive cough in the early stages Approximately 25% of Caucasian patients will develop painless, erythematous, blanchable, subcentimeter, maculopapular “rose spots” on the trunk Constipation is more common than diarrhea in young children The severity of illness is influenced by the particular strain virulence, quantity of inoculum, the age of the patient, duration of illness before initiation of treatment, and current vaccination status Complications of severe disease include shock, meningitis, pneumonia (primary Salmonella pneumonia or secondary bacterial infection), gastrointestinal perforation, or hemorrhage Chronic carriers play an important role in the transmission of the disease; they typically excrete a large number of organisms yet have a high level of immunity Carriage is uncommon in young children Triage considerations: Clinicians should consider typhoid fever in patients with abdominal pain, fever, and chills, and with recent travel to developing nations Clinical assessment: Diagnosis is made by blood culture Stool cultures are positive in approximately 30% of bacteremic patients Bone marrow cultures may be useful because they remain positive long after treatment has been initiated and are more sensitive than blood culture Serology is not recommended as it often cross-reacts with other Salmonella serotypes Management: Empiric management of children with suspected typhoid is reviewed in e-Table 94.18 Historically, fluoroquinolones have been the treatment of choice However, the recent evolution and recognition of multidrug-resistant Salmonella isolates has complicated empiric therapy In general, fluoroquinolones should not be first-line therapy if typhoid fever in patient from South Asia or other regions where there is a known increase in resistance to fluoroquinolones For travelers to this area, use of third-generation cephalosporins and high-dose azithromycin (1 g) is recommended Bacteremia should be treated for a total 7- to 10-day total course, with transition from parenteral to oral therapy after bacteremia has cleared and antibiotic susceptibilities are available In some sub-Saharan African nations, up to 40% of Salmonella isolates are cephalosporin In patients with severe systemic illness, such as typhoid-associated shock or encephalopathy, dexamethasone (3 mg/kg followed by mg/kg every hours for 48 hours), should be considered The chronic carrier state can be eradicated by weeks of oral fluoroquinolones Contact and standard precautions should be used for providers caring for children with suspected typhoid fever Dengue CLINICAL PEARLS AND PITFALLS Dengue is the most prevalent mosquito-transmitted viral illness and should be considered in the differential diagnosis of any febrile patient presenting in the ED within weeks of return from a tropical or subtropical region Clinical manifestations include self-limited dengue fever to life-threatening dengue hemorrhagic fever with shock syndrome Treatment is with supportive care and fluid resuscitation, including blood transfusion Current Evidence Dengue is transmitted by the Aedes aegypti mosquitoes, which are most active during the day, but can bite at any time of day or night The disease is endemic to central and South America, sub-Saharan Africa, the Indian subcontinent, and Southeast Asia Recently there has been a broadening of the geographic distribution of the disease In the last decade, outbreaks have been reported in Texas, Florida, and Hawaii, and the mosquito vector already is widespread throughout the southern United States The worldwide incidence has been increasing in the past several decades due to a number of factors including population growth, overcrowded urban living with poor sanitation, increasingly mobile/transient population and therefore increased mobility of the mosquitoes, virus and infected individuals, and lack of effective mosquito control Each year there are an estimated 50 to 100 million dengue infections, with >500,000 cases of dengue hemorrhagic fever, and >22,000 deaths, primarily in children Goals of Treatment The goal of dengue management is to identify which children are at risk for dengue based on travel history and for the PEM clinician to be aware that rapid fluid shifts after fluid resuscitation can lead to volume overload Clinical Considerations Clinical recognition: The differential diagnosis includes febrile illness with similar clinical manifestations such as influenza, enteroviral infection, measles, and rubella The diagnosis is typically a clinical one when treating patients with recent travel to dengue endemic regions Only 50% of patients infected with dengue develop symptoms Clinical manifestations range from self-limited dengue fever to dengue hemorrhagic with shock syndrome Symptoms typically develop within to 14 days after the bite of an infected mosquito; the risk of severe disease is much higher in sequential infections In 2009, the World Health Organization (WHO) published revised dengue case definitions ( e-Table 94.19 ) Three distinct phases exist The first is the febrile phase Here, children develop pyrexia (or hyperpyrexia), vomiting, joint pain Some develop a transient maculopapular rash, lasting approximately to days Most patients not progress to the next phase and improve without intervention Phase is called the critical or capillary leak phase and consists of clinical or radiographic evidence of serositis, ascites, or pulmonary edema Children in phase are at risk for developing hypotension and uncompensated shock Patients may be refractory to fluid resuscitation and may develop abdominal pain, persistent emesis, tender hepatomegaly, mucosal bleeding, and altered mentation Phase (the convalescence or reabsorption phase) begins approximately to days after the initiation of phase Patients typically experience both clinical and laboratory rapid improvement as the body reabsorbs extravasated plasma and fluid Some patients develop a pruritic vasculitic rash that may desquamate during resolution of the illness (2 to weeks) Triage considerations: Dengue should be considered in every patient seen in the ED presenting with fever and recent return (