Botulism
Botulism is a neuroparalytic disease caused by a neurotoxin elaborated by Clostridium botulinum, a Gram-positive, spore-forming, obligate anaerobe whose natural habitat is the soil. Botulinum toxin is tasteless, odorless, and extremely toxic. It acts by irreversibly blocking the release of acetylcholine in peripheral somatic and autonomic synapses as well as at the motor end plates.
Infants lack the Clostridium inhibiting bile acids and protective bacterial flora found in the normal adult intestinal tract, so botulism spores can germinate in the intestinal tract. There are approximately 100 cases of infant botulism annually in the United States, with a peak incidence between 2–4 months of age. Honey consumption and parental employment at construction sites are significant risk factors.
In contrast, in older children, botulism usually occurs after the ingestion of preformed toxin in spoiled food. Raw, home canned, or inadequately prepared foods may be contaminated with the toxin, which is heat labile. Heating food to the boiling point destroys the toxin, but the bacterial spores are resistant to heat and may survive the home-canning process. Canned fish, vegetables, and potatoes have been implicated in outbreaks of botulism.
In wound botulism, C. botulinum grows in the injured tissue and produces toxin. Most cases of wound botulism in the United States occur either in intravenous drug users or children with compound extremity fractures.
Clinical Presentation
Infantile botulism begins gradually, 2–4 weeks after ingestion of the spores. Breastfed infants are infected later than formula-fed infants, and breastfeeding may moderate the severity of the illness. Constipation is often the first symptom, followed by weak cry, weak suck, drooling, difficulty feeding, dysphagia, loss of head control, signs of descending cranial nerve palsies, and hypotonia. Progressive paralysis can lead to respiratory failure.
After infancy, botulism manifests as a symmetric, descending, flaccid paralysis, without fever. Symptoms of food-borne botulism begin within 12–36 hours of ingestion of contaminated food. The patient develops blurred vision, diplopia, ptosis, ophthalmoplegia, dysarthria, and dysphagia. Autonomic signs include constipation, dry mouth, postural hypotension, urinary retention, and pupillary dilation with a sluggish or absent light reflex. Nausea and vomiting may also occur in one-third of patients. A descending weakness follows, which, in severe cases, may involve the respiratory muscles. Weakness is usually bilateral, but may be asymmetric. The sensory nerves and mentation are notably spared.
After a 4–14-day incubation period, the presentation of wound botulism is similar to food-borne botulism. There may be fever, but not nausea and vomiting. The wound may exhibit no signs of infection.
Diagnosis
The initial diagnosis is clinical, and CSF studies may be normal. The diagnosis can be confirmed by analyzing suspected food, serum, gastrointestinal contents/stool, or wound exudates for evidence of toxin or organisms. However, do not delay treatment while waiting for laboratory confirmation.
Other causes of paralysis include Guillain-Barré syndrome (ascending paralysis with an elevated CSF protein), poliomyelitis (asymmetric involvement, fever, CSF pleocytosis), myasthenia gravis (muscle fatigability, reversal of ptosis with edrophonium), spinal muscular atrophy (severe weakness, absent DTRs, tongue fasciculations), and tick paralysis (rapidly progressive generalized paralysis, absent DTRs, normal CSF protein, possible dysesthesias). In a febrile infant who is lethargic and feeding poorly, consider bacterial sepsis or meningitis. Metabolic causes of acute weakness include hypokalemia, hypo- and hypercalcemia, and hypo- and hyperthyroidism
ED Management
Admit the patient to an ICU for monitoring, as respiratory arrest from ascending paralysis can occur at any time. If clinically indicated (focal neurologic examination; signs of increased intracranial pressure), obtain a CT or MRI of the head.
The mainstay of therapy is supportive. Give human-derived antitoxin (BIG-IV; BabyBIG), which is produced and distributed by the California Department of Public Health (24-hour telephone number: 510-231-7600; www.infantbotulism.org). Equine-derived heptavalent botulinum antitoxin is available from the CDC for older children and adults.
Although antibiotics are not necessary to eradicate the bowel colonization of infants, treat wound botulism with antitoxin and antibiotics (penicillin or clindamycin). If sepsis cannot be excluded, obtain a CBC, blood culture, and lumbar puncture, and start age-appropriate empiric antibiotics (see pp. 391–394). Do not use aminoglycosides because they may potentiate the effects of the toxin. Notify the state health department of any suspected cases of botulism.
Indications for Admission
Suspected botulism
Bibliography
Chikungunya
Chikungunya is transmitted to humans by the Aedes mosquito. In Swahili, the name means “to become contorted,” describing the characteristic joint pain that is part of the disease. Travelers returning from Africa, Asia, parts of Central/South America, islands in the Indian Ocean, the Western and South Pacific, and the Caribbean are at risk. Local transmission can occur if infected travelers return to an area where Aedes mosquitoes exist.
Clinical Presentation
The incubation period is generally 2–4 days (range 1–12 days). The disease presents with the sudden onset of high fever, arthralgias, myalgias, headaches, photophobia, and variable rash. The arthralgias are usually symmetrical, polyarticular, and frequently involve the fingers, wrists, ankles, elbows, toes, and knees. Joint swelling is common, especially of the ankles and wrists. While the other symptoms resolve in 1–2 weeks, the arthralgias commonly persist or recur for months or years. Atypical, severe disease is associated with neurologic complications, including encephalitis and febrile seizures, and/or multiorgan failure and death.
Diagnosis
Consider Chikungunya, as well as dengue fever, in a patient with fever and arthralgias or arthritis who has traveled to an endemic area within 15 days of symptom onset. Laboratory diagnosis includes viral isolation in culture, detection of viral RNA via RT-PCR, the presence of IgM antibodies, or a four-fold increase in IgG in paired samples.
ED Management
Treatment is supportive, including NSAIDS for management of arthralgias.
Follow-up
Primary care in one week
Indications for Admission
Neurologic complications
End-organ complications
Bibliography
Dengue Viruses
Dengue viruses are transmitted to humans by certain species of Aedes mosquitoes, so that most infections are contracted during travel to tropical and subtropical areas. The incidence of travel-associated dengue has increased during the past decade due to epidemics in tropical regions, including Puerto Rico, the Caribbean, and Latin America. There are four serotypes and infection with one serotype does not provide immunity to the other serotypes.
Clinical Presentation
The typical incubation period is 4–7 days. The course ranges from asymptomatic infection to mild febrile illness to a severe and fatal hemorrhagic disease. Initial symptoms include fever for 3–7 days, abdominal pain, nausea and vomiting, cough, headache, retro-orbital pain, constipation, body aches, and joint pain (“breakbone fever”). On physical examination the patient may have a relative bradycardia, hepatomegaly, conjunctival injection, pharyngeal erythema, lymphadenopathy, and mild hemorrhagic manifestations such as petechiae. Approximately half of patients describe a variable rash, often macular, that starts on the trunk and spreads to the face and extremities. A second rash that results in desquamation may present after recovery from severe dengue.
The most severe infections cause dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), with vascular leak. DSS presents at the time of initial defervescence, often when it seems that the patient is improving. Warning signs include abdominal pain, vomiting, clinical fluid accumulation (pleural effusions, ascites), mucosal bleeding, altered mental status, hepatomegaly, and/or a rising hematocrit (reflecting hemoconcentration) with a falling platelet count. DSS is heralded by a narrow pulse pressure (<20 mmHg). It can progress rapidly, resulting in irreversible shock and death. Rare complications include myocarditis, hepatitis, and neurologic symptoms. Laboratory abnormalities may include severe liver dysfunction, hypoproteinemia, elevated PTT, and decreased fibrinogen. The critical phase lasts 48–72 hours and is followed by the recovery phase. The patient can develop a second variable rash that resolves with desquamation over 1–2 weeks.
Diagnosis
Include dengue in the differential diagnosis of any febrile patient who lives in or who has traveled to a dengue-endemic area within two weeks and has at least two of the following criteria:
nausea/vomiting
rash
aches and pains
positive tourniquet test (>10 petechiae/inch2 distal to a BP cuff inflated midway between systolic and diastolic)
any warning signs: abdominal pain/tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, liver enlargement >2 cm, and an increase in hematocrit with concurrent rapid decrease in platelet count
Criteria for severe dengue include severe plasma leakage resulting in shock or fluid accumulation with respiratory distress, severe bleeding, and severe organ impairment (liver, CNS, cardiac, other organs)
In acute disease, the diagnosis can be confirmed with a dengue RT-PCR. If molecular detection is not available, obtain paired acute and convalescent phase testing for anti-dengue antibodies.
ED Management
The management of dengue is supportive. A patient with suspected dengue who can tolerate oral fluids can be managed at home, with daily follow-up and strict instructions to return if bleeding or the warning signs develop. Hospitalize any patient with warning signs, for close monitoring for vascular leak syndrome. Treat dengue shock with careful administration of isotonic crystalloid solutions to maintain cardiovascular stability while avoiding volume overload. Avoid aspirin, nonsteroidal anti-inflammatories (NSAIDS), and other anticoagulants due to the risk of hemorrhagic complications.
Indications for Admission
Bibliography
Encephalitis
Approximately 20,000 cases of encephalitis occur in the United States each year, most of which are mild. Enteroviruses (enterovirus, echovirus, Coxsackieviruses) are the cause of epidemics in the summer and fall. Sporadic cases of encephalitis are secondary to the herpes simplex viruses (HSV-1 and -2), arthropod-borne viruses (St. Louis encephalitis, California encephalitis, eastern, western, Venezuelan equine encephalitis, and West Nile [WNV] virus), and other herpes viruses (Epstein–Barr, cytomegalovirus, varicella zoster).
Bacterial causes include Haemophilus influenzae, Neisseria meningitides, Streptococcus pneumoniae, and Mycobacterium tuberculosis, although these organisms more often cause meningitis (pp. 422–425). Spirochetal infections include Treponema pallidum, Leptospira species, and Borrelia burgdorferi (Lyme disease). Other non-viral causes of encephalitis include C. pneumoniae, Mycoplasma pneumoniae, M. hominis, and Coccidiodes immitus. Additionally, Toxoplasma gondii, Cryptococcus neoformans, and Listeria monocytogenes can cause encephalitis in an immunocompromised patient.
Post-infectious encephalitis is thought to be an autoimmune phenomenon initiated by viral (influenza, varicella, measles) or bacterial (Mycoplasma) pathogens in children with symptoms of CNS inflammation in the absence of an acute bacterial or fungal infection. Characteristically, there is a latent phase between the acute illness and the onset of neurologic symptoms.
Clinical Presentation
Encephalitis most commonly begins as an acute systemic illness with fever and headache. Most patients have diffuse disease with behavioral or personality changes, altered level of consciousness, or generalized seizures. Some patients may have localized findings, such as ataxia, cranial nerve defects, hemiparesis, or focal seizures. Alternatively, there may be high fever, convulsions with bizarre movements, and hallucinations alternating with periods of clarity. Nuchal rigidity, if present, is less pronounced than with meningitis.
Herpes Viruses
Approximately 50% of newborns with HSV infection have CNS involvement. Morbidity and mortality depend on whether the infant has isolated CNS involvement or disseminated disease. Encephalitis in an older child or adolescent is usually secondary to HSV-1, which presents with fever, focal or generalized seizures, focal neurologic signs, and altered level of consciousness. Epstein–Barr virus encephalitis causes a focal encephalopathic disease in conjunction with fever, pharyngitis, lymphadenopathy, atypical lymphocytosis, and a positive heterophile test. Varicella encephalitis follows the distinctive exanthem and may lead to nystagmus, dysarthria, and cerebellar ataxia.
Arthropod and Mosquito Borne
These infections are transmitted by mosquitoes and ticks, and outbreaks occur primarily during the summer and fall seasons. Human WNV has been reported throughout the continental United States. The vector is mosquitoes that prey on birds and humans are the principal vectors. After an incubation period of 3–6 days, there is an abrupt onset of a febrile, flu-like illness. In addition, there may be conjunctivitis, retrobulbar pain, and a maculopapular rash that spreads from the trunk to the extremities and head. In contrast to adults, CNS involvement is rare in children. Other severe complications of WNV include hepatitis, pancreatitis, myocarditis, and hepatosplenomegaly.
Enteroviruses
Enteroviral infection usually occurs in the summer. Following a prodrome of fever and upper respiratory tract symptoms, the patient develops acute neurologic findings such as confusion, altered level of consciousness, or irritability. Neurologic manifestations are usually global rather than focal, although flaccid paralysis may occur. Other possible manifestations include photophobia and a macular or petechial rash.
Diagnosis
Obtain a detailed history, including whether there has been any antecedent viral infection, systemic symptoms, ill contacts, or exposure to mosquitoes, ticks, or animals. Inquire about the immunologic status of the patient, recent travel or immunizations, and the possibility of accidental exposure to heavy metals or pesticides. Perform a thorough physical examination looking for rashes, lymphadenopathy, focal neurologic abnormalities, cerebellar signs, and evidence of increased intracranial pressure (including fundoscopy). Have a high index of suspicion for neonatal HSV infection in an acutely ill infant <21 days of age.
ED Management
Perform a lumbar puncture to exclude bacterial meningitis unless there are focal neurologic signs or evidence of increased intracranial pressure. In such a case, give the first doses of empiric antibiotics for suspected bacterial meningitis (see Table 13.8), and arrange for a CT scan of the head prior to performing the lumbar puncture. HSV is associated with hemorrhagic inflammation of the temporal lobe and sylvian fissure.
Send the CSF for Gram stain, cell count, protein, glucose, culture, rapid antigen identification test, viral culture, and if tuberculosis is a possibility, acid fast stain, culture and/or PCR for Mycobacterium. The CSF in viral encephalitis is usually clear, and the leukocyte count can range from none to several thousand with a polymorphonuclear predominance early in the course. The protein is normal to moderately elevated, and the glucose is initially normal (see Table 13.7).
Obtain a CBC, platelet count, electrolytes, BUN, creatinine, glucose, blood culture, and a urinalysis. If specific viral etiologies are being considered, send urine, stool, CSF, and throat swabs for viral diagnostic tests and sera for viral titers. In particular, if HSV or enterovirus is a possibility, send CSF for PCR, which is 98% sensitive and 94% specific. In several states, the Department of Health offers additional CSF testing for a PCR panel (along with serological testing) of most likely pathogens for cases of encephalitis with additional testing (arbovirus or West Nile serology), as the history warrants.
Admit patients with encephalitis for close observation of vital signs and fluid status. Treat for bacterial meningitis pending culture results. Better outcomes after neonatal HSV infection are strongly associated with a shorter interval between diagnosis and initiation of treatment. If herpes is suspected, treat with acyclovir (≤14 days: 20 mg/kg q 12h; >14 days to <3 months: 20 mg/kg q 8h; ≥3 months to 12 years: 10–15 mg/kg q 8h; ≥12 years: 10 mg/kg q 8h)
During enteroviral epidemics in the summer and fall, a patient older than six years of age who develops meningitis without encephalitis with a stable presentation (mild to moderate headache that responds to acetaminophen or ibuprofen, nontoxic appearance, CSF with a monocytic pleocytosis and normal chemistries) can be discharged for supportive care. Admit any patient with nuchal rigidity, unresponsive moderate to severe headache, lethargy, or inability to maintain hydration.
Indications for Admission
Bibliography
Enteric Parasitic Infections
Roundworms, hookworms, whipworms, and treadworms (Strongyloides) are found throughout the world in communities where the soil is contaminated by eggs or larvae. While uncommon in the United States, these infections can occur when there is breakdown of hygiene or sanitation or, more commonly, in immigrants and travelers returning from endemic regions.
Clinical Presentation
Pinworms
Pinworm (Enterobius vermicularis) is the most common helminth infection in the United States. Pinworms are acquired from ingestion of eggs, which hatch in the duodenum and migrate to the cecum where they mature over 4–6 weeks. Gravid adult females migrate to the perineum where they lay eggs. Person to person and fomite (toys, bedding, etc.) to person transmission are common, as the eggs remain viable for 2–3 weeks in the environment. Autoinfection may occur, either from reingesting eggs or when hatched pinworms crawl back into the anus. Anal pruritus is the most common complaint, although pinworms can be asymptomatic. Vulvitis can rarely occur if a worm migrates into the vagina. There is no tissue migration of the larvae and no eosinophilia.
Roundworms
Roundworm (Ascaris lumbricoides) is one of the most common nematode infections worldwide, but it is relatively uncommon in the United States. The worms enter the body through ingestion of eggs, which hatch in the small intestine. Larvae then migrate by lymphatics or venules into the portal and then systemic circulation, ultimately arriving at the lungs, penetrating the pulmonary capillaries, and entering the airway. The larvae mature in the lungs for 10–14 days and then travel up the bronchial tree to the throat, where they are swallowed and mature into adults in the small intestine. Patients may develop Loeffler’s syndrome, presenting with fever, cough, dyspnea, hemoptysis, and pulmonary eosinophilia, during the larval migration through the lungs. Adult worms (15–35 cm) in the intestine are usually asymptomatic, but they can cause intermittent abdominal pain and may sometimes be vomited up or passed in stool. Other less common complications are intestinal obstruction, blockage of the bile or pancreatic ducts, appendicitis, intussusception, and volvulus. Ascaris can affect the nutritional status of infected children by causing malabsorption of fats, proteins, and carbohydrates.
Hookworms
Hookworm (Necator americanus and Ancyclostoma duodenale) was previously widespread in the southeastern United States, but is now less common. The infection is typically acquired through penetration of the soles of the feet by the larvae. This causes a papulovesicular dermatitis sometimes referred to as “ground itch” that lasts for 1–2 weeks. The larvae enter the circulatory system where they penetrate the pulmonary alveoli, ascend the bronchial tree to the throat, and are then swallowed. Migrating worms may cause Loeffler’s syndrome, an eosinophilic pneumonitis. Approximately 4–12 weeks after exposure, the larvae attach to the mucosa of the small intestine causing mild abdominal pain, nausea, and anorexia. Blood loss occurs secondary to parasite mediated destruction of capillaries in the intestinal mucosa and may cause a hypochromic, microcytic anemia and hypoalbuminemia. Eosinophilia is common.
Strongyloidiasis
Strongyloides stercoralis is found in tropical regions and the southeastern United States. Filariform (parasitic) larvae in contaminated soil invade the skin. They migrate via the circulatory system to the lungs and then up the tracheobronchial tree and into the intestinal tract.
There is a spectrum of illness due to Strongyloides stercoralis. Acute strongyloidiasis can present with a local reaction at the site of larval entry. This dermatitis can occur almost immediately and may last up to several weeks. Pulmonary symptoms (Loeffler’s syndrome) may develop as larvae migrate through the lungs. Gastrointestinal symptoms (diarrhea, anorexia, abdominal pain) may occur about two weeks after infection. Larvae are detectable in the stool 3–4 weeks after infection. Chronic infection is most often asymptomatic, but has been associated with intermittent vomiting, diarrhea, constipation, and recurrent asthma.
Hyperinfection is a rare syndrome of accelerated autoinfection generally secondary to immunocompromise, most commonly associated with HTLV-1 infection or corticosteroid use. Patients may have diarrhea, abdominal pain, ileus, or small bowel obstruction. Massive larvae penetration through the lungs results in pulmonary hemorrhage and infiltrates on chest x-ray. Hyperinfection is often complicated by bacteremia and/or meningitis with enteric bacteria.
Whipworm
Trichuris trichuria is found throughout tropical regions and in the southeastern United States. It has a simple lifecycle in which ingested eggs develop in the intestine. There is no tissue invasion stage, so eosinophilia is rare. Infections are usually asymptomatic, although heavy infections can cause nausea, vomiting, diarrhea, abdominal distention and tenderness, rectal prolapse, and occasionally intestinal bleeding.
Entamoeba Histolytica
Entamoeba histolytica is found worldwide, but is most common in areas with poor sanitation. It is transmitted via fecal–oral ingestion of mature amebic cysts. Infection is usually asymptomatic, although there can be a spectrum of disease from asymptomatic intraluminal infection/colonization to colitis to extraintestinal infection. Patients with amebic colitis typically present with a several-week history of gradual onset of abdominal pain and tenderness, diarrhea, and bloody stools. Fever is usually absent or low grade. The presentation can occasionally mimic inflammatory bowel disease. Patients with liver abscesses complain of right upper quadrant pain and fever, generally without colitis. Though rare, spread to the lungs, pleura, and skin can occur by direct extension. Treatment is indicated for asymptomatic patients to prevent transmission to others and progression to symptomatic disease.
Diagnosis
The diagnosis of most parasitic infections can only be made if the possibility is considered. Recent travel to or emigration from endemic areas makes infestation more likely. A history of chronic or bloody diarrhea, dysentery, weight loss, or cutaneous eruptions suggests the possibility of a parasitic infection. Eosinophilia suggests roundworms, hookworms, or strongyloidiasis. Occasionally the patient or parent will report seeing a worm in the stool, vomitus, sputum, or perianal region. Often the physical examination is not helpful in determining the diagnosis.
A history of anal pruritus, particularly if multiple close contacts have similar symptoms, is suggestive of pinworm infestation. If confirmation is necessary, the cellotape (unfrosted Scotch tape) test can demonstrate parasite eggs under a microscope. Specialized collection kits are also available. The sensitivity of the test increases when performed in the morning prior to the first bowel movement or washing and if multiple samples are collected on different days. Stool samples are not helpful.
Roundworm, hookworm, and whipworm are diagnosed by finding eggs in a fresh stool specimen (“stool for ova and parasites”), with increased yield if three successive morning specimens are submitted. Refrigerate stool that cannot be examined within one hour. Additionally, adult Ascaris may sometimes be brought in by a child’s family and can be identified based upon its size and gross physical characteristics.
Strongyloides larvae are excreted in low volumes in stool and is therefore difficult to diagnose by stool examination (ova and parasites). Specialized processing of stool can aid in diagnosis, while an enzyme immunoassay for Strongyloides IgG is very sensitive but it cannot differentiate between current or past infection and can also cross-react with other parasitic infections. Consultation with the microbiology laboratory or an infectious disease specialist will assist in making the diagnosis.
Entamoeba histioloytica is morphologically indistinct from Enantomoeba dispar, a non-pathogenic amoeba that can also be found in stool. Antigen tests or PCR on stool specimens can distinguish between the two. In extraluminal disease such as liver abscess, the organism may not be found in the stool, but an enzyme-linked immunosorbent assay (EIA) antibody test is very sensitive. Conversely, the EIA antibody test does not perform well in luminal disease and cannot distinguish between current and past infection. The diagnosis and management of enteric parasitic infections is summarized in Table 13.1.
| Diagnosis | Treatment |
|---|---|
| Pinworms | |
| Presumptive or Scotch tape-test | Pyrantel pamoate (≥2 years of age 11 mg/kg) × 1, repeat in 2 weeks Albendazole and mebendazole are effective but much more expensive. Treat household members if repeated infection |
| Bathe, change underwear, and wash bedding daily | |
| Ascarasisa | |
| Ova and parasites | Albendazole (≥1 year of age): 400 mg once |
| Mebendazole (≥ 2 years of age): 100 mg BID for 3 days or 500 mg × 1 Ivermectin (≥15 kg): 150–200 mcg/kg once | |
| Hookwormsa | |
| Ova and parasites | Albendazole (≥1 year of age): 400 mg once |
| Mebendazole (≥ 2 years of age): 100 mg BID for 3 days or 500 mg × 1 Pyrantel pamoate (≥2 years of age): 11 mg/kg daily × 3 days | |
| Whipwormsa | |
| Ova and parasites | Albendazole (≥1 year of age): 400 mg daily × 3 days |
| Mebendazole (≥ 2 years of age): 100 mg BID × 3 days | |
| Ivermectin (≥15 kg): 200 mcg/kg/day × 3 days) | |
| Strongyloides | |
| Ova and parasites | Ivermectin (>15 kg): 200 mcg/kg/day × 2 days |
| EIAb | Albendazolec (≥1 year of age): 400 mg bid × 7 days |
| Enantomoeba histiolytica | |
| Ova and parasites antigen | Asymptomatic: iodoquinol 40 mg/kg/day div tid × 20 days |
| PCRd | or paromomycin: 25–35 mg/kg/day div tid × 7 days |
| EIA if extraluminal | Symptomatic: metronidazole (35–50 mg/kg/day div tid × 7–10 days) |
| or tinidazole (≥3 years of age): 50 mg/kg daily × 3–5 days) | |
| followed by either iodoquinol or paromomycin (as above) | |
a Repeat ova and parasites testing two weeks after therapy for test of cure.
b Enzyme-linked immunosorbent assay.
c Albendazole is less effective than ivermectin for Strongyloides.
d Polymerase chain reaction.
ED Management
Although a pinworm infection may be treated on the presumptive evidence of rectal itching in the absence of local pathology, treat other parasitic infections only if positive identification is available. Otherwise, arrange for the collection of specimens and refer the patient for primary care follow-up. Note that albendazole was briefly discontinued and then reintroduced to the United States as a patented 100 mg chewable tablet that is much more expensive than previous formulations.
Refugee populations who have not had presumptive treatment prior to arrival in the United States may require empiric treatment. See the CDC guidelines for further recommendations (www.cdc.gov/immigrantrefugeehealth/guidelines/domestic/intestinal-parasites-domestic.html#figure1).
Some laboratories may report the presence of non-pathogenic protozoa in the stool. These are harmless, are not associated with disease, and do not require any therapy. The Centers for Disease Control and Prevention has a list of these protozoa as well as a handout to discuss with patients’ families to allay their concerns (www.cdc.gov/parasites/nonpathprotozoa/).
Indications for Admission
Dehydration or severe weight loss
Extraintestinal amoebiasis
Strongyloidiasis in immunocompromised patients
Bibliography
Evaluation of the Febrile Child
Fever is one of the most common causes for a visit to the ED. For the purpose of ED evaluation, one set of fever definitions based on an increased risk of severe disease include:
≤56 of age: 38.0 °C (100.4 °F);
>56 days of age: 38.5 °C (101.3 °F);
immunocompromised patient: 38.5 °C (101.3 °F) once or 38.0 °C (100.4 °F) three times within 24-hour period (one hour apart).
Fever may be the presenting sign for a viral illness, a minor bacterial infection, or a life-threatening bacterial process. Rarely, fever may be the presenting sign of collagen vascular disease, drug intoxication, or malignancy. In many cases, the etiology of the fever remains unclear even after a thorough history and physical examination.
The priority is the identification of the child with a serious bacterial illness (SBI). Despite efforts to develop reliable methods for diagnosis, these patients may be clinically indistinguishable from children with self-limited viral diseases, and they may have no localizing signs whatsoever. The widespread use of the Haemophilus influenza type b vaccination and conjugate pneumococcal vaccine has led to a dramatic decline in the incidence of occult bacteremia in children and invalidated previously published management guidelines for the evaluation of nontoxic-appearing febrile children aged three months to three years. The most common SBI in the febrile young infant is now a urinary tract infection.
Clinical Presentation
Clinical impression is a component of every strategy for evaluating febrile infants and young children. The best-known tool is the Yale Observation Scale (YOS), an objective scoring system based on the child’s alertness, playfulness, interaction with the environment, color, state of hydration, quality of cry, and ability to be consoled (www.thecalculator.co/health/Yale-Observation-Scale-for-Infant-Fever-Calculator-922.html). In the young infant (<8 weeks), however, the clinical presentation has been shown to be neither sensitive nor specific for identifying which patient is at risk for SBI. Furthermore, focal infections in young infants typically do not present with localized findings. Meningeal signs may be absent despite the presence of meningitis. The older the patient, the more reliable the clinical impression becomes as a predictor of serious underlying illness and the more likely that the patient has specific localizing signs of illness.
Diagnosis
Clinical impression and physical examination are the mainstays of diagnosis in older children. Laboratory tests help predict the risk of serious infection when the results of the clinical evaluation is equivocal or known to be unreliable, as in the case of the young infant (<8 weeks). However, because of the low prevalence of bacteremia, the positive predictive value of any single test remains very low.
ED Management
The management of the well-appearing febrile infants and children is summarized below by age. Modify these guidelines and use a more conservative approach in high-risk patients, including but not limited to the immunocompromised host, children with cerebrospinal fluid shunts or other indwelling lines, or if unusual pathogens are suspected. An ill-appearing child in any age group warrants a full sepsis evaluation and empiric antibiotics.
Under 28 Days of Age
Since clinical impression is unreliable in young infants, perform a full evaluation for sepsis including a complete blood count (CBC) with differential count, blood and urine cultures, urinalysis, and lumbar puncture (LP) for cell count, glucose, protein, Gram’s stain, and culture. Obtain urine by catheter insertion or suprapubic aspiration. A chest radiograph is indicated if there are respiratory signs or symptoms.
Regardless of the initial test results, give empiric antibiotics (ampicillin and cefotaxime) and admit pending culture results. Ampicillin doses (IV/IM) are: <1 week of age: 75–150 mg/kg/day div q 8h (use 200–300 mg/kg/day div q 8h if group B streptococcal meningitis is suspected); >1 week of age: 100–200 mg/kg/day div q 6h (use 300 mg/kg/day div q 4–6 hours if group B streptococcal meningitis is suspected). Cefotaxime doses (IV/IM) are: <1 week: 100–150 mg/kg/day div q 8–12h; 1–4 weeks: 150–200 mg/kg/day div q 6–8h. If meningitis is suspected, use 200 mg/kg/day div q 6h, but give higher doses (225–300 mg/kg/day div q 6–8h) in combination with vancomycin for meningitis due to penicillin-resistant S. pneumoniae.
Most patients in this age group with HSV infection are afebrile or hypothermic. Add empiric acyclovir (<35 weeks postconceptional age: 20 mg/kg every 12 hours; ≥35 weeks postconceptional age: 20 mg/kg every 8 hours) if HSV is suspected in patients who are ill-appearing, or present with abnormal neurological status, a vesicular rash, hepatitis, and/or a maternal history of primary HSV infection
28–56 Days of Age
The evaluation of the well-appearing 28- to 56-day-old varies by institution. Regardless of whether there is an identifiable source of infection, obtain a urinalysis, urine culture, CBC, and a blood culture, as well as a chest x-ray if the patient has signs or symptoms of respiratory illness. If the patient has diarrhea, send stool to evaluate for white blood cells, as well as a culture. Infants with clinical bronchiolitis, or documented RSV or influenza, have a much lower rate of SBI than infants without bronchiolitis, although there is still a risk of a urinary tract infection.
Classify infants as low-risk if they are well-appearing, with normal vital signs after defervescence, and they meet all of the following criteria:
full-term birth (>37 weeks’ gestation);
no chronic medical conditions;
no prolonged NICU stay;
no antibiotics within 72 hours;
WBC >5000/mm3 and <15,000/mm3;
urinalysis with ≤10 WBC per high-power field and no bacteria;
band:neutrophil ratio <0.2;
if sent, ESR <30 mm/h or a CRP < 1;
if diarrhea is present, stool is heme negative and has ≤5 WBC per high-power field;
normal chest radiograph (if obtained).
Recently developed protocols now suggest a stepwise approach to guide the need for an LP in these patients, as the risk of meningitis is very low in this population. Infants who meet all the above criteria for low risk for SBI may be managed as outpatients, with close follow-up and without expectant antibiotic therapy. A more conservative approach, including an LP, is appropriate when there is any uncertainty regarding the use of the stepwise approach. If the LP is negative, these infants may also be managed as outpatients without antibiotics.
Perform a full sepsis evaluation, including an LP, if the patient is ill-appearing or does not meet low-risk criteria. Admit these infants to the hospital and start empiric antibiotics with cefotaxime (IV/IM) 100–200 mg/kg/day div q 6–8h. Use higher doses (150–225 mg/kg/day div q 6–8h) for infections outside the CSF due to resistant S. pneumoniae. Treat for HSV in infants with abnormal neurological status, a vesicular rash, hepatitis or a maternal history of primary HSV infection (acyclovir 60 mg/kg/day IV div q 8h). Obtain CSF samples prior to the initiation of antibiotics unless the infant is too ill-appearing to delay treatment.
An exception is an infant who does not meet the low-risk criteria, but has clinical bronchiolitis and/or documented RSV or influenza, in whom the LP may be deferred if the plan is to admit without empiric antibiotics.
56–90 Days of Age
Clinical impression is slightly more reliable in this age group. If the patient is well-appearing, with otherwise normal vital signs, and no fever source found on careful examination, evaluate for a urinary tract infection. Obtain a chest radiograph if there are any concerning respiratory signs or symptoms, including tachypnea. Admit infants with suspected focal infections, such as otitis media, UTI, or pneumonia, and start treatment with IV/IM ceftriaxone. If the patient is ill-appearing, perform a full sepsis evaluation, begin empiric treatment with ceftriaxone 100 mg/kg/day div q 12h (IV/IM), and admit to the hospital.
If the patient is being discharged, the priorities are careful and frequent follow-up and parental vigilance for clinical deterioration. Give the parents specific guidelines for controlling the fever (15 mg/kg of acetaminophen q 4h), and for assessing the child at home (increased irritability or lethargy, decreased PO intake) and provide for a follow-up visit within 24–48 hours, or sooner if the patient seems worse to the parents.
90 Days to 36 Months of Age
Clinical impression continues to be more reliable in this age group and the patient may present with localizing symptoms. Additionally, the widespread use of the Haemophilus influenza B (HIB) and conjugate pneumococcal vaccine (PCV-7) has reduced occult bacteremia rates to <1%. It is important to verify the child’s immunization status to stratify their risk, as the following recommendations apply to patients who are fully immunized.
The well-appearing child with otherwise normal vital signs may be discharged home with close follow-up and parental vigilance for clinical deterioration. Screen for a urinary tract infection in males under one year of age or females with fever without a source for >2 days.
If a febrile child is irritable, but has no signs of poor perfusion, administer an antipyretic (acetaminophen: <6 months of age: 15 mg/kg per dose q 6h; ≥6 months of age: 15 mg/kg per dose q 4h; or ibuprofen: >6 months of age: 10 mg/kg dose q 6h) and reevaluate in one half-hour. If the child is well-appearing and vital signs have normalized after defervescence, discharge home is appropriate. If the child is well-appearing but the vital signs do not normalize (i.e., persistent tachycardia) further evaluation may be warranted to exclude a SBI or myocarditis. Admit ill-appearing infants younger than six months of age with any focal bacterial infection, other than otitis media.
Any child who appears toxic requires immediate further evaluation based on the presenting symptoms and severity of disease, which may include CBC, blood culture, urinalysis, urine culture, chest x-ray, and possibly an LP.
≥36 Months of Age
Older children may be able to vocalize their symptoms and the clinical examination is generally reliable. The well-appearing patient with otherwise normal vital signs may be discharged home with follow-up if symptoms persist. Children who are not toilet trained are at higher risk of urinary tract infections. Obtain a screening urinalysis if a female has fever >39 °C (102 °F) without a source for >2–3 days.
Follow-up
Indications for Admission
All infants <4 weeks of age with a temperature >38.0 °C (100.4 °F)
Infants <56 days of age who do not meet low-risk criteria
Most infants <6 months of age with focal bacterial infection other than otitis media
Toxic-appearing child regardless of age or degree of fever
Bibliography
Fever of Unknown Origin
Fever of unknown origin (FUO) is defined as temperature higher than 38 °C (100.4 °F), for eight or more days, without a definitive diagnosis. Do not confuse FUO with “fever without a source,” which is of shorter duration. In addition “pseudo-FUO” can occur when back-to-back episodes of self-limited infections are perceived by parents as one prolonged fever episode.
Clinical Presentation
The evaluation begins with a thorough, if not exhaustive, history and physical examination (Table 13.2), the results of which will guide the laboratory work-up. Determine the fever duration, height, pattern (sustained, relapsing, recurrent), and method of temperature-taking. Ask about any constitutional symptoms (weight loss, sweating) or associated symptoms, as well as travel (dengue, malaria) or unusual exposures (HIV), ethnic or genetic background (familial fever disorders), and exposure to medications (drug fever).
| Finding | Common possible diagnoses |
|---|---|
| Abdominal pain, vomiting, diarrhea | Bacterial enteritis |
| Inflammatory bowel disease | |
| Intra-abdominal abscess | |
| Arthritis/arthralgia | Rheumatologic disorders |
| Diaphoresis | Dysautonomia |
| Hyperthyroidism | |
| Lymphadenopathy: general | Mono-like illness |
| Oncologic process | |
| Lymphadenopathy: localized | Bartonella |
| Mycobacterium | |
| Limb/bone pain | Leukemia/oncologic process |
| Osteoarticular infection | |
| Nasal discharge | Sinusitis |
| Rash | Idiopathic rheumatoid arthritis |
| Kawasaki disease | |
| Preventable childhood diseases | |
| Typhoid fever | |
| Red eyes | Autoimmune diseases |
| Kawasaki disease |
Diagnosis
Obtain an initial battery of tests, including a CBC with differential and peripheral smear, inflammatory markers (CRP and/or ESR), comprehensive metabolic panel, urinalysis, and chest radiograph, as well as urine and aerobic and anaerobic blood cultures. Perform tuberculin skin testing, if indicated. Use the results of the history, physical examination, and basic laboratories to obtain additional tests. These may include:
serology: EBV, CMV, parvovirus, and Bartonella, HIV;
chemistry: uric acid, LDH, ferritin – concern for oncologic process or hemophagocytic lymphohistiocytosis (HLH);
ANA, rheumatoid factor, C3/C4/CH50 – concern for an autoimmune process;
immunoglobulins, antibody titers to known vaccines – concern for an immunodeficiency;
echocardiogram – concern for Kawasaki disease or infectious endocarditis;
MRI – concern for osteomyelitis;
abdominal ultrasound, CT, or MRI – concern for abscesses, tumors, and lymphadenopathy (e.g., psoas abscess, liver abscess).
At the same time, consult with the appropriate subspecialist (infectious diseases, rheumatology, oncology, cardiology, gastroenterology, etc.).
ED Management (While the Diagnosis is Pending)
Do not give empiric antibiotics or other treatments (e.g., steroids) if the patient is clinically stable. These may mask or delay the diagnosis. If the patient is not stable or appears toxic, however, admit and initiate broad-spectrum antibiotic therapy (see pp. 391–393). In addition, stop all non-essential medications.
Follow-up
Indications for Admission
Unstable vital signs, toxic or ill appearance
Dehydration requiring intravenous fluids
Abnormal findings on diagnostic testing that require urgent further evaluation
Inadequate outpatient follow-up or further work-up cannot be addressed as an outpatient
Bibliography
HIV-Related Emergencies
Human immunodeficiency virus (HIV) can be transmitted via sexual contact, mucous membrane contact with contaminated bodily fluids, percutaneous exposure from contaminated sharp instruments or needles, and contaminated blood products (essentially eliminated in the United States), as well as from mother-to-child (either in utero, during delivery, or during breastfeeding). Optimal management during pregnancy, delivery, and the postpartum period has reduced the risk of transmission to the infant to less than 1% in many areas, but there are still about 100 perinatally infected infants born in the United States each year. Victims of rape or sexual abuse and teenagers engaging in unprotected sex may also present to the ED for HIV counseling, testing, and post-exposure chemoprophylaxis.
Clinical Presentation and Diagnosis
Previously Unknown Infection
Previously unrecognized perinatal transmission may present in infancy or childhood as failure to thrive, recurrent invasive bacterial infections, recurrent or recalcitrant oropharyngeal candidiasis, unexplained lymphadenopathy or hepatosplenomegaly, and/or chronic diarrhea. Adolescents with non-perinatally acquired acute HIV may present with a mononucleosis-like illness, including fever, malaise, headache, pharyngitis, rash, and generalized lymphadenopathy lasting 5–7 days. Therefore, routinely assess the sexual history and transmission risk factors (blood transfusion, needle sharing, needle sick, unprotected intercourse [especially receptive anal]) in adolescents presenting with this clinical picture, as many may not be forthcoming with this information.
In patients over 24 months of age, the diagnostic test of choice, including for possible acute infection, is a fourth-generation combined HIV-1 p24 antigen and HIV-1/2 antibody test. HIV RNA can be detected several days before antigenemia. Therefore, it can be used if clinical suspicion of acute retroviral syndrome remains, despite a negative fourth-generation test. The RNA NAAT can also be falsely positive, so confirmation then requires evidence of seroconversion. In perinatally exposed infants, maternal antibodies may be detectable in the infant until 24 months of age. Thus, in this age group, when the mother is known to be HIV-positive, order a qualitative HIV DNA or RNA NAAT.
Known HIV Infection
In the combined antiretroviral therapy (cART) era, most children with known HIV are well-controlled, and opportunistic infections are uncommon. Poor adherence to therapy, particularly during adolescence, increases the risk of opportunistic infections. HIV infection is staged (in addition to stage-defining infections) by age-specific CD4 count ranges (Table 13.3). If a child’s recent CD4 count is unknown, one can generally predict severe immunodeficiency if they are being prescribed prophylactic antimicrobials such as trimethoprim-sulfamethoxazole (TMP-SMX) (for Pneumocystis jiroveci pneumonia [PJP] when given beyond one year of age) or azithromycin or clarithromycin (for Mycobacterium avium complex).
| Stage | <1 year of age | ≥1–5 years of age | ≥6 years of age | |||
|---|---|---|---|---|---|---|
| CD4 count (cells/microliter | CD4% | CD4 count (cells/microliter) | CD4% | CD4 count (cells/microliter | CD4% | |
| 1 | ≥1500/mm3 | ≥34% | ≥1000/mm3 | ≥30% | ≥500/mm3 | ≥26% |
| 2 | 750–1499/mm3 | 26–33% | 500–999/mm3 | 22–29% | 200–499/mm3 | 14–25% |
| 3 (AIDS) | <750/mm3 | <26% | <500/mm3 | <22% | <200/mm3 | <14% |
For patients who have moderate (Stage 2) to severe (Stage 3) immunodeficiency, consult a pediatric HIV specialist for a differential diagnosis of potential opportunistic infections during acute illness. Two specific opportunistic infections bear mentioning.
Pneumocystis Jiroveci Pneumonia
As a consequence of cART and the widespread provision of prophylaxis, PJP has become increasingly rare. The peak incidence is 3–6 months of age, although all infants under one year of age with HIV are prescribed PJP prophylaxis regardless of CD4 count. It is rare outside of infancy unless the child has a very low CD4 count (Stage 3). It may present rapidly or insidiously with varying symptoms of fever, cough, dyspnea, and poor feeding. Tachypnea is almost universally present and may be out of proportion to the degree of adventitious breath sounds. Quiet tachypnea or widespread crackles are typical, as is hypoxia. The typical radiologic findings begin as mild bilateral perihilar infiltrates, which progresses to a diffuse interstitial pattern. However, chest radiographs may be normal or just show hyperinflation early in illness. Serum lactate dehydrogenase (LDH) levels are often elevated, and can be used as a screening laboratory test in the ED, but the LDH is not sensitive nor specific for PJP. Direct fluorescence antibody (DFA) testing of lower respiratory specimens is more sensitive and specific than conventional stains such as GMS (silver) stain.
Oropharyngeal and Esophageal Candidiasis
Oropharyngeal candidiasis is still relatively common in HIV-infected children. In patients with good immune function, it will generally present and respond to therapies in the same way as in uninfected children. Esophageal candidiasis usually occurs with severe immunosuppression (CD4 <100 cells/microliter) with symptoms of fever, odynophagia/dysphagia, poor feeding, or emesis. Oropharyngeal candidiasis is usually concomitantly present with esophageal candidiasis, but may occasionally be absent in children on cART.
ED Management
Acute Febrile Illness
Well-appearing children with HIV who have adequate immune function (as evidenced by a high or Stage 1 CD4 count and no recent history of recurrent invasive bacterial infections) have a slightly higher risk of acute otitis media, community-acquired pneumonia, and possibly bacteremia than their HIV-negative peers. Therefore, ED management is similar to uninfected children for the age group and vaccination status. In patients with Stage 2 or 3 illness (or unknown CD4 counts), consult with a pediatric infectious disease or HIV specialist for recommendations on work-up.
Chronic Fever Without Focus
The goal of the ED evaluation is to evaluate for possible bacterial infection. Obtain a CBC, liver function tests, ESR and CRP, urinalysis, chest x-ray, and blood, urine, and stool cultures. Admit the patient for further diagnostic evaluation. In patients with Stage 2 or 3 illness (or unknown CD4 counts), consult with a pediatric infectious disease or HIV specialist.
Oropharyngeal and Esophageal Candidiasis
Treat mild oropharyngeal candidiasis with topical therapy such as clotrimazole troche 10 mg 4–5 times daily or nystatin suspension 4–6 mL four times daily for 7–14 days. Treat moderate or severe oropharyngeal candidiasis with fluconazole 6–12 mg/kg/day (400 mg maximum) PO for 7–14 days. If the child has symptoms concerning for concomitant esophageal candidiasis, obtain a fungal culture of scrapings from the oropharynx (to confirm Candida species and susceptibility), start fluconazole 6–12 mg/kg/day (600 mg maximum); it can be given PO if the child can tolerate it. In either case, consult an infectious disease specialist for fluconazole refractory disease or known fluconazole-resistant species of Candida.
PJP
If PJP is suspected, consult a pediatric HIV specialist. Start TMP-SMZ (20 mg/kg/day of TMP div q 6h) and also give prednisone (2 mg/kg/day div q 12h, 80 mg/day maximum) if recommended by the HIV specialist. If the child is able to produce sputum or is intubated, send a lower respiratory tract for PJP stains (the specific stain will vary by institution) and DFA. Consult a pediatric HIV specialist to determine the use of steroids in mild PJP.
Follow-up
Indications for Admission
Guidelines for Managing Blood and Body Fluid Exposures
The efficacy of HIV post-exposure prophylaxis following nonoccupational exposures (nPEP) is unclear and guidelines rely heavily upon indirect inferences from data such as occupational exposures as well as expert opinion. Consult with a pediatric infectious diseases or HIV specialist if your institution does not have an nPEP policy. Factors that may increase the risk of HIV transmission include sexually transmitted diseases, acute and late-stage HIV infection, and high viral load. Factors that may decrease the risk include condom use, male circumcision, antiretroviral treatment, and pre-exposure prophylaxis. Accidental needlestick injuries following exposure to discarded needles, such as in parks or alleyways, are associated with a negligible risk for HIV exposure and to date there are no reported cases of HIV transmitted through this mechanism. The CDC guidelines can be found at: www.cdc.gov/hiv/risk/estimates/riskbehaviors.html.
ED Management
General considerations and specific elements necessary for a rational and consistent approach to HIV PEP after potential HIV exposure in children and adolescents are outlined in Figure 13.1 and Tables 13.4 and 13.5. In cases involving no- or low-risk exposures, reassure the caregiver that the child will not contract HIV infection and that post-exposure chemoprophylaxis is not necessary. For an individual presenting to the ED more than 72 hours following an exposure, chemoprophylaxis is not indicated, although exceptions may be made for high-risk exposures. In this case, or if selection of alternative prophylactic drug regimens is indicated, consult a local HIV expert. If local expertise is not available, advice may be obtained 9 a.m. to 12 a.m. (EST) from the National Clinicians’ Consultation Center PEP line at 1-888-HIV-4911. Federal, state, and local HIV PEP guidelines are subject to modification based upon the epidemiology of HIV in the community, resource availability, and the continued advancement of knowledge in this complex area. Refer to for the most up-to-date national guidelines. Obtain a fourth-generation antigen/antibody blood (not oral) test at baseline prior to starting nPEP.
