1 A 10-day-old, full-term male infant presents to the emergency department (ED) with a 1-day history of being fussy but consolable, slightly decreased oral intake, and a temperature of 38.5° C rectally. What is the risk for serious bacterial illness?

A published study demonstrated that the incidence in infants with fever who are < 28 days old is approximately 13%. Among 372 such infants, the etiology of fever was determined to be a nonspecific viral syndrome (65%), serious bacterial infection (12%), aseptic meningitis (8.1%), otitis media (5.1%), bronchiolitis (5.1%), nonbacterial gastroenteritis (2.7%), and viral stomatitis (1.0%).

Kadish H, Loveridge B, Tobey J, Bolte RG, Corneli HM: Applying outpatient protocols in febrile infants 1–28 days of age: Can the threshold be lowered?. Clin Pediatr 39:81–88, 2000.

Teague JA, Harper MG, Bachur R, et al: Epidemiology of febrile infants 14–28 days of age. Pediatr Res 53:214A, 2003.

2 Which bacterial agents are of most concern in an infant < 28 days old presenting to the ED with a fever?

Group B streptococci, gram-negative enteric organisms (Escherichia coli, Enterococcus spp.), Listeria monocytogenes, and, less commonly, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Neisseria meningitidis, and Salmonella spp.

3 A 26-day-old infant presents to the ED with a 1-day history of fever up to 39° C rectally. What should your initial management include?

For initial management of a newborn infant < 28 days old presenting to the ED with a temperature of 38.0° C:

4 How is an infant < 28 days of age classified as low-risk?

Several screening tools (Boston and Philadelphia protocols for the outpatient management of infants with fever) have been applied to infants < 28 days old presenting with fever to predict which of these newborns are less likely to have a positive bacterial culture on initial evaluation. Several of these criteria are as follows: gestational age > 37 weeks, uncomplicated prenatal course, no history of hyperbilirubinemia, no focal bacterial infection on physical examination except otitis media, no previous use of antibiotics, nontoxic appearance, and normal laboratory values (white blood count [WBC], 5000–15,000 cells/mm³, absolute band count < 1500 cells/mm³, < 10 WBCs/high-power field on urinalysis, and < 5 WBCs/high- power field on stool sample). Negative predictive values determined on infants assigned to the low-risk category were 95.4–99.1%.

5 A 6-week-old male infant presents to the ED with a temperature of 38.4° C. The infant appears nontoxic and is without an obvious source for the fever. How likely is this infant to have a bacterial infection?

A normal physical examination does not correlate well with the presence of a bacterial infection in this age group. In a study evaluating 747 febrile infants age 1–2 months, two thirds of infants with a documented bacterial infection appeared well to the attending pediatric emergency physician. The incidence of serious bacterial infection in febrile infants 1–2 months of age is 7.3%.

Bachur RG, Harber MB: Predictive model for serious bacterial infections among infants younger than three months of age. Pediatrics 108:311–316, 2001.

Baker MD, Bell LM, Avner JR: Outpatient management without antibiotics of fever in selected infants. N Engl J Med 329:1437–1441, 1993.

6 What is the cause of a temperature of 38.0° C in infants age 1–3 months who present to the ED?

A published study of 422 such infants determined the following sources:

Baker MD, Bell LM, Avner JR: The efficacy of routine outpatient management without antibiotics of fever in selected infants. Pediatrics 103:627–630, 1999.

7 A 2-month-old presents with a temperature of 40.5° C and otherwise appears nontoxic. Do infants with hyperpyrexia have a higher risk of having a serious bacterial infection?

A recently published retrospective study of infants younger than 3 months of age demonstrated that the prevalence of serious bacterial infection among febrile infants with temperatures > 40° C was 38% compared with 8.8% of those with temperature < 40° C.

Stanley R, Pagon Z, Bachur R: Hyperpyrexia among infants younger than 3 months. Pediatr Emerg Care 21:291–294, 2005.

8 What is the most common cause of sepsis in newborns?

Early-onset (birth to 7 days) group B streptococcal (GBS) infections, which may be secondary to maternal obstetric complications, prematurity, or lack of prophylactic antibiotics prior to delivery. Late-onset GBS infection (7 days to 3 months) is uncommonly associated with these factors (Table 38-1).

TABLE 38-1 EARLY-ONSET VERSUS LATE-ONSET GROUP B STREPTOCOCCAL INFECTIONS

GBS = group B streptococcus.

9 Does the immature neutrophil (band) count help in distinguishing bacterial infections from viral infections in infants age 3–36 months presenting to the ED with a temperature > 39.0° C?

In a prospective cohort study of 100 febrile children younger than 2 years old, the investigators concluded that there was no difference in percentage band count, absolute band count, or band–neutrophil ratio between bacterial and viral infections. Furthermore, children with bacterial infections had a higher mean absolute neutrophil count than children with respiratory viral infections.

Kuppermann N: Immature neutrophils in the blood smears of young febrile children. Arch Pediatr Adolesc Med 153:261–266, 1999.

10 Has the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) affected the incidence of occult bacteremia?

A retrospective cohort study of febrile infants age 2 months to 36 months conducted from 2001 to 2003 demonstrated that three of 329 blood cultures yielded a pathogenic bacterium (0.91% [95% confidence interval, 0–2.4%]); all were Streptococcus pneumoniae. One patient had a nonvaccine serotype, one was unimmunized, and the third was infected with an unknown serotype.

Stoll ML, Rubin LG: Incidence of occult bacteremia among highly febrile young children in the era of the pneumococcal conjugate vaccine. Arch Pediatr Adolesc Med 158:671–675, 2004.

11 How helpful is C-reactive protein in detecting serious bacterial infection in febrile children?

In a prospective cohort study of febrile children (> 39° C) age 1–36 months with clinically undetectable source of fever, only C-reactive protein (CRP) remained a predictor of serious bacterial infection after multivariate logistic regression analysis compared with WBC count and absolute neutrophil count. Receiver-operating characteristic analysis demonstrated CRP to be superior to WBC count and absolute neutrophil count. A CRP cutoff point of 7 mg/dL maximized both sensitivity and specificity.

Pulliam PN, Attia MW, Cronan KM: C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection. Pediatrics 108:1275–1279, 2001.

12 Do prophylactic antibiotics have a role in children with presumed bacteremia?

Studies comparing one dose of intramuscular ceftriaxone versus oral amoxicillin have had varied results. One study found that the use of ceftriaxone correlated with less persistent fever as compared to amoxicillin, although the incidence of subsequent bacterial infections was equivalent in both groups. Another study using meta-analysis to evaluate the efficacy of oral antibiotics in children with pneumococcal bacteremia concluded that there is a decrease in the risk of serious bacterial infections, but insufficient evidence to prove that oral antibiotics prevent meningitis.

13 Are febrile infants with influenza at lower risk for a serious bacterial infection?

A recently published retrospective cross-sectional study of infants age 0–36 months presenting to the ED with fever demonstrated that febrile infants with influenza A had lower prevalence of bacteremia (0.6% vs. 4.2%), urinary tract infections (1.8% vs. 9.9%), consolidated pneumonia (25.4% vs. 41.9%), meningitis (0% vs. 2.2%), or any serious bacterial infection (9.8% vs. 28.2%) compared with infants without influenza A.

Smitherman HF, Caviness AC, Macias CG: Retrospective review of serious bacterial infections in infants who are 0 to 36 months of age and have influenza A infection. Pediatrics 115:710–718, 2005.

14 Distinguish between the presentation of preseptal and orbital cellulitis in children.

See Table 38-2.

TABLE 38-2 PRESEPTAL VERSUS ORBITAL CELLULITIS IN CHILDREN

22 What organisms are associated with deep neck infections (peritonsillar abscess, retropharyngeal abscess, and lateral pharyngeal abscess) in children?

Aerobic (Streptococcus pyogenes, Staphylococcus aureus, and H. influenzae) and anaerobic (Prevotella, Fusobacterium, and Peptostreptococcus spp.) organisms are typically associated with deep neck infections in children. Almost 66% of deep neck abscesses contain β-lactamase–producing organisms.

23 Distinguish the features of deep neck infections in children.

See Table 38-4.

24 Which IV antibiotics are appropriate for retropharyngeal abscess?

As with other pediatric deep neck infections, the antibiotics expected to be efficacious include cefoxitin, clindamycin, imipenem or meropenem, and combination penicillin and β-lactamase inhibitors (ticarcillin-clavulanate).

25 Do all children with retropharyngeal abscess require surgical treatment?

Recent evidence suggests that the majority of patients with retropharyngeal abscess can be treated successfully with IV antibiotics. Surgical incision and drainage should be used in cases that do not respond to antibiotic therapy or in cases of persistent large abscesses.

Craig FW, Shunk JE: Retropharyngeal abscesses in children: Clinical presentation, utility of imaging, and current management. Pediatrics 111:1394–1398, 2003.

26 A 3-year-old boy with a history of mild to moderate eczema presents to the ED with ear pain and drainage. On physical examination, his tympanic membrane appears normal, although swelling of the ear canal makes it difficult to view the entire tympanic membrane. There is pain on movement of the tragus. There is no lateral displacement of the ear and no signs of mastoiditis. What is the likely diagnosis?

The clinical findings are consistent with otitis externa. Otitis externa is associated with Pseudomonas spp. in > 50% of patients; Escherichia, Proteus, Enterobacter, and Klebsiella spp. affect the other half. There is an increased incidence of otitis externa in children with eczema and other dermatologic disorders, as well as in children with a history of swimming, extensive cleaning of the ear, hearing aid use, immunocompromised state, and histiocytosis X.

27 How should otitis externa be managed?

Management of otitis externa includes the following: (1) gentle irrigation and suction of debris with hypertonic saline, 2% acetic acid, or alcohol with acetic acid; (2) topical antibiotics, such as neomycin-polymyxin B-hydrocortisone mixture or fluoroquinolone (using a wick in cases of severe canal edema); and (3) culturing the exudate in severe or unresponsive cases.

28 What is the best treatment for a young child with a runny nose, sore throat, cough, and fever?

The “common cold” or rhinosinusitis is caused by viruses, primarily rhinoviruses and coronaviruses. Rhinovirus has been associated with wheezing in the asthmatic child. Coronavirus causes most of the colds in young children. Antibiotics should not be used to treat the common cold because of their lack of efficacy and, more importantly, to prevent the further emergence of resistant bacteria. Over-the-counter cold remedies, such as antihistamines and decongestants, have not shown significant benefit, and in younger children may have significant side effects such as somnolence or hyperactivity. Nasal saline drops can be safely used for nasal congestion, although aggressive suctioning should be avoided.

29 List the three major causes of exudative pharyngitis in children.

Exudate refers to white or gray debris on the tonsils or pharynx. Causes include:

In developing countries, Corynebacterium diphtheriae should be included in this list. In sexually active adolescents or abused children, Neisseria gonorrhoeae should be considered. More recently, Arcanobacterium haemolyticum has been shown to cause an exudative pharyngitis, especially in adolescents.

30 A 7-year-old has fever, sore throat, tender anterior cervical lymph nodes, and lack of significant upper respiratory tract symptoms. Are these clinical features suggestive of GABHS pharyngitis?

Unfortunately, there are no clinical findings that are specific or sensitive for streptococcal pharyngitis. The absence of symptoms of upper respiratory tract infection and the presence of tender cervical nodes and a scarlatiniform rash are suggestive of the diagnosis. Some children may present with headache, abdominal pain, or nausea and vomiting. Exudative pharyngitis in children younger than 3 years of age does not tend to be streptococcal. Viral causes, such as adenovirus, predominate, especially in younger children. The diagnosis of GABHS infection is best made through culture or rapid streptococcal antigen tests.

Gerber MA: Diagnosis and treatment of pharyngitis in children. Pediatr Clin North Am 52:729–747, 2005.

31 What is the drug of choice for the treatment of streptococcal pharyngitis?

Amoxicillin or penicillin for a full 10 days to prevent rheumatic fever is the oral drug of choice. Erythromycin can be used in the penicillin-allergic patient. A single dose of intramuscular penicillin G benzathine may be indicated in specific cases in which nonadherence is a concern.

Gerber MA: Diagnosis and treatment of pharyngitis in children. Pediatr Clin North Am 52:729–747, 2005.

32 How is the diagnosis of otitis media made?

Otitis media is diagnosed as an acute otitis media or otitis media with effusion. See Table 38-5.

33 Which pathogens are implicated in acute otitis media?

Pelton SI: Otitis media: Re-evaluation of diagnosis and treatment in the era of antimicrobial resistance, pneumococcal conjugate vaccine, and evolving morbidity. Pediatr Clin North Am 52:711–728, 2005.

34 What is the drug of choice for treatment of acute otitis media?

Amoxicillin remains the drug of choice. High-dose amoxicillin (80–90 mg/kg) divided twice daily for 10 days is the best for the treatment of drug-resistant strep pneumococci, which causes 35% of cases and is less likely to resolve without treatment. Acute otitis media caused by H. influenzae and M. catarrhalis is more likely to resolve spontaneously. Recurrent acute otitis media may require the use of other antibiotics to address the problem of β-lactamase–producing bacteria or highly resistant Streptococcus pneumoniae. Shorter courses of treatment may be considered in nontoxic children older than 2 years.

35 What is the mechanism of pneumococcal resistance?

Pneumococcal resistance is mediated by alterations in the penicillin-binding proteins. Resistance of H. influenzae and M. catarrhalis is mediated by a β-lactamase. This difference has important therapeutic implications, since β-lactamase–stable agents, such as amoxicillin-clavulanate, are more effective against H. influenzae and M. catarrhalis, but do not provide any advantage over amoxicillin in treating penicillin-resistant pneumococci.

36 Which antibiotics are considered second-line agents for the treatment of acute otitis media?

Amoxicillin-clavulanic acid, newer macrolides such as azithromycin, or cephalosporins such as cefdinir are suitable alternative agents if amoxicillin has failed. Intramuscular ceftriaxone, a broad-spectrum, third-generation cephalosporin, should be reserved for children who are vomiting and cannot tolerate oral medication, or for those with possible concomitant occult bacteremia.

37 List the risk factors for infection with drug-resistant pneumococci.

38 You decide to intubate the trachea of a young patient who presents with severe respiratory distress and stridor. On endotracheal intubation, purulent tracheal secretions are seen. What is the likely diagnosis?

Bacterial tracheitis, also called pseudomembranous tracheitis. This infection requires immediate attention and treatment. Copious amounts of secretions can obstruct the trachea or a major bronchus. This condition may resemble croup, which may be a predisposing risk factor. Because of inspiratory and expiratory wheezing, foreign-body aspiration may also be part of the differential diagnosis. The most common organisms recovered from infected patients are Staphylococcus aureus, H. influenzae, Streptococcus pyogenes, Streptococcus pneumoniae, and M. catarrhalis. Antimicrobial selection should be based on these pathogens, and cefuroxime or a combination of oxacillin plus a third-generation cephalosporin is a reasonable choice.

39 What are the common causes of stomatitis? How can they be distinguished?

Inflammation of the oral mucous membrane (stomatitis) is a common finding in children, usually presenting with ulcers or vesicles (“canker sores”). The differential diagnosis is based on the location of the lesions and clinical picture:

Recurrent lesions may be due to abnormalities in the immune system, such as in cyclic neutropenia or chemotherapy-induced neutropenia and chronic granulomatous disease. In association with recurrent fever, stomatitis may be due to PFAPA (periodic fever, adenitis, pharyngitis, and aphthous stomatitis).

Fisher RG, Boyce TG: Moffet’s Pediatric Infectious Diseases: A Problem-Oriented Approach. 4th ed. Philadelphia, Lippincott Williams & Wilkins, 2005, pp 62–67.

40 What are the clinical manifestations and management of a child with suspected acute mastoiditis?

Mastoiditis is an infection of the mastoid bones or air spaces that surround them. The mastoid air cells transmit to the middle ear, and their mucous membrane is in contact with the middle ear. It is a severe but rare complication of otitis media. It manifests as fever, ear pain, erythema, and retroauricular swelling resulting in a downward and outward deviation of the auricle. Computed tomography (CT) may be helpful when intracranial complications of mastoiditis are suspected. Children with mastoiditis should be admitted to the hospital and treated with IV antibiotics and myringotomy with tympanostomy tube placement.

41 What are the typical organisms causing sinusitis?

The typical organisms associated with acute sinusitis include:

42 What criteria define sinusitis?

American Academy of Pediatrics: Clinical practice guideline: Management of sinusitis. Pediatrics 108:798–808, 2001.

43 What is the differential diagnosis of acute bacterial sinusitis?

44 When is imaging necessary in the diagnosis of acute bacterial sinusitis?

The American Academy of Pediatrics recommends that for children < 6 years of age who have persistent respiratory symptoms that have not improved for > 10 but < 30 days, the diagnosis of acute bacterial sinusitis can be made on clinical criteria without radiographs. For children > 6 years of age with persistent symptoms and for all children with severe symptoms, radiography may be indicated. CT and plain radiographic findings in children with acute sinusitis include:

In children < 6 years old with persistent upper respiratory tract symptoms, 88% have abnormal sinus radiographs. Therefore, in uncomplicated cases of sinusitis in children < 6 years, radiographs are not necessary.

American Academy of Pediatrics: Clinical practice guideline: Management of sinusitis. Pediatrics 108:798, 2001.

Wald ER: Clinical features, diagnosis, and evaluation of acute bacterial sinusitis in children, 2006: www.uptodate.com

45 When is CT useful in the diagnosis of sinusitis?

CT (Fig. 38-1) is helpful in children with complications of acute bacterial sinus infection or those with very persistent or recurrent infections that do not respond to medical management.

Figure 38-1 Computed tomographic scan of sinusitis.

46 Describe the treatment of acute bacterial sinusitis.

1 For uncomplicated acute bacterial sinusitis of mild to moderate severity:

Amoxicillin (45–90 mg/kg/d twice daily)

Or amoxicillin-clavulanate (45–90 mg/kg/d in two divided doses)

2 For children with acute bacterial sinusitis of at least moderate severity or who have received an antibiotic in the past 90 days or who attend day care:

Amoxicillin-clavulanate (80–90 mg/kg/d in two divided doses)

Or cefdinir (14 mg/kg/d in one or two doses)

Or cefuroxime (30 mg/kg/d)

Or cefpodoxime (10 mg/kg/d once daily)

3 Children with vomiting can be treated with one dose of IV ceftriaxone followed by oral antibiotics after vomiting has subsided.

Wald ER: Microbiology and treatment of acute bacterial sinusitis, 2006: www.uptodate.com

47 What is Pott’s puffy tumor?

Pott’s puffy tumor (Fig. 38-2) was first described by Sir Percivall Pott in 1760, and appears as a soft, fluctuant, painful forehead or scalp swelling usually associated with frontal sinusitis. Patients tend to be febrile and appear toxic. It is usually seen in children after 8 years of age when the frontal sinuses begin to develop. It represents osteomyelitis of the frontal bone with subsequent subperiosteal elevation. CT is essential for diagnosis and to evaluate other possible areas of spread. Successful treatment usually involves both antibiotics and surgical drainage.

Figure 38-2 Pott’s puffy tumor.

48 Which infectious organisms are associated with the three primary cardiac infections?

See Table 38-6.

49 What are some of the signs and symptoms of myocarditis in infants and children?

Children presenting to the ED with myocarditis may initially report a nonspecific, flulike illness or gastroenteritis. Within 1–4 weeks, fever, malaise, dyspnea, tachypnea, chest pain, pallor, or cool, poorly perfused distal extremities may develop. Infants may present with feeding difficulties, listlessness, cardiac signs, or respiratory distress. The cardiac examination may reveal sinus tachycardia at rest, muffled and distant heart sounds, lateral displacement of the point of maximal impulse, and a gallop rhythm suggestive of congestive heart failure. Other findings on physical examination associated with heart failure include jugular venous distention, weak pulses, cyanosis, poor perfusion, or hepatosplenomegaly.

50 What diagnostic test results in the ED support the suspicion of myocarditis?

51 What is the acute management of myocarditis in infants and children?

52 What are the common symptoms, signs, and laboratory findings in infants and children with infective endocarditis?

See Table 38-7.

TABLE 38-7 SYMPTOMS, SIGNS, AND LABORATORY FINDINGS IN INFECTIVE ENDOCARDITIS

53 Differentiate among Osler nodes, Janeway lesions, and Roth spots.

Although commonly seen in adults, these findings are rare in infants and children with infective endocarditis. Other embolic phenomena associated with endocarditis include splinter hemorrhages and conjunctival hemorrhages.

54 How do you make the diagnosis of infective endocarditis?

For a definitive diagnosis of infective endocarditis, you must have evidence, either based on surgery or autopsy histology or positive bacteriology, of valvular vegetations or peripheral embolus. Probable diagnosis is based on (1) persistently positive blood culture plus either a new or changing cardiac murmur or predisposing heart disease plus vascular phenomenon (petechiae, splinter hemorrhages, conjunctival hemorrhages, Roth spots, Osler nodes, Janeway lesions, aseptic meningitis, glomerulonephritis, pulmonary emboli, or coronary or peripheral emboli), or (2) negative or intermittently positive blood cultures plus all three of the following: fever, new or changing cardiac murmur, and vascular phenomenon as defined above.

55 What antibiotics are recommended for the presumptive diagnosis of infective endocarditis?

Vancomycin plus gentamicin is recommended for nosocomial infections associated with a vascular cannula or “early” prosthetic valve endocarditis (< 60 days after surgery), and a penicillinase-resistant penicillin plus gentamicin for a natural valve or “late” prosthetic valve endocarditis (> 60 days after surgery).

56 What are the clinical manifestations and diagnostic findings associated with pericarditis?

Clinical Manifestations:

Diagnostic Findings:

57 What is the antimicrobial agent of choice for the presumptive diagnosis of bacterial pericarditis?

Until pericardial cultures return, initial antibiotics should include oxacillin or nafcillin or vancomycin plus cefotaxime or ceftriaxone.

58 How common are urinary tract infections in infants and children?

Among infants and young children (males < 1 year and females < 2 years) who present to the ED with a temperature of 38.5° C without a source, approximately 3.3% have a urinary tract infection (UTI). The highest prevalence occurs in white females with temperature > 39.0° C without a potential source of fever on examination (30.6%).

Shaw KN, Gorelick M, McGowan KL, Yakscoe NM, Schwartz JS: Prevalence of urinary tract infections in febrile young children in the emergency department. Pediatrics 102:e16, 1998.

59 What are the signs and symptoms of UTIs in infants and children?

See Table 38-8. Approximately 50% of adolescents who present to the ED with dysuria, increased frequency, and urgency on urination have a UTI. Only 10% of children who present with these symptoms have a UTI; their symptoms may instead be due to bubble bath irritation, vaginitis, pinworms, or sexual abuse.

TABLE 38-8 SIGNS AND SYMPTOMS OF URINARY TRACT INFECTIONS ACCORDING TO AGE

60 What is the definition of pyuria?

Pyuria is the presence of 5 WBCs/high-power field (uncentrifuged) or 10 WBCs/mm³ (centrifuged) specimens. Although pyuria can be an indication of a UTI, it also is seen with chemical irritation, fever, viral infection, appendicitis, glomerulonephritis, Kawasaki disease, and renal tuberculosis.

61 What screening tests are most useful to rule out a UTI?

Several rapid screening tests are used frequently in the ED to evaluate for a UTI in an infant or child presenting with a fever without a source. They include a dipstick biochemical analysis of urine for nitrites or leukocyte esterase and a microscopic analysis of urine for WBCs or bacteria. A meta-analysis examining screening tests for UTIs concluded that both Gram stain on an uncentrifuged urine specimen and dipstick analysis of an uncentrifuged urine specimen for nitrite and leukocyte esterase performed similarly, and these tests were superior to microscopic analysis for pyuria.

Gorelick MH: Screening tests for urinary tract infection in children: A meta-analysis. Pediatrics 104:e54, 1999.

62 Should all infants age 2–24 months with a fever be evaluated for a UTI?

In females, features increasing the likelihood of UTI include temperature of 39.0° C, fever for 2 or more days, white race, age < 1 year, and absence of another potential source of fever. In males, clinical features predictive of a UTI include age < 6 months, being uncircumcised, and absence of another potential source for the fever. Consider screening tests and urine cultures in all infants and children with these risk factors.

63 Can a urine specimen collected with a bag be used to diagnose a UTI in an infant < 2 years old?

No. The false-positive rate of a positive urine culture obtained by the bag method is approximately 85%, although a negative result from bagged urine rules out a UTI. If a UTI is considered in an infant < 2 years of age, then transurethral catheterization of the urinary bladder (sensitivity of 95% and specificity of 99%) or suprapubic aspiration should be implemented. In older, toilet-trained children, the midstream clean-catch method is preferred (contamination rates of 0–29%).

64 What treatment options are available for infants and children with simple cystitis?

Outpatient therapy may be considered in infants who are well hydrated and nontoxic appearing, those who can tolerate oral medication, those without underlying urologic abnormalities, and those with reliable parents and social situations. When empiric therapy is chosen, the antibiotic should be based on patterns of antibiotic sensitivity in your community. A 5- to 7-day course of oral antibiotics is recommended. Cefixime or cefdinir is the first-line choice. There are increasing rates of resistance of E. coli to amoxicillin, trimethoprim, and first-generation cephalosporins are adequate for simple cystitis.

Ladhani S, Gransden W: Increasing antibiotic resistance among urinary tract isolates. Arch Dis Child 88:444–445, 2003.

65 Which young children with UTIs need to be admitted to the hospital?

Most pediatric and emergency medicine textbooks recommend treating febrile children with UTIs and those with acute pyelonephritis, regardless of age, with IV antibiotics. Recent literature concludes that if an infant or child suspected of having acute pyelonephritis is nontoxic and well hydrated, with a reliable social situation, then he or she may be treated with oral antibiotics. A multicenter, randomized clinical trial evaluated children age 1–24 months presenting with temperature > 38.3° C and either pyuria or bacteruria. Some children received either oral cefixime for 14 days (double dose on day 1) or IV cefotaxime for 3 days followed by oral cefixime for 11 days. Both groups responded equally.

Hoberman A: Oral versus intravenous therapy for urinary tract infections in young febrile children. Pediatrics 104:79–86, 1999.

66 What are the most likely etiologic agents for pelvic inflammatory disease (PID)?

The etiologic agents causing PID include N. gonorrhoeae (25–50%), C. trachomatis (25–43%), and anaerobes (Peptococcus, Peptostreptococcus, Bacteroides spp.; 25–84%), although most cases of PID are of polymicrobial etiology.

67 What is the etiology of vaginitis in postpubertal girls? What characteristics distinguish the infections?

Patients with vaginitis typically present with a history of dysuria, vaginal discharge, burning, or vulvar lesions. Physical examination reveals vulvar irritation and vaginal discharge. The infectious etiologies in postpubertal girls include bacterial vaginosis (40–50%), vulvovaginal candidiasis (20–25%), and Trichomonas vaginitis (15–20%) (Table 38-9).

68 What is the differential diagnosis for genital ulcers? How do you distinguish between each disease process?

See Table 38-10.

69 What organisms most commonly cause cellulitis?

Cellulitis, which is an infection of the dermis and subcutaneous fat, is caused most often by Staphylococcus aureus and β-hemolytic streptococci in children.

70 Are cultures helpful in diagnosing cellulitis?

In a published study, blood cultures were positive in only 2% of children with cellulitis. Furthermore, cultures of fluid aspirated from the point of maximum inflammation along with blood cultures are positive in only 25% of children with cellulitis.

Sadow KB: Blood cultures in the evaluation of children with cellulitis. Pediatrics 101:e4, 1998.

71 When is parenteral treatment recommended for cellulitis?

Criteria for parenteral antibiotics include signs of systemic toxicity, rapidly progressing involvement, lymphangitis, involvement of face or neck, and absence of improvement following 48 hours of outpatient management. A penicillinase-resistant penicillin or a first-generation cephalosporin may be used for empiric outpatient therapy. Consider clindamycin or trimethoprim-sulfamethoxazole for suspected methicillin-resistant Staphylococcus aureus (MRSA) infection.

72 A 9-year-old child presents to the ED with a chief complaint of right foot pain. Four days ago he stepped on a nail that went through his sneaker into his sole. He presents with no history of fever, but with erythema and warmth of the sole of his foot and point tenderness at the proximal end of his fifth metatarsal. What diagnosis do you suspect?

This scenario is classic for a Pseudomonas aeruginosa infection (most likely osteochondritis) in a child who has a history of stepping on a nail through a sweaty sneaker. This child should be admitted for IV antibiotics following a workup for osteomyelitis (i.e., magnetic resonance imaging or nuclear bone scanning, CBC with differential, erythrocyte sedimentation rate/CRP, blood culture). Consult orthopedic surgery for probable surgical debridement.

73 What is the differential diagnosis of perianal dermatitis/cellulitis?

Streptococcal infections (GBS in infants, group A β-hemolytic streptococci [GABHS] in older children), inflammatory bowel disease, sexual abuse, pinworms, diaper dermatitis, psoriasis, and seborrheic dermatitis.

74 Match the superficial bacterial skin infection with its classical presentation and treatment.

Answers: 1, B; 2, D; 3, F; 4, A; 5, C; 6, E

75 A 4-year-old presents with a boggy, purulent, eczematoid mass measuring 5 × 5 cm on his right temporal scalp area. He also has alopecia and a right-sided, posterior chain cervical adenopathy. What is the likely diagnosis?

This presentation is consistent with a kerion, which is a cell-mediated response to tinea capitis often confused with a bacterial skin infection. Therapy includes a minimum of 4 weeks of oral antifungal therapy (griseofulvin or ketoconazole). Systemic antibiotics are not indicated.

76 What findings may be associated with an invasive skin or soft tissue infection?

77 What characteristics of lymph nodes distinguish infectious from noninfectious causes?

Soft, nontender, small (usually < 2 cm), and discrete nodes either found in a specific region or generalized may be associated with hyperplasia secondary to a viral infection. These nodes typically lack signs of edema, erythema, or abscess formation. Acute bacterial lymphadenitis is associated with soft, unilateral, fixed, and large (usually > 2 cm) nodes with surrounding erythema or swelling. These usually are tender and warm, and poorly defined. When acute bacterial lymphadenitis progresses to chronic infections, the nodes become larger, less erythematous, and more fluctuant, and adhere to overlying skin.

Lymph nodes associated with malignancy are firm, discrete, freely movable, nontender, rubbery in texture, and lacking in signs of inflammation. They increase in size and, over time, become matted with adjacent lymph nodes.

78 Lymphadenopathy isolated to a particular region may indicate a specific infection. List some of these associations

See Table 38-11.

TABLE 38-11 REGIONAL LYMPHADENOPATHY AND ASSOCIATED INFECTIOUS ETIOLOGY

79 How does a child with cat scratch disease typically present?

Typically there is a history of a scratch by a kitten on an extremity or the face, followed by the appearance (3–10 days after the inoculation) of a macule, papule, or vesicle, which may last several days to weeks. Single lymph nodes occur 1–2 weeks after the scratch in approximately 50% of children; several lymph nodes appear in the same region in 20%. Other clinical manifestations of cat scratch disease include fever, malaise/fatigue, headaches, splenomegaly, anorexia/emesis/weight loss, sore throat, exanthems, conjunctivitis, and parotid swelling. Lymphadenopathy associated with cat scratch disease is self-limited, although recent studies demonstrate the efficacy of azithromycin in decreasing the duration of local and systemic symptoms.

Spach DH, Myers SA, Kaplan SL: Cat scratch disease, 2006: www.uptodate.com

80 What are atypical clinical manifestations seen in cat scratch disease (5–20% of all presentations)?

81 What is appropriate treatment for a nontoxic-appearing child who presents with lymphadenitis?

For a child with a nonfluctuant node consistent with an acute bacterial infection, or a staphylococcal or streptococcal infection, a β-lactamase–resistant penicillin (e.g., dicloxacillin) or a cephalosporin (e.g., cephalexin) for 2 weeks is appropriate treatment. For a penicillin-allergic child, clindamycin or erythromycin may be used. In those patients who are toxic-appearing or unresponsive to oral antibiotics, or in young infants, IV antibiotics (e.g., nafcillin, cefazolin, or clindamycin) are effective. Percutaneous aspiration or incision and drainage may be necessary for fluctuant nodes.

82 Distinguish among bacteremia, systemic inflammation response syndrome (SIRS), sepsis, severe sepsis, and septic shock.

Bacteremia: The presence of bacteria in the blood

SIRS: A clinical syndrome in response to a variety of insults (e.g., infection, trauma, acute respiratory distress syndrome, neoplasms, pancreatitis, burns) manifested by at least two of the following conditions:

Temperature > 38.0° C or < 36.0° C

Tachycardia (heart rate > 160 beats per minute in infants, > 150 beats per minute in children)

Tachypnea (respiratory rate > 60 breaths per minute in infants, > 50 breaths per minute in children)

WBC count > 12,000 cells/mm³ or > 10% immature forms

Sepsis: The systemic response to infections manifested by two or more of the criteria for SIRS

Severe sepsis: Sepsis associated with hypotension (systolic blood pressure < 65 mmHg in infants, < 75 mmHg in children, and < 90 mmHg in adolescents, or reduction > 40 mmHg from baseline), hypoperfusion (lactic acidosis, oliguria, hypoxemia, or acute change in mental status), or organ dysfunction

Septic shock: Sepsis with hypotension, despite adequate fluid resuscitation, with the presence of perfusion abnormalities, which may include lactic acidosis, oliguria, or acute change in mental status.

83 What are the common signs/symptoms and laboratory values associated with septic shock in infants and children?

Infants:

Children

84 What are the antibiotic choices for empirical therapy in infants and children presenting in septic shock?

See Table 38-12.

TABLE 38-12 EMPIRICAL THERAPY FOR SEPTIC SHOCK ACCORDING TO AGE

GAS = group A streptococci, GAB = group B streptococci.

85 What is the differential diagnosis of fever and petechiae?

Children and infants who present to the ED with fever and petechiae require immediate attention because there are life-threatening causes that may progress rapidly to death. The differential diagnosis of common infectious causes includes both treatable and nontreatable organisms:

86 When is fever associated with a petechial rash less concerning?

A child with fever and petechiae is less likely to have serious bacterial illness if he or she appears well and has one isolated petechial lesion, petechiae only above the nipple line, a mechanical cause of the petechiae (coughing, emesis, screaming or crying, blood pressure cuff or tourniquet), or normal WBC count. Most can be safely discharged from the ED.

Mandl KD: Incidence of bacteremia in infants and children with fever and petechiae. J Pediatr 131:398–404, 1997.

87 What factors predict poor prognosis in infants and children with meningococcemia?

88 What is acute arthritis and dermatitis syndrome?

Also known as disseminated gonococcal infection, acute arthritis and dermatitis syndrome occurs in approximately 1–3% of persons with untreated mucosal gonorrhea. Clinical findings include dermatitis (tender necrotic pustule with an erythematous base located distally on an upper extremity), migratory polyarthralgias or tenosynovitis affecting smaller joints, and arthritis (pyogenic monoarticular or polyarticular with effusion, especially of knee, ankle, or wrist). Gonococcal bacteremia may also be seen.

89 List clinical criteria that define toxic shock syndrome.

The diagnosis is made by the presence of three major criteria and at least three minor criteria, with negative blood, throat, and CSF cultures (except for Staphylococcus aureus) and no rise in titers to Rocky Mountain spotted fever (RMSF), leptospirosis, and rubeola antigens.

90 Distinguish between staphylococcal and streptococcal toxic shock syndrome.

See Table 38-13.

TABLE 38-13 STAPHYLOCOCCAL VS. STREPTOCOCCAL TOXIC SHOCK SYNDROME

91 Which two infectious agents are most commonly associated with erythema multiforme minor and major (Stevens-Johnson syndrome), respectively?

Erythema multiforme minor is most commonly associated with HSV, and Stevens-Johnson syndrome is most commonly associated with Mycoplasma pneumoniae.

92 What is staphylococcal scalded skin syndrome?

Staphylococcal scalded skin syndrome is a dermatosis caused by an epidermolytic toxin produced by certain strains of staphylococci. It generally affects children < 5 years old, and classically presents with fever, irritability, and tender erythematous skin. The skin begins to exfoliate, with crusting and exudation around the mouth, eyes, and paranasal areas, within 2–3 days of the initial rash. The presence of the Nikolsky sign (wrinkling of the upper layer of the epidermis and removal of the layer by light stroking, like the peeling of wet tissue paper) may be present. A skin biopsy from the blister base can distinguish staphylococcal scalded skin syndrome from toxic epidermal necrolysis. The mortality rate is < 4%. Hospitalization is often required for skin care, fluid management, and IV antibiotics.

93 What are the typical cutaneous findings associated with scarlet fever?

These follow a 2- to 5-day incubation period and accompany the abrupt onset of fever, headache, vomiting, malaise, abdominal pain, and sore throat:

94 Match the following ED scenarios with the appropriate management.

95 What is PANDAS?

This is a condition that has been described as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. The association between group A streptococci and PANDAS is not proven.

American Academy of Pediatrics: Group A streptococcal infections. In: Pickering, LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, p 611.

96 What are the most common etiologic agents of bacterial meningitis?

Wubbel L, McCracken GH: Management of bacterial meningitis: 1998. Pediatr Rev 19:78–84, 1998.

97 You are evaluating a 12-month-old infant for possible meningitis. He comes from a community that does not believe in immunization for religious reasons. Given the history, of the three possible pathogens, which should you be most concerned about?

Haemophilus influenzae type B (Hib). The epidemiology and microbiology of childhood meningitis have changed dramatically since the introduction of the Hib conjugate vaccines. Prior to the vaccine, Hib caused the majority of cases of bacterial meningitis in children. Peak incidence of meningitis was between 6 and 18 months. It is no longer a significant pathogen in countries where Hib vaccination is used because of the vaccine’s ability to decrease pharyngeal colonization. Since 1988, when the Hib vaccine was introduced, we now see < 1/100,000 cases of meningitis caused by Hib in children younger than 5 years old. Hib disease is currently seen in the United States in closed communities that do not believe in immunizations, or in very young infants who have not completed their vaccination series.

Wubbel L, McCracken GH: Management of bacterial meningitis: 1998. Pediatr Rev 19:78–84, 1998.

98 Which antibiotics should be used to treat neonatal meningitis (age 0–3 months)?

Ampicillin and cefotaxime. Ampicillin and gentamicin are commonly used for the treatment of neonatal sepsis, but if the CSF findings are consistent with meningitis, consider a third-generation cephalosporin in addition to ampicillin because of its superior CNS penetration.

99 Why is ampicillin used to treat meningitis in the 0- to 3-month-old infant?

It is used to provide adequate antimicrobial coverage for Listeria monocytogenes. Frequently, an aminoglycoside, such as gentamicin, is added to improve the effectiveness of the ampicillin. Penicillin-allergic patients may be treated with trimethoprim-sulfamethoxazole.

100 What empirical antibiotic therapy should be initiated for the treatment of bacterial meningitis outside the neonatal period (> 3 mo)?

Administer vancomycin and ceftriaxone to all infants with definite or presumed bacterial meningitis. Vancomycin is recommended for all CNS infections that may involve pneumococcus as a pathogen because of pneumococcal resistance to penicillin and other β-lactam antibiotics. For the child with hypersensitivity to β-lactam antibiotics, consider the combination of rifampin plus vancomycin. Vancomycin should not be given alone.

American Academy of Pediatrics: Pneumococcal infections. In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 529–530.

101 Should corticosteroids be administered as adjunctive therapy in the treatment of bacterial meningitis?

Corticosteroids have been shown to reduce hearing loss and neurologic sequelae in children with Hib meningitis. The effectiveness of corticosteroids in disease caused by Streptococcus pneumoniae and N. meningitidis is less clear, although retrospective studies have shown significant reductions in hearing loss among those treated with dexamethasone with antibiotics versus antibiotics alone. There is evidence that dexamethasone reduces the incidence of neurologic complications in adults with Streptococcus pneumoniae meningitis. Current recommendations suggest that dexamethasone be considered for children with pneumococcal meningitis. If used, dexamethasone should be given before or at the time of antibiotic administration.

van de Beek D, de Gans J, McIntyre P, Prasad K: Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev 2003; CD004305

102 What is aseptic meningitis?

This term has become synonymous with viral meningitis but in fact describes meningitis caused by viruses, fungi, or certain bacteria that cannot be seen on Gram stain. It also applies to meningitis caused by drugs (nonsteroidal anti-inflammatory drugs), systemic illness, neoplasms, or parameningeal conditions. This term does not imply an aseptic course of illness or an aseptic-appearing child. A more accurate term would be Gram stain–negative meningitis.

103 How can viral meningitis be distinguished from bacterial meningitis?

It is often difficult to distinguish these two clinical entities. Both can present with fever, headache, stiff neck, vomiting, and photophobia. Young infants may show nonspecific signs such as irritability, poor oral intake, and somnolence. The typical CSF findings can sometimes be used to distinguish viral from bacterial meningitis, although considerable overlap can exist (Table 38-14).

TABLE 38-14 TYPICAL CEREBROSPINAL FLUID FINDINGS IN VIRAL AND BACTERIAL MENINGITIS

CSF = cerebrospinal fluid, WBC = white blood cell.

104 On a hot summer day, a 5-year-old boy presents with fever, headache, and photophobia. You suspect meningitis and perform a lumbar puncture. The CSF evaluation reveals a WBC count of 400 cells/mL with a polymorphonuclear cell predominance, normal glucose, normal protein, and negative Gram stain. What is the most likely diagnosis?

Enteroviral meningitis is the most likely diagnosis. Nonpolio enteroviruses are the leading cause of viral meningitis, accounting for 80–90% of all cases from which an etiologic agent is identified. This group includes group A and B coxsackie viruses, echoviruses, and enteroviruses (types 68–71 and 73). They are called summer viruses because resulting infections occur during the warmer months. The CSF examination in this patient is typical of enterovirus infection. The predominance of neutrophils is often seen early in the course of the disease. The presence of other identifiable enteroviral syndromes in the community, such as herpangina and hand-foot-mouth disease, can be useful in diagnosis because outbreaks tend to be epidemic and seasonal. The availability of reliable enteroviral polymerase chain reaction in CSF makes it easier to distinguish these two entities.

Zaoutis TE, Klein JD: Enterovirus infections. Pediatr Rev 19:183–191, 1998.

105 A 2-week-old infant presents with fever and focal seizures. What therapy should be instituted immediately?

Ampicillin, cefotaxime, and acyclovir should be started as soon as possible. This child’s presentation, especially the seizures, is consistent with HSV encephalitis. Typically, fever, lethargy, and seizures occur at 2–3 weeks of age. Skin lesions are present in about 50% of patients, and in most will appear late in the illness if at all. CSF examination usually reveals fewer than 100 WBCs, but may have an increased number of red blood cells. CSF cultures are usually negative for HSV. HSV DNA in the CSF can best be detected using polymerase chain reaction. Neonatal infections are serious, with high mortality and morbidity rates even with prompt treatment. About one third of neonatal HSV infections involve the CNS, and while most patients survive, there is a high incidence of neurologic impairment. This patient should begin receiving empirical therapy for both bacterial and HSV infection.

Kohl S: Herpes simplex infections in newborn infants. Semin Pediatr Infect Dis 10:154–160, 1999.

106 A 10-year-old boy has a fever and is suddenly acting strangely, with combative behavior and garbled speech. What is the differential diagnosis for this presentation?

Fever in combination with a change in mental status suggests a diagnosis of encephalitis. Increased intracranial pressure without signs of meningitis can also be seen. Infectious causes of encephalitis are predominately viral in origin. Epidemic acute encephalomyelitis is usually due to arboviruses (arthropod borne viruses) such as West Nile and LaCrosse viruses. Sporadic acute encephalitis can be due to many viruses such as enteroviruses, HSV, varicella, cytomegalovirus, and Epstein-Barr virus. Bacterial causes are less common, but in a child with exposure to cats (especially kittens), consider infection with Bartonella henselae (cat scratch disease). Other infectious diseases that cause encephalitis include RMSF, Lyme disease, and Mycoplasma pneumoniae infection. Acute disseminated encephalomyelitis (ADEM), also known as a postinfectious encephalomyelitis, is a rare monophasic inflammatory disorder of the CNS that can also present in this manner. ADEM has a propensity to occur after minor upper respiratory tract infections. CSF, by definition, reveals no bacterial or viral etiology. The existence of bilateral optic neuritis and transverse myelitis, however, is consistent with the diagnosis of ADEM.

Russell CD: Acute disseminated encephalomyelitis. Semin Pediatr Infect Dis 14:90–95, 2003.

107 A 12-year-old boy with a 2-week history of sinusitis presents with persistent fever, headache, and altered mental status. What serious complication of sinusitis should be considered?

Brain abscess is an uncommon but serious complication of frontal sinusitis. It is seen in older children and teenagers because of the late development of the frontal sinuses. Maintain a high index of suspicion when patients with sinusitis present with persistent symptoms and neurologic findings. Other potential complications include epidural abscess or meningitis.

Wald ER: Clinical features, evaluation and diagnosis of acute bacterial sinusitis in children, 2006: www.uptodate.com

108 An 8-year-old boy has fever and back pain. What is your approach to diagnosis and management?

Back pain is an unusual reason for children to be seen in the ED. Frequently, back pain in children indicates significant disease. The differential diagnosis includes infectious, neoplastic, and rheumatologic disorders. The major infections producing back pain in children include discitis, vertebral osteomyelitis, spinal epidural abscess, and sacroiliac joint infection (Table 38-15).

109 What is the appropriate treatment for a child who presents with erythema migrans?

Erythema migrans is the characteristic rash of Lyme disease, seen in approximately 70% of patients. It begins as a red papule or macule that rapidly expands to become a round or oval lesion at least 5 cm in diameter, with an erythematous periphery and central clearing. The treatment of choice is doxycycline, for children 8 years old or older. Amoxicillin is recommended for younger children (because of possible tetracycline toxicity). Treatment for 2–3 weeks is recommended. Cefuroxime axetil is an approved alternate therapy.

110 What is the recommended treatment for Lyme disease in children?

See Table 38-16.

TABLE 38-16 TREATMENT OF LYME DISEASE BY STAGE

Penicillin-allergic patients can be treated with cefuroxime axetil and erythromycin.

* ≥8 years old, treat with doxycycline; <8 years old, treat with amoxicillin.

Adapted from American Academy of Pediatrics: Lyme disease. In: Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 428–432.

111 A child presents with bilateral facial palsy. What disease entities would you consider?

In areas that are endemic for Lyme disease in the United States (Northeast, upper Midwest, and Pacific Northwest), Lyme disease should always be suspected. It is one of the few diseases that can produce bilateral facial palsy. Other causes of facial palsy, usually unilateral, include mastoiditis, Guillain-Barré syndrome, herpesvirus infection, and tumors.

112 A 16-year-old otherwise healthy girl presents with a syncopal episode. electrocardiography reveals complete heart block. What is the differential diagnosis?

113 What is the time course of clinical manifestations of Lyme disease?

See Table 38-17.

TABLE 38-17 TIME COURSE OF CLINICAL MANIFESTATIONS OF LYME DISEASE

EM = erythema migrans.

114 Describe the distribution of the rash in RMSF.

RMSF is a small vessel vasculitis caused by Rickettsia rickettsii. The rash usually occurs before the sixth day of the febrile illness (temperature, 38.5° C) as a blanching maculopapular rash on the ankles and wrists. It spreads centripetally to the trunk but spares the face. In most patients, the rash involves the palms and soles and eventually becomes petechial or purpuric.

Other clinical features of RMSF include headache, myalgia, conjunctival hyperemia, and photophobia. Approximately 20% of cases never develop a rash.

American Academy of Pediatrics: Rocky Mountain spotted fever. In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 570–572.

115 What electrolyte abnormality is commonly associated with RMSF?

Hyponatremia (sodium level < 130 mEq/L) is seen in about 25% of affected patients. Other laboratory abnormalities commonly include thrombocytopenia, anemia, and a variable WBC count with a left shift.

116 In which Rocky Mountain state is RMSF most commonly seen?

None. “Rocky Mountain” is a misnomer. Most cases of RMSF occur in the South Atlantic, South Central, and the Southeastern United States.

117 What laboratory abnormalities are found in ehrlichiosis?

118 When a child is found to have bloody diarrhea, which infectious agents are most likely responsible?

The most common agents are Salmonella, Shigella, and Campylobacter spp.; shiga toxin producing E. coli (E. coli O157:H7); and Yersinia spp. Other infectious agents, including Vibrio parahaemolyticus, Aeromonas spp., and acute amebiasis, should be considered.

119 Which bacterial stool pathogens require antimicrobial treatment?

American Academy of Pediatrics: Escherichia coli diarrhea. In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 291–295.

120 A 2-year-old presents with vomiting, profuse diarrhea, and new-onset seizures. What could be responsible for this clinical picture?

Shigella infections are associated with CNS symptoms, including seizures and toxic encephalopathy (Ekiri syndrome). Severe diarrhea regardless of the etiology, however, may cause electrolyte abnormalities that result in seizures.

Fisher RG, Boyce TG: Moffet’s Pediatric Infectious Diseases: A Problem-Oriented Approach, 4th ed. Philadelphia, Lippincott Williams & Wilkins, 2005, p 551.

121 Should antimotility agents be used to manage gastroenteritis in children?

No. The medications have limited benefit and have a high rate of side effects. Products with opiate derivatives are actually contraindicated. Nonnarcotic antimotility agents may be used in afebrile patients with nonbloody diarrhea.

122 Which organisms cause food-borne illnesses? How can you distinguish them?

See Table 38-18.

TABLE 38-18 ONSET, SYMPTOMS, AND ETIOLOGY OF FOOD-BORNE ILLNESS

Adapted from American Academy of Pediatrics: Appendix VI: Clinical syndromes associated with food borne diseases. In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 858-860.

123 A 3-month-old infant presents with a 3-day history of constipation, progressively poor feeding, and lethargy. On physical examination you notice a quiet, inactive child who is otherwise alert with good perfusion. The neurologic examination reveals a weak cry, poor suck, and hypotonia. What is the likely diagnosis?

Infant botulism. Infants with botulism may appear to be septic, but usually are afebrile and have stable vital signs. Botulism occurs after ingestion of airborne spores from soil or dust. The ingested spores produce toxin in the intestine of the infant. Peak incidence is infants 6 weeks to 6 months of age. Breast-feeding is a significant risk factor. The ingestion of honey or corn syrup is often implicated, but not proven to be a risk factor. A history of soil disruption, which occurs near construction sites, has been a common epidemiologic finding in reported cases. Infants should be hospitalized and observed for progressive weakness and respiratory failure. Botulism immune globulin intravenous is an antitoxin that, when given early, has been found to decrease duration of illness and hospital stay.

American Academy of Pediatrics: Clostridial infections. In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 257–260.

124 Why is the diagnosis of Clostridium difficile colitis difficult in infants?

Almost 50% of infants (< 2 years) can have asymptomatic colonization, so toxin production is present without symptoms. Immature enterocytes with decreased amount of toxin-binding capacity and maternal antibodies have been postulated as mechanisms for disease protection in infants. Disease is sometimes seen in infants younger than 3 months of age.

American Academy of Pediatrics: Clostridial infections. In Pickering LK (ed): Red Book: 2003 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 261–263.

125 A 5-year-old who resides in a group home is transported to the ED because he looks “yellow.” What are the diagnostic considerations?

Hepatitis A virus (HAV) is highly contagious and spreads among children with poor hygiene or those in close quarters. Outbreaks at child care facilities usually represent an extension of a community outbreak. HAV infection is abrupt in onset and self-limiting, consisting of fever, anorexia, nausea, and headache. Jaundice is uncommon in young children compared with older children and adults, in whom jaundice can occur in 70% of cases. Liver failure in HAV is not common. The differential diagnosis should include hepatitis B or C (obtain a good history for associated risk factors: maternal history, blood transfusions, sexual contact), Epstein-Barr virus, adenoviruses, enteroviruses, varicella zoster, and HIV.

126 Which animals should be considered at high risk for transmission of rabies? How is rabies managed?

Bats, foxes, and raccoons should be considered rabid. Between 1990 and 2001, 74% of human deaths from rabies have been associated with bats. Cats and dogs also carry rabies. Rabies in small rodents (squirrels, hamsters, rats, and mice) is uncommon. If bitten, patients should receive postexposure prophylaxis, including both passive and active therapy. Rabies immune globulin can be used for passive immunization. An exposed individual will need five total doses of active immunization with an approved rabies vaccine. Domestic animals, such as dogs, can be observed for 10 days after a bite for observation, since canine rabies in the United States is rare.

American Academy of Pediatrics: Rabies. In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 552–558.

127 Should a child who has been in proximity to bats (e.g., in the same room during sleep), but without known physical contact, receive prophylaxis?

Yes. Cases of rabies have been reported in the absence of known contact with a rabid animal. Insignificant physical contact or airborne transmission of the virus may be responsible.

American Academy of Pediatrics: Rabies. In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 552–558.

128 True or false: Cat bites have a greater chance of becoming infected than dog bites.

True. Wounds from cat bites are more than twice as likely to become infected, in part because of the deep puncture wound they cause. Rate of infection from cat bites can be more than 50% in some cases. Pasteurella multicoda is the most common organism seen in cat bite infections; it is seen in 25% of dog bites.

129 When should antibiotics be prescribed for animal bites?

Antibiotic use is recommended for all deep puncture wounds (e.g., cat bites), moderate and severe wounds (with edema or crush injury), bites involving certain areas of the body (face, hand/foot, genitals), and bites in the immunocompromised or asplenic patients. Recommended oral antibiotics include amoxicillin-clavulanate or amoxicillin. Intravenous antibiotics include ampicillin-sulbactam. Include coverage for Staphylococcus aureus and anaerobes as well as Pasteurella multocida.

130 An afebrile 2-month-old presents with tachypnea and cough. What are the causes of pneumonia in this age group?

Respiratory viruses account for up to 90% of pneumonias in the 1- to 3-month-old age group. Pneumonitis without fever in this age group may represent an infection with Chlamydia trachomatis or Bordetella pertussis. C. trachomatis is perinatally acquired and peaks at 4–11 weeks of age. Infants usually present with nasal discharge and a staccato cough, and have a history of conjunctivitis (50%). The chest radiograph reveals interstitial infiltrates and hyperinflation. B. pertussis in this age group presents with paroxysms of cough, often followed by vomiting, and a recent history of upper respiratory tract symptoms.

131 Describe the acute management of bronchiolitis due to respiratory syncytial virus.

132 What is the treatment of choice for presumed C. trachomatis infection (either conjunctivitis or pneumonia)?

Oral erythromycin, clarithromycin, or azithromycin. Treatment for chlamydial pneumonia or conjunctivitis should be systemic. Chlamydial conjunctivitis alone is treated systemically to prevent the pneumonitis. Caution should be exercised with use of macrolides in infants younger than 6 weeks of age since they have been associated with hypertrophic pyloric stenosis.

American Academy of Pediatrics: Chlamydial infections. In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 252–256.

133 Describe the characteristics of pertussis in infancy.

Most pertussis cases occur in infants younger than 6 months of age. This population does not often have the classic “whoops” with cough. Apnea can be a common presenting symptom. Fever is absent or low grade. Adolescents and adults in the household are a major reservoir for transmission of pertussis because of their waxing vaccine-induced immunity. Pertussis should be considered in any infant with cough longer than 10–14 days. Pertussis in infants has a high mortality and morbidity. Complications in infants with pertussis include pneumonia, seizures, encephalopathy, and death.

134 What is the drug of choice for the treatment of pertussis?

Oral erythromycin estolate for 14 days is preferred. After the cough is present, however, antibiotics have no effect on the illness and are used more for prevention of spread to others. Oral azithromycin for 5 days has also been shown to be effective and is associated with better adherence.

135 What are the most common types of pneumonia in a 2-year-old?

Respiratory viruses are the most common causes of pneumonia in toddlers. Causes include:

Viral pneumonia is usually gradual in onset and preceded by upper respiratory tract symptoms; examination reveals diffuse auscultatory findings. Most of these children appear ill but not toxic.

Hendricskon KJ: Viral pneumonia in children. Semin Pediatr Infect Dis 3:217–233, 1998.

136 When should you consider admitting an older child with pneumonia?

137 What clinical clues suggest typical bacterial pneumonia?

Bacterial pneumonia is usually characterized by abrupt onset of high fever, respiratory distress (tachypnea, shortness of breath, hypoxia), and sometimes vomiting. Physical examination may reveal rales or decreased breath sounds. Chest radiograph may show lobar or segmental dense infiltrates associated with pleural effusion. A WBC count > 15,000 cells/ mm³ or elevated CRP level may indicate a bacterial process.

Lichenstein R, Suggs A, Campbell J: Pediatric pneumonia. Emerg Med Clin North Am 21:437–451, 2003.

138 What are the typical bacterial causes of pneumonia in children outside the neonatal period?

Streptococcus pneumoniae accounts for most bacterial pneumonias in children. Other uncommon causes include group A streptococci and Staphylococcus aureus. All these pathogens may cause severe, life-threatening pneumonias often associated with pneumatoceles.

139 A 10-year-old presents with nonproductive cough, low-grade fever, and malaise. On physical examination, the patient appears well, has minimal respiratory distress, and has bilateral lower lung field crackles. What is the most frequent cause of pneumonia in this age group?

This is a classic presentation of a child with atypical pneumonia caused by Mycoplasma pneumoniae or C. pneumoniae. M. pneumoniae is a common cause of pneumonia in older children and young adults. It accounts for about 40% of community-acquired pneumonias in certain populations. Bilateral diffuse infiltrates are the most common radiographic findings, which are frequently out of proportion to clinical findings. Extrapulmonary manifestations, including a maculopapular rash (10%), CNS disease, hemolytic anemia, arthritis, and hepatitis, are occasionally seen in atypical pneumonia syndromes caused by M. pneumoniae.

Katz B, Waites K: Emerging intracellular bacterial infections. Clin Lab Med 24:627–649, 2004.

140 What test can be used to assist in the diagnosis of M. pneumoniae infection?

Cold agglutinins are IgM antibodies that agglutinate human red blood cells and are found in approximately 50% of patients with acute mycoplasma infection, and in some viral infections as well (adenovirus, Epstein-Barr virus, and measles virus). Although available, cold agglutinins have a poor specificity profile. Serology is not very useful in the ED management of these patients. If available, culture may be used for diagnosis as well.

141 Which antimicrobials can be used for outpatient treatment of community-acquired pneumonia?

The treatment of community-acquired pneumonia (CAP) is based on the most likely etiologic agents. When typical bacterial pneumonia is suspected, treatment should include adequate coverage against penicillin-resistant Streptococcus pneumoniae. Among available oral antibiotics, amoxicillin at high dose (80–100 mg/kg) provides the best coverage against resistant Streptococcus pneumoniae. Two recent studies comparing erythromycin, azithromycin, and amoxicillin-clavulanate showed comparable efficacy for the treatment of CAP. In the older child, treatment options should include coverage against atypical organisms such as M. pneumoniae and C. pneumoniae with erythromycin-azithromycin (< 8 years of age); tetracycline-doxycycline is an option in children > 8 years of age.

142 What are the most common sites for septic arthritis?

The lower-extremity joints, such as the hip, knee, and ankle (less common), are common sites for septic arthritis. Primary pyogenic arthritis is uncommon in the post–H. influenzae era. Always suspect associated osteomyelitis when the joint “looks septic.”

143 A 2-year-old presents with a limp. A radiograph of the suspected limb is negative. Does a negative radiograph eliminate the possibility of osteomyelitis?

No. In the first 2 weeks of osteomyelitis, plain radiographs are not sensitive for the detection of osteomyelitis (bony changes may not be evident yet). The gold standard for diagnosis is magnetic resonance imaging or radionuclide bone scanning.

Frank G, Mahoney HM, Eppes SC: Musculoskeletal infections in children. Pediatr Clin North Am 52:1083–1106, 2005.

144 What is the classically described position that the leg is held in by a child with septic arthritis of the hip?

The leg is externally rotated and abducted.

145 What are the most common bones affected in osteomyelitis?

The long bones of the leg—femur and tibia—are most affected. In neonates and infants, osteomyelitis may affect any bone, including the humerus, hips, mandible, or calcaneus.

146 Aspiration of the hip joint in a 2-year-old febrile child with a limp reveals a WBC count of 60,000 cells/mm³ with a neutrophil predominance. What diagnosis is likely?

Septic arthritis is most likely. However, Table 38-19 can aid in diagnosis based on the WBC count and differential but demonstrates considerable overlap. Epidemiology, presence of fever, and detailed history may help.

TABLE 38-19 DIFFERENTIAL DIAGNOSIS OF SEPTIC ARTHRITIS BASED ON WHITE BLOOD CELL COUNT AND NEUTROPHILS

Frank G, Mahoney HM, Eppes SC: Musculoskeletal infections in children. Pediatr Clin North Am 52:1083–1106, 2005.

147 Match the disease with the appropriate management plan.

Answers: 1 B 2 C; 3 A

148 What are the most common organisms found in bone and joint infections?

See Table 38-20.

TABLE 38-20 Organisms Most Commonly Found in Bone and Joint Infections*

* In sexually active adolescents, also consider Neisseria gonorrhoeae. Salmonella sp. is a common cause of osteomyelitis in children with sickle cell disease.

Adapted from Frank G, Mahoney HM, Eppes SC: Musculoskeletal infections in children. Pediatr Clin North Am 52:1083–1106, 2005; and Gutierrez K: Bone and joint infections in children. Pediatr Clin North Am 52:779–794, 2005.

149 What is pyomyositis?

Pyomyositis is an infection of skeletal muscle that may be associated with antecedent trauma. The etiology is often Staphylococcus aureus or GABHS in immunocompetent children, but gram-negative organisms may also be involved in infections seen in immunocompromised children. Fever, myalgias, muscle tenderness to palpation, or swelling of the involved muscle may be seen. Magnetic resonance imaging is extremely helpful in making the diagnosis. Treatment includes surgical drainage if abscesses are involved and IV antibiotics.

150 What is the classic description of roseola (primary human herpesvirus-6 infection)?

High fever (temperature > 39.5° C) for 3–7 days, nonspecific signs (e.g., irritability, decreased feeding, or toxic appearance), and a diffuse maculopapular rash soon after defervescence (about day 4–6 of illness) lasting hours to days. This classic presentation is seen in only 20% of patients. Human herpesvirus 6 infection accounts for approximately 20% of acute febrile illness visits for children 6–8 months of age. Seizures may occur in about 10% patients during the febrile period. A bulging anterior fontanel occurs occasionally.

151 A medical student reports to you that a 3-year-old, febrile child appears to have been slapped on both cheeks by someone. What infectious disease are you considering?

Erythema infectiosum is the most common manifestation of parvovirus B19 infection. This infection is associated with a rash, characterized by intense erythema of the cheeks (slapped-cheek appearance) with circumoral pallor. On the trunk and extremities, the rash is maculopapular with a lacelike or reticular appearance.

152 A 15-year-old with fever, exudative pharyngitis, lymphadenopathy, and splenomegaly presents to the ED. You suspect infectious mononucleosis. What laboratory tests should be obtained to aid in diagnosis?

A CBC and heterophil antibody (IgM) test should be done. The WBC count can vary, but sometimes anemia, leukopenia, and thrombocytopenia can be seen. An increase in the number of atypical lymphocytes (10%) is a characteristic finding. The heterophil antibody test (Monospot) is specific for Epstein-Barr virus. In adolescents, the heterophil response occurs more reliably after the first week of illness. Its sensitivity is poor in young children (< 4 years of age). The younger child is more likely to be asymptomatic or have a nonspecific infection.

153 What should you recommend to a patient with infectious mononucleosis upon discharge from the ED?

The patient should avoid contact sports until examined by a physician and until the spleen is no longer palpable to avoid traumatic rupture of the spleen, which can be life-threatening.

154 Should patients with infectious mononucleosis be treated with corticosteroids?

Steroids are indicated for significant tonsillar inflammation with impending airway obstruction, hemophagocytic syndrome, massive splenomegaly, hemolytic anemia, and carditis.

American Academy of Pediatrics: Epstein Barr viral infections. In: Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, pp 286–290.

155 Match the disease with the clinical description.

Answers: 1 C; 2 A; 3 B.

156 How long is the child with chicken pox contagious?

The period of communicability begins 1–2 days prior to the outbreak of lesions and lasts until all lesions are crusted over.

157 A child with varicella presents with chicken pox, high fever, and toxic appearance. What should you suspect?

Examine the child closely for evidence of secondary bacterial infection with Staphylococcus aureus and Streptococcus pyogenes (group A). Secondary bacterial infection is the most common cause of morbidity in children with varicella infection. Clinical features include high fever, toxic appearance, and a varicella lesion that has become erythematous, warm, and painful. Superinfection with group A streptococci can progress to soft tissue necrosis, necrotizing fasciitis, and sepsis.

158 A 1-year-old infant has fever and rash 10 days after the annual visit to the pediatrician. What important history should be obtained regarding the recent visit to the pediatrician?

Immunization history. Determine if the measles, mumps, and rubella vaccine was administered. Fever with body temperature as high as 39 °C develops in 5–15% of children 7–12 days after vaccination. The fever typically lasts 1–2 days, and approximately 5% of patients develop a rash. Varicella vaccination may also be given at 1 year of age. Within 1 month of vaccination, 5–10% of children develop a mild maculopapular or varicelliform rash. The rash is limited to only a few lesions that can be at the injection site or elsewhere.

159 A 4-year-old boy presents with a chief complaint of body temperature of 40° C for 7 days. On physical examination, you notice bilateral conjunctivitis, a strawberry red tongue, anterior cervical lymphadenopathy, and diffuse erythema of the perineal area. What is your diagnosis?

Kawasaki disease. This is a multisystem vasculitis with a peak incidence in childhood; 80% of cases occur in children < 4 years old.

160 What are the diagnostic criteria for Kawasaki disease?

1 Fever for at least 5 days

2 Presence of four of the following:

Swelling and erythema of hands and feet

Cervical lymphadenopathy

Bilateral, nonpurulent conjunctival injection

Mucous membrane changes

Diffuse polymorphous rash

Newburger JW: Diagnosis, treatment and long-term management of Kawasaki disease: A statement for health professionals from the committee on rheumatic fever, endocarditis, and Kawasaki disease. Council on Cardiovascular Disease in the Young; American Heart Association. Pediatrics 114:1708–1733, 2004.

161 What is the differential diagnosis of Kawasaki disease?

Dedeoglu F, Sundei RP: Vasculitis in children. Pediatr Clin North Am 52:547–575, 2005.

162 What laboratory findings support the diagnosis of Kawasaki disease?

163 What is the management of a patient with suspected Kawasaki disease?

Management includes admission to the hospital for treatment with high-dose aspirin and IV immunoglobulin within 10 days of fever onset. All patients should have echocardiography performed as part of the initial hospital evaluation and then a repeat test 6–8 weeks after onset. Treatment within the first 10 days of the illness has been shown to substantially decrease the risk of coronary artery disease (a known complication of Kawasaki disease) from 20% to < 5%.

Newburger JW: Diagnosis, treatment and long-term management of Kawasaki disease: A statement for health professionals from the committee on rheumatic fever, endocarditis, and Kawasaki disease. Council on Cardiovascular Disease in the Young; American Heart Association. Pediatrics 114:1708–1733, 2004.

164 What are some agents of bioterrorism?

Agents are broken down into categories A, B, and C. Category A agents provide the greatest risk. They can be easily transmitted from person to person and tend to have the highest mortality rates. Category B agents have lower mortality rates and are not as easily spread as category A agents. Category C agents can be engineered to be biological weapons of mass destruction with the potential for high morbidity and high mortality rates.

Shannon M: Management of infectious agents of bioterrorism. Clin Pediatr Emerg Med 5:63–71, 2004.

165 Match the bioterrorist disease with the organism and symptoms.

Answers: A, 2; B, 3; C,1; D, 4.

Shannon M: Management of infectious agents of bioterrorism. Clin Pediatr Emerg Med 5:63–71, 2004.

166 What are some epidemiologic concerns regarding community-acquired MRSA?

Community-acquired MRSA infections have increased dramatically in the last 3–4 years. They may include furunculoses, carbuncles, and invasive staphylococcal infections. There are apparent differences between racial groups, with African-American children having two to four times the frequency of these types of infections. Community-acquired MRSA infection may be seen in multiple family members, day care attendees, and athletes.

Kaplan SL: Implications of methicillin-resistant Staphylococcus aureus as a community-acquired pathogen in pediatric patients. Infect Dis Clin North Am 19:747–757, 2005.

167 What antimicrobials would you use to treat community-acquired MRSA?

When considering community-acquired MRSA as a source of infection, antibiotics such as β-lactams, oxacillin, or cefazolin should not be used. Clindamycin and trimethoprim-sulfamethoxazole can be considered. However, in parts of the United States where community-acquired MRSA with resistance to clindamycin is greater than 10%, alternative therapies such as vancomycin and linezolid should be used.

Lowy FD, Kaplan SL: Treatment of methicillin-resistant Staphylococcus aureus in children, 2006: www.uptodate.com

168 What is the relevance of the D-test?

The D-test is a disk diffusion test to evaluate isolates of community-acquired MRSA, which may have macrolide inducible resistance to clindamycin. It looks for the presence of macrolide lincosamide streptogramin B (MLS_B) resistance coded for by ermA and ermC. In the laboratory, an erythromycin disk is placed 15–26 mm away from the clindamycin disk. An observed “D” shape indicates an induced resistance to clindamycin.

169 What is SARS and how can it be diagnosed?

SARS stands for “severe acute respiratory syndrome.” It is a severe lower respiratory tract infection caused by a coronavirus also called SARS-associated coronavirus (SARS-CoV). Symptoms are often nonspecific, including fever, dyspnea, and extreme hypoxia in adults. Children appear to have a less severe course and outcome. Children younger than age 12 years present with fever, rhinorrhea, cough, and lymphopenia. Children older than 12 years of age present with malaise, chills, rigors, and higher fevers. A good history is crucial in the diagnosis of SARS, including a recent travel history to China, Hong Kong, or Taiwan, contact with someone from that region or recent travel to, or occupation in a high-risk environment (hospital, laboratory). Diagnosis can be made by culture of respiratory secretions or by using reverse-transcriptase polymerase chain reaction. Serum can be tested for coronavirus serologies.

Williams JV The clinical presentation and outcomes comes of children infected with newly identified respiratory tract viruses. Infect Dis Clin North Am 19:569–584, 2005.

Centers for Disease Control and Prevention: www.cdc.gov.

170 What do pigs and birds have in common with the flu?

The influenza A (H5N1) virus is a virus that occurs mainly in birds. During late 2003–2004, outbreaks occurred among poultry in Asia. In 1997, the first cause of spread from bird to human was seen in Hong Kong, with more cases seen with the outbreaks during 2003–2004. It is also possible for strains that have passed through an intermediate host, most often the pig, to infect a human. H5N1 virus spread from person to person is rare.

Williams JV: The clinical presentation and outcomes of children infected with newly identified respiratory tract viruses. Infect Dis Clin North Am 19:569–584, 2005.

Centers for Disease Control and Prevention: www.cdc.gov

171 What is the treatment for H5N1 virus? Is there a vaccine to protect humans?

H5N1 has been shown to be resistant to amantadine and rimantadine, two antiviral medications we use now for influenza. Both oseltamavir and zanamavir may be active against H5N1, but more studies need to be done. To date, there is no human vaccine for the H5N1 virus.

Centers for Disease Control and Prevention: www.cdc.gov

172 What are the distinguishing features of malaria?

Malaria is characterized by paroxysms of fever, chills, and rigors occurring at certain time intervals depending on the species. Infection with Plasmodium falciparum carries a high morbidity and mortality (secondary to cerebral malaria in addition to renal and respiratory failure).