Infectious Diseases, Part I
Camille Sabella
Johanna Goldfarb
This chapter addresses the following pediatric infections:
Gastrointestinal infections
Skin, soft-tissue, bone, and joint infections
Central nervous system (CNS) infections
Pneumonia
GASTROINTESTINAL INFECTIONS
Bacterial, viral, and parasitic agents cause gastrointestinal infections in infants and children that range from mild and self-limited conditions to severe and life-threatening. Differentiating among the many pathogens that cause infectious gastroenteritis relies on an understanding of the epidemiology and clinical manifestations of the disease caused by each of them. This chapter focuses on the epidemiologic and clinical features of the most common infections, in addition to therapeutic considerations.
Bacterial Infections
Salmonella Infection
Nontyphoidal Salmonella infections are most commonly acquired by ingesting contaminated foods, milk, or water (Table 48.1). Poultry, pork products, eggs, and dairy products are the foods most likely to be contaminated. Infected reptiles, including pet turtles and iguanas, are increasingly being recognized as important sources of infection for infants and children. Although person-to-person transmission occurs with household exposure, transmission and outbreaks in child care centers are uncommon. The incubation period for nontyphoidal Salmonella infection is 6 hours to 4 days, and the incidence of infection is the highest among children <5 years.
Humans are the only known reservoir of Salmonella typhi, which is the cause of enteric or typhoid fever. Infection is acquired by ingesting foods or water contaminated by human feces. Most cases of enteric fever in the United States are related to travel to foreign areas in which S. typhi infection is endemic. Clinical presentations of Salmonella infections include:
Acute asymptomatic infection
Acute gastroenteritis/enterocolitis
Bacteremia with or without focal infection
Enteric fever
Asymptomatic chronic carrier state
Because of the large number of organisms (105-106) required to cause symptomatic disease, asymptomatic infection is likely more common than symptomatic disease. Acute gastroenteritis usually manifests with nausea, vomiting, cramping abdominal pain, nonbloody diarrhea, and fever. Bloody diarrhea can occur if an invasive serotype is responsible for the infection. Symptoms resolve within 2 to 7 days in most cases. Bacteremia is most common in infants <1 month and may be present in a patient without gastrointestinal symptoms. Focal complications such as osteomyelitis and meningitis occur in approximately 10% of bacteremic children. Salmonella osteomyelitis is most common in children with hemoglobinopathies, whereas meningitis occurs almost exclusively in neonates.
Enteric fever is caused by S. typhi or S. paratyphi. Manifestations include nonspecific symptoms, high fever, abdominal pain, hepatosplenomegaly, altered mentation, lymphadenopathy, relative bradycardia, and erythematous rash on the anterior chest wall (rose spots). Laboratory features include anemia, leukopenia, and elevated transaminase levels.
Asymptomatic chronic carriage is not uncommon following Salmonella gastrointestinal infection, and antimicrobial therapy can prolong the time during which the organism is excreted.
TABLE 48.1 CHARACTERISTICS OF NONTYPHOIDAL SALMONELLA VERSUS SHIGELLA INFECTIONS | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Antimicrobial therapy is not recommended for otherwise healthy children with gastroenteritis (Table 48.2). Patients with gastroenteritis who are at high risk and should be treated with antimicrobial therapy include infants <3 months, immunocompromised patients, children with hemoglobinopathies, and those with gastrointestinal dysfunction. Patients with bacteremia, osteomyelitis, meningitis, or enteric fever should also be treated with antimicrobial agents. The choice of antimicrobial therapy should be based on the susceptibility patterns and severity of infection. Cefotaxime or ceftriaxone is appropriate initial therapy for invasive infections or severe gastroenteritis in a high-risk patient. Ampicillin or trimethoprim/sulfamethoxazole can be utilized for susceptible strains.
Prevention
Since nontyphoidal Salmonella infections are not commonly transmitted in childcare centers, children with Salmonella infection who attend such centers can be readmitted when they are asymptomatic. Stool cultures negative for Salmonella are not required for re-entry to a child care center, and contacts need not be tested unless they are symptomatic.
TABLE 48.2 SALMONELLA INFECTIONS THAT WARRANT ANTIMICROBIAL THERAPY | ||||||||||||||||||
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For child care attendees or staff who develop S typhi infections, contacts should be cultured and excluded if infected, until they have three negative stool samples (for children <5 years of age), or until they are asymptomatic (for those 5 years of age or older).
Shigella Infection
Because humans are the principal hosts, person-to-person transmission by fecal-oral spread accounts for most cases of shigellosis (Table 48.1). A small inoculum of organisms (102) can cause symptomatic disease and the incubation period is from 12 to 48 hours. Although Shigella infections are uncommon in the first year of life, they are important causes of outbreaks of infection in child care centers. Chronic carrier states are thought to be very rare among healthy children. Shigella sonnei is the most common serotype causing infection in the United States.
The clinical presentation of Shigella gastroenteritis varies from mild or no symptoms to severe symptoms. Infections with S. sonnei usually result in watery diarrhea. Infection with other species of Shigella may reflect the major virulent factor of these organisms, which is invasiveness. The classic picture of invasive Shigella gastroenteritis includes an abrupt onset of high fever, cramping abdominal pain, and early watery diarrhea that is followed by the development of mucous diarrhea with or without blood, associated with urgency and tenesmus. Approximately 50% of patients with invasive infection have bloody diarrhea, and symptoms may continue for a week or longer if specific antimicrobial therapy is not administered.
Extraintestinal manifestations of Shigella infections include:
Seizures
Hemolytic uremic syndrome
Septicemia
Reactive arthritis/Reiter syndrome
Toxic encephalopathy (ekiri syndrome)
Seizures are the most common extraintestinal manifestation, occurring in 10% to 45% of hospitalized children with shigellosis. They are generalized, brief, and benign, often appearing before the onset of diarrhea. Bacteremia and sepsis are rare complications of infection and usually occur in neonates and immunocompromised or malnourished patients.
Antimicrobial therapy for Shigella results in symptomatic improvement and prompt eradication of the organism from feces. Treatment is recommended for patients with severe symptoms, dysentery, and underlying conditions. Although most infections caused by S. sonnei are self-limited and may not require antimicrobial therapy, treatment is often given to prevent the spread of the organism. Since a significant percentage of Shigella strains in the United States are now resistant to ampicillin and trimethoprim/sulfamethoxazole, antimicrobial susceptibility testing of isolates is recommended. Third-generation cephalosporins, such as cefotaxime and ceftriaxone, and azithromycin, are effective alternatives.
Children who become infected with Shigella while attending child care centers should be treated with an appropriate antimicrobial agent and excluded from the center until they are asymptomatic and stool cultures test negative for Shigella. Stool specimens should be obtained from all symptomatic contacts and cultured; if the cultures are positive for Shigella, the children should be excluded from the center until they are asymptomatic and stool cultures are negative for the organisms.
Diarrheal Illness Caused by Escherichia coli
Several diarrhea-producing strains of E. coli have been identified. Three of the most important are described briefly.
Enterotoxigenic Escherichia coli
Transmission is most often from contaminated water and food, including dairy, meat, and seafood products. These organisms account for a significant percentage of cases of diarrhea in the developing world and are the most common cause of traveler’s diarrhea. Enterotoxin-mediated disease is manifested as watery diarrhea and abdominal cramps. Antimicrobial therapy is usually not indicated.
Shiga Toxin-Producing Escherichia coli (formerly known as enterohemorrhagic Escherichia coli)
Transmission is from contaminated foods and by personto-person contact. Undercooked and contaminated ground beef and unpasteurized milk have served as important transmission vehicles, although a wide variety of foods (salami, raw vegetables), water, petting zoos, and personto-person transmission have been implicated in outbreaks. A small inoculum of organisms can cause significant illness, which tends to occur during the summer and is most likely to affect children between the ages of 2 and 10 years. The prototype organism is E. coli O157:H7, which can be identified in the laboratory by its inability to ferment sorbitol. This organism elaborates a shiga-like toxin, which causes invasive gastroenteritis characterized by bloody diarrhea. The major complication of infection is hemolytic uremic syndrome, which occurs in 5% to 10% of individuals infected with E. coli O157:H7; most cases of hemolytic uremic syndrome in the United States are caused by this organism. Antimicrobial therapy for these infections is generally not indicated because they have not been shown to be effective and may increase the incidence of hemolytic uremic syndrome. Children infected with this organism should be excluded from child care centers until they are asymptomatic and two consecutive stool cultures are negative for the organisms.
Enteropathogenic Escherichia coli
These organisms have been associated with outbreaks of infection in nurseries for newborns and child care centers. They cause either epidemic or sporadic disease, mainly in neonates and children <2 years of age, which is characterized by severe, dehydrating watery diarrhea.
Campylobacter Infection
Campylobacter jejuni organisms account for most cases of Campylobacter infection. Along with Salmonella species, they are the major cause of food-borne illness in the United States. Transmission is mainly from ingested untreated water and contaminated foods, including poultry, meats, and unpasteurized milk. Domestic and wild young animals, including chicken, turkeys, and many farm animals, serve as reservoirs of infection. Person-to-person spread is a much less frequent mode of transmission, and transmission in child care settings is uncommon. The incidence of infection is the highest in children <5 years, and the incubation period usually is from 1 to 7 days.
C. jejuni causes enteritis that mainly involves the terminal ileum and colon. Symptoms range widely, from mild diarrhea to severe inflammatory diarrhea. Fever, abdominal pain, vomiting, generalized malaise, headache, and dehydration are not uncommon. In most cases, the course is self-limited, but the illness can be protracted and severe. Without treatment, fecal shedding occurs for 2 to 3 weeks in most cases. Asymptomatic chronic carriage of the organism is uncommon. Bacteremia and sepsis are very rare complications of C. jejuni infection. Campylobacter fetus has been associated with neonatal bacteremia and meningitis.
Immunoreactive complications can occur following C. jejuni infection; these include Guillain-Barré syndrome, reactive arthritis, and Reiter syndrome.
When given early during an infection, appropriate antimicrobial therapy shortens the duration of illness and eradicates the organism within 2 to 3 days. The need for antimicrobial therapy in most cases of gastroenteritis is controversial. Treatment should be considered for patients with severe gastrointestinal or systemic symptoms and for those who are immunocompromised. Erythromycin or azithromycin can be used to treat Campylobacter infection.
Children with Campylobacter gastroenteritis should be excluded from child care settings until they are asymptomatic. It is not necessary to culture stool specimens from asymptomatic contacts.
Yersinia Infection
Yersinia enterocolitica and Yersinia pseudotuberculosis can cause food-borne illness in children and adolescents. Domestic and wild animals serve as major reservoirs, and transmission occurs most commonly when uncooked pork products, unpasteurized milk, and untreated water are ingested; raw pork intestines (chitterlings) are implicated occasionally. Children aged 5 to 15 years are at the highest risk for infection, which tends to occur in cooler climates and during the winter months.
Yersinia organisms can cause acute diarrheal illness in children and adolescents, manifested with fever, diarrhea (which may be bloody), colicky abdominal pain, and vomiting. Occasionally, an intense suppurative mesenteric adenitis develops that causes acute abdominal pain and tenderness in the right lower abdominal quadrant, mimicking acute appendicitis. This condition is most common in older children and adolescents. Individuals with iron overload states, including those being treated with deferoxamine, are more susceptible to severe infection and complications such as sepsis and cardiac involvement. Reactive arthritis, Reiter syndrome, and erythema nodosum have been described as complications of Yersinia infection.
Patients who are at risk for severe disease and those with severe infection should be treated with antibi-otics. Aminoglycosides, cefotaxime, and trimethoprim/ sulfamethoxazole are active against these organisms.
Clostridium difficile Infection
C. difficile, through the actions of its elaborated toxins A and B, can cause colitis in patients who are receiving or have recently received antimicrobial therapy for other infections. It is the most common organism that causes antibiotic-related diarrhea. Nosocomial transmission has been documented. Any antibiotic can be implicated, but cephalosporins and clindamycin are most often associated with antibiotic-related diarrhea.
Gastrointestinal symptoms may be mild or severe. Bloody or nonbloody diarrhea with fever, nausea, vomiting, abdominal pain, and leukocytosis are common manifestations.
The presence of pseudomembranes or plaques in the colon is diagnostic. The organism or its toxins can be demonstrated in the stool and are helpful in making the diagnosis. Many neonates, infants, and young children normally harbor the organism and its toxins in the gastrointestinal tract. Therefore, testing for these toxins in infants is not recommended, as a positive result may not explain the etiology of the symptoms.
The treatment of infection should include discontinuing antimicrobial agents when it is safe to do so and administering antimicrobial therapy with specific action against the organism. Metronidazole (given orally or intravenously) and vancomycin (only when administered orally) are equally effective in eradicating the infection. Vancomycin should not be given as the first-line agent because its use is associated with the development of resistant organisms in the gastrointestinal tract. Infection can recur in up to 40% of cases, but usually responds to a repeated course of the same treatment.
Washing with water and soap appears to be a more effective method of eliminating spores from contaminated hands than with alcohol-containing products, and is the recommended method of hand hygiene for this organism.
Viral Gastroenteritis
Viral agents are responsible for most cases of acute gastroenteritis in infants and children. When compared with bacterial causes of gastroenteritis, viral causes are more likely to be associated with vomiting, a shorter duration of illness, an absence of fecal blood and leukocytes, and seasonal epidemics. The most common viral agents, with an emphasis on epidemiology, are discussed briefly.
Rotavirus Infection
Rotavirus infections are the most common cause of acute gastroenteritis in infants and young children, accounting for 15% to 35% of cases. Rotaviruses show a striking tendency to cause illness during the winter in temperate climates. The highest incidence of infection is in infants aged 6 to 36 months. Almost all the children are infected by their third birthday. Asymptomatic infection, especially in older children and adults, is common. Person-to-person spread is the most frequent mode of transmission, and rotaviruses are an important cause of nosocomial gastroenteritis and gastroenteritis in children attending child care centers. Fomites may also serve as a mechanism of transmission.
The incubation period is 2 to 4 days, and the clinical features include vomiting, diarrhea, and fever. Dehydration and electrolyte imbalance may develop. Bloody stools or fecal leukocytes are noted in 10% to 15% of infants. Infection can be severe and life threatening in immunocompromised and malnourished patients.
Enzyme immunoassays and latex agglutination assays are utilized to detect rotavirus antigens in the stool.
Infection with Caliciviruses (including Noroviruses [formerly Norwalk-like viruses])
Caliciviruses are transmitted by person-to-person spread and the ingestion of contaminated food and water. Shellfish and water sources have been identified in outbreaks. Outbreaks in closed populations, such as child care centers and cruise ships, have recently been documented. Sporadic and epidemic infection with these agents has been documented in all age groups.
The incubation period is 12 to 72 hours, and a brief illness manifested by vomiting, diarrhea, fever, headache, and abdominal cramps is usual.
Astrovirus Infection
Astroviruses are transmitted from person to person. The incidence of infection appears to be the highest in children <4 years, and infection tends to occur during the winter. Self-limited acute gastrointestinal symptoms are common.
Enteric Adenovirus Infection
Adenovirus serotypes 40 and 41 are associated with acute gastroenteritis in infants and children and are spread by the fecal-oral route. The median age of affected children is 12 to 24 months; no seasonal predilection has been noted. Although self-limited vomiting and diarrhea are the most common manifestations, dehydration requiring hospitalization is not infrequent; these agents are probably second only to rotaviruses in causing diarrheal illness requiring hospitalization.
Gastroenteritis Caused by Parasites
Giardia lamblia Infection
G. lamblia infection is the most common protozoal illness in the United States. The organisms infect the proximal small intestine and biliary tract and exist in trophozoite and cyst forms. The cyst form is most commonly isolated from stools and is the infective form.
The organism is acquired through the fecal-oral route, either by person-to-person transmission or by the ingestion of contaminated water or food. Outbreaks caused by contaminated water supplies and outbreaks in child care centers have been documented. Asymptomatic infection is common, and as many as 20% of children attending day care centers may harbor the organism without signs of infection.
The clinical spectrum of symptomatic giardiasis is broad; acute gastrointestinal symptoms with diarrhea and abdominal pain may occur, and a subacute or chronic illness manifested with chronic abdominal pain, weight loss or failure to thrive, malabsorption, and abdominal distension has also been well described. Peripheral eosinophilia is rare. Children with immunodeficiencies are more susceptible to infection and have a higher rate of chronic diarrhea and recurrent infection. Children with hypogammaglobulinemia and those infected with human immunodeficiency virus (HIV) are most susceptible, although children with immunoglobulin A- or T-cell deficiency and cystic fibrosis may also be at increased risk for chronic and recurrent infection.
The diagnosis can be made by demonstrating the presence of trophozoites or cysts in the stool with direct microscopic examination or by a commercially available immunofluorescent assay or enzyme immunoassay. The sensitivity of direct smear examination of three stool specimens is approximately 95%, whereas the sensitivity of immunofluorescent assay or enzyme immunoassay of one stool specimen is 70% to 80%. A commercially available string test of duodenal aspirates is more sensitive than tests of stool specimens, and a duodenal biopsy is occasionally required to make the diagnosis.
Metronidazole is the drug of choice for the treatment of giardiasis. Nitazoxanide, tinidazole, furazolidone, and albendazole are also effective therapies for giardiasis. Infection recurs in 10% to 20% of patients; most respond to a second course. Immunocompromised patients may require repeated or prolonged courses of treatment. Treatment of asymptomatic individuals is not recommended.
Children attending day care centers in whom G. lamblia infection is diagnosed must be excluded until they are asymptomatic. Excluding carriers and culturing specimens from asymptomatic individuals are not recommended.
Cryptosporidium Infection
Cryptosporidium species are protozoa that cause diarrheal illness in normal and immunocompromised hosts. The proximal small intestine is most commonly affected, but the entire bowel may be involved in patients infected with HIV. Transmission of the organism is by person-toperson spread, ingestion of contaminated water, or close contact with farm livestock. Large-scale community outbreaks have been caused by contaminated water supplies and swimming pools, as have smaller outbreaks in child care centers. Groups at high risk include children attending day care centers, farmers and animal handlers, travelers to foreign countries, and individuals with T-cell immunodeficiencies. Children aged 6 to 24 months appear to be at highest risk for infection.
Cryptosporidiosis in healthy children can result in asymptomatic infection or a self-limited, nonbloody, watery diarrhea associated with vomiting, abdominal pain, and fever. In immunodeficient individuals, including those infected with HIV, unremitting and profuse diarrhea may develop and cause malabsorption, weight loss, and malnutrition, in addition to disseminated infection and cholangitis.
Oocytes can be visualized in stool by means of a modified acid-fast stain after obtaining appropriate concentration of the stool sample. Commercially available antigen detection assays can also be used to identify oocytes.
Nitazoxanide oral suspension has been licensed for the treatment of diarrhea caused by cryptosporidiosis in children 12 months of age and older.
Amebiasis
Entamoeba histolytica frequently causes intestinal infection in the developing world. Amebiasis is the third most common parasitic infection causing death, after malaria and schistosomiasis. The organism is ingested during its cystic stage, and the trophozoite causes invasive disease in the colon.
The cysts are most frequently transmitted through the fecal-oral route. The organism is more frequently found in developing countries and areas with poor sanitation, where as many as 50% of the population may be infected. Asymptomatic carriers of cysts are common.
Asymptomatic infection is most common; approximately 10% of the world’s population is infected. Invasive infection can result in amebic dysentery or extraintestinal amebiasis.
Amebic dysentery presents as severe, bloody, inflammatory diarrhea that is associated with severe abdominal pain and fever and less frequently with abdominal distension and dehydration. Intussusception, perforation, and strictures are known complications. Liver abscess is the most common extraintestinal manifestation of amebiasis, occurring in 1% to 7% of children with invasive disease, in whom it causes high fever, abdominal distension, irritability, tachypnea, and hepatomegaly. Right upper quadrant pain is less common in children than in adults. Rupture of an abscess into the abdomen or chest is associated with a high mortality rate.
The identification of amebic cysts or trophozoites in stool samples is diagnostic, but it may be necessary to obtain several stool samples. Serologic assays may be useful in patients with liver involvement. Radiographic studies such as ultrasonography or computed tomography scan may be helpful in identifying liver abscess.
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