NELSON TEXTBOOK OF PEDIATRICS, 17TH EDITION

Chapter 181 - Salmonella

Thomas G. Cleary

Salmonella infections occur worldwide. Acute enteritis, the most frequent presentation, is usually self-limited, although bacteremia and focal extraintestinal infections may develop, especially in immunocompromised patients. The latter group has become more important and complex because of the increasing number of children who are compromised by AIDS, organ transplantation, or chemotherapy. Enteric fever, or typhoid fever, is a severe systemic disease that is classically caused by Salmonella ser. Typhi (Salmonella typhi) and is found mainly in developing countries, but it is encountered worldwide because of international travel.Molecular technology has enabled classification at the gene level. DNA analysis has proved that all Salmonella organisms are closely related genetically as a single species with six subgroups; most isolates causing human or animal disease belong to subgroup 1. The medical slang usage that treated each of the nearly 2,500 serotypes as though it were a separate species has fallen out of favor. The preferred designation currently is the abbreviated version of the formal name by the Centers for Disease Control and Prevention (CDC) ( Table 1811 ).181.1 Nontyphoidal SalmonellosisEtiology.Salmonellae are motile, nonsporulating, nonencapsulated, gram-negative rods. Most strains ferment glucose, mannose, and mannitol to produce acid and gas, but they do not ferment lactose or sucrose. S. ser. Typhi does not produce gas. Salmonella organisms grow aerobically and are capable of facultative anaerobic growth. They are resistant to many physical agents but can be killed by heating to 130F (54.4C) for 1hr or 140F (60C) for 15min. They remain viable at ambient or reduced temperatures for days and may survive for weeks in sewage, dried foodstuffs, pharmaceutical agents, and fecal material. Like other members of the Enterobacteriaceae, Salmonella possesses somatic O antigens and flagellar H antigens. The O antigens are the heat-stable lipopolysaccharide components of the outer membrane; the H antigens are heat-labile proteins that can be present in phase 1 or 2. The Kauffmann-White scheme commonly used to classify salmonellae serotypes is based on O and H antigens. Serotyping is important clinically because certain serotypes tend to be associated with specific clinical syndromes and because detection of an unusual serotype is sometimes useful in recognizing a common-source outbreak. A virulence capsular polysaccharide (Vi), present on S. ser. Typhi, is also found on strains of S. ser. Dublin and S. ser. Paratyphi C (S. ser. Hirschfeldii).Epidemiology.About 35,00045,000 cases of culture-proven salmonellosis, approximately 98% of which are caused by nontyphoidal salmonellae, are reported annually in the United States. Because culturing and reporting are incomplete, the actual number of cases has been estimated as 15 million/yr. These figures are higher than those of the 1970s and may be related to modern practices of mass food production, which increase the potential for epidemic salmonellosis. About half of reported cases occur in persons 1 yr. A prolonged carrier state after nontyphoidal salmonellosis is rare (12min, Salmonella may remain viable. Because large outbreaks are often related to mass food production, it should be recognized that contamination of just one piece of machinery used in food processing may cause an outbreak; meticulous cleaning of equipment is essential. No vaccine against nontyphoidal Salmonella infections is available. Infections should be reported to public health authorities so that outbreaks can be recognized and investigated.181.2 Enteric FeverEtiology.Enteric fever, or typhoid fever, is caused by S. ser Typhi, S. ser. Paratyphi A, S. ser. Paratyphi B (Schottmuelleri), and S. ser. Paratyphi C (Hirschfeldii). Rarely, other Salmonella serotypes can cause a similar prolonged febrile illness.Epidemiology.The incidence, mode of transmission, and consequences of enteric fever differ significantly in developed and developing countries. The incidence has decreased markedly in developed countries. In the United States, about 400 cases of typhoid fever are reported each year, giving an annual incidence of less than 0.2 cases/100,000 population, which is similar to that in Western Europe and Japan. In Southern Europe, the annual incidence is 4.314.5 cases/100,000 population. In developing countries, S. ser. Typhi is often the most common Salmonella isolate, with an incidence that can reach 500 cases/ 100,000 population (0.5%) and a high mortality rate. The World Health Organization has estimated that at least 12.5 million cases occur annually worldwide.Because humans are the only natural reservoir of S. ser. Typhi, direct or indirect contact with an infected person (sick or chronic carrier) is necessary for infection. Ingestion of foods or water contaminated with human feces is the most common mode of transmission. Water-borne outbreaks due to poor sanitation and direct fecal-oral spread due to poor personal hygiene are encountered, mainly in developing countries. Oysters and other shellfish cultivated in water contaminated by sewage are also a source of widespread infection. In the United States about 65% of the cases result from international travel. Travel to Asia (especially to India) and Central or South America (especially Mexico) is usually implicated. Domestically acquired enteric fever is most frequent in the southern and western United States and is usually caused by consumption of foods contaminated by individuals who are chronic carriers. Congenital transmission of enteric fever can occur by transplacental infection from a bacteremic mother to her fetus. Intrapartum transmission is also possible, occurring by a fecal-oral route from a carrier mother.Pathogenesis.In younger children, the morphologic changes of S. ser. Typhi infection are less prominent than in older children and adults. Hyperplasia of Peyer patches with necrosis and sloughing of overlying epithelium produces ulcers that may bleed. The mucosa and lymphatic tissue of the intestinal tract are severely inflamed and necrotic. Ulcers heal without scarring. Strictures and intestinal obstruction virtually never occur after typhoid fever. The inflammatory lesion may occasionally penetrate the muscularis and serosa of the intestine and produce perforation. The mesenteric lymph nodes, liver, and spleen are hyperemic and generally reveal areas of focal necrosis. Hyperplasia of reticuloendothelial tissue with proliferation of mononuclear cells is the predominant finding. A mononuclear response may be seen in the bone marrow in association with areas of focal necrosis. Inflammation of the gallbladder is focal, inconstant, and modest in proportion to the extent of local bacterial multiplication. Bronchitis is common. Inflammation also may be observed in the form of localized abscesses, pneumonia, septic arthritis, osteomyelitis, pyelonephritis, endophthalmitis, and meningitis.The inoculum size required to cause enteric fever in volunteers is 105 109 S. ser. Typhi organisms. These estimates may be higher than in naturally acquired infection because the volunteers ingested the organisms in milk; stomach acidity is an important determinant of susceptibility to Salmonella. The bacteria invade through the Peyer patches. Organisms are transported to intestinal lymph nodes, where multiplication takes place within the mononuclear cells. Monocytes, unable to destroy the bacilli early in the disease process, carry these organisms into the mesenteric lymph nodes. Organisms then reach the bloodstream through the thoracic duct, causing a transient bacteremia. Circulating organisms reach the reticuloendothelial cells in the liver, spleen, and bone marrow and may seed other organs. After proliferation in the reticuloendothelial system, bacteremia recurs. The gallbladder is particularly susceptible to being infected. Local multiplication in the walls of the gallbladder produces large numbers of salmonellae, which reach the intestine through the bile.Several virulence factors seem to be important. Invasion of Peyer patches is encoded by genes closely related to the invasion genes of Shigella and enteroinvasive E. coli. However, S. ser. Typhi possesses a number of additional genes not found in Shigella that are responsible for the features of typhoid fever. The surface Vi capsular antigen found in S. ser. Typhi interferes with phagocytosis by preventing the binding of C3 to the surface of the bacterium. The ability of organisms to survive within macrophages after phagocytosis is an important virulence trait encoded by the phoP regulon; it may be related to metabolic effects on host cells. Circulating endotoxin, a lipopolysaccharide component of the bacterial cell wall, is thought to cause the prolonged fever and toxic symptoms of enteric fever, although its levels in symptomatic patients are low. Alternatively, endotoxin-induced cytokine production by human macrophages may cause the systemic symptoms. The occasional occurrence of diarrhea may be explained by presence of a toxin related to cholera toxin and E. coli heat-labile enterotoxin.Cell-mediated immunity is important in protecting the human host against typhoid fever. Decreased numbers of T lymphocytes are found in patients who are critically ill with typhoid fever. Carriers show impaired cellular reactivity to S. ser. Typhi antigens in the leukocyte migration inhibition test. In carriers, a large number of virulent bacilli pass into the intestine daily and are excreted in the stool, without entering the epithelium of the host.Clinical Manifestations.The incubation period is usually 714 days, but it may range from 330 days, depending mainly on the size of the ingested inoculum. The clinical manifestations of enteric fever depend on age.SCHOOL-AGED CHILDREN AND ADOLESCENTS.The onset of symptoms is insidious. Initial symptoms of fever, malaise, anorexia, myalgia, headache, and abdominal pain develop over 23 days. Although diarrhea having a pea soup consistency may be present during the early course of the disease, constipation later becomes a more prominent symptom. Cough and epistaxis may ensue. Severe lethargy may develop in some children. Temperature, which increases in a stepwise fashion, becomes an unremitting and high fever within 1 wk, often reaching 40C.During the 2nd week of illness, high fever is sustained, and fatigue, anorexia, cough, and abdominal symptoms increase in severity. Patients appear acutely ill, disoriented, and lethargic. Delirium and stupor may be observed. Physical findings include a relative bradycardia, which is disproportionate to the high fever. Hepatomegaly, splenomegaly, and distended abdomen with diffuse tenderness are very common. In about 50% of patients with enteric fever, a macular or maculopapular rash (rose spots) appears on about the 7th10th day. Lesions are usually discrete, erythematous, and 15mm in diameter; the lesions are slightly raised and blanch on pressure. They appear in crops of 1015 lesions on the lower chest and abdomen and last 23 days. They leave a slight brownish discoloration of the skin on healing. Cultures of the lesions have a 60% yield for Salmonella organisms. Rhonchi and scattered rales may be heard on auscultation of the chest. Nausea and vomiting if occurring in the 2nd or 3rd week suggest a complication. If no complications occur, the symptoms and physical findings gradually resolve within 24 wk, but malaise and lethargy may persist for an additional 12 mo. Patients may be emaciated by the end of the illness. Enteric fever caused by nontyphoidal Salmonella is usually milder, with a shorter duration of fever and a lower rate of complications.INFANTS AND YOUNG CHILDREN (