Enterobacteriaceae Opportunistic pathogens Escherichia coli Meningitis Opportunistic pathogens Escherichia coli Klebsiella pneumoniae Enterobacter aerogenes Serratia marcescens Proteus spp. Providencia spp. Citrobacter spp. Pneumonia Sepsis Diarrhea UTI Obligate pathogens Salmonella spp. Shigella spp. Yersinia spp. Some E. coli strains

Salmonella General characteristics Salmonella spp. do not ferment lactose. Most species of Salmonella are motile with peritrichous flagella. Some Salmonellae have capsular antigens; that of S. Typhi is ferred to as Vi antigen. Groups and species of Salmonella are identified by serologic analysis of O and H antigens (> 2,500 serotypes).

Salmonella important pathogenic members S.typhi-causes typhoid fever S. paratyphi A, B & C –cause paratyphoid fevers S.typhimurium, cause salmonellosis A complex system of classification of Salmonella based upon antigenic structure exists (Kaufmann-White scheme)

Salmonella Epidemiology S. Typhi and S. Paratyphi are primarily infective for humans. Other salmonellae are chiefly pathogenic in animals (poultry, pigs, rodents, cattle, pets etc.) that constitute the reservoir for human infection. Humans usually become infected by ingestion of contaminated food or drink (mean infective dose: 106-108, but that of S. typhi is lower). In children, infections can result from direct fecal-oral spread. The most common sources of human infections: poultry, eggs, dairy products, and foods prepared on contaminated work surfaces. However, the major source of infection for enteric fever is the carriers (convalescent or healthy permanent).

Pathogenesis and Immunity Virulence factors: Endotoxin. Type III secretion system. These are encoded by several Salmonella pathogenicity Islands such as SPI-I which mediate invasion of non phagocytic cell. SPI-2 facilitate survival and replication of Salmonella within the macrophages. Fimbriae: mediate binding of Salmonella to M cell present in peyer patches of the terminal part of intestine. Acid tolerance response gene (ATR) ,protect the salmonella from stomach acidity and acidity of phagosome. Enzymes such as catalase and superoxid dismutase wich protect bacteria from intercellular killing in macrophage.

Salmonella Pathogenesis and Immunity Invasion Survival in macrophages Acid tolerance response (ATR) gene protects the organism from gastric acid. The bacteria invade into (by inducing membrane ruffling) and multiply in the M cells and enterocytes of the small intestine. They can also be transported across the enterocytes and released into the blood and lymphatic circulation. Inflammatory response confines the infection to the GI tract in non-typhoid salmonellosis. Survival in macrophages Salmonellae are facultative intracellular pathogen.

Salmonella Clinical diseases 1. Enteritis Incubation period: 6-48 hours. Symptoms: nausea, headache, vomiting, nonbloody profuse diarrhea, with few leukocytes in the stools. Low-grade fever, abdominal cramp, myalgia, and headache are also common. Episode resolves in 2-7 days. Inflammatory lesions of the small and large intestine are present. Stool cultures remain positive for several weeks after clinical recovery.

The events of salmonellosis Figure 20.13

Salmonella Clinical diseases 2. Bacteremia Most common causal species: S. Choleraesuis, S Typhi and S. Paratyphi. Symptoms: like sepsis caused by other gram-negative bacteria. 10% of patients may have localized suppurative infections, e.g., osteomyelitis, endocarditis, arthritis, etc. High risk population: pediatric and geriatric patients; AIDS patients.

Salmonella Clinical diseases 3. Enteric fever (typhoid fever) Causal species: S. Typhi, S. Paratyphi A, Mouth small intestine lymphatics and bloodstream infect liver, spleen and bone marrow multiply and pass into the blood second and heavier bacteremia onset of clinical illness colonization of gallbladder invasion of the intestine typhoid ulcers and severe illness. Chronic carriers (1%-5% of patients): bacteria persist in the gallbladder and the biliary tract for more than one year.

Symptoms: incubation time: 10-14 days Symptoms: incubation time: 10-14 days. Gradually increasing fever, malaise, headache, myalgias, and anorexia, which persist for a week or longer. In severe cases: intestinal hemorrhage and perforation. Principal lesions: hyperplasia and necrosis of lymphoid tissue, hepatitis, focal necrosis of the liver, and inflammation of the gallbladder, periosteum, lungs and other organs.

Diagnosis of enteric fever The definitive diagnosis of typhoid fever depends on the isolation of S. typhi from blood, bone marrow or a specific anatomical lesion. The presence of clinical symptoms characteristic of typhoid fever or the detection of a specific antibody response is suggestive of typhoid fever but not definitive. Blood culture is the mainstay of the diagnosis of this disease. Diagnosis is made by any blood, bone marrow or stool cultures and with the Widal test (demonstration of antibodies  against salmonella  antigens O-somatic and H-flagellar). Determination of the O antigen and the phase 1 H antigen only is usually sufficient for the identification of typhoid fever organisms and paratyphoid fever organisms. During the first week of illness: blood culture. During the second week: blood culture, urine culture. Serology: Widal test, tube agglutination test use antigen of S.typhi and S.paratyphi A&B to be agglutinated by the patient serum. The stool culture also positive in the second and third weeks of illness. They are Indole negative ,urease negative and produce H2S in the culture.

Salmonella Treatment Enteric fever and bacteremia require antibiotic treatment: chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole. Surgical drainage of metastatic abscesses may be required. Salmonella enterocolitis needs only supportive therapy (antibiotic treatment may prolong the symptoms and excretion of the salmonellae). Drugs to control hypermotility of the gut should be avoided because it is easy to transform a trivial gastroenteritis into a life-threatening bacteremia by paralyzing the bowel. Chronic carriers of S. Typhi may be cured by antibiotics alone or combined with cholecystectomy.

Salmonella Prevention and control Sanitary measures. Carriers must not be allowed to work as food handlers. Strict hygienic precautions for food handling. Vaccines against S. Typhi: Purified Vi antigen Oral, live attenuated vaccine.

Shigella Pathogenesis and Immunity S. dysenteriae, S. flexneri , S. sonnei , & S. boydii: bacillary dysentery > 45 O serotypes; have no H antigen; do not ferment lactose. Pathogenesis and Immunity Shigellosis is primarily a pediatric disease, and is restricted to the GI tract. Mean infective dose: 103. Mouth colon invade M cells and subsequently spread to mucosal epithelial cells cause microabscess in the wall of colon and terminal ileum necrosis of the mucous membrane, superficial ulceration, bleeding, and formation of pseudomembrane. Shiga toxin An A-B toxin inhibiting protein synthesis. Damages intestinal epithelium and glomerular endothelial cells (associated with HUS) .

The events of shigellosis Figure 20.15

M cell Destablize the intestinal wall Activates the invasion genes on the virulence plasmid M cell Internalized shigellae induce apoptosis of macrophage and release of the bacteria Attracted by the cytokines released by macrophage

Shigella Clinical diseases Incubation period: 1-3 days Sudden onset of abdominal pain, fever and watery diarrhea number of stools increase, less liquid, often contain mucus and blood, rectal spasms with resulting lower abdominal pain (tenesmus) symptoms subside spontaneously in 2-5 days in adult cases, but loss of water and electrolytes frequently occur in children and the elderly a small number of patients remain chronic carriers. Some cases were accompanied by hemolytic uremic syndrome (HUS).

Shigella Laboratory diagnosis Treatment Specimens: fresh stool, mucus flecks, and rectal swabs. Large numbers of fecal leukocytes and some RBC may often be seen microscopically. Culture: differential and selective media as used for salmonellae. Treatment Antibiotic treatment: chloramphenicol, ampicillin, tetracycline, and trimethoprim-sulfamethoxazole. Drug resistance is common. Opiates should be avoided.

Shigella Prevention and control Humans are the only reservoir for shigellae. Transmission of shigellae: water, food, fingers, feces, and flies. Most cases occur in children under 10 years of age. Prevention and control of dysentery: 1. Sanitary control of water, food and milk; sewage disposal; and fly control. 2. Isolation of patients and disinfection of excreta. 3. Detection of subclinical cases and carriers.

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