Salmonella Infections

Salmonella Infections • • • • •

200/2300 serotypes are pathogenic to humans Almost all pathogens are from Subgrp1 (enterica / choleraesuis) Only S.gallinarum-pullorum doesn’t have peritrichous flagella Only S. typhi doesn’t produce gas on fermentation 3 major antigenic determinants: o Somatic O Ag (LPS cell wall component) o Surface V Ag (S. typhi & S. paratyphi) o Falgellar H Ag

Pathogenesis • All Salmonella infections begin through oral ingestion • 103-106 CFU- infectious dose • Can resist low pH of the stomach, so conditions that ↓ stomach acidity or intestinal integrity, ↑ susceptibility to infections (pg 897) • Penetrate mucus layer and traverse phagocytic M (microfold) cells found in Peyer’s patches • Salmonella proteins are delivered in non-phagocytic cells through Type III secretion triggering the formation of membrane ruffles (in non-phagocytic cells) capable of bacteria mediated endocytosis (BME) • These proteins mediate actin cytoskeleton alterations for Salmonella uptake • Internalization of bacteria by macrophages protects them from other immune responses (pg 898) • PhoP/PhoQ- regulatory sys in phagocytosed bacteria that senses changes in bacterial location and alters bacterial protein expression • Second Type III secretion- is responsible for the survival of bacteria inside macrophage • Invades lymphatics and RES • Asymptomatic initial incubation period • Fever and abdominal pain- secretion of cytokines when ↑ organisms have replicated

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Enlargement & necrosis of Peyer’s, Hepatosplenomegaly- ↑ mononuclear recruitment Non-typhoidal: PMN’s are the ones recruited by IL-8 (secreted by intestinal cells)→ inflammatory diarrhea, damage to mucosa, due to degranulation and release of toxic substance

Enteric Fever • Systemic disease char by fever(75%) and abdominal pain(20-40%) (dissemination of S typhi & paratyphi) • History of travel: 10% Philippines • Incubation pd: 3-21d • Diarrhea- only common in < 1y/o and AIDS px • Prolonged fever (38.8 – 40.5 C)- most prominent symptom • Rose Spots- early finding, faint, blanching, salmon colored maculopapular rash (1st wk, 2-5 d duration) • Neuropsychiatric symptom (Typhoid Psychosis)- muttering delirium, coma vigil, with picking at bed clothes or imaginary objects • GI complications are late complications (perforation and bleeding, necrosis of Peyer’s ) • 1-5%- bec chronic carriers Diagnosis • Majority have normal WBC count • 1st 10 days & (+) complications, children- leukocytosis • 10-25%- leukopenia and neutropenia • Culture- diagnostic gold std • Blood- 90% yield 1st wk, 50% 3rd wk • Bone Marrow- ↑ sensitive despite antibiotic tx • Intestinal secretions (string test)- (+) despit (-) BM culture • Stool- (+) on 3rd wk in untreated cases, (+) for 1 yr for chronic carriers • Others: WIDAL test, PCR, DNA probe assay Treatment

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All strains should be tested for Nalidixic Acid resistance and Ciproflox (& other quinolones) sensitivity! Mainstays: o Quinolones (Ciprofloxacin)- for MDR S. typhi o Third gen cephalosporins (Ceftriaxone)- alt is Azithromycin • NARST strain infection- ↑dose ciprofloxacin / longer course ofloxacin • Severe infection (fever + alt mental status)- Dexamethasone • Chronic carriers- 6 wks amox, TMP-SMX, ciproflox, etc (pg 900) Vaccines: • Whole cell vaccine (2 doses)- heat-killed at least 6y/o • Ty21a (4 doses)- attenuated • ViCPS (1 dose)- purified polysaccharide at least 2y/o • Vi-rEPA (2 doses)- ViCPS bound to recombinant CHON at least 6m/o Non-typhoidal Salmonellosis • Majority are S. typhimurium & S. enteritidis • S. enteritidis associated with Chicken egg- major food borne infection • Less commonly- pet exposure esp.reptiles Gastroenteritis • Self-limited (3-7d) • Diarrhea (loose, nonbloody) & N/V 6 to 48 hr after ingestion • Stool culture may be (+) 4-5wks after infection and 1 yr for chronic carriers • No Antibiotic regimen except for= neonates, elderly & immunocompromised (+ hospitalization) Bacteremia and Endovascular infections • 5% - (+) Bld culture • 5-10%- localized infection • >50% of 3 or more BC are (+)→ suspect endovascular infections Endocarditis • ↑in px with valvular heart disease • Complications: cardiac valve perforation, septal abscess Arteritis

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↑ risk: atherosclerotic plaques, prosthetic graft, aortic aneurysm Suspect if prolonged fever (elderly), back, chest / abd pain preceding gastroenteritis Assoc with mycotic aneurysms, ruptured aneurysms / vertebral osteomyelitis • • •

6wks intravenous β-lactam Ab Surgical resection or lifelong suppressive Ab S. chloraesus & Dublin- invasive / metastatic, with absence of gastroenteritis, (+) sustained bacteremia and fever

Localized Infections Tx in gen: 2-4 wks Ab and/or surgical intervention Intraabdominal Abscess and cholecystitis • ↑risk in pips with anatomical abn in hepatobiliary system, malignancy & sickle cell disease • Tx: o Surgical resection o Drainage of abscess o CNS Meningitis (<4m/o) • Abscess Pulmonary • Lobar pneumonia • ↑ risk in pips with abn in lung/ pleura, malignancy & sickle cell disease GUT • Cystitis • pyelonephritis Bone, Jt & soft tissue • Osteomyelitis o ↑ risk in pips with bone disease • Septic arthritis • Reactive arthritis (Reiter’s syndrome)assoc with HLA-B27 histocompatibility Diagnosis: • Stool Culture • Blood Culture- for suspected bacteremia • Other body fluids- for suspected metastic / invasive disease Treatment:

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No Antibiotics – self-limited! Preemptive Ab tx Oral or IV 2-3 days until defervescence for immunocompetent px, 7-14 (?) for immunocompromised ↑ risk for metastatic infection : neonates <3mos, elderly>50y/o bec of possibility of atherosclerosis, transplant recipients, etc. (pg 902) Fluid and electrolyte replacement- for dehydration 2˚ diarrhea