salmanellosis

Salmonellae are gram-negative motile bacilli.

The genus Salmonella,which belongs to the family Enterobacteriaceae

was named after Daniel E. Salmon, an American veterinarian who first isolated Salmonella choleraesuis from pigs with hog cholera in 1884

consists of two species: S. choleraesius and S. bongori.

S. choleraesuis subspecies I contains almost all the serotypes pathogenic for humans

Term s.enterica is used instead of s.choleraesius

Members of the seven Salmonella subspecies are classified into >2400 serotypes (serovars)

somatic O antigen [lipopolysaccharide (LPS) cell-wall components]

the surface Vi antigen (restricted to S. Typhi and S. Paratyphi C) and the flagellar H antigen.

most Salmonella serotypes are named for the city where they were identified

Serotypes is often used as species identification

Salmonellae grow under both aerobic and anaerobic conditions.

oxidase negative

lactose negative (white on MacConkey agar plates)

produce hydrogen sulfide, which is easily detected on selective indicator plates such as Hektoen, or Salmonella-Shigella agar, which are used for plating stool specimens.

serotyping of all surface antigens can be used for formal identification

most laboratories perform a few simple agglutination reactions that define specific O-antigen serogroups, designated A, B, C1, C2, D, and E.

Strains in these six serogroups cause ~99% of Salmonella infections in humans and warm-blooded animals

enteric fever, also called typhoid fever or paratyphoid fever, is a systemic febrile illness that is most commonly caused by Salmonella typhi;

less frequent causes are S. paratyphi A, S. typhi B (also known as S. schottmuelleri), and S. paratyphi C (also known as Salmonella hirschfeldii). 

in the early 1800s, typhoid fever was clearly defined pathologically as a unique illness on the basis of its association with enlarged Peyer's patches and mesenteric lymph nodes.

In 1869, given the anatomic site of infection, the term enteric fever was proposed

food-borne or waterborne transmission results from fecal contamination by ill or asymptomatic chronic carriers.

Sexual transmission between male partners has been described.

Health care workers

Worldwide, however, there were an estimated 22 million cases of enteric fever, with 200,000 deaths, in 2002.

The incidence is highest (>100 cases per 100,000 population per year) in south-central and Southeast Asia; medium (10–100 cases per 100,000) in the rest of Asia, Africa, Latin America, and Oceania (excluding Australia and New Zealand); and low in other parts of the world.

A high incidence of enteric fever correlates with poor sanitation

Multidrug-resistant (MDR) strains of S. Typhi emerged in 1989 in China and Southeast Asia

These strains contain plasmids encoding resistance to chloramphenicol, ampicillin, and trimethoprim—antibiotics long used to treat enteric fever.

With the increased use of fluoroquinolones to treat MDR enteric fever, strains of S. Typhi and S. Paratyphi with reduced susceptibility to ciprofloxacin have emerged

All Salmonella infections begin with ingestion of organisms in contaminated food or water.

The infectious dose is 103–106 colony-forming units.

Conditions that decrease either stomach acidity

Loss of intestinal integrity increase susceptibility to Salmonella infection

traverse the intestinal layer through phagocytic microfold (M) cells that reside within Peyer's patches.

Salmonellae can trigger the formation of membrane ruffles in normally nonphagocytic epithelial cells.

These ruffles reach out and enclose adherent bacteria within large vesicles by a process referred to as bacteria-mediated endocytosis (BME).

salmonellae disseminate throughout the body in macrophages via the lymphatics and colonize reticuloendothelial tissues (liver, spleen, lymph nodes, and bone marrow).

relatively few or no signs and symptoms during this initial incubation stage.

Signs and symptoms, including fever and abdominal pain, probably result from secretion of cytokines by macrophages and epithelial cells

The Vi antigen of S typhi is important in preventing antibody-mediated opsonization and complement-mediated lysis.

Within 14 days, the bacteria appear in the bloodstream, facilitating secondary metastatic foci (eg, splenic abscess, endocarditis).

In some patients, gallbladder infection leads to long-term carriage of S typhi or S paratyphi in bile and secretion to the stool.

hepatosplenomegaly is likely to be related to the recruitment of mononuclear cells

and the development of a specific acquired cell-mediated immune response to S. typhi colonization.

marked enlargement and necrosis of the Peyer's patches

NTS gastroenteritis is characterized by massive polymorphonuclear leukocyte (PMN) infiltration into both the large- and small-bowel mucosa.

This response appears to depend on the induction of interleukin (IL) 8.

The degranulation and release of toxic substances by neutrophils may result in damage to the intestinal mucosa, causing the inflammatory diarrhea

Predisposing conditions

corticosteroid use, malignancy, diabetes, HIV infection,prior antimicrobial therapy, and immunosuppressive therapy.

 malaria, schistosomiasis, bartonellosis,  pernicious anemia,sickle cell desease

altered urinary or biliary tract, atherosclerotic aorta, or endovascular devices may facilitate persistent focal Salmonella infection.

Clinical features

First week

Fever

Headache

Myalgia

Constipation

Diarrhoea and vomiting in children

Relative bradycardia

End of first week

Rose spots on trunk

Hepatosplenomegaly

Cough

Abdominal distension

diarrhoea

End of second week

Delerium

Coma

Complications-perforation,haemarrhage

bone and joint infection

meningitis,cholecystitis

myocarditis,nephritis

Chronic carriage-persistent gall bladder carriage

Neurologic manifestations occur in 2–40% of patients

meningitis

Guillain-Barré syndrome,

neuritis, and neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects.

Rare complications include

disseminated intravascular coagulation, hematophagocytic syndrome

pancreatitis, hepatic and splenic abscesses and granulomas, endocarditis, pericarditis, myocarditis,

orchitis, hepatitis, glomerulonephritis, pyelonephritis and hemolytic uremic syndrome, severe pneumonia, arthritis, osteomyelitis, and parotitis.

Up to 10% of patients develop mild relapse, usually within 2–3 weeks of fever resolution

Up to 10% of untreated patients with typhoid fever excrete S. Typhi in the feces for up to 3 months,

1–4% develop chronic asymptomatic carriage, shedding S. Typhi in either urine or stool for >1 year.

Chronic carriage is more common among women, infants, and persons with biliary abnormalities

concurrent bladder infection with Schistosoma haematobium

Modern blood culture systems are 80%-100% accurate in detecting bacteremia.

As the disease duration increases, the sensitivity of blood cultures decreases, while the sensitivity of stool isolation increases.

Freshly passed stool is the preferred specimen for isolation of nontyphoidal Salmonella species.

Bone marrow aspirate and culture is superior to blood culture

S typhi or S paratyphi may also be isolated from urine, rose spot biopsy, or gastric or intestinal secretions.

Grouping of Salmonella isolates is usually performed with polyvalent antisera specific for O and Vi antigen.

S typhimurium belongs to group B; S enteritidis and S typhi belong to group D.

In 15–25% of cases, leukopenia and neutropenia are detectable.

Leukocytosis is more common among children, during the first 10 days of illness, and in cases complicated by intestinal perforation or secondary infection.

Other nonspecific laboratory findings include moderately elevated liver function tests and muscle enzyme levels

The Widal test is used to measure antibodies against O and H antigens of S typhi.

Newer diagnostic tests (Typhidot, Tubex) allow direct detection of immunoglobulin M (IgM) antibodies against specific S typhi antigens.

Nested polymerase chain reaction (PCR) using H1-d primers has been used to amplify specific genes of S typhi, with high sensitivity and specificity.

symmetrical and homogenous thickening of the wall of the terminal ileum

circumferential thickening of the cecum and descending colon.

specific findings in usg are

prominent haustration of cecum and right colon and symmetrical mural thickening of terminal ileum and cecum

Empirical Treatment    

Ceftriaxonea  1–2 g/d (IV) 7–14 days

  Azithromycin 1 g/d (PO) 5 days

Fully Susceptible 

  Ciprofloxacinb (first line)   500 mg bid (PO) or 400 mg q12h (IV) 5–7 days 

Amoxicillin (second line) 1 g tid (PO) or 2 g q6h (IV) -14  

Chloramphenicol 25 mg/kg tid (PO or IV) -14–21  

Trimethoprim-sulfamethoxazole 160/800 mg bid (PO) -14

Multidrug-Resistant   

Ciprofloxacin 500 mg bid (PO) or 400 mg q12h (IV) 5–7  days

Ceftriaxone 2–3 g/d (IV) 7–14 days

  Azithromycin 1 g/d (PO)- 5 day

Nalidixic Acid–Resistant

  Ceftriaxone 1–2 g/d (IV) 7–14 days

  Azithromycin 1 g/d (PO) 5 days  

High-dose ciprofloxacin 750 mg bid (PO) or 400 mg q8h (IV) 10–14 days

critically ill patients with enteric fever (i.e., those with shock and obtundation)

the administration of dexamethasone (3-mg initial dose followed by eight doses of 1 mg/kg every 6 h)

severe enteric fever remains one of the few indications for glucocorticoid treatment of an acute bacterial infection

The 1–5% of patients who develop chronic carriage of Salmonella can be treated for 4–6 weeks

oral amoxicillin, trimethoprim-sulfamethoxazole (TMP-SMX), ciprofloxacin, or norfloxacin is ~80% effective in eradicating chronic carrier

in cases of anatomic abnormality (e.g., biliary or kidney stones), eradication often requires both antibiotic therapy and surgical correction

Prevention and control

Two typhoid vaccines are commercially available

:(1) Ty21a, an oral live attenuated S. Typhi vaccine (given on days 1, 3, 5, and 7, with a booster every 5 years); and

(2) Vi CPS, a parenteral vaccine consisting of purified Vi polysaccharide from the bacterial capsule (given in 1 dose, with a booster every 2 years).

The old parenteral whole-cell typhoid/paratyphoid A and B vaccine is no longer licensed, largely because of significant side effects

The minimal age for vaccination is 6 years for Ty21a and 2 years for Vi CPS.

Currently, there is no licensed vaccine for paratyphoid fever.

CDC and the World Health Organization recommend typhoid vaccination for travelers to typhoid-endemic countries.

Recent analyses from the CDC found that 16% of travel-associated cases occurred among persons who stayed at their travel destination for 2 weeks.

vaccination should be strongly considered even for persons planning short-term travel to high-risk areas

gastroenteritis

Infection with NTS most often results in gastroenteritis indistinguishable from that caused by other enteric pathogens.

Nausea, vomiting, and diarrhea occur 6–48 h after the ingestion of contaminated food or water.

Patients often experience abdominal cramping and fever (38–39°C; 100.5–102.2°F)

Diarrheal stools are usually loose, nonbloody, and of moderate volume

large-volume watery stools, bloody stools, or symptoms of dysentery may occur.

Rarely, NTS causes pseudoappendicitis or an illness that mimics inflammatory bowel disease.

Gastroenteritis caused by NTS is usually self-limited. Diarrhea resolves within 3–7 days and fever within 72 h.

Stool cultures remain positive for 4–5 weeks after infection and—in rare cases of chronic carriage (<1%)—for >1 year

Fewer than 5 percent of individuals with documented Salmonella gastroenteritis develop bacteremia .

Bacteremia can lead to a variety of extraintestinal manifestations such as endocarditis, mycotic aneurysm, and osteomyelitis .

Two species, S. choleraesuis  and S. heidelberg appear to be more invasive.

antibiotic resistant strains of S. typhimurium, are associated with a two- to threefold increase in the risk of bacteremia

NTS endovascular infection should be suspected in high-grade bacteremia in those

preexisting valvular heart disease,

atherosclerotic vascular disease,

prosthetic vascular graft

aortic aneurysm.

Endocarditis and arteritis are rare (<1% of cases)

but are associated with potentially fatal complications

valve perforation,

endomyocardial abscess,

pericarditis, mycotic aneurysms,

aneurysm rupture, aortoenteric fistula, and vertebral osteomyelitis

Salmonella and Shigella are lactose-negative organisms that form translucent colonies on MacConkey agar

Most nontyphoidal Salmonellae produce hydrogen sulfide, which causes

colonies to appear light greenish with black centers on Hektoen enteric agar or

white with black centers on Salmonella-Shigella agar.

Enrichment broths (tetrathionate or selenite) are used to facilitate identification of Salmonella or Shigella when low numbers of organisms are present.

Overnight incubation in these broths inhibits the growth of E. coli but not Salmonella or Shigella.

Suspicious colonies from plates are further evaluated biochemically with commercial polyvalent antisera specific for Salmonella O and Vi antigens

Severe Gastroenteritis

    Ciprofloxacin 500 mg bid (PO) or 400 mg q12h (IV) 3–7 days

Trimethoprim-sulfamethoxazole 160/800 mg bid (PO)    

Amoxicillin 1 g tid (PO)    

Ceftriaxone 1–2 g/d (IV)  

Preemptive treatment — Preemptive therapy in an attempt to prevent complications of Salmonella intestinal infection.

Older adults and the very young

those with known atherosclerotic disease, are at higher risk of endovascular infection and aortitis if bacteremia develops.

An organ transplant

AIDS

Those receiving corticosteroids or other immunosuppressive drugs

Sickle cell disease, hemoglobinopathies, disorders of the reticuloendothelial system, (eg, cirrhosis)

Cancer or lymphoproliferative disease with current or recent chemotherapy.

Bacteremia   

Ceftriaxone  2 g/d (IV) 7–14 days  

Ciprofloxacin 400 mg q12h (IV),

then 500 mg bid (PO)  

Endocarditis or Arteritis   

Ceftriaxone 2 g/d (IV) 42 days

  Ciprofloxacin 400 mg q8h (IV), then 750 mg bid (PO)

    Ampicillin 2 g q4h (IV)