SALMONELLA INFECTIONS

(salmonelloses)

• The Enterobacteraceae comprise Salmonella, Shigella, Escherichia, Klebsiella, Enterobacter, Serratia, Proteus, Morganella, Yersenia, and other less common genera. This oxidase-negative, Gr. (-), catalase-positive organisms are readily cultured on ordinary media, ferment glucose and reduce nitrates to nitrites.

The 2200 known serotypes of Salmonella may be grouped into

these• highly adapted to human hosts

• adapted to non-human hosts

• unadapted to specific host

• The first group includes S. typhi and S. paratyphi A, B and C, which are pathogenic only in humans and commonly cause enteric fever.

• The second group causes disease almost exclusively in animals, although 2 strains within this group, S. dublin and S. choleraesuis also cause disease in humans.

• The third group designated S. enteritidis, includes > than 2000 serotypes that cause gastroenteritis.

TYPHOID FEVER

• A systemic disease caused by S. typhi and characterized by fever, prostration, abdominal pain, and a rose-colored rash

Pathogenesis

• S. typhi invades first the alimentary tract by ingestion, then via the lymphatic system, via the thoracic duct into the blood stream.

• This first septicemic phase leads to infection of the reticuloendothelial system and the gall bladder.

• Infection of the gall bladder causes discharge of organisms into the intestine, with heavy infection of the Peyer’s pathes and septicemia – and the onset of symptoms.

Symptoms and signs

• IP – 8-14 (14-21 days)• Onset is usually gradual, with fever, headache,

arthralgias, pharyngitis, constipation, anorexia, and abdominal pain and tenderness.

• If no therapy is began the temperature raises in steps over 2 to 3 days, remains elevated (usually to 39-40C) for another 10 to 14 days, begins to fall gradually at the end of the 3rd wk, and reaches normal levels during the fourth week.

• Prolonged fever is often accompanied by relative bradycardia and prostration and CNS symptoms such as delirium, stupor, or coma occur in severe cases.

• In about 10% of the patients discreet pink, blanching lesions (rose spots) appear in crops on the chest and abdomen during the 2nd wk and resolve in 2 to 5 days.

• Intestinal perforation, usually involving the distal ileum, occurs in 1-2% of patients.

• Splenomegaly, leucopenia, anemia, liver function abnormalities, proteinuria, and a mild consumption coagulopathy are common

• Diarrhea is a late symptom, usually in the third week of illness and still may contain blood. In about 2% of patients, severe bleeding occurs during the third week with a mortality rate of about 25%.

• In addition bacteriemia, occasionally leads to focal infections, such as osteomyelitis, endocarditis, menengitis, soft tissue abscesses, glumerulonephritis, or GU tract involvement.

Complications

• Relapse, intestinal perforation and hemorrhage are the most serious. Relapse is common, with recrudescence of symptoms about a week after the end of the primary illness

• Carriers – around 2-5% of patients with typhoid fever become chronic carriers, owing to persistent infection of the gall bladder.

Diagnosis

• Best made by isolation of the infecting organism from feces, blood and urine. Blood culture is positive in over 80% of patients in the first week of illness.

• Blood and urine: Mac Conkey medium

• Feces: use selective and enrichment media

Identification = biochemical reactions: S typhi, unlike other salmonellae, produces no gas on fermentation of sugars.

= serological: preliminary identification with salmonella polyvalent H and O antisera

= phagotyping

• Serology: the classic test is the Widal test: agglutination test for antibodies to flagellar H antigens and somatic O antigens of S. typhi and S. paratyphi A and B, but the results are difficult to interpret, especially if the patients has been immunized with typhoid vaccine. This test is no longer used in routine diagnostic laboratories.

Treatment

• Ciprofloxacin 500mg po q12h; is the drug of choice, especially with the emergence of multiresistance involving other antibiotics – but care is needed with children. Ceftriaxone is a useful alternative in such cases.

• Ceftriaxone 30mg/kg/day im or iv in 2 divided doses for 2 week (eg. 1 g iv q 12h for adults).

• Cefoperazone is given 60mg/kg/day iv in 2 divided doses for 2 weeks.

• Co-trimoxazole.

PARATYPHOID FEVER• Causal organisms: S. paratyphi A, B and C• Clinically a milder febrile illness than typhoid fever, with a

shorter duration and incubation period. Transient diarrhea and symptomless infection are common.

• Carriers: patients become carriers less frequently than after typhoid fever.

• Diagnosis: best made by isolation of the infecting organism from feces, blood and urine. Blood culture is positive in over 80% of patients in the first week of illness.

• Treatment: Ciprofluxacin is the drug of choice, but care is needed with children. Ceftriaxone is a useful alternative in such cases. Chloramphenicol is as effective, but resistance is now a problem. Co-trimoxazole is less good than Chloramphenicol, but has less serious side effects.

NON-TYPHOIDAL SALMONELLA INFECTIONS

• Formerly the commonest cause of diarrhea in Europe and the USA.

• Diarrhea due to Salmonella is traditionally called food poisoning, although this term is somewhat misleading. Infected meat-producing animals, poultry, raw milk, eggs and egg products are common sources of Salmonella.

• There are more than 2000 serotypes of Salmonella, but only about 14 are important or common causes of infection.

• In recent years the commonest serotype has been S. enteritidis. Other common Salmonellae are S. typhi murium, S. heidelberg, S. Newport, S. agona

Pathogenesis

• Sight of infection is the small or large intestine. Many strains produce enterotoxins similar to those of toxigenic strains of E. colli. NB!: The Salmonella enterotoxins are still poorly defined. Other Salmonellae invade the mucosa of the small intestine like Shigellae.

Symptoms and signs

• Salmonella infection may present clinically as gastroenterits, enteric fever (S. paratyphi A, B and C), a bacteremic syndrome, or focal disease.

• IP is short: around 12-36-48 hours. • Main symptoms are acute onset of abdominal pain

and diarrhea, sometimes with fever and vomiting. Dehydratation may require correction, especially in babies.

• Usually the stool is watery, but made be paste – like semisolid. Rarely, mucus or blood is present.

Bacteremia

• (S. choleraesuis, S. typhimurium, S. heidelberg). Although blood cultures are positive, stool cultures are generally negative.

Focal manifestation

• of Salmonella infections may occur with or without sustained bacteriemia. In patients with bacteriemia localized infection may occur, involving the GI tract (liver, gall bladder and appendix), endothelial surfaces.(heart valves), pericardium, meninges, lungs, joints, bones, GU tract.

Diagnosis

• Is made by isolating the organism from stool or another infected site. The prognosis is usually good unless severe underlying disease is present. Asymptomatic carriage is usually self-limited and antibiotics treatment is rarely required. Eradication may be attempted with Ciprofluxacin – 500 mg po q12h for 1 month, but follow up stool cultures should be obtained in the weeks after drug administration to document elimination of Salmonella.

Treatment• Rarely necessary: rehydratation may be required in babies:

oral isotonic fluid replacement can be life-saving in infants with diarrhea.

• Antibiotics are contraindicated except in septicemia cases: they do not affect symptoms and may prolong convalescent carriage of the organism; they also contribute to the emergence of antibiotic resistant strains.

• Trimethoprim-Sulphamethaxazole (TMP-SMX) 5mg/kg of TMP component po every 12h for children, or Ciprofluxacin 500mg po q12 hours for adults.

• Neledix 50mg/kg• Gentamycin - 2-5mg/kg • Amikacin 5-15mg/kg.

SHIGELLOSIS(Dysenteriae)

• Shigellosis is an acute infectious inflammatory colitis due to one of the members of the genus Shigella. The less severe illness predominates in industrialized countries, whereas more severe, often fatal dysenteria occurs in patients in developing countries.

The four species of Shigella are:

S. dysenteriae

S. flexneri

S. boydii

S. sonnei

All the species except S. sonnei contain several distinguishable serotypes.

 

Pathogenesis and pathology

• Shigella are orally ingested and because they survive low pH better than other enteric pathogens, they seem to have little difficulty in passing the gastric acid barrier

• An essential step in pathogenesis is invasion of colonic epithelial cells and cell-to-cell spread of infection.

• Invasion and cell-to-cell spread involve the initial attachment of the organism to colonic cells, entry by and an endocytic mechanism, in which organisms are initially incased in and then escape from plasma membrane-enclosed vesicles, and a jet propulsion-like movement to the epithelial cell surface that is powered by bacteria-induced actin polymerization at the trailing end of the bacterium

• A second property of apparent importance in virulence, at least for S. dysenteriae type I is the ability to produce cytotoxic proteins. Shiga toxin composed of two distinct peptide subunits, each with highly conserved active regions.

• Shigella organisms penetrate the mucosa of the lower intestini, causing mucous secretion, hyperemia, leucocytic infiltration, edema and often superficial mucosal ulceration. The watery diarrhea associated with shigella infection may be mediated by an enterotoxin that causes increased intestinal secration.

• S. dysenteriae has invasive properties and produces a powerful neurological exotoxin, but this probably does not play a role in shiga dysenteriae. An enterotoxin and cytotoxin are also produced: their role is uncertain, but they may be partly responsible for invasiveness. Shiga toxin, is very closely related to E. colli verocytotoxin 1(VT1). Cytotoxins, which cause destruction of mucosal cell and associated inflammatory diarrhea; and neurotoxins, which act directly on the central or peripheral nervous system.

Symptoms and signs

• IP: 1-9 days.• Diarrhea with blood, mucus and often pus in the

stools, which varies from a severe life threatening to a mild and symptomless infection.

• In young children onset is sudden, with fever, irritability or drowsiness, anorexia, nausea or vomiting, diarrhea, abdominal pain and distention and tenesms. The number of stools may increase to more than 20/day, and weight loss and dehydratation may become severe.

• In adults first symptoms may be episodes of abdominal pain, urgency to defecate and little or no tenesms.

Complications:

• severe mucosal ulcerations may cause significant acute blood loss.

• Intestinal perforation

• Hemolytic-uremic syndrome in children

• Arthritis, myocarditis, toxic neuritis

Laboratory findings and diagnosis

Diagnosis: isolation – culture feces and rectal swabs on MacConckey medium and selective media. Identify by biochemical tests, then serology.

WBC count is often reduced at onset; hemoconcentration is common, as is diarrhea-induced metabolic acidosis.

The mucosal surface, as seen through a prostoscope, is diffusely erithematous with numerous small ulcers.

DD

• Should include invasive E. colli, Salmonella, Yersenia, Campylobacter, Amebiasis, and viral diarrheas.

Treatment• Fluid therapy. Diarrhea usually causes isotonic dehydratation

(equal salt and water loss), with metabolic acidosis and significant potassium loss. Thirst from dehydratation can lead to a proportionately excessive water intake, causing hypotonicity.

• Antibiotics. The decision to use antibiotics requires consideration of disease severity, age of the patient and other factors. In children, TMP-SMX at 4mg/kg/po of the TMP component q12h is the treatment of choice.

• In adults the dose is one double strand tablet q12h (320 mg TMP). An alternative for adults is norfluxacin or ciprofluxacin – 500mg po bid (two times a day). Many shigella isolates are likely to be resistant to Ampicillin and Tetracyclin

CHOLERA

• An acute infection by Vibrio cholerae involving the entire small bowel characterized by profuse watery diarrhea, vomiting muscular cramps, dehydratation, oliguria, and collapse.

Etiology

The causative organism, V. cholerae, serogroups 01 and 1039. Epidemic cholera is caused by V. cholerae serogroup 01. which is divided into three serotypes, Ogava, Inaba, Hikojima. However, antigenic structure may change within the human gut.

Biotypes: two biotypes of V. cholerae 01, classic and El Tor. Any serotype can be of either classic or El Tor biotype.

Non-01 vibrios, deficient in the 01 antigen, were classified as non-cholera vibrios – but a cholera epidemic in Bangladesh in 1992 was due to serogroup 0139.

Pathogenesis

• V. cholerae produces a potent exotoxin – cholera toxin (CT), vary similar to the LT enterotoxin of ETEC, which is plasmid coded. The toxin stimulates the activity of the enzyme adenylcyclase, which raises the concentration of cyclic AMP is cell; this causes an increase in the flow of water and electrolytes into the bowel lumen. The fluid lost has relatively high concentration of bicarbonate and potassium.

• V. cholerae is not invasive and does not penetrate the gut mucose membrane, although adhesion to gut epithelium plays a part in its pathogenesity.

Clinical feature

IP – 6h to 5 days. Acute onset of abdominal pain and diarrhea – the

diarrhea being typically of exceptional severity, progressing to the continuous passage of “rice-water” stools.

Vomiting, dehydratation, acidosis and collapse may follow.

• Some cases are much les severe with only mild diarrhea. Two forms of disease are recognized:

• severe classic cholera• milder cholera associated with the 01 El Tor

biotype.

CHOLERA

Diagnosis

Culture feces on alkaline selective medium. Observe for typical colonies, which can be identified by slight agglutination, with polyvalent antiserum.

Treatment

Correction of dehydratation by intravenous administration of fluid and electrolytes to restore the acid-base balance. Mortality can be reduced from more the 50% to 0 with fluid replacement treatment.

Tetracycline, given orally or intravenously, may help to limit the duration of diarrhea and reduce fluid loss.

Composition of World Health Organization oral rehydratation solution (WHO ORS).

In 1000ml pre-boiled water:

20g glucose3.5g NaCl2.5g NaHCO3 1.5g KCl

Concentration (mmol/l): Na 90, K 20, HCO3 30ex tempore Rehydrin - Phillips solution

ESHERICHIOSES INTESTINALES

(COLIBACILLOSES)

Enteric infections are common cause of diarrhea:

• infantile gastroenteritis

• travelers diarrhea

• hemorrhagic diarrhea– hemorrhagic colitis– hemolytic-uremic syndrome

• ETEC – enterotoxigenic E. coli – travelers diarrhea (“Delhi belly”, “Tokyo two step” etc)

• EPEC – enteropathogenic (eneteroadherent) E. coli – childhood diahhrea.

• EIEC – enteroinvasive E. coli – a dysentery-like disease

• EHEC – enterohemorrhagic E. coli – hemorrhagic colitis and HUS in children.

EPEC (055; 0111) strains

• cause childhood diarrhea, especially in underdeveloped countries and in nursery outbreaks. These bacteria bind to the membranous cells of Peyer’s patches and disrupt the overlying mucous gel of the host cell.

• EPEC do not produce toxins and are non-invasive, but produce an attaching end effacing lesion in the small intestine

• ETEC – there are more than 100 0 serogroups. Important examples are 06, 078.

• ETEC produce heat-labile toxin (LT) or heat-stabile toxin (ST) or both. They also posses colonization factors, which facilitate the attachment of the organism to the epithelium of the small intestine.

• EIEC (0124, 0164) invade the host cell and provoke significant inflammatory response. Manifestations are those of bacterial dysentery with fever and bloody diarrheal stool, containing polymorphonuclear leukocytes.

EHEC strains

• all belong to the serotype 0157:H7, cause hemorrhagic colitis.

• These strains produce shiga-like toxins that kill certain cells in tissue culture.

• Although the typical patient is afebrile the sequel can be severe. In the elderly the disease is often confused with ischemic colitis. It can lead to death. Children (1-4 years) and occasionally adults with EHEC infection can develop HUS, which also can lead to death. HUS is seen occasionally with bacteria other than 0157:H7, including other E.coli serotypes and Shigella.

HUS in children – diarrheal prodrome, followed by uremia, throbocytopenia and hemolytic anemia.

Shiga-like toxins have a cytopathic effect on Vero (monkey kidney) cells. There are two Vero cytotoxins, VT1 and VT2, which are antigenically distinct from each other. Vero cytotoxin – producing E.coli strains are known as VTEC. Over 80% phagotypes of serogroup 0157 can be distinguished.

Diagnosis

Culture feces on MacConckey medium.

Identify by serology and biochemical tests.

Treatment

• Rehydratation with correction of fluid loss and electrolyte and acid base balance

• Antibiotics therapy is of doubtful value, although it may be useful in severe cases

• Treatment may be started empirically, than modified on the basis of antibiotic sensitivity studies. Although many strains are still sensitive to Ampicillin (Piperacillin, cephalosporins, amynoglucosides, TMP-SMX, and quinolons in adults).

DEHYDRATION SYNDROME

Rehydration oral rehydratation – WHO ORS In 1000ml pre-boiled water:

20g glucose3.5g NaCl2.5g NaHCO3 1.5g KCl

Concentration (mmol/l): Na 90, K 20, HCO3 30, Cl 80ex tempore

Rehydrin – a commercial solution

i.v. fluids:

• Classification of dehydratation in infants:

• Ist grade – up to 5% loss of body weight (infuse with 80-100ml/kg/24h)

• IInd grade – between 5-10% loss of body weight (120-150ml/kg/24h)

• IIIrd grade – more than 15% loss of body weight (150-170ml/kg/24h)

• At the end of the rehydratation period (about 4 hours), the patient should be reassessed. If signs of dehydratation persist, rehydratation therapy should be repeated until dehydratation is corrected

Metabolic acidosis – ph<7.37

• The amount of NaHCO3 can be approximated by the formula:

• NaHCO3 required (mEq) = BE(base excess) x 0.4 x body wt(kg)

• First 1/3rd of the received quantity is applied and if fails to correct the acidosis, the rest is added.

Hypokaliemia

• a decrease in the serum potassium concentration, below 3.5 mEq/l. It is a result of excessive losses of K from GI tract. It is characterized my muscle weakness and can lead to paralysis and respiratory failure. ECG – ST depression.

• Treatment – i.v. KCl – amp.15% 10ml 2mEq/kg slowly!

• The use a antibiotics therapy in bacterial diarrheas is controversial and generally not necessary in patients with mild or resolving disease, but should be considered in patients with Shigellosis, travelers diarrhea, cholera.

Reference:

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