Tuesday, February 26, 2013

Shigellosis: All You Need To Know


Although dysenteric syndromes have long been recognized as a scourge of man, it is only in the last 90 yr that the bacteriology of the most common form of epidemic dysentery has been appreciated. Four species of Shigella are responsible for illness: S. dysenteriae (serogroup A), S. flexneri (serogroup B), S. boydii (serogroup C), and S. sonnei (serogroup D). There are 12 serotypes in group A, 6 serotypes and 13 subserotypes in group B, 18 serotypes in group C, and 1 serotype in group D.

PATHOPHYSIOLOGY. The basic virulence trait shared by all shigellae is the ability to invade colonic epithelial cells. This characteristic is encoded on a large (120–140 MD) plasmid that is responsible for synthesis of a group of polypeptides involved in cell invasion and killing. Shigellae that lose the virulence plasmid no longer act as pathogens. Escherichia coli that naturally or artificially harbor this plasmid behave like shigellae. In addition to the major plasmid-encoded virulence traits, chromosomally encoded factors are also required for full virulence; some of these chromosomal traits are important for all shigellae (e.g., lipopolysaccharide synthesis), whereas others are important only in some serotypes (e.g., shigatoxin synthesis). Shigatoxin, a potent protein synthesis–inhibiting exotoxin, is produced in significant amounts only by S. dysenteriae serotype 1 and certain E. coli (enterohemorrhagic E. coli or shiga-like toxin–producing E. coli). The watery diarrhea phase of shigellosis may be caused by unique enterotoxins: shigella enterotoxin 1 (ShET-1), encoded on the bacterial chromosome, and ShET-2, encoded on the virulence plasmid.

Shigellae require very low inocula to cause illness. Ingestion of as few as 10 S. dysenteriae serotype 1 organisms can cause dysentery in some susceptible individuals. This is in contrast to organisms such as Vibrio cholerae, which require ingestion of 108–1010 organisms to cause illness. The inoculum effect explains the ease of person-to-person transmission of shigellae in contrast to V. cholerae.

Immune Responses. Secretory IgA and serum antibodies develop within days to weeks after infection with Shigella. Although both antilipopolysaccharide and antivirulence plasmid polypeptide antibodies have been described, identification of the major determinant of protection against subsequent infection remains unclear. There is evidence that protection is serotype specific, but there is also the suggestion that a degree of cross-protection against all shigellae follows infection with a given serotype. Cell-mediated immunity may also play some role in protection, although it appears to be minor.

PATHOLOGY. The pathologic changes of shigellosis take place primarily in the colon, the target organ for shigellae. The changes are most intense in the distal colon, although pancolitis may occur. Grossly, localized or diffuse mucosal edema, ulcerations, friable mucosa, bleeding, and exudate may be seen. Microscopically, ulcerations, pseudomembranes, epithelial cell death, infiltration extending from the mucosa to the muscularis mucosae by polymorphonuclear and mononuclear cells, and submucosal edema occur.

EPIDEMIOLOGY. Infection with shigellae occurs most often during the warm months in temperate climates and during the rainy season in tropical climates. The sexes are affected equally. Although infection can occur at any age, it is most common in the 2nd and 3rd yr of life. Infection in the first 6 mo is rare for reasons that are not clear. Breast milk, which in endemic areas contains antibodies to both virulence plasmid-coded antigens and lipopolysaccharides, may partially explain the age-related incidence. Asymptomatic infection of children and adults occurs but is uncommon.

In industrialized societies, S. sonnei is the most common cause of bacillary dysentery, with S. flexneri second in frequency; in preindustrial societies, S. flexneri is most common with S. sonnei second in frequency. S. dysenteriae serotype 1 tends to occur in massive epidemics, although it is also endemic in Asia.

Contaminated food (often a salad or other item requiring extensive handling of the ingredients) and water are important vectors. However, person-to-person transmission is probably the major mechanism of infection in most areas of the world. Spread within families, custodial institutions, and day-care centers demonstrates the ability of low numbers of organisms to cause disease on a person-to-person basis.


Bacillary dysentery is clinically similar regardless of whether the disease is caused by an enteroinvasive E. coli (see Chapter 184) or any of the four species of Shigella; however, there are some clinical differences, particularly relating to the severity and risk of complications with S. dysenteriae serotype 1 infection.

After ingestion of shigellae there is an incubation period of several days before symptoms ensue. Characteristically, severe abdominal pain, high fever, emesis, anorexia, generalized toxicity, urgency, and painful defecation occur. Physical examination at this point may show abdominal distention and tenderness, hyperactive bowel sounds, and a tender rectum on digital examination.

The diarrhea may be watery and of large volume initially, evolving into frequent small-volume, bloody mucoid stools; however, some children never progress to the stage of bloody diarrhea, whereas in others the first stools are bloody. Significant dehydration related to the fluid and electrolyte losses in both feces and emesis can occur. Untreated diarrhea may last 1–2 wk; only about 10% of patients have diarrhea persisting for more than 10 days. Chronic diarrhea is uncommon except in malnourished infants.

Neurologic findings are among the most common extraintestinal manifestations of bacillary dysentery, occurring in as many as 40% of hospitalized infected children. Convulsions, headache, lethargy, confusion, nuchal rigidity, or hallucinations may be present before or after the onset of diarrhea. The cause of these neurologic findings is not understood. In the past, these symptoms were attributed to the neurotoxicity of shigatoxin, but it is now clear that that explanation is wrong. Seizures sometimes occur when little fever is present, suggesting that simple febrile convulsions do not explain their appearance. Hypocalcemia or hyponatremia may be associated with seizures in a small number of patients. Although symptoms often suggest central nervous system infection, and cerebrospinal fluid pleocytosis with minimally elevated protein levels can occur, meningitis due to shigellae is rare.

The most common complication of shigellosis is dehydration with its attendant risks of renal failure and death (see Chapter 56.1). Inappropriate secretion of antidiuretic hormone with profound hyponatremia may complicate dysentery, particularly when S. dysenteriae is the etiologic agent.

Other major complications, particularly in very young, malnourished children, include sepsis and disseminated intravascular coagulation. Given that these organisms penetrate the intestinal mucosal barrier, these events are surprisingly uncommon. Shigellae and sometimes other gram-negative enterics are recovered from blood cultures in 1–5% of cases in whom blood cultures are taken; because patients selected for blood cultures represent a biased sample, the risk in unselected cases of shigellosis is presumably lower. Bacteremia is more common with S. dysenteriae serotype 1 than with other shigellae. The mortality rate is high (20–50%) when sepsis occurs.

In those who have S. dysenteriae serotype 1 infection, hemolysis, anemia, and hemolytic uremic syndrome are common complications; these events may occasionally follow S. flexneri infection. This syndrome is thought to be related to shigatoxin, because those E. coli that produce toxins closely related to shigatoxin (enterohemorrhagic E. coli) also cause hemolytic uremic syndrome (see Chapter 184).

Rectal prolapse, toxic megacolon or pseudomembranous colitis (usually associated with S. dysenteriae), cholestatic hepatitis, conjunctivitis, iritis, corneal ulcers, pneumonia, arthritis (usually 2–5 wk after enteritis), Reiter syndrome, cystitis, myocarditis, and vaginitis (typically with a blood-tinged discharge associated with S. flexneri) are uncommon events. The rare syndrome of extreme toxicity, convulsions, hyperpyrexia, and headache followed by brain edema and a rapidly fatal outcome without sepsis or significant dehydration (Ekiri syndrome or "lethal toxic encephalopathy") is not well understood. Death is a rare outcome in the well-nourished, older child; malnutrition, illness in the 1st yr of life, hypothermia, severe dehydration, thrombocytopenia, hyponatremia, renal failure, and bacteremia are common in children who die during bacillary dysentery.

DIAGNOSIS. Although clinical features suggest shigellosis, they are insufficiently specific to allow confident diagnosis. Infection by Campylobacter jejuni, Salmonella sp, enteroinvasive E. coli, enterohemorrhagic E. coli, Yersinia enterocolitica, and Entamoeba histolytica as well as inflammatory bowel disease may cause confusion. Unfortunately, the laboratory is often not able to confirm the clinical suspicion of shigellosis even when it is present. Presumptive data supporting a diagnosis of bacillary dysentery include the finding of fecal leukocytes (confirming the presence of colitis) and demonstration in peripheral blood of leukocytosis with a dramatic left shift (often with more bands than segmented neutrophils). The total peripheral white blood cell count is usually 5,000–15,000 cells/mm3, although leukopenia and leukemoid reactions occur.

Culture of both stool and rectal swab specimens optimizes the chance of diagnosing Shigella infection. Culture media should include MacConkey agar as well as selective media such as xylose-lysine deoxycholate (XLD) and SS agar. Transport media should be used if specimens cannot be cultured promptly. Appropriate media should be used to exclude Campylobacter and other agents. Culture is the gold standard for diagnosis, but it is not absolute. Stool cultures of adult volunteers with dysentery after ingestion of shigellae failed to detect the organism in nearly 20% of subjects. Studies of foodborne outbreaks suggest that a single culture allows diagnosis in about half of symptomatic patients with shigellosis. Although additional tools to improve diagnosis (e.g., gene probes) are being developed, the diagnostic inadequacy of cultures makes it incumbent on the clinician to use judgment in the management of clinical syndromes consistent with shigellosis. In children who appear to be toxic, blood cultures should be obtained; this is particularly important in very young or malnourished infants because of their increased risk of bacteremia.


As with gastroenteritis of other causes, the first concern about a child with suspected shigellosis should be for fluid and electrolyte correction and maintenance. Drugs that retard intestinal motility should not be used because of the risk of prolonging the illness.

The next concern is a decision about the use of antibiotics. Although some authorities recommend withholding antibacterial therapy because of the self-limited nature of the infection, the cost of drugs, and the risk of emergence of resistant organisms, there is a persuasive logic in favor of empiric treatment of all children in whom shigellosis is suspected. Even if not fatal, the untreated illness may cause the child to be quite ill for 2 weeks or more; chronic or recurrent diarrhea may ensue. There is a risk of malnutrition developing or worsening during prolonged illness, particularly in children in developing countries. The risk of continued excretion and subsequent infection of family contacts further argues against the strategy of withholding antibiotics.

There are major geographic variations in drug susceptibility. In the United States, shigellae are so frequently resistant to ampicillin that it should not be used for empiric therapy; occasional strains are also resistant to trimethoprim-sulfamethoxazole (TMP-SMX). Cefixime and ceftriaxone are effective alternative drugs in areas where TMP-SMX resistance is common. Nalidixic acid is also an acceptable option in this setting. Resistance to nalidixic acid is uncommon. With the exception of nalidixic acid, the quinolones that have been recommended for use in adults have not been used in children (because of the putative risk of arthropathy). Treatment regimens involve a 5-day course. For strains known to be susceptible to ampicillin, this drug is given at 100 mg/kg/24 hr divided into four doses each day. The usual empiric choice before the availability of susceptibility data is TMP-SMX, given at 5–10 mg/kg/24 hr of the TMP component in two divided doses. For strains known to be resistant to the usual drugs, cefixime (8 mg/kg/24 hr in two divided doses given orally for 5 days), ceftriaxone (50 mg/kg/24 hr as a single daily dose given parenterally for 2–5 days), or nalidixic acid (55 mg/kg/24 hr in four divided doses for 5 days) can be given. Of these agents, given a susceptible organism, TMP-SMX is preferred because of the rapidity with which it causes resolution of symptoms. In patients too ill to take oral medications, intravenous therapy with TMP-SMX is effective if the organism is susceptible. Oral first- and second-generation cephalosporins are inadequate as alternative drugs. Amoxicillin is less effective than ampicillin in therapy of ampicillin-sensitive strains.

Treatment of patients suspected on clinical grounds of having Shigella infection should be started when the patient is first examined. Stool culture is obtained to exclude other pathogens and to assist in antibiotic selection should the child fail to respond to empiric therapy. A child who has typical dysentery and who responds to initial empiric antibiotic treatment should be continued on that drug for a full 5-day course even if the stool culture is negative. The logic of this recommendation is based on the difficulty of culturing Shigella and on the fact that enteroinvasive E. coli, which cause dysentery indistinguishable from that due to shigellae, cannot be diagnosed in routine clinical microbiology laboratories. In a child who fails to respond to therapy of a dysenteric syndrome in the presence of initially negative stool cultures, cultures should be retaken and the child re-evaluated for other possible diagnoses.

PREVENTION. Two simple measures decrease the risk of shigellosis in children. The first is to encourage prolonged breast-feeding in settings in which shigellosis is common. Breastfeeding decreases the risk of symptomatic shigellosis and lessens its severity in infants who acquire infection despite breast-feeding. The second measure is to educate families in handwashing techniques, especially after defecation and before food preparation and consumption. Other public health measures, including water and sewage treatment, are expensive and are unlikely to be universally available in the near future in developing countries.

Short statement of the material
Shigelloses (dysenteries) are acute human infectious diseases with enteral infection that is characterized by colitic syndrome and symptoms of general intoxication, quite often with development of primary neurotoxicosis.

Etiology: Shigella, gram negative bacteria, immobile, sized 2-3 mkm, without sporing and incapsulation, product endotoxin, resistant to the environment (in milk, water, food stay for several days, in soil –for several weeks), stable to the freezing, but sensitive for boiling. By antigen structure and biochemical properties shigella are devided into 4 subgroups: A, B, C, D:
·        Sh.dysenteriae – belongs to group A
·        Sh. flexneri – belongs to group B
·        Sh.boydii – belongs to group C
·        Sh.sonnei – belongs to group D
Sh. flexneri and Sh.sonnei are the most often agents for bacterial dysentery nowadays.

Source of infection –
         Contagious patient
         Bacillus carrier
Shigella is spread through fecal-oral mechanism of transmission.
The way of transmission
Susceptibility: 60-70% especially infants and preschoolers.
Seasonality is summer-autumn.

1.     Entrance Shigella to gastrointestinal tract.
2.     Destruction of them under the influence of ferments.
3.     Toxemia.
4.     Toxic changes in organs and systems (especially in CNS).
5.     Local inflammatory process (due to colonizing of distal part of the colon).
6.     Diarrhea.

Morphological changes in shigellosis

      I.            Clinical Form
         With dominance of toxicosis
         with dominance of local inflammation
   II.             Severity (mild, moderate and severe)
III.            Duration
         acute (up to 1.5 mo)
         subacute (up to 3 mo)
         chronic (about 3 mo)
ü     recurrent
ü     constantly recurring
IV.            Course
         Uneven (with complication)
V. Bacterium carrier

Clinical criterions (With dominance of toxicosis):
·        Period of incubation: a few hours to 7 days.
·        Toxicosis is the first sing even may be neurotoxicosis (lose of appetite, headache, fatigue, vomiting, hallucinations, unconsciousness, seizure, febrile temperature 39-40°C).
·        Colitis is secondary (abdominal pain, tenesmus, false urge to defecate, sigmoid colon is tender, spastic, anus is open in hard cases. Feces in the form of a spit of mucus and blood (rectal spit), enlargement of number of defecation).
·        Dehydration isn’t developed (except infants).

Marble skin in toxicosis

With dominance of local inflammation
         Sudden onset of high-grade fever
          abdominal cramping
         abdominal pain,
         and large-volume mucus, cylindrical epithelial cells diarrhea →
         fecal incontinence, and small-volume mucous diarrhea with frank blood

False urge to defecate

Typical color of feces in shigellosis, rectal spit

Sunken abdomen

Rectal prolapse

Peculiarities of shigellosis in infants:
·        Acute beginning with slow development of signs and symptoms (for 3-5 days).
·        Distal colitis is less common
·        Enterocolitis is more often with enterocolitic feces, hemocolitis is rare.
·        Hepato- and splenomegaly
·        Crying, anxiety, red face during defecation is equivalent to tenesmus.
·        Always occurs gaping anus, sphincteritis
·        Dehydration is more often
·        Prolonged duration of the disease

Criteria of the Shigellosis Severity
Mild form
         Consistent or acute onset of diarrhea
          Stool is 5-8 times per day with mucous and blood
         Not permanent pain in abdominal region.
         The temperature is normal
         Loss of appetites
         Can be vomiting 
Moderate form
         Acute onset of diarrhea
         Symptoms of toxicosis
          The temperature is 38-39°C
         Crampy abdominal pain
          Stool is 10-15 times per day
         Pain during palpation in left inguinal region
Severe form
        Multiple vomiting not only after receiving the food, but also independent, can be with bile, sometimes - as coffee lees,
        excrements - more 15 times per day, sometimes - with each diaper, much mucus, there is blood, sometimes - an intestinal bleeding
        General condition is sharply worsened,
        quite often - sopor, loss of the consciousness, cramps,
        changes in all organs and systems,
        severe toxicosis, may be dehydration (in infants),
        significant weight loss

Laboratory tests:
         The white blood cell count is often within reference range, with a high percentage of bands. Occasionally, leucopenia or leukemic reactions may be detected.
         In HUS, anemia and thrombocytopenia occur.
         Stool examination Increasing of red blood cells and leukocytes
         Stool culture Specimens should be plated lightly onto Endo-Levin, Ploskirev, McConkey, xylose-lysine-deoxycholate, or eosin-methylene blue agars.
         Serological test: (AR, PHAR in dynamics with fourfold title increasing in 10-14 days) in children elder than 1 year if fecal culture is negative.
Diagnosis example:
         Shigellosis (Sh. sonnei), typical form (with dominance of toxicosis), severe degree, acute duration.
         Shigellosis (Sh. flexneri), typical form (with dominance of local inflammation), moderate degree, constantly recurring duration, complicated by the rectum prolapse

Differential diagnosis should be performed with: salmonellosis, escherichiosis, acute appendicitis, bowel invagination, Krohn’s disease, nonspecific necrotizing colitis.

Differential-Diagnostic Criteria of Diarrheal Diseases
 functional Diarrhea
Epidemiological anamnesis
Sporadic diseases on background of wrong feeding, care, etc.
More often group diseases, connected with source of infection (products, contact with ill person or carrier of salmonellas)
Both sporadic, and group diseases, contact with ill person, connection with infected products
Poor fermentation (dyspepsia)
High temperature
Short (2-3 days), or normal
7 and more days
 5-7 days and more
Short, small on background of the diarrhea
Moderate degree, 5-7 days, prevails on diarrhea
Different degree, 3-7 days, precedes intestinal manifestations
Little denominated or absent
 Often denominated
Moderately denominated
2-3 days
 7-30 days
 7 and more days
looks like cut eggs, liquid
Dark-green with mucus (as mud), with blood
Big amount of mucus, sometimes - blood and pus - rectal spit 
Short (1-2 days), or absent
Moderate or long-lasting (5-7 days)
Expressed, is not long-lasting (3-5 days)
Sparingly denominated, short (1-2 days)
Always denominated, long-lasting
Abdomen is sealed
Enzyme changes
Mainly enzyme changes
Inflammatory changes
is not enlarged
is increased
Can be increased
is not enlarged
is increased
Not increased
Staphylococcal enterocolitis
Viral diarrhea
Epidemiological anamnesis
Sporadic diseases of children before 1 year old, more often in hospital, contact with ill person
Sporadic diseases of children before 1 year old on background of Staphylococcal damage of other organs, or Staphylococcal diseases of the mother
Group, less sporadic diseases, on background of other catarrhal manifestations in the upper respiratory tract 
Pathogenic Escherichia
Viruses, more often rotaviruses
High temperature
7-14 days and more, quite often - wave-like
Long-lasting subfebril (during weeks, months)
5-7 days, subfebril, rare - high
More often moderately denominated, as a rule not less 7 days, prevails over dyspeptic phenomena
Little denominated, long-lasting (weeks, months)
Moderately denominated, 3-5 days
Often denominated, long-lasting
Absent, or little denominated
Little denominated or absent
7-30 days
Weeks, months
5-7 days
Big amount weakly painted or brightly yellow liquid
Rare, yellow, sometimes - with blood
Moderate or long-lasting (5-7 days)
Is absent
Short (1-3 days), small (2-3 times in day) or, more often, is absent
Always denominated, long-lasting
Small denominated, but long-lasting
Moderately denominated, short (1-2 days)
enzyme changes
Inflammatory changes
Enzyme changes
is Increased
is increased 
is not increased
is not increased
More often is increased
is not increased

Treatment: see treatment of Ecsherichiosis 

·        Epidemiological control for water and food.
·        Isolation and sanation of ill person
·        Reconvalescent may be discharged from hospital after one negative feces culture ( taken 2 days after course of antibiotic therapy)
·        Dispensarization of reconvalescent for 1-3 months
·        Feces culture in contacts, carriers
·        Looking after contacts for 7 days, quarantine
·        Disinfection in epidemic focus

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3.      Principles and Practice of Pediatric Infectious Diseases. / Edited by Saran S. Long, Larry K. Pickering, Charles G. Prober, PhiladelphiaPa: Churchill Livingstone; 1997. – 1921 p.

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