shigella nelson 2011

CLINICAL MANIFESTATIONS AND COMPLICATIONS

Bacillary dysentery is clinically similar regardless of infecting

serotype. There are some clinical differences, particularly relating

to the greater severity and risk of complications with S. dysenteriae

serotype 1 infection. Ingestion of shigellae is followed by an

incubation period of 12 hr to several days before symptoms

ensue. Severe abdominal pain, high fever, emesis, anorexia, generalized

toxicity, urgency, and painful defecation characteristically

occur. The diarrhea may be watery and of large volume

initially, evolving into frequent, small-volume, bloody mucoid

stools. Most children never progress to the stage of bloody diarrhea,

but some have bloody stools from the outset. Significant

dehydration is related to the fluid and electrolyte losses in feces

and emesis. Untreated diarrhea can last 1-2 wk; only about 10%

of patients have diarrhea persisting for> 10 days. Persistent diarrhea

occurs in malnourished infants, children with AIDS, and

occasionally previously normal children. Even nondysenteric

disease can be complicated by persistent illness.

Physical examination initially shows abdominal distention

and tenderness, hyperactive bowel sounds, and a tender rectum

on digital examination. Neurologic findings are among the most

common extraintestinal manifestations of bacillary dysentery,

occurring in as many as 40% of hospitalized children. Enteroinvasive

E. coli can cause similar neurologic toxicity. Convulsions,

headache, lethargy, confusion, nuchal rigidify, 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 Shiga toxin,

but it is now clear that this explanation is wrong because the

organisms isolated from children with Shigella-related seizures

are usually not Shiga toxin producers. 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. Based on animal studies, it has been suggested that

proinflammatory mediators, including TNF-a and interleukinl~,

nitric oxide, and corticotropin-releasing hormone, all play

a role in the enhanced susceptibility to seizures caused by S.

dysenteriae.

The most common complication of shigellosis is dehydration.

Inappropriate secretion of antidiuretic hormone with profound

hyponatremia can complicate dysentery, particularly when S.

dysenteriae is the etiologic agent. Hypoglycemia and proteinlosing

enteropathy are common. Other major complications

include sepsis and disseminated intravascular coagulation, particularly

in very young, malnourished children. Given that shigellae

penetrate the intestinal mucosal barrier, these events are

surprisingly uncommon.

Shigella and sometimes other gram-negative enteric bacilli are

recovered from blood cultures in 1-5% of patients in whom

blood cultures are taken; because patients selected for blood

cultures represent a biased sample, the risk of bacteremia 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%) when sepsis occurs.

Neonatal shigellosis is rare. Neonates might have only lowgrade

fever with mild, non bloody diarrhea. However, complications

occur more commonly than in older children and include

septicemia, meningitis, dehydration, colonic perforation, and

toxic megacolon.

S. dysenteriae serotype 1 infection is commonly complicated

by hemolysis, anemia, and HUS. This syndrome is caused by

Shiga toxin-mediated vascular endothelial injury. E. coli that

produce Shiga toxins (e.g.,E. coli 0157:H7, E. coli 0111:NM,

E. coli 026:Hl1) also cause HUS (Chapter 512).

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), reactive arthritis, cystitis, myocarditis, and

vaginitis (typically with a blood-tinged discharge associated with

S.flexneri) are uncommon events. Although rare, surgical complications

of shigellosis can be severe; the most common are intestinal

obstruction and appendicitis with and without perforation.

On average, severity of illness and risk of death are least with

disease caused by S. sonnei and greatest with infection by S.

dysenteriae type 1. Risk groups for severe illness and poor outcomes

include infants; adults >50 yr; children who are not breastfed;

children recovering from measles; malnourished children and

adults; and patients who develop dehydration, unconsciousness,

or hypo- or hyperthermia or have a history of convulsion when

first seen. Death is a rare outcome in well-nourished older children.

Multiple factors contribute to death in malnourished children

with shigellosis, including illness in the first year of life,

altered consciousness, dehydration, hypothermia, thrombocytopenia,

anemia, hyponatremia, renal failure, hyperkalemia hypoglycemia,

bronchopneumonia, and bacteremia.

The rare syndrome of severe toxicity, convulsions, extreme

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.

DIFFERENTIAL DIAGNOSIS

Although clinical features suggest shigellosis, they are insufficiently

specific to allow confident diagnosis. Infection by Campylobacter

jejuni, Salmonella spp, enteroinvasive E. coli, Shiga

toxin-producing E. coli (e.g. E. coli 0157:H7), Yersinia enterocolitica,

Clostridium difficile, and Entamoeba histolytica as well

as inflammatory bowel disease can cause confusion.

DIAGNOSIS

Presumptive data supporting a diagnosis of bacillary dysentery

include the finding of fecal leukocytes (usually >50 or 100 PMNs

per high power field, confirming the presence of colitis), fecal

blood, 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 spp and

other agents. Studies of outbreaks and illness in volunteers show

that the laboratory is often not able to confirm the clinical suspicion

of shigellosis even when the pathogen is present. Multiple

fecal cultures improve the yield of Shigella. The diagnostic inadequacy

of cultures makes it incumbent on the clinician to use

judgment in the management of clinical syndromes consistent

with shigellosis. Use of polymerase chain reaction (PCR) analysis

of stool for specific genes such as ipaH, lIirF, or lIirA can detect

cases not diagnosed by culture, but it is usually available only in

research laboratories. In children who appear to be toxic, blood

cultures should be obtained, especially in very young or malnourished

infants because of their increased risk of bacteremia.

TREATMENT

As with gastroenteritis from other causes, the first concern in a

child with suspected shigellosis should be for fluid and electrolyte

correction and maintenance (Chapter 332). Drugs that retard

intestinal motility (e.g., diphenoxylate hydrochloride with atropine

[Lomotil) or loperamide [Imodium)) should not be used

because of the risk of prolonging the illness.

Nutrition is a key concern in areas where malnutrition is

common. A high-protein diet during convalescence enhances

growth in the following 6 mo. A single large dose of vitamin A

(200,000 IU) lessens severity of shigellosis in settings where

vitamin A deficiency is common. Zinc supplementation (20 mg

elemental zinc for 14 days) has been shown to significantly

decrease the duration of diarrhea, improve weight gain during

recovery and immune response to the Shigella, and decrease diarrheal

disease in the subsequent 6 mo in malnourished children.

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 empirical treatment of all

children in whom shigellosis is strongly suspected. Even if not

fatal, the untreated illness can cause a child to be quite ill for

weeks; chronic or recurrent diarrhea can ensue. Malnutrition can

develop or worsen 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.

Shigella species have variable antimicrobial susceptibility. In

general, S. flexneri tends to be more resistant than S. boydii.

There are major geographic variations in antibiotic susceptibility

of shigellae. In most developing countries and in some industrialized

countries such as the USA, Shigella strains are often resistant

to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMX).

Therefore, these drugs should usually not be used for empirical

treatment of suspected shigellosis. Oral ampicillin (100 mg!

kg!24 hr orally, divided 4 times/day) or TMP-SMX (10 mg!

kg!24 hr orally of the TMP component in 2 divided doses) may

be used if the strain is known to be susceptible (e.g., in an outbreak

due to a defined strain). Amoxicillin is less effective than

ampicillin for treatment of ampicillin-sensitive strains. Ceftriaxone

(50 mg!kg!24 hr as a single daily dose IV or 1M) can be used

for empirical therapy, especially for small infants.

The oral 3rd-generation cephalosporin cefixime can also be

used. Oral 1st and 2nd-generation cephalosporins are inadequate

as alternative drugs despite in vitro susceptibility. Nalidixic acid

(55 mg!kg!24 hr orally divided 4 times/day) is also an acceptable

alternative drug when available. Azithromycin (12 mg!kg!24 hr

orally for the first day, followed by 6 mg/kg!24 hr for the next 4

days) has proven to be an effective alternative drug for shigellosis.

Ciprofloxacin (30 mg!kg!24 hr divided into 2 doses) used to be

a back-up drug to treat shigellosis but is now the drug of choice

recommended by WHO for all patients with bloody diarrhea,

irrespective of their ages.

Although quinolones have been reported to cause arthropathy

in immature animals, the risk of joint damage in children appears

to be minimal and is outweighed by the value of these drugs for

treatment of this potentially life-threatening disease. However,

some experts recommend that these agents be reserved for seriously

ill children with bacillary dysentery due to an organism that

is suspected or known to be resistant to other agents, because

overuse of quinolones promotes development of resistance to

these drugs. Treatment in general is for a 5-day course.

Treatment of patients in whom Shigella infection is suspected

on clinical grounds of should be initiated when they are first

evaluated. Stool culture is obtained to exclude other pathogens

and to assist in antibiotic changes should a child fail to respond

to empirical therapy. A child who has typical dysentery and who

responds to initial empirical 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  during adult volunteer infection studies. In a child who fails to

respond to therapy of a dysenteric syndrome in the presence of

initially negative stool culture results, additional cultures should

be obtained and the child should be re-evaluated for other possible

diagnoses.

PREVENTION

PREVENTION

Numerous measures have been recommended to decrease the risk

of Shigella transmission to children. Mothers should be encouraged

to prolong breast-feeding of infants. Families and day care

personnel should be educated in proper handwashing techniques

and encouraged to wash hands after using the toilet, changing

diapers, or engaging in preparation of foods. They should be

taught how to manage potentially contaminated materials such

as raw vegetables, soiled diapers, and diaper-changing areas.

Children with diarrhea should be excluded from child care facilities.

Children should be supervised when handwashing after they

use the toilet. Caretakers should be informed of the risk of transmission

if they prepare food when they are ill with diarrhea.

Families should be educated regarding the risk of swallowing

contaminated water from ponds, lakes, or untreated pools.

There is not yet a vaccine that is effective for preventing infection

by Shigella. Several candidate vaccines are under development,

mostly against S. flexneri. Measles immunization can substantially reduce the incidence and severity of diarrheal diseases,

including shigellosis. Every infant should be immunized

against measles at the recommended age.