ShigellosisShigellosisInfectious Diseases, AIDS & Clinical Infectious Diseases, AIDS & Clinical Immunology Research Center TbilisiImmunology Research Center Tbilisi

Shigellosis = inflammation of intestines Shigellosis = inflammation of intestines (especially the colon) with (especially the colon) with accompanying severe abdominal accompanying severe abdominal cramps, tenesmus and frequent, low-cramps, tenesmus and frequent, low-volume stools containing blood, mucus volume stools containing blood, mucus and fecal leukocytes.and fecal leukocytes.

Shigella causes abdominal pain Shigella causes abdominal pain (Intestinal cramps) and bloody (Intestinal cramps) and bloody diarrhea ± sudden fever, diarrhea ± sudden fever, headache and occasionally neck headache and occasionally neck stiffness. stiffness.

EtiologyEtiology

Gram-negative non-spore forming, Gram-negative non-spore forming, nonmotile bacteria;nonmotile bacteria;

Primarily parasite of the digestive tract Primarily parasite of the digestive tract of humans;of humans;

Infective dose is small;Infective dose is small; Cause a severe form of dysentery Cause a severe form of dysentery

called shigellosis;called shigellosis; Resistant to bile salts;Resistant to bile salts; Discovered by a Japanese scientist K. Discovered by a Japanese scientist K.

Shiga.Shiga.

Four well-defined speciesFour well-defined species

Shigella sonneiShigella sonnei (most common in industrial (most common in industrial world)world)

Shigella flexneri Shigella flexneri (most common in (most common in developing countries)developing countries)

Shigella boydiiShigella boydii Shigella dysenteriae Shigella dysenteriae – produces a more – produces a more

serious disease than the other species.serious disease than the other species.

Shigella dysenteriae produces an Shigella dysenteriae produces an exotoxin (Shiga Toxin) which acts exotoxin (Shiga Toxin) which acts as an enterotoxin, a neurotoxin as an enterotoxin, a neurotoxin (meningismus and coma) and a (meningismus and coma) and a cytotoxin. cytotoxin.

Shiga Toxin is similar to the Shiga Toxin is similar to the Shiga-like toxin of Shiga-like toxin of enterohemorrhagic E. coli (EHEC).enterohemorrhagic E. coli (EHEC).

EpidemiologyEpidemiology

Low infectious dose (10Low infectious dose (1022-10-1044 CFU) CFU)The human intestinal tract represents the The human intestinal tract represents the

major reservoir of Shigella.major reservoir of Shigella.Transmission Transmission – – person to person, person to person,

primarily fecal-oral by contaminated hands.primarily fecal-oral by contaminated hands. Although onsumption of contaminatedAlthough onsumption of contaminated water or food. water or food.

Who is at risk?Who is at risk? – Anyone exposed to carrier, – Anyone exposed to carrier, particularly young children. particularly young children.

In a review of WHO, the total annual In a review of WHO, the total annual number of cases in 1966-1997 wasnumber of cases in 1966-1997 was estimated at 165 million and 69% of theseestimated at 165 million and 69% of these cases occurred in children < 5 years of cases occurred in children < 5 years of age.age.

Shigella is common in developing countries or refugee camps.

Outbreaks of shigellosis are associated with poor sanitation, contaminated food and water, and crowded living conditions.

Pandemics of ShigellosisPandemics of Shigellosis

More recent data (2000-2004) from six More recent data (2000-2004) from six Asian countries (Bangladesh, China, Asian countries (Bangladesh, China, Pakistan, Indonesia, Vietnam and Pakistan, Indonesia, Vietnam and Thailand) indicate that even though the Thailand) indicate that even though the incidence of shigellosis remain stable.incidence of shigellosis remain stable.

Epidemics follow a cyclic pattern in Epidemics follow a cyclic pattern in areas such as the Indian subcontinent areas such as the Indian subcontinent and sub-Saharan Africa.and sub-Saharan Africa.

pathogenesispathogenesis Bacteria shigella are able to invade intestinal Bacteria shigella are able to invade intestinal

epithelial cells. epithelial cells. Shigella attaches to epithelial cell of colon;Shigella attaches to epithelial cell of colon; Shigella triggers phagocytosis;Shigella triggers phagocytosis; Shigella multiplies in cytosol;Shigella multiplies in cytosol; Shigella invades neighboring epithelial cells, Shigella invades neighboring epithelial cells,

thus avoiding immune defenses;thus avoiding immune defenses; An mucosal abscess forms as epithelial cells An mucosal abscess forms as epithelial cells

are killed by the infection;are killed by the infection; Shigella that enters the blood is quickly Shigella that enters the blood is quickly

phagocytized.phagocytized.

pathogenesispathogenesis

Clinical ManifestationsClinical Manifestations Incubation periodIncubation period: : 1-4 days, but may 1-4 days, but may

be as long as 8 days.be as long as 8 days. Watery diarrhea period: Watery diarrhea period:

– Transient feverTransient fever– Watery diarrheaWatery diarrhea– MalaiseMalaise– AnorexiaAnorexia(Unlike most diarrheal syndromes, (Unlike most diarrheal syndromes,

dysenteric syndromes do not have dysenteric syndromes do not have dehydration as a major feature).dehydration as a major feature).

Dysentery period: Dysentery period: – Small volumes of bloody Small volumes of bloody

mucopurulent stools with increased mucopurulent stools with increased tenesmus and abdominal cramps. tenesmus and abdominal cramps.

– At this stage, Shigella produces At this stage, Shigella produces acute colitis involving mainly the acute colitis involving mainly the distal colon and the rectum. distal colon and the rectum.

ComplicationsComplications

Most often in children <5 years of ageMost often in children <5 years of ageIntestinal:Intestinal:Toxic megacolonToxic megacolonIntestinal perforationsIntestinal perforationsRectal prolapseRectal prolapseMetabolic:Metabolic:HypoglycemiaHypoglycemiaHyponatremiaHyponatremiadehydrationdehydration

The postinfectious immunologic complication known The postinfectious immunologic complication known as reactive arthritis (Reiter’s syndrome) can develop as reactive arthritis (Reiter’s syndrome) can develop weeks or months after shigellosis. weeks or months after shigellosis.

About 3% of patients infected with S. flexneri later About 3% of patients infected with S. flexneri later develop Reiter’s syndrome, with arthritis, ocular develop Reiter’s syndrome, with arthritis, ocular inflammation and urethritis – a condition that can last inflammation and urethritis – a condition that can last for months or years and progress to difficult-to-treat for months or years and progress to difficult-to-treat chronic arthritis. chronic arthritis.

Postinfectious arthropathy occurs only after infection Postinfectious arthropathy occurs only after infection with S. flexneri and not after the other Shigella with S. flexneri and not after the other Shigella serotypes.serotypes.

Laboratory DiagnosisLaboratory Diagnosis

The “gold standard” for the The “gold standard” for the diagnosis of Shigella infection is diagnosis of Shigella infection is the isolation and identification of the isolation and identification of the pathogen from fecal material. the pathogen from fecal material.

TreatmentTreatment

Antibiotic treatmentAntibiotic treatment Rehydration and nutritionRehydration and nutrition Non-specific, symptom-based Non-specific, symptom-based

therapytherapy Treatment of complicationsTreatment of complications(Beause of the ready transmissibility of Shigella, (Beause of the ready transmissibility of Shigella,

current public health recommendations in the current public health recommendations in the United States are that every case be treated with United States are that every case be treated with antibiotics).antibiotics).

Antibiotic treatmentAntibiotic treatment

Antimicrobial agent In Children In adults

First lineCiprofloxacin 15mg/kg 2 times per

day for 3 days PO500 mg 2 times per day for 3 days PO

Second line

Ceftriaxon 50-100 mg/kg – Once a day IM for 2-5 days

Azithromycin 6-20 mg/kg Once a day for 1-5 days, PO

1-1,5 g Once a day for 1-5 days, PO