Shigellosis overview

# Overview
Shigellosis is a common foodborne or waterborne infectious illness caused by Shigella species, a gram-negative, non-motile, facultatively anaerobic, non-spore-forming rod. Shigella was first discovered by Dr. Kiyoshi Shiga following a bacillary dysentery outbreak in Japan in 1896. It is commonly spread by the fecal-oral route in regions of poor sanitation. Although individuals of all age groups may acquire shigellosis, high risk patients include young children, elderly patients, and immunocompromised patients. Clinical manifestations typically include diffuse, colicky abdominal pain, fever, and mucoid/bloody diarrhea that develop as early as 12 hours to 3 days following ingestion of Shigella and typically self-resolve within 5 to 7 days of symptom onset. If left untreated, the majority of patients recover spontaneously, but intestinal and systemic complications, such as post-infectious arthritis (Reiter's syndrome) or hemolytic uremic syndrome (HUS), may develop in a few individuals. Individuals with suspected infection should undergo blood and stool work-up for appropriate diagnosis and choice of antimicrobial agents. The cornerstones of the treatment of shigellosis are fluid and salt replacement and antibiotic therapy. Antibiotic therapy is recommended among all patients and usually consists of a 3 day course of trimethoprim/sulfamethoxazole or ciprofloxacin in patients with a documented resistant strain. Although there is currently no vaccine for shigellosis, primary prevention consists of proper hand hygiene, as well as safe food and water practices.

# Historical Perspective
Shigella was first discovered by Dr. Kiyoshi Shiga following a bacillary dysentery outbreak in Japan in 1896. Since then, several outbreaks have occurred.

# Pathophysiology
A small inoculum of Shigella (10 to 200 organisms) is sufficient to cause shigellosis. Shigella is commonly spread by the fecal-oral route in regions of poor sanitation (foodborne or waterborne transmission). Shigella first invades the epithelial cells of the large intestine by using M cells as entry ports for transcytosis. Shigella then invades macrophages and induces cellular apoptosis, which results in inflammation, generation of proinflammatory cytokines, and recruitment of polymorphonuclear neutrophils (PMNs). Following transcytosis and macrophage apoptosis, Shigella avoids extracellular exposure and spreads intercellularly using actin polymerization processes (rocket propulsion). As PMNs invade the site of active inflammation, the integrity of the intestinal epithelial barrier is lost, and adsorption of fluids and nutrients is impaired, resulting in clinical manifestations of shigellosis (e.g. diarrhea). On gross pathology, hyperemia with development of ulcers and edema are typical findings. On microscopic pathology, infiltration of PMNs and inflammatory pseudomembranes are characteristic features.

# Classification
Shigella species are classified into four serogroups: Shigella dysenteriae, Shigella flexneri, Shigella boydii, and Shigella sonnei.

# Causes
Shigellosis is usually a foodborne or waterborne illness caused by an infection with Shigella species. Shigella is a gram-negative, non-motile, facultatively anaerobic, non-spore-forming rod.

# Differential Diagnosis
Shigellosis must be differentiated from other diseases that cause fever, bloody diarrhea, dehydration, tachycardia and low blood pressure, such as Enterohemorrhagic E.coli (EHEC) infection, Ebola, Typhoid fever, Malaria, and Lassa fever.

# Epidemiology and Demographics
Although individuals of all age groups may acquire shigellosis, the majority of affected individuals are children between the age of 2 to 5. There is no gender or racial predominance of shigellosis. More than 160 million cases are reported annually, of which more than 95% are reported in the developing countries. Shigella sonnei accounts for the majority of shigellosis cases in the developed (industrialized) countries, while Shigella flexneri accounts for the majority of shigellosis cases in the developing countries.

# Risk Factors
All individuals are at risk of developing shigellosis. Individuals at high risk of developing shigellosis or complications of shigellosis are young children between the age of 2 to 5, elderly individuals, and individuals who engage in anal sexual intercourse, HIV-positive individuals, and travelers to developing countries in regions of poor sanitation.

# Natural History, Complications and Prognosis
Clinical manifestations of shigellosis typically develop 12 hours to 3 days following ingestion of Shigella. Patients often first develop colicky, diffuse abdominal pain and fever, followed by diarrhea and tenesmus. If left untreated, shigellosis typically self-resolves within 5 to 7 days of onset of clinical manifestations in the majority of patients. High risk patient populations (young children, elderly, or immunocompromised patients) are at increased risk of developing complications, which may be intestinal or extra-intestinal. Classical complications include post-infectious arthritis (Reiter's syndrome) and hemolytic uremic syndrome (HUS). Prognosis is generally excellent for immunocompetent individuals. Factors that are associated with poorer prognosis include prolonged duration of disease, development of complications, and infection of high risk patients.

# Diagnosis

## History and Symptoms
Symptoms may range from mild abdominal discomfort to severe colicky, diffuse abdominal pain. Patients may initially have small volume watery diarrhea that precedes dysentery. The majority of patients report mucoid diarrhea, and up to 50% of patients report bloody diarrhea. Other common symptoms include fever, nausea and vomiting, and tenesmus.

## Physical Examination
Patients with shigellosis usually appear lethargic. Physical examination of patients with shigellosis is usually remarkable for diffuse abdominal tenderness in more than 70% of cases and fever in approximately 25% to 40% of cases. Less commonly, physical examination is remarkable for signs of dehydration, such as hypotension, tachycardia, and dry mucous membranes.

## Laboratory Findings
The majority of patients with shigellosis have no significant derangements in either blood or stool work-up. Common findings include leukocytosis with left shift on blood examination, and blood and/or mucus in stools on stool examination. Multiple blood and stool cultures are needed to rule out bacteremia and to obtain antibiotic susceptibility testing, but the majority of cases yield negative cultures. Hematology, renal, and liver function testing may be required in some cases to rule out the development of any complications associated with shigellosis, such as severe dehydration, cholestatic liver disease, or hemolytic uremic syndrome (HUS).

## Other Diagnostic Studies
Other diagnostic studies, such as enzyme-linked immunoassay (ELISA), polymerase chain reaction (PCR), or colon/rectal biopsies, are not always necessary but may be required for the diagnosis of shigellosis in the minority of patients, such as high risk patients who are hospitalized and in need of urgent management).

# Treatment

## Medical Therapy
The cornerstones of the treatment of Shigellosis are fluid and salt replacement and antibiotic therapy. For the majority of patients, oral fluid replacement is adequate and should consist of water, glucose, and electrolytes such as sodium, chloride, potassium and bicarbonate. IV fluids should be reserved for patients with severe disease who cannot tolerate oral therapy, and should be tailored to their lab findings. Antimotility agents should be avoided as they prolong the duration of the infection. Antibiotic therapy is recommended among all patients and usually consists of a 3 day course of either ciprofloxacin, azithromycin, or extended-spectrum penicillin antibiotics.

## Primary Prevention
There is no vaccine to prevent shigellosis. Primary prevention consists of proper hand hygiene, as well as safe food and water practices. Special care should be taken when handling diapers as they may be an important source for the spread of Shigella.