Shigella (Shigellosis)

Article Author:
Aysha Aslam
Article Editor:
Chika Okafor
Updated:
4/21/2019 11:03:43 AM
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Shigella (Shigellosis)

Introduction

Shigellosis is a form of bacterial diarrhea caused by gram-negative bacteria Shigella species. It is common in developing countries and results from contaminated food, poor sanitation conditions, or direct person to person contact. It can result in all age groups, but high-risk groups include very young, elderly, and immunocompromised person. Shigella species is relatively resistant to acid in the stomach, and few organisms are required to cause the disease.[1] Once ingested, it multiplies in the small intestine and enters the colon. In the colon, it produces shigella enterotoxins and serotype toxin 1, resulting in watery or bloody diarrhea. Clinical manifestations usually result within 12 hours to 3 days of ingestion of the organism with an averange incubation period of 3 days. These symptoms include high fever, vomiting, diffuse colicky abdominal pain followed by bloody mucoid diarrhea and tenesmus.[2][3][4][5] It self-resolves within 5 to 7 days of onset of symptoms. However, high-risk individuals may end up in complications.

Etiology

Shigellosis is a food-borne or water-borne illness caused by Shigella. Shigella is a gram-negative, nonmotile, facultatively anaerobic, non-spore-forming rod. It has 4 serotypes:

  • Serotype A: Shigella dysenteriae (12 serotypes)
  • Serotype B: Shigella flexneri (6 serotypes)
  • Serotype C: Shigella boydii (23 serotypes)
  • Serotype D: Shigella soneii (1 serotypes)

 Shigella sonnei is different from the other serotypes by the expression of ornithine decarboxylase while serotypes A, B and C cannot be differentiated with any biochemical marker.

Epidemiology

Incidence

The incidence of shigellosis is reported to be One hundred eighty-eight million cases per year with approximately 1 million deaths annually.[6] In developed countries, the incidence is around 1.5 million cases per year. In the United States, it results in about 450,000 cases annually. The majority of cases reported in the United States are caused by S. sonnei (77%). The serotype responsible for mainly causing disease in developing countries is S. flexneri). It is more common in young children with the majority of cases reported in children (28 cases/100,000 in children younger than 4 years and 25 cases/100,000 in 4 to 11-year-olds). There is no gender predominance for shigellosis. There is no racial predilection for shigellosis.

Pathophysiology

Route of Transmission

The path of transmission of shigellosis is mostly water-borne or food-borne. However, it can also be transmitted sexually or by flies.

Size of Innoculum

The number of organisms required to cause the disease is usually 10 to 200 due to the low sensitivity to stomach acid and downregulation of antibacterial proteins of the host by the organism.

Pathogenesis

Once ingested, it enters the small intestine and multiplies there and enters large intestine. Shigella causes cell injury and resulting manifestation by 2 mechanisms: Direct invasion and production of enterotoxins.

Direct Invasion of Epithelial Cells

In the large intestine, it invades using transcytosis and transports through basolateral epithelium using M cells which are mainly responsible for immune activation of intestinal lymphoid tissue by antigen recognition. Following transcytosis, it induces macrophages and induces cellular apoptosis. This results in the release of inflammatory cytokines such as IL-1 and IL-18 which results in intestinal inflammation and subsequent activation of the innate immune system. Shigella is released from the macrophages after following apoptosis and inflammation. It continues to invade the adjacent epithelium and invades the immune system by using intercellular actin polymerization process. As it invades the epithelial cells, it activates nuclear factor (kappa B) in the cells causing the production of IL-8 which stimulates recruitment of neutrophils at the site causing more inflammation and epithelial damage. It causes impaired absorption of nutrients causing diarrhea.

Toxin production

Another mechanism for cell injury by Shigella is through the production of enterotoxin 1 and 2 which play a part in impaired fluid and nutrient absorption causing Shigella-associated diarrhea. Cytotoxin Shigella dysenteriae serotype 1 is responsible for cytotoxicity and vascular lesions in the colon and other organs such as kidneys causing bloody diarrhea and complications such as hemolytic uremic syndrome (HUS).

Histopathology

Microscopic examination of the infected tissue such as colon, rectum, or distal ileum may result in following findings: PMN infiltration of the epithelial cells, and the formation of inflammatory patch pseudomembranes.

History and Physical

Common symptoms may include mild abdominal discomfort to severe diffuse colicky abdominal pain (70% to 90%). Patient reports of small volume mucoid diarrhea (70% to 80%) that precedes bloody diarrhea (30% to 50%). Other symptoms include fever, nausea, vomiting, anorexia, lethargy, and tenesmus. Rare but severe symptoms include delirium, obtundation, anuria, seizures, meningismus, and coma.

Physical examination of patients suffering from shigellosis may indicate lethargic or toxic individual. Vital signs may reveal fever, tachycardia, tachypnea, and hypotension. Abdominal examination may show distended abdomen with hyperactive bowel sounds. Tenderness may be present especially in the lower abdomen due to the involvement of sigmoid colon and rectum.

Evaluation

Laboratory Evaluation

  • Complete blood count (CBC): Leukocytosis with left shift, leucopenia may also be present. Anemia and thrombocytopenia may also be present.
  • Stool examination: Stool analysis shows fecal leucocytes and blood. Microscopic evidence of stool examination may show evidence of leukocytes in stool smear. A stool culture may also be used which requires multiple cultures and may be positive in early disease. 
  • LFTs: Mild elevation of bilirubin may be possible in severe disease.
  • RFTs: Elevated BUN and creatinine may be present in dehydrated or very young and elderly patients. 
  • Inflammatory markers: May be elevated such as ESR and CRP
  • Blood culture: May be positive in complicated cases having bacteremia
  • Elisa and PCR: May be required in minority of patients. Elisa usually S. dysenteriae type-1 toxin in stool, and PCR may be used to identify the virulent genes of Shigella such as ipaH gene, virF gene, and virA gene.

Treatment / Management

The mainstay of treatment of shigellosis is medical and includes fluid and electrolyte management.

  • Antimotility drugs such as loperamide or diphenoxylate are not recommended for patients with Shigella infection as they may prolong the infection and increase the shedding of the organism.
  • The antibiotic regimen used for the treatment can be divided into two groups based on the age. The antibiotic susceptibility testing is highly recommended before starting the treatment as resistance to the drugs is common and may vary regionally.

The preferred drug treatment for adults is a ciprofloxacin 500 mg twice per day for 5 days. The alternative regimen includes pivmecillinam 100 mg once per day for 5 days or azithromycin 1 to 1.5 gm by mouth for 3 days.

In pediatrics, the preferred drug is ciprofloxacin 15 mg/kg by mouth twice per day bid for 3 days. The alternative regimen includes pivmecillinam 20 mg/kg by mouth once per day for 5 days or ceftriaxone 20 to 100 mg/kg intramuscularly (IM) every day for 2 to 5 days or azithromycin 6 to 20 mg/kg by mouth every day for 1 to 5 days.

Differential Diagnosis

Differential diagnosis of shigellosis include infection with the following organisms due to overlapping symptoms of fever, nausea, vomiting and abdominal pain:

  • Salmonella
  • Escherichia coli infection
  • Campylobacter infection
  • Clostridium difficile
  • Typhoid fever
  • Entamoeba histolytica
  • Aeromonas

Other diseases causing chronic diarrhea which might be differentiated include:

  • Crohn disease
  • VIPoma
  • Hyperthyroidism
  • Lactose intolerance
  • Celiac disease 
  • Irritable bowel syndrome

Prognosis

If diagnosed and treated on time, the prognosis of shigellosis is good, and patients recover without sequelae. However, certain poor prognostic factors include a delay in treatment and development of complications, immunocompromised, prolonged duration of disease (more than 7 days), and extremes of age such as elderly and very young individuals.

Pearls and Other Issues

There is no vaccine to prevent shigellosis. However, the disease can be limited by practicing certain precautions:

  • Frequent and careful handwashing with soap
  • Supervised handwashing of children in day care centers and homes with children who are not completely toilet trained
  • People with shigellosis should not handle food and water for others unless they are disease free
  • Children who wear diapers and have the disease, precautions are required in handling the diapers and their disposal
  • While traveling to developing countries, drink only boiled or treated water and avoid eating raw poorly handled food from the vendors
  • Avoid sexual contact with a patient having diarrhea or recently recovered from diarrhea. Practice safe sex.

Enhancing Healthcare Team Outcomes

The diagnosis of shigellosis often takes time and the infection can be confused with many other abdominal conditions. Thus, it is best managed by a multidisciplinary team that includes the emergency department physician, infectious disease consult, gastroenterologist and internist. The mainstay of treatment of shigellosis is medical and includes fluid and electrolyte management. The antibiotic regimen used for the treatment can be divided into two groups based on the age. The antibiotic susceptibility testing is highly recommended before starting the treatment as resistance to the drugs is common and may vary regionally.

Because there is no vaccine to ptevent the infection, the primary care provide and nurse specialist play a vital role in educating the public about prevention. This includes hand washing, maintaining personal hygiene, drinking boiled water while traveling and avoiding sexual contact with a patient with a recent diagnosis of shigellosis.[7][8]

The outlook for patients who are treated promptly is good but delays in treatment can lead to multiorgan failure and even death.[9]


References

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[2] Epidemiologic and clinical features of patients infected with Shigella who attended a diarrheal disease hospital in Bangladesh., Stoll BJ,Glass RI,Huq MI,Khan MU,Banu H,Holt J,, The Journal of infectious diseases, 1982 Aug     [PubMed PMID: 7108270]
[3] Barrett-Connor E,Connor JD, Extraintestinal manifestations of shigellosis. The American journal of gastroenterology. 1970 Mar;     [PubMed PMID: 5435635]
[4] Microbiology and diagnosis of infections with Shigella and enteroinvasive Escherichia coli., Echeverria P,Sethabutr O,Pitarangsi C,, Reviews of infectious diseases, 1991 Mar-Apr     [PubMed PMID: 2047641]
[5] Gastrointestinal and extra-intestinal manifestations of childhood shigellosis in a region where all four species of Shigella are endemic., Khan WA,Griffiths JK,Bennish ML,, PloS one, 2013     [PubMed PMID: 23691156]
[6] Kotloff KL,Riddle MS,Platts-Mills JA,Pavlinac P,Zaidi AKM, Shigellosis. Lancet (London, England). 2018 Feb 24;     [PubMed PMID: 29254859]
[7] Wilmer A,Romney MG,Gustafson R,Sandhu J,Chu T,Ng C,Hoang L,Champagne S,Hull MW, Shigella flexneri serotype 1 infections in men who have sex with men in Vancouver, Canada. HIV medicine. 2015 Mar;     [PubMed PMID: 25656740]
[8] Das JK,Tripathi A,Ali A,Hassan A,Dojosoeandy C,Bhutta ZA, Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC and rotavirus. BMC public health. 2013;     [PubMed PMID: 24564510]
[9] Baker KS,Dallman TJ,Field N,Childs T,Mitchell H,Day M,Weill FX,Lefèvre S,Tourdjman M,Hughes G,Jenkins C,Thomson N, Horizontal antimicrobial resistance transfer drives epidemics of multiple Shigella species. Nature communications. 2018 Apr 13;     [PubMed PMID: 29654279]