Shigella infection

Shigellosis is caused by the bacteria group Shigella. Of the 4 species in the US and the UK, Shigella sonnei and S flexneri account for most reported cases.[2][5] Shigella species can survive in stomach acid, and therefore infection may be caused by as few as 10 to 100 organisms.[8] Transmission by direct fecal-oral contact occurs frequently because the organisms do not have to multiply in order to achieve a larger inoculating dose. Transmission also occurs via contaminated water and food. S dysenteriae produces Shiga toxin, which may cause hemolytic uremic syndrome (HUS).[9] The other species also produce enterotoxins, but these are not associated with severe illness.

Travelers to low- and middle-income countries who contract shigellosis may be infected with serotypes that are more antibiotic-resistant compared with strains acquired in resource-rich areas, which often leads to more widespread and prolonged outbreaks.[10]

Most studies describing pathophysiology relate to Shigella flexneri. Once in the small bowel, Shigella organisms multiply and many bacteria reach the colon. They enter the colonic mucosa via microfold (M) cells by inducing micropinocytosis, where the cell membrane invaginates around the bacterium, forming a vacuole that is released into the cytoplasm.[8][11][12] The bacterium is then able to lyse the vacuole, escape into the cytoplasm, and multiply further. Bacteria use host cell actin to propel themselves around the cytoplasm. Once inside the intraepithelial space, bacteria are taken up by macrophages. The bacteria then induce apoptosis of the macrophages, spilling out and causing an inflammatory reaction due to released proinflammatory cytokines. The cytokines attract natural killer (NK) cells and polymorphonuclear neutrophils, which destroy the epithelial cells lining the gut mucosa, allowing further direct invasion by Shigella. The Shigella bacteria emanating from apoptosed macrophages are able to directly invade adjacent epithelial cells from the basolateral side and then spread to adjacent cells. The result is infectious diarrhea with loss of water and solutes, associated with abdominal cramps, fever, and the loss of blood and mucus in the stools.

All species of Shigella produce enterotoxins. These are known to induce secretion of salt and water by the intestinal mucosa. S dysenteriae type 1 produces a potent toxin called the Shiga toxin, which is associated with the development of HUS.[9] Enterohemorrhagic Escherichia coli (strain O157) can produce a similar Shiga-like toxin, which also can cause HUS. Shiga toxin causes damage to endothelial cells, leading to a thrombotic microangiopathy and hemolysis. HUS associated with S dysenteriae is often more severe than that associated with enterohemorrhagic E coli (strain O157), probably due to the enteroinvasive nature of Shigella, and because shigellosis tends to occur in more deprived areas where there is a higher at-risk population of malnourished children who have comorbidities.

Classification by serogroup

Shigella dysenteriae (serogroup A)[4][5]

Commonly seen in low- and middle-income countries
Causes a more severe illness
Produces Shiga toxin, which damages vascular endothelium and causes HUS
15 serotypes recognized.

S flexneri (serogroup B)[2][5]

Second most common cause of shigellosis cases in the US
Similar to S dysenteriae in that it causes a more severe illness
8 serotypes recognized.

S boydii (serogroup C)[5]

Less severe illness and similar to S sonnei
20 serotypes recognized.

S sonnei (serogroup D)[2][5]

Causes a less severe illness
Most common cause of shigellosis cases in the US and the UK
1 serotype recognized.

Etiology

Pathophysiology

Classification

Classification by serogroup