Shigella

Named after the Japanese bacteriologist Shiga, who in 1898 proved the causative agent of bacterial dysentery, 2 years before the German Kruse independently succeeded in doing so.

Shigella, the causative agent of shigellosis (shigellosis, shigella dysentery) are immobile (without flagella), sporeless, gram-negative rod-shaped bacteria of the Enterobacteriaceae family, genus Shigella. Shigellae cannot ferment lactose or metabolize citrate or urea. They are relatively acid-stable (so they can survive the passage through the stomach). They are closely related to Escherichia coli. All shigellae produce an endotoxin consisting of lipopolysaccharides, which is responsible for the inflammatory irritation of the intestinal mucosa. Only Shigella dysenteriae 1 additionally forms an exotoxin(Shiga toxin), which can lead to severe clinical pictures with CNS involvement.

Shigellae are divided into the following serogroups, each with several serovars, according to biochemical characteristics and specific O antigens:

• Group A: Shigella dysenteriae: causative agent of the dreaded Shiga-crustacean dysentery, which occurs mostly in tropical regions. There are 13 known serovars.
• Group B: Shigella flexneri: pathogen of Flexner's dysentery which occurs mainly in Central Europe; >10 serovars.
• Group C: Shigella boydii: Occurs in tropical countries; 20 serovars
• Group D: Shigella sonnei: Pathogen of the relatively harmless summer or E dysentery. Occurs in Central Europe. 1 serovar.

Shigella occurs worldwide as a pathogen. All shigellae are human pathogens and cause bacterial dysentery or dysentery. It is a disease of times of emergency and crisis and an epidemic of unhygiene.

The infection shows a characteristic accumulation in warm months. In Germany, infections caused mainly by S. sonnei (currently about 70%) and S. flexneri (currently about 20%) are of importance. These two species predominantly lead to milder diseases, which, however, start highly acutely and can be very infectious.

The pathogens penetrate the intestinal epithelia of the terminal ileum and colon.Shigellae cannot penetrate the enterocytes from the lumen side. They use the M cells of the Peyer's plaques as an invasion portal. From there, they can invade the epithelial cells from behind. From there they migrate from cell to cell. Intracellular arrest leads to damage of the enterocytes and focal necrosis. This ensures the further spread of the infection. Damrulation with hemorrhage and tenesmus are typical features of Shigella infection. The shigatoxin as well as verotoxins have cyto-, entero- and neurotoxic potential. They are also important in other Enterobactericae.

Children and young adults (age group 20-39 years) are frequently affected.

Reservoir: Humans are the only relevant reservoir for Shigella.

Route of infection: Transmission is faecal-oral by contact or smear infection inthe context of close personal contacts, e.g. in kindergarten or in the common household, or by contaminated food, water or utensils. The infectious dose is very small <100 bacteria. Fecal-oral transmission is also possible during sexual contact, for example, oro-anal sexual practices. Shigellosis outbreaks are known to occur among men who have sex with men (MSM). When travelling to countries with lower hygiene standards, direct transmission via drinking water or bathing water contaminated with faeces can be significant. The pathogens can also be transmitted by flies, e.g. from faeces to uncovered food. In Germany, the number of cases is relatively small, at about 400. Of these, only 40% are acquired in Germany (Hof H et al. 2019). The remaining cases are imported.

Incubationperiod: The incubation period is usually 12-96 hours.

Duration of contagiousness: Contagiousness exists during the acute infection and as long as the pathogen is excreted in the stool (about 1-4 weeks after the acute phase of illness). Excretion over a longer period is very rare.

Risk Populations:

• Children < 5 years of age are most likely to be affected by Shigella infection.
• Individuals living in group housing or participating in group activities.
• Living in areas where sanitation is lacking. People who live or travel in developing countries are at higher risk of contracting shigella.
• The majority of shigellosis cases are imported by travelers (about 60-70% of cases - RKI communication). Imported shigellosis is often acquired in Egypt, India and Morocco (communication RKI).
• Men who have sex with men have a higher risk of Shigella infection due to direct or indirect oral-anal contact during sexual activity.

Shigella-Ruhr (A03.9): Oral ingestion is followed by invasion of the colonic mucosa. The disease usually begins as watery diarrhea and may progress to inflammatory colitis. The disease varies between mild courses with minor watery diarrhea and severe disease with fever, bloody and purulent diarrhea. Especially patients with immunosuppression (including HIV) or elderly patients or malnourished children are more often affected by severe to fulminant courses. The occurrence of bloody-mucous stools corresponds to the clinical picture of 'dysentery' (hence the terms "shigella dysentery" or "bacterial dysentery"). Abdominal cramps (colics and tenesmus) are typical of shigellosis. As the disease progresses, focal ulcerations may occur, predominantly in the distal colon. Complications include colonic dilatation and colonic perforations. Other possible sequelae: dehydration and protein loss. Infection is usually confined to the colon. Rare extraintestinal complications include:

Hemolytic uremic syndrome(HUS); caused by shiga toxin (produced mainly by S. dysenteriae serovar 1).

Reiter's syndrome: Reiter's syndrome may develop as an immunopathological secondary disease.

Clinically or clinico-epidemiologically, only a tentative diagnosis can be made. Confirmation of the diagnosis by bacteriological examination. Fresh stool samples or freshly taken rectal swabs in a transport medium are suitable as examination material (Note: Shigella v. S.dysenterica die relatively quickly in the environment. They must be processed quickly!)

The identification of the species and, if necessary, the serovar is the first step in the detection of sources of infection and the clarification of infection routes. At the National Reference Center for Salmonella and other bacterial enteritis pathogens, further pathogen typing can beperformed (e.g., by molecular biological characterization with core genome multilocus sequence typing; cg MLST) (information from the RKI).

Only low levels of antibodies are produced by patients with the disease(absence of the very immunogenic H antigens). Serological tests are therefore not indicated.

Due to the high infectivity and the occasionally very severe course of the disease, antibiotic treatment is generally recommended for shigellosis according to the S2k guideline "Gastrointestinal infections and Whipple's disease". This reduces bacterial excretion and shortens the duration of the disease. Quinolones and azithromycin are the drugs of choice (S2k guideline). Important: Due to the increasing resistance problem in shigella, therapy should be given after resistance testing has been performed. Especially isolates from travelers returning from Asia and Africa and from MSM may show increased resistance.

In patients in good general health, symptomatic therapy with oral fluid replacement may also be sufficient. In patients with underlying chronic diseases and in the very young and elderly, fluid and electrolyte losses must be compensated parenterally. Motility inhibitors should not be used for treatment.

After surviving the dysentery, a moderate immunity exists temporarily. There is currently no vaccine available in Germany. The measures to prevent this infection are of an exposure-prophylactic nature (see below Shigellosis infection prevention and hygiene measures).

Dysentery is an infection of the colon. It can be caused by Shigella (bacteria) or by amoebae (protozoa).

Obligation to report according to IfSG: According to § 7 Abs. 1 IfSG the direct or indirect detection of Shigella sp., as far as it indicates an acute infection, has to be reported by name to the public health department.

Furthermore, according to § 6 para. 1 no. 2 IfSG, the suspicion of and illness from acute infectious gastroenteritis must be reported if the person concerned handles food or is employed in communal catering facilities (e.g. kitchens, restaurants) (see measures for patients and contact persons), or if two or more similar illnesses occur for which an epidemic connection is probable or suspected.

The notifications must be submitted to the public health department no later than 24 hours after they become known. In § 8 IfSG the persons obliged to report are named . In § 9 IfSG is defined what information may contain the notification by name to the health department.

Obligation to notify according to IfSG: According to § 34 Abs. 6 IfSG, managers of community facilities have to notify the responsible public health department immediately if persons cared for in their facility are ill with shigellosis or are suspected of it, if persons cared for in their facility excrete shigella sp. or if, according to medical opinion, an illness with or a suspicion of shigellosis has occurred in the living communities of the persons cared for in their facility.

Transmission: In accordance with § 11 Para. 1 IfSG, the public health department only transmits cases of illness or death and evidence of pathogens to the competent state authority that meet the case definition in accordance with § 11 Para. 2 IfSG.

Shigellosis infection control and hygiene measures see there.

1. DGVS Gi infections guidelines: see below https://www.dgvs.de/wissen/leitlinien/leitlinien-dgvs/gi-infektionen/
2. Hof H et al (2019) Shigella. In: Hof H, Schlüter D, Dörries R, eds Dual series medical microbiology. 7th, completely revised and expanded edition. Stuttgart: Thieme pp 407-410.
3. Raspe M et al (2016) Shigellosis (shigella dysentery, bacterial dysentery). In: Suttorp N, Möckel M, Siegmund B et al, eds Harrison's internal medicine. 19th ed. Berlin: ABW Wissenschaftsverlag; 2016.
4. RKI guidebook - Shigellosis - RKI.
5. RKI: travel-associated infectious diseases 2017. epid bull 2018; 44:469.
6. RKI: Shigellosis: increased incidence in men in Berlin in 2004. epid bull 2005; 8:59-63.