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You are watching: Is shigella bacteria a physical hazard

Baron S, editor. Clinical Microbiology. 4th edition. Galveston (TX): college of Texas medical Branch at Galveston; 1996.


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Clinical Manifestations

Symptoms of shigellosis include abdominal pain, tenesmus, watery diarrhea, and/or dysentery (multiple scanty, bloody, mucoid stools). Other signs may include abdominal muscle tenderness, fever, vomiting, dehydration, and convulsions.


Structure, Classification, and Antigenic Types

Shigellae space Gram-negative, nonmotile, facultatively anaerobic, non-spore-forming rods. Shigella are identified from the carefully related Escherichia coli ~ above the communication of pathogenicity, physiology (failure to ferment lactose or decarboxylate lysine) and also serology. The genus is separated into four serogroups through multiple serotypes: A (S dysenteriae, 12 serotypes); B (S flexneri, 6 serotypes); C (S boydii, 18 serotypes); and also D (S sonnei, 1 serotype).


Pathogenesis

Infection is initiated by sloop down of shigellae (usually via fecal-oral contamination). Very early symptom, diarrhea (possibly elicited by enterotoxins and/or cytotoxin), may occur as the biology pass through the little intestine. The hallmarks of shigellosis are bacterial invasion of the colonic epithelium and also inflammatory colitis. These space interdependent processes magnified by local release the cytokines and also by the infiltration of inflammation elements. Colitis in the rectosigmoid mucosa, v concomitant malabsorption, results in the characteristic authorize of bacillary dysentery: scanty,. Unformed stools tinged through blood and also mucus.


Host Defenses

Inflammation, copious mucus secretion, and regeneration that the damaged colonic epithelium border the spread out of colitis and also promote voluntary recovery. Serotype-specific immune is induced by a main infection, arguing a protective duty of antibody recognizing the lipopolysaccharide (LPS) somatic antigen. Various other Shigella antigens encompass enterotoxins, cytotoxin, and also plasmid-encoded proteins the induce bacterial invasion of the epithelium. The protective function of immune responses versus these antigens is unclear.


Epidemiology

Shigellosis is endemic in developing countries to be sanitation is poor. Frequently 10 to 20 percent of enteric disease, and 50% the the bloody diarrhea or dysentery that young children, have the right to be defined as shigellosis, and also the pervasiveness of this infections decreases considerably after five years the life. In developed countries, single-source, food or water-borne outbreaks occur sporadically, and pockets the endemic shigellosis have the right to be discovered in institutions and also in remote areas with substandard restroom facilities.


Diagnosis

Shigellosis can be appropriately diagnosed in most patients top top the communication of new blood in the stool. Neutrophils in fecal smears is also a strongly suggestive sign. Nonetheless, watery, mucoid diarrhea might be the only symptom of many S sonnei infections, and also any clinical diagnosis need to be shown by growing of the etiologic agent from stools.


Control

Prevention that fecal-oral infection is the many effective manage strategy. Major dysentery is treated v ampicillin, trimethoprim-sulfamethoxazole, or, in patients end 17 year old, a 4-fluorquinolone such as ciprofloxacin. Vaccines are not currently available, yet some promise candidates room being developed.


Introduction

Gram-negative, facultative anaerobes that the genus Shigella are the major agents that bacillary dysentery. This condition differs from profuse watery diarrhea, together is typically seen in choleraic diarrhea or in enterotoxigenic Escherichia coli diarrhea, in the the dysenteric stool is scant and contains blood, mucus, and inflammatory cells. In some individuals suffering native shigellosis, however, center volume diarrhea is a prodrome or the sole manifestation the the infection. Bacillary dysentery constitutes a significant proportion the acute intestinal an illness in the kids of arising countries, and this epidemic is a major contributor come stunted development of this children. Shigellosis likewise presents a significant risk come travelers from occurred countries as soon as visiting in endemic areas, and also sporadic food or water-borne outbreaks happen in arisen countries.

The pathogenic system of shigellosis is complex, including a feasible enterotoxic and/or cytotoxic diarrheal prodrome, cytokine-mediated inflammation the the colon, and necrosis that the colonic epithelium. The underlying physiological insult the initiates this inflammation cascade is the invasion of Shigella right into the colonic epithelium and the lamina propria. The result colitis and ulceration of the mucosa result in bloody, mucoid stools, and/or febrile diarrhea.


Clinical Presentation

Shigellosis has actually two straightforward clinical presentations: (1) watery diarrhea connected with vomiting and mild to moderate dehydration, and (2) dysentery characterized by a little volume that bloody, mucoid stools, and abdominal muscle pain (cramps and also tenesmus) (Table 22-1). Volunteer challenge studies display that shigellosis have the right to be evoked by one extremely small inoculum (10-100 organisms), and also the time of onset of symptoms is somewhat affected by the dimension of the challenge. The salient allude is the shigellosis is an acute infection v onset of symptoms usually arising within 24–48 hrs of gulp down of the etiologic agent. The median duration of symptom in untreated adult is 7 days, and also the organism may be cultivated from stools because that 30 job or longer.


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The clinical functions of shigellosis room summarized in figure 22-1. Watery diarrhea occurs as a prodrome, or as the sole clinical manifestation, in a majority of patients infected with S sonnei. Diarrhea is frequently a prodome that the dysentery characterizing infection with other types of Shigella. Recently uncovered enterotoxins secreted by S flexneri may add to the diarrheal phase together the etiologic agents traverse the small intestine. However, diarrhea is most common in patients who have actually colitis entailing the transverse colon or cecum. This patients proof net water secretion and impaired absorption in the inflamed colon. In patients suffering dysentery, authorized is many severe in the distal colon, and the resulting inflammatory colitis is evidenced in frequent scanty stools showing the ileocecal liquid flow. Dysentery is also characterized by the everyday loss the 200–300 ml that serum protein right into the feces. This ns of serum proteins outcomes in depletion of nitrogen stores that exacerbates malnutrition and growth stunting. Depletion of immune factors additionally increases the danger of concurrent, unrelated infectious an illness and contributes to considerable mortality.


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Possible complications of shigellosis include bacteremia, convulsions and other neurological complications, reactive arthritis, and hemolytic-uremic syndrome. Bacteremia occasionally accompanies S dysenteriae serotype 1 epidemic in malnourished infants, however this complication is uncommon in otherwise healthy and balanced individuals. Convulsions have actually been reported in up to 25% that Shigella infections involving youngsters under the period of 4 years. Both high fever and a family history of seizures room risk determinants for a convulsive episode. Ekiri syndrome, an extremely rare, deadly encephalopathy has also been described in Japanese youngsters with S sonnei or S flexneri infections. Reactive arthritis, a self-limiting sequela the S flexneri infection, wake up in an incidence as high together 2% in individuals expressing the HLA-B27 histocompatibility antigen. Hemolytic-uremic syndrome, characterized by a triad the microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, is a rare complication in children infected through S dysenteriae serotype 1.


Structure, Classification, and also Antigenic Types

Organisms of the genus Shigella belong come the tribe Escherichia in the family members Enterobacteriaceae. In DNA hybridization studies, Escherichia coli and Shigella species cannot be differentiated on the polynucleotide level; however, the virulence phenotype of the latter varieties is a distinctive distinguishing feature. Enteroinvasive E coli (EIEC), are very comparable to shigellae biochemically and they also evoke diarrhea and/or dysentery. Part EIEC are also serologically pertained to shigellae. Because that example, EIEC serotype O124 agglutinates in S dysenteriae serotype 3 antiserum.

The genus Shigella is distinguished into 4 species: S dysenteriae (serogroup A, consists of 12 serotypes); S flexneri (serogroup B, consists of 6 serotypes); S. Boydii (serogroup C, consisting of 18 serotypes); and S sonnei (serogroup D, consist of of a single serotype). Serogoups A, B, and C are very similar physiologically when S. Sonnei deserve to be identified from the other serogroups by confident β-D-galactosidase and ornithine decarboxylase biochemical reactions. The identification of shigellae by species in the clinical activities is usually accomplished by slide agglutination using commercially available, soaked up rabbit antisera.


Pathology

The rectosigmoidal lesions of shigellosis resemble those the ulcerative colitis. With frequencies suggested in number 22-2, over there is proximal extension of erythema, edema, ns of vascular pattern, focal distance hemorrhage, and adherent class of purulent exudate. Biopsy specimens from impacted areas are generally edematous, with capillary congestion, focal length hemorrhage, crypt hyperplasia, goblet cell depletion, mononuclear and also polymorphonuclear (PMN) cell infiltration, shedding of epithelial cells and erythrocytes, and microulcerations.


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The pathogenic system that underlies this pathological manifestations is diagrammed in number 22-3. This cartoon incorporates speculative observations from tissue cultures and also from pet models that shigellosis such together rabbit ligated ileal loops injected with virulent organisms. In the last model, Shigella epidemic is initiated at the membranous (M) cells that are associated with macroscopic lymphoid follicles (Peyer"s patches). Biopsy studies in rhesus monkeys suggest the shigellae likewise infect microscopic lymphoid follicles the the primate colon. During the at an early stage stages that infection, bacteria are transcytosed through the M cells right into the subepithelial space. In the subepithelial space, the organisms room phagocytosed by residents macrophages. However, virulent shigellae space not killed and digested in the macrophage phagolysome. The bacteria lyse the phagosome and initiate apoptosis (programmed cabinet death). During this process, the infected macrophage publication the inflammation cytokine IL-1, i m sorry elicits infiltration that PMN.


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Figure 22-3

Histopathology of acute colitis complying with peroral infection through shigellae. The organisms are initially ingested by membranous (M) cells that are associated with lymphoid microfollicles in the colon. ~ transcytosis through the M cell, the bacteria (more...)


Transmigration of infiltrating PMNs with the chop junctions of neighborhood epithelial cells and into the minister lumen enables the turning back migration that shigellae from the lumen into the subepithelial spaces. This organisms then infect the columnar epithelial cells by inducing endocytic uptake at the basolateral surface. Immediately after infection of enterocytes, intracellular shigellae lyse endocytic vacuoles and attach to the actin cytoskeleton in the area the the junctional complex. As these organisms multiply within the enterocyte cytoplasm, sometimes daughter cells induce polar nucleation of filamentous actin resulting in a “tail” that propels the shigellae into protrusions impinging top top contiguous enterocytes. Plasma membrane enveloping the organisms are again lysed, and the organisms space deposited in ~ the contiguous organize cell bring about intercellular bacterial spread.

In summary, shigellosis deserve to be identified as one acute inflammatory bowel condition initiated through the uptake of just a few organisms right into lymphoid follicles. Intracellular replication and intercellular spread leads come an enhanced inflammatory cascade in ~ the initial website of entry, and as this inflammation persists and expands, the infiltration of PMN facilitates the entry of added bacteria right into the epithelium. The inflammatory infiltrate can also cause detachment of sheets that epithelial cells in locations devoid the lymphoid structures or bacter cells.


Genetics the Virulence

Shigella room exquisitely adapted for reproduction within the colonic epithelium the the person host. Plenty of of the bacter virulence factors that mediate the complex interactions between these bacteria and mammalian host cells have actually been figured out by genetic and also immunological means. This virulence factors are encoded by large extra-chromosomal aspects (plasmids) that are functionally the same in every Shigella varieties and in EIEC. A complex of two plasmid-encoded determinants, designated intrusion Plasmid Antigens (Ipa) B and also C, is recognized by antibody in the sera of convalescent patients. Ipa proteins are maximally express in conditions approximating the minister lumen (e.g., bile salts, high osmolarity, and human body temperature), and release that the IpaBC complicated is motivated by call with the mammalian hold cell. This complicated induces the endocytic uptake of shigellae by M cells, epithelial cells, and also macrophages. IpaB likewise mediates lysis of endocytic secret in epithelial cells or macrophages. In the last case, Ipa proteins likewise cause release of the IL-1 cytokine and macrophage apoptosis. Another plasmid-encoded virulence determinant is secreted at the poles of Shigella daughter cells as these organisms multiply within the cytoplasm the infected hold cells. This InterCellular spread (IcsA) protein elicits polymerization of filamentous actin. Formation of this actin tail provides a motive force for shigellae impinging ~ above the plasma membrane of the infected cell. The result protrusions deform the plasma membrane that contiguous cells. The IcsB plasmid-encoded protein climate lyses the plasma membranes, causing intercellular bacterial spread. Biochemical characterization the the interaction between these Shigella virulence determinants and also host cell contents is a remaining research challenge. Characterizing and enhancing the neutralizing potential the antibody recognizing this protein virulence determinants is also critical research goal.


Toxins

Spent tool from S flexneri or EIEC societies elicits fluid build-up in rabbit ligated ileal loops and ion secretion in diverted ileal tissue. Making use of these assays, enterotoxins designated ShET1 and also ShET2 have been identified, and also the genetic loci encoding these toxins have been localized to the chromosome and plasmid, respectively. ShET1 is neutralized by convalescent sera native volunteers tested with S flexneri 2a, saying that this toxic moiety is express by shigellae growing in the human intestine. The ShET1 locus is existing on the chromosome that S flexneri2a, but it is just occasionally discovered in other serotypes. In contrast, ShET2 is much more widespread and also detectable in 80% that shigellae representing all four species. This enterotoxins might elicit the diarrheal prodrome that often precedes bacillary dysentery; however, their function in the disease process continues to be to be identified by controlled challenge studies using toxin-negative mutants.

S dysenteriae serotype 1 expresses Shiga toxin, really potent, ricin-like, cytotoxin that inhibits protein synthesis in at risk mammalian cells. This toxin additionally has enterotoxic activity in hare ileal loops, yet its duty in human diarrhea is unclear, because shigellae reportedly express a variety of enterotoxins. Experimental infection that rhesus monkeys with S dysenteriae 1, and with a Shiga toxin-negative mutant, suggests that this cytotoxin causes capillary destruction and also focal hemorrhage that exacerbates dysentery (see Table 22-1). More importantly, Shiga toxin is connected with the hemolytic-uremic syndrome, a complication of infections through S dysenteriae 1. Closely related toxins are expressed by enterohemorrhagic E coli (EHEC) including the perhaps lethal, food-borne O157-H7 serotype.


Host Defense

Shigellae room remarkably contagious enteric pathogenes that have the right to cause condition after the ingestion of as couple of as 10 organisms. Nonetheless, shigellosis is normally an acute, self-limiting disease that illustration the regenerative volume of the minister epithelium. Shigella virulence most likely reflects both the effective uptake by the follicle linked epithelium (M cells) and also the amplifying impact of the inflammatory cascade created by apoptic macrophages. Tenesmus and evacuation of mucus by intestinal goblet cell may efficiently eliminate both extracellular shigellae and infected enterocytes from the minister lumen, but this protective response, in conjunction v PMN infiltration, additionally constitutes the definitive sign of bacillary dysentery.

In endemic areas, shigellosis is essentially a childhood disease, and the incidence decreases drastically in the indigenous populace over 5 years of age. Controlled volunteer an obstacle studies in phibìc American adults also indicate the prior infection with S flexneri protects against reinfection through the homologous serotype (70% efficacy). Serotype-specific immune protection versus shigellosis says that antibody recognizing the O-polysaccharide of LPS protects versus clinical symptoms. Ingested bovine colostrum comprise antibody recognizing the O-polysaccharide that S flexneri 2a passively protects volunteers challenged with the homologous Shigella serotype. These observations have motivated the advancement of a number of parenteral and also mucosally administered O-polysaccharide vaccines that are right now in safety and/or efficacy trials. These vaccines market the opportunity of effective control of shigellosis elevation of the needed renovations in the public wellness infrastructure of developing countries, however licensure and delivery of handy Shigella vaccines stays a remote prospect.


Epidemiology

Humans space the main reservoir that Shigella species, with captive subhuman primates together accidental hosts. In arising countries through prevailing conditions of poor sanitation and also overcrowded housing, the infection istransfer most often by the excreta the infected individuals via direct fecal-oral contamination. Paris may contribute to spread from feces come food. The most common species, S dysenteriae and S flexneri, are also the many virulent. In emerged countries, thin common-source outbreaks, predominantly including S sonnei, space transmitted by uncooked food or contaminated water. The latter outbreaks generally involve semipublic water systems such together those discovered in camps, trailer parks, and Indian reservations. Straight fecal-oral spread can likewise occur in institutional atmospheres such as boy day-care centers. Mental hospitals, and also nursing homes. Homosexual men are likewise at boosted risk for direct transmission of Shigella flexneri infections, and also chronic, recrudescent illness complicating HIV infection has been reported.


Clinical

Patients presenting through watery diarrhea and fever have to be suspected of having actually shigellosis. The diarrheal stage of the epidemic cannot be distinguished clinically from various other bacterial, viral, and protozoan infections. Nausea and also vomiting deserve to accompany Shigella diarrhea, yet these symptom are additionally observed throughout infections through nontyphoidal salmonellae and also enterotoxigenic E coli. Bloody, mucoid stools are very indicative of shigellosis, but the differential diagnosis should incorporate EIEC, Salmonella enteritidis, Yersinia enterocolitica, Campylobacter species, and Entamoeba histolytica. Although blood is typical in the stools that patients v amebiasis, that is usually dark brown rather than bright red, together in Shigella infections. Microscopic examination the stool smears indigenous patients v amebiasis should reveal erythrophagocytic trophozoites in the absence of PMN, conversely, bacillary dysentery is defined by sheets the PMN. Sigmoidoscopic examination of a shigellosis patient reveals a diffusely erythematous mucosal surface with tiny ulcers, vice versa, amebiasis is defined by discrete ulcers in the lack of generalised inflammation.


Laboratory

Although clinical indicators may evoke the skepticism of shigellosis, diagnosis is dependent ~ above the isolation and also identification the Shigella native the feces. Positive cultures are many often acquired from blood-tinged plugs of rubber in fresh passed stool specimens obtained during the acute phase of disease. Rectal swabs may also be provided to culture shigellae if the specimen is processed rapidly or is deposited in a buffered glycerol saline stop solution. Isolation the shigellae in the clinical laboratory generally involves an initial streaking for isolation ~ above differential/selective media through aerobic incubation come inhibit the development of the anaerobic regular flora. Frequently used major isolation media encompass MacConkey, Hektoen Enteric Agar, and Salmonella-Shigella (SS) Agar. These media save on computer bile salts to inhibit the development of other Gram-negative bacteria and also pH indications to identify lactose fermenters (Coliforms) from non-lactose fermenters such as shigellae. A liquid enrichment tool (Hajna Gram-negative broth) may also be inoculated with the stool specimen and subcultured ~ above the selective/differential agarose media after a short growth period. Complying with overnight incubation of major isolation media at 37° C, colorless, non-lactose-fermenting swarms are streaked and also stabbed right into tubed slants that Kligler"s steel Agar or Triple sugar Iron Agar. In this differential media, Shigella species produce one alkaline slant and also an mountain butt through no balloon of gas in the agar. This reaction provides a presumptive identification, and slide agglutination tests v antisera because that serogroup and serotype check the identification.

Some E coli biotypes the the typical intestinal flora closely resemble Shigella types (i.e. They room nonmotile, delayed lactose fermenters). These coliforms can usually be distinguished from shigellae by the ability to decarboxylate lysine. However, some coliforms cause enteroinvasive an illness because they carry the Shigella-like virulence plasmid, and also these pathogens are conventionally identified by productive serological screening for EIEC serotypes. Sensitive and also rapid methodology for identification the both EIEC and Shigella types utilizes DNA probes that hybridize with typical virulence plasmid genes or DNA primers that amplify plasmid genes by polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) making use of antiserum or monoclonal antibody recognizing Ipa proteins can additionally be offered to display screen stools because that enteroinvasive pathogens. These experimental diagnostic techniques are helpful for epidemiological researches of enteroinvasive infections, but they are more than likely too devoted for regimen use in the clinical laboratory.


Treatment

Although serious dehydration is uncommon in shigellosis, the an initial consideration in treating any kind of diarrheal condition is correction of abnormalities that result from isotonic dehydration, metabolic acidosis, and significant potassium loss. The oral rehydration treatment emerged by the civilization Health Organization has proven effective and safe in the treatment of acute diarrhea, detailed that the patient is not vomiting or in shock from severe dehydration. In the latter case, intravenous liquid replacement is forced until early fluid and electrolyte losses space corrected. With proper hydration, shigellosis is usually a self-limiting disease, and also the decision to prescribe antibiotics is predicated ~ above the severity that disease, the period of the patient, and also the likelihood of more transmission of the infection. Effective antibiotic treatment reduces the median duration of illness from approximately 5–7 days to roughly 3 work and likewise reduces the duration of Shigella excretion after symptom subside. Absorbable drugs such together ampicillin (2 g/day because that 5 days) are likely to be reliable when the isolation is sensitive. Trimethoprim (8 mg/kg/day) and also sulfamethoxazole (40 mg/kg/day) will certainly eradicate perceptible organisms quickly from the intestine, yet resistance to this certified dealer is increasing. Ciprofloxacin (1 g/day for 3 days) is effective versus multiple drug resistant strains, but this antibiotic is no approved through the United claims Food and Drug administration for use in children less than 17 year of age due to the fact that there is a theoretical danger of cartilage damage. Opiates, such as paregoric, induce intestinal stasis and may promote bacter invasion, expanding the febrile state.


Control

As is the case with other intestinal infections, the most effective methods for regulating shigellosis are provision that safe and abundant water and effective feces disposal. These public health and wellness measures are, in ~ best, long range strategies for manage of enteric infections in occurring countries. The approximated five million deaths each year attributed come diarrheal an illness in this countries, in enhancement to the malabsorption and also growth stunting amongst survivors, require more immediate and also practical approaches. The most efficient intervention strategy to minimize morbidity and also mortality would involve an extensive media and personal outreach program consisting of the complying with components: (1) education of all citizens to proactively avoid fecal contamination of food and water and also to encourage hand washing ~ defecation; (2) encourage mother to breast-feed infants; (3) promote the use of dental rehydration therapy to offset the effects of acute diarrhea; (4) encourage mother to administer convalescent nutritional care in the form of extra food for kids recovering native diarrhea or dysentery.

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Keusch, GT, Bennish ML: Shigellosis. P. 593. In Evans A S, Brachman PS (ed): bacterial Infections that Humans, Epidemiology and also Control. Plenum, new York, 1991.