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Shigellosis

Chapter 172 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial

Detailed clinical reference synthesised from Harrison's Principles of Internal Medicine, 22nd Edition

🔑 Key Clinical Points

  1. Shigellosis is defined as a clinical syndrome of fever, intestinal cramps, and frequent passage of small, bloody, mucopurulent stools caused by Shigella species.
  2. The human intestinal tract is the major reservoir of Shigella; excretion is greatest in the acute phase of disease.
  3. High infectivity is reflected by a very small inoculum required for experimental infection (100 colony-forming units [CFU]).
  4. Shigella dysenteriae type 1 produces Shiga toxin, a potent cytotoxin that inhibits protein synthesis by expressing RNA N-glycosidase activity on 28S ribosomal RNA.
  5. Hemolytic-uremic syndrome (HUS) is an early complication most often developing after several days of diarrhea, defined by a diagnostic triad: microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.
  6. Reactive arthritis can develop weeks or months after shigellosis, especially in patients expressing the histocompatibility antigen HLA-B27, and occurs only after infection with S. flexneri.
  7. Antibiotic treatment is recommended for every case due to transmissibility; fluoroquinolones (e.g., ciprofloxacin) are first-line, but resistance rates are high in many regions.
  8. Toxic megacolon is a consequence of severe inflammation extending to the colonic smooth-muscle layer, presenting with abdominal distention and tenderness.
  9. S. flexneri isolates predominate in the least developed areas, whereas S. sonnei is more prevalent in economically emerging countries and the industrialized world.
  10. Recovery without treatment typically takes 1 week; with appropriate treatment, recovery takes place within a few days to a week, with no sequelae.

📑 Table of Contents

📋 Figures in This Chapter

# Type Description
1 🖼 Figure Invasive strategy of Shigella flexneri

1. DEFINITION & OVERVIEW

📖 Harrison's defines this as:

Shigella is a non-spore-forming, gram-negative bacterium that, unlike E. coli, is nonmotile and does not produce gas from sugars, decarboxylate lysine, or hydrolyze arginine.

  • Shigellosis is a clinical syndrome characterized by fever, intestinal cramps, and frequent passage of small, bloody, mucopurulent stools.
  • The discovery of Shigella as the etiologic agent of dysentery is attributed to the Japanese microbiologist Kiyoshi Shiga, who isolated the Shiga bacillus (now known as Shigella dysenteriae type 1) from patients' stools in 1897 during a large and devastating dysentery epidemic.
  • Shigella cannot be distinguished from Escherichia coli by genome comparison and remains a separate species only on historical and clinical grounds.
  • Some serovars produce indole, and occasional strains utilize sodium acetate.
  • Shigella dysenteriae, Shigella flexneri, Shigella boydii, and Shigella sonnei (serogroups A, B, C, and D, respectively) can be differentiated on the basis of biochemical and serologic characteristics.
  • Genome sequencing of E. coli K12, S. flexneri 2a, S. sonnei, S. dysenteriae type 1, and S. boydii has revealed that these species have ~93% of genes in common.
  • The three major genomic 'signatures' of Shigella are (1) a 215-kb virulence plasmid that carries most of the genes required for pathogenicity (particularly invasive capacity); (2) the lack or alteration of genetic sequences encoding products (e.g., lysine decarboxylase) that, if expressed, would attenuate pathogenicity; and (3) in S. dysenteriae type 1, the presence of genes encoding Shiga toxin, a potent cytotoxin.

1.1 Historical Context

  • The annual number of cases in 1966–1997 was estimated at 165 million, and 69% of these cases occurred in children <5 years of age.
  • The annual number of deaths was calculated to range between 500,000 and 1.1 million.
  • Data (2000–2004) from six Asian countries indicate that, even though the incidence of shigellosis remains stable, mortality rates associated with this disease may have decreased significantly, possibly as a result of improved nutritional status.
  • Extensive and essentially uncontrolled use of antibiotics, which may also account for declining mortality rates, has increased the emergence of multidrug-resistant Shigella strains.

1.2 Species Differentiation

  • Shigella dysenteriae, Shigella flexneri, Shigella boydii, and Shigella sonnei (serogroups A, B, C, and D, respectively) can be differentiated on the basis of biochemical and serologic characteristics.
  • S. flexneri isolates predominate in the least developed areas.
  • S. sonnei is more prevalent in economically emerging countries and in the industrialized world.

2. EPIDEMIOLOGY

  • The human intestinal tract is the major reservoir of Shigella, which is also found (albeit rarely) in the higher primates.
  • Because excretion of shigella is greatest in the acute phase of disease, the bacteria are transmitted most efficiently by the fecal–oral route via hand carriage.
  • Some outbreaks reflect foodborne or waterborne transmission.
  • In impoverished areas, Shigella can be transmitted by flies.
  • The high-level infectivity of Shigella is reflected by the very small inoculum required for experimental infection of volunteers (100 colony-forming units [CFU]).
  • Very high attack rates during outbreaks in day-care centers (33–73%).
  • High rates of secondary cases among family members of sick children (26–33%).
  • Shigellosis can also be transmitted sexually.
  • Throughout history, bacillary dysentery epidemics have often occurred in settings of human crowding under conditions of poor hygiene—e.g., among soldiers in campaigning armies, inhabitants of besieged cities, groups on pilgrimages, and refugees in camps.
  • Epidemics followed a cyclical pattern in areas such as the Indian subcontinent and sub-Saharan Africa.
  • These patterns of devastating epidemics, which were most often caused by S. dysenteriae type 1, were characterized by high attack and mortality rates.
  • In Bangladesh, for instance, an epidemic caused by S. dysenteriae type 1 was associated with a 42% increase in mortality rate among children 1–4 years of age.
  • This pattern of severe cyclic disease has steeply declined over the last few decades.
  • Along with the increasingly rare isolation of S. dysenteriae 1, the current epidemiology of shigellosis is generally attributed to a significant global reduction of extreme poverty; this coincides with the tremendous decrease in child mortality.
  • Nevertheless, apart from these severe epidemics of the past, shigellosis remains an endemic disease, with 99% of cases occurring in developing countries, with the highest prevalence in the most impoverished areas, where personal and general hygiene is below standard.
  • In pediatric populations, local outbreaks occur when proper and adapted hygiene policies are not implemented in group facilities such as day-care centers and institutions for the developmentally disabled.
  • In adults, as in children, sporadic cases occur among travelers returning from endemic areas, and rare outbreaks of varying size can follow waterborne or foodborne infections.

2.1 Age and Nutritional Factors

  • Peaking in incidence in the pediatric population, endemic shigellosis is rare among young and middle-aged adults, probably because of naturally acquired immunity.
  • Incidence then increases again in the elderly population.
  • Poverty and poor standards of hygiene are strongly related to the number and severity of diarrheal episodes, especially in children <5 years following weaning.
  • Combined with anorexia, the exudative enteropathy resulting from mucosal abrasions contributes to rapid deterioration of the patient's nutritional status.
  • Shigellosis thus now appears as a major contributor to stunted growth among children in endemic regions.

3. ETIOLOGY & PATHOPHYSIOLOGY

  • Shigella infection occurs essentially through oral contamination via direct fecal–oral transmission, the organism being poorly adapted to survive in the environment.
  • Resistance to low-pH conditions allows Shigella to survive passage through the gastric barrier.
  • The watery diarrhea that usually precedes dysenteric symptoms is attributable to active secretion and abnormal water reabsorption in the jejunum, as described in experimentally infected rhesus monkeys.
  • This initial purge is possibly due to the combined action of an enterotoxin (ShET-1) and mucosal inflammation.
  • The dysenteric syndrome, manifested by bloody and mucopurulent stools, reflects invasion of the colonic mucosa.
  • The pathogenesis of Shigella is essentially determined by a large virulence plasmid of 214 kb comprising ~100 genes, of which 25 encode a type III secretion system that inserts into the membrane of the host cell to allow effectors to transit from the bacterial cytoplasm to the host cell cytoplasm.
  • Bacteria are thereby able to invade intestinal epithelial cells by inducing their own uptake either directly at the opening of colonic crypts or following the initial crossing of the epithelial barrier through M cells (the specialized translocating epithelial cells in the follicle-associated epithelium that covers mucosal lymphoid nodules).
  • Shigella induces apoptosis of subepithelial resident macrophages.
  • Once inside the cytoplasm of intestinal epithelial cells, Shigella effectors trigger the cytoskeletal rearrangements necessary to direct uptake of the organism into the epithelial cell.
  • The Shigella-containing vacuole is then quickly lysed, releasing bacteria into the cytosol.
  • Intracellular shigellae next use cytoskeletal components to propel themselves inside the infected cell; when the moving organism and the host cell membrane come into contact, cellular protrusions form and are engulfed by neighboring cells.
  • This series of events permits bacterial cell-to-cell spread.
  • Cytokines released by a growing number of infected intestinal epithelial cells massively attract immune cells—particularly polymorphonuclear leukocytes [PMNs]—to the infected site, thus further destabilizing the epithelial barrier, exacerbating inflammation, and leading to the acute colitis that characterizes shigellosis.
  • Evidence indicates that some type III secretion system–injected effectors can control the extent of inflammation, thus facilitating bacterial survival.
  • Shiga toxin produced by S. dysenteriae type 1 increases disease severity.
  • This toxin belongs to a group of A1-B5 protein toxins whose B subunit binds to the receptor globotriaosylceramide on the target cell surface and whose catalytic A subunit is internalized by receptor-mediated endocytosis and interacts with the subcellular machinery to inhibit protein synthesis by expressing RNA N-glycosidase activity on 28S ribosomal RNA.
  • This process leads to inhibition of binding of the amino-acyl-tRNA to the 60S ribosomal subunit and thus to a general shutoff of cell protein biosynthesis.
  • Shiga toxins are translocated from the bowel into the circulation.
  • After binding of the toxins to target cells in the kidney, pathophysiologic alterations may result in hemolytic-uremic syndrome (HUS; see below).
  • Shiga toxin produced by S. dysenteriae type 1 has been linked to HUS in developing countries but rarely in industrialized countries, where enterohemorrhagic E. coli (EHEC) predominates as the etiologic agent of this syndrome.

3.1 Pathogenesis Cascade

  • Oral contamination via direct fecal–oral transmission.
  • Survival through gastric barrier via resistance to low-pH conditions.
  • Watery diarrhea phase: active secretion and abnormal water reabsorption in the jejunum.
  • Invasion of colonic mucosa: induced uptake directly at crypt openings or via M cells.
  • Apoptosis of subepithelial resident macrophages.
  • Intracellular survival: cytoskeletal rearrangements, vacuole lysis, cell-to-cell spread.
  • Inflammation: Cytokine release attracts PMNs, destabilizing epithelial barrier.
  • Shiga toxin: A1-B5 protein toxin inhibits protein synthesis, translocated to circulation, causes HUS in kidney.

4. CLINICAL FEATURES

  • The presentation and severity of shigellosis depend to some extent on the infecting serotype but even more on the age and the immune and nutritional status of the host.
  • Shigellosis typically evolves through four phases: incubation, watery diarrhea, dysentery, and the postinfectious phase.
  • The incubation period usually lasts 1–4 days but may be as long as 8 days.
  • Typical initial manifestations are transient fever, limited watery diarrhea, malaise, and anorexia.
  • Signs and symptoms may range from mild abdominal discomfort to severe cramps, diarrhea, fever, vomiting, and tenesmus.
  • The manifestations are usually exacerbated in children, with temperatures up to 40°–41°C (104.0°–105.8°F) and more severe anorexia and watery diarrhea.
  • This initial phase may represent the only clinical manifestation of shigellosis, especially in developed countries.
  • Otherwise, dysentery follows within hours or days and is characterized by uninterrupted excretion of small volumes of bloody mucopurulent stools with increased tenesmus and abdominal cramps.
  • At this stage, Shigella produces acute colitis involving mainly the distal colon and the rectum.
  • Unlike most diarrheal syndromes, dysenteric syndromes rarely present with dehydration as a major feature.
  • Endoscopy, if performed, shows an edematous and hemorrhagic mucosa, with ulcerations and possibly overlying exudates resembling pseudomembranes.
  • The extent of the lesions correlates with the number and frequency of stools and rectal prolapse.
  • Most episodes are self-limited and resolve without treatment in 1 week.
  • With appropriate treatment, recovery takes place within a few days to a week, with no sequelae.
  • Acute life-threatening complications are seen most often in children <5 years (particularly those who are malnourished) and in elderly patients.
  • Risk factors for death in a clinically severe case include nonbloody diarrhea, moderate to severe dehydration, bacteremia, absence of fever, abdominal tenderness, and rectal prolapse.
  • Major complications are predominantly intestinal (e.g., toxic megacolon, intestinal perforations, rectal prolapse) or metabolic (e.g., hypoglycemia, hyponatremia, dehydration).
  • Bacteremia is rare and is reported most frequently in severely malnourished and HIV-infected patients.
  • Alterations of consciousness, including seizures, delirium, and coma, may occur, especially in children <5 years, and are associated with a poor prognosis; fever and severe metabolic alterations are more often the major causes of altered consciousness than is meningitis or the Ekiri syndrome (toxic encephalopathy associated with bizarre posturing, cerebral edema, and fatty visceral degeneration), which has been reported mostly in Japanese children.
  • Pneumonia, vaginitis, and keratoconjunctivitis due to Shigella are rarely reported.
  • In the absence of serious malnutrition, severe and very unusual clinical manifestations, such as meningitis, may be linked to genetic defects in innate immune functions (i.e., deficiency in interleukin 1 receptor–associated kinase 4 [IRAK-4]) and may require genetic investigation.
  • Two complications of particular importance are toxic megacolon and HUS.
  • Toxic megacolon is a consequence of severe inflammation extending to the colonic smooth-muscle layer and causing paralysis and dilation.
  • The patient presents with abdominal distention and tenderness, with or without signs of localized or generalized peritonitis.
  • The abdominal x-ray characteristically shows marked dilation of the transverse colon (with the greatest distention in the ascending and descending segments); thumbprinting caused by mucosal inflammatory edema; and loss of the normal haustral pattern associated with pseudopolyps, often extending into the lumen.
  • Pneumatosis coli is an occasional finding.
  • If perforation occurs, radiographic signs of pneumoperitoneum may be apparent.
  • Predisposing factors (e.g., hypokalemia and use of opioids, anticholinergics, loperamide, psyllium seeds, and antidepressants) should be investigated.
  • HUS is an early complication that most often develops after several days of diarrhea.
  • Clinical examination shows pallor, asthenia, and irritability and, in some cases, bleeding of the nose and gums, oliguria, and increasing edema.
  • HUS is a nonimmune (Coombs-negative) hemolytic anemia defined by a diagnostic triad: microangiopathic hemolytic anemia (hemoglobin level typically <80 g/L [<8 g/dL]), thrombocytopenia (mild to moderate in severity; typically <60,000 platelets/μL), and acute renal failure due to thrombosis of the glomerular capillaries (with markedly elevated creatinine levels).
  • Anemia is severe, with fragmented red blood cells (schizocytes) in the peripheral smear, high serum concentrations of lactate dehydrogenase and free circulating hemoglobin, and elevated reticulocyte counts.
  • Acute renal failure occurs in 55–70% of cases; however, renal function recovers in most of these cases (up to 70% in various series).
  • Leukemoid reactions, with leukocyte counts of 50,000/μL, are sometimes present in association with HUS.
  • The postinfectious immunologic complication known as reactive arthritis can develop weeks or months after shigellosis, especially in patients expressing the histocompatibility antigen HLA-B27.
  • About 3% of patients infected with S. flexneri later develop this syndrome, with arthritis, ocular inflammation, and urethritis—a condition that can last for months or years and can progress to difficult-to-treat chronic arthritis.
  • Postinfectious arthritis occurs only after infection with S. flexneri and not after infection with the other Shigella serotypes.

4.1 Complications

  • Toxic megacolon: Consequence of severe inflammation extending to colonic smooth-muscle layer, causing paralysis and dilation. Presents with abdominal distention and tenderness. X-ray shows marked dilation of transverse colon, thumbprinting, loss of haustral pattern.
  • Hemolytic-uremic syndrome (HUS): Early complication developing after several days of diarrhea. Defined by triad: microangiopathic hemolytic anemia (Hb <80 g/L), thrombocytopenia (<60,000 platelets/μL), acute renal failure. Associated with Shiga toxin in developing countries.
  • Reactive arthritis: Postinfectious immunologic complication developing weeks or months after shigellosis. Occurs only after infection with S. flexneri. Associated with HLA-B27. Can progress to chronic arthritis.
  • Bacteremia: Rare. Reported most frequently in severely malnourished and HIV-infected patients.
  • Altered consciousness: Seizures, delirium, coma in children <5 years. Associated with poor prognosis. Fever and metabolic alterations are major causes.

4.2 Radiographic Findings

  • Abdominal x-ray in toxic megacolon: Marked dilation of transverse colon (greatest distention in ascending and descending segments).
  • Thumbprinting caused by mucosal inflammatory edema.
  • Loss of normal haustral pattern associated with pseudopolyps.
  • Pneumatosis coli: Occasional finding.
  • Pneumoperitoneum: Radiographic signs if perforation occurs.

5. DIFFERENTIAL DIAGNOSIS

  • The differential diagnosis in patients with a dysenteric syndrome depends on the clinical and environmental context.
  • In developing areas, infectious diarrhea caused by other invasive pathogenic bacteria (Salmonella, Campylobacter jejuni, Clostridium difficile, Yersinia enterocolitica) or parasites (Entamoeba histolytica) should be considered.
  • Only bacteriologic and parasitologic examinations of stool can truly differentiate among these pathogens.
  • A first flare of inflammatory bowel disease, such as Crohn's disease or ulcerative colitis, should be considered in patients in industrialized countries.
  • Despite the similarity in symptoms, anamnesis discriminates between shigellosis, which usually follows recent travel in an endemic zone, and these other conditions.
  • Microscopic examination of stool smears shows erythrophagocytic trophozoites with very few PMNs in E. histolytica infection.
  • Bacterial enteroinvasive infections (particularly shigellosis) are characterized by high PMN counts in each microscopic field.

5.1 Microscopic Findings

  • Entamoeba histolytica: Erythrophagocytic trophozoites with very few PMNs.
  • Bacterial enteroinvasive infections (Shigellosis): High PMN counts in each microscopic field.

6. INVESTIGATIONS & DIAGNOSIS

  • The 'gold standard' diagnosis of Shigella infection remains the isolation and identification of the pathogen from fecal material.
  • One major difficulty, particularly in endemic areas where laboratory facilities are not immediately available, is the fragility of Shigella and its common disappearance during transport, especially with rapid changes in temperature and pH.
  • In the absence of a reliable enrichment medium, buffered glycerol saline or Cary-Blair medium can be used as a holding medium, but prompt inoculation onto isolation medium is essential.
  • The probability of isolation is higher if the portion of stools that contains bloody and/or mucopurulent material is directly sampled.
  • Rectal swabs can be used, as they offer the highest rate of successful isolation during the acute phase of disease.
  • Blood cultures are positive in fewer than 5% of cases but should be done when a patient presents with a clinical picture of severe sepsis.
  • In addition to quick processing, the use of several media increases the likelihood of successful isolation: a nonselective medium such as bromocresol-purple agar lactose; a low-selectivity medium such as MacConkey or eosin-methylene blue; and a high-selectivity medium such as Hektoen, Salmonella-Shigella, or xylose-lysine-deoxycholate agar.
  • After incubation on these media for 12–18 h at 37°C (98.6°F), shigellae appear as non-lactose-fermenting colonies that measure 0.5–1 mm in diameter and have a convex, translucent, smooth surface.
  • Suspected colonies on nonselective or low-selectivity medium can be subcultured on a high-selectivity medium before being specifically identified or can be identified directly by standard commercial systems on the basis of four major characteristics: glucose positivity (usually without production of gas), lactose negativity, HS negativity, and lack of motility.
  • The four serogroups (A–D) can then be differentiated by additional characteristics.
  • This approach adds time and difficulty to the identification process; however, after presumptive diagnosis, the use of serologic methods (e.g., slide agglutination, with group- and then type-specific antisera) should be considered.
  • Group-specific antisera are widely available; in contrast, because of the large number of serotypes and subserotypes, type-specific antisera are rare and more expensive and thus are often restricted to reference laboratories.
  • Molecular methods of diagnostics, including polymerase chain reaction based on Shigella-specific virulence gene sequences or mass spectrometry, are not yet standardized for global use.
  • However, serotyping may soon be replaced by genome-based techniques.

6.1 Diagnostic Media and Colony Morphology

  • Holding media: Buffered glycerol saline or Cary-Blair medium.
  • Nonselective medium: Bromocresol-purple agar lactose.
  • Low-selectivity medium: MacConkey or eosin-methylene blue.
  • High-selectivity medium: Hektoen, Salmonella-Shigella, or xylose-lysine-deoxycholate agar.
  • Colony appearance after 12–18 h at 37°C: Non-lactose-fermenting, 0.5–1 mm diameter, convex, translucent, smooth surface.
  • Biochemical characteristics: Glucose positivity (usually without production of gas), lactose negativity, HS negativity, lack of motility.

7. MANAGEMENT & TREATMENT

  • As an enteroinvasive disease, shigellosis requires antibiotic treatment.
  • Since the mid-1960s, however, increasing resistance to multiple drugs has been a dominant factor in treatment decisions.
  • Resistance rates are highly dependent on the geographic area.
  • Clonal spread of particular strains and horizontal transfer of resistance determinants, particularly via plasmids and transposons, contribute to multidrug resistance.
  • The current global status—i.e., high rates of resistance to classic first-line antibiotics such as amoxicillin—has led to a rapid switch to quinolones such as nalidixic acid.
  • However, resistance to such early-generation quinolones has also emerged and spread quickly as a result of chromosomal mutations affecting DNA gyrase and topoisomerase IV; this resistance has necessitated the use of later-generation quinolones as first-line antibiotics in many areas.
  • For instance, a review of the antibiotic resistance history of Shigella in India found that, after their introduction in the late 1980s, the second-generation quinolones norfloxacin, ciprofloxacin, and ofloxacin were highly effective in the treatment of shigellosis, including cases caused by multidrug-resistant strains of S. dysenteriae type 1.
  • However, investigations of subsequent outbreaks in India and Bangladesh detected resistance to norfloxacin, ciprofloxacin, and ofloxacin in 5% of isolates.
  • In the United States, the resistance rate of Shigella to fluoroquinolones reached 87% during 2014−2015.
  • The incidence of multidrug resistance parallels the widespread, uncontrolled use of antibiotics and calls for the rational use of effective drugs.
  • Despite the alarming proportion of resistant Shigella, there is a lack of studies assessing the resistance of community-acquired strains.
  • With effective antibiotic therapy, clinical improvement occurs within 48 h, resulting in a decreased risk of complications and death, shorter duration of symptoms, and elimination of Shigella from the stools.
  • Because of the transmissibility of Shigella, current public health recommendations in the United States are that every case be treated with antibiotics.
  • The use of fluoroquinolones (first-line, preferably ciprofloxacin) and cephalosporins and β-lactams (second-line) for 7−10 days is recommended for the treatment of shigellosis.
  • Whereas infections caused by non-dysenteriae Shigella in immunocompetent individuals are routinely treated with a 3-day course of antibiotics, it is recommended that S. dysenteriae type 1 infections be treated for 5 days and that Shigella infections in immunocompromised patients be treated for 7–10 days.
  • Treatment schedule and limitations are detailed in Table 172-1.
ANTIMICROBIAL AGENT TREATMENT SCHEDULE (CHILDREN) TREATMENT SCHEDULE (ADULTS) LIMITATIONS
Ciprofloxacin 15 mg/kg 500 mg 2 times per day for 3 days, PO
Pivmecillinam 20 mg/kg 100 mg 4 times per day for 5 days, PO; Cost; Frequent administration; Emerging resistance; No pediatric formulation
Ceftriaxone 50–100 mg/kg — Once a day IM for 2–5 days; Efficacy not validated
Azithromycin 6–20 mg/kg 1–1.5 g Once a day for 1–5 days, PO; Efficacy not validated

7.1 Antibiotic Therapy

  • First-line: Fluoroquinolones (e.g., ciprofloxacin).
  • Second-line: Cephalosporins and β-lactams.
  • Duration: Non-dysenteriae Shigella (3 days), S. dysenteriae type 1 (5 days), Immunocompromised (7–10 days).
  • Clinical improvement: Within 48 h with effective therapy.
  • Public health recommendation: Every case be treated with antibiotics due to transmissibility.

8. PROGNOSIS & COMPLICATIONS

  • Most episodes are self-limited and resolve without treatment in 1 week.
  • With appropriate treatment, recovery takes place within a few days to a week, with no sequelae.
  • Acute life-threatening complications are seen most often in children <5 years (particularly those who are malnourished) and in elderly patients.
  • Risk factors for death in a clinically severe case include nonbloody diarrhea, moderate to severe dehydration, bacteremia, absence of fever, abdominal tenderness, and rectal prolapse.
  • Major complications are predominantly intestinal (e.g., toxic megacolon, intestinal perforations, rectal prolapse) or metabolic (e.g., hypoglycemia, hyponatremia, dehydration).
  • Bacteremia is rare and is reported most frequently in severely malnourished and HIV-infected patients.
  • Alterations of consciousness, including seizures, delirium, and coma, may occur, especially in children <5 years, and are associated with a poor prognosis.
  • Fever and severe metabolic alterations are more often the major causes of altered consciousness than is meningitis or the Ekiri syndrome.
  • Acute renal failure occurs in 55–70% of cases; however, renal function recovers in most of these cases (up to 70% in various series).
  • Leukemoid reactions, with leukocyte counts of 50,000/μL, are sometimes present in association with HUS.
  • Postinfectious arthritis can last for months or years and can progress to difficult-to-treat chronic arthritis.

8.1 Complication Rates

  • Acute renal failure in HUS: 55–70% of cases.
  • Renal recovery: Up to 70% in various series.
  • Reactive arthritis incidence: About 3% of patients infected with S. flexneri.

9. SPECIAL CONSIDERATIONS

  • Immunocompromised patients: Shigella infections in immunocompromised patients be treated for 7–10 days.
  • Malnourished children: Acute life-threatening complications are seen most often in children <5 years (particularly those who are malnourished).
  • Elderly patients: Acute life-threatening complications are seen most often in elderly patients.
  • HIV-infected patients: Bacteremia is reported most frequently in HIV-infected patients.
  • Genetic defects: Severe and very unusual clinical manifestations, such as meningitis, may be linked to genetic defects in innate immune functions (i.e., deficiency in interleukin 1 receptor–associated kinase 4 [IRAK-4]) and may require genetic investigation.

9.1 Host Factors

  • Age: Children <5 years and elderly patients are at higher risk for severe complications.
  • Nutritional status: Malnutrition contributes to rapid deterioration and severe complications.
  • Immune status: Immunocompromised patients require longer antibiotic courses (7–10 days).
  • Genetics: Deficiency in interleukin 1 receptor–associated kinase 4 [IRAK-4] may link to severe manifestations like meningitis.

10. KEY PEARLS & CLINICAL TRAPS

  • Infectivity: Very small inoculum required (100 CFU).
  • HUS Triad: Microangiopathic hemolytic anemia (Hb <80 g/L), thrombocytopenia (<60,000 platelets/μL), acute renal failure.
  • Reactive Arthritis: Occurs only after infection with S. flexneri, associated with HLA-B27.
  • Antibiotic Resistance: High rates of resistance to classic first-line antibiotics (amoxicillin); resistance to fluoroquinolones reached 87% in the United States during 2014−2015.
  • Toxic Megacolon: Consequence of severe inflammation extending to colonic smooth-muscle layer.
  • Shigella vs E. coli: Cannot be distinguished from E. coli by genome comparison; remains a separate species only on historical and clinical grounds.
  • Geographic Variation: S. flexneri in least developed areas; S. sonnei in industrialized world.
  • Transmission: Fecal–oral route via hand carriage; high attack rates in day-care centers (33–73%).
  • Clinical Course: Watery diarrhea precedes dysenteric symptoms; initial phase may be only manifestation in developed countries.

Figures & Illustrations

Reproduced from Harrison's 22nd Edition.

Figure 1

Invasive strategy of Shigella flexneri

Caption: FIGURE 172-1 Invasive strategy of Shigella flexneri. IL, interleukin; NF-κB, nuclear NOD-like receptor; PMN, polymorphonuclear leukocyte. are engulfed by neighboring cells. This series of events permits bacte- rial cell-to-cell spread. Cytokines released by a growing number of infected intestinal epithelial cells massively attract immune cells—particularly poly- morphonuclear leukocytes [PMNs]—to the infected site, thus further destabilizing the epithelial barrier, exacerbating inflammation, and leading to the acute colitis that characterizes shigellosis. Evidence indi- — FIGURE 172-1 Invasive strategy of Shigella flexneri. The diagram illustrates the pathogenesis cascade including: IL-1β and Cell-to-cell spread, Activation of NF-κB caused by IcsA, Macrophage apoptosis, Cytokines released by a growing number of infected intestinal epithelial cells massively attract immune cells—particularly polymorphonuclear leukocytes [PMNs]—to the infected site, Disruption of epithelial permeability barrier by PMNs, Massive invasion of epithelium, Initiation of inflammation, Bacterial survival, and Shiga toxin produced by S. dysenteriae type 1 increases disease severity. IL, interleukin; NF-κB, nuclear factor κB; NLR, NOD-like receptor; PMN, polymorphonuclear leukocyte.

Generated from Harrison's Principles of Internal Medicine, 22nd Edition.