Introduction to Shigella
Shigella is a species of enteric bacteria that causes disease in humans and other primates. [16, 20] The disease caused by the ingestion of Shigella bacteria is referred to as shigellosis, which is most typically associated with diarrhea and other gastrointestinal symptoms. [11, 16] “Shigella infection is the third most common cause of bacterial gastroenteritis in the United States, after Campylobacter infection and Salmonella infection and ahead of E. coli O157 infection.” 
The global burden of shigellosis has been estimated at 165 million cases per year, of which 163 million are in developing countries.  More than one million deaths occur in the developing world yearly due to Shigella infection. [23, 29] By one estimate, Shigella infections are responsible for 300,000 illnesses and 600 deaths per year in the United States.  By another estimate, each year 450,000 Americans are infected with Shigella, causing 6,200 hospitalizations and 70 deaths. 
In general, Shigella is one of the most communicable and severe forms of the bacterial-induced diarrheas.  No group of individuals is immune to shigellosis, but certain individuals are at increased risk.  Small children acquire Shigella at the highest rate, and [24, 28] persons infected with HIV experience shigellosis much more commonly than other individuals. 
Shigella is easily spread person-to-person because of its relatively tiny (compared to other bacteria) infectious dose. [16, 23] Infection can occur after ingestion of fewer than 100 bacteria. [1, 16, 17] Another reason Shigella so easily cause infection is because the bacteria thrive in the human intestine and are commonly spread both by person-to-person contact and through the contamination of food. [11, 22, 32]
The Discovery and Naming of Shigella
The several types of Shigella bacteria have been named after the lead workers who discovered each one. [11, 16, 20] The first bacterium to be discovered, Shigella dysentariae, was named after Kiyoshi Shiga, a Japanese scientist who discovered it in 1896 while investigating a large epidemic of dysentery in Japan. [22, 37] The bacterium was also referred to more generally as the dysentery bacillus (the term “bacillus” referring to a genus of Gram-positive, rod-shaped bacteria of which Shigella is a member). 
Dr. Shiga dedicated his life to eradicating the disease. In 1936, while an honored guest at the 300th anniversary of the founding of Harvard University, he gave a speech that began as follows:
The discovery of the dysentery bacillus stirred my young heart with hopes of eradicating the disease…Many thousands still suffer from this disease every year, and the light of hope that once burned so brightly has faded as a dream of a summer night. This sacred fire must not burn out. 
Dr. Shiga died at the age of 85 years on 25 January 1957. Shigella has not yet been eradicated.
In a summary published annually, the CDC provides an overview of the classification of various types (species) of Shigella bacteria, as follows:
There are 4 major subgroups of Shigella, designated A, B, C and D, and 44 recognized serotypes. Subgroups A, B, C and D have historically been treated as species: subgroup A for Shigella dysenteriae; subgroup B for Shigella flexneri; subgroup C for Shigella boydii and subgroup D for Shigella sonnei. These subgroups and serotypes are differentiated from one another by their biochemical traits (ability to ferment D-mannitol) and antigenic properties. The most recently recognized serotype belongs to subgroup C (S. boydii). 
S. sonnei, also known as Group D Shigella, accounts for over two-thirds of shigellosis in the United States. Shigella flexneri, or group B Shigella, accounts for almost all the rest. [11, 19] More specifically, according to one recent study, “From 1989 to 2002, S. flexneri accounted for 18.4% of Shigella isolates submitted to CDC.  From 1973 to 1999, only 49 S. flexneri-associated outbreaks of foodborne disease were reported.”  In contrast, in developing countries, S. flexneri is the most predominant cause of shigellosis, but S. dysinteriae type 1 is still a frequent cause of epidemic throughout the developing world. [1, 16, 23, 37]
The Incidence of Shigella Infection
The number of shigellosis cases reported annually to the Centers for Disease Control and Prevention (CDC) has varied over the past several years, from more than 17,000 during 1978–2003, to an all-time low of 14,000 in 2004, to almost 20,000 in 2007. [11, 19] But a majority of cases go undiagnosed or unreported. [12, 16, 37] In one study done in Oregon, 430 confirmed Shigella cases from July 1995 through June 1998 were examined.  Among the several findings about those most likely to fall ill was the following:
Of 430 isolates, 410 were identified to the species level: Shigella sonnei accounted for 55% of isolates, and Shigella flexneri, for 40%. The overall annual incidence of shigellosis was 4.4 cases per 100,000 population. Children aged [less than] 5 years (annual incidence, 19.6 cases per 100,000 population) and Hispanics (annual incidence, 28.4 cases per 100,000 population) were at highest risk. 
The CDC estimates that 450,000 total cases of shigellosis occur in the U.S. every year. [4, 11, 21] Shigellosis is also characterized by seasonality, with the largest percentage of reported cases occurring between July and October, and the smallest proportion occurring in January, February, and March.  Sporadic (or non-outbreak) infections account for the majority of cases and, in general, the exact means by which persons are infected (risk factors) are not yet well documented or understood. [21, 36]
Shigella is an especially common cause of disease among young children, in large part because it is difficult to control the spread of the bacteria in daycare settings. [16, 28] The symptoms of shigellosis vary so widely that children shedding Shigella in their stool may exhibit no symptoms of infection. A person infected with Shigella can be asymptomatic (show no symptoms of illness), suffer from moderate to severe diarrhea, or suffer complications up to and including death. [11, 17, 26]
More on Incidence Rates and How Shigella is Transmitted
As previously noted, Shigella species are transmitted by the fecal-oral route, and most infections are transmitted from person to person, reflecting the low infectious dose.  As also noted, as few as ten Shigella bacteria can result in clinical infection.  Where persons who are infected may be present, the risk of transmission and infection increases with poor hand hygiene, ingestion of contaminated food or water, inadequate sanitation and toileting, overcrowding, and sexual contact. [4, 14, 21, 24, 28] Shigella bacteria are present in the stools of infected persons while they are sick and for up to a week or two afterwards. [11, 16, 17] It is estimated that up 80% of all infection is the result of person-to-person transmission. 
Because of its quite common person-to-person spread, shigellosis has long been associated with outbreaks in daycare centers, nursing homes, institutional settings (like prison), and cruise ships. [11, 14, 17, 23, 24] Explaining the significance of daycare centers as a source of Shigella infection, one well-respected study explains as follows:
High shigellosis rates in children are attributable to several factors. Young children are unable to practice good personal hygiene and have not yet acquired immunity to S. sonnei. The infectious dose is as low as 10–200 organisms, and person-to-person transmission is highly effective. Day-care centers play an important role in the person-to-person spread of shigellosis and its subsequent dissemination in communities. Inadequate hand washing, diapering practices, and fecal contamination of water-play areas, such as kiddie pools, have been associated with S. sonnei transmission in day-care centers. 
Several studies have demonstrated an increased frequency of shigellosis cases in young adult men residing in urban settings who have little, if any, exposure to these traditionally recognized risk groups. [4, 36] Although some of these studies indicated that sex between men can be a risk-factor, most of these studies occurred before the HIV epidemic. [4, 23]
Shigella infections also may be acquired from eating contaminated food. A study published in 2010 estimated more than one-third of U.S. shigellosis cases annually might be caused by the consumption of contaminated food.  In the United States, incidence of foodborne illness is documented through FoodNet, a reporting system used by public health agencies that captures foodborne illness in over 13% of the population. [8, 9] Of the 10 pathogens tracked by FoodNet, Salmonella, Campylobacter, and Shigella are responsible for most cases of foodborne illness.  An estimated 20% of the total number of cases of shigellosis involve food as the vehicle of transmission. 
In one oft-cited study summarizing food-related illness and death in the United States, the following synopsis is set forth at the end, summarizing Shigella.
Reported cases: Outbreak-related cases based on reports to CDC, 1983-1992. Passive surveillance estimate based on average number of cases reported annually to CDC, 1992-1997. Active surveillance estimate based on extrapolation of average 1996-1997 FoodNet rate to the 1997 U.S. population.
Total cases: Because Shigella frequently causes bloody diarrhea, total cases assumed to be 20 times the number of reported cases, based on similarity to E. coli O157:H7.
Hospitalization rate: Based on hospitalization rate for culture-confirmed cases reported to FoodNet, 1996-1997.
Case-fatality rate: Average case-fatality rate among cases reported to FoodNet, 1996-1997 (23,24).
Percent foodborne: Assumed to be 20%. Although most cases are due to person-to-person transmission (60), foodborne outbreaks are responsible for a substantial number of cases 
According to the CDC, Shigella is the third most common pathogen transmitted through food. In FoodNet surveillance areas in 2008, the rate of Shigella was 6.6 per 100,000 population, exceeded only by Salmonella (15.2/100,000) and Campylobacter (12.7/100,000).  During 2006, public health officials reported a total of 1,270 foodborne-related outbreaks from 48 states in the U.S.  Although Shigella was responsible for only 10 (1%) of those outbreaks, 183 confirmed cases of shigellosis were nonetheless reported.  This reporting rate contrasts with an average of 659 cases annually in the previous five years, making it potentially an aberration or outlier.
Shigella is also responsible for a substantial portion of foodborne outbreaks on cruise ships. [16, 34] In a review of cruise ship outbreaks worldwide over several years, 16% of outbreaks were attributed to Shigella, affecting over 2,000 passengers.  Sanitation violations related to food handling and communicable disease have decreased substantially, however, over the past 15 years. 
Symptoms of Shigella Infection
Most people who are infected with Shigella develop diarrhea, fever, and stomach cramps after being exposed to the bacteria. [11, 16, 26] Symptoms may start 12 to 96 hours after exposure, usually within 1 to 3 days. [1, 16] Diarrhea may range from mild to severe, and it usually contains mucus.  When more severe, the diarrhea is bloody 25% to 50% of the time. [1, 16, 22] Rectal spasms, which are technically referred to as “tenesmus,” are common. 
Shigellosis usually resolves in 5 to 7 days. [1, 11, 26] A severe infection with high fever may be associated with seizures in children less than two years old. [16, 19] Some persons who are infected may have no symptoms at all, but may still pass the Shigella bacteria to others. [11, 17]
Persons with shigellosis in the U.S. do not often require hospitalization, although the hospitalization rate has been estimated to be in excess of 50,000 per year.  Predictably, the hospitalization rate tends to be highest among older individuals. [9, 10, 16] Those who are immune-compromised, like persons infected with HIV, are also more likely to face hospitalization because of the risk of complications. 
The relationship between HIV infection and the subsequent risk for shigellosis has yet to be conclusively evaluated, although it is known that “HIV-associated immunodeficiency leads to more severe clinical manifestations of Shigella infection.”  Moreover, persons infected with HIV “may develop persistent or recurrent intestinal Shigella infections, even in the presence of adequate antimicrobial therapy. They also face an increased risk of Shigella bacteraemia, which can be recurrent, severe or even fatal.” 
What are the serious and long-term risks of Shigella infection?
Persons with diarrhea caused by S. sonnei in particular usually recover completely, although it may be several months before their bowel habits are entirely normal. [1, 11, 26] About 2% of persons who are infected with S. flexneri later develop pains in their joints, irritation of the eyes, and painful urination—something typically diagnosed as Reiter’s Syndrome. [1, 6]
Reiter’s syndrome is more generally referred to as reactive arthritis, a complication that accompanies other kinds of bacterial infections as well. [27, 37] This complication occurs because the immune system, intending to fight Shigella, attacks the body instead. [6, 31] Reactive arthritis is most common in persons with the HLA-B27 gene.  (About 80% of people with reactive arthritis have the HLA-B27 gene. Only 6% of people who do not have the syndrome have the HLA-B27 gene.) Reactive arthritis can last for months or years and may be difficult to treat. 
Once someone has suffered a Shigella infection, a certain level of immunity develops, meaning that the person is not likely to get infected with that specific type again for at least several years.  This temporary immunity does not, however, protect against other types of Shigella. [16, 29]
Shigella bacteria multiply in the human intestinal tract and invade the cells, which results in much tissue destruction.  Many strains produce a toxin called Shiga toxin, which is very potent and destructive. [16, 22] Shiga toxin is very similar to the verotoxin of E. coli O157:H7. Complications of shigellosis include severe dehydration, seizures in small children, rectal bleeding, and invasion of the blood stream by the bacteria (bacteremia or sepsis). [1, 11, 16, 26] In some cases, the bacteria that cause shigellosis may also cause inflammation of the lining of the rectum (proctitis) or rectal prolapse. 
In rare cases (but more common in S. dysenteriae infection), there can also be a deadly complication called “toxic megacolon.” [1, 26] This rare complication occurs when the colon becomes paralyzed, preventing bowel movements or passing gas. [16, 26] Signs and symptoms include abdominal pain and swelling, fever, weakness, and disorientation.  Untreated, the colon may rupture and cause peritonitis, a life-threatening condition requiring emergency surgery. 
The other relatively rare complication that can occur with a Shigella infection is the development of hemolytic uremic syndrome. This rare complication is more commonly caused by E. coli O157:H7, and it can lead to a low red blood cell count (hemolytic anemia), low platelet count (thrombocytopenia), and acute kidney failure. [26, 37] It is more common to develop HUS after being infected with S. dysenteriae. 
Diagnosis and Treatment of Shigella Infections
Because the symptoms of a Shigella infection are consistent with a fairly large number of potential illnesses, including most foodborne infections, a diagnosis must be confirmed by a laboratory test. [5, 11, 26] First a stool sample must be obtained from the potentially infected person, and then the sample is placed on a medium to encourage the growth of bacteria. If and when there is growth, the bacteria are identified, usually by looking at the growth under a microscope. [20, 26] The laboratory can also do special tests to tell which species of Shigella the person has, and which antibiotics would be best to treat the infection. [16, 22, 30] Antibiotic-sensitivity tests are important because Shigella is often resistant to multiple antibiotics. [16, 30]
More advanced testing and surveillance methods, such as plasmid profiling and chromosomal fingerprinting, can also be used. [11, 20, 29] So-called “genetic fingerprinting” of the bacterial isolate, using pulsed-field gel electrophoresis (PFGE) is a molecular technique that can help to characterize Shigella isolates, whether obtained from human or food samples. [11, 27] Taken together, all of these tests can assist public health officials in determining whether cases (confirmed infections) are isolated or associated with common-source outbreaks. [19, 20, 27]
Efforts to identify outbreaks of foodborne illness—whether caused by Shigella or other pathogens—are important to preventing the secondary spread of infection, especially with bacteria as highly communicable as Shigella. [1, 11, 21] One major advance in these efforts was the creation of FoodNet, an active surveillance system for foodborne illness. As described by the CDC:
FoodNet workers regularly contact more than 300 laboratories for confirmed cases of foodborne infections in 10 states encompassing a population of more than 44 million persons. In addition to monitoring the number of Shigella infections, investigators monitor laboratory techniques for isolation of bacteria, perform studies of ill persons to determine exposures associated with illness, and administer questionnaires to people living in FoodNet sites to better understand trends in the eating habits of Americans. 
Although shigellosis is usually a self-limited illness, antibiotics can shorten the course, and in the most serious cases, might be life-saving. [1, 16, 22] Historically, the antibiotics commonly used for treatment of bacterial infections, like those caused by Shigella, are ampicillin, trimethoprim/sulfamethoxazole (TMP-SMZ, also known as Bactrim or Septra), or ceftriaxone (Rocephin). [1, 11, 26] Ciprofloxacin is also used commonly to treat adults who are infected. [11, 26, 30].
Unfortunately, Shigella bacteria have become resistant to one or more of these antibiotics. [16, 30] This means some antibiotics might not be effective for treatment, and that using (or overusing) antibiotics to treat shigellosis can sometimes make the bacteria more resistant.  As noted in one recent study:
Of 369 isolates tested, 59% were resistant to TMP-SMZ, 63% were resistant to ampicillin, 1% were resistant to cefixime, and 0.3% were resistant to nalidixic acid; none of the isolates were resistant to ciprofloxacin. Thirteen percent of the isolates had multidrug resistance to ampicillin, chloramphenicol, streptomycin, sulfisoxazole, and tetracycline. Infections due to multidrug-resistant shigellae are endemic in Oregon. 
This study therefore suggests that “[n]either ampicillin nor TMP-SMZ should be considered appropriate empirical therapy for shigellosis any longer; when antibiotics are indicated, a quinolone or cefixime should be used.” 
More on Antimicrobial Resistance in Bacteria
Antimicrobial resistance in bacteria is an emerging and increasing threat to human health. [2, 3] Physicians are increasingly aware that antimicrobial resistance is increasing in foodborne pathogens and that, as a result, patients who are prescribed antibiotics are at increased risk for acquiring antimicrobial-resistant foodborne infections. [3, 29] Indeed, “increased frequency of treatment failures for acute illness and increased severity of infection may be manifested by prolonged duration of illness, increased frequency of bloodstream infections, increased hospitalization or increased mortality.” 
The use of antimicrobial agents in the feed of food animals is estimated by the FDA to be over 100 million pounds per year.  It is estimated that 36% to 70% of all antibiotics produced in the United States are used in food animal feed or in prophylactic treatment to prevent animal disease. [2, 3] In 2002, the Minnesota Medical Association published an article by David Wallinga, M.D., M.P.H. who wrote:
According to the [Union of Concerned Scientists], 70 percent of all the antimicrobials used in the United States for all purposes—or about 24.6 million pounds annually—are fed to poultry, swine, and beef cattle for nontherapeutic purposes, in the absence of disease. Over half are “medically important” antimicrobials; identical or so closely related to human medicines that resistance to the animal drug can confer resistance to the similar human drug. Penicillin, tetracycline, macrolides, streptogramins, and sulfonamides are prominent examples. 
Based on recent research, it is now recommended that doctors avoid the use of commonly prescribed antibiotics, like tetracycline and ampicillin, in favor of drugs for which Shigella has not shown resistance, such as ciprofloxacin.  European countries have reduced the use of antibiotics in animal feed and have seen a corresponding reduction in antibiotic-resistant illnesses in humans. 
The Economic Impact of Shigella Infections
The USDA Economic Research Service (ERS) published its first comprehensive cost estimates for sixteen foodborne bacterial pathogens in 1989.  Five years later, it was estimated that the medical costs and productivity losses that Shigella infections caused each year ran from $907 million to over $1 billion, based on an estimate of 2.1 million cases and between 120-360 deaths.  The average length of a related hospital stay was 4.6 days, with the cost (based on a 1990 average cost per day of $687) was $16,888. 
Using a different kind of economic analysis, this same 1996 study estimated that the annual cost of Shigella infections was $63 million, while the average cost of each confirmed and treated infection was $390; however, these estimates are based on significantly lower (and outdated) incidence and death rates.  Most recent estimates are all much higher. For example, a study published in 2010 estimated the cost per case (in 2009 dollars) for a treated Shigella infection to be $7,092, with an estimate of 96,686 cases and 1,227 deaths per year, and a total cost to U.S. residents of $686 million. 
Real Life Impacts of Shigella Infection
Because the illnesses caused by the ingestion of Shigella bacteria range from mild to severe, the real life impacts of Shigella infection vary from person to person.
While anyone can become ill with Shigella infection, very young children, the elderly, and persons with compromised immune systems are most likely to develop severe illness.
- About 2% of persons who are infected with one type of Shigella, Shigella flexneri, later develop pains in their joints, irritation of the eyes, and painful urination. This is called post-infectious arthritis, or reactive arthritis. The arthritis can last for months or years, and can lead to chronic arthritis. Post-infectious arthritis is caused by a reaction to Shigella infection that happens only in people who are genetically predisposed to it. 
- An unknown percentage of patients with Shigella infections develop digestive disorders, including irritable bowel syndrome.
Although most patients with Shigella infections recover within a few months, some continue to experience complications for years.
How to Prevent Shigella Infection
According to the World Health Organization, “Despite the continuing challenge posed by Shigella, there is room for optimism as advances in biotechnology have enabled the development of a new generation of candidate vaccines that shows great promise for the prevention of Shigella disease.”  But such a vaccine has yet to be perfected. Thus, in the meantime, preventing infection is the best approach, and that means implementing proper sanitation measures. [1, 14] Indeed, as noted in one authoritative text summarizing the research:
A safe water supply is important for the control of shigellosis and is probably the single most important factor in areas with substandard sanitation facilities. Chlorination is another factor important in decreasing the incidence of all enteric bacterial infections. Of critical importance to the establishment of a safe water supply is the general level of sanitation in the area and the establishment of an effective sewage disposal system. 
As previously noted, it takes but a few—far less than 100—Shigella bacteria to cause infection.  Moreover, a person can be infectious even if there are no symptoms, either because he remained asymptomatic (never exhibited symptoms of shigellosis), or because the person continued to shed the bacteria in his stool for a week or two after recovering. [11, 16, 17]
The spread of Shigella from an infected person to other persons can be avoided by frequent and careful hand-washing with soap and hot water. [1, 14, 15] Hand-washing among children should be frequent and supervised by an adult in daycare centers and homes with children who have not been fully toilet trained. [24, 28]
If a child in diapers has shigellosis, everyone who changes the child’s diapers should be sure the diapers are disposed of properly in a closed-lid garbage can, and should wash his or her hands and the child’s hands carefully with soap and warm water immediately after the diaper has been changed. [15, 39] After use, the diaper changing area should be wiped down with a disinfectant such as diluted household bleach, Lysol, or bactericidal wipes. [15, 24, 39] When possible, young children with a Shigella infection who are still in diapers should not be in contact with uninfected children. [1, 11, 15]
Basic food safety precautions and disinfection of drinking water should prevent Shigella bacteria from contaminating food and water. [11, 15, 39] Nonetheless, it should go without saying that people with shigellosis should not prepare food or drinks for others until they have been confirmed (by a stool culture) to no longer be shedding Shigella bacteria in their stool. [1, 15] At swimming beaches, there should be bathrooms and handwashing stations near the swimming area to help keep the water from becoming contaminated. [14, 29] Daycare centers should not provide water play areas. 
Simple precautions taken while traveling to the developing world can prevent shigellosis. [1, 39] Drink only treated or boiled water, and eat only cooked hot foods or fruits you peel yourself. [1, 11] The same precautions prevent other types of traveler’s diarrhea. 
Bill Marler is an accomplished personal injury and products liability attorney. He began litigating foodborne illness cases in 1993, when he represented Brianne Kiner, the most seriously injured survivor of the Jack in the Box E. coli O157:H7 outbreak. Bill settled Brianne’s case for $15.6 million, creating a Washington state record for an individual personal injury action.
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