GASTROINTESTINAL INFECTIONS

Bacterial gastroenteritis
C Nic Fhogartaigh DAB Dance

Abstract
Infectious diarrhoea is a major public health concern worldwide. Bacteria, the focus of this review, are responsible for 20e40% of diarrhoeal episodes, contributing to high rates of childhood mortality in developing regions, and substantial morbidity and economic losses in developed regions. The epidemiology is changing with salmonellosis decreasing in industrialized countries and diarrhoeagenic Escherichia coli contributing to an increasing burden of disease worldwide. Molecular diagnostics have improved our understanding of the epidemiology, aetiology and pathogenesis of bacterial gastroenteritis, and have revealed new pathogenic agents, although widespread introduction of such diagnostics into clinical practice will require careful cost-benet analyses. The development of antimicrobial resistance in gastrointestinal pathogens has implications for treatment options. We review the epidemiology of infectious diarrhoea, the principal aetiological agents and their clinical features, and the diagnosis, treatment and prevention of bacterial gastroenteritis; we also propose an investigation and management algorithm.

there is a greater burden of diarrhoeal disease and associated childhood mortality. Although mortality has declined with the introduction of oral rehydration therapy (ORT), morbidity is unchanged, and prolonged or recurrent diarrhoea is associated with malnutrition and adverse effects on growth and development.2 Certain bacteria, such as shiga toxin-producing Escherichia coli and Campylobacter spp., are also associated with serious complications, including haemolyticeuraemic syndrome (HUS) and GuillaineBarr e syndrome (GBS). With increasing international travel and globalization of the food industry, clinicians must be alert for imported and unusual pathogens and outbreaks, and consider increasing antibiotic resistance when choosing empirical treatment.

Epidemiology
Infectious diarrhoea is a major public health concern worldwide. In developing countries, children under 5 years suffer three or four diarrhoeal episodes per year, with signicant but declining mortality.3 In contrast, less than 0.3 episodes occur per person per year in developed regions4 but this still equates to over 5 million cases each year in the USA, 80% of which are foodborne.5 The large majority do not present to healthcare facilities, but result in substantial morbidity and economic losses estimated at billions of dollars annually.

Keywords Campylobacter; diagnosis; diarrhoea; diarrhoeagenic Escherichia coli; gastroenteritis; management; pathogenesis; Salmonella; Shigella; Vibrio cholerae

Causative bacterial pathogens

A recent UK study combining culture and molecular methods to detect intestinal pathogens found campylobacter to be the commonest cause of bacterial gastroenteritis1 particularly in more severe cases presenting to general practitioners, followed by enteroaggregative Escherichia coli, non-O157 shiga toxin-producing E. coli (STEC), and non-typhi salmonellae (NTS).1 Diarrhoeagenic E. coli strains other than O157:H7 appear to be contributing increasingly to diarrhoeal disease1,5 and are not included in routine screening procedures. Over the past 20 years, food-borne outbreaks of diarrhoea have increasingly been attributed to campylobacter and STEC, whereas the incidence of salmonella has been declining.6 Bacteria are also the main cause of travellers diarrhoea (TD). Using conventional culture methods, shigella and NTS are identied in the majority of TD acquired in Africa, Latin America and the Caribbean; and shigella, NTS and campylobacter are identied in similar proportions of TD in South Asia.7 However, molecular techniques have shown that enterotoxigenic E. coli causes the majority of cases in all regions, except for South East Asia where campylobacter accounts for around 33%.7 Clostridium difcile, an important cause of hospital-acquired diarrhoea, is reviewed in a separate article and will not be discussed here.

Introduction
Gastroenteritis refers to syndromes of diarrhoea or vomiting due to non-inammatory infection in the upper small bowel or inammatory infection in the colon; it is usually self-limiting, and may be caused by bacteria, viruses, or parasites. In approximately half of all suspected cases, no pathogen is identied.1 Aetiological agents vary with geographical region and population factors. Viruses are more common causes in infants and children, particularly in developed countries. Bacteria, the focus of this review, are responsible for 20e40% of diarrhoeal episodes in which an infective agent is identied in the UK1 but are likely to contribute more signicantly in developing regions, where

C Nic Fhogartaigh MBBS (Hons) MSc MRCP FRCPath DTM&H is a Specialist Registrar in Infectious Diseases and Microbiology currently seconded by Public Health England to the Lao Oxford Mahosot Hospital Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao Democratic Peoples Republic. Competing interests: none declared. DAB Dance MB ChB MSc FRCPath is a Clinical Research Microbiologist from the Centre for Tropical Medicine, University of Oxford, UK, working at the Lao Oxford Mahosot Hospital Wellcome Trust Research Unit Mahosot Hospital, Vientiane, Lao Democratic Peoples Republic. Competing interests: none declared.

Risk factors8
Many host and environmental factors inuence the development of bacterial gastroenteritis, including:  Weaning: loss of mucosal immunity from maternal antibody.  Age: young children lack immunity to certain pathogens (e.g. enteropathogenic E. coli). The elderly are at increased risk of infection due to age-related alterations in mucus

MEDICINE 41:12

693

2013 Elsevier Ltd. All rights reserved.

GASTROINTESTINAL INFECTIONS

 

  

production, gut ora, and cell surface receptors for microbial adhesins or toxins (e.g. C. difcile). Gastric acidity: achlorhydria, gastrectomy and use of antacids/proton pump inhibitors decrease the bactericidal effect of gastric acid. Intestinal dysmotility: adversely affects the distribution of normal intestinal ora and prevents removal of pathogens. Antibiotics: reduce normal intestinal ora (particularly anaerobes) thereby increasing colonization opportunities for pathogens. Immunosuppression: impaired adaptive immunity (e.g. human immunodeciency virus (HIV) infection) predisposes to some enteric pathogens such as NTS. Genetic predisposition: blood group O is associated with increased susceptibility to cholera. Overcrowded living conditions: enhance spread of organisms with a low infective dose (e.g. Shigella spp.). Poor sanitation: increases the acquisition of food- and waterborne infection as well as person-to-person transmission.

recommended,5,11 taking account of increasing uoroquinolone resistance worldwide, particularly in South East Asia where rates of 80% are reported.11 Diarrhoeagenic E. coli (DEC) E. coli is part of the normal gut ora, but at least ve groups of pathogenic strains can cause a range of gastrointestinal illness. Advances in molecular methods of detection have increased understanding of the epidemiology and pathogenesis of these organisms. Humans are reservoirs of infection, with the exception of STEC for which cattle are the main reservoir. Enteropathogenic (EPEC): causes watery diarrhoea in infants in developing countries, and sporadic diarrhoea during summer months in industrialized countries. Transmission is from person to person as a result of overcrowded, unhygienic conditions, or from ingestion of contaminated food and infant feeds. Institutional outbreaks are common. Enterotoxigenic (ETEC): causes watery diarrhoea in developing countries, particularly in children, and is the commonest cause of TD. Transmission is via contaminated food and water. The infective dose is high (108 organisms). Enteroinvasive (EIEC): displays epidemiology is similar to EPEC, but clinical presentation ranges from watery diarrhoea to invasive dysentery. Spread is from person to person or food-borne. Enterohaemorrhagic/shiga toxin-producing (STEC): non-O157 STEC now appears to outnumber O157:H7 as a cause of diarrhoeal illness in children and adults.1 Infections are more common in the summer months, and occur after consumption of undercooked meat, although vegetables and unpasteurized milk have also been implicated, as well as animal contact. Person-toperson transmission occurs with a low infective dose (<100 organisms). Disease ranges from mild to grossly bloody diarrhoea with abdominal pain, usually without fever. In 8e15% of cases STEC O157:H7 is associated with life-threatening HUS. This causes acute renal failure, microangiopathic haemolytic anaemia and thrombocytopenia, mainly in children under 5 years,12,13 and is due to a toxin homologous to the shiga toxin of Shigella dysenteriae. By contrast, in an outbreak of E. coli O104:H4 in Germany, rates of HUS of 25% were seen and adults were predominantly affected.14 Antibiotics appear to increase toxin production in animal models of STEC, and although retrospective studies have shown variable associations between antibiotic use and development of HUS in humans, a prospective study demonstrated increased rates of HUS in those treated with antibiotics (36%) compared to those who did not (12%).13 A high leucocyte count and vomiting were also associated with higher risk of HUS.13 Enteroaggregative (EaggEC): causes chronic diarrhoea in children in developing regions and TD. Although previously rare in developed countries, it is increasing in frequency.1 Occasional outbreaks have occurred in Europe. Antibiotics should be avoided in patients with DEC and treatment is symptomatic, particularly where STEC is suspected. In moderate-to-severe cases of TD (three or more loose stools/24 hours, with additional enteric symptoms), a uoroquinolone e or

Pathogenic mechanisms and associated clinical syndromes

Bacteria cause gastroenteritis by three main mechanisms associated with distinctive but overlapping clinical syndromes (Table 1):  Production of preformed toxin: induces vomiting and abdominal cramps within a few hours of ingestion.  Secretion of toxin after adhering to intestinal epithelium: causes a syndrome of watery diarrhoea, without blood or mucus or associated fever (non-inammatory).  Invasion of intestinal mucosa: causes dysentery, the passage of small-volume stools containing blood, mucus and pus associated with fever, lower abdominal pain and tenesmus (inammatory).

Principal bacterial causes of gastroenteritis

Campylobacter Campylobacter jejuni and Campylobacter coli are leading causes of bacterial gastroenteritis worldwide, children and young adults being most susceptible. Organisms usually reside in the intestine of cattle, poultry, domestic pets and birds. Infection occurs after ingestion of contaminated undercooked food, or close contact with infected animals. Person-to-person transmission is uncommon. The infective dose is approximately 102e105 organisms. Clinical presentation varies, from an asymptomatic carrier state, through mild enteritis with abdominal cramps and watery diarrhoea, to dysentery with severe abdominal pain, fever and bloody diarrhoea. The incubation period is typically 1e6 days, often with a prodrome of fatigue and myalgia. Symptoms last a few days but persist beyond a week in around 10% of cases. Complications include bacteraemia and osteomyelitis. There is an increasing appreciation of the role of C. jejuni in uncommon but signicant postinfectious sequelae, such as reactive arthritis, transverse myelitis, GBS, and myocarditis.9 Campylobacter has also been linked to a rare lymphoma called immunoproliferative small intestinal disease, which may respond to antimicrobial therapy in the early stages.10 Symptoms are usually self-limiting, but if treatment is considered (see Figure 1) azithromycin 500 mg daily for 3 days is

MEDICINE 41:12

694

2013 Elsevier Ltd. All rights reserved.

GASTROINTESTINAL INFECTIONS

1. Assess hydration

Features of severe dehydration Parched mucous membranes Sunken eyes Skin fold recoil/CRT >2 seconds Rapid, low-volume pulse Hypotension Decreased urine output Decreased level of consciousness Unable to drink

Yes

Initiate IV fluids and monitor fluid balance Initiate ORT Continue breastfeeding. Normal diet to resume once hydrated If acutely unwell/unstable/ acute abdomen: FBC, U&E, LFTs, CRP Blood cultures AXR Surgical/gastroenterology opinion

No

2. Clinical history and examination 1

2

3. Exclude important differentials

Features of inflammatory diarrhoea Fever Blood/mucus/pus Tenesmus Risk factors for complications >65 years Renal impairment; diuretics Immunocompromise, e.g. HIV, DM, chemotherapy, corticosteroids IBD Prosthesis/valvular heart disease

Stool microscopy Stool culture for Camp, Sal, Shig, E. coli 0157:H7 Consider empirical antibiotics3 Avoid antimotility agents 4. Specific cultures/assays if indicated by: Prolonged culture with cold enrichment for Yersinia

Yes Posit ive

No

Stool microscopy Negat ive CDT

ORT +/ antimotility agents Consider antibiotics for travellers diarrhoea3 Consider testing for norovirus/parasites

Recent antibiotics Coastal/seafood exposure in tropical region Persistent fever and RIF pain Bloody diarrhoea, severe abdominal pain and tenderness, in absence of fever/abundant stool white cells

TCBS for Vibrio sp.

Look for evidence of HUS

Avoid antibiotics and antimotility agents

Microscopy for ova, cysts, and parasites; consider mycobacteria

1

Symptoms >2 weeks/immunocompromise

Clinical history and examination Epidemiological: Contacts including sexual (especially MSM) Travel Food consumption Undercooked meat/poultry/seafood/ soft cheese/ unpasteurized milk Recreation Water/animal exposure Occupation Food handler/ healthcare worker Examination: Fever Hypovolaemia Septic Abdominal tenderness Acute abdomen Rectal exam (+/ proctoscopy) Complications: toxic megacolon/HUS/ disseminated infection Exclude important differentials

Differential diagnoses

Clinical: Onset and duration Characteristics of stool Profuse watery Presence of blood/mucus/pus Fever Associated symptoms Comorbidities/ immunocompromise Medication including recent antibiotics and allergies

Empiric antibiotics

Must take into consideration local pathogens and resistance patterns, as well as patient age, allergy and concurrent medications Azithromycin 1 g single dose orally followed by 500 mg daily for 3 days (preferred in pregnancy/children) OR ciprofloxacin 500 mg twice daily orally for 3 days Travellers diarrhoea: azithromycin 1 g single dose orally (especially if travel to Asia) OR ciprofloxacin 500 mg single dose orally Longer courses required in immunocompromised (seek microbiology advice) Adjust therapy based on culture and susceptibility results Antibiotics are generally avoided in children <3 years: if premature infant, chronic illness, or immunocompromise exists seek paediatric/microbiology advice

Colonic inflammation: IBD Ischaemic colitis Diverticulitis Rectosigmoid abscess Appendicitis Colonic carcinoma Radiation colitis Malabsorption: Pancreatic insufficiency Coeliac disease Pernicious anaemia Scleroderma Excessive intestinal secretions: Disrupted enterohepatic circulation of bile Villous adenoma Enterotoxin-like endocrine causes: Thyrotoxicosis Carcinoid Pancreatic non- islet cell tumour Autonomic disturbance: Diabetic enteropathy In children: Intussusception Malrotation Volvulus NEC in premature infants

AXR, abdominal X-ray; Camp, Campylobacter; CDT, Clostridium difficile toxin; CRP, C-reactive protein; CRT, capillary refill time; DM, diabetes mellitus; FBC, full blood count; HIV, human immunodeficiency virus; HUS, haemolytic uraemic syndrome; IBD, inflammatory bowel disease; IV, intravenous; LFTs, liver function tests; MSM, men who have sex with men; NEC, necrotizing enterocolitis; ORT, oral rehydration therapy; RIF, right iliac fossa; Sal, Salmonella; Shig, Shigella ; TCBS, thiosulphate citrate bile salt sucrose agar; U&Es, urea & electrolytes.

Figure 1 Algorithm for management of suspected infectious diarrhoea.

MEDICINE 41:12

695

2013 Elsevier Ltd. All rights reserved.

GASTROINTESTINAL INFECTIONS

azithromycin for cases acquired in South East Asia e is recommended.5,15 Non-typhi salmonellae (NTS) Salmonella enterica var. Typhimurium and var. Enteritidis are common gastrointestinal pathogens worldwide. The incidence of NTS infections increased dramatically in the UK and USA in the 1980se1990s due to outbreaks linked to poultry and egg products, but has declined since 1998 due to vaccination of broiler hens and greater restrictions on imported eggs.1 NTS are also responsible for a proportion of the incidence of TD and childhood diarrhoea in developing countries. Invasive NTS strains have emerged as a prominent cause of bacteraemia in Africa (particularly in those with HIV, malnutrition or concomitant malaria), where fever and respiratory symptoms are more common than diarrhoea.16 Infection is due to consumption of contaminated meat, poultry, eggs and dairy produce; however, exposure to exotic pets (e.g. snakes, terrapins) is an emerging risk, implicated in up to 5% of infections.8 Person-to-person spread also occurs. The infective dose is variable, and the incubation period is usually 12 e48 hours. Disease is normally self-limiting over a few days but may be more severe, particularly in the very young, elderly or immunocompromised. Transient bacteraemia occurs in 5e17% of cases, higher rates being seen in hospitalized cases.17 Persistent fever is an indication for blood cultures and investigation for metastatic infection, particularly in individuals with risk factors5 (Figure 1). Faecal excretion of NTS may persist for weeks after recovery, and in chronic carriers for periods greater than a year, with bacteria residing in the gall-bladder. Age affects carriage, with

10% of those over 50 years becoming chronic carriers, compared with less than 1% of those under 20 years.18 Management is usually supportive, as antibiotic use is associated with prolonged faecal carriage, without reducing symptom duration or severity.19 In those at risk of metastatic infection or complications (Figure 1), treatment with ciprooxacin or azithromycin for 7 days is advisable.11 Shigella The majority of shigella infection occurs in children in underdeveloped regions, although it has also been responsible for outbreaks in daycare and nursery schools in the UK and USA. Shigella sonnei is most commonly isolated in the UK, whereas Shigella exneri causes most endemic disease in the developing world. The highly virulent shiga toxin-producing S. dysenteriae, which caused epidemics with high rates of mortality in developing countries, appears to be declining. Person-to-person spread is common due to the low infective dose (10e100 organisms), but contaminated food and water also contribute. After an incubation period of 2e3 days there is sudden-onset abdominal pain and watery diarrhoea accompanied by fever, malaise and anorexia, which may progress to frequent bloody, mucous stool with tenesmus. Symptoms may persist for up to 14 days. Severe infections, typically due to S. dysenteriae serogroup 1, may be complicated by febrile convulsions, hyponatraemia, hypoglycaemia, toxic megacolon, encephalitis, reactive arthritis and HUS. Antibiotic treatment, when indicated in severe and unremitting infection, is with ciprooxacin 500 mg twice daily for 3 days. Azithromycin is preferred in children and pregnancy.5,11 Vibrio cholerae Cholera is endemic in Asia, Africa, and Central and South America. Most epidemics in Africa and Asia are due to the El Tor (O1) biotype, although the classical biotype persists in Bangladesh. Infection usually occurs after ingestion of faecally contaminated food or water, although sporadic infections have originated from natural aquatic reservoirs, such as those associated with seafood consumption in the Gulf of Mexico. The infectious dose is high (106 organisms) and most individuals remain asymptomatic or mildly symptomatic after exposure. The incubation period varies from 18 hours to 5 days. Abrupt-onset profuse, painless, watery diarrhoea leads to varying degrees of dehydration. Vomiting is also common. The mainstay of therapy is rehydration, with uid balance monitoring to avoid hypovolaemic shock, electrolyte disturbance and renal failure. Antimicrobial treatment reduces the duration and volume of diarrhoea. Doxycycline 300 mg as a single dose, or ciprooxacin 500 mg twice daily for 3 days (depending on local susceptibility patterns), is recommended for suspected cases but resistance rates are increasing.20 Azithromycin is a suitable alternative and is the treatment of choice in children.20

Major bacterial causes of gastroenteritis and the most commonly associated clinical syndromes
Intoxication C Staphylococcus aureus C Bacillus cereus C Clostridium perfringens Watery diarrhoea C Vibrio cholerae C Non-typhi salmonellae C Enterotoxigenic E. coli C Enteroaggregative E. coli C Enteropathogenic E. coli C Enteroinvasive E. coli C Campylobacter spp. C Yersinia spp. Dysentery C Shigella spp. C Enteroinvasive E. coli C Enterohaemorrhagic/shiga toxin-producing E. coli C Campylobacter spp. C Yersinia spp. Table 1

Emerging infections
Improvements in molecular detection of gastrointestinal bacteria have led to the identication of new possible pathogens. Laribacter hongkongensis, a Gram-negative bacillus, was described

MEDICINE 41:12

696

2013 Elsevier Ltd. All rights reserved.

GASTROINTESTINAL INFECTIONS

in community-acquired diarrhoea and TD originating in Asia where freshwater sh seem to be the main reservoir.21 Plesiomonas shigelloides also causes acute diarrhoea associated with seafood consumption and international travel.5 In developed regions, enterotoxigenic Bacteroides fragilis and Klebsiella oxytoca have been associated with diarrhoea and C. difcile-negative antibiotic-associated haemorrhagic colitis respectively, supported by animal models of infection,21 although these agents were also detected in signicant proportions of controls, making their signicance unclear.

Diagnosis
Macroscopic evidence of blood or white blood cells on stool microscopy conrms an inammatory process. An immunoassay for faecal lactoferrin e a neutrophil marker (Leukotest, Techlab) e may be more sensitive but is not widely available. Stool culture is the most widely used diagnostic test in sporadic cases, and should be performed in all cases of inammatory diarrhoea and in outbreak settings. Culture is not routinely recommended in TD, except in certain circumstances (Figure 1), due to low diagnostic yield.5 Indeed, culture methods are very poor at detecting most DEC. In the UK, selective media are usually inoculated for Campylobacter spp., Salmonella spp, Shigella spp. and E. coli O157, all of which take 2 days for identication, with antibiotic susceptibilities available on day 3. Samples should be sent to a reference laboratory if outbreaks of STEC infection are suspected as most non-O157 STEC go unrecognized in non-specialist laboratories. The Centres for Disease Control now recommend that an enzyme immunoassay or polymerase chain reaction (PCR) for STEC be performed in addition to culture in all cases of community-acquired diarrhoea, and not just in cases of bloody diarrhoea and HUS.12 PCR methods, including multiplex real-time PCR for simultaneous and rapid detection of multiple pathogens, have been shown to increase diagnostic yield from stool samples, although an increased number positive results were also seen in stools from healthy controls, making results difcult to interpret.22 Conventional culture combined with qualitative or quantitative molecular techniques may be the optimal approach, but careful cost-benet analyses and adequate training are required before widespread introduction of novel diagnostics into clinical practice.

Assessment and management

Bacterial gastroenteritis rarely requires hospital admission, although signicant dehydration, severe disease and certain comorbidities increase the risk of complications and may warrant admission for observation and treatment. Mortality is commonly due to dehydration particularly in the very young and elderly. A management algorithm is presented in Figure 1.  Rehydration is the priority: ORT is preferred, if tolerated, as glucose-coupled sodium absorption occurs with oral rehydration, and is less likely to cause the uid shifts and electrolyte disturbance associated with rapid intravenous uids. WHO reduced osmolarity ORT (Na 75 mmol/litre) has replaced standard ORT (Na 90 mmol/litre), but ricebased ORT is an effective alternative.

 Nutrition: normal diet should recommence as soon as dehydration is corrected. Breastfeeding should continue in infants. Children under 5 years in developing countries benet from vitamin A and zinc supplementation during the current diarrhoeal illness and in preventing future episodes.20  Empiric antibiotic therapy: where there are no clinical or epidemiological clues to the causative pathogen (e.g. an outbreak setting), antibiotics may be considered in adults with inammatory features (Figure 1), sepsis, risk factors for complications, and TD.5 In children, antibiotics are generally avoided as they do not ameliorate symptoms, aetiology is often viral, and children with bloody diarrhoea are more likely to have E. coli O157 and are therefore at risk of HUS. However, antimicrobials may be considered in premature infants, the immunocompromised, or children with chronic illnesses. For many years the preferred empirical therapy was a uoroquinolone, such as ciprooxacin. However, recent dramatic increases in resistance, particularly in campylobacter, but also in NTS, shigella and ETEC has led to a trend towards macrolide therapy with, for example, azithromycin,5 which has the added advantage of a better safety prole in children and pregnant women. Randomized controlled trials using macrolides in unselected populations with inammatory diarrhoea due to a range of bacterial pathogens are lacking, but single-dose azithromycin was as effective as single-dose uoroquinolone in treating noninammatory diarrhoea in a military group where pathogens other than campylobacter predominated.23 Rifaximin, a rifamycin with less than 0.4% absorption form the gastrointestinal tract, is an alternative option that has been licensed in the USA to treat uncomplicated TD, but is not yet available in the UK.  Adjunctive therapy: antimotility agents such as loperamide may be used in non-inammatory diarrhoea in adults, but are contraindicated in inammatory diarrhoea and in children under 2 years. Bismuth subsalicylate (PeptoBismol) has anti-secretory, anti-inammatory and mild antimicrobial properties, and appears to reduce frequency and duration of diarrhoea. It should be avoided in children aged under 3 years, in patients with salicylate allergy or renal impairment, and in those taking doxycycline or warfarin, absorption of which may be compromised.  Notication: suspected food poisoning, cholera and infectious, bloody diarrhoea are mandatorily notiable by clinicians in the UK, and Campylobacter spp, Salmonella spp., Shigella spp., vero-toxigenic E. coli and V. cholerae are notiable by laboratories.  Prevention of nosocomial transmission: hand hygiene, and contact isolation, preferably in a side-room are recommended.

Prevention of gastroenteritis
Five main strategies may be used in an attempt to prevent diarrhoeal illness, including bacterial gastroenteritis.  Dietary awareness: improvements in food safety from farm to fork aim to prevent outbreaks of food-borne disease. Individuals should also adhere to hand hygiene and

MEDICINE 41:12

697

2013 Elsevier Ltd. All rights reserved.

GASTROINTESTINAL INFECTIONS

safe food storage and preparation. Raw foods and unpasteurized milk should be avoided. Often quoted advice to travellers is Boil it, peel it, cook it, wash it, or forget it. Non-antibiotic options: daily probiotics have been shown to reduce rates of diarrhoea in children in developing regions.24 Bismuth subsalicylate 262 mg, two tablets four times a day, reduced the incidence of TD from 40% to 14% when compared to placebo5 but this should be taken for no more than 3 weeks. Prophylactic antibiotics: a short course of antibiotic prophylaxis is reserved for special individual circumstances, such as immunocompromised patients, those with inammatory bowel disease, diabetes or renal impairment, or those taking diuretics.5 Rifaximin, where available,5 is the drug of choice. Vaccines: the oral, killed, whole-cell cholera vaccine combined with the recombinant B subunit of cholera toxin (rCTB-WC) gives protection against serotype O1 for 4e6 months in endemic regions, with lower levels of protection for up to 3 years.25 This may reduce the burden of illness in local populations, and may be considered in travellers or relief workers spending prolonged periods in epidemic areas or refugee settings. Antigenic similarities between cholera toxin and heat-labile toxin of ETEC means that the vaccine should give cross-protection against ETEC, but a systematic review failed to demonstrate this benet26 and its use to prevent TD is not recommended. Despite ongoing research and development, there are no other effective vaccines to prevent bacterial diarrhoea. Hygiene and sanitation: public health measures such as provision of clean water and adequate sanitation facilities are of utmost importance in prevention and control of gastrointestinal infections, and improvements in developing regions will benet both local populations and travellers alike, although this will require a coordinated effort between public health and government authorities.

Conclusion
Increased international travel and globalization of the food industry have heightened the need for doctors to consider imported pathogens as causes of gastroenteritis. We must also consider the increased prevalence of antibiotic resistance when choosing empirical therapy. Advances in molecular and rapid detection of enteric pathogens have enhanced our understanding of the epidemiology of diarrhoeal disease and highlighted emerging bacterial pathogens. This knowledge may help to inform future diagnostic, therapeutic, preventative and control strategies. A

REFERENCES 1 Tam CC, OBrien S, Tompkins DS, et al. Changes in causes of acute gastroenteritis in the United Kingdom over 15 years: microbiologic ndings from 2 prospective, population-based studies of Infectious Intestinal Disease. Clin Infect Dis 2012; 54: 1275e86.

2 Guerrant RL, DeBoer MD, Moore SR, Scharf RJ, Lima AA. The impoverished gut e a triple burden of diarrhoea, stunting and chronic disease. Nat Rev Gastroenterol Hepatol 2013; 10: 220e9. 3 Kosek M, Bern C, Guerrant RL. The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ 2003; 81: 197e204. 4 Tam CC, Rodrigues LC, Viviani L, et al. Longitudinal study of infectious intestinal disease in the UK (IID2 study): incidence in the community and presenting to general practice. Gut 2012; 61: 69e77. 5 DuPont H. Bacterial diarrhea. N Engl J Med 2009; 361: 1560e9. 6 Gormley FJ, Little CL, Rawal N, Gillespie IA, Lebaigue S, Adak GK. A 17-year review of foodborne outbreaks: describing the continuing decline in England and Wales (1992e2008). Epidemiol Infect 2011; 139: 688e99. 7 Shah N, DuPont HL, Ramsey DJ. Global etiology of travelers diarrhea: systematic review from 1973 to the present. Am J Trop Med Hyg 2009; 80: 609e14. 8 Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennetts principles and practice of infectious diseases. 7th edn. Edinburgh: Churchill Livingstone, 2009. 9 Kirkpatrick BD, Tribble DR. Update on human Campylobacter jejuni infections. Curr Opin Gastroenterol 2011; 27: 1e7. 10 Lecuit M, Abachin E, Martin A, et al. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med 2004; 350: 239e48. 11 Ross AGP, Olds GR, Cripps AW, Farrar JJ, McManus DP. Enteropathogens and chronic illness in returning travellers. New Engl J Med 2013; 368: 1817e25. 12 Gould LH, Bopp C, Strockbine N, et al. Recommendations for diagnosis of Shiga Toxin-producing Escherichia coli infections by clinical laboratories. MMWR October 16, 2009; 58 (RR12): 1e14. http://www. cdc.gov/mmwr/preview/mmwrhtml/rr5812a1.htm. 13 Wong CS, Mooney JC, Brandt JR, et al. Risk factors for the hemolytic uremic syndrome in children infected with Escherichia coli O157:H7: a multivariable analysis. Clin Infect Dis 2012; 55: 33e41. 14 Frank C, Werber D, Cramer JP, et al. Epidemic prole of Shiga-toxin producing E. coli O104:H4 outbreak in Germany e preliminary report. New Engl J Med 2011; 365: 771e80. 15 Hill DR, Beeching NJ. Travelers diarrhoea. Curr Opin Infect Dis 2010; 23: 481e7. 16 Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA. Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet 2012; 379: 2489 e99. 17 Parry CM, Thomas S, Aspinall EJ, et al. A retrospective study of secondary bacteraemia in hospitalised adults with community acquired non-typhoidal Salmonella gastroenteritis. BMC Infect Dis 2013; 13: 107. 18 Chart H. Salmonella. In: Greenwood D, Slack R, Peutherer J, Barer M, eds. Medical microbiology. 18th edn. Edinburgh: Churchill Livingstone, 2012. 19 Onwuezobe IA, Oshun PO, Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev 2012. Issue 11. Art. No.:CD001167. 20 Harris JB, LaRocque RC, Qadri F, Ryan ET, Calderwood SB. Cholera. Lancet 2012; 379: 2466e76.

MEDICINE 41:12

698

2013 Elsevier Ltd. All rights reserved.

GASTROINTESTINAL INFECTIONS

21 Marcos LA, DuPont H. Advances in dening the aetiology and new therapeutic approaches in acute diarrhea. J Infect 2007; 55: 385e93. 22 Operario DJ, Houpt E. Dening the aetiology of diarrhea: novel approaches. Curr Opin Infect Dis 2011; 24: 464e71. 23 Sanders JW, Frenck RW, Putman SD, et al. Azithromycin and loperamide are comparable to levooxacin and loperamide for the treatment of travellers diarrhea in United States military personnel in Turkey. Clin Infect Dis 2007; 45: 294e301. 24 Sur D, Manna B, Niyogi SK, et al. Role of probiotic in preventing acute diarrhoea in children: a community-based, randomized, double-blind placebo-controlled eld trial in an urban slum. Epidemiol Infect 2011; 139: 919e26. 25 Quadri F, Ahmed F, Begum YA, Sack DA, Svennerholmn AM. Reduced doses of oral killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine is safe and immunogenic in Bangladeshi infants 6e17 months of age: dosing studies in different age groups. Vaccine 2006; 24: 1726e33. 26 Ahmed T, Bhuiyan TR, Zaman K, Sinclair D, Qadri F. Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea. Cochrane Database Syst Rev 2013. Issue 7. Art. No.:CD009029.

Practice points
C

Mortality due to diarrhoeal disease has fallen, but morbidity is unchanged Molecular advances have provided new data on epidemiology of gastrointestinal pathogens, including the discovery of new pathogenic agents, and offer promising targets for rapid diagnosis The mainstay of therapy is rehydration with oral rehydration therapy, but antibiotics are indicated in inammatory diarrhoea and in individuals at risk of complications, and may be considered in travellers diarrhoea; avoid antibiotics in children Fluoroquinolone resistance has increased dramatically in many pathogens, particularly Campylobacter spp., and in South East Asia; as a result, azithromycin is the empirical therapy of choice, but randomized controlled trials in unselected populations and in various regions are lacking Wider public health issues must be considered when managing infectious diarrhoea, including infection control and notication

MEDICINE 41:12

699

2013 Elsevier Ltd. All rights reserved.