Acute diarrhoea and fever

S Dundas, Consultant Physician, Infectious Diseases Unit, Monklands District General Hospital, Airdrie, UK
WTA Todd, Consultant Physician, Infectious Diseases Unit, Monklands District General Hospital, Airdrie, UK

Introduction

Diarrhoeal disease is an important cause of morbidity worldwide and represents a leading cause of childhood death in the developing world. In the developed world the mortality rate has fallen sharply due to a decline in illness caused by Clostridium perfringens and salmonellas. The elderly remain especially susceptible to the complications of diarrhoea and account for 85% of related deaths.

Diarrhoea may be defined as acute if present for less than 2 weeks, persistent if present for 2–4 weeks, and chronic if greater than 4 weeks in duration. Acute diarrhoea and fever may be the presenting symptoms of a number of underlying conditions and although infectious agents account for 90% of cases, inflammatory bowel disease, ischaemic colitis, acute diverticulitis, toxins, medications, and overflow from constipation should also be considered.

Infectious gastroenteritis

The majority of patients with acute diarrhoea do not seek medical attention, and investigations are frequently omitted in those who do, therefore the prevalence of infectious diarrhoea is grossly underestimated. Most cases are viral with bacterial stool cultures positive in less than 5% of presentations. Higher rates of stool culture positivity are observed in more severe cases, those with bloody diarrhoea, and those admitted to hospital.

Patients at increased risk of infectious gastroenteritis include travellers who have visited tropical or semitropical regions, the elderly, men who have sex with men, infants, the immunocompromised, or those who have received antibiotic agents.

In the UK notifications of organisms isolated in infectious gastroenteritis are collated by the Health Protection Agency and Health Protection Scotland. Campylobacter spp. (46%) are the most commonly isolated organisms and account for almost half of confirmed infections. Rotavirus (19%), small round structured virus (14%), and Salmonella (12%) infections are confirmed with similar frequencies. Shiga toxin-producing Escherischia coli (STEC 2%) and Shigella (1%) infections are infrequent.

Clinical features

Table 1 Major food-borne organisms by principal presenting gastrointestinal

A careful history may determine a possible source of infection, or whether the diarrhoea is of small or large bowel origin, thereby indicating the most likely pathogen (see Table 1). Relevant details are the duration of diarrhoea, the frequency and volume of stools, and the presence of blood or fever. Suspect foods within relevant incubation periods, recent antibiotic use or travel, hobbies, pets, medications, and affected contacts should also be considered. Indications for hospitalisation and investigation include profuse diarrhoea with signs of hypovolaemia, grossly bloody stools, fever, duration greater than 48 hours without improvement, severe abdominal pain, and diarrhoea in the elderly or immunocompromised.

Incubation period

Symptoms that begin within six hours suggest the ingestion of preformed toxin of Staphylococcus aureus or Bacillus cereus. Symptoms that occur 8–14 hours after ingestion suggest C. perfringens. Symptoms that begin more than 14 hours after ingestion can result from viral or bacterial infection.

Fever

Fever suggests infection with invasive bacteria such as Campylobacter, Salmonella, or Shigella, enteric viruses, or a cytotoxin-producing organism such as Clostridium difficile or STEC.

Diarrhoea

The enteric locus of infection and the dominant pathogenic process will determine the clinical presentation.

Acute dysentery is defined as frequent, small bowel movements accompanied by blood and mucous with tenesmus or pain on defecation. The syndrome implies inflammatory invasion of the colonic mucosa and in this context invasive bacteria such as Campylobacter, Shigella, and STEC are the most likely causes. Faecal leukocytes are present. The epidemiological patterns of acute dysentery are influenced by the low inoculum required for infection and consequently there is a high risk of person-to-person spread.

Large volume watery diarrhoea and diffuse abdominal cramps are typical of small intestinal infection. There is only a modest increase in the number of stools because the colonic reservoir is intact. This is a non-inflammatory process confirmed by the absence of faecal leukocytes. The diarrhoea is mediated by bacterial enterotoxins that alter fluid and electrolyte transport (Vibrio cholerae, enterotoxigenic E. coli, enteropathogenic E. coli, Salmonella spp., Cryptosporidium, Clostridium perfringens, Bacillus cereus) or organisms that characteristically affect the proximal small bowel (Giardia lamblia, Rotavirus, Norovirus: previously known as Norwalk agent).

Investigations

Faecal leukocytes

The ability of faecal leukocytes to predict inflammatory diarrhoea has varied greatly, with reported sensitivity and specificity ranging from 20–90%. Consequently, it is not recommended as a routine investigation of diarrhoea.

Stool cultures

Stool culture is important in those with severe illness, the immunocompromised, and for employees such as food handlers, who require negative stools to return to work. A routine culture will identify Campylobacter, Salmonella, and Shigella. Culture for Shiga toxin-producing organisms such as E. coli O157, although requiring a specific McConkey sorbital medium, is now carried out routinely in the UK. Bacterial pathogens are excreted continuously and a negative result is generally accurate. Stool cultures are of little value in those developing diarrhoea following more than 72 hours hospitalisation, in whom stool examination for C. difficile toxin is a much more relevant investigation.

Routine stool examination for ova, cysts, and parasites (OCP), such as Giardia, Cryptosporidium, Cyclospora, Entamoeba histolytica, is not cost effective. Stools should be investigated for OCP in cases of persistent diarrhoea, patients who have travelled to an endemic area such as Eastern Europe, within a community water-borne outbreak, in men who have sex with men, and in cases of bloody diarrhoea where amoebiasis is suspected. Due to the intermittent excretion of OCP three stool specimens should be sent on consecutive days.

Further investigation

Flexible sigmoidoscopy or colonoscopy are rarely indicated but may be required to identify inflammatory bowel disease or ischaemic colitis, and in immunocompromised patients. Additional investigations are determined by the most likely pathology, and abdominal CT, barium enema, or isotope-labelled white cell scan may be required in specific circumstances.

Management

All suspected infective cases require single-room isolation with ‘enteric’ precautions.

Fluid and electrolyte replacement constitutes the cornerstone of treatment of diarrhoeal illness. Intravenous rehydration is grossly overused and rehydration should preferably be by the oral route with solutions that contain water, salt, and sugar. Antimotility agents should be avoided as they may exacerbate or prolong symptoms.

In otherwise healthy patients there is a lack of benefit from antibiotic therapy. The British Infection Society has identified patients with ‘high risk criteria’ for whom antibiotics should be considered on admission. These are:

The duration of gastroenteritis and the most likely organism should also be taken into consideration. If criteria for antibiotic therapy are met, oral ciprofloxacin, to which the majority of isolates remain susceptible, is generally recommended.

Important organisms

Viral infections

Thirty to forty per cent of all acute episodes of gastroenteritis are caused by viruses, which may be grouped into four categories: Rotavirus, enteric adenovirus, astrovirus, and calicivirus (including Norovirus) (see Figure 1).

Norovirus infections have become the most important cause of institutional, particularly healthcare-associated, outbreaks of gastroenteritis and are difficult to contain. A large human reservoir of infection, a very low infectious dose, and the ability to be transmitted by a variety of routes, including aerosol and faecal-oral, contribute to the impact of the disease. Infection by this virus has now become the most common cause of gastroenteritis in adults in the UK. A new genotype (2.4) has emerged recently and the previous clear winter peak has changed with the loss of the seasonal characteristic. Generally there is little merit in sending stools for viral cultures or PCR as knowing the identity of the virus does not alter management, which involves careful infection control and supportive fluids as above.

Bacterial pathogens

Figure 2 Gastrointestinal infections: Laboratory Reports Scotland 1983–2004

The annual number of cases of notified gastroenteritis by causative organism is shown in Figure 2.

Campylobacter

Campylobacter is now the most common cause of bacterial infective gastroenteritis in the UK. Infection is transmitted from raw or undercooked meat, especially poultry, and is often linked to fast food outlets, unpasteurised milk, and domestic pets with diarrhoea. Person-to-person transmission is unusual. The organism does not multiply in food and food-borne outbreaks are rare. The incubation period is 2–5 days. Presentation is usually with abdominal pain and bloody diarrhoea, vomiting is uncommon. Campylobacter may be confused with ulcerative colitis or Crohn’s disease and findings on rectal biopsy are not specific. Toxic megacolon has been reported and may necessitate colectomy. Transient bacteraemia occurs in 1% of infections and does not require specific treatment in the immunocompetent host. The majority of patients do not require antibiotics and although patients with ‘high risk’ features are usually treated with ciprofloxacin, significant resistance is emerging and recommendations may change.

Salmonella

Salmonella infections have reduced considerably in the UK over the last decade largely due to rigorous management of infection in poultry flocks. Transmission is predominantly from red and white meats, raw or undercooked eggs, milk, and dairy products. Person-to-person spread is common during the diarrhoeal phase of illness. Salmonellosis presents with watery diarrhoea, vomiting, and fever. Blood cultures are positive in 1–4% of infections and the elderly and the immunocompromised are at increased risk of both bacteraemia and metastatic infection. Endovascular infection occurs in 10–25% of persons over 50 years of age, usually involves the aorta, and most commonly results from seeding of atherosclerotic plaques or aneurysms. Mortality rates from endovascular infection range from 14–60% and are lower with prompt diagnosis and combined medical and surgical therapy. Ciprofloxacin is the antibiotic of choice for ‘high risk’ patients with severe gastrointestinal infection and bacteraemia. Prolonged antibiotic therapy is required for endovascular infection. Following the resolution of gastrointestinal symptoms the mean duration of carriage is 4–5 weeks but may be prolonged by antibiotic therapy.

Shiga-toxin producing E. coli (STEC)

STEC infections such as E. coli O157, although infrequent, attract significant attention because of potentially serious complications, particularly the haemolytic uraemic syndrome (HUS). Transmission is from undercooked ground beef, water, and cross-contamination of cooked products. The low infectious dose of STEC strains, estimated to be less than 100 organisms, facilitates transmission. Gastrointestinal symptoms range from mild diarrhoea to haemorrhagic colitis with often dominant and severe abdominal pain.

Haemolytic uraemic syndrome develops in 10% of patients overall, with children under the age of five and the elderly most at risk. Haemolytic uraemic syndrome is characterised by acute renal failure, haemolytic anaemia, and thrombocytopenia. Although the kidneys are the most vulnerable target organs, any tissue may be affected. Mortality rates following HUS have improved recently but remain around 5% in children and more in the elderly due to an increased incidence of neurological complications. Antibiotics should be avoided, as there is some evidence that they may promote the release of Shiga toxin and increase the risk of HUS.

Clostridium difficile-associated diarrhoea

Clostridium difficile-associated diarrhoea (CDAD) usually occurs 4–9 days after starting antibiotics, and almost all antibiotics have now been implicated in causation. It predominantly affects frail elderly people in whom the mortality rate may be as high as 25%. Clinical severity varies from mild watery diarrhoea to severe bloody diarrhoea. Complications include hypovolaemic shock, toxic megacolon, perforation, haemorrhage, and sepsis. C. difficile is spread indirectly by the faecal-oral route via spores left on surfaces. CDAD is characterised by progression from an uncolonised state through to C. difficile colonisation followed by, in response to antibiotic pressure, toxin production. Asymptomatic colonisation occurs in over 20% of hospital patients and UK infection rates are increasing exponentially, particularly in vulnerable hospitalised patients.

To eradicate CDAD oral metronidazole, 400 mg every 8 hours, is the treatment of choice. Oral vancomycin, in an initial dose of 125 mg every 6 hours, is at least as effective as metronidazole but in view of its greater cost should be reserved for those who have failed to respond to metronidazole or for the severely unwell patient. If patients are unable to take oral medications a nasogastric tube is necessary because the enteral route is required to treat infection. Current antibiotic therapy should be withdrawn if possible. Evidence is inadequate to support the use of prebiotics or probiotics for treatment of established CDAD.

HIGHLIGHTS

All cases of acute diarrhoea must be considered infective until proven otherwise and managed in appropriate single-room isolation with ‘enteric precautions’.
The incidence of the well-known pathogens in the aetiology of food poisoning/acute gastroenteritis has changed significantly in the last decade.
In adults, viral gastroenteritis due to Norovirus has become a major cause of institutional outbreaks of diarrhoea.
Clostridium difficile is an increasingly important cause of healthcare-associated infection.
Diarrhoea and fever as a syndrome has a heterogeneous aetiology and antibiotics should not be administered unless there are indications of specific risk or severity.