Leader in digital CPD Earn 3 for Southern African Gastroenterology healthcare professionals free CEUs An approach to acute and chronic diarrhoea Learning objectives You will learn: • The causes of and risk factors for acute and chronic diarrhoea • How to screen and diagnose acute and chronic diarrhoea • The general principles of treating diarrhoea, with a focus on anti-diarrhoeal agents used adjunctively to oral rehydration and, if necessary, antimicrobials. Introduction In the healthy adult, diarrhoea is often viewed as a ‘nuisance’ disease. However, serious complications including severe dehydration and renal failure can occur and may necessitate admission to hospital. Elderly people and those in long-term care have an increased risk of death as a consequence of diarrhoea. Diarrhoea is reported to cause more deaths, an estimated 2.5 million annually, than any other condition Oral rehydration in children under five years of age living in resource-poor countries. In South Africa, therapy is central to diarrhoea accounts for 19% of deaths of children under five years of age; dehydration 1-3 the management of is the key factor in these deaths. acute diarrhoea, being Diarrhoea is classified as acute (short-term, less than 7 days), prolonged (a form of sufficient in most acute diarrhoea lasting more than 7 days), or chronic (long-term, more than 2 weeks patients to prevent in children or 4 weeks in adults). It is also classified as mild, moderate, or severe, complications due to with dehydration reflecting severity of symptoms. Oral rehydration therapy (ORT) is dehydration, but it central to the management of acute diarrhoea, being sufficient in most patients to prevent complications due to dehydration, but it has no effect on the duration of the has no effect on the disease or frequency of bowel motions.4,5 duration of the disease or frequency of bowel This review considers an approach to the management of acute and chronic diarrhoea motions in adults and children, with a special focus on anti-diarrhoeal agents that safely decrease the duration of diarrhoea adjunctive to ORT. This report was made possible by an unrestricted educational grant from Cipla. The content of the report is independent of the sponsor. © 2020 deNovo Medica NOVEMBER 2020 I 1 An approach to acute and chronic diarrhoea Causes of diarrhoea Diarrhoea almost always occurs by one or normal secretory processes; disruption of epi- more of four mechanisms: disruption of thelial cells or the epithelial tight junctions; or osmotic forces in the intestine; disruption of motility disorders (Table 1).5 Table 1. Mechanisms by which diarrhoea can occur5 Osmotic Large quantities of poorly absorbed, low molecular-weight solutes in the lumen drive the transport of excessive water into the lumen via osmotic forces Secretory Overstimulation of the secretory capacity of the intestinal tract, usually as a result of bacterial and viral enterotoxins Exudative Bacterial and viral pathogens destroy epithelial cells or disrupt the tight junctions of the intestinal epithelium; this allows water and electrolytes, mucus, and proteins to exude into the lumen due to the hydrostatic pressure differential, where they may accumulate and cause diarrhoea Motility Accelerated intestinal transit time can decrease absorption, causing diarrhoea even when disorders the absorptive process itself is proceeding normally Parasitic There are numerous potential causes of Infectious causes often lead to acute symp- pathogens are diarrhoea (Table 2). Viral pathogens are toms, but in some cases can result in chronic less common, most likely to be responsible for infectious diarrhoea in immunodeficient patients or in although there diarrhoea in infants, with rotavirus being persistent diarrhoea due to a malabsorptive is a higher the most severe enteric pathogen in children. enteropathy. It remains unclear whether gut likelihood of this Norovirus is the most common viral cause microbiota alterations are the cause or the of diarrhoea in adults. Many bacterial spe- consequence of chronic disorders with multi- being the cause cies produce toxins that can cause diarrhoea factorial pathogenesis, such as inflammatory of diarrhoea through different mechanisms. Parasitic bowel disorder (IBD). Non-infectious aetiolo- in HIV-positive pathogens are less common, although there gies of diarrhoea include medications, food individuals is a higher likelihood of this being the cause allergy or intolerance, digestive disorders, and of diarrhoea in HIV-positive individuals. anatomical disorders.4,6 Table 2. Causes of diarrhoea4,6 Viral infection Norovirus Adenovirus Rotavirus Astrovirus Cytomegalovirus Sapovirus Bacterial infection Escherichia coli Bacillus cereus Shigella dysenteriae Aeromonas hydrophila Clostridium perfringens Campylobacter jejuni Clostridium difficile Salmonella enterica Staphylococcus aureus Parasitic infection Cryptosporidium parvum Cyclospora cayetanensis Entamoeba histolytica Listeria monocytogenes Giardia lamblia Medication Antibiotics Long-term use of proton pump inhibitors Magnesium-containing products 2 I NOVEMBER 2020 An approach to acute and chronic diarrhoea Food allergy or Cow’s milk Soy intolerance Egg Fructose/lactose intolerance Seafood Digestive disorder Coeliac disease Inflammatory bowel disease (IBD) Crohn’s disease Ulcerative colitis Irritable bowel syndrome (IBS) Anatomical disorder Gastroschisis Acute volvulus can cause short-bowel Necrotising enterocolitis (NEC) syndrome (SBS) Surgical resection Risk factors for diarrhoea The cause of infectious diarrhoea depends with a high number of cases due to bacterial The cause of on geographical location, standards of food enteropathogens in the summer months and infectious hygiene, sanitation, water supply, and season. rotavirus in the winter months. Prolonged Exposure to infectious agents is the major diarrhoea, due to a longer and more serious diarrhoea risk factor for acute diarrhoea, with bacteria infection, is associated with reduced growth.4,6 depends on and viruses often transmitted by the faecal- geographical oral route. Hand washing and hygiene are People living with HIV are at increased risk location, important to prevent infection. of diarrhoea because of drug interactions standards of with antiretroviral therapy. This may be Diarrhoea is common in infants and is further aggravated by malnutrition and other food hygiene, usually acute. If chronic, it is commonly infectious diseases, which are frequent, and sanitation, caused by allergies and by infectious agents. the complications of immunocompromise, water supply, Incidence of diarrhoeal disease varies greatly gastrointestinal manifestations of primary and season with the seasons and child’s age but is mostly HIV disease, and other challenges.1,2 due to either bacterial or viral pathogens, Screening and diagnosis Acute diarrhoea Acute diarrhoea of infectious aetiology to diarrhoeal disease (Table 3) are seldom is generally associated with other clini- used or required in patients with acute watery cal features suggesting enteric involvement diarrhoea. Routine clinical laboratory detec- including nausea, vomiting, abdominal pain tion of bacterial pathogens requires the use and cramps, bloating, flatulence, fever, pas- of differential culture media, which select for sage of bloody stools, tenesmus, and faecal the growth of certain bacteria but may fail to urgency. Specific investigation is not normally detect other bacteria, especially in the setting required in the majority of cases of acute of antibiotic use. Features that may warrant watery diarrhoea because it is usually self- microbiological stool testing are outlined in limiting and resolves without specific treat- Table 4.5,7 EARN FREE ment. Conventional diagnostic approaches CPD POINTS Table 3. Conventional diagnostic approaches to diarrhoeal disease7 Join our CPD community at www.denovomedica.com • Bacterial culture • Microscopy with and without stains or immunofluorescence and start to earn today! • Stool antigen tests for detection of protozoa and for detecting viral agents • Electron microscopy • Antigen-based tests. NOVEMBER 2020 I 3 An approach to acute and chronic diarrhoea Table 4. Indications for considering microbiological stool testing • Severe illness with: – Profuse watery diarrhoea with signs of hypovolaemia – >6 unformed stools per 24 hours – Severe abdominal pain – Need for hospitalisation • Other signs and symptoms of inflammatory diarrhoea: – Bloody diarrhoea – Many small volume stools containing blood and mucus – Fever ≥38.5°C • High-risk host features: – Age ≥70 years – Comorbidities such as cardiac disease which may be exacerbated by hypovolaemia or rapid infusion of fluid – Immunocompromising condition, including AIDS – IBD – Pregnancy • Public health concerns. Specific In the evaluation of the patient with persis- • Travel history tent symptoms that have not responded to • Nature of the initial symptoms investigation empiric treatment, it is important to test for • Onset (sudden or gradual) is not normally parasitic organisms and to evaluate other • Duration, frequency, and characteristics required in non-infectious processes that may be the of bowel movements (particularly the pres- the majority cause of the diarrhoea. Every child with ence of blood or mucus) of cases of persistent diarrhoea should be examined for • Stool volume non-intestinal infections such as pneumo- • Tenesmus acute watery nia, sepsis, urinary tract infection, and otitis • Association with particular foods diarrhoea media, and