INTRODUCTION — Diarrheal diseases are one of the leading causes of death globally [1,2]. Most cases of diarrhea are associated with contaminated food and water sources, and more than 2 billion people globally have no access to basic sanitation [3].
The World Health Organization (WHO) provides guidelines for the management of diarrheal illness in resource-limited countries in "The Treatment of Diarrhea: A Manual for Physicians and Other Senior Health Workers" [4]. Specific WHO guidelines for the management of epidemic shigellosis [5] and cholera [6,7] are also available. The recommendations in this topic are consistent with those guidelines.
This topic reviews the clinical assessment, treatment, and prevention of acute diarrhea, including watery diarrhea and dysentery, in adults in resource-limited countries.
The clinical assessment and management of children with acute diarrhea in resource-limited countries and of individuals with diarrhea in resource-rich settings are discussed elsewhere. (See "Approach to the child with acute diarrhea in resource-limited countries" and "Causes of acute infectious diarrhea and other foodborne illnesses in resource-rich settings" and "Approach to the adult with acute diarrhea in resource-rich settings" and "Approach to the adult with chronic diarrhea in resource-abundant settings" and "Diagnostic approach to diarrhea in children in resource-rich countries" and "Overview of the causes of chronic diarrhea in children in resource-rich settings".)
CLASSIFICATION OF DIARRHEA — Diarrhea is defined as the passage of loose or watery stools, typically at least three times in a 24-hour period [8]. Acute diarrhea is defined as diarrhea of ≤14 days in duration, in contrast to persistent (>14 days and ≤30 days) or chronic (>30 days) diarrhea. Invasive diarrhea, or dysentery, is defined as diarrhea with visible blood, in contrast to watery diarrhea. Dysentery is commonly associated with fever and abdominal pain.
EPIDEMIOLOGY
Worldwide incidence — In contrast to the available data for younger children, incidence of diarrheal disease in older children and adults has not been calculated for many countries. In a systematic review of 23 prospective studies of diarrheal disease in individuals older than five years, estimated diarrhea morbidity rates ranged from 30 episodes per 100 person-years among adults in southeast Asia to 88 episodes per 100 person-years in the eastern Mediterranean region; rates had not changed substantially over 30 years [9]. Incidence in Africa was not evaluated in any of the studies included in the review.
Diarrheal illness occurs at a baseline frequency in resource-limited countries, superimposed with epidemic cases of diarrhea, either dysentery or watery diarrhea. Epidemics are generally due to Shigella dysenteriae serotype 1 (Sd1) and Vibrio cholerae. Major outbreaks due to Sd1 have occurred in Africa, South Asia, and Central America. In 1994, an explosive outbreak among Rwandan refugees in Zaire caused approximately 20,000 deaths during the first month alone [10]. Epidemics due to V. cholerae have occurred throughout Africa, Asia, the Middle East, South and Central America, and the Caribbean [11]. A cholera epidemic in Yemen has been ongoing since 2017 and is the largest in epidemiologically recorded history [12]. (See "Cholera: Clinical features, diagnosis, treatment, and prevention", section on 'Epidemiology' and "Shigella infection: Epidemiology, microbiology, and pathogenesis", section on 'Resource-limited settings'.)
Outbreaks due to Escherichia coli O157:H7, which is occasionally responsible for diarrheal epidemics in resource-limited settings, have been reported in Swaziland in 1992, as well as in Cameroon from 1997 to 1998 [13].
Risk factors
Crowding and poor sanitation — Individuals in refugee camps and unplanned urban settlements, with limited access to water and sanitation facilities, are at particular risk of diarrheal epidemics. Contaminated food and water play an important role in such epidemics. Direct contact with an infected individual may also contribute to the spread of epidemic dysentery due to S. dysenteriae.
HIV infection — Human immunodeficiency virus (HIV) infection is prevalent in many of the resource-limited areas where acute diarrheal diseases occur, and diarrhea-related morbidity and mortality may be increased in these individuals. Several enteric bacteria, such as Campylobacter, Salmonella, Shigella, enteroaggregative E. coli, and Vibrio species, occur with increased frequency and/or severity in individuals with HIV/acquired immunodeficiency syndrome (AIDS) [14,15]. Coinfection with multiple pathogens may also occur. Nontyphoidal salmonellosis is a particular concern in HIV-infected individuals, who have a higher risk for recurrent or extraintestinal infection. (See "Nontyphoidal Salmonella bacteremia".)
Although individuals with HIV are susceptible to a broader variety of enteric pathogens, common causes of infectious diarrhea should be considered first among adults with acute diarrhea in resource-limited settings. (See "Evaluation of the patient with HIV and diarrhea".)
MICROBIOLOGY — A variety of bacteria, viruses, and parasites can cause acute diarrhea in resource-limited settings. Relatively new microbiologic causes of diarrhea have also been identified over time, including Norwalk-like viruses, enteroaggregative E. coli, and enterotoxigenic Bacteroides fragilis.
Information about the host, the type of diarrhea, and the clinical setting may be useful in indicating possible pathogens. However, a microbiologic diagnosis is not made in the majority of clinical cases in resource-limited countries and is not routinely required for clinical management.
Epidemic diarrhea — S. dysenteriae and V. cholerae are the most common organisms associated with epidemic diarrhea. Epidemic refers to an increase, often sudden, in the number of cases of a disease above what is normally expected in that population in that area. Outbreak carries the same definition as epidemic, but it is often used for a more limited geographic area.
●Four species of Shigella cause bloody diarrhea; they are distinguished serologically as S. dysenteriae, Shigella flexneri, Shigella boydii, and Shigella sonnei (see "Shigella infection: Epidemiology, microbiology, and pathogenesis"). Of those, S. dysenteriae serotype 1 (Sd1) is uniquely responsible for epidemic dysentery.
Four important features account for the association between Sd1 and large, regional epidemics of dysentery [16-18]:
•It produces a potent cytotoxin (Shiga toxin) that causes patchy destruction of the colonic epithelium.
•The low infective dose (10 to 100 organisms) facilitates person-to-person spread of infection.
•Illness due to Sd1 is more severe and more prolonged than illness due to other species of Shigella.
•Resistance to antimicrobials is more common than in other species of Shigella.
●Cholera is a secretory diarrheal disease caused by enterotoxin-producing strains of V. cholerae. More than 200 serogroups of V. cholerae have been identified to date, but historically, the O1 serogroup has caused the vast majority of disease. The O139 serogroup emerged as a cause of disease in 1992 [19], but has remained limited to a few countries in Asia. (See "Cholera: Clinical features, diagnosis, treatment, and prevention".)
Countries are said to be endemic for cholera if cholera cases have been reported in three of the previous five years. An outbreak of cholera occurs when a higher-than-expected number of cases are reported in a given area during a specific period of time. Outbreaks may occur in endemic or non-endemic areas and are more limited in scope compared to epidemics. In Africa, some countries appear to have cholera nearly every year, while other countries suffer from outbreaks every few years [20-22].
Rarely, enterohemorrhagic E. coli may cause epidemics of bloody diarrhea, similar to Sd1.
Acute watery diarrhea — A variety of pathogens can cause acute watery diarrhea in resource-limited settings (table 1). In a non-epidemic situation, enterotoxigenic E. coli is the most common cause. In addition to causing epidemic disease, V. cholerae is endemic in approximately 50 countries in Asia, Africa, and Central and South America, where predictable seasonal outbreaks occur. Norovirus, Campylobacter species, nontyphoidal Salmonellae, Aeromonas species, and enteroaggregative E. coli are other pathogens that can cause acute watery diarrhea.
Acute bloody diarrhea — Worldwide, Shigella species, particularly S. flexneri, are the most important causes of acute bloody diarrhea. Other causes in resource-limited settings include Campylobacter jejuni, enteroinvasive and enterohemorrhagic E. coli, nontyphoidal Salmonella species, Entamoeba histolytica, and Schistosoma mansoni (table 1).
CLINICAL FEATURES
Typical findings — As above, diarrhea is the passage of loose stools, typically at least three times in a 24-hour period [8]. Watery diarrhea is characteristically nonbloody, whereas dysentery is defined as diarrhea with visible blood.
In an outbreak setting, these clinical features can be used to distinguish cholera (watery diarrhea) from epidemic dysentery due to S. dysenteriae serotype 1 (Sd1), as the distinction has therapeutic and public health implications (table 2). (See 'Antibiotic therapy' below.)
A "rice-water" appearance of stool flecked with mucous is suggestive of cholera (picture 1) [11]. Furthermore, diarrhea caused by V. cholerae may present very suddenly with vomiting and abdominal cramping but not frank pain or tenesmus. Fever is uncommon in cholera. (See "Cholera: Clinical features, diagnosis, treatment, and prevention", section on 'Diarrhea'.)
In contrast, shigellosis is typically characterized by the frequent passage of small liquid stools that contain visible blood, with or without mucous [23]. Abdominal cramps and tenesmus are common, along with fever and anorexia. (See "Shigella infection: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)
However, within these two categories of diarrhea, the specific infectious causes cannot be determined based on signs or symptoms. The clinical illnesses caused by the various pathogens associated with watery diarrhea are typically indistinguishable. Similarly, Shigellosis cannot be distinguished reliably from other causes of bloody diarrhea on the basis of clinical features alone, nor can illness caused by Sd1 be distinguished with certainty from that caused by other Shigella species.
Complications of acute diarrheal diseases in adults — The sequelae of severe volume depletion are the most important systemic complications of acute diarrheal disease in adults. Various clinical features can be helpful in determining the severity of hypovolemia, with sunken eyes, dry mouth and tongue, thirst, and decreased skin turgor seen with moderate hypovolemia and decreased consciousness, inability to drink, and a weak pulse seen in more severe stages.
Hypovolemia and accompanying electrolyte imbalances are the most important complications of cholera. In contrast, severe volume depletion does not usually occur with Shigella infection.
Other systemic complications of diarrheal illness may occur in adults (table 3):
●Bacteremia (see "Nontyphoidal Salmonella bacteremia")
●Hemolytic-uremic syndrome (see "Shigella infection: Clinical manifestations and diagnosis", section on 'Hemolytic-uremic syndrome' and "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment", section on 'Complications')
●Guillain-Barré syndrome (see "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis" and "Clinical manifestations, diagnosis, and treatment of Campylobacter infection", section on 'Guillain-Barré syndrome')
●Reactive arthritis (see "Reactive arthritis", section on 'Clinical manifestations')
Serious complications may occur with Shigella infection, including sepsis, seizures, rectal prolapse, toxic megacolon, and the hemolytic-uremic syndrome.
Among HIV-infected individuals in resource-limited settings, bacteremia with non-typhoidal Salmonella enterica is a particular concern [24].
DIFFERENTIAL DIAGNOSIS — Acute diarrhea in adults in resource-limited settings is most frequently caused by an infectious agent. In addition to the pathogens above, diarrhea may also occur in the context of other systemic infections, such as influenza, HIV infection, dengue fever, and malaria. Non-infectious etiologies of diarrhea are often missed and should be considered in patients with repeated episodes of self-limiting or acute diarrhea or chronic diarrhea. Such causes include inflammatory bowel disease and malabsorptive syndromes. (See "Approach to the adult with chronic diarrhea in resource-abundant settings".)
CLINICAL ASSESSMENT — The initial evaluation of adults with acute diarrhea should include a careful history and physical exam in order to assess the type of diarrhea and the severity of hypovolemia.
Based on the appearance of the stool, diarrhea can be classified as watery or bloody.
The physical exam should focus on characterizing the degree of volume depletion (table 4) [4]:
●Early hypovolemia – signs and symptoms may be absent
●Moderate hypovolemia – thirst, restless or irritable behavior, decreased skin turgor, sunken eyes
●Severe hypovolemia – diminished consciousness, lack of urine output, cool moist extremities, rapid and feeble pulse, low or undetectable blood pressure, peripheral cyanosis
Laboratory studies are not typically needed. However, when available, certain diagnostic tests can help to identify the microbial etiology, which is especially useful in an epidemic situation.
●Routine microscopy of fresh stool is inexpensive and can identify the presence of numerous fecal leukocytes, suggesting an invasive bacterial infection.
●Microscopic evidence of Entamoeba trophozoites containing red blood cells provides sufficient basis for treating for amoebic dysentery instead of shigellosis (picture 2). Notably, finding cysts or trophozoites without red blood cells in a bloody stool does not indicate that Entamoeba is the cause of illness, since asymptomatic infection is frequent among healthy persons in resource-limited countries. (See "Intestinal Entamoeba histolytica amebiasis".)
●Cholera can be diagnosed using dark-field microscopy, in which motile Vibrios appear as "shooting stars," or by using a commercially available rapid dipstick.
Serum electrolyte and glucose testing is not routinely required for the treatment of an adult patient with an uncomplicated case of acute watery diarrhea. Testing may be considered in patients with ileus, confusion, or seizure, or in those with no urine output in response to fluid replacement.
TREATMENT — Adequate fluid and electrolyte replacement and maintenance are essential to the management of diarrheal illness. Antimicrobials are not routinely warranted, but they do play a role in the treatment of bloody diarrhea and during diarrheal outbreaks.
Rehydration — Fluid management, including the type and quantity of fluids to administer, in an adult patient with diarrhea depends on the level of volume depletion (algorithm 1) [25].
None to moderate hypovolemia — In the vast majority of cases, volume depletion from acute diarrhea of any etiology, except when it is severe, can be effectively treated with oral rehydration salts (ORS) (algorithm 1) [26]. An improved, reduced osmolarity ORS solution, containing 75 mEq/L of sodium and 75 mmol/L of glucose (table 5), is officially recommended by the World Health Organization (WHO) and The United Nations Children’s Fund (UNICEF). This reduced osmolarity solution reduces the need for supplemental IV fluid therapy by 33 percent compared with the previous standard WHO ORS solution [27,28]. (See "Oral rehydration therapy".)
The use of glucose polymers (primarily rice, but also wheat, sorghum, or maize) in ORS has been shown to decrease mean 24-hour stool output in adults with cholera when compared to the traditional, high osmolarity ORS [29,30]. However, the preparation of such polymer-based ORS is more tedious than that of traditional ORS, and further data are needed to assess its efficacy compared with the reduced osmolarity ORS solution.
Severe hypovolemia — Adults with severe hypovolemia should receive intravenous fluids (algorithm 1) [4]. Ringer’s lactate or Ringer’s lactate with 5 percent dextrose are preferred, but normal saline can also be used. Normal saline is less preferable because it does not contain potassium to replace losses nor a base to correct acidosis.
Antibiotic therapy
Watery diarrhea — Antimicrobial therapy is not typically indicated for the treatment of acute watery diarrhea in adults in resource-limited settings, as most cases resolve spontaneously. In trials of adults from resource-rich settings with travelers’ diarrhea, appropriate antibiotics can decrease the duration of symptoms for certain bacterial etiologies by one to two days [31-34]. However, in resource-limited countries, this possible modest benefit is outweighed by the risk of adverse effects, the risk of selection of drug resistance, and the impracticality of selection and distribution of antimicrobials for the number of individuals affected [4].
An important exception is the treatment of severe cholera in outbreak settings, for which antibiotics can decrease the duration of illness and the volume of fluid losses, thus simplifying patient management during a complex emergency [11]. Reports of resistance in V. cholerae are increasing; data on local susceptibility should therefore be used to guide treatment choices. Antibiotic treatment of cholera is discussed in detail elsewhere (table 6). (See "Cholera: Clinical features, diagnosis, treatment, and prevention", section on 'Antibiotic therapy'.)
Dysentery — In contrast to the treatment of watery diarrhea, adults with bloody diarrhea should be treated promptly with an antimicrobial that is effective against Shigella (table 7) [4]. Patients who do not respond within a couple days can be switched to a different antimicrobial agent. If there is still no response after a couple days, treatment for amebic dysentery due to E. histolytica can be given. Although initial empiric treatment for amebic dysentery is not routinely warranted, it should be given at any point if trophozoites are visualized on stool microscopy. Treatment for amebic dysentery usually entails metronidazole (500 to 750 mg orally three times daily for 7 to 10 days) followed by an intraluminal agent; this is discussed elsewhere.
Treatment should be particularly targeted at those with higher risks of complications, including individuals with AIDS and the elderly. The choice of antimicrobial should be based on recent susceptibility data from Shigella strains isolated in the area, if available. Because resistance of Shigella to ampicillin, trimethoprim-sulfamethoxazole, and nalidixic acid has become widespread in resource-limited settings, ciprofloxacin is the drug of choice for all patients with acute bloody diarrhea in resource-limited settings [5]. However, resistance to ciprofloxacin has also widespread in many parts of the world, which highlights the increasing importance of local susceptibility data. If no such data are available, ciprofloxacin or azithromycin are reasonable first line antibiotics, although clinicians should be aware that failure due to resistance is possible and second-line drugs may be required.
In several trials of patients with dysentery, antibiotics reduced the duration of diarrhea and fever in infections caused by Shigella, which is the most common cause of dysentery in resource-limited settings and can otherwise be associated with severe complications [5,35]. Antibiotic therapy for shigellosis is discussed in detail elsewhere. (See "Shigella infection: Treatment and prevention in adults", section on 'Antibiotic treatment'.)
Antimicrobial resistance — Antimicrobial resistance in enteric pathogens in resource-limited settings is increasingly common [36,37] and is, in part, due to the misuse and overuse of antibiotics in the treatment of diarrheal diseases. Multidrug resistance has been identified in nontyphoidal Salmonella, Shigella spp, and V. cholerae [38-42]; resistance complicates the antibiotic treatment of severely ill patients and the management of diarrheal outbreaks. A recent study of diarrheal stool samples in rural western Kenya determined that most persons had been treated with an antimicrobial to which their isolate was resistant [43]. When possible, the selection of antimicrobial treatment for acute diarrheal diseases should therefore be based on recent susceptibility testing of strains from the area. Restriction of public retail availability of antimicrobial agents may also play a role in containing resistance. (See "Cholera: Clinical features, diagnosis, treatment, and prevention", section on 'Antibiotic therapy' and "Shigella infection: Treatment and prevention in adults", section on 'Antimicrobial resistance'.)
Dietary recommendations — The continuous provision of nutritious food is important for all patients with diarrhea. Small meals can be provided frequently, as soon as the patient is able to tolerate.
PREVENTION — Acute diarrheal diseases can be prevented with a variety of measures focused on preventing the spread of organisms from person to person and within the community [44,45]. These include:
●Hand washing with soap
●Ensuring the availability of safe drinking water
●Appropriate disposal of human waste
●Breastfeeding of infants and young children
●Safe handling and processing of food
●Control of flies (particularly for Sd1)
Two killed whole-cell oral cholera vaccines are internationally licensed and prequalified by the World Health Organization (WHO). A WHO global cholera vaccine stockpile of the lower cost bivalent vaccine was created in 2013 and has led to increasing use of killed oral cholera vaccines globally; the monovalent vaccine has been used primarily in travelers from resource-rich countries. (See "Cholera: Clinical features, diagnosis, treatment, and prevention", section on 'Vaccines'.)
Candidate vaccines for shigellosis are undergoing testing.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults".)
SUMMARY AND RECOMMENDATIONS
●Epidemiology − Diarrheal illness in resource-limited settings is extremely common, but incidence rates for adults have not been systematically calculated. Cases of diarrhea can occur as baseline endemic disease or in the setting of epidemics. Poor sanitation is a major risk factor for the prevalence of diarrhea in both endemic and epidemic forms. (See 'Epidemiology' above.)
●Microbiology − Multiple pathogens can cause watery and bloody diarrhea (dysentery) (table 1). Shigella dysenteriae serotype 1 and Vibrio cholerae are the most important causes of diarrheal epidemics, and certain clinical features can distinguish between the two (table 2). (See 'Microbiology' above and 'Clinical features' above.).
●Complications − Severe volume depletion is the most important complication of acute diarrheal illness in adults. However, several other systemic complications can occur, including bacteremia, hemolytic-uremic syndrome, Guillain-Barré syndrome, and reactive arthritis. (See 'Complications of acute diarrheal diseases in adults' above.)
●Clinical assessment − The clinical assessment of the adult patient with acute diarrhea should focus on characterizing the type of diarrhea (watery versus bloody) and the degree of volume depletion. A microbiologic diagnosis is not needed in the majority of clinical cases of adults with diarrheal illness in resource-limited countries. (See 'Clinical assessment' above.)
●Rehydration − Adequate fluid and electrolyte replacement and maintenance are essential to the management of all diarrheal illnesses (algorithm 1 and table 5). (See 'Rehydration' above.)
●Role of antibiotic therapy
•Watery diarrhea − For most patients with acute watery diarrhea, we suggest not routinely administering empiric antimicrobial therapy (Grade 2B). One exception is in the epidemic setting, in which antibiotic therapy against cholera can decrease the duration of illness and the volume of fluid losses and thus simplify patient management during a complex emergency (table 6). (See 'Watery diarrhea' above and "Cholera: Clinical features, diagnosis, treatment, and prevention", section on 'Antibiotic therapy'.)
•Bloody diarrhea − For adults with bloody diarrhea, we suggest prompt empiric antibiotic treatment (Grade 2B). An antimicrobial that is effective against Shigella should be used (table 7). (See 'Dysentery' above and "Shigella infection: Treatment and prevention in adults", section on 'Antibiotic treatment'.)
