Disclosures: Regina LaRocque, MD, MPH Nothing to
disclose. Mark Pietroni, MA, MBBChir, FRCP, DTM&H Nothing
to disclose. Stephen B Calderwood, MD Patent Holder: Vaccine
Technologies Inc. [Vaccines (Cholera vaccines)]. Equity Ownership/Stock Options:
Pulmatrix [Inhaled antimicrobials]; PharmAthene [Anthrax (Anti-protective
antigen monoclonal antibody)]. Allyson Bloom, MD Nothing to
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INTRODUCTION — The
Global Burden of Disease study estimated that there were 1.4 million deaths due
to diarrheal diseases in 2010 [1]. According to this report,
diarrheal diseases represent one of the five leading causes of death worldwide
and are the second leading cause of death in children under five years of age
(behind acute respiratory infections). Most cases of diarrhea are associated
with contaminated food and water sources, and around 2.4 billion people
globally have no access to basic sanitation [2].
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" [3]. Specific WHO guidelines for
the management of epidemic shigellosis [4] and cholera [5] 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 "Epidemiology and causes of acute diarrhea in resource-rich
countries" and "Approach to the adult with acute diarrhea in resource-rich
countries" and "Approach to the adult with chronic diarrhea in developed
countries" and "Evaluation of diarrhea in children" and "Overview of the causes of chronic diarrhea in children".)
CLASSIFICATION OF DIARRHEA — Diarrhea is defined as the passage of
loose or watery stools, typically at least three times in a 24-hour period [6]. 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 systematically 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 [7]. 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
dysenteriaeserotype 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 [8]. Epidemics due to V.
cholerae have occurred throughout Africa, Asia, the Middle East, South
and Central America, and the Caribbean [9]. Cholera outbreaks can be
particularly extensive [10]. (See "Overview of cholera", section on 'Epidemiology' and "Shigella infection: Epidemiology, microbiology, and
pathogenesis", section on 'Developing countries'.)
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 [11]. (See "Microbiology, pathogenesis, epidemiology, and prevention of
enterohemorrhagic Escherichia coli (EHEC)", section on 'Epidemiology'.)
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 — 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/AIDS [12,13]. 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 HIV-infected patient with 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.
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 [14-16]:
●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 [17], but has remained limited to
a few countries in Asia. (See "Overview of cholera".)
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,
andSchistosoma mansoni (table 1).
CLINICAL FEATURES — As above, diarrhea is the passage of
loose stools, typically at least three times in a 24-hour period [6]. 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) [9]. 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 "Overview of cholera", 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 [18]. 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.
●Hemolytic-uremic syndrome (see "Shigella infection: Clinical manifestations and diagnosis", section
on 'Hemolytic-uremic syndrome' and "Clinical manifestations, diagnosis and treatment of enterohemorrhagic
Escherichia coli (EHEC) infection", section on 'Hemolytic-uremic syndrome')
●Guillain-Barré syndrome (see "Clinical features and diagnosis of Guillain-Barré syndrome in
adults" and"Clinical manifestations, diagnosis, and treatment of Campylobacter
infection", section on 'Guillain-Barré syndrome')
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 Shigella enterica is a
particular concern [19].
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 developed
countries".)
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.
●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. (See "Approach to the adult with acute diarrhea in resource-rich
countries", section on 'Fecal leukocytes and occult blood'.)
●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."
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) [20].
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) [21]. 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 [22,23]. (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 [24,25]. 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) [3]. 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 [26-29]. 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 [3].
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 [9]. 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 "Overview of cholera", 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.
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 [4,30].
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 Shigellastrains 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
now the drug of choice for all patients with acute bloody diarrhea [4]. Antibiotic therapy for
shigellosis is discussed in detail elsewhere (table 7). (See "Shigella infection: Treatment and prevention in adults", section
on 'Antibiotic treatment'.)
If amebic dysentery due to E. histolytica is
suspected based on stool microscopy, metronidazole (500
to 750 mg orally three times daily for 7 to 10 days) is the usual treatment
(see "Intestinal Entamoeba histolytica amebiasis"). A diagnosis of amebic dysentery should also be
considered in a patient who does not respond within two days to empiric
treatment for shigellosis.
Antimicrobial resistance — Antimicrobial resistance in enteric
pathogens in resource-limited settings is increasingly common [31,32] 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 [33-37]; 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 [38]. 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 "Overview of cholera", 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 [39,40]. 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)
Several vaccines for V. cholerae have
been developed, but none are in widespread use in resource-limited settings at
the present time. However, the World Health Organization has recently
recommended that cholera vaccination should be implemented in endemic areas and
in areas at risk for outbreaks [41]. Candidate vaccines for
shigellosis are undergoing testing.
SUMMARY AND RECOMMENDATIONS
●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.)
●Multiple pathogens can cause watery and bloody
diarrhea (dysentery) (table 1). Shigella dysenteriaeserotype
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.).
●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.)
●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.)
●Adequate fluid and electrolyte replacement and
maintenance are essential to the management of all diarrheal illnesses (algorithm 1 and table 5). (See 'Rehydration' above.)
●For most patients with acute watery diarrhea, we
suggest not routinely administering empiric antimicrobial therapy (Grade 2B). However,
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 "Overview of cholera", section on 'Antibiotic therapy'.)
●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'.)
REFERENCES
2. World Health Organization.
Water Sanitation and Health. Geneva, Switzerland: World Health Organization,
2004.
3. World Health Organization. The
treatment of diarrhoea, a manual for physicians and other senior health
workers. -- 4th revision. Geneva, Switzerland: World Health Organization, 2005.
4. Guidelines for the control of
shigellosis, including epidemics due to Shigella dysenteriae type 1. Geneva,
Switzerland: World Health Organization, 2005.
5. Cholera outbreak: assessing the
outbreak response and improving preparedness. Geneva, Switzerland: World Health
Organization, 2004.
20. World Health Organization.
First steps for managing an oubreak of acute diarrhea. Geneva, Switzerland:
World Health Organization, 2004.
37. Surveillance Update.
ICDDR,B:Health and Science Bulletin 2010; 8:19.
41. World Health Organization.
Potential use of oral cholera vaccines.
http://www.who.int/topics/cholera/vaccines/use/en/index.html (Accessed on July
13, 2012).
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