Unit 1 - The Epidemiology and Etiology of Diarrhoea
Medical Education: Teaching Medical Students about Diarrhoeal Diseases
World Health Organization 1992
http://apps.who.int/iris/handle/10665/40343
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UNIT 1 - THE EPIDEMIOLOGY AND ETIOLOGY OF DIARRHOEA
INTRODUCTION: DIARRHOEA IS A GLOBAL PROBLEM
Diarrhoea is a leading cause of illness and death among children in
developing countries, where an estimated 1.3 thousand million episodes and 4
million deaths occur each year in under-fives. Worldwide, these children
experience an average of 3.3 episodes each year, but in some areas the average
exceeds nine episodes each year. Where episodes are frequent, young children may
spend more than 15% of their days with diarrhoea (Figure 1.1). About 80% of
deaths due to diarrhoea occur in the first two years of life. The main cause of
death from acute diarrhoea is dehydration, which results from the loss of fluid
and electrolytes in diarrhoeal stools. Other important causes of death are
dysentery and undernutrition.
Diarrhoea is an important cause of undernutrition. This is because patients
eat less during diarrhoea and their ability to absorb nutrients is reduced;
moreover, nutrient requirements are increased as a result of infection. Each
episode of diarrhoea contributes to undernutrition; when episodes are prolonged,
their impact on growth is increased.
Diarrhoeal disease also represents an economic burden for the developing
countries. In many nations more than a third of the hospital beds for children
are occupied by patients with diarrhoea. These patients are often treated with
expensive intravenous fluids and ineffective drugs. Although diarrhoeal disease
is usually less harmful to adults than to children, it can also affect a
country's economy by reducing the health of its work force.
Fortunately, simple and effective treatment measures are available that can
markedly reduce diarrhoea deaths, make hospitalization unnecessary in most
cases, and prevent the adverse effect of diarrhoea on nutritional status.
Practical preventive measures can also be taken that substantially reduce the
incidence and severity of diarrhoeal episodes. This unit provides information on
the epidemiology and etiology of diarrhoea that is essential for an
understanding of the principles of treatment and prevention. The treatment and
prevention of diarrhoea are considered in later units.
THREE TYPES OF DIARRHOEA
Diarrhoea is usually defined in epidemiological studies as the passage of
three or more loose or watery stools in a 24-hour period, a loose stool being
one that would take the shape of a container. However, mothers may use a variety
of terms to describe diarrhoea, depending, for example, upon whether the stool
is loose, watery, bloody or mucoid, or there is vomiting. It is important to be
familiar with these terms when asking whether a child has diarrhoea. Exclusively
breast-fed infants normally pass several soft, semi-liquid stools each day; for
them, it is practical to define diarrhoea as an increase in stool frequency or
liquidity that is considered abnormal by the mother.
Three clinical syndromes of diarrhoea have been defined, each reflecting a
different pathogenesis and requiring different approaches to treatment. These
are described briefly below and considered in detail in Units 3-6.
Acute watery diarrhoea
This term refers to diarrhoea that begins acutely, lasts less than 14 days
(most episodes last less than seven days), and involves the passage of frequent
loose or watery stools without visible blood. Vomiting may occur and fever may
be present. Acute watery diarrhoea causes dehydration; when food intake is
reduced, it also contributes to undernutrition. When death occurs, it is usually
by acute dehydration. The most important causes of acute watery diarrhoea in
young children in developing countries are rotavirus, enterotoxigenic
Escherichia coli, Shigella, Campylobacter jejuni, and
cryptosporidia. In some areas, Vibrio cholerae 01, Salmonella and
enteropathogenic E. coli are also important causes.
Dysentery
The term dysentery refers to diarrhoea with visible blood in the faeces.
Important effects of dysentery include anorexia, rapid weight loss, and damage
to the intestinal mucosa by the invasive bacteria. A number of other
complications may also occur. The most important cause of acute dysentery is
Shigella; other causes are Campylobacter jejuni and, infrequently,
enteroinvasive E. coli or Salmonella. Entamoeba histolytica
can cause serious dysentery in young adults but is rarely a cause of dysentery
in young children.
Persistent diarrhoea
This term refers to diarrhoea that begins acutely but is of unusually long
duration (at least 14 days). The episode may begin either as watery diarrhoea or
as dysentery. Marked weight loss is frequent. Diarrhoeal stool volume may also
be great, with a risk of dehydration. There is no single microbial cause for
persistent diarrhoea; enteroadherent E. coli and cryptosporadia may play
a greater role than other agents. Persistent diarrhoea should not be confused
with chronic diarrhoea, which refers to recurrent or long-lasting diarrhoea due
to non-infectious causes, such as sensitivity to gluten or inherited metabolic
disorders.
EPIDEMIOLOGY
Transmission of agents that cause diarrhoea
Routes of transmission
The infectious agents that cause diarrhoea are usually spread by the
faecal-oral route, which includes the ingestion of faecally contaminated water
or food, person-to-person transmission, and direct contact with infected faeces.
Examples of behaviours that help enteric pathogens to spread are: preparing food
with hands that have been soiled during defecation and not washed; or allowing
an infant to crawl, or a child to play in an area where human or animal faeces
are present.
Behaviours that increase the risk of diarrhoea
A number of specific behaviours help enteric pathogens to spread and thus
increase the risk of diarrhoea. These include:
-
Failing to breast-feed exclusively for the first 4-6 months of life. The
risk of developing severe diarrhoea is many times greater in non-breast-fed
infants than in infants who are exclusively breast-fed; the risk of death from
diarrhoea is also substantially greater.
-
Failing to continue breast-feeding until at least one year of age.
Prolonged breast-feeding reduces the incidence or severity of certain types of
diarrhoeal disease, such as shigellosis and cholera.
-
Using infant feeding bottles. These easily become contaminated with faecal
bacteria and are difficult to clean. When milk is added to an unclean bottle
it becomes contaminated; if it is not consumed immediately, further bacterial
growth occurs.
-
Storing cooked food at room temperature. When food is cooked and then
saved to be used later, it may easily be contaminated, for example, by contact
with contaminated surfaces or containers. If food is kept for several hours at
room temperature, bacteria in it can multiply many times.
-
Drinking water that is contaminated with faecal bacteria. Water may be
contaminated at its source or during storage in the home. Contamination in the
home may occur when the storage container is not covered, or when a
contaminated hand comes into contact with the water while collecting it from
the container.
-
Failing to wash hands before handling food, after defecation, or after
handling faeces.
-
Failing to dispose of faeces (including infant faeces) hygienically. It is
often believed that infant faeces are harmless, whereas they may actually
contain large numbers of infectious viruses or bacteria; animal faeces also
can transmit enteric infections to man.
Host factors that increase
susceptibility to diarrhoea
Several host factors are associated with increased incidence, severity, or
duration of diarrhoea. They include:
-
Undernutrition. The frequency, severity, duration, and risk of death from
diarrhoea are increased in undernourished children, especially those with
severe undernutrition.
-
Current or recent measles. Diarrhoea and dysentery are more frequent or
severe in children with measles or who have had measles in the previous four
weeks. This presumably results from immunological impairment caused by
measles.
-
Immunodeficiency or immunosuppression. This may be a temporary effect of
certain viral infections (e.g., measles), or it may be prolonged, as in
persons with the acquired immunodeficiency syndrome (AIDS). When immunosuppression is severe diarrhoea can be caused by unusual pathogens and
may also be prolonged.
Age
Most diarrhoeal episodes occur during the first two years of life. Incidence
is highest in the age group 6-11 months, when weaning often occurs (Figure 1.2).
This pattern reflects the combined effects of declining levels of
maternally-acquired antibodies, the lack of active immunity in the infant, the
introduction of food that may be contaminated with faecal bacteria, and direct
contact with human or animal faeces when the infant starts to crawl. Most
enteric pathogens stimulate at least partial immunity against repeated infection
or illness, which helps to explain the declining incidence of disease in older
children and adults.
Seasonality
Distinct seasonal patterns of diarrhoea occur in many geographical areas. In
temperate climates, bacterial diarrhoeas tend to occur more frequently during
the warm season, whereas viral diarrhoeas, particularly disease caused by
rotavirus, peak during the winter. In tropical areas, rotavirus diarrhoea tends
to occur throughout the year, increasing in frequency during the drier, cool
months, whereas bacterial diarrhoeas tend to peak during the warmer, rainy
season. The incidence of persistent diarrhoea follows the same seasonal pattern
as that of acute watery diarrhoea.
Asymptomatic infections
Most enteric infections are asymptomatic, and the proportion that is
asymptomatic increases beyond 2 years of age owing to the development of active
immunity. During asymptomatic infections, which may last for several days or
weeks, stools contain infectious viruses, bacteria, or protozoal cysts. Persons
with asymptomatic infections play an important role in the spread of many
enteric pathogens, especially as they are unaware of their infection, take no
special hygienic precautions and move normally from place to place.
Epidemics
Two enteric pathogens, Vibrio cholerae 01 and Shigella
dysenteriae type 1, cause major epidemics in which morbidity and mortality
in all age groups may be high. Since 1961, cholera caused by the El Tor biotype
of V. cholerae 01 has spread to countries in Asia, the Eastern
Mediterranean, and Africa, and to some areas in Europe and North America. During
the same period, S. dysenteriae type 1 has been responsible for large
epidemics of severe dysentery in Central America, and more recently in Central
Africa and Southern Asia.
ETIOLOGY
General considerations
Until a few years ago, pathogenic organisms could be identified in the faeces
of only about 25% of patients with acute diarrhoea. Today, using new techniques,
experienced laboratories can identify pathogens in about 75% of cases seen at a
treatment facility and up to 50% of milder cases detected in the community.
The organisms most frequently associated with diarrhoea in young children in
developing countries are shown in Table 1.1. Several of these pathogens are
important causes of acute diarrhoea in all developing countries. They
are:
- Rotavirus
- Enterotoxogenic Escherichia coli
- Shigella
- Campylobacter jejuni
- Cryptosporidium
Others may be of local importance; these
include V. cholerae 01 (in endemic areas and during epidemics),
non-typhoid Salmonella (in areas where commercially processed foods are
widely used), and enteropathogenic E. coli (in infants in
hospitals). Mixed infections involving two or more enteropathogens occur in
5-20% of cases seen at health facilities. A number of other pathogens are not shown in Table 1.1. In general, their
importance as causes of acute diarrhoea in children in developing countries is
either minimal or not yet well defined. They include:
- Viruses: Norwalk agent, enteric adenoviruses.
- Bacteria: Aeromonas hydrophila, enteroadherent
Escherichia coli, enteroinvasive Escherichia coli,
enterohaemorrhagic Escherichia coli, Plesiomonas shigelloides,
Vibrio cholerae non-O group 1, Vibrio parahaemolyticus,
Yersinia enterocolitica.
- Protozoa: Giardia lamblia, Entamoeba histolytica,
Isospora belli.
Enteric pathogens can also be found in about
30% of healthy children under 3 years of age, making it difficult to know
whether a pathogen isolated from a child is actually the cause of that child's
illness. This is especially true for Giardia lamblia, cysts of which are
found nearly as often in healthy children as in those with diarrhoea; it is also
true for enteropathogenic E. coli or C. jejuni isolated from
children older than 1 year. On the other hand, Shigella and rotavirus are
rarely identified in healthy children; their presence in a child with diarrhoea
is strong evidence that they are the cause of the illness. Table 1.1 also shows that antimicrobials are ineffective in the
majority of acute diarrhoeal episodes in young children seen at a
treatment facility. In the remainder, the effective antibiotic varies according
to the specific infecting agent and in some cases it is effective only when
given early in the illness. For some bacteria, such as Shigella or E.
coli, susceptibility to antibiotics varies from place to place, making it
difficult to know which antibiotic might be effective. For all of these reasons
antibiotics given "blindly" or routinely to patients with diarrhoea are usually
ineffective. The few instances in which antimicrobials should be given
are considered in Units 5 and 6.
Pathogenetic mechanisms
Microbial agents cause diarrhoea by a number of mechanisms, several of which
are considered below.
Viruses
-
Viruses, such as rotavirus, replicate within the villous epithelium of the
small bowel, causing patchy epithelial cell destruction and villous
shortening. The loss of normally absorptive villous cells and their temporary
replacement by immature, secretory, crypt-like cells causes the intestine to
secrete water and electrolytes. Villous damage may also be associated with the
loss of disaccharidase enzymes, leading to reduced absorption of dietary
disaccharides, especially lactose. Recovery occurs when the villi regenerate
and the villous epithelium matures.
Bacteria
-
Mucosal adhesion. Bacteria that multiply within the small intestine
must first adhere to the mucosa to avoid being swept away. Adhesion is caused
by superficial hair-like antigens, termed pili or fimbriae, that bind to
receptors on the intestinal surface; this occurs, for example, with
enterotoxigenic E. coli and V. cholerae 01. In some instances,
mucosal adherence causes changes in the gut epithelium that may reduce its
absorptive capacity or cause fluid secretion (e.g., in infection with
enteropathogenic or enteroadherent E. coli).
-
Toxins that cause secretion. Enterotoxigenic E. coli, V.
cholerae 01 and possibly other bacteria, e.g., Salmonella,
cause intestinal secretion by producing toxins that alter epithelial cell
function; these toxins reduce the absorption of sodium by the villi and may
increase the secretion of chloride in the crypts, resulting in net secretion
of water and electrolytes (see Unit 2). Recovery occurs when the intoxicated
cells are replaced by healthy ones after 2-4 days.
-
Mucosal invasion. Shigella, C. jejuni and
enteroinvasive E. coli cause bloody diarrhoea by invading and
destroying mucosal epithelial cells. This occurs mostly in the colon and the
distal part of the ileum. Invasion is followed by the formation of
microabscesses and superficial ulcers, and hence the presence of red and white
blood cells, or frank blood, in the stool. Toxins produced by these organisms
cause tissue damage and possibly also mucosal secretion of water and
electrolytes.
Protozoa
- Mucosal adhesion. G. lamblia and Cryptosporidium
adhere to the small bowel epithelium and cause shortening of the villi, which
may be how they cause diarrhoea.
-
ausing microabscesses and ulcers, in much the same way as Shigella.
This only happens, however, when the infecting strain of E. histolytica
is virulent. In about 90% of human infections the strains are non-virulent; in
such cases there is no mucosal invasion and no symptoms occur, although
amoebic cysts are present in the faeces.
Important
enteropathogens
-
Rotavirus. Rotavirus is the most important cause of severe,
life-threatening diarrhoea in children under 2 years of age worldwide. There
are four serotypes of human rotavirus; infection with one serotype causes a
high level of immunity to that serotype, and partial protection against the
other serotypes. Nearly all children are infected at least once before the age
of 2 years, and repeat infections are common. Usually only the first rotavirus
infection causes significant illness. About one-third of children under 2
years of age experience an episode of rotavirus diarrhoea. Rotavirus is
probably spread from person to person.
-
Enterotoxigenic E. coli (ETEC). ETEC is an important cause of acute
watery diarrhoea in adults and children in developing countries. ETEC does not
invade the bowel mucosa and the diarrhoea it causes is toxin-mediated; there
are two ETEC toxins - heat-labile (LT) and heat-stable (ST). Some strains
produce only one type of toxin, some both. The LT toxin is closely related to
cholera toxin. ETEC is spread mostly by means of contaminated food and water.
-
Shigella. Shigella are the most important cause of
dysentery, being found in about 60% of all episodes, and in nearly all severe
episodes; watery diarrhoea may also occur. There are four serogroups: S.
sonnei, S. boydii, S. flexneri and S. dysenteriae.
S. flexneri is the most common serogroup in developing countries, but
S. dysenteriae type 1, which occurs in regional epidemics, causes the
most severe disease. Tissue destruction and possibly watery diarrhoea are
caused in part by the extremely potent Shiga toxin, produced in relatively
large amounts by S. dysenteriae type 1. Shigella are spread
mostly by person-to-person transmission. Antibiotics to which Shigella
are sensitive provide effective treatment, but antibiotic resistance is a
common problem. Resistance to multiple antibiotics may occur, especially among
S. dysenteriae type 1. The most useful antibiotics are co-trimoxazole
and nalidixic acid; ampicillin is effective in some areas.
-
Campylobacter jejuni. In developing countries, C. jejuni
causes disease mostly in infants. C.jejuni also infects animals,
especially chickens and dogs, and is spread by contact with their faeces or
consumption of contaminated food, milk, or water. C. jejuni can cause
both watery diarrhoea (two-thirds of cases) or dysentery (one third of cases).
Fever may be present. Disease is not usually severe and lasts 2-5 days.
Although erythromycin shortens the illness if given soon after the symptoms
start, it is not recommended because cases caused by C. jejuni cannot
be distinguished clinically from those due to other agents; erythromycin is
ineffective if therapy is delayed until the diagnosis is confirmed by a
laboratory.
-
Vibrio cholerae 01. V.cholerae 01 has two biotypes
(classical and El Tor) and two serotypes (Ogawa and Inaba). V. cholerae
01 is non-invasive, diarrhoea being mediated by cholera toxin which causes a
profuse secretion of water and electrolytes in the small bowel. Diarrhoea may
be severe, leading to dehydration and collapse within a few hours if the lost
fluids and salts are not replaced. In endemic areas, cholera occurs mostly in
children, adults having substantial immunity from previous infections. In
non-endemic areas, epidemics cause disease with equal frequency in adults and
children. Antibiotics can shorten the duration of the illness and thus
simplify case management. Tetracycline (or doxycycline) is most widely used,
but resistance has been observed in some areas; in this event, other
antibiotics, e.g., furazolidone, co-trimoxazole, erythromycin, or
chloramphenical, are usually effective.
-
Salmonella. Most Salmonella infections can be traced to
infected animals or contaminated animal products. Salmonella are an
unusual cause of diarrhoea in most developing countries, but may be important
in communities where commercially processed foods are widely used. Diarrhoea
is usually watery, but dysentery may occur. Antibiotics are not effective, and
may cause delayed clearance of Salmonella from the intestinal tract.
-
Cryptosporidium. This is a coccidian parasite that causes disease
in infants, immunodeficient patients, and a variety of domestic animals. In
developing countries infection is frequent, and most episodes of illness occur
in the first year of life. Thereafter, infections are usually asymptomatic.
Diarrhoea is usually neither severe nor prolonged, except in immunodeficient
patients, such as those with severe malnutrition or AIDS. In such individuals,
Cryptosporidium is an important cause of persistent diarrhoea with
wasting.
IMPLICATIONS FOR TREATMENT AND PREVENTION OF DIARRHOEA
Treatment of diarrhoea
Routine determination of the etiology of diarrhoea in a laboratory is not
practical, and the clinical aspects of an illness usually do not permit a
specific etiological diagnosis to be made. The treatment of diarrhoea must
therefore be based on the major features of the disease and an understanding of
the underlying pathogenetic mechanisms. The main principles of treatment are as
follows:
- Watery diarrhoea requires fluid and electrolyte replacement - irrespective
of its etiology.
- Feeding should be continued during all types of diarrhoea to the greatest
extent possible, and should be increased during convalescence so as to avoid
any adverse effect on nutritional status.
- Antimicrobials and anti-parasitic agents should not be used
routinely: most episodes, including severe diarrhoea and diarrhoea with fever
do not benefit from treatment with antimicrobials or antiparasitic
agents. The exceptions are:
- dysentery, which should be treated with an antibiotic effective for
Shigella; cases not responding to this treatment should be studied for
possible amoebiasis;
- suspected cases of cholera; and
- persistent
diarrhoea, when trophozoites or cysts of Giardia are seen in faeces or
intestinal fluid, or when pathogenic enteric bacteria are identified by stool
culture.
The treatment of acute watery
diarrhoea, dysentery, and persistent diarrhoea is considered in detail in Units
4-7.
Prevention of diarrhoea
Measures that interrupt transmission of pathogens
Although a wide variety of infectious agents cause diarrhoea, they are all
transmitted by common faecal-oral pathways, such as contaminated water, food,
and hands. Measures taken to interrupt the transmission of the causative agents
should focus on these pathways. Important measures of proven efficacy include:
- giving only breast milk for the first 4-6 months of life;
- avoiding the use of infant feeding bottles;
- improving practices related to the preparation and storage of weaning
foods (to minimize microbial contamination and growth);
- using clean water for drinking;
- washing hands (after defecation or handling faeces, and before preparing
food or eating); and
- safely disposing of faeces, including infant faeces.
Measures that strengthen host defences
A number of risk factors for frequent or severe diarrhoea reflect impaired
host defences. Measures that can be taken to improve host defences and thus
diminish the risk of diarrhoea include:
- immunizing against measles;
- continuing to breast-feed for at least the first year of life; and
- improving nutritional status (by improving the nutritional value of
weaning foods and giving children more food).
Measures to prevent diarrhoea are
considered in greater detail in Unit 8.
EXERCISES
1. For which of the following reasons is diarrhoea in young children an
important public health problem? (There may be more than one correct answer.)
- It places a heavy burden on health facilities and resources
- It is a major cause of mortality in young children
- It is a major cause of malnutrition in young children
- It accounts for a large proportion of the days of illness in young
children
2. Mohan is 9 months old and was
healthy until he developed diarrhoea 3 weeks ago. The episode began with stools
that were loose and sometimes watery. During the last few days Mohan's mother
has noted some blood in his stool. Mohan has vomited several times in the past
week. His mother says that he does not eat as much as usual and seems to have
lost weight. He was weaned from breast milk to cow's milk 6 weeks ago. What type
of diarrhoea does Mohan have?
- Acute diarrhoea
- Acute dysentery
- Chronic diarrhoea
- Allergic diarrhoea
- Persistent diarrhoea with blood
3. List the 5 most important
causes of acute diarrhoea among children in developing countries (including
viral, bacterial, and protozoan agents).
-
4. In what proportion of cases can the etiology of acute watery
diarrhoea be correctly determined on the basis of the clinical features of the
illness?
- 0%
- 10%
- 25%
- 40%
- 75%
5. In which of the following
situations is it correct to give an antibiotic to a child with diarrhoea? (There
may be more than one correct answer.)
- The child has had bloody diarrhoea with fever for 2 days.
- The child has watery diarrhoea and the family keeps chickens.
- The child has had watery diarrhoea with fever for 2 days.
- The child has severe dehydration from acute watery diarrhoea and cases of
cholera have recently been confirmed in the area.
- The child has had diarrhoea for 12 days and shows signs of dehydration and
weight loss.
6. Which of the following agents
are important causes of acute diarrhoea or dysentery in young children in
developing countries? (There may be more than one correct answer.)
- Entamoeba histolytica
- Yersinia enterocolitica
- enterohaemorrhagic E. coli
- enterotoxigenic E. coli
- Plesiomonas shigelloides
7. Which of the following
factors can reduce the incidence and severity of diarrhoea in young children?
(There may be more than one correct answer.)
- Washing hands after defecation and before preparing food
- Bathing the child frequently
- Exclusive breast-feeding for the first 4-6 months of life
- DPT immunization
- Immunization against measles
Answers
1. All answers are correct.
2. Mohan has persistent diarrhoea with blood, i.e., diarrhoea that begins
acutely and lasts more than 14 days. His illness would not be considered acute
dysentery because it has lasted more than 14 days. The term chronic diarrhoea
should not be used in this case; it refers to diarrhoea of long duration that is
due to a non-infectious cause.
3. Viruses - rotavirus; Bacteria - enterotoxigenic E. coli,
Shigella, C. jejuni; Protozoa - Cryptosporidia
4. The answer is A, 0%. The features of acute diarrhoea are not specific. It
is not possible to determine the etiology on the basis of the clinical features
of the illness.
5. The answers are A and D. Antibiotics are indicated only for
dysentery, in which case treatment for shigellosis should be given, or for
suspected cholera. Diarrhoea of longer than usual duration, diarrhoea with
fever, and diarrhoea following exposure to animals do not benefit from
antibiotics.
6. The answer is D, enterotoxigenic E. coli (ETEC). ETEC is the most
frequent cause of acute diarrhoea among cases detected in community surveys.
None of the other agents listed are important causes of acute diarrhoea or
dysentery in young children.
7. The correct answers are A, C, and E. Some other protective factors are the
use of a cup rather than a bottle to give milk formula, the use of clean
drinking water, cooking weaning foods well and reheating to the boil any foods
that are not eaten immediately after being cooked, and safe disposal of infant,
adult, and animal faeces.
