Diarrhea in Neonatal Ruminants

By Walter Gruenberg, DrMedVet, MS, PhD, DECAR, DECBHM, Assistant Professor,

Department of Farm Animal Health, Utrecht University

Diarrhea is common in newborn calves, lambs, and kids. The clinical presentation can range from
mild diarrhea without systemic disease to profuse, acute diarrhea associated with rapid dehydration,
severe disturbance of acid-base and electrolyte balance, and death, sometimes in as few as 12 hr.
This discussion emphasizes the disease in calves, but the principles of pathophysiology and
treatment apply to lambs and kids as well.

Etiology:
Several enteropathogens are associated with diarrhea in neonates. Their relative prevalence varies
geographically, but the most prevalent infections in most areas are Escherichia coli, rotavirus,
coronavirus, and Cryptosporidium parvum. Cases of neonatal diarrhea are commonly associated
with more than one of these agents, and the cause of most outbreaks is multifactorial. Determining
the particular agents associated with an outbreak of diarrhea can be important, because specific
therapy and prophylaxis are available for some. Also, some agents have zoonotic risk. Diarrhea is
also present in septicemic colibacillosis.

Bacteria:

Enterotoxigenic Escherichia coli , intestine, calf

Courtesy of Dr. J. J. Hadad and Dr. Carlton Gyles

1
E coli is the most important bacterial cause of diarrhea in calves during the first week of life; at
least two distinct types of diarrheal disease are produced by different strains of this organism. One
type is associated with enterotoxigenic E coli, which has two virulence factors associated with
production of diarrhea. Fimbrial antigens enable them to attach to and colonize the villi of the small
intestine of neonatal calves in the first days of life. Strains in calves most commonly possess K99
(F5) or F41 fimbrial antigens, or both. These antigens are the focus of immunologic protection.
Enterotoxigenic E coli also elaborate a thermostable, nonantigenic enterotoxin (Sta) that influences
intestinal ion and fluid secretion to produce a noninflammatory secretory diarrhea. Diarrhea in
calves and lambs also has been associated with enteropathogenic E coli that adhere to the intestine
to produce so-called attaching and effacing lesions, with dissolution of the brush border and loss
of microvillous structure at the site of attachment, a decrease in enzyme activity, and changes in
ion transport in the intestine. These enteropathogens are also called “attaching and effacing E coli.”
Some produce verotoxin, which may be associated with a more severe hemorrhagic diarrhea. The
infection most frequently is in the cecum and colon, but the distal small intestine can also be
affected. The damage in severe infections can result in edema and mucosal erosions and ulceration,
leading to hemorrhage into the intestinal lumen.

Salmonella spp, especially S Typhimurium and S Dublin, but occasionally other serovars, cause
diarrhea in calves 2–12 wk old. Salmonellae produce enterotoxins but are also invasive and produce
inflammatory change within the intestine. In calves, infection commonly progresses to a
bacteremia.

Clostridium perfringens types A, B, C, and E produce a variety of necrotizing toxins and cause a
rapidly fatal hemorrhagic enteritis in calves. The disease in calves is rare and usually sporadic.
Infection with type B or C is a common cause of enteritis and dysentery in lambs.

Campylobacter jejuni and Yersinia enterocolitica may be present in the feces of calves and lambs
with diarrhea but also may be found in the feces of healthy animals.

Viruses:
Rotavirus is the most common viral cause of diarrhea in calves and lambs. Groups A and B
rotavirus are involved, but group A is most prevalent and clinically important and contains several
serotypes of differing virulence. Rotavirus replicates in the mature absorptive and enzyme-
producing enterocytes on the villi of the small intestine, leading to rupture and sloughing of the
enterocytes with release of virus to infect adjacent cells. Rotavirus does not infect the immature
cells of the crypts. With virulent strains of rotavirus, the loss of enterocytes exceeds the ability of
the intestinal crypts to replace them; hence, villous height is reduced, with a consequent decrease
in intestinal absorptive surface area and intestinal digestive enzyme activity.

Coronavirus is also commonly associated with diarrhea in calves. It replicates in the epithelium of
the upper respiratory tract and in the enterocytes of the intestine, where it produces similar lesions
to rotavirus but also infects the epithelial cells of the large intestine to produce atrophy of the
colonic ridges.

Other viruses, including Breda virus (torovirus), a calici-like virus, astrovirus, and parvovirus, have
been demonstrated in the feces of calves with diarrhea and can produce diarrhea in calves

2
experimentally. However, these agents have also been found in the feces of healthy calves. The
importance of these agents in the syndrome of diarrhea in neonates has yet to be determined. The
viruses of bovine virus diarrhea and infectious bovine rhinotracheitis are reported to cause calf
diarrhea, but this is not a common manifestation of these infections.

Protozoa:
Cryptosporidium parvum is a common cause of diarrhea in calves and lambs. The parasite does not
invade but adheres to the apical surface of enterocytes in the distal small intestine and the colon.
This results in loss of microvilli, decreased mucosal enzyme activity with villous blunting and
fusion (leading to a reduced villous surface absorptive area), and inflammatory changes in the
submucosa. Mammalian cryptosporidia lack host specificity.

Giardia duodenalis is a common asymptomatic infection in the intestine of young calves and
lambs. It has been found in the feces of poorly growing calves that have a chronic mucoid diarrhea,
but there is little evidence for a causative association of this organism with diarrhea in calves or
lambs.

Other Causes:
Calves fed large amounts of milk or inappropriately formulated milk replacers produce a large
volume of feces with a greater than normal fluid content but do not have a fluid diarrhea with
weight loss. Similarly, calves sucking high-producing beef cows grazing lush pasture may have
loose feces. Milk replacers with poor quality, heat-denatured proteins or with excessive amounts
of soybean or fish protein or carbohydrates of nonmilk origin have a higher risk of producing
diarrhea.

There is some evidence that oral administration of chloramphenicol, neomycin, or tetracycline to

young calves for 3–5 days can result in villous change with resultant malabsorption and mild
diarrhea. Prolonged and high-dose antibiotic treatment of calves can lead to diarrhea associated
with bacterial superinfection of the intestine. Colisepticemia and ruminal drinking can also be
accompanied by diarrhea.

Epidemiology and Transmission:

Enteropathogens associated with diarrhea are commonly found in the feces of healthy calves;
whether intestinal infection leads to diarrhea depends on a number of determinants, including
differences in virulence of different strains of a pathogen and the presence of more than one
pathogen. The resistance of the calf is of major importance and is largely determined by successful
passive transfer of colostral immunoglobulins. Colostrum-deprived calves are highly susceptible
to infection with enteropathogens and develop severe and often fatal disease.

The progression of infection, the severity of lesions produced, and the severity of the diarrhea can
be modulated by immunoglobulins received via colostrum. Immunoglobulins act directly on
pathogens in the intestinal lumen during the period of colostrum ingestion as well as after, because
significant amounts of circulating immunoglobulins are re-secreted into the intestine, especially
when the concentration of circulating immunoglobulin is high. The lack of specific antibodies in
dams that have not been exposed to specific pathogens, and the use of specific vaccines, further

3
modulate this influence. Stress caused by a poor environment, inadequate protection from the
weather, or an insufficient or inappropriate diet also increases the risk of disease.

With all of the enteropathogens, healthy adult cattle may be carriers and periodically excrete the
organism in feces. Excretion may increase around parturition and be more frequent in primiparous
cows. This can lead to contaminated calving areas and infection of the udder and perineum of the
dam. Other sources of infection include the feces of healthy calves and the feces of diarrheic calves,
which contain large numbers of organisms early in the course of infection. A few scouring calves
can result in severe contamination of the calf-rearing area. Transmission is by fecal-oral contact,
fecal aerosol, and, in the case of coronavirus, by respiratory aerosol.

Pathogenesis:
Diarrhea in neonatal ruminants is usually associated with disease of the small intestine and can be
caused by hypersecretion or malabsorption. Hypersecretory diarrhea develops when an abnormal
amount of fluid is secreted into the gut, exceeding the resorptive capacity of the mucosa. In
malabsorptive diarrhea, the capacity of the mucosa to absorb fluid and nutrients is impaired to the
extent that it cannot keep up with the normal influx of ingested and secreted fluids. This is usually
the result of villous atrophy, in which the loss of mature enterocytes at the tips of the villi results
both in a decrease in villous height (with a consequent decrease in the surface area for absorption)
and in loss of the brush border digestive enzymes. The extent and distribution of villous atrophy
varies with different pathogens and can explain variation in the severity of clinical disease.
Malabsorptive diarrhea may be aggravated by the colonic fermentation of nutrients that normally
would have been absorbed in the small intestine. Fermentation products, especially lactic acid,
appear to draw water into the colon osmotically, which contributes to the severity of diarrhea.

Inflammation contributes to the pathophysiology of diarrhea in most intestinal infections, and

mediators of inflammation can affect ion flux within the intestine. Inflammation also leads to
vascular and lymphatic damage and to structural damage of the crypt-villus unit. Most infectious
forms of diarrhea have hypersecretory, inflammatory, and malabsorptive components, although
one usually predominates. These lead to a net loss of water, sodium, potassium, and bicarbonate;
if severe, the calf develops hypovolemia, hyponatremia, acidemia, and prerenal azotemia.

Enterotoxigenic E coli produce the enterotoxin Sta, which stimulates marked hypersecretion by
activating guanylate cyclase and by inducing a net secretion of sodium and chlorine. The
membrane-bound sodium-glucose cotransport system remains functional but cannot compensate
for the increased secretory activity. Salmonellae also elaborate enterotoxins. Inflammation, leading
to necrosis of the enterocyte, submucosal inflammatory infiltration, and villous atrophy, is also a
major component of the pathophysiology of diarrhea produced by salmonellae, as well as of
diarrhea produced by enteropathogenic E coli and by toxigenic C perfringens. Infections with
verotoxin-producing enteropathogenic E coliresult in accumulation of fluid within the large
intestine and extensive damage to the large intestinal mucosa, with edema, hemorrhage, and erosion
and ulceration of the mucosa, which results in blood and mucus in the lumen.

Viruses usually produce a malabsorptive diarrhea by destroying the absorptive cells of the mucosa,
thus shortening the intestinal villi. The mechanism by which cryptosporidia produce diarrhea is not
completely understood, but it appears to have both malabsorptive and inflammatory components.

4
Inappropriately formulated milk replacers produce diarrhea by two mechanisms, both associated
with malabsorption. Vegetable (especially soybean) products are commonly used as protein
sources in the manufacture of milk replacers. Depending on the degree of refinement, these
products may contain carbohydrates that are indigestible in young calves. Such carbohydrates are
not absorbed in the small intestine and may contribute to diarrhea via colonic fermentation. In
addition, most calves <3 wk old appear to have an allergic reaction to soy proteins that results in
villous atrophy, leading to diarrhea that is probably malabsorptive.

Clinical Findings:
The major signs are diarrhea, dehydration, profound weakness, and death within one to several
days of onset.

Diarrhea due to enterotoxigenic (K99-bearing) E coli is seen in calves <3–5 days old, rarely later.
However, the age of susceptibility may be extended in the presence of other pathogens. Onset is
sudden. Profuse amounts of liquid feces are passed, and the calves rapidly become depressed and
recumbent. Calves may lose >12% of body weight in fluid, and hypovolemic shock and death may
occur in 12–24 hr. Body temperature may be increased but is commonly normal or subnormal. If
fluid and electrolyte therapy is administered early, response is usually good. Disease produced by
attaching and effacing E coli is seen predominantly in calves from 4 days to 2 mo old and may
manifest with diarrhea or primarily as dysentery with blood and mucus in the feces. The clinical
course is short.

Diarrhea due to Salmonella spp usually is not seen in calves <14 days old. It is characterized by
feces that are foul smelling and contain blood, fibrin, and copious amounts of mucus. Septicemia,
with high fever and depression progressing to prostration and coma, is the salient manifestation of
salmonellosis in calves and, although diarrhea is present, death is usually from septicemic rather
than from hypovolemic shock. Calves with salmonellosis usually lose weight rapidly and often die
despite vigorous therapy.

Hemorrhagic enterotoxemia due to C perfringens type B or C is characterized by acute onset of

depression, weakness, bloody diarrhea, abdominal pain, and death within a few hours. It usually
develops in vigorous calves just a few days old that have large appetites and a ready source of milk.
Calves affected with C perfringens usually die before treatment can be instituted.

Diarrhea due to rotavirus, coronavirus, and other viruses usually is seen in calves 5–15 days old
but can affect calves up to several months of age. Affected calves are only moderately depressed
and often continue to suck or drink milk. The feces are voluminous, soft to liquid, and often contain
large amounts of mucus. Diarrhea commonly persists for 3 to several days, with some cases of
coronaviral diarrhea becoming chronic. Cases of viral diarrhea that are uncomplicated by other
pathogens commonly respond within a few days to fluid and electrolyte therapy and adequate
nutritional support.

Cryptosporidiosis is seen in calves 5–35 days old but most commonly in the second week of life.
It is characterized by persistent diarrhea that does not respond to therapy. Diarrhea due solely
to Cryptosporidium spp is often mild and self-limiting, although the severity may be related to the
general strength of the calf and to the intensity of challenge with the organism. Combination

5
infections with cryptosporidia, rotavirus, and coronavirus are common and result in persistent
diarrhea often characterized by emaciation and death. Death from hypoglycemia also occurs as a
sequela of cryptosporidiosis in calves 3–4 wk of age that have recovered from diarrhea but are still
emaciated. Death often occurs during a bout of cold weather and is more likely to occur on farms
where there is a policy of reducing the amount of milk fed to calves during periods of diarrhea.

Dietary diarrheas are seen in calves <3 wk old and are characterized by voluminous feces of pasty
to gelatinous consistency. Initially, the calves are bright and alert and have good appetites.
Eventually, however, they become weak and emaciated if the diet is not corrected. Infectious forms
of diarrhea are often complicated by poor-quality diets or insufficient nutritional intake.

Diagnosis:
It is difficult to make a definite etiologic diagnosis for diarrhea based solely on clinical findings.
However, the history, age of the animal(s) affected, and clinical signs may permit a presumptive
diagnosis. Fecal samples can be submitted for isolation and characterization of the common
enteropathogens. Samples should be taken from several untreated calves in the early stages of
diarrhea. Special techniques are necessary for the demonstration of viruses, cryptosporidia, and
K99-bearing E coli. The interpretation of fecal microbiology can be difficult because of mixed
infections and because enteropathogens are commonly present in the feces of healthy calves.

The best diagnostic information is usually obtained by submitting untreated, acutely affected
animals for necropsy. This allows examination of intestinal mucosa for evidence of diagnostic
lesions and for the presence of enteropathogens such as cryptosporidia. It may be the only way that
disease such as that associated with attaching and effacing strains of E coli can be diagnosed. The
diagnostic value of a necropsy diminishes quickly with time after death; important lesions can
disappear within minutes due to autolysis.

Complete laboratory examination can be expensive, and it has also been argued that there is little
value in expending large amounts of money on diagnosis unless there are specific control
procedures that can be implemented based on the information gained. In all cases, information on
total milk or milk replacer consumption should be obtained. When milk replacer is being fed, the
composition of the diet should be evaluated. Nonspecific immunity should be assessed by
determining immunoglobulin and vitamin A concentrations in serum.

Treatment:
Many of the factors involved in disease resistance are nonspecific; thus, important preventive
measures can be taken and therapy can be started before an etiologic diagnosis has been established.
Treatment includes fluid therapy for water and electrolyte replacement and correction of acid-base
disturbances, alteration of the diet, and antimicrobial and anti-inflammatory therapy.

Fluid and electrolyte therapy is most important and should be started as soon as possible regardless
of whether clinical evidence of dehydration has developed (clinical signs of dehydration are not
apparent until the calf has lost at least 6% of its body weight in fluid). Calves still able to stand and
willing and able to suck can often be treated with oral electrolyte solutions alone. Fluids for oral
rehydration should promote the cotransport of sodium with glucose and amino acids and should

6
contain sodium, glucose, glycine or alanine, potassium, and either bicarbonate or citrate or acetate
as alkalinizing agents. Several commercial preparations are available. These can be administered
by nipple bottle or, if necessary, by stomach tube. The solutions should be used liberally until the
animal is rehydrated.

Whether milk should be fed during the rehydration period remains controversial. Feeding milk may
increase fecal volume, but it provides energy to the calf and may promote gut healing. Calves have
large energy requirements and little reserve. Electrolyte solutions do not meet calf energy
requirements, and milk should not be withheld for >24 hr, if at all.

Calves that are recumbent, weak, and show evidence of water loss of ≥8% of their body weight
require IV fluid therapy. These calves are usually acidotic, and the fluid and base deficits can be
corrected initially by rapidly administering a hypertonic solution of sodium bicarbonate (either 500
mL of a 4.2% solution, or 250 mL of an 8.4% solution), followed by a physiologically balanced
electrolyte solution administered at up to 40 mL/kg/hr until the volume deficit is corrected. Because
diarrheic calves are frequently hypoglycemic, adding 25–50 g of dextrose to the electrolyte solution
is often beneficial in the initial treatment phase. Oral electrolyte solutions should be used
concurrently with and after IV fluid therapy to compensate for ongoing fluid and electrolyte losses.

Although mild diarrhea without systemic disease is not an indication for antimicrobial therapy, use
of parenteral antibiotics should be considered whenever calves are systemically ill or recumbent.
Field studies revealed that at least 30% of diarrheic calves with systemic disease are bacteremic—
a clear indication for parenteral antimicrobial therapy. Because the large majority of cases of
bacteremia and septicemia in neonatal calves are associated with E coli, the chosen antibiotic
should be effective against gram-negative bacteria.

In several studies, severely affected diarrheic calves treated with NSAIDs in conjunction with fluid
therapy showed fewer signs of pain, made a faster recovery, and had better weight gains in the
reconvalescent period. These effects reported for several NSAIDs have been attributed to their
analgesic, anti-inflammatory, antipyretic, and antisecretory properties.

The use of drugs to reduce intestinal motility such as hyoscine-N-butylbromide or atropine is

sometimes advocated, because they decrease fecal output. Although reducing fecal production may
be interpreted as a positive treatment outcome, it can also be seen as sequestration of gut fluid
containing bacteria, toxins, and undigested nutrients in the intestinal tract. The literature does not
provide any strong supportive evidence for or against the use of antimotility drugs.

Intestinal gels and adsorbents, such as kaolin and pectin, are in general use, but their only
established effect is to increase fecal consistency; they do not reduce the loss of water and ions.

Prevention and Control:

Because of the complex nature of diarrhea in neonates, it is unrealistic to expect total prevention—
economical control is the major objective. The incidence of clinical disease and the case fatality
rate depend on the balance between the levels of exposure to infectious agents and the resistance
in the calf. Differences in herd size; availability of facilities, land, and labor; and general
management objectives make it impossible to recommend specific management procedures

7
applicable to all situations. However, three broad principles apply in all herds: 1) the degree of
exposure of neonates should be reduced by isolating diseased animals or by moving calving and
calf rearing to a separate area, and by practicing good general hygiene; 2) nonspecific resistance
should be maximized by providing good nutrition to the dam and neonate and assuring that
newborn calves consume ≥5% of their body wt of high-quality colostrum, preferably within 2 hr
and certainly within 6 hr of birth, followed by equivalent amounts at 12-hr intervals for the next 48
hr; and 3) the specific resistance of the newborn should be increased by vaccinating the dam or the
newborn. A significant portion of both naturally sucking dairy calves and calves handfed colostrum
do not acquire adequate amounts of immunoglobulin because of delayed sucking or feeding,
ingestion of an inadequate volume of colostrum, or ingestion of colostrum of inferior
immunoglobulin concentration. When time constraints on labor preclude an ensured intake of
colostrum by nipple-bottle feeding, administration of 4 L of colostrum by esophageal feeder within
the first 2 hr of life can be the best colostrum feeding policy.

Immunization of calves against colibacillosis by vaccination of pregnant dams can control

enterotoxigenic colibacillosis. The pregnant dam is vaccinated 6 and 2 wk before parturition to
stimulate antibodies to strains of enterotoxigenic E coli; these antibodies are then passed on to the
newborn through the colostrum (provided the calf ingests it). A single booster is given in
subsequent years. Monoclonal K99 E coli antibody is commercially available for oral
administration to calves immediately after birth. It is an effective substitute for the K99-specific
antibody in the colostrum of vaccinated cows, although calves that receive this product should also
receive colostrum for its nonspecific protection.

Vaccination of pregnant cows with rotavirus and coronavirus vaccines increase the amount of
specific antibody in colostrum and milk, but the concentration of antibodies in milk may be
insufficient to provide local antibody in the intestinal lumen during the period of peak prevalence
of infection, which, in calves, is 5–15 days of age. Controlled trials of commercial vaccines have
shown variable results. The addition of small amounts of immune colostrum to milk fed during the
period of susceptibility can provide some protection against disease.

Zoonotic Risk:
Several of the agents that produce diarrhea in calves can also produce diarrheal disease in
people. Cryptosporidium parvum and S Typhimurium can produce serious disease, particularly in
immunocompromised individuals. These organisms are commonly present as subclinical infections
in the gut of calves and lambs; immunocompromised people should avoid contact with young
ruminants and possibly all farm animals.

Cattle, including calves, are one of the reservoirs for the verotoxic E coli serotype O157:H7
associated with human hemorrhagic colitis and the hemolytic uremic syndrome. Infection in people
is usually acquired by consumption of contaminated food, but the infective dose is low and the
possibility of infection by direct contact exists. Other verotoxic E coli associated with human
disease can also be isolated from the feces of healthy cattle. Human disease from infection with
enteric livestock pathogens has occurred after seemingly trivial contact associated with visits to
livestock fairs, petting zoos, and farm educational tours. Hand cleansing and disinfection should
be a component of these visits.