Calf diarrhea is attributed to both infectious and non-infectious factors. Multiple enteric pathogens (e.g., viruses, bacteria, and protozoa) are involved in the development of this disease. Co-infection is frequently observed in diarrheic calves although a single primary pathogen can be the cause in some cases. The prevalence of each of pathogen and disease incidence can vary by geographical location of the farms, farm management practices, and herd size.

I-Infectious causes

1-Viral causes of calf diarrhea

1- Bovine rotavirus is a primary etiological agent of calf diarrhea.

▪️ Bovine rotavirus usually causes diarrhea in calves at 1 to 2 weeks of age.

▪️  The milk uptaken by calves can provide a good environment for rotavirus survival under a wide range of gastrointestinal pH levels and infection of the intestinal epithelial cells.

▪️The virus has a very short incubation period (12~24 h) and induces peracute diarrhea in affected calves. Once infected, the calves shed a large amount of virus via feces for 5~7 days, thus contaminating the environment and allowing the virus to be transmitted to pen mates.

2- Bovine coronavirus

▪️ This pathogen is a member (Betacoronavirus 1) of the genus Betacoronavirus that was formerly classified as group 2a coronaviruses.

▪️ Virus infection can present as three distinct clinical syndromes in cattle: a) calf diarrhea in calves at 1 to 2 weeks of age; b) winter dysentery with hemorrhagic diarrhea in adult animals; and c) respiratory diseases including bovine respiratory disease complex in both young and adult cattle.

▪️ The spike (S) protein of the virus plays an important role in virus entry and pathogenesis besides the ability to neutralize antibody. The S protein consists of two subunits (S1 and S2) and is crucial for virus-host interaction. While the S1 subunit facilitates binding of the virus to host cell receptors, the S2 subunit functions in the fusion of the viral envelope to host cellular membranes.

3- Bovine viral diarrhea virus

▪️ The clinical symptoms of BVDV infection vary from subclinical to fatal disease depending upon host immune status, pregnancy and gestation period, and the presence or absence of co-infection with other pathogens.

▪️ Most infected animals develop mild clinical signs such as low-grade fever, leukopenia, anorexia, and decreased milk production.

▪️ Acute BVD infection is characterized by diarrhea, pyrexia, depression, anorexia, decreased milk production, oral ulcerations, hemorrhagic syndrome, and lymphopenia/leucopenia leading to immunosuppression.

▪️ Immunosuppressed cattle become susceptible to other diseases due to the concurrent infection with other pathogens (e.g., bovine respiratory disease complex).

▪️ Although most immunocompetent animals eventually clear the virus and recover from the disease, some infected cattle occasionally harbor the virus for a long time with periodical appearance of transiently detectable viremia from time to time (e.g., transiently infected animals).

2- Bacterial causes of calf diarrhea

1-Salmonella

▪️ Salmonella enterica colonizes the gastrointestinal tract of a wide range of hosts. S. enterica serovar Typhimurium (S. typhimurium) and serovar Dublin (S. dublin) are the most common etiologic agents that cause salmonellosis in cattle.

▪️ Salmonella infection has a wide variety of clinical symptoms ranging from asymptomatic to clinical salmonellosis. Acute diarrheal disease is most common with S. typhimurium and systemic disease is associated with S. dublin. Calves less than 3 weeks of age are commonly infected by Salmonella. The lesions frequently observed in affected calves involve the pseudomembrane on the mucosa of the small intestine as well as enlargement of the mesenteric lymph nodes. Infected cattle can serve as a source of zoonosis through food-borne routes or direct contact.

▪️ Clinical presentation of salmonellosis is characterized by watery and mucoid diarrhea with the presence of fibrin and blood. Even though Salmonella can cause diarrhea in both adult cattle and calves, infection is much more common and often causes severe symptoms in 10-day to 3-month old calves.

▪️ Calves can shed the organism for variable periods of time and intermittently depending on the degree of infection (e.g., clinical or subclinical infection).

2- Escherichia coli

▪️The E.coli can be classified into different pathogroups based on virulence scheme: enterotoxigenic E. coli (ETEC), shiga toxin-producing E. coli (enterohaemorrhagic E. coli), enteropathogenic E (EPEC). coli, enteroinvasive E. coli, and enteroaggresive E. coli.

▪️ Among these bacteria, the most common cause of neonatal diarrhea is ETEC strains that produce the K99 (F5) adhesion antigen (commonly referred to as E. coli K99+).

▪️ Neonatal calves are most susceptible to ETEC infection during first 4 days after birth and develop watery diarrhea if infected. Following ingestion, ETEC infects the gut epithelium and multiplies in enterocytes of the intestinal villi. The distal portion of the small intestine provides the most favorable environment for ETEC colonization due to the low pH (less than 6.5).

3- Clostridium perfringens

▪️ Gram-positive, spore forming anaerobic bacterium that causes a wide range of diseases. These microorganisms can be subdivided into five toxin types (A, B, C, D, and E) based on the production of four major toxins: alpha (α), beta (β), epsilon (ε), and iota (ι).

▪️ Enterotoxin causes diarrhea and intestinal cramping due to its effects on epithelial tight junction protein. Beta-2 toxin, which is produced by all types of C. perfringens, has been recently postulated to synergistically function with enterotoxin.

3- Protozoa

1.  Cryptosporidium parvum is a protozoan parasite that is frequently associated with gastrointestinal tract disease in humans and neonatal cattle. There are approximately 24 species of Cryptosporidium. Cattle are commonly infected by C. parvum, C. bovis, C. ryanae, and C. andersoni. C. parvum is considered to be primary cause of calf diarrhea and is a potential zoonotic agent

2. Coccidiosis: Eimeria zuernii and Eimeria bovis are the two most common Eimeria species which cause coccidiosis in calves 6 to 12 months of age. In cattle, oocyst counts of greater than 500 per gram of feces in combination with typical clinical signs are highly suggestive of coccidiosis

II- Non-infectious causes diarrhea

1-  Nutritional cause of diarrhea

Nutritional deficiency of copper related to excess molybdenum in diet (secondary deficiency) can cause profuse diarrhea in calf called teart or peat scour.

2-  Dietetic diarrhea

-  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.

-  Incorrectly prepared oral electrolyte solutions or mixtures of milk with electrolyte solutions with excessively high osmolarity of the final solution can result in osmotic diarrhea.

3-  Antibiotic-related diarrhea

-  oral administration of antimicrobials such as 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 intestinal dysbiosis (destroy normal microflora)