Veterinary and Animal Science 15 (2022) 100238

Contents lists available at ScienceDirect

Veterinary and Animal Science

journal homepage: www.elsevier.com/locate/vas

Vaccination for the Prevention of Neonatal Calf Diarrhea in Cow-Calf

Operations: A Scoping Review
Gabriele Ute Maier a, *, Jefferson Breitenbuecher a, 1, Jose Pablo Gomez a, 2, Festus Samah a,
Erik Fausak b, Megan Van Noord b
a
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, 1 Shields Ave, Davis, CA, 95616, USA
b
University Library, University of California, Davis, 1 Shields Ave, Davis, CA, 95616, USA

A R T I C L E I N F O A B S T R A C T

Keywords: Neonatal calf diarrhea (NCD), also known as scours, is an important disease of preweaned calves that affects the
Calf scours production and welfare of beef herds. While hygiene and nutrition are important in reducing the incidence of
diarrhea NCD, vaccination of dams or calves is often employed for the prevention of NCD. The present scoping review
enteritis
summarizes the available peer-reviewed scientific English literature on vaccination of dams or calves for the
vaccine
prevention of NCD over the past decades. The online databases Medline, CAB Abstracts, and Biosis were searched
Abbreviations
CDFA-AUS California Department of Food and for articles on the topic published between 1950 and 2020. Online software was used to systematically evaluate
Agriculture–Antimicrobial Use and 2807 citations for inclusion through pre-determined criteria in a 2-step process. In the 113 articles included in
Stewardship the review, vaccines tested targeted the pathogens E. coli (n = 43), bovine rotavirus (BRV, n = 38), Salmonella (n
SYREAF Systematic Reviews for Animals and = 29), bovine coronavirus (BCV, n = 14), bovine viral diarrhea virus (n= 7), and other pathogens (n = 8). Field
Food trials for commercial vaccines have been published for the most important pathogens, and results on efficacy are
PRISMA preferred reporting items for variable for such vaccines targeting BRV, BCV, and E. coli. Meta-analyses exploring efficacy of these vaccines
systematic review and meta-analysis protocols
would be helpful to practitioners and producers. No field studies on commercial products have shown efficacy for
Salmonella vaccines so that a meta-analysis would unlikely come to a different conclusion. Further research is
needed on vaccines for protozoal pathogens like Cryptosporidium parvum as well as on the importance of several
emerging enteric viruses in calves.

1. Introduction infectious causes involve a variety of pathogens including viral, proto­

zoal, and bacterial pathogens, where one or more can be involved in the
Neonatal calf diarrhea (NCD), also known as calf scours or enteritis, disease process (Cho et al., 2013). Diagnosis of the disease-causing
is a gastrointestinal disease affecting pre-weaned calves. The disease can pathogen requires laboratory examination of samples from diseased
be fatal to young calves as a consequence of hypovolemia and acidosis animals (Cho & Yoon, 2014).
that may also result in anorexia and ataxia. The standard treatment for scouring calves includes oral or intra­
Neonatal calf diarrhea can be economically devastating to producers venous fluid therapy, isolation of infected animals, supportive care
due to high mortality and impaired growth of affected animals (de Graaf including anti-inflammatories and may include the use of antimicrobials
et al., 1999; Hasler et al., 2012). In cow-calf operations in the U.S. in (Constable, 2009; Smith & Berchtold, 2014). Antimicrobial treatment of
2007, losses from digestive problems made up 14% of deaths in calves calf diarrhea is, however, controversial. While opponents of antimicro­
less than three weeks old and 23% of deaths in calves three weeks of age bial use in the treatment of NCD state the potential for the emergence of
and older (USDA, 2010). antimicrobial resistant bacteria, proponents argue that a proportion of
The disease can be attributed to both infectious and non-infectious calves with diarrhea are bacteremic and are at risk of developing
causes. Non-infectious causes of NCD include vitamin deficiency or septicemia, and could therefore benefit from antimicrobial treatment
abrupt changes in diet, or errors in milk replacer feeding, while (Smith, 2015).

* Corresponding author
E-mail address: [email protected] (G.U. Maier).
1
current address: Center for Immunology and Infectious Diseases, University of California Davis, 1 Shields Ave, Davis, CA, 95616, USA
2
current address: Center for Animal Disease Modeling and Surveillance, University of California Davis, 1 Shields Ave, Davis, CA, 95616, USA

https://doi.org/10.1016/j.vas.2022.100238
Received 7 November 2021; Received in revised form 16 February 2022; Accepted 16 February 2022
Available online 19 February 2022
2451-943X/© 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

Methods recommended for the prevention of NCD include proper 2.3. Eligibility Criteria
cow nutrition during pregnancy, dystocia management, reduction of
environmental stress and contamination, and ensuring transfer of pas­ Based on the focus group discussion, original scientific reports in the
sive immunity to the calf via colostrum, enhancing the presence of form of peer reviewed research studies or conference proceeding of ≥
specific antibodies in the gut lumen during the calf’s most vulnerable 500 words published in English language in or after 1950 involving
age for NCD (Snodgrass, 1986), and bolstering the calf’s immunity via outcomes in calves under 6 months of age belonging to the genus Bos at
systemic uptake of antibodies (Al-Alo et al., 2018; Cho & Yoon, 2014). the individual or herd level were eligible for inclusion in the review. All
Colostrum quality depends partly on vaccination of the cow during observational or experimental study designs were included except case
pregnancy (Geletu et al. 2021, Meganck et al., 2014, Menichetti et al. studies or case series. No studies were excluded based on geographical
2021). Currently, commercial vaccines for the most important patho­ study location.
gens that cause calf diarrhea are available and are intended for vacci­ Studies had to compare a vaccination regime for the prevention of
nation of either the dam or the calf. NCD to either placebo or another intervention and have a clinical
The California Department of Food and Agriculture’s Antimicrobial quantifiable outcome beyond immune responses including but not
Use and Stewardship group (CDFA-AUS) conducts a statewide program limited to disease incidence, disease-specific mortality, duration of dis­
to promote the judicious use of antimicrobials in livestock species and ease, or weight gain. Studies had to include a diagnosis of any of the
poultry with the goal of preserving efficacy of these essential drugs as causative agents bovine rotavirus (BRV), bovine coronavirus (BCV),
well as protecting public health through measures that minimize the bovine viral diarrhea virus (BVDV), torovirus, norovirus, nebovirus,
emergence of antimicrobial resistant bacteria. A 2016 survey of cow-calf Salmonella, E. coli, Clostridium perfringens, Shigella, Yersinia, Cryptospo­
producers in California showed that NCD is one of three diseases that ridium, or Giardia, or a clinical diagnosis of diarrhea. Studies had to be
was most frequently treated with antimicrobials by respondents applicable to cow-calf operations, however, this did not necessarily
(CDFA-AUS, 2020). Although recommendations for prevention methods preclude studies conducted on dairies or in dairy breeds, as the princi­
such as vaccination are available in the form of review papers on the ples of immunology apply to both production settings. In the broadest
topic, we are not aware of any scoping reviews or meta-analyses on the terms, the question was whether the intervention could be implemented
efficacy of vaccines for NCD. as described or in a modified way by producers in the daily operation of
The objective of this study was to provide a comprehensive overview a cow-calf herd in terms of invasiveness of procedures or applicability to
of the literature on studies of vaccines to prevent NCD relevant to Cal­ beef production, as opposed to dairy or calf ranch environments.
ifornia cow-calf operations. We aimed to identify the existing literature
and describe vaccines used and outcomes reported. Further objectives 2.4. Sources of Information
were to identify the need for meta-analyses in specific areas with
abundant information or further research in areas with a lack of The database search was designed and conducted through the Carl­
information. son Health Library at the University of California, Davis. The databases
The resulting scoping review is part of the effort by CDFA-AUS to Medline (Pubmed interface, 1966 to 2020), CAB Abstracts (CAB Direct
develop best practices for California cow-calf operations. It is expected interface, 1972 to 2020) and Biosis (Web of Science interface, 1926 to
that the usefulness of the resulting tools and documents will expand 2020) were searched on November 22, 2019, and results combined in
beyond the state boundaries. Although the scoping review was con­ the reference manager software Endnote (Endnote, Clarivate Analytics,
ducted with practices and conditions in California in mind, the infor­ Philadelphia, Pennsylvania) where duplicates were deleted. The search
mation gained may be applicable to a much broader audience. strategy employed terms describing the population, disease, pathogens,
and intervention with restrictions on language and publication date.
2. Materials and Methods Keywords from key references were collected and compared with the
keywords utilized previously. Yale MeSH Analyzer (http://mesh.med.
2.1. Protocol and Registration yale.edu/) was also utilized to compare common Medical Subject
Headings across articles. The full electronic search strategy for Medline,
The preferred reporting items for systematic review and meta- CAB Abstracts, and Biosis including limits used, is available in Appendix
analysis protocols (PRISMA-P) (Liberati et al., 2009) as well as the A as well as in the study protocol (Maier, 2020).
PRISMA Extension for Scoping Review guidelines (Tricco et al., 2018) Conference proceedings and vaccine manufacturers’ unpublished
were used as references to conduct the review. An a priori review pro­ studies were searched and evaluated as part of the grey literature.
tocol was developed and archived in eScholarship, the online repository Conference proceedings for the American Association of Bovine Practi­
of the University of California (Maier, 2020) and was registered with tioners, the World Buiatrics Association, American College of Veterinary
Systematic Reviews for Animals and Food (SYREAF) (http://www. Internal Medicine, and the Conference of Research Workers in Animal
syreaf.org). Diseases, were extracted from S-Pac (Searchable Proceedings of Animal
Conferences) and citations hand searched for suitable inclusions into the
2.2. Focus Group Engagement review. The webpages of NCD vaccine manufacturers were searched for
studies that were not included in the above search and their technical
Before study start, in May 2019, a group of stakeholders consisting of services contacted where possible to inquire about any additional
bovine practitioners in private practice, academia, and from the state studies.
animal health regulatory body, a veterinary laboratory diagnostician, Finally, as an additional quality control step, articles included in the
and an animal science faculty member were invited to an in-person data extraction level of the review underwent a search through the
meeting to discuss the objectives and scope of the review. Topics dis­ Scopus database (www.Scopus.com) for their citations and those that
cussed during the focus group meeting were inclusion criteria, such as cited these articles. Results of the Scopus search were compared to ar­
timeframe, geographic limitations, allowable study designs, relevant ticles already identified in the previous database searches and any new
study populations, outcomes and interventions, and which pathogens to articles hand selected for inclusion into the review.
consider to best meet the objective of creating science-based guidelines
applicable to cow-calf producers in helping them prevent NCD. 2.5. Study selection and data extraction

After importation of study references into the systematic review

online software platform DistillerSR (Evidence Partners, Ottawa,

2
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

Canada) and an additional de-duplication step, the remaining studies citations were identified following the SCOPUS search of data-charted
underwent a two-level screening by two reviewers who independently articles. After manually scanning through articles identified in the
assessed the relevance of studies by title and abstract and then by full SCOPUS search published during the last 20 years (since the year 2000)
text using predefined eligibility questions based on PICOS (Population - one additional reference was added to the review for a total of 2808
Intervention - Comparison – Outcome – Study type) elements of eligi­ references. Vaccine manufacturers did not provide any additional
bility criteria (Schardt et al., 2007). studies. There were 213 (7.6 %) articles that underwent a full text re­
The questions to pass two levels of screening were as follows: Is the view for eligibility with 113 (4.0 %) undergoing data extraction
full text available in English? Is the study a case report or case series? (Figure 1). Citations for all 113 studies are listed in Appendix B cate­
Does the study compare vaccination regimes for the prevention of gorized by targeted pathogen.
scouring, diarrhea, or enteritis in pre-weaned calves or calves 6 months
old or younger? Is there a concurrent comparison group? Does the study 3.2. Study characteristics
make a diagnosis of scours/diarrhea/enteritis based on the pathogen
(viral, protozoal, or bacterial) or a clinical diagnosis? Can the inter­ Study characteristics including pathogens targeted, vaccine recip­
vention be generalized to cow-calf operations in California (not only ient, vaccine type, region where study was performed, study size, breed
specific for dairies or calf ranches)? Does the study report a quantifiable type, and study design are summarized in Table 2. Study sizes were
outcome to evaluate the efficacy (e.g. incidence of diarrheic calves, recorded as number of calves in the study, i.e., when dams were vacci­
cause specific mortality due to gastrointestinal disease)? Is the study nated, they were not counted. The number of calves in three studies
published in a peer-reviewed journal or conference proceedings ≥ 500 could not be determined, because the study design only described
words? number of herds enrolled, and these studies are not included in the
Studies were excluded if both reviewers responded “no” to any of the calculation of the total study size parameters in table 2. The number of
questions, except to the question “Is this study a case report or case publications for the different target pathogens per year is depicted in
series”, to which reviewers had to answer “yes” to exclude the study. Figure 2. Peer reviewed journal publications made up 109 articles, while
Disagreements were resolved by a third reviewer. Screening questions three were conference abstracts of 500 words or more and one was a
were pre-tested on a random selection of twenty studies included in the from a chapter of studies published in book format. While the majority
first level and ten studies included in the second level by reviewers to of studies were performed in preweaned calves, eight publications
validate screening questions and reach consensus on wording and mentioned the use of weaned calves only, and two used both weaned
interpretation of criteria. Data extraction from each study that passed and preweaned calves. Predominantly beef breeds were used in 14
the screening steps was performed by one reviewer in DistillerSR. The studies including the breeds Angus, Hereford, Angus/Charolais mix,
type of data extracted from each study is described in Table 1. Data was Japanese Black, native Korean, Slovak Red, Gascon, Limousin, Aubrac,
exported to Microsoft Excel and analyzed in R studio (version 1.2.5019). and Blonde Aquitaine. Predominantly dairy breeds were mentioned in
54 articles, including Holstein, Friesian, Jersey, Brown Swiss, Ayrshire,
3. Results Guernsey, and various crosses of those breeds. Dairy/beef crosses
including Friesian/Hereford crossbred cattle were mentioned in three
3.1. Sources of studies articles. No specific breed of cattle was mentioned in 42 articles. Sex of
study calves was not mentioned in 78 articles, 19 used only male calves,
There were 2807 unique citations identified through the initial 2 used only female calves, and 14 had both male and female calves in
literature searches including grey literature. An additional 1682 unique their studies. Commercial herds were used in 46 articles, research herds
were used in 47 articles, both research and commercial herds were
mentioned in 3 articles, and in 17 studies we could not determine what
Table 1 the herd type was. Barns were used as housing type in 3 studies, 46
Description of data charting items for relevant journal articles or proceedings for studies mentioned individual pens, boxes, isolation facilities with indi­
a scoping review on vaccination for the prevention of neonatal calf diarrhea in vidual pens, or a laboratory or experimental type setting as the housing
cow-calf operations
type during the study period, 13 articles mentioned studies that were
Variable Description of information extracted carried out on pasture, and 51 did not specifically state what the housing
Study Year of publication, region and country where study was or environment was. Randomization to study groups was mentioned in
characteristics performed (North America, Central America, South America, 28 articles, blinding of researchers to group allocation was described in
Europe, Asia, Africa, Australia/New Zealand), publication 10 articles. Combination vaccines covering more than one pathogen
type (Peer reviewed journal, conference abstract), study
were studied in 19 articles.
population: production system (beef, dairy, not stated), calf
age group (preweaned, weaned), breed (Angus, Hereford,
Holstein, etc.), sex (female, steers, bulls, not stated), herd 3.3. Individual pathogens
type (commercial, research, not stated), housing type
(pasture, barn, laboratory, etc.), study type (experimental,
3.3.1. Bovine rotavirus
observational), vaccine recipient (dam, calf), when was
vaccine given, route of administration (intramuscular, Bovine rotavirus is in the family of Reoviridae and named Reovirus
subcutaneous, oral, etc.), for experimental studies: in earlier studies. We counted studies on reovirus vaccines together with
randomized group allocation, control group type (placebo, no the BRV vaccines. Timing of the first vaccination given to calves ranged
intervention, different intervention), researchers blinded to between the first 6 hours to the first 3 days of life, with only 5 studies
group allocation, how was diagnosis established (culture,
clinical diagnosis)
vaccinating calves, while 34 studies relied on vaccination of the dams for
Study outcomes Disease incidence, disease severity (severity score, duration calf protection from BRV. Timing of dam vaccination varied widely
of illness), weight gain, disease specific mortality, risk ratio between studies and consisted in many of the studies of two doses during
Study groups Verbal description of group (vaccinated, control, etc.), how the last two months of pregnancy. However, in some studies, dam
many animals in the group
vaccination was performed with wider intervals, e.g. one article
Intervention per Type of vaccine studied (none (for controls), modified live,
group killed, toxoid, subunit/conjugate, recombinant, etc) mentioned vaccination prior to mating and seven months later approx­
Results per study Intervention statistically improved outcome between study imately two to three months before calving (Snodgrass et al., 1980).
group groups, statistically worsened outcome between study Killed vaccines were used in 22 articles, modified live vaccines in 14
groups, statistically did not change outcome between groups, articles, one article used a recombinant BRV vaccine, and one used both
or statistical results not provided
a modified live and killed vaccine. While 5 of the articles used beef

3
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

Fig. 1. Scoping review on vaccination for the prevention of neonatal calf diarrhea: PRISMA flow diagram of citations form the literature search to relevance
screening and data extraction.

breeds or herds to study BRV vaccines, 3 used beef and dairy cattle, 19 vaccines, while 25 articles studied vaccinated calves. Study size varied
only dairy cattle and 11 did not state the production type. There were 16 between 8 and 1007 animals. While the majority of 17 studies was
studies involving commercial vaccines for BRV, 10 of which studied conducted in dairy cattle, one study was performed with beef cattle, one
combination vaccines and 6 that studied vaccines for BRV alone. Results with both beef and dairy cattle and 10 did not state the production type.
for 11 field trials for commercial BRV vaccines are summarized in In studies that mentioned calf age at vaccination, calves received their
Table 3. Of the 11 field trials with commercial BRV vaccines, 3 reported first dose between 1 day and 4 weeks of age. Four studies relied on
statistically significantly improved outcomes in calves of vaccinated clinical diagnoses only, while all others performed culture or additional
dams, while 3 did not provide statistical results. The remaining studies diagnostics to establish a diagnosis of salmonellosis. Salmonella dublin
either saw no differences in outcomes between groups or found unde­ was the vaccine serovar in 9 articles, Salmonella typhimurium in 14. Two
sirable outcomes in groups receiving BRV vaccine with one reporting articles included vaccines with both Salmonella dublin and Salmonella
higher case fatality in calves vaccinated for BRV and dams receiving a typhimurium, one article studied a Salmonella saint-paul serovar vaccine,
placebo compared to those calves receiving a placebo, or where the dam one a Salmonella newport serovar vaccine, one article compared a Sal­
had received an E. coli bacterin additionally to calves receiving the BRV monella serotype Cholerasuis vaccine to both a Salmonella montevideo
vaccine (Acres and Radostits 1976). Another study found a higher serovar vaccine and control, while one article studied dialyzable
number of calves treated for all diseases in vaccinated herds versus leukocyte extract as a Salmonella vaccine. The same serovar, although
unvaccinated herds (Waltner-Toews et al. 1985). often a different strain, was used to challenge vaccinated animals in 14
of the 22 articles that described a challenge, while in 7 articles a
3.3.2. Salmonella different serovar was used and 1 article used both the same as well as a
Dams were vaccinated in only 4 of the 29 articles on Salmonella different serovar from the vaccine serovar, although not in the same

4
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

Table 2
Counts of published literature for different study design characteristics, across three time periods, identified in a scoping review on vaccination for the prevention of
neonatal calf diarrhea relevant to cow-calf operations.
Years
Characteristic pre 1980 1980-1989 1990-2020 Total

Pathogen targeted
E. coli 14 15 14 43
Salmonella 4 11 14 29
Bovine rotavirus 3 24 11 38
Bovine coronavirus 1 6 7 14
Bovine viral diarrhea virus 0 0 7 7
Other 0 1 7 8
Vaccine recipient
Dam 14 34 20 68
Calf 6 14 25 45
Vaccine type
Commercial 3 15 18 36
Experimental 17 33 27 77
Region
North America 13 17 20 50
Australia/New Zealand 0 1 4 5
Europe 7 26 8 41
Africa 0 0 2 2
Asia 0 3 6 9
South America 0 1 5 6
Total study size
Median (IQR) 51 (40, 307) 43 (22, 110) 29 (16, 101) 41 (23, 132)
Mean, (SD) 563 (1149) 497 (1386) 308 (781) 435 (1134)
Range 10 - 4068 8 - 6787 6 - 4053 6 – 6787
Breed Type
Beef 8 4 6 18
Dairy 0 20 28 48
Beef & Dairy 2 2 0 4
Not Stated 10 21 11 42
Dairy & Not Stated 0 1 0 1
Study Design
Experimental 20 47 40 107
Observational 0 1 5 6
Challenge Type
Natural 7 12 17 36
Experimental 13 30 28 71
Both1 0 6 0 6
1
Articles in this category contained trials with both natural and experimental challenge.

group of animals. for BRV and E. coli K99 did not evaluate the E. coli component as no
Results for three field trials for commercial Salmonella vaccines are natural challenge was evident and was only counted under BRV field
summarized in Table 4. None of the field trials was able to find any studies for commercial vaccines (McNulty & Logan, 1987).
statistically significant differences between vaccinated and control
calves in the outcomes they evaluated. One of the field trials used an 3.3.4. Bovine coronavirus
injectable vaccine in extra-label fashion orally in calves. There were 14 articles that evaluated vaccines for BCV of which
thirteen included vaccines in combination with either BRV, BRV and
3.3.3. Escherichia coli E. coli, or BRV, E. coli, BVD, and bovine parvovirus. Study sizes for BCV
Articles studying vaccines for E. coli made up most articles in this vaccines varied between 6 and 5770. Dairy was the production system in
review with a total of 43. The production system of 15 articles was 5 articles on BCV vaccines, 2 named beef as the production system, 1
described as beef herds or beef breed types, in 11 articles as dairy herds conducted trials in both beef and dairy herds and 6 did not state the
or dairy breed types, 1 article involved both beef and dairy cattle and 16 production system. The vaccine recipient was the dam in 10 of the ar­
articles did not state the production type of cattle involved. Study sizes ticles, while 4 articles described vaccinating calves. Results for six field
varied between a total of 10 and 4053 animals. Of the 43 articles on trials with commercial BCV vaccines are described in Table 3. Two
E. coli vaccines, 39 described vaccinating dams, while three reported on studies in Table 3 that used vaccines for BCV tested for excretion of BRV
calf vaccination and one on vaccination of both calves and dams. Calves only and were not counted as a field trial for commercial BCV vaccines
were challenged in 20 of the studies with either homologous (7 articles) (de Leeuw et al., 1980; Rocha et al., 2017). Of the 6 field trials that
or heterologous strains (5 articles) or had a combination of groups where included BCV vaccines, 2 reported advantageous results for the vacci­
some received homologous and some heterologous challenges (7 arti­ nated animals, 2 reported no difference, 1 found worse outcomes for
cles). In one of the articles, the challenge strain was not described. The vaccinated animals, and 1 did not report statistics.
results of 12 field trials involving commercial E. coli vaccines are
described in Table 5, some of which also appear in Table 3 since they are 3.3.5. Other pathogens
combination vaccines with BRV/BCV. While 3 of the field trial articles Bovine Viral Diarrhea virus was the sole target pathogen in 6 articles.
showed advantageous results for incidence or treatment for calf diarrhea Four studies were performed in dairy herds, one in beef herds and one
in vaccinated calves, 3 showed the opposite effect and 4 did not detect a did not state the production system. Study sizes were small, ranging
difference between vaccinated and unvaccinated calves and 2 did not between 10 and 48 animals and in all studies, calves were the vaccine
provide any statistics. One study that evaluated a combination vaccine recipients and were challenged intranasally. Four of the studies used

5
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

Fig. 2. Scoping review on vaccination for the prevention of neonatal calf diarrhea: number of studies published per year between 1960 and 2020 color-coded by
target pathogen. Studies with multivalent vaccines are counted multiple times.

commercial vaccines versus 2 that tested experimental vaccines. One vaccine in gnotobiotic calves, however no statistics were offered in this
study focused mostly on the effect of added injection of trace minerals preliminary study with 15 calves in 7 different trial groups (Han et al.,
concurrently with vaccination but found no differences to calves that did 2006).
not receive the injectable trace minerals with respect to clinical out­ One article studied a commercial vaccine that included bovine
comes. However, all calves were protected from BVDV2 infection (Bittar parvovirus besides BRV, BCV, E. coli and BVD (Kohara et al., 1997).
et al., 2018). The study in beef herds compared three types of com­ Dams were the vaccine recipient in this trial. The authors could not
mercial vaccines and placebo given to early weaned calves (at 62 – 92 detect an increase in virus neutralizing antibody titers in either dams or
days of age, median age 72.2 days), which were subsequently challenged calves post vaccination and did not detect bovine parvovirus in any of
with BVD2. There were no clinical differences between the groups, the calves by examining fecal suspensions by electron microscopy.
which was thought to be due to protection from maternally derived
antibodies in these calves (Chamorro et al., 2015). 4. Discussion
Five articles studied vaccines for Cryptosporidium, all of which
involved experimental vaccines. Three of the studies on Cryptosporidium 4.1. Available literature
vaccines targeted the dam, while two had calves vaccinated. In 4 arti­
cles, calves were challenged orally while 1 field study relied on natural While there are many review articles and book chapters on NCD as a
infection. Vaccines used were recombinant P23 protein, killed oocysts, disease complex and the various pathogens including the use and effi­
or whole oocysts. Four of the five studies showed favorable results in cacy of vaccines, a Pubmed search on meta-analyses of the terms
vaccinated calves with respect to duration of diarrhea and/or number of “scours” or “diarrhea” AND “calf” or “calves” resulted in no meta-
oocysts shed, however the one large field trial was unsuccessful in analysis studies evaluating the efficacy of vaccines for the prevention
showing efficacy of the vaccine under investigation. of NCD. The present scoping review was therefore needed to summarize
One article evaluated an experimental vaccine for Giardia duodenalis the available literature and to point out areas where meta-analyses will
prepared from sonicated trophozoites (Uehlinger et al., 2007). The au­ be useful or where further research is needed.
thors were unable to show efficacy in preventing giardiasis or reducing Unfortunately, the full text for 40 articles included in the 213 articles
cyst shedding in a small trial with three vaccinated and three control that passed the screening level was not available through the Carlson
calves that underwent an oral challenge of G. duodenalis cysts. Health Library. The search for older articles that might have been
One article compared diarrhea scores and virus shedding post chal­ retrievable on the shelves of partner libraries could have been impacted
lenge depending on the route of vaccination in a trial for a norovirus by the concurrent Covid-19 pandemic, which impaired in-person access

6
 Table 3

G.U. Maier et al.

Scoping review on vaccines for neonatal calf diarrhea: results of field trials for commercial bovine rotavirus and bovine coronavirus vaccines with natural challenge
Author(s), year Vaccine name, vaccine type, Study Group name (number in Outcome Result
pathogens, route, recipient group)

Acres & Radostits, Scourvax-Reo, modified live, BRV, 1. E. coli bacterin to cows, modified live Incidence of calf diarrhea, diarrhea-specific mortality No significant differences
1976 oral, calf BRV to calves (247)

2. E. coli bacterin to cows, placebo to Case fatality Statistically higher in group 3 (placebo to cows, modified live BRV
calves (268) vaccine to calves)

3. Placebo to cows, modified live BRV

vaccine to calves (217)

4. Placebo to cows, placebo to calves

(264)
de Leeuw et al., Scourvax-reo 1, modified live, BRV, 1. Vaccinated (74) Incidence of BRV-associated diarrhea, No statistics provided; BRV excretion: 20/74 in vaccinated, 19/76 in
1980 BCV, oral, calf Severity score of BRV-associated diarrhea, Incidence of placebo; severity score of BRV associated diarrhea: 3.0 in vaccinated
undifferentiated diarrhea, versus 1.5 in placebo on farm A and 1.0 in vaccinated versus 1.1 in
Severity score of undifferentiated diarrhea placebo on farm C (higher score = more severe).
2. Placebo (76)
Hudson, 1981 Calf Guard, modified live, BRV, BCV, 1. Vaccinated (3879) Incidence of calf diarrhea, case fatality Statistically lower in vaccinated
intramuscular, dam
2. Non-vaccinated (1891) Number of treatments required for diarrhea No statistics provided: 0.77% (30/3879) of vaccinated requiring two
or more treatments versus 3.91% (74/1891) of controls
Bürki et al., 1983 Calf Guard, modified live BRV, BCV 1. Vaccinated day 1 (31) Incidence of diarrhea, severity of diarrhea No statistics provided
oral, calf
2. Vaccinated day 3 (24)
3. Unvaccinated control (4)
Waltner-Toews Scourguard3, modified live BRV, 1. Calves of vaccinated cows, trial A Treatment for diarrhea, mortality, days to first treatment or No significant differences
et al., 1985 BCV, K99 bacterin, intramuscular, (182) duration of treatment all diseases, days to first treatment or
7

dam duration of treatment for diarrhea, estimated weight gain

(trial A)
2. Calves of placebo cows, trial A (95) Calves treated for all diseases or treated for scours or No significant differences
treated for scours from day 5 – 14, mortality (trial B)
1. Vaccinated herds, trial B (11 herds, n Calves treated for all diseases from day 5 – 14 (trial B) Statistically higher in vaccinated herds
not stated)
2. Non-vaccinated herds, trial B (12
herds, n not stated)
McNulty & Logan, Rotavec K99, killed, BRV, E. coli K99, 1. Vaccinated (19) Incidence of abnormal feces or diarrhea No statistics provided; 1/19 in vaccinated versus 9/29 unvaccinated
1987 intramuscular, dam
2. Unvaccinated (29)
Kohara et al., Lactovac, killed, BRV, BCV, 1. Vaccinated (48) Incidence of diarrhea, mean age of onset, duration of No significant differences
1997 Parvovirus, E. coli K99 pilus, diarrhea, mortality
subcutaneous, dam

Veterinary and Animal Science 15 (2022) 100238

2. Unvaccianted (48)
Le Rousic et al., Lactovac, killed BRV, BCV, E. coli 1. Vaccinated (12) Severity score of BRV associated diarrhea Statistically lower in vaccinated
2000 K99/F41 antigen, subcutaneous, dam
2. Unvaccinated (12) Weight gain No significant difference
Perk et al., 2000 Rotavac, killed, E. coli K99 and BRV, 1. Vaccinated with Rotavac, trial 1 Morbidity, mortality, time to diarrhea, days of diarrhea, No statistics provided; mortality in Rotavac group (16/190) versus
route not stated, dam (190) severity of diarrhea, number of treatments, trial 1 Nobivac group (18/65). No numbers provided for other outcomes
2. Vaccinated with Nobivac (E. coli Morbidity, mortality, time to diarrhea, days of diarrhea, No significant differences between groups
K99), trial 1 (65) severity of diarrhea, number of treatments, trial 2
3. Vaccinated with Rotavac and 13 days
of supplementary hyperimmune K99/
RV colostrum, trial 2, n not stated
4. Vaccinated with Rotavac and 13 days
of placebo, trial 2, n not stated
Incidence of diarrhea Statistically lower in treatment herds
(continued on next page)
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

to library buildings. Although criteria for the inclusion of references into

the review listed only peer reviewed journals and conference abstracts of
500 words or more, 1 reference is from a book titled “Advances in

positive for BRV in vaccinated (6/77) versus unvaccinated (3/74).

No statistics provided; diarrheic fecal samples collected that are
Experimental Medicine and Biology” (Welter, 1998). Its contributions
are peer-reviewed and therefore it was deemed appropriate to include
the article.

4.2. General comments on vaccination for NCD

Calf diarrhea is often described as a management problem that

should be addressed with improved hygiene and colostrum management
(Tyler et al., 1999). Failure of transfer of passive immunity (Bragg et al.,
2020) or inadequate transfer of passive immunity (Pearson et al., 2019)
is prevalent in beef calves and have been associated with risk factors
No significant difference

such as births requiring assistance, twin births, and heifer dams, and
may be an important contributor to NCD in beef calves. Vaccination of
calves or dams for the prevention of calf diarrhea is sometimes described
as a band-aid for poor management. For example, one prospective
cohort study in this review found that vaccination of dams for E. coli was
Result

associated with an increased risk for calf diarrhea. The authors hy­
pothesized that those farms with high incidence of diarrhea try to
eliminate the disease by vaccination (Bendali et al., 1999). As such,
vaccination should not be regarded as the only component for the pre­
vention of NCD as part of a herd health program but may be helpful to
enhance other measures.
Vaccination of calves for neonatal diarrhea is commonly viewed as
Diarrheic fecal samples positive for BRV

problematic depending on the pathogen, because disease often occurs

early on in life, often within the first days, when the administration of
vaccines may be less effective due to an immature immune system or the
Duration of diarrhea, mortality

interference of maternal antibodies. It is therefore not surprising that a

majority of studies investigated vaccination of pregnant cows to eval­
uate its effect on calf diarrhea-related outcomes. On the other hand, how
successful vaccination of dams for the protection of calves from NCD is
in the field depends on the transfer of passive immunity, which can vary
with timing and amount of colostrum consumed by calves. Poor uptake
Outcome

of colostrum by calves may be part of an NCD herd problem so that dam

vaccination is unlikely to be the only solution.
The randomized blinded placebo-controlled field trial is the refer­
1. Vaccinated, calves also treated with

ence standard to evaluate vaccine efficacy. We found a limited number

oral halofuginone (13 herds, n = 296)
2. Control, no treatments (11 herds, n

2. Non-vaccinated herd (28 calves)

of field trials of variable quality, based on whether randomization to

Study Group name (number in

study groups, blinding of researchers, or use of a placebo in the control

1. Vaccinated herd (28 calves)

group was mentioned, for vaccines for each of the major pathogens. An
assessment of study quality is not part of a scoping review, therefore
none of the available articles were excluded based on limitations of
study design or analysis (Tricco et al., 2018). Moreover, USDA does not
require the publication of efficacy data for vaccine licensure (Moon &
Bunn, 1993), which limits the available information. A common expla­
group)

= 234)

nation for why a given vaccine did not show efficacy during a field trial
provided in the included articles, is a mismatch between outbreak and
vaccine strain or the contribution of other non-target pathogens.
Therefore, the use of appropriate diagnostics to identify an outbreak
Name not stated, killed, BRV, BCV,
Rotavec-Corona, killed, BRV, BCV,

perfringens toxoid, intramuscular,

strain and careful selection of a vaccine appear to be important in the

E. coli K99 bacterin, Clostridium
Vaccine name, vaccine type,
pathogens, route, recipient

successful implementation of vaccines for the prevention of calf

E. coli, intramuscular, dam

diarrhea.

4.3. Individual pathogens

4.3.1. Bovine rotavirus

Bovine rotavirus is divided into eight groups or species A – H based
dam

on properties of an inner viral capsid protein V6, with group A being the
most prevalent. Groups are further subdivided into strains via charac­
Table 3 (continued )

terization of G (glycoprotein) and P (protease-sensitive) types (Mat­

Author(s), year

Meganck et al.,

Gomes Rocha
et al., 2017

thijnssens et al., 2012). A relatively recent study concluded that even

though strain prevalence fluctuates over space and time, a predominant
2014

genotype (G6P[5]) exists (Papp et al., 2013). Vaccine failure has been
attributed to a mismatch between field and vaccine strains (Kohara

8
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

Table 4
Scoping review on vaccines for neonatal calf diarrhea: results of field trials for commercial Salmonella vaccines with natural challenge
Author, Vaccine name, vaccine type, Study Group names Outcome Result
year pathogens, route, recipient (number in group)

Peters et al., Bovivac Plus, killed, Salmonella, E. 1. Vaccinated (125) Morbidity or mortality from all No difference
1987 coli, Pasteurella, subcutaneous, calf causes
2. Unvaccinated (33)
House et al., SC-54, modified live, Salmonella 1. Vaccinated Incidence of Salmonella shedding, No difference
2001 Cholerasuis, intramuscular, dam commercial vaccine (31) mortality
2. Vaccinated Frequency of shedding Statistically significantly lower in vaccinated with
autogenous bacterin commercial vaccine versus autogenous bacterin but not
(31) versus unvaccinated
3. Unvaccinated (18)
Habing Entervene-D, modified live, 1. Vaccinated (140) Morbidity from all causes, No difference
et al., Salmonella Dublin, oral, calf Salmonella-specific morbidity,
2011 weight gain, mortality
2. Placebo (148)

et al., 1997; Rocha et al., 2017). Based on the number and outcomes of virulence factors, namely adhesins, which include fimbriae, and
published field trials for commercial vaccines, a meta-analysis of the heat-labile and heat-stable enterotoxins (Dubreuil et al., 2016). Colos­
available data would be helpful to further characterize the usefulness of tral antibody cross-protection to different fimbrial antigens does not
these vaccines for herds struggling with BRV infections. exist so that even calves with good transfer of passive immunity may be
susceptible to ETEC with different F antigens. Vaccines must be matched
4.3.2. Salmonella to the outbreak F antigen to be effective.
Salmonella enterica (abbreviated Salmonella from here on), a zoonotic Given the relative abundance of field trials with commercial vaccines
agent, is divided into serogroups based on the O antigen and named by targeting E. coli, a meta-analysis of the available studies would be
capital letters A, B, C, etc (Peek & Divers, 2018). Salmonella are further helpful in further evaluating the usefulness of these vaccines under field
subdivided into serovars of which Salmonella typhimurium, and Salmo­ conditions.
nella dublin are most commonly isolated from clinical cases in cattle
(Mizuno et al., 2008). Salmonella dublin is the host adapted serotype in 4.3.4. Bovine coronavirus
cattle that can result in calf diarrhea and pneumonia outbreaks as well as Bovine coronavirus is part of the Betacoronavirus 1 species, which
subclinically infected carriers (Habing et al., 2011). Antimicrobial also includes human enteric coronavirus, equine coronavirus, canine
resistance to Salmonella is widespread, emphasizing the need for pre­ respiratory coronavirus and others (Hodnik et al., 2020). Coronaviruses
ventative measures as treatment options are limited (Peek & Divers, have been isolated from diarrheic calves and adult cattle (winter dys­
2018). entery) as well as cattle with respiratory disease. Antigenic variation
Failure of killed Salmonella vaccines has been attributed to antigenic exists but seems unrelated to the different disease syndromes (Bidokhti
variety of Salmonella organisms as well as the inability of killed vaccines et al., 2012; Hasoksuz et al., 1999; Tsunemitsu & Saif, 1995). Further­
to stimulate a cell-mediated immune response, which is deemed more, cross-protection after exposure to BCV and reinfection with a BCV
important to combat Salmonella infections besides a humoral response isolated from a different disease syndrome has been observed (Cho et al.,
(Curtiss et al., 1993; Habing et al., 2011; Johnson et al., 1985). Salmo­ 2001) leading to the hypothesis that clinical signs do not depend on
nella in live vaccines are attenuated through mutations in global regu­ specific strains but rather on host factors (Suzuki et al., 2020). As
latory networks, e.g. in the DNA adenine methylase (dam) (Mohler et al., virtually all field trials summarized in this review are combination
2008) or through aromatic-dependent mutants (aroˉ) (Mukkur et al., vaccines covering mostly BRV or BRV and E. coli in addition to BCV, a
1991; Smith et al., 1993). Fecal shedding of the vaccine strain and meta-analysis exploring the efficacy of these products should either
colonization of lymphoid tissue as well as side effects of vaccination combine all such vaccines or focus on BRV/BCV vaccines.
from endotoxins are of concern when developing and using modified
live Salmonella vaccines. A commercial vaccine targeting Salmonella 4.3.5. Other pathogens
newport is on the market in the U.S. but was not captured by our review There are many studies that evaluate the use of vaccines for BVD.
as its effect on calf health has not been evaluated (Hermesch et al., However, we specifically searched for those studies where diarrhea was
2008). Given the sparsity of available field trials for commercially among the outcomes analyzed. Bovine Viral Diarrhea virus is a virus
available Salmonella vaccines and given that none showed efficacy of the with complex pathogenicity and many studies on vaccines for this
respective vaccines, a meta-analysis of those data is not likely to provide pathogen are interested in outcomes such as bovine respiratory disease,
useful information. Given the complexity of Salmonella serovars and reproductive failure in female cattle, persistently infected calves, or
immunogenicity of Salmonella infections as well as the risks associated mucosal disease of calves. Even though vaccination for BVD should be
with vaccination, a systematic review of Salmonella vaccines would be part of all cattle operations, BVD is typically not considered as one of the
more helpful in guiding veterinarians and producers faced with NCD due common pathogens involved in NCD. A herd infected with BVD would
to Salmonella infections. likely see other disease manifestations such as abortions or poor-doing
persistently infected calves that would point towards a problem with
4.3.3. Escherichia coli BVD. We included BVD vaccines for completion in this review but realize
Escherichia coli is a commensal important member of the gut micro­ the limited scope of publications on BVD vaccines we were able to
biota in cattle. However, multiple pathogenic types exist, which are include based on our criteria.
classified based on cell wall (O), capsular (K), fimbrial (F) or flagellar Cryptosporidiidae are coccidial protozoa with C. parvum being the
(H) antigens. It is important to understand that pilus antigens were species of most clinical importance in causing diarrhea in preweaned
formerly classified as K antigens, but have recently been reclassified as F calves (Peek & Divers, 2018; Thomson et al., 2017). Despite widespread
antigens to avoid confusion, e.g. K-99 is now F-5 (Peek & Divers, 2018). occurrence of cryptosporidiosis, there are few treatment options. One of
The enterotoxigenic E. coli (ETEC) F-5 and F-41 are most commonly the available drugs for the prevention of diarrhea caused by Cryptospo­
associated with diarrhea in calves. Enterotoxigenic E. coli produce two ridium is halofuginone lactate, which is, however, not approved for use

9
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

Table 5
Scoping review on vaccines for neonatal calf diarrhea: results of field trials for commercial E. coli vaccines with natural challenge
Author, year Vaccine name, vaccine type, Study Group names Outcome Result
pathogens, route, recipient (number in group)

Krogh, 1983 Coligen, killed, 4-strain E. coli, route 1. Coligen (109) Incidence of diarrhea in first week Statistically lower in Vicogen group than placebo
not stated, dam of life
Vicogen, killed, K99 E. coli, route
not stated, dam
2. Vicogen (73) Diarrhea-specific mortality No statistics provided; mortality: Coligen group 1/
109, Vicogen group 2/73, placebo group 2/114.
3. Placebo (114)
Schipper et al., Vicoten, killed, E. coli, route not 1. Vicoten (1137) Incidence of diarrhea No difference between groups in year 1 of study;
1984 stated, dam statistically lower in unvaccinated group in year 2
Coligen, killed, E. coli, route not of study
stated, dam
K99, killed, E. coli, route not stated,
dam
2. Coligen (754)
3. K99 (365)
4. Unvaccinated (948)
Loucks et al., 1985 Vicogen, killed, E. coli, 1. Vaccinated (51) Diarrhea severity scores, No difference between groups
subcutaneous, dam treatments for diarrhea (major
and minor), mortality
2. Unvaccinated (51)
Sihvonen & Coligen, killed E. coli, 1. Vaccinated (45) Incidence of diarrhea No statistics provided; abnormal or diarrheic feces
Miettinen, 1985 intramuscular, dam with K 99 E. coli in vaccinated (30/45) versus non-
vaccinated (31/56).
2. Non-vaccinated (56)
Waltner-Toews
et al., 1985*
Kohara et al., 1997*
Bendali et al., 1999 No specific vaccine named, E. coli, 1. Vaccinated (777) Incidence of diarrhea Statistically higher in vaccinated
no route specified, dam
2. Non-vaccinated
(2303)
Le Rousic, 2000*
Perk et al., 2000*
Younis et al., 2009 Scour Guard 3, modified live BRV, 1. Vaccinated (no group K99 infection in diarrheic calves Statistically lower in vaccinated
BCV, K99 bacterin, no route stated, size stated)
dam
2. Non-vaccinated (no
group size stated)
Meganck et al.,
2014*
Gomes Rocha et al.,
2017*

*See Table 3

in cattle everywhere. No commercial vaccines are currently marketed Conclusions

for the prevention of cryptosporidiosis in calves despite preliminary
trials that have shown some promise for successful vaccination. Further Vaccines for NCD have mainly focused on the pathogens BRV, BCV,
research into the possibility of preventing cryptosporidiosis is desirable. E. coli, and Salmonella. Commercial products have been tested in field
Giardia duodenalis is another protozoan organism that has been trials for these pathogens and shown variable efficacy. Hence, meta-
associated with calf diarrhea in dairy calves (O’Handley et al., 1999) analyses exploring efficacy of these vaccines in field trials would be
and beef calves, although one study found no performance differences useful. No commercial Salmonella vaccine has shown efficacy for the
between infected and uninfected feedlot calves with regards to average prevention of NCD in a published field trial. A systematic review of
daily gain, dry matter intake and feed efficiency (Ralston et al., 2003). Salmonella vaccines describing the complex nature of different serovars
Giardia infection appears to be ubiquitous and may play a role in and immunogenicity of Salmonella infection in calves is needed. For
exacerbating the effects of other pathogens or nutritional or environ­ various other pathogens implicated in causing NCD, e.g. Cryptospo­
mental stressors (Olson et al., 2004). Its role in calf health is poorly ridium, available studies have not evolved beyond experimental stage
described and further research may help better understand its trials and require further research.
contributions.
A number of other viruses have been identified in the feces of diar­ Ethical Statement
rheic calves, including calicivirus, torovirus, astrovirus, norovirus, and
enterovirus, some of which have also been found in the feces of healthy The research conducted in this manuscript meets the criteria for
calves complicating the interpretation of such findings (Gomez & conduct, reporting, editing and publication of scholarly work in medical
Weese, 2017). We only found one article on a norovirus vaccine and one journals.
on a combination vaccine that included parvovirus antigen. The path­ In particular, guidelines on authorship, disclosure of financial sup­
ogenesis and epidemiology of many viruses are still poorly understood port, conflicts of interest, non-author contributions, duplicate sub­
and research at the basic level is needed to better understand their missions and prior publication have been followed.
importance and role in NCD. No animal or human subjects have been involved in the research;
therefore, no corresponding approvals of review boards are necessary.

10
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

The preferred reporting items for systematic review and meta- de Graaf, D. C., Vanopdenbosch, E., Ortega-Mora, L. M., Abbassi, H., & Peeters, J. E.
(1999). A review of the importance of cryptosporidiosis in farm animals. Int J
analysis protocols (PRISMA-P) as well as the PRISMA Extension for
Parasitol, 29(8), 1269–1287. https://doi.org/10.1016/s0020-7519(99)00076-4
Scoping Review guidelines were used as references to conduct the re­ de Leeuw, P. W., Ellens, D. J., Talmon, F. P., Zimmer, G. N., & Kommerij, R. (1980).
view, further ensuring that relevant guidelines were followed. Rotavirus infections in calves: efficacy of oral vaccination in endemically infected
herds. Res Vet Sci, 29(2), 142–147.
Dubreuil, J. D., Isaacson, R. E., & Schifferli, D. M. (2016). Animal Enterotoxigenic
Funding Escherichia coli. EcoSal Plus, 7(1). https://doi.org/10.1128/ecosalplus.ESP-0006-
2016
Geletu, U. S., Usmael, M. A., & Bari, F. D. (2021). Rotavirus in Calves and Its Zoonotic
This work was supported by a grant from the California Department Importance. Vet Med Int, 2021, Article 6639701. https://doi.org/10.1155/2021/
of Food and Agriculture, agreement number 18-0623-000-SG 6639701
Gomez, D. E., & Weese, J. S. (2017). Viral enteritis in calves. Can Vet J, 58(12),
1267–1274. https://www.ncbi.nlm.nih.gov/pubmed/29203935.
Habing, G. G., Neuder, L. M., Raphael, W., Piper-Youngs, H., & Kaneene, J. B. (2011).
Declaration of interests Efficacy of oral administration of a modified-live Salmonella Dublin vaccine in
calves. J Am Vet Med Assoc, 238(9), 1184–1190. https://doi.org/10.2460/
javma.238.9.1184
The authors declare that they have no known competing financial Han, M. G., Cheetham, S., Azevedo, M., Thomas, C., & Saif, L. J. (2006). Immune
interests or personal relationships that could have appeared to influence responses to bovine norovirus-like particles with various adjuvants and analysis of
the work reported in this paper. protection in gnotobiotic calves. Vaccine, 24(3), 317–326. https://doi.org/10.1016/
j.vaccine.2005.07.071. Epub 2005 Aug 10.
Hasler, B., Howe, K. S., Presi, P., & Stark, K. D. (2012). An economic model to evaluate
Acknowledgements the mitigation programme for bovine viral diarrhoea in Switzerland. Prev Vet Med,
106(2), 162–173. https://doi.org/10.1016/j.prevetmed.2012.01.022
Hasoksuz, M., Lathrop, S., Al-dubaib, M. A., Lewis, P., & Saif, L. J. (1999). Antigenic
The authors thank the members of the focus group Roselle Busch, variation among bovine enteric coronaviruses (BECV) and bovine respiratory
Kristine Clothier, David Daley, Michael Karle, Bret McNabb, Emmanuel coronaviruses (BRCV) detected using monoclonal antibodies. Arch Virol, 144(12),
Okello, James Oltjen and Charles Tobias for their valuable input. 2441–2447. https://doi.org/10.1007/s007050050656
Hermesch, D. R., Thomson, D. U., Loneragan, G. H., Renter, D. R., & White, B. J. (2008).
Effects of a commercially available vaccine against Salmonella enterica serotype
Supplementary materials Newport on milk production, somatic cell count, and shedding of Salmonella
organisms in female dairy cattle with no clinical signs of salmonellosis. Am J Vet Res,
69(9), 1229–1234. https://doi.org/10.2460/ajvr.69.9.1229
Supplementary material associated with this article can be found, in Hodnik, J. J., Jezek, J., & Staric, J. (2020). Coronaviruses in cattle. Trop Anim Health
the online version, at doi:10.1016/j.vas.2022.100238. Prod, 52(6), 2809–2816. https://doi.org/10.1007/s11250-020-02354-y
Johnson, E. H., Hietala, S., & Smith, B. P. (1985). Chemiluminescence of bovine alveolar
macrophages as an indicator of developing immunity in calves vaccinated with
References aromatic-dependent Salmonella. Vet Microbiol, 10(5), 451–464. https://doi.org/
10.1016/0378-1135(85)90027-6
Kohara, J., Hirai, T., Mori, K., Ishizaki, H., & Tsunemitsu, H. (1997). Enhancement of
Acres, S. D., & Radostits, O. M. (1976). The efficacy of a modified live reo-like virus
passive immunity with maternal vaccine against newborn calf diarrhea. J Vet Med
vaccine and an E. coli bacterin for prevention of acute undifferentiated neonatal
Sci, 59(11), 1023–1025. https://doi.org/10.1292/jvms.59.1023
diarrhea of beef calves. Can Vet J, 17(8), 197–212.
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gotzsche, P. C., Ioannidis, J. P.,
Al-Alo, K. Z. K., Nikbakht Brujeni, G., Lotfollahzadeh, S., Moosakhani, F., &
Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009). The PRISMA statement
Gharabaghi, A. (2018). Correlation between neonatal calf diarrhea and the level of
for reporting systematic reviews and meta-analyses of studies that evaluate health
maternally derived antibodies. Iran J Vet Res, 19(1), 3–8. https://www.ncbi.nlm.nih.
care interventions: explanation and elaboration. PLoS Med, 6(7), Article e1000100.
gov/pubmed/29805455.
https://doi.org/10.1371/journal.pmed.1000100
Bendali, F., Sanaa, M., Bichet, H., & Schelcher, F. (1999). Risk factors associated with
Maier, G. U., Gomez, J. P. P., Breitenbuecher, J. G. C., Fausak, E. D., & Van Noord, M. G.
diarrhoea in newborn calves. Vet Res, 30(5), 509–522.
(2020). Protocol for a Scoping/Systematic Review: Scoping Review of Vaccination for the
Bidokhti, M. R., Traven, M., Ohlson, A., Baule, C., Hakhverdyan, M., Belak, S., Liu, L., &
Prevention of Calf Scours in Cow-Calf Operations. Retrieved August 4, 2021 from htt
Alenius, S. (2012). Tracing the transmission of bovine coronavirus infections in
ps://escholarship.org/uc/item/67f1g9mq.
cattle herds based on S gene diversity. Vet J, 193(2), 386–390. https://doi.org/
Matthijnssens, J., Otto, P. H., Ciarlet, M., Desselberger, U., Van Ranst, M., & Johne, R.
10.1016/j.tvjl.2011.12.015
(2012). VP6-sequence-based cutoff values as a criterion for rotavirus species
Bittar, J. H. J., Hoyos-Jaramillo, A., Hurley, D. J., Woolums, A. R., Havenga, L. J.,
demarcation. Arch Virol, 157(6), 1177–1182. https://doi.org/10.1007/s00705-012-
Lourenco, J. M., Barnett, G., Gomes, V., Saliki, J. T., Harmon, D. D., &
1273-3
Palomares, R. A. (2018). Effects of injectable trace minerals administered
McNulty, M. S., & Logan, E. F. (1987). Effect of vaccination of the dam on rotavirus
concurrently with a modified live virus vaccine on long-term protection against
infection in young calves. Vet Rec, 120(11), 250–252. https://doi.org/10.1136/
bovine viral diarrhea virus acute infection in dairy calves. Res Vet Sci, 119, 250–258.
vr.120.11.250
https://doi.org/10.1016/j.rvsc.2018.07.003. Epub 2018 Jul 21.
Meganck, V., Hoflack, G., & Opsomer, G. (2014). Advances in prevention and therapy of
Bragg, R., Macrae, A., Lycett, S., Burrough, E., Russell, G., & Corbishley, A. (2020).
neonatal dairy calf diarrhoea: a systematical review with emphasis on colostrum
Prevalence and risk factors associated with failure of transfer of passive immunity in
management and fluid therapy. Acta Vet Scand, 56, 75. https://doi.org/10.1186/
spring born beef suckler calves in Great Britain. Prev Vet Med, 181, Article 105059.
s13028-014-0075-x
https://doi.org/10.1016/j.prevetmed.2020.105059
Menichetti, B. T., Garcia-Guerra, A., Lakritz, J., Weiss, W. P., Velez, J. S., Bothe, H.,
California Department of Food and Agriculture. (2020). Antimicrobial Use and Stewardship
Merchan, D., & Schuenemann, G. M. (2021). Effect of timing of prepartum
Program Annual Report 2020.
vaccination relative to pen change with an acidogenic diet on lying time and
Chamorro, M. F., Walz, P. H., Passler, T., van Santen, E., Gard, J., Rodning, S. P.,
metabolic profile in Holstein dairy cows. J Dairy Sci, 104(10), 11059–11071. https://
Riddell, K. P., Galik, P. K., & Zhang, Y. (2015). Efficacy of multivalent, modified- live
doi.org/10.3168/jds.2021-20242
virus (MLV) vaccines administered to early weaned beef calves subsequently
Mizuno, T., McLennan, M., & Trott, D. (2008). Intramuscular vaccination of young calves
challenged with virulent Bovine viral diarrhea virus type 2. BMC Vet Res, 11, 29.
with a Salmonella Dublin metabolic-drift mutant provides superior protection to oral
https://doi.org/10.1186/s12917-015-0342-8
delivery. Vet Res, 39(3), 26. https://doi.org/10.1051/vetres:2008001. Epub 2008
Cho, K. O., Hasoksuz, M., Nielsen, P. R., Chang, K. O., Lathrop, S., & Saif, L. J. (2001).
Feb 15.
Cross-protection studies between respiratory and calf diarrhea and winter dysentery
Mohler, V. L., Heithoff, D. M., Mahan, M. J., Walker, K. H., Hornitzky, M. A.,
coronavirus strains in calves and RT-PCR and nested PCR for their detection. Arch
Shum, L. W., Makin, K. J., & House, J. K. (2008). Cross-protective immunity
Virol, 146(12), 2401–2419. https://doi.org/10.1007/s007050170011
conferred by a DNA adenine methylase deficient Salmonella enterica serovar
Cho, Y. I., Han, J. I., Wang, C., Cooper, V., Schwartz, K., Engelken, T., & Yoon, K. J.
Typhimurium vaccine in calves challenged with Salmonella serovar Newport.
(2013). Case-control study of microbiological etiology associated with calf diarrhea.
Vaccine, 26(14), 1751–1758. https://doi.org/10.1016/j.vaccine.2008.01.018. Epub
Vet Microbiol, 166(3-4), 375–385. https://doi.org/10.1016/j.vetmic.2013.07.001
2008 Feb 4.
Cho, Y. I., & Yoon, K. J. (2014). An overview of calf diarrhea - infectious etiology,
Moon, H. W., & Bunn, T. O. (1993). Vaccines for preventing enterotoxigenic Escherichia
diagnosis, and intervention. J Vet Sci, 15(1), 1–17. https://doi.org/10.4142/
coli infections in farm animals. Vaccine, 11(2), 213. https://doi.org/10.1016/0264-
jvs.2014.15.1.1
410x(93)90020-x. -200.
Constable, P. D. (2009). Treatment of calf diarrhea: antimicrobial and ancillary
Mukkur, T. K., Walker, K. H., Jones, D., Wronski, E., & Love, D. N. (1991). Immunizing
treatments. Vet Clin North Am Food Anim Pract, 25(1), 101–120. https://doi.org/
efficacy of aromatic-dependent Salmonella dublin in mice and calves. Comp Immunol
10.1016/j.cvfa.2008.10.012. vi.
Microbiol Infect Dis, 14(3), 243–256. https://doi.org/10.1016/0147-9571(91)90005-
Curtiss, R., 3rd, Kelly, S. M., & Hassan, J. O. (1993). Live oral avirulent Salmonella
x
vaccines. Vet Microbiol, 37(3-4), 397–405. https://doi.org/10.1016/0378-1135(93)
90038-9

11
G.U. Maier et al. Veterinary and Animal Science 15 (2022) 100238

O’Handley, R. M., Cockwill, C., McAllister, T. A., Jelinski, M., Morck, D. W., & Snodgrass, D. R., Fahey, K. J., Wells, P. W., Campbell, I., & Whitelaw, A. (1980). Passive
Olson, M. E. (1999). Duration of naturally acquired giardiosis and cryptosporidiosis immunity in calf rotavirus infections: maternal vaccination increases and prolongs
in dairy calves and their association with diarrhea. J Am Vet Med Assoc, 214(3), immunoglobulin G1 antibody secretion in milk. Infect Immun, 28(2), 344–349.
391–396. https://www.ncbi.nlm.nih.gov/pubmed/10023403. Suzuki, T., Otake, Y., Uchimoto, S., Hasebe, A., & Goto, Y. (2020). Genomic
Olson, M. E., O’Handley, R. M., Ralston, B. J., McAllister, T. A., & Thompson, R. C. Characterization and Phylogenetic Classification of Bovine Coronaviruses Through
(2004). Update on Cryptosporidium and Giardia infections in cattle. Trends Parasitol, Whole Genome Sequence Analysis. Viruses, 12(2). https://doi.org/10.3390/
20(4), 185–191. https://doi.org/10.1016/j.pt.2004.01.015 v12020183
Papp, H., Laszlo, B., Jakab, F., Ganesh, B., De Grazia, S., Matthijnssens, J., Ciarlet, M., Thomson, S., Hamilton, C. A., Hope, J. C., Katzer, F., Mabbott, N. A., Morrison, L. J., &
Martella, V., & Banyai, K. (2013). Review of group A rotavirus strains reported in Innes, E. A. (2017). Bovine cryptosporidiosis: impact, host-parasite interaction and
swine and cattle. Vet Microbiol, 165(3-4), 190–199. https://doi.org/10.1016/j. control strategies. Vet Res, 48(1), 42. https://doi.org/10.1186/s13567-017-0447-0
vetmic.2013.03.020 Tricco, A. C., Lillie, E., Zarin, W., O’Brien, K. K., Colquhoun, H., Levac, D., Moher, D.,
Pearson, J. M., Pajor, E., Campbell, J., Levy, M., Caulkett, N., & Windeyer, M. C. (2019). Peters, M. D. J., Horsley, T., Weeks, L., Hempel, S., Akl, E. A., Chang, C.,
A randomised controlled trial investigating the effects of administering a non- McGowan, J., Stewart, L., Hartling, L., Aldcroft, A., Wilson, M. G., Garritty, C.,
steroidal anti-inflammatory drug to beef calves assisted at birth and risk factors Lewin, S., Godfrey, C. M., Macdonald, M. T., Langlois, E. V., Soares-Weiser, K.,
associated with passive immunity, health, and growth. Vet Rec Open, 6(1), Article Moriarty, J., Clifford, T., Tuncalp, O., & Straus, S. E. (2018). PRISMA Extension for
e000364. https://doi.org/10.1136/vetreco-2019-000364 Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med, 169(7),
Peek, S. F., & Divers, T. J. (2018). Rebhun’s Diseases of Dairy Cattle (3rd edition). Elsevier. 467–473. https://doi.org/10.7326/M18-0850
https://doi.org/10.1016/B978-0-323-39055-2.01001-9 Tsunemitsu, H., & Saif, L. J. (1995). Antigenic and biological comparisons of bovine
Ralston, B. J., Cockwill, C. L., Guselle, N. J., Van Herk, F. H., McAllister, T. A., & coronaviruses derived from neonatal calf diarrhea and winter dysentery of adult
Olson, M. E. (2003). Prevalence of Giardia and Cryptosporidium andersoni and their cattle. Arch Virol, 140(7), 1303–1311. https://doi.org/10.1007/BF01322757
effects on performance in feedlot beef cattle. Canadian Journal of Animal Science, 83 Tyler, J. W., Hancock, D. D., Thorne, J. G., Gay, C. C., & Gay, J. M. (1999). Partitioning
(1), 153–159. https://doi.org/Doi 10.4141/A01-001. the mortality risk associated with inadequate passive transfer of colostral
Rocha, T. G., Silva, F. D., Gregori, F., Alfieri, A. A., Buzinaro, M. D., & Fagliari, J. J. immunoglobulins in dairy calves. J Vet Intern Med, 13(4), 335–337. https://doi.org/
(2017). Longitudinal study of bovine rotavirus group A in newborn calves from 10.1892/0891-6640(1999)013<0335:ptmraw>2.3.co;2
vaccinated and unvaccinated dairy herds. Trop Anim Health Prod, 49(4), 783–790. Uehlinger, F. D., O’Handley, R. M., Greenwood, S. J., Guselle, N. J., Gabor, L. J., Van
https://doi.org/10.1007/s11250-017-1263-2. Epub 2017 Mar 20. Velsen, C. M., Steuart, R. F., & Barkema, H. W. (2007). Efficacy of vaccination in
Smith, B. P., Dilling, G. W., Da Roden, L., & Stocker, B. A. (1993). Vaccination of calves preventing giardiasis in calves. Vet Parasitol, 146(1-2), 182–188. https://doi.org/
with orally administered aromatic-dependent Salmonella dublin. Am J Vet Res, 54 10.1016/j.vetpar.2007.01.013. Epub 2007 Mar 12.
(8), 1249–1255. USDA APHIS Veterinary Services. (2010). Mortality of Calves and Cattle on U.S. Beef Cow-
Smith, G. (2015). Antimicrobial decision making for enteric diseases of cattle. Vet Clin calf Operations.
North Am Food Anim Pract, 31(1), 47–60. https://doi.org/10.1016/j. Waltner-Toews, D., Martin, S. W., Meek, A. H., McMillan, I., & Crouch, C. F. (1985).
cvfa.2014.11.004. v. A field trial to evaluate the efficacy of a combined rotavirus-coronavirus/Escherichia
Smith, G. W., & Berchtold, J. (2014). Fluid therapy in calves. Vet Clin North Am Food coli vaccine in dairy cattle. Can J Comp Med, 49(1), 1–9.
Anim Pract, 30(2), 409–427. https://doi.org/10.1016/j.cvfa.2014.04.002. vi. Welter, M. W. (1998). Adaptation and serial passage of bovine coronavirus in an
Snodgrass, D. R. (1986). Evaluation of a combined rotavirus and enterotoxigenic established diploid swine testicular cell line and subsequent development of a
Escherichia coli vaccine in cattle. Vet Rec, 119(2), 39–42. https://doi.org/10.1136/ modified live vaccine. Adv Exp Med Biol, 440, 707–711. https://doi.org/10.1007/
vr.119.2.39 978-1-4615-5331-1_91

12