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Veterinary Parasitology
journal homepage: www.elsevier.com/locate/vetpar
a r t i c l e
i n f o
Keywords:
Anthelmintic resistance
Gastrointestinal nematodes
Cattle
Cows
Bovine
Drug
a b s t r a c t
The rst documented case of macrocyclic lactone resistance in gastrointestinal (GI) nematodes of cattle was seen in the US approximately 10 years ago. Since that time the increase
incidence of anthelmintic resistance has continued at an alarming rate. Currently parasites
of the genera Cooperia and/or Haemonchus resistant to generic or brand-name macrocyclic
lactones have be demonstrated in more than half of all operations examined. Both of these
parasite genera are capable of causing economic losses by decreasing food intake and subsequently animal productivity. Currently, there are no easy and quick means to detect
anthelmintic resistant GI nematodes. Denitive identication requires killing of cattle. The
most commonly used eld detection method is the fecal egg count reduction test (FECRT).
This method can be adapted for use as a screening agent for Veterinarians and producers to
identify less than desired clearance of the parasites after anthelmintic treatment. Further
studies can then dene the reasons for persistence of the egg counts. The appearance of
anthelmintic resistance is largely due to the development of very effective nematode control programs that have signicantly improved the productivity of the US cattle industry,
but at the same time has placed a high level of selective pressure on the parasite genome.
The challenges ahead include the development of programs that control the anthelmintic
resistant nematodes but at the same time result in more sustainable parasite control. The
goal is to maintain high levels of productivity but to exert less selective pressures on the
parasites. One of the most effective means to slow the development of drug resistance is
through the simultaneous use of multiple classes of anthelmintics, each of which has a different mode of action. Reduction of the selective pressure on the parasites can be attained
through a more targeted approach to drug treatments where the producers needs are met
by selective treatment of different classes of animals and not by blanket treatment at a
location. The implementation of such programs will vary by the sector of the industry and
the individual site. In general, the feedlot will be the easiest sector for developing of programs, while stocker/backgrounder operations will provide the most challenging problems.
A major question that must be addressed is whether it is important that parasite control
programs to be sustainable over time, or if the pharmaceutical industry develop new control
agents at a rate sufcient to render sustainability unimportant.
2014 Published by Elsevier B.V.
such resistance demonstrated in parasites infecting cattle. The rst documented case of such resistance in GI
nematodes of cattle in the US was seen approximately
10 years ago in an intensively grazed stocker operation
(Gasbarre et al., 2009a, 2009b). In that study less than
desired reductions in both fecal egg counts and worm
numbers after anthelmintic treatment were seen mainly
against the macrocyclic lactones, and the predominate surviving parasite was Cooperia punctata. In addition, a small
number of Haemonchus placei remained after treatment
with macrocyclic lactones, and Haemonchus contortus resistant to both the macrocyclic lactones and benzimidizoles
were also isolated. The cattle in this study were initially
acquired from the southeastern US and then shipped to
a stocker operation in the north central US. Soon after
this report was published, a second report demonstrated
that adult Cooperia sp were not reduced in number after
treatment with ivermectin (Edmonds et al., 2010). In addition, necropsy of treated animals indicated that treatment
with ivermectin was ineffective in reducing the number of developing or arrested Ostertagia ostertagi. Cattle
from this study were obtained from pastures in northern California prior to shipment to a dry lot operation.
These two denitive studies indicated that macrocyclic
lactones were not effectively removing members of the
genus Cooperia at levels consistent with label claims. In
both studies, necropsy of the cattle were done at 14 days
post anthelmintic treatment to demonstrate the continued
presence of the parasites. Additionally, the results showed
that such anthelmintic resistance was demonstrable in
widely separated geographical regions of the US, i.e. the
Southeast and Northwest.
In a preliminary attempt to assess the magnitude of the
problem posed by the potential selection for GI nematodes
resistant to the most commonly used agents for control
of nematode parasites in the US, a study was initiated as a
part of the United States Department of Agriculture, Animal
and Plant Health inspection Services periodic survey of the
American cow-calf industry (USDA, 2010). These surveys
are performed at irregular intervals to assess health issues
of the industry. For this survey, producers in 24 States
covering about 88% of US cattle in cow-calf operations
were given the opportunity to participate (Ballweber et al.
submitted for publication). Producers were asked to follow
their usual management protocols with the exception of
collecting 20 random samples at the time of their next
scheduled anthelmintic treatment. Samples were taken
from the rectum or taken from an observed defecation. The
producers were asked to take a second sample 14 days after
the anthelmintic treatment, Samples were again to be random from the rectum or an observed defecation. Animals
sampled were from 6 to 18 months of age, pastured for at
least 4 weeks, and not treated with any anthelmintic for at
least 45 days (Stromberg et al. submitted for publication).
A total of 61 producers from 17 States submitted samples that met all the study criteria. The results of the
fecal egg count reduction test (FECRT) showed that more
than one-third of all participating operations did not reach
the recommended reduction of at least 90% (Coles et al.,
1992, 2006). All operations with less than a 90% reduction
in the FECRT had used either an injectable or a pour-on
data set calves from the same cow/calf operation in Maryland were sampled for 3 consecutive days at the same time
of year over a 4 year span. This resulted in just under 4000
samples. All samples were processed and read by the same
two individuals. Analysis of these data showed that both
the year of sampling and the day of sampling were very
minor components of the total variance. In other words,
the grand mean of the 3 days each year, and the mean
on each of the 3 days were very close. In contrast the
two largest sources of variation were between the different calves and between samples taken on consecutive days
from the same calf respectively. In fact these two variables
accounted for 8085% of the total variance over the 4 year
period. From this we concluded that fecal egg counts are a
reliable measure of the group, but without repeated sampling, are less reliable when assessing an individual animal
(Gasbarre et al., submitted for publication).
Based on these analyses, the FECRT was used as a
measure of change in a group and not to measure the
change within an individual animal. Based on the previous estimate that the minimum number required was 17,
collection of feces from 20 different individuals, should
provide an accurate measure of the change in the group
mean 14 days after drug treatment. While sampling of the
same animals each time might further reduce variance, this
likely would have reduced the total number of participating operations and thus reduce substantially our ability
to make broader implications from the nal data set. This
number is in agreement with a recent paper by Levecke
et al. (2012).
Other factors that need to be considered in dening a
sampling protocol are time between treatment and sampling, the counting technique to use, and whether there
should there be a threshold egg count value for inclusion
in the study. In terms of time between treatment and second sampling, experience a freshly isolated eld stain of
C. punctata indicates that these parasites have a shorter
prepatent period than expected (Stromberg et al., 2012).
The time interval between treatment and follow-up sample should ensure that the drug is given sufcient time to
act, but that also ensure that there is insufcient time for
reinfection and subsequent parasite patency. Ten to 14 days
seems to be optimal. Regarding the counting methodology,
it appears that a modied Wisconsin otation method is
the best suited procedure (Cox and Todd, 1962; Bliss and
Kvasnicka, 1997). As practiced in most laboratories, this
methodology had a sensitivity of from 0.5 to 3 eggs per
gram of feces. In contrast the minimal detectable limit of
the McMaster technique is 25, 50 or 100 eggs per gram of
feces depending upon the exact methodology used. Cattle fecal egg counts are much lower than those of small
ruminants for which the McMaster technique was developed. The use of this methodology on cattle samples that
are expected to have means less than 100 eggs per gram
of feces is likely inappropriate. Finally, the WAAVP guidelines which suggest the McMaster technique, also indicate
that fecal egg counts cannot be used on samples where the
egg counts are less than 150 eggs per gram (Coles et al.,
2006). Data analyses performed on data derived from the
NAHMS study indicated that the using the greater sensitivity of the modied Wisconsin technique the effect of
Table 1
Characteristics of cattle production systems in the US and the danger of developing anthelmintic resistance and management of refugia.
Production type
Operation type
Parasite impact
Production needs
Target for
control
Probability of
selection for AR
Ability to
manage refugia
Dairy
Conventional
Low
High
Low
Easy
Grazing
Moderate
Moderate to high
Replacement
heifers
Replacement
heifers
Milking cows
Low to
moderate
Moderate
Cow-calf
Moderate to high
Moderate to high
Difcult
Stocker
Feedlot
Very high
High
Very high
Maximal
Moderate to
high
Very high
Very low
Beef
Calves
Yearlings
All
All
Very difcult
Not an issue
All animals should be treated on arrival. Also the operators must assume that the animals coming into the facility
from such a wide variety of sources are harboring resistant parasites. As such, this is the ideal location for the use
of anthelmintic combinations on all animals. Once treated
at the therapeutic dosage on arrival most parasite issues
should be over. Occasionally outbreaks of Oesophagostomum radiatium are seen in feedlots during the winter
(Gasbarre, unpublished observation). This is likely the
result of parasites that survived treatments on arrival at the
feedlot, with subsequent egg shedding of a parasite that can
be a skin-penetrator if given sufcient exposure time. This
problem is seen in the form of condemned intestinal tracts
at the slaughter plant. Usually by the time such outbreaks
are detected by the identication of colonic nodules at the
slaughter facility it is too late for meaningful action, and
the problem usually resolves within a short time period.
7. Beef cow-calf
Based upon the NAHMS survey, there is a very signicant level of macrocyclic lactone resistance in major
cow-calf areas of the US. In spite of this, there are ways to
maintain a refugia in most operations and the high levels of
resistance are likely a result of non-sustainable control programs. In most cases, maximal growth of the pre-weaned
calves is not absolutely necessary, and unweaned calves
can maintain what for cattle are relatively high egg counts
without serious weight loss. Additionally, this early exposure to parasites is important for the generation of immune
responses that will protect the animals throughout life. In
most cases it is not necessary to treat the unweaned calves
until the time of weaning. Treatment at this time will be
important both for animals being marketed and for the
replacement stock. Similarly, the dams do not need to be
parasite free as milk production will not usually be signicantly impacted by low parasite numbers. As a result, it is
very possible to attain adequate levels of parasite control
without placing undue selective pressure on the parasite
genome. Generally, a treatment of the cows about one
month into the grazing season will lower parasite numbers to a manageable level. At weaning the calves should
be treated with an anthelmintic for the rst time. The producer may want to treat the cows a second time at the
end of the grazing season to remove an additional nutritional stress prior to a period of a lower nutritional plane
especially in the case of a Northern, spring calving operation. In years with very high moisture or in areas with a
prolonged grazing season (i.e. more than 6 months) additional treatments may be necessary. In almost all cases,
very aggressive suppressive anthelmintic programs such
a multiple early season treatments or slow-release formulations are unnecessary and can have the negative effect
of increased selection for anthelmintic resistance in cowcalf operations. If used on the calves they may impede the
development of immune responses in the calves, and the
economic gain of treatment in the cows would be highly
variable. In general the focus should be on keeping a low
level of parasite transmission on the pastures with treatments aimed at aiding animals through periods of stress.
In operations where the presence of anthelmintic resistant
10
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