PARASITISM

Even so, intensively grazed cattle on a commercial dairy farm may have stresses due to parasitism simply because animals are kept on the same land base, whereas in the wild, they would freely roam and keep moving to fresh grasses and land. Parasites, when exposed to a captive population, can potentially explode in numbers and cause disease, especially among naïve young stock that have yet to establish lasting immunity while rotating through the pasture system. It is interesting to note that ruminants grazing birdsfoot trefoil (Lotus corniculatus) have been shown to have lower fecal egg counts (FECs), and ruminants grazing chicory (Cichorium intybus) had fewer adult abomasal helminths than those grazing a ryegrass/white clover mix (Marley, 2003). Similarly, feeding of sulla (Hedysarum coronarium) was associated with higher antibody titers against the secretory-excretory antigens of Ostertagia circumcincta; it also resulted in lower numbers of the adult parasite when compared with feeding alfalfa (Medicago sativa) (Niezen, 2002). Additionally, sainfoin (Onobrychis viciifolia), a legume forage with polyphenols and condensed tannins, had significant effects in vitro on third-stage larvae and abomasal adult worms of Haemonchus contortus, Trichostrongylus colubriformis, and lungworm (Dictyocaulus viviparous) (Paolini, 2004; Molan, 2000).

Prevention of parasitism should be a major goal for producers who lack access to or cannot afford to constantly use parasiticides, and for farmers who manage their herds under a certified organic program whereby conventional wormers are severely restricted. It is generally recognized that strong reliance on chemical wormers can lead to resistance. Even with the use of alternatives to chemotherapy, such as plant-based parasiticides, parasite resistance can still emerge because of reliance on a single product. Such plant-based products should still be used strategically.

Effective parasite control requires a holistic, multipronged approach that takes into account factors such as nutrition, pasture management, shelter, and water quality, even before a parasiticide is selected. If animals are kept in proper nutritional balance (i.e., not lacking major nutrients such as energy or minerals) and are rotated through well-managed pastures (with previously deposited manure in an advanced state of decomposition), with access to shelter from bad weather and fresh water of high quality, it is unlikely that strong parasite pressures will be present. At the least, the animals’ immune systems will be able to cope with the parasite pressures in the best possible way. This situation contrasts with that of animals put onto ground with little to graze, drinking stagnant or slowly moving water in drainage ditches and having no shelter from the blazing sun or chilly rains. It is obvious that the latter conditions are poor and, even with chemical parasiticides, raising animals in this manner is unlikely to be productive or profitable. Efforts should be made to keep parasite infestation from occurring through good management of land and animals. Under such circumstances phytotherapies offer potential benefits in helping to protect animals from parasites.

Many studies conducted in the past decade have involved the use of plant extracts against various nematode infections. Some in vitro studies have used crude extracts or isolated compounds; in vivo studies have sometimes performed statistical comparisons between phytotherapy and conventional anthelmintics. Many studies are being conducted in tropical or developing countries by European, South American, African, or Indian researchers. In many cases, results are being published in well-known peer-reviewed journals; in other cases, lesser known scientific journals are documenting the findings. Few studies have been conducted in the United States, perhaps because of the lack of a tropical environment and because of the strong relationship between pharmaceutical firms and agribusiness.

The vast majority of investigations have studied phytotherapy-based parasiticides in sheep (or goats), probably because of their economic importance in developing parts of the world, and also because they are less expensive to maintain. Many, but certainly not all, of the parasite species that infect one type of ruminant also affect other ruminants. Thus, extrapolation, if needed, is justifiable. Results of studies must be considered with regard to whether the animals were naturally infected or were experimentally or artificially infected, and whether the researchers used crude extracts as made by traditional methods or isolated active ingredients. It is reasonable to consider that animals that are naturally infected may have adaptive capabilities that may somehow act synergistically with treatment; however, experimentally infecting an animal may jolt the system to a point at which adaptive mechanisms are absent (or not yet equilibrated), and thus certain treatments are hindered. Many studies have investigated phytotherapy targeted to H. contortus in sheep; the findings of these studies should be valuable for cattle as well, because these two animal species are both affected by Haemonchus species.

Summaries of in vivo research follow. It was shown that albendazole provided 100% fecal egg count reduction by day 4 posttreatment in an experimentally induced mixed infection (60% Haemonchus spp) in sheep; however, a botanical preparation of pyrethrum showed significant reductions by day 8 of treatment (Mbaria, 1998). Very favorable results were presented in two other studies that compared botanical products with albendazole in the treatment of patients with naturally occurring mixed nematode infection. With the use of 1600 mg/kg Nauclea latifolia stem bark extract orally for 5 consecutive days, Onyeyili and colleagues found significantly reduced fecal egg counts in sheep (93.8%). This reduction was equivalent to that attained with 5 mg/kg albendazole (94.1%). Gathuma and associates showed that Myrsine afriacana, Albizia anthelmintica, and Hilderbrantia sepalosa yielded 77%, 89.8%, and 90% efficacy, respectively, versus albendazole (100% efficacy) in sheep that were harboring mixed natural helminthosis. It is interesting to note that improved packed cell volume (Gathuma, 2004) and improved hemoglobin and leukocytosis (Onyeyili, 2001) were observed with phytotherapy. When examining Moniezia species, Gathuma found that herbal remedies were 100% efficacious versus 63% efficacy for albendazole. However, Githoria (2002, 2004) reported nine plants (including M. africana) that were not effective against sheep experimentally infected with H. contortus. In a study in which Tinospora rumphii was used to treat goats experimentally infected with H. contortus, the effective dose (ED₅₀) and lethal dose (LD₅₀) were identified, and 4.5 grams of a concentrated extract was found to be as effective as the commercial dewormer (mebendazole) (Fernandez, 2004).

In another study of five plant products tested against Trichostrongylus in artificially infected lambs, 183 mg/kg of an ethanol extract of Fumaria parviflora yielded a 100% reduction in fecal egg count, as well as 78% and 88% reductions in adult H. contortus and T. colubriformis; thus, according to the authors, it was as effective as pyrantel tartrate (Hordegen, 2003). Researchers in Egypt used a commercial compound (Mirazid®) that contained an oleoresin solution of Commiphora molmol as its active ingredient; they found that doses of 600 mg and 1200 mg cured 83% and 100%, respectively, of sheep with natural fascioliasis infection (Haridy, 2003); another group found that natural infection of sheep and goats with Dicrocoeliasis dendriticum was also cured by Mirazid containing C. molmol when the liquid equivalent of 2 capsules was given orally once daily for 4 consecutive days (Massaud, 2003).

After 6 weeks of experimental infection with Schistosoma mansoni, mice were given 200 mg/kg body weight of praziquantel daily or 200 mg/kg body weight of Balantines aegyptiaca fruits daily for 10 weeks; each treatment resulted in significant reduction of egg count per gram and egg burden in tissues, as well as recovery of adult worms from S. mansoni infection obtained from mice (Koko, 2004).

When the in vitro effects of plant materials against H. contortus were measured, it was shown that an essential oil and eugenol, both extracted from Ocimum gratissimum, caused maximal inhibition at 0.50% concentration in the egg hatch test from goat feces (Pessoa, 2002). The same laboratory found that ethyl acetate of Spigelia anthelmia used at 50 mg/mL inhibited 100% of egg hatching and 81% of larval development of H. contortus, and the methanolic extract inhibited 97% of egg hatching and 84% of larval development (Assis, 2003). As was mentioned previously, pasture plants such as birdsfoot trefoil and chicory contain tannins and possess anthelmintic attributes. Similarly, some woody plants known to contain tannins have been studied. Via the tannin inhibitor polyethylene glycol, it was shown that tannins, at least in part, are responsible for some anthelmintic effects observed within livestock (Paolini, 2004).

Protozoal parasites can cause disease, especially in neonatal young stock. Although garlic was shown to be helpful against cryptosporidiosis in a clinical trial of patients with acquired immunodeficiency syndrome (AIDS; Anonymous, 1996), a study of Holstein calves that were administered an allicin-based product (an active ingredient isolated from garlic) showed no effect on the duration of diarrhea, although with high doses, onset of diarrhea was delayed (Olson, 1998). However, other protozoal parasite infections do seem to be amenable to plant-based products, such as those derived from Bertholletia excelsa (Campos, 2004), Ranunculus sceleratus, Coptis chinensis (Schinella, 2002), and Zanthoxylum liebmannianun (Arrieta, 2001). An in vivo murine study demonstrated that 50% alcoholic extracts of Xanthium strumarium leaves, Parthenium hysterophorus flower, and Nycanthes arbortristis leaves at dosages of 100 and 300 mg/kg body weight were effectively trypanocidal (Dwivedi, 2004).

Overall, mixed results were obtained in studies that used phytotherapy for internal parasitism; however, these studies do not state how the animals were managed in terms of previous nutrition or pressure of exposure to nematodes. Sole reliance on therapeutic treatment (of whichever type) for parasitism is not good livestock management. It must be emphasized again that proper feed, water, and shelter contribute significantly to an animal’s ability to emerge from an internal parasite problem. Given that phytotherapies thus far show more variable effects compared to known efficacy of anthelmintics, therapy that uses plant-based products will work best if management steps are also taken to improve pasture plant species, hasten manure decomposition, and provide proper nutrition, water, and shelter.

MASTITIS

A dairy cow’s main role in life is to provide milk. Ideally, milk should have a low somatic cell count (SCC), the number of leukocytes per milliliter of milk). It is all too common for a cow or a number of cows to show increases in SCC. This is likely—but not always—due to pathogenic bacteria entering the teat canal. The usual ways in which bacteria gain entry into the mammary gland involve the environment (hot and humid weather), bad bedding, poor milking hygiene and milking technique, milking machine malfunction, and individual differences between immune systems in response to various other common stresses. When SCCs reach a particular point, visible abnormalities of the milk occur. This is called clinical mastitis; when abnormalities are confined solely to elevated SCC, these instances are considered subclinical mastitis. Bacteria associated with mastitis (or diagnosed as the etiologic agent) dictate which treatment measures should be taken. Environmental factors and milking machine problems must be corrected (if present) before medication is given because medications cannot effectively overcome major problems that are present in the environment.

Typically, mainstream dairy farmers infuse an antibiotic into a quarter that is exhibiting mastitis. This is often done empirically at the time of observed irregularities during milking. However, once the antibiotic does not seem to be effective, culture and sensitivity testing and selection of specific antibiotic treatment takes place. On organic farms that cannot use any antibiotics (otherwise the animal must be removed from the herd), alternative techniques are used to counter chronically elevated SCC or actual cases of mastitis. One rational technique is to stimulate the immune system of the animal, on the assumption that the immune system is integral to resolving infection in the mammary gland. Local irrigation of the gland via infusion of a medicinal substance makes sense as well. In addition, veterinarians working with organic cows can culture milk samples to identify the organism presumed to be the causative agent; this reveals proper management steps for stopping the spread or correcting other factors. Keeping a record of which bacteria are positively identified and recording the therapies used (any kind) helps to build data that do or do not support certain clinical therapies for a given animal or herd.

A common biologic (via extralabel usage) used to stimulate the immune system (and therefore lower SCC) is a US Department of Agriculture (USDA)-licensed product (Immunoboost®). It is derived from fractionation of the cell wall of a Mycobacterium species. When it is administered to an animal, the nonspecific branch of the immune system is enhanced by increased production of interferon-γ. It is often of clinical benefit in lowering the SCC of cows for a couple of months when they are subclinically infected by various Streptococcus species and coagulase-negative Staphylococcus species. One strain of Staphylococcus, S. aureus, produces a contagious type of mastitis that may cause large economic losses to the farmer because of poor milk quality and lost milk production by infected quarters. Cows are often culled, or they may be treated with relevant antibiotics at dry-off (when udder involution occurs), in the hope that the animal will clear the walled-off S. aureus microabscesses. Obviously, this is not an option for cows living on organic farms, where such antibiotic use (even in the dry period) necessitates that the animal be culled. It should be noted that in vitro sensitivity analysis of S. aureus usually indicates that any antibiotic will successfully kill that pathogen; invariably, however, the effectiveness of such antibiotics against S. aureus in vivo is universally disappointing.

In an in vivo experiment that used the extract from Panax ginseng (8 mg/kg body weight daily for 6 days) to treat cows infected with S. aureus, their innate immunity was activated, reducing S. aureus infection in quarters and lowering SCC (Hu, 2001). It is well known that the defense of the mammary gland against mastitis-causing pathogens is mediated primarily by cell-mediated immunity. One experiment (using Echinacea purpura and Thuja occidentalis) was carried out to see whether pharmacologic compounds from these phytopreparations have effects on bovine immune cells; it was found that flow cytometric characterization of neutrophil viability and shape changes constitute a reliable approach for quality testing of immunomodulating phytomedicines (Schuberth, 2002). In the ginseng experiment, it was demonstrated that neutrophil phagocytosis and oxidative burst, as well as the number of monocytes and lymphocytes, were significantly greater in the ginseng-treated cows than in saline controls (Hu, 2001). In another in vivo study in which 0.77 kg of dried Persicaria senegalense leaf powder was fed for 5 days, apparent cure of mastitis was better than with antibiotic treatment. The intramammary antibiotic was used for 3 consecutive days and consisted of 300,000 IU procaine penicillin G, 100 mg dihydrostreptomycin sulphate, 100 mg neomycin sulphate and 10,000 IU vitamin A propionate (Abaineh, 2001).

In a different in vivo study, an herbal gel containing Cedrus deodara, Curcuma longa, Glycyrrhiza glabra, and Eucalyptus globulus showed high levels of efficacy in the treatment of subclinical mastitis (Saxena, 1995). Promising results in a field study against mastitis were attained with a decoction of concentrated liquid Herba taraxici (dandelion leaf, Taraxacum officinale), Flos lonicera (honeysuckle flowers, species unspecified), Radix isatidis (Isatis root, species unspecified), Radix scutellariae (skullcap root, species unspecified), and Radix angelica sinensis (Angelica sinensis, or Chinese angelica root) (Hu, 1995). Another commercially available product (Masfrigao®, Vet Hon, China) contains Herba violae (violet leaf, species unspecified), Flos lonicera (honeysuckle flowers, species unspecified), Radix angelica sinensis (Angelica sinensis, or Chinese angelica root), Radix angelicae dahuricae (Angelica dahurica root), and Flos fraxini (flowers of the Korean ash tree) in Oleum brassica campestris (Brassica campestris, or field mustard oil). It is infused in the quarter every 12 hours for 4 doses. This product is convenient because it is dispensed in standard mastitis tubes, and farmers like the results they see, especially if it is used with a colostrum-whey product (Biocel CBT®, Agri-Dynamics, Pennsylvania, USA) that is injected subcutaneously.

Mastitis requires a two-prong approach if antibiotics are not used. Stimulation of the immune system in general and local infusion of affected quarters are both warranted. The in vivo studies cited earlier suggest that phytotherapy can be a useful tool in the treatment of subclinical and clinical mastitis. Phytotherapy for mastitis can be administered orally, subcutaneously, topically, or as intramammary infusion—route of administration selected hinges on product availability or farmer preference.

Because milk quality is of utmost importance, the use of phytotherapy, especially in relation to mastitis treatment, must be tempered by consideration of commercial end use. In other words, could residues be involved with the use of herbs? Because it is well recognized that phytotherapy most likely involves pharmacologically active substances, the answer needs to be, yes—but what types of residue are of concern, and what levels would be acceptable from a public health standpoint? Therefore, anytime that phytotherapy is used for mastitis, especially when it is infused directly into the mammary gland, milk from the treated quarter should not be co-mingled with other milk. In general, bad milk should never be put into the bulk tank; co-mingling of milk should not occur until the milk visually looks normal and is negative on a California Mastitis Test (CMT). Specifically, in relation to residues such as growth inhibitors (e.g., antibiotics) that affect cheese production, it is always wise to test the milk of cows treated by phytotherapy for antibiotic activity before milk is added to the bulk tank.

Various milk testing devices (Delvo®, Snap®, Charm II®) have been designed to detect the presence of antibiotics or growth inhibitors; each detects a specific panel of typical antibiotics that are commonly used. These devices should be used as needed. Information regarding potential toxic residues of public health concern is difficult to find. The US Food and Drug Administration (FDA) Food Animal Residue Avoidance Database (FARAD) is the best source of information concerning this in the United States. Yet only veterinarians and regulatory professionals can access FARAD. In Europe, the European Agency for the Evaluation of Medicinal Products (EMEA) would be a good starting point for such information because it delineates various plant concentrations and provides a strong section on the toxicology of each product. In the Summary Report of Substances, the EMEA includes sections on botanical name, parts used, known constituents, intended use, known toxicities, LD₅₀ (especially genotoxicity or teratogenicity), margin of safety regarding concentration to be used as intended, and a formal conclusion and recommendation. The public Web site can be accessed at www.emea.eu.int/htms/vet/mrls/a-zmrl.htm. Substances that are generally recognized as safe (GRAS) by the FDA are of interest when questions arise regarding the safety of listed herbs. This list can be found in the US 21CFR182.1–21CFR182.50. It can be accessed on the Internet at www.cfsan.fda.gov/~lrd/FCF182.htm. Through the study of information regarding known potential toxicities, cross-referencing between FARAD and EMEA, and the use of cow side antibiotic/growth inhibitor assays, the use of phytotherapy for cows with elevated SCC or mastitis can be accomplished safely and with confidence.