RESEARCH WORK

Anthelmintic resistance in sheep: a review of reports of southeastern Mexico and alternatives for the control of gastrointestinal nematodes

P. Medina¹, F. Guevara²*, M. La O³, N. Ojeda⁴ and E. Reyes⁵

¹Master of Science Student in Tropical Agricultural Production, Universidad Autónoma de Chiapas, Boulevard Belisario Domínguez, kilómetro 1081, Terán, Tuxtla Gutiérrez, Chiapas, México, C.P. 29050
² Facultad de Ciencias Agronómicas, Universidad Autónoma de Chiapas, México
³Instituto de Investigaciones Agropecuarias Jorge Dimitrov, Granma, Cuba
⁴División Académica de Ciencias Agropecuarias, Universidad Juárez Autónoma de Tabasco
⁵Facultad de Medicina, Veterinaria y Zootecnia. Universidad Autónoma de Chiapas, México
E-mail: francisco.guevara@unach.com

ABSTRACT

One of the main limitations in ruminant production is parasitic diseases, because they can cause a high mortality rate. Recently, in southeastern Mexico, farmers, technicians and veterinarians have observed that anthelmintic drugs have lost their efficacy and this has caused a phenomenon known as anthelmintic resistance, in which parasites acquire the capacity to tolerate the treatments that should normally kill them. As a response to this phenomenon alternative parasite control strategies have been designed, in order to decrease the use of drugs and preserve the efficacy of such compounds. This work constitutes a review of the current status of anthelmintic resistance in southeastern Mexico, as well as of the alternative parasite control strategies used in sheep.

Key words: Alternative control, parasites, ruminants.

The sheep exploited under grazing conditions maintains a direct relation to the environment, which brings about the emergence of parasite diseases caused by gastrointestinal nematodes (GINs). These diseases constitute the main cause of economic losses in Latin America and other livestock production regions of the tropics and subtropics in the world (Miller et al., 2012).

At present, anthelmintic drugs are the main control method of parasites in ruminants, and in the market there are several families of antiparasitics with different action mechanisms (Coles et al., 2006). This control strategy has been effective during several years; however, the decrease of the efficacy of these treatments has been remarkable worldwide, due to the administration frequency, underdosage, erroneous choice of drug, or fast re-infestation, which has generated a phenomenon known as anthelmintic resistance (AR).

Due to the AR, alternative control strategies of GINs have been adopted, many of which have been evaluated and have decreased the use and dependence on drugs, allowing to delay or prevent resistance. The objective of this work was to review the current status of anthelmintic resistance in sheep production areas of southeastern Mexico, as well as of the main strategies used for alternative control.

Parasite diseases and their impact on sheep production

Among domestic ruminants, sheep is the most susceptible species to parasite diseases. GINs are the most frequent parasites –with highly pathogenic genera‒, due to their hematophagy and histiophagy, as well as to the survival mechanisms they have to evade the defense response of their hosts. The degree of the pathophysiological alterations caused depends on the infection, immunity, age, genera involved and the environment; which bring about disorders in feed intake, as well as deficient digestion, absorption and secretion of metabolites (Lippi et al., 2013).

Because of this, the nematode infestation of sheep is one of the most frequent causes of the biological and economic inefficiency of production systems (Nari, 2011). The impact of nematode infestation is shown in the high economic losses, due to the reduction of the weight gain (up to 50 %), the mortality (20-50 %) (Luna et al., 2010), as well as to the expenses because of the intervention of the veterinary doctor and the treatments used for its control (López and Mendoza, 2011).

Conventional control

Since the appearance of broad-spectrum deworming drugs more than 40 years ago many farmers and veterinarians have learned that the correct way to control GINs in sheep flocks is the regular deworming of all the animals (Molento et al., 2011). Total dependence on only one control method has proven to be little sustainable and efficient at long term. In spite of the search for diverse control strategies of the nematodes that cause parasite diseases conducted by scientists and farmers, for many years, deworming with drugs has been proposed as the only effective parasite control method (Coles et al., 2006).

The available anthelmintics nowadays are grouped according to their chemical nature and their effects on parasites. In this sense, benzimidazoles, imidazotiazoles and macrocyclical lactones are the most used for the treatment of nematode infestation, because they are considered broad-spectrum antiparasitics. Most of these compounds are highly effective; but they must be adequately used and chosen based on technical criteria, in order to obtain favorable clinical responses. Some factors, such as the chemical nature of the compound, the pharmacokinetic properties, the characteristics of the animals, the biological characteristics of the parasites and the inadequate use, limit and decrease the effect of drugs; in addition to originate parasite populations resistant to these active principles.

Anthelmintic resistance

AR is a cosmopolitan phenomenon that gradually decreases the anthelmintic effect on the parasites of all the species, including man (Jabbar et al., 2006). In addition, it is an inheritable capacity of parasites to survive treatments which, in therapeutic dosages normally cause the inhibition of growth or the death of the individuals of a normal or susceptible population (Martínez, 2010). The first case of GINs resistant to anthelmintics was reported in 1977, in the United States (Drudge et al., 1977). On the other hand, in Mexico, Campos et al. (1990) reported the first case of AR, in which they identified a GIN strain resistant to albendazole. Likewise, resistant parasites are a reality in many flocks of southeastern Mexico, Latin America and the world (Torres et al., 2011; Torres et al., 2012). At present, a multi-resistance phenomenon is expanding, which consists in the fact that all the antiparasitic families available in the market have lost efficacy on several GIN genera (table 1).

If AR continues to increase, in a few years the viability of sheep production systems can be compromised. Because of this concern, it has been considered convenient to decrease the dependence on drugs and to maintain a portion of the parasite population without exposure to treatments, through the implementation of alternative control strategies and selective deworming (Torres et al., 2012).

Alternatives of gastrointestinal nematode control in sheep

There are diverse alternatives for GIN control, with different advance and efficacy degrees; in general, they have focused on decreasing the use of anthelmintic drugs, as well as on the consequences of the delay in the appearance or increase of anthelmintic resistance. The main alternatives of nematode control in sheep are the following: grazing management, immunization with larvae and vaccines, biological control, phytotherapy, copper needles, and selective deworming.

Grazing management

In grasslands the external or exogenous stage of the biological cycle of GINs occurs until producing the infective larva (L3), which is ingested along with the pasture when the animals are fed. Paddock rotation provides the resting period of the grassland after being grazed, with which the pasture is recovered and grows to be subject again to grazing. In addition to the grassland rest, the prolonged environmental exposure and desiccation caused by solar radiation decrease the viability and number of L3 that the animal would normally consume along with the forage. Vásquez et al. (2006), when comparing a continuous grazing system with a rotational one (4 days of occupation and 28 days of resting), found that the animals under continuous grazing had a lower elimination of GIN eggs per gram of feces and that there was no difference in the weight gain. Nevertheless, the animals under rotational grazing conditions showed a better hematocrit, a higher body condition and a better coloration of the palpebral mucosa.

Immunization with larvae and vaccines

Immunization has been used as alternative method of GIN control. In this sense, Rodríguez et al. (2011) inoculated 3 700 larvae L3 of H. contortus in lambs, which reduced the number of eggs per gram of feces (EPG); however, this immunization did not improve the weight gain in grazing sheep.

Regarding vaccines, the most important advances have been the discovery and characterization of the antigens that confer immunity. Antigen H-11 has been used for the production of vaccines against H. contortus, and it is already possible to develop this vaccine commercially (Martínez, 2011). However, the production of antigens for sheep vaccination is a relatively new strategy and there are not sufficient studies to prove its effectiveness, for which it is necessary to conduct research on this topic. Likewise, vaccines against the other genera of parasite nematodes in sheep are still to be discovered.

Biological control

In nature there is a large diversity of organisms antagonistic to parasites which have had a beneficial impact as biological controls in the case of sheep. Aguilar (2012) states that the main natural enemies of GINs include bacteria, mites and fungi. This author evaluated the adhesion capacity of the spores of the bacteria Pausteria sp. to decrease the populations of H. contortus, and obtained adhesion percentages of 0-40 % in different biological stages. The predator ability of the mite Lasioseius penicilliger on infective larvae of H. contortus was also studied, and they were reduced in 79,5 %.

In an in vitro study in which the predator capacity of the nematophagous fungus Duddingtonia flagrans on Ostertagia circumcinta, H. contortus and Trichostrongylus colubriformis was evaluated, the larvae capture oscillated between 40 and 93 % (González, 2006). Likewise, Ojeda et al. (2008) observed that the predator capacity of D. flagrans on the larvae of gastrointestinal nematodes was shown in 37-92 % of their reduction. Undoubtedly, the results of these studies are encouraging and show that such alternative of GIN control in sheep has great potential.

Phytotherapy

Diverse plants which contain biochemical substances with anthelmintic effect have been used in parasite control. The main compounds of these plants are terpenes, alkaloids, saponins, anthraquinones, and tannins; they have been used by the indigenous communities of Latin America in traditional phytotherapy, as a millenarian practice, and are evaluated at present in diverse studies worldwide with an ethnobotanical concept (Alonso et al., 2010). In this sense, Hernández and López (2000) studied the anthelmintic effect of the extracts of the following medicinal plants: Artemisia ludoviciana, Dysphania ambrosioides, Cucurbita sp. seed, Carica papaya seed and Allium sativum, and found a variable antiparasitic action, with a moderate to low efficacy. Likewise, Martínez (2010) evaluated the effect of tannin-rich plants (Lysiloma latisiliquum, Onobrychis viciifolia and Chinopsis sp.), and his results suggest that the compounds of the foliage of those plants can intervene in vital functions of GINs such as motility, nutrition and, possibly, reproduction; but in both cases the anthelmintic effect is reduced if compared with that of commercial anthelmintic products.

Copper needles

Copper oxide, when administered orally in capsules, goes through the rumen and it is lodged in the abomasum folds, where it releases copper ions that exert an anthelmintic effect (Martínez, 2010). Aguilar et al. (2011) found that copper oxide needles reduce the rates of H. contortus between 75 and 90 %; but do not improve the weight gain of the animals. Likewise, Galindo et al. (2011) proved the positive effect of the application of copper oxide needles on the control of GINs in sheep, because they found a reduction of up to 73 % in adult parasites when performing the post-slaughter inspection of the abomasum. In spite of the positive anthelmintic effect of copper oxide, it has been proven that the accumulation of copper in the liver of treated animals constitutes a risk, for which the use of this alternative method has been limited (Aguilar et al., 2011).

Selective deworming

In a flock most of the animals have few parasites, while only a small number of them have high parasite rates. These few animals are the ones that generally show clinical parasitism signs, and are the only ones that should be dewormed. Torres et al. (2009), having knowledge of these phenomena, established selective deworming strategies in which the antiparasitic treatments are exclusively destined to the animals that really require them. Such strategies allow the increase of parasite populations susceptible to anthelmintics, as well as the decrease of the costs per treatment and a higher efficiency and sustainability in the control strategy. The selective deworming strategies used in sheep are shown in table 2.

The joint implementation of more than one selective deworming strategy (SDS) has been proposed in order to improve the deworming criterion and to obtain an integral strategy. Torres et al. (2011) proposed the joint utilization of the FAMACHA® technique and body condition; a FAMACHA® value of 4 or 5 and a body condition lower than 2 serve as criterion to decide from which animals a feces sample should be taken. These samples are analyzed in the laboratory and, from the determination of the number of eggs per gram of feces, deworming is confirmed or discarded. The animals with EPG higher than 750 will be dewormed, which reduces the number of animals to be treated.

The utilization of such a strategy in the Mexican tropic is based on the fact that the animals under production in grazing systems show anemia and low body condition. This is due not only to parasitism, but also to the insufficient quantity and quality of the diet, in addition to the constant reproductive activity. Thus, if the decision is made to deworm only according to FAMACHA® or to body condition, many dewormings would have to take place throughout the year, which would mean the application of unnecessary consecutive treatments. In sheep flocks of Yucatán this selective deworming strategy has allowed to decrease the use of drugs (Torres et al., 2009).

Anthelmintic resistance is an irreversible reality in many sheep flocks in southeastern Mexico, and even in some of these flocks multi-resistance has been diagnosed. Due to the nature of this phenomenon the success possibilities in the use of drugs to control the parasite diseases of ruminants have been reduced. Taking into consideration this problem, it is important to consider that there are alternative strategies available for parasite control, with which the dependence on drugs can be decreased. The implementation of such strategies and the joint usage of more than one of them have proven to be effective and allow to use more efficiently antiparasitic treatments, to not depend on the use of anthelmintics, to prevent the parasite-host contact, to increase the populations of susceptible parasites and to delay or avoid the presence of the anthelmintic resistance phenomenon.

Received: April 22, 2013
Accepted: January 13, 2014