Cooperia oncophora

C. oncophora females are about 6–8 mm long, males about 5.5–9 mm. They are light red in color and have a coiled shape. Male worms have a large bursa as shown in Figure 2a. The spicules are 240-300 μm long and have a rounded end and a longitudinal line pattern. L3 stage larvae are hard to differentiate between different species, because they are very similar interspecies-wise. Eggs of C. oncophora however can be easily identified by their parallel walls. == Life cycle ==

The life cycle of C. oncophora is direct. Free-living L3 stage larvae residing on the pasture are taken up by grazing cattle and pass to the small intestine. Here, they molt to L4 larvae and then to adults. Eggs are passed in the faeces to the pasture. The larvae hatch and grow to L3 stage larvae. Infective L3 stage larvae are then again taken up by grazing cattle and the life cycle repeats. The pre-patent period, which includes the time between infection and egg laying, lasts between two and three weeks. Like other trichostrongylids, early C. oncophora L4 larvae are able to arrest their development under unfavourable environmental conditions such as low temperatures and high dryness, a process termed hypobiosis. L4 larvae can stay arrested up to five months. Arrested development is characterized by a large number of individuals stopping at the same stage of development, a bimodal distribution of worm sizes, and a recent exposure of the host animal to the infectious agent prior to the prepatent period of the infectious agent. During this period of arrested development, the worms stop growing and slow down their metabolism. Arrested development allows the worms to evade many of the anthilmentics commonly used. The recommended doses are based on adult worms and normally developing larvae. Arrested development can be triggered by the following situations: seasonal influences on the larvae while outside the host, the normal host immune response interrupting the normal parasitic phase of the life cycle, or overpopulation of adults that leads to negative feedback preventing the further development of more larvae. It is advantageous for nematodes to enter arrested development as they can survive in hostile environments, cause disease in the host by a large portion of the larvae resuming development, produce large numbers of infectious eggs when the environmental conditions are once again favorable, and avoid susceptibility to various anthilmentics. == -Omics ==

Genome project The C. oncophora genome sequencing project has been recently approved for funding. The project was initially submitted by an international consortium of universities and research institutes and has been undertaken at the Washington University Genome Sequencing Center. The major goal is to aide with identification of novel target molecules for the development of new drugs and vaccines. The genomic data might prove as an invaluable resource for fundamental biological research, comparative genomics and provide new insights in genetic mechanisms involving drug susceptibility, resistance, host parasite relationships, host immunity, possibility to maintain the life of currently available drugs and improved molecular diagnostics. Transcriptome project Recent transcriptomic data of C. oncophora from different developmental stages identified protein and domain families that are important in stage-related development. The transcriptome of C. oncophora resulted in approximately 9,600,000 reads and 29,900 assembled transcripts. These transcripts represent an estimated 81% of complete transcriptome (based on estimation from the conserved low copy eukaryotic genes). Further detailed analysis of transcriptomic data and their comparison with genomic data will provide more depth insights about parasite lifecycle and what different genes are important in the free living and parasitic stages. Excretome/secretome project Excretome/secretome (ES) components essentially consist of proteins and other compounds that are secreted from the parasite and it constitutes the primary interface between parasite and host and may be further exploited as potential vaccine candidates. Analysis of the adult-stage C. oncophora ES, covered both the protein and glycan components. Several proteins were identified that have also been detected in the ES of other nematode species. though they await experimental characterization. Other proteins identified from ES fraction are aldose reductase and thioredoxin. These proteins are known to be involved in detoxification process. Innexin plays a role intercellular communication may be involved in modulating the response of anthelmintic; ivermectin. The above-mentioned findings are also consistent with transcriptomic data, showed the importance of these proteins because there transcripts were consistently observed in all C. oncophora life-stages, which further highlight their importance in parasite development. == Pathology ==

Cooperia are considered less pathogenic to livestock than other common gastrointestinal nematode worms: Haemonchus or Ostertagia. However, the pathology caused by Cooperia coupled to its wide range of distribution has huge economic impact to cattle producers. Typically calves are affected most adversely. Infection causes appetite reduction and inefficient uptake of necessary nutrients which effects body weight, reproduction and can lead eventually to calf death. Although C. oncophora does not feed on host-blood, it has the capacity to burrow through the gut wall, especially in the proximal location (duodenum) which can lead to anemia in the host. == Host defense mechanisms ==

Ruminants respond to C. oncophora infection using multiple mechanisms, and the degree of response varies based on various host-parasitic factors. Based on the response pattern, a small host proportion is classified as "high responder". These are capable of clearing the parasite rapidly, so that no eggs are detected in the feces, or there is only a very low worm burden after 42 days post infection (p.i.) with 100,000 L3 stage larvae. On the other hand, the "low responder" group is highly susceptible to infection, having a high worm burden and high egg output after 42 days p.i.. Most animals however belong to the intermediate responder group. They react initially similar to the low responder group. Although they can significantly reduce egg output after 35–42 days while worm burden in the intestine remains in range of low to high number. C. oncophora generally tends to reside in the proximal gut, the first six meters. An effective host immune response subsequently drives the adults towards more distal locations. The fecundity of the parasite decreases in the proximal gut after immune activation, although fecundity in the distal gut remains higher. On the other hand, response to secondary exposure involves increase in CD4+ T-cell in the lymph node, in the peripheral blood and in Payer's patches of the proximal gut. However, CD4+ T-cell numbers decrease in the lamina propria after 28 days of secondary experimental infection. Activated cells from the lamina propria migrate to the lymph node and peripheral blood. Acute inflammation in the primed proximal gut occur earlier and eosinophil level normalizes before 14 days of infection. On the contrary, there is an accumulation of eosinophils in the distal gut at around 14 days while proportion of eosinophil increase again in proximal gut after 28 days. This indicates two waves of eosinophil influx where CD4+ T-cell induces second influx rather first one. Generally, mast cells are also involved with eosinophils in the protection against nematodes. In case of primary and secondary infections with C. oncophora, no direct involvement mast cells have been proved yet. There is a general decrease in the expression of apoproteins after C. oncophora infection. However, the resistant host still maintains higher level of apoproteins compared to low responder. There is a disruption of lipid metabolism. It is known that dietary rearrangement of lipid metabolism can give protection against nematode infections. Dietary poly unsaturated fatty acids (PUFA) omega-3 and omega-6 can boost up the protection. Therefore, treatment with omega-3 PUFA has been associated low egg count in the feces. CDH26 level is positively correlated with Cooperia specific IgA. == Prevention and control ==

Prevention is a difficult task. Cooperia larvae can withstand in adverse environmental conditions and can survive in grass lands even up to a year. Larvae can undergo dormant during winter and can comeback upon suitable conditions. Combined efforts that are taken to prevent typical worm infection are also applicable for Cooperia. These include maintaining a healthy herd, pasture management, careful grazing, plowing the field, avoiding congested and humid environments, keeping calves separately and ensuring hygiene. Resistance has been reported to all broad spectrum anthelmintics, which are benzimidazoles (BZs), levamisole/morantel (LEV) and macrocyclic lactones (ML). There are numbers of reports about resistance of C. oncophora to MLs. MLs include ivermectin (IVM), which has been extensively used to treat livestock gastrointestinal parasites since the 1980s. MLs bind irreversible to Glutmate gated chloride ion (GluCl) channels, leading to hyperpolarisation. Pharyngeal and somatic muscle cells get paralyzed, which results in starvation of the worms and also their removal from the gastrointestinal tract. Reason for emerging resistance is selection for resistant individuals, particularly by high treatment frequency and under-dosing of the drugs. In C. oncophora, a P-glycoprotein called pgp-11 was found to be up-regulated in resistant adult worms compared to susceptible worms, but so far it has not been proven that up-regulation of pgp-11 actually protects the worm from MLs. == Epidemiology ==

The epidemiology of this species can vary by geographic distribution. For example, the northern hemisphere sees arrested development of the L4 stage more often during the winter. The subtropical areas see arrested development more often during the dry seasons. There is not a lot of relevant epidemiology information available. It is known that C. oncophora has been found in temperate climates such as the United States and Brazil. Studies have been done to establish the prevalence in these areas. The lack of information may be due to less frequent reporting of cattle nematodes as compared to the frequency of human nematodes, and that Cooperia oncophora is not commonly reported as the sole cause of infection. C. oncophora often causes secondary infection alongside the infection caused by Ostertagia ostertagi and Haemonchus contortus. O. ostertagi and H. contortus cause more severe signs of infection than C. oncophora. Because of this difference in signs, O. ostertagi and H. contortus are often reported as the cause of disease rather than C. oncophora. ==References==