PubMed · 14213724
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A PANCALDO, F LOSCHIAVO. 1964-10-19. [BONE MARROW IMPLANTS].. https://pubmed.ncbi.nlm.nih.gov/14213724/
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Recent studies on sheep and goat farms in the southern United States indicate that multiple-anthelmintic resistance in Haemonchus contortus is becoming a severe problem. Though many factors are involved in the evolution of resistance, the proportion of the parasite population under drug selection is believed to be the single most important factor influencing how rapidly resistance develops. Therefore, where prevention of resistance is an important parallel goal of worm control, it is recommended to leave a portion of the animals untreated. Recently, a novel system called FAMACHA was developed in South Africa, which enables clinical identification of anemic sheep and goats. When H. contortus is the primary parasitic pathogen, this system can be applied on the farm level to reduce the number of treatments administered, thereby increasing the proportion of the worm population in refugia. Since most studies validating the FAMACHA method have been performed in South Africa, it is important that the method be tested in other regions before its use is broadly recommended. We performed a validation study of FAMACHA by testing the system in sheep (n = 847) and goats (n = 537) of various breeds and ages from 39 farms located in Arkansas, Georgia, Louisiana, Florida, and the US Virgin Islands. The color of the ocular conjunctiva of all animals were scored on a 1-5 scale using the FAMACHA card, and blood samples were collected from each animal for determination of packed cell volume (PCV). Fecal samples were also collected from a majority of the animals tested for performance of fecal egg counts (FEC). Correlations between PCV and eye scores, PCV and FEC, and FEC and eye scores were all highly significant for both sheep and goats (P < 0.001). Data for both FAMACHA scores and PCV were evaluated using two separate criteria for anemia: eye score values of 3, 4 and 5 or 4 and 5, and PCV values of < or =19 or < or =15 were considered anemic. Specificity was maximized when eye score values of 4 and 5 were considered anemic and PCV cut off for anemia was < or =19, but sensitivity was low. In contrast, sensitivity was 100% for both sheep and goats when eye score values of 3, 4 and 5 were considered anemic and PCV cut off was < or =15, but specificity was low. In both sheep and goats, predictive value of a negative was greater than 92% for all anemia and eye score categories, and was greater than 99% for both eye score categories when an anemia cutoff of < or =15 was used. Predictive value of a positive test was low under all criteria indicating that many non-anemic animals would be treated using this system. However, compared to conventional dosing practices where all animals are treated, a large proportion of animals would still be left untreated. These data indicate that the FAMACHA method is an extremely useful tool for identifying anemic sheep and goats in the southern US and US Virgin Islands. However, further studies are required to determine optimal strategies for incorporating FAMACHA-based selective treatment protocols into integrated nematode control programs.
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Erythropoietin (EPO) activates many distinct signal transduction cascades on engagement of its receptor. Deletion of the EPO, EPO receptor (EPO-R), or JAK2 genes in mice results in embryonic lethality due to a fatal anemia. EPO activates signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5a/b transcription factors in erythroid cell lines. Studies have focused on STAT5 as the primary target of EPO-dependent JAK2 activation. However, STAT5a/b(-/-) mice are viable, displaying a nonfatal anemia during embryogenesis, and delayed differentiation in adult erythropoiesis. Importantly, EPO-R cytoplasmic tyrosines are dispensable for viability in vivo. Interestingly, no cytoplasmic tyrosines are required for phosphorylation of STAT1. This led us to examine whether STAT1-deficient mice have altered erythropoiesis. A shift in erythropoiesis was observed in STAT1(-/-) mice, with reduced bone marrow-derived erythroid colony-forming units (CFU-Es) and a compensatory increase in splenic burst-forming units (BFU-Es) and CFU-Es. Both types of splenic-derived cells displayed EPO hyperresponsiveness. A 1.6-fold reduction in total CFU-Es was observed in STAT1-deficient mice, whereas total BFU-Es were comparable. Flow cytometry of STAT1-deficient erythroid cells revealed a less differentiated phenotype, associated with increased apoptosis of early erythroblasts. STAT1-deficient erythroblasts from phenylhydrazine-primed mice displayed enhanced phosphorylation of STAT5a/b, Erk1/2, and protein kinase B (PKB)/Akt. These results illustrate that STAT1 plays an important role in the regulation of erythropoiesis.