Evaluation of host cell responses and potential biomarkers for therapeutic effectiveness of Mannheimiosis in goats

Mannheimiosis is one of the most common acute respiratory diseases in small ruminants worldwide and it is caused by M. haemolytica. The disease has led to economic losses and a high mortality rate. Veterinarians and farmers are still facing the problem of practicing effective treatment regimens for pneumonia, especially in small ruminant industries. Besides, there is limited information on the application of biomarkers (interleukins and acute phase proteins) in measuring the treatment effectiveness of Mannheimiosis in goats. Therefore, the present study was conducted to evaluate the potential biomarkers to measure the therapeutic effectiveness of goats infected with Mannheimiosis. Twenty male goats were equally divided into five groups (n=4). All groups except group 1 (negative control) were inoculated intranasally with M. haemolytica (10 cfu/ml). Goats in group 2 were a positive control. Goats in groups 3 and 4 were treated with an antimicrobial (oxytetracycline, SID) on days 6 and 9 of post-infection and an anti-inflammatory drug (flunixin meglumine, BID) for 5 days of post-infection (days 6, 7, 8, 9 and 10), respectively. Goats in group 5 received combined treatment regimens of both antimicrobial and anti-inflammatory drugs. All animals were observed daily for clinical signs with rectal temperature measurement and lung auscultation which were performed throughout the study period. Blood samples were collected via jugular vein at 24 hours, on days 5, 9, 11, 14, 21 and 28 of post-infection for haematology, serum biochemistry, interleukins (IL-1ß and IL-6) and acute-phase proteins (SAA, Hp and Fib) analysis. The goats were euthanized on the 28th post-infection and all organs were collected for bacterial re-isolation and histopathological examination. The haematological evaluation revealed all RBC, Hb and HCT levels were significantly (p<0.05) reduced post-inoculation. The TWBC count showed a significant (p<0.05) reduction in the value at 24 hours and day 28 post-infection. Serum biochemistry findings of the post-infection LDH levels had increased significantly (p<0.05). The interleukin analyses of IL-1ß and IL-6 demonstrated a significant (p<0.05) reduction in all treatment groups and a greater reduction in the anti-inflammatory and combined treatment regimens (groups 4 and 5) on day 11 compared to the positive control. Serum amyloid A concentrations levels in groups 3, 4 and 5 showed a significant (p<0.05) decrease post-treatment on days 9 and 11 compared to the positive control group. The Hp concentration levels revealed a significant (p<0.05) decrease, particularly in treatment group 5, on both days 9 and 11 of the post-treatments compared to the positive control. Gross evaluation of the lung showed a significantly (p<0.05) reduced percentage of area affected in the lung of treatment group 5 compared to the positive control. Histopathological evaluation of the lungs revealed that treatment group 5 had reduced (mild) (p<0.05) lesions score of alveolar fibrosis and thickening of alveolar septa compared to the positive control group and other treatment groups. Liver tissue evaluation revealed that group 5 had reduced (mild) (p<0.05) lesion score of degeneration compared to the positive control and a lower lesion score of necrosis compared to group 3. The treatment intervention during Mannheimiosis in the goats, particularly in group 5, was able to reduce the severity of the disease in the infected goats. This study has proven the effectiveness of combined treatment regimens in reducing the levels of interleukins, acute phase proteins and thus reduced the severity of tissue injury in the affected goats.