Temporal Changes in Routine Health Markers and Their Association with Illness and Mortality Rates in Cats Naturally Infected with Feline Immunodeficiency Virus

Jamieson J Nichols, Purdue University

Abstract

Feline immunodeficiency virus is an important lentiviral infection in cats. Infection is life-long and results in immune compromise, increased susceptibility to opportunistic infections and early mortality. Infection is commonly referred to in three stages: acute, (asymptomatic) and end stage (symptomatic); although not all cats will progress to end stage disease. Acute infection lasts several months during which cats may have mild, transient anorexia, lethargy, fever, lymphadenomegaly and diarrhea. There is loss of mucosal and peripheral CD4 T cells, expansion of a subset of CD8 T cells, CD8βlow, and establishment of viremia during this period. Asymptomatic infection lasts a variable period of years during which progressive decreases in CD4 T cells and inversion of the CD4:CD8 ratio occurs. End stage infection does not occur in all infected cats. It is characterized by a rapid decline in health including generalized muscle wasting, treatment-refractory opportunistic infection and / or neoplasia leading to death within months. A marked decrease in CD4 T cell counts and CD4:CD8 ratio and several fold increase in viremia occurs during end stage disease but reported literature is sparse. Longitudinal studies of specific pathogen free cats experimentally infected with FIV infection have focused primarily on acute and early asymptomatic stages of infection. Little has been reported on the transition from late chronic to end stage disease. Longitudinal studies of cats naturally infected with FIV are needed to better characterize the course of infection. In this study, a cohort of cats naturally infected with FIV (n = 87) and uninfected cats (n = 87) were monitored over a period of 3 to 5 years, depending on when they were enrolled. FIV-infected cats were examined twice yearly and uninfected were examined once yearly. At each examination blood samples were collected for routine hematological and biochemical screening and lymphocyte immunophenotyping. It was hypothesized that FIV-infected cats, compared to FIV-uninfected cats, will have: 1) an increased rate of illness and mortality; 2) differences in temporal patterns for routine hematological and biochemical tests, and lymphocyte immunophenotype; and 3) changes in lymphocyte immunophenotype and clinical pathology markers associated with illness and mortality rates. The same hypotheses were also tested between FIV-infected cats in sanctuary housing and FIV-infected cats living in private homes of <7 cats. Results showed that mortality rate was increased by 11.7 fold in FIV-infected cats in sanctuary housing and 4.1 fold in FIV-infected cats in private homes compared to FIV-uninfected cats. Illness rates were increased 15.1 fold higher in sanctuary housed cats and 3.0 fold higher in privately homed cats compared to FIV-uninfected cats. FIV-infected cats in sanctuary housing had a 5.1 fold increased mortality rate associated with FIV infection compared to FIV-infected cats living in private homes. Differences in temporal patterns were statistically significantly different for absolute CD4 T cell>counts, total CD8 T cell counts, lymphocytes numbers, albumin, blood urea nitrogen (BUN), and cholesterol levels for FIV-infected cats compared to uninfected cats. Although T cell and lymphocyte counts decreased in both groups, the decreases were greater for FIV-infected cats. Albumin and BUN values decreased and globulin values increased in FIV-infected cats compared to uninfected cats but the changes were small. Differences in CD8β low cells counts, CD4:CD8 ratio, globulin and total protein levels were seen but remained stable between the groups over time. FIV-infected cats in sanctuary housing showed statistically significantly different temporal patterns for absolute white blood cell counts (WBC), hematocrit, total protein (TP), BUN, creatinine and alanine aminotransferase (ALT) but the changes were small. WBC and TP values increased in FIV-infected cats in sanctuary housing compared to cats in private homes. Decreasing temporal patterns in BUN, creatinine, ALT and hematocrit were found in FIV-infected cats in sanctuary housing compared to cats in private homes but changes were small and median values remained within the reference intervals. Higher absolute neutrophil counts and globulin levels and lower values for albumin and cholesterol levels were seen in FIV-infected cats in sanctuary housing compared to cats in private homes but differences remained stable between the two groups. In FIV-infected cats, a greater decrease in CD4 T cell and albumin percentages and a greater increase in CD4:CD8 ratios and neutrophil counts were associated with an increase in illness rate. An increase in mortality rate was associated with a greater increase in total protein and greater decreased in albumin and hematocrit percentages. However, associations were weak and use of any of these parameters as a stand-alone monitoring tool cannot be recommended. There were no associations between any parameter and illness or mortality in FIV-uninfected cats. Results of this study showed FIV-infected cats had increased illness and mortality rates compared to FIV-uninfected cats. Furthermore, FIV-infected cats living in sanctuary housing had higher illness and mortality rates compared to FIV-infected cats living in private housing. This raises the question of what role environmental conditions may play in disease progression in FIV infection. This has not been previously reported in the literature and further investigation into the potential environmental impact on disease progression is warranted. The most notable differences in temporal patterns for health parameters were associated with inflammation and immune cells. Illness and mortality rates were associated with greater changes in inflammatory parameters and lymphocyte immunophenotype in FIV-infected cats, although, associations were weak. While considered exploratory in this study population, these findings further support the roles of chronic inflammation and immune activation in disease progression following FIV infection that have been reported in the literature. Given the limited availability of monitoring techniques for FIV-infected cats, further investigation into the use of these health markers of inflammation and lymphocyte immunophenotype as a panel to monitor disease progression is warranted. However, continued research into new, reliable and easily performed techniques that accurately measure chronic inflammation and immune activity in FIV infection is needed.

Degree

M.S.

Advisors

Guptill, Purdue University.

Subject Area

Veterinary services

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