Insight

Fall 2004

Researcher Uses Clinical Cases to Focus Investigative Work in the Laboratory

Malignant catarrhal fever was an illness Dr. Rob Callan had seen only once in 10 years while working as a large animal veterinarian. When he arrived at CSU, however, he saw several cases over a six-month period and became intrigued by the disease’s seemingly greater prevalence in Colorado. There weren’t many answers as to why or even basic information on transmission and viral properties, so Dr. Callan took the disease from clinic to laboratory with a variety of collaborative research projects.

In 2002, Dr. Callan was faced with a similar situation, though this time with a disease that had a worrisome impact on animals and humans and had gained national attention. West Nile virus was gaining a foothold in Colorado and, though alpacas and llamas originally were thought to have lower rates of infection and illness, the Large Animal Clinic soon began to see critically ill animals succumbing to the ravaging effects of the virus. Clinical work once again led to laboratory investigations and launched projects focusing on vaccine testing, transmission paths, and infection rates, particularly in alpacas for which very little information on WNV was available.

“I spend 26 weeks out of the year on hospital duty and get to see cattle, sheep, goats, bison, and llamas – even a baby moose – so my research focus stems from what I see in the clinics,” said Dr. Callan, an Associate Professor in the Department of Clinical Sciences and faculty member in the Integrated Livestock Management (ILM) Program. “I enjoy being able to bridge the gap between clinicians and researchers, working both sides toward a common goal of improving animal health.”

Dr. Callan’s initial research with malignant catarrhal fever (MCF) examined transmission of the virus, a form known as sheep-associated MCF in the United States (in Africa, the form is wildebeest-associated MCF). Sheep are asymptomatic carriers of the virus, infecting cattle or bison when they come in contact or herds are near each other. Epidemiological studies showed that cattle and bison appear to be dead-end hosts, developing a fatal illness but rarely if ever transmitting the virus. Dr. Callan’s research team also showed that, in some circumstances, infected cows never develop signs of disease. Questions being examined now include why some animals develop symptoms and others don’t; what triggers onset of the disease; and how does the virus disregulate the infected cells? The team also is in the process of developing cell culture systems for the virus to help identify and pick apart the virus/host interactions and how they cause disease. Successfully developing a cell culture system also will aid in vaccine development.

“MCF is generally a fatal disease when an animal becomes symptomatic,” Dr. Callan said. “We have seen numerous outbreaks in dairy herds and on feedlots, and the disease is particularly devastating to bison populations, often wiping out an entire herd. We hope with continued progress at CSU, especially with the development of a cell culture system, we will be able to advance the prevention of MCF.”

Dr. Callan works collaboratively on MCF with Dr. James DeMartini, a Professor in the Department of Microbiology, Immunology and Pathology; and with Dr. Tshida Tsibane, a veterinarian from South Africa working toward her doctoral degree and supported with a joint fellowship from the USDA and South African government.

Another collaborative research project for Dr. Callan is his work with Dr. Richard Bowen, a Professor in the Department of Biomedical Sciences, on West Nile virus, one more case of clinical work focusing Dr. Callan’s research programs.

“In 2002, West Nile virus just started to get into Colorado,” said Dr. Callan. “States east of us had very few reports of WNV in llamas, alpacas, and even sheep and cattle. In 2003, we were getting calls from llama and alpaca owners concerned about WNV and their animals. At the time, we didn’t recommend vaccinations because, one, vaccines had not been tested in these animals and, two, it didn’t look like these animals were susceptible.”

In late summer of 2003, however, the situation changed. The Veterinary Teaching Hospital admitted an alpaca with acute cranial neurological signs that died within 24 hours and subsequently tested positive for WNV. More cases showed up, and researchers quickly realized that the WNV situation was different in Colorado, possibly because one particular mosquito – Culex tarsalus – is more prevalent and particularly good at transmitting the West Nile virus. In December 2003, a vaccine study was initiated in alpacas and llamas. Drs. Callan and Bowen are now testing serum samples to determine seroconversion rates and are also looking for adverse effects of the vaccine in llamas and alpacas, including pregnant alpacas and their offspring (to date, none have been found). Further evaluation of vaccine efficacy, in collaboration with Dr. Michelle Kutzler from Oregon State University, is being planned for the future. Drs. Callan’s and Bowen’s WNV work is supported in part by donations from the Alpaca Breeders of the Rockies and individual private alpaca breeders.

“What we’ve learned during the past two years is that WNV can be devastating to alpaca herds – every one of our teaching llamas at CSU became infected, though interestingly none were symptomatic – so we are interested in vaccine studies,” said Dr. Callan. “We also want to understand basic questions of why rates of infection are so high here, why some animals get sick, and why others show no symptoms. This work, and work on MCF, couldn’t be done without the James L. Voss Veterinary Teaching Hospital, and it couldn’t be done without the ties to basic researchers like Dr. Bowen and Dr. DeMartini. The hospital brings an immediacy to the research, and the research brings us closer to preventing and treating illnesses that are not only affecting animals, but humans as well.”