Dr. Issel Gives Us The Straight Facts On EIA

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The recently announced suspicion that a case of equine infectious anemia in Ireland may have been transmitted from horse to horse via the air has drawn a great deal of attention (see page 18). Prior to that, blood transmission through biting insects or contaminated needles was believed to be the only means of spreading the virus.

With the ongoing discussions that the Ireland story generated, we noted that a great deal of misunderstandings surround EIA and the purpose of Coggins tests. For those reasons, we decided to ask Dr. Charles Issel, a long-time expert in EIA and its transmission, to help our readers sort through the facts.

How did you become interested in EIA research'

In 1974 I was a veterinary medical officer for the USDA working at Plum Island and studying foot-and-mouth disease when I was offered a faculty position at Louisiana State University, with research on equine infectious anemia as a top priority. Once I learned what EIA was, I found it fascinating as it involved complicated interchanges between viruses, horses, blood feeding insects, and people. I had always been interested in how vector-borne diseases persist in nature, especially once I learned that the rodents nearby our house in San Francisco were persistently infected with plague, the cause of the Black Death in the Middle Ages.

What factors determine whether an infected horse develops serious symptoms or not' Are dose and strain more important than the health and immunocompetence of the horse'

Both are important. To produce disease in a given host, multiple host and virus factors interact to determine if the virus induces an infection with/without signs of disease. For example, pathogenic EIA virus strains in horses produce no disease in donkeys. Likewise, an adapted strain of EIA virus that does not cause disease in horses or donkeys, kills early term fetuses (if infected before they become immune competent, about 200 days of gestation).

How many strains of the EIA virus have been identified'

No one has done an extensive cataloging of EIA virus strains because they all share common antigenic determinants in the major core protein of the virus. As a result, all infected horses develop antibodies against the protein that are detected in the Coggins test and other approved serologic tests for diagnosis of EIA.

Within each infected horse, however, EIA virus mutates at a high rate, whether or not the horse is showing clinical signs. EIA virus is thought of as a ”quasispecies” because of this inherent high rate of variation, a feature shared with other related lentiviruses, e.g., HIV, the cause of AIDS in man. One consequence of the variation is that it may be difficult to find a single vaccine strain that will protect against all strains of the virus in nature.

Are these strains all ”variations on the same theme,” i.e. mutations the virus has produced to evade the immune system, or are they truly different strains'

A combination of both. When we compare our laboratory strains of EIA virus with isolates from around the world, there are major differences in gene sequences.

But for the virus to assemble, certain sequences are critical for production of given structural proteins. The same building blocks of the proteins (amino acids), however, can be synthesized from different combinations of gene sequences. Thus a great deal of variation is possible and appears to occur, especially in the surface proteins that adorn the virus particle.

The surface proteins have ”hypervariable” gene sequences that are found where the proteins they code for interact with immune pressure, e.g., antibody. Mutants in these regions have a better chance of replicating in the face of active immune responses and are commonly called ”escape mutants.”

If a horse is asymptomatic and hosting a strain of low virulence, could that strain mutate into a more pathogenic form'

Yes. But the inapparent carrier may already be carrying a strain that would induce disease in other horses. The horse’s immune system may be controlling the virus to a level that doesn’t produce symptoms, but the virus would cause disease if placed into another horse. Because of that fact, we say that all infected horses pose the same high risk for transmission and severe disease. We know that is not true, but we have no methods that would reliably quantitate the risk from an individual, especially as over time the status changes.

There are many people who feel strongly that asymptomatic carriers pose no threat at all to other horses. Do you agree'

No. They may be healthy and live long productive lives, but we know their blood has the EIA virus in it and the potential for transmission and disease is present. I always recommend segregating test-positive horses to stop transmission completely.

The experience at the FRIENDS Rescue (a Florida farm dedicated to saving EIA horses and EIA research), where no transmission has occurred between positive and negative horses, is often used as an argument in support of not euthanizing or segregating Coggins positive horses. Could their nonstressful lifestyle have a lot to do with that'

It could. But when steroids are given to inapparent carriers of EIA, one effect is the release of immune control on EIA virus replication. The result could be a recrudescence of clinical disease signs, e.g., fever, anemia, decrease in platelet counts, associated with a marked increase in virus concentration in the blood. In some cases we have documented an increase from undetectable to 100,000 infective doses per ml in 1 day! For this reason, care must be exercised in administering steroids to patients, e.g., horses with chronic obstructive pulmonary disease, without first testing them for EIA. If such stress was placed on the horses at FRIENDS, we would expect some horses to breakout with clinical signs of EIA. In fact, when we gave 2 ml of plasma from one of the horses at FRIENDS to a uninfected horse, severe clinical signs of EIA were observed. Because it is not possible to estimate the risk from any inapparent carrier accurately, we recommend methods to break the chance of transmission completely, i.e., segregation by 200 yards.

Is there any reason to do tests other than the Coggins test'

Yes. The ELISA test formats (four are commercially available now, see page 19) offer results in less time (minutes compared to at least one day) and could be applied to horse-side testing applications where they are needed, e.g., at horse sales or congregations. The ELISA tests offer an additional benefit: The results of ELISA tests are more easily interpreted, especially on samples with low levels of antibody. Because of this advantage, the state of Oklahoma requires that all private laboratories test all Oklahoma horses in ELISA tests and forward all positive samples to the state laboratory for confirmatory testing in the Coggins and ELISA tests.

While the number of positive reactors has dropped tremendously since Coggins testing was instituted, with the 2005 NAHMS (National Animal Health Monitoring System) equine survey estimating only 37.6% of horse owners are testing, do we really know how much EIA is out t here'

We do not know with accuracy the rate of infection with EIA virus, but testing numbers and historical records give us some informed guesses. At this moment, the USDA National Surveillance Unit is putting together the best estimates of EIA prevalence rates across the US from estimated horse numbers, previous testing statistics, and with several assumptions on how accurate each of those is. Once this task is completed, we may be able to more accurately estimate the risk of acquiring EIA in different regions of the country, from which regional strategies can be developed.

We understand you are in favor of states or regions developing new strategies that could allow for longer intervals between required Coggins tests for horses that travel and compete, but also make Coggins testing mandatory whenever a horse is sold. Is that correct' How would wild horses fit into this scheme'

I am a strong advocate for smarter testing, defined by me as testing according to risk not just by regulation. Today the industry pays in excess of $50 million each year for EIA tests. In essence, the same mobile horse population is tested each year with little recruitment of previously untested horses. I urge states to review their data from past years and determine where/how new cases are found, apply that knowledge and design strategies to find cases of EIA more efficiently. We estimate that owners in the northeastern states pay about $1.5 million in testing costs to find each positive horse. If states agreed that their immediate neighbors had the same risks for EIA, regional requirements could be developed, testing intervals where the risk is near zero could be reduced, and testing could be encouraged/sponsored for high-risk populations. The net result could be a savings to owners of more than $20 million each year. To me, this is an absolute no-brainer.

States that require testing for all transfers of ownership have found them to be productive means to monitor EIA and better protect the public. Today, all feral horses under the aegis of the BLM are tested for EIA before being adoption.

What are some of the difficulties with producing safe and effective lentivirus vaccines' Do you think recombinant or other more advanced vaccine technologies will hold the answer'

Lentiviruses induce persistent infections in their hosts. In other words, the virus has evolved strategies to persist in the host despite potent host immune responses. The challenge is to discover the basic mechanisms of persistence and the normal host responses and then change the way the virus is presented or change the way the host responds. It will take all the knowledge we can gain through basic studies in virology and immunology to better understand the normal responses to infection and to maximize protective responses. The biggest challenge remains: Can we ever produce a vaccine for lentiviruses that completely protects hosts against infection when challenged with pathogenic strains'

In human medicine, a vaccine that does not protect against infection but which protects people against disease caused by HIV strains might be acceptable in many countries, especially those with high morbidity and mortality rates assigned to HIV. In the U.S., with EIA being found so infrequently, a vaccine that afforded full protection against disease but allowed the vaccinated horses to become infected would have no value. The challenges are huge and pose excellent targets for budding researchers.

If you had free rein, what changes would you like to see made in the existing testing strategies and how would you like research money to be spent'

The changes I urge have essentially no cost to owners and regulators. I’m asking them to analyze their data and to design strategies to more effectively manage the risks of EIA. The testing system of today was designed in 1974 and has not adjusted to the decreased risk of EIA. State veterinarians hesitate to change without a mandate from their constituencies.

It would be wonderful if the savings from proposed changes could be diverted for research on issues of high priority to the industry. Today, equine research is so underfunded at the national level that it’s difficult to recruit talented researchers into the field. To put it into real terms, if only 10% of the money spent to test horses for EIA were invested in equine research, annual funding for research priorities would nearly triple!

Is freedom from EIA in our future'

It’s already in the tested mobile population. Programs like the N.Y. State Horse Health Assurance Program are developing certification schemes for facilities that should be adopted more widely by the industry. (http://www.agmkt.state.ny.us/NYSHHAP/horsehealth.html). We’re moving toward eradication, and certification is the next logical step.