Pathology in Context

Issue Highlights

Leukocyte Diapedesis: More Complicated Than Swipe Access

Orchestration of leukocyte diapedesis is complex, whether a direct transcellular migration or around the side, employing a paracellular approach at endothelial borders. Familiarity with the molecules and mechanisms involved and the temporal and spatial relationships is essential for more reasons than success on the general pathology portion of certification examination! Understanding this process is critical to the evolution of novel anti-inflammatory approaches. Disease conditions such as myocardial infarction, ulcerative colitis and Crohn disease are only a few examples that could benefit from minimizing leukocyte diapedesis. The review in this issue (“Getting Leukocytes to the Site of Inflammation,” Vet Pathol, 2013;50:7–22) provides an essential update as to how leukocytes arrive at an inflamed area.

The More You Look . . . Novel Genital Alphapapillomaviruses in Baboons

The unexpected discovery of 3 new alphapapillomaviruses associated with specific lesions in the female reproductive tract in wild-caught baboons is of interest, as it provides a new model for a common human disease in a nonhuman primate species where these infections were not known previously (“Novel Genital Alphapapillomaviruses in Baboons (Papio hamadryas Anubis) With Cervical Dysplasia,” Vet Pathol, 2013;50:201–209). Some of these new viruses are phylogenetically close to human papillomaviruses, which makes the model even more useful, as it provides clues for understanding oncogenic viral evolution. The model is also a reminder of the risks associated with experimentation in wild-caught animals, as they can be reservoirs of background conditions that in some cases might not even be described for certain species.

Perspective on Porcine Circovirus Type 2: What We’ve Learned Since the 1990s

Porcine circovirus type 2 (PCV2) global disease outbreaks appeared in the early 1990s. PCV2 was first described as a small, circular ssDNA virus in 1998, and widespread effective vaccination has occurred since 2006. Updates on the disease research findings and summation of PCV2 clinical manifestations illustrate the importance of reviewing aspects of the disease to understand the global issue (“Current State of Knowledge on Porcine Circovirus Type 2–Associated Lesions,” Vet Pathol, 2013;50:23–38). Even in the short time that they have been recognized, the PCV-associated diseases have evolved and shifted. For example, reports of PCV2b were concurrent with a large increase in cases of systemic disease. No tissue or organ system appears to be spared the potential effects of this virus, and virulence of viral isolates, variability in coinfections, host immune status, and host state of immune stimulation have all been shown to alter disease outcome. In a relatively short period, porcine circovirus has emerged as a costly and omnipresent disease in pigs.

PCV2 research in Spain is evaluating whether vaccination of sows and piglets on a massive scale could eradicate PCV2. Considerations of the feasibility for disease eradication were recently reported in Science and highlights from this article follow.

In the News

How to Eradicate a Scourge

After smallpox, rinderpest is the only infectious disease that has been globally eradicated. ⁷ What determines whether one viral disease can be eradicated and another not? Apart from vaccine efficacy, understanding the dynamics of how a disease spreads is crucial to its control. The potential for a disease to spread in a naive population can be approximated mathematically using the basic reproductive ratio, R(0). R(0) is defined as the expected number of secondary cases produced by a single typical infection in a completely susceptible population. ³ R(0) is a dimensionless number calculated using 3 variables: transmissibility of the agent (τ), the rate of contact between susceptible and infected individuals (c), and the duration of infectiousness (d). These 3 variables are themselves the product of equations that define the contextual complexity of any given outbreak. ⁶ For example, the R(0) for the British foot and mouth disease outbreak of 2001 was 4.6, ² whereas in an outbreak in intensive dairy farms in Saudi Arabia, R(0) was estimated to be greater than 70. ¹² The practical use of R(0) is that it is used to estimate the proportion of herd immunity that must be established to prevent spread within a given context, calculated as 1 – 1/R(0). In general, the smaller the R(0) of an agent, the easier it is to control—the foot and mouth disease examples would require herd immunity of 77% and 99%, respectively. ⁷ For comparison, the estimated R(0) of now-extinct rinderpest is 2 to 4.6; for the H1N1 influenza pandemic, 1.4 to 1.6; ⁴ and for African swine fever currently sweeping through the Russian Federation, an estimated range of 2 to 11. ⁵ Of note for laboratory animal veterinarians and parents alike, the R(0) of measles varies from 7 to 18. ⁹

Pass Another Slice, Please

Followers of the Michelin guide can breathe a sigh of relief. The results of a long-awaited National Institute on Aging (NIA) trial in macaques indicate that caloric restriction does not significantly prolong lifespan. ⁸ These results counter those of a similar macaque study ¹ at the Wisconsin National Primate Research Center (WNPRC) as well as numerous studies in worms, flies, and rodents. In the NIA study, restricted animals died at more or less the same rate as control macaques regardless of when dietary restriction was instituted. Restriction imposed in older animals did not protect against the usual panoply of age-related ills; however, macaques restricted at an early age did experience less neoplasia. Differing results of the 2 macaque studies may well lie in the nature of the diets used. The NIA study used natural ingredient diets with low glucose content, whereas the WNPRC study used a purified diet with much higher glucose. Additionally, control animals in the latter study were fed ad lib and thus heavier than control macaques in the NIA study, which were somewhat portion-controlled to avoid obesity. As indicated by rodent studies, in which the benefits of caloric restriction are highly strain dependent, ¹¹ genetic diversity almost certainly plays a role in nonhuman primates. ¹⁰ The WNPRC study used Indian macaques, whereas as the NIA study used macaques of mixed Indian and Chinese origin. Regardless of whether restricted monkeys live longer, they demonstrated improved clinical pathologic indicators of metabolic health in both studies. Ongoing results in this field could hold the key, not to living longer, but to living better.