High Seropositivity Rate of Neutralizing Antibodies to Astrovirus VA1 in Human Populations.

Astroviruses are common pathogens of the human gastrointestinal tract, but they have been recently identified from cases of fatal meningoencephalitis. Astrovirus VA1 is the most frequently detected astrovirus genotype from cases of human encephalitis, but the prevalence of neutralizing antibodies to VA1 in human sera is unknown. We developed a focus reduction neutralization assay (FRNT) for VA1 and measured the seroprevalence of neutralizing antibodies from two cohorts of adult and pediatric serum samples: (i) an age-stratified cohort from St. Louis, MO, collected from 2007 to 2008 and (ii) a cohort from the Peruvian Amazonian River Basin collected in the late 1990s. In the St. Louis cohort, the lowest seropositivity rate was in children 1 year of age (6.9%), rising to 63.3% by ages 9 to 12, and 76.3% of adults ≥20 years were positive. The Peruvian Amazon cohort showed similar seropositivity rates across all ages, with individuals under age 20 having a rate of 75%, while 78.2% of adults ≥20 years were seropositive. In addition, we also identified the presence neutralizing antibodies to VA1 from commercial lots of intravenous immunoglobulin (IVIG). Our results demonstrate that a majority of humans are exposed to VA1 by adulthood, with the majority of infections occurring between 2 and 9 years of age. In addition, our results indicate that VA1 has been circulating in two geographically and socioeconomically divergent study cohorts over the past 20 years. Nonetheless, a significant proportion of the human population lacks neutralizing immunity and remains at risk for acute infection. IMPORTANCE Astroviruses are human pathogens with emerging disease associations, including the recent recognition of their capacity to cause meningoencephalitis. Astrovirus VA1 is the most commonly identified astrovirus genotype from cases of human encephalitis, but it is unknown what percentage of the human population has neutralizing antibodies to VA1. We found that 76.3 to 78.2% of adult humans ≥20 years of age in two geographically and socioeconomically distinct cohorts are seropositive for VA1, with the majority of infections occurring between 2 and 9 years of age. These results demonstrate that VA1 has been circulating in human populations over the past 2 decades and that most humans develop neutralizing antibodies against this virus by adulthood. However, a subset of humans lack evidence of neutralizing antibodies and are at risk for diseases caused by VA1, including encephalitis.

Dereplications can amplify the extent and worth of traditional pharmacopeias.

As aculturization and globalization continues, there is an urgent need to carefully record and delineate traditional pharmacopeias so that their true worth is understood and protected and any possible benefits related to their commercial development are equitably distributed. In the past most of these endeavors resulted in a list of plants with their associated uses without providing further explanations as to the extent of this knowledge within the traditional group, or if this knowledge was known elsewhere. This practice tended to generate the notion of finite exclusivity without providing proof that this was actually the case. Moreover, since the talents and methods of those conducting these initial studies varied widely, little effort was made to provide adequate information on how selective processes and preferences as well as modes of collection, preparation and use were achieved. Without these data, the potential of their clinical worth, bioreactive capacities or chemical compositions were often compromised. This frequently led to expending much time, effort and treasure on a pharmacopeia's evaluation without guidance on how these efforts could be optimized to achieve its best possible medicinal potential. This paper will review how types of dereplications and other techniques are helpful in amplifying this process.

Evolving concepts related to achieving benefit sharing for custodians of traditional knowledge.

In the context of evolving intellectual property law, defining ownership of traditional knowledge can be challenging when claims of origin are conflicting and requires accepting parameters of how uniqueness is defined and patent law is applied to protect this information. For purposes of this paper, the complexities of evolving benefit sharing for custodians of traditional knowledge are discussed in relationship to the use of medicinal plants. Parameters of ownership can vary not only by the perception of individuals that lay claim to the information but also by international, regional and national laws that govern how benefits should be fairly appropriated. Examples are provided to exemplify the wide variation that presently exists in this evolving process with illustrations of how this information, novel or otherwise, can be utilized to optimize its commercial worth.

Natural antimycobacterial metabolites: current status.

Over the years the introduction of very effective drugs has revolutionized the treatment of tuberculosis. In recent years, however, emerging multiple drug resistance has become a major threat and thus calls for an urgent search for new and effective treatments for this deadly disease. This review is complementary to earlier reviews and covers more recent reports of naturally occurring compounds, and in some cases synthetic analogs, largely from plants, fungi and marine organisms that demonstrate significant activity in the in vitro bioassays against Mycobacterium tuberculosis, and other mycobacterial species. Included also are traditional medicinal uses of specific plants when utilized to treat tuberculosis and other pulmonary diseases.

Geographic distribution of three alkaloid chemotypes of Croton lechleri.

Three known alkaloids, isoboldine (2), norisoboldine (1), and magnoflorine (8), have been isolated for the first time from Croton lechleri, a source of the wound healing latex "sangre de grado". An HPLC system was developed, and a large number of latex and leaf samples of C. lechleri from 22 sites in northern Peru and Ecuador were analyzed to gain an understanding of the natural variation in alkaloid content for the species. Up to six alkaloids were found to occur in the leaves including, in addition to those listed above, thaliporphine (3), glaucine (4), and taspine (9), whereas the latex contained only 9. Taspine (9) is the component that has been previously found to be responsible for the wound healing activity of C. lechleri latex, and its mean concentration throughout the range examined was found to be 9% of the latex by dry weight. In addition, three chemotypes are defined based on the alkaloid content of the leaves, and the geographic distribution of these chemotypes is discussed along with a quantitative analysis of the alkaloid content as a function of chemotype.