Sequestration and Destruction of Rinderpest Virus-Containing Material 10 Years after Eradication.

In 2021, the world marked 10 years free from rinderpest. The United Nations Food and Agriculture Organization and World Organisation for Animal Health have since made great strides in consolidating, sequencing, and destroying stocks of rinderpest virus-containing material, currently kept by only 14 known institutions. This progress must continue.

The Opportunity To Eradicate Peste des Petits Ruminants.

Peste des petits ruminants (PPR) is a highly infectious disease of sheep and goats that is caused by PPR virus, a member of the genus Morbillivirus that includes the viruses that cause rinderpest (RP) in cattle. RP was the first animal disease to be globally eradicated in 2011 and is only the second disease, after smallpox, to have ever been eradicated. PPR is one of the principal constraints to small ruminant production in Africa, Asia, and the Middle East. The epidemiology of PPR and RP as well as the technologies available for their diagnosis and control are similar. The conditions that favored the eradication of RP are also largely present for PPR. In this work, we outline the evolving strategy for eradication in light of current opportunities and challenges, as well as the lessons from other eradication programs in animal and human health. The global PPR situation and technology for its control are summarized. A strategy based on the lessons from previous eradication efforts that integrate epidemiology, social science, and economics as tools to target and motivate vaccination is summarized. Major aspects of the cost and benefit-cost analysis of the indicated program are presented. The overall undiscounted cost of eradication was estimated as $3.1 billion, and the benefit-cost ratio for the most likely scenario was estimated at 33.8. We close with a discussion of the possible next steps.

World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection.

The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [-13910*T (rs4988235), -13907*G (rs41525747), -13915*G (rs41380347), -14009*G (rs869051967) and -14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the 'Old World' and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection.

Eco-social processes influencing infectious disease emergence and spread.

The complexity and connectedness of eco-social processes have major influence on the emergence and spread of infectious diseases amongst humans and animals. The disciplinary nature of most research activity has made it difficult to improve our understanding of interactions and feedback loops within the relevant systems. Influenced by the One Health approach, increasing efforts have recently been made to address this knowledge gap. Disease emergence and spread is strongly influenced by host density and contact structures, pathogen characteristics and pathogen population and molecular evolutionary dynamics in different host species, and host response to infection. All these mechanisms are strongly influenced by eco-social processes, such as globalization and urbanization, which lead to changes in global ecosystem dynamics, including patterns of mobility, human population density and contact structures, and food production and consumption. An improved understanding of epidemiological and eco-social processes, including their interdependence, will be essential to be able to manage diseases in these circumstances. The interfaces between wild animals, domestic animals and humans need to be examined to identify the main risk pathways and put in place appropriate mitigation. Some recent examples of emerging infectious disease are described to illustrate eco-social processes that are influencing disease emergence and spread.

In Vitro Functional Analyses of Infrequent Nucleotide Variants in the Lactase Enhancer Reveal Different Molecular Routes to Increased Lactase Promoter Activity and Lactase Persistence.

The genetic trait that allows intestinal lactase to persist into adulthood in some 35% of humans worldwide operates at the level of transcription, the effect being caused by cis-acting nucleotide changes upstream of the lactase gene (LCT). A single nucleotide substitution, -13910 C>T, the first causal variant to be identified, accounts for lactase persistence over most of Europe. Located in a region shown to have enhancer function in vitro, it causes increased activity of the LCT promoter in Caco-2 cells, and altered transcription factor binding. Three other variants in close proximity, -13907 C>G, -13915 T>C and -14010 G>C, were later shown to behave in a similar manner. Here, we study four further candidate functional variants. Two, -14009 T>G and -14011 C>T, adjacent to the well-studied -14010 G>C variant, also have a clear effect on promoter activity upregulation as assessed by transfection assays, but notably are involved in different molecular interactions. The results for the two other variants (-14028 T>C, -13779 G>C) were suggestive of function, -14028*C showing a clear change in transcription factor binding, but no obvious effect in transfections, while -13779*G showed greater effect in transfections but less on transcription factor binding. Each of the four variants arose on independent haplotypic backgrounds with different geographic distribution.

Diversity of lactase persistence alleles in Ethiopia: signature of a soft selective sweep.

The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (-13910(∗)T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene LCT is responsible for lactase persistence and appears to have been under strong directional selection in the last 5,000 years, evidenced by the widespread occurrence of this allele on an extended haplotype. In Africa and the Middle East, the situation is more complicated and at least three other alleles (-13907(∗)G, rs41525747; -13915(∗)G, rs41380347; -14010(∗)C, rs145946881) in the same LCT enhancer region can cause continued lactase expression. Here we examine the LCT enhancer sequence in a large lactose-tolerance-tested Ethiopian cohort of more than 350 individuals. We show that a further SNP, -14009T>G (ss 820486563), is significantly associated with lactose-digester status, and in vitro functional tests confirm that the -14009(∗)G allele also increases expression of an LCT promoter construct. The derived alleles in the LCT enhancer region are spread through several ethnic groups, and we report a greater genetic diversity in lactose digesters than in nondigesters. By examining flanking markers to control for the effects of mutation and demography, we further describe, from empirical evidence, the signature of a soft selective sweep.