Environmental spillover of emerging viruses: Is it true?

The concept of environmental "spillover" of pathogens to humans is widely used in the scientific literature about emerging diseases with the idea that it is scientifically proven. However, the exact characterization of the mechanism of spillover is simply lacking. A systematic review retrieved 688 articles using this term. The systematic analysis revealed an irreducible polysemy covering ten different definitions. It also demonstrated the absence of explicit definition in most of the articles, and even antinomies. A modeling analysis of the various processes described by these ten definitions showed that none of them corresponded to the complete trajectory leading to the emergence of a disease. There is no article demonstrating a mechanism of spillover. There are only ten articles proposing ideas on how a putative spillover could work but they merely are intellectual constructions. All other articles only reuse the term with no demonstration. It is essential to understand that since there is no scientific concept behind the "spillover", it might be dangerous to base public health and public protection against future pandemics on it.

There is no "origin" to SARS-CoV-2.

Since the beginning of the COVID-19 pandemic in 2020 caused by SARS-CoV-2, the question of the origin of this virus has been a highly debated issue. Debates have been, and are still, very disputed and often violent between the two main hypotheses: a natural origin through the "spillover" model or a laboratory-leak origin. Tenants of these two options are building arguments often based on the discrepancies of the other theory. The main problem is that it is the initial question of the origin itself which is biased. Charles Darwin demonstrated in 1859 that all species are appearing through a process of evolution, adaptation and selection. There is no determined origin to any animal or plant species, simply an evolutionary and selective process in which chance and environment play a key role. The very same is true for viruses. There is no determined origin to viruses, simply also an evolutionary and selective process in which chance and environment play a key role. However, in the case of viruses the process is slightly more complex because the "environment" is another living organism. Pandemic viruses already circulate in humans prior to the emergence of a disease. They are simply not capable of triggering an epidemic yet. They must evolve in-host, i.e. in-humans, for that. The evolutionary process which gave rise to SARS-CoV-2 is still ongoing with regular emergence of novel variants more adapted than the previous ones. The real relevant question is how these viruses can emerge as pandemic viruses and what the society can do to prevent the future emergence of pandemic viruses.

Origin of COVID-19: Dismissing the Mojiang mine theory and the laboratory accident narrative.

The origin of SARS-CoV-2 is still the subject of a controversial debate. The natural origin theory is confronted to the laboratory leak theory. The latter is composite and comprises contradictory theories, one being the leak of a naturally occurring virus and the other the leak of a genetically engineered virus. The laboratory leak theory is essentially based on a publication by Rahalkar and Bahulikar in 2020 linking SARS-CoV-2 to the Mojiang mine incident in 2012 during which six miners fell sick and three died. We analyzed the clinical reports. The diagnosis is not that of COVID-19 or SARS. SARS-CoV-2 was not present in the Mojiang mine. We also bring arguments against the laboratory leak narrative.

COVID-19 and emerging infectious diseases: The society is still unprepared for the next pandemic.

The whole human society was caught unprepared by the emergence of SARS-CoV-2 and the related COVID-19 pandemic. This should have not been. We already had on hand all information to organize properly and prevent this emergence. However, this information was never translated into preparedness because the current system of sanitary crises management is not adapted. We keep implementing a medical, symptomatic, post-emergence approach which cannot stop an emerging pandemic. The only preventive action considered is the screening for viruses in the wild but it is not efficient since pandemic viruses do not exist in the wild, and indeed, have never been found. The emergence of a viral pandemic is the result of a double accident: the in-host evolution of the causative virus and its amplification to the epidemic threshold by societal factors. To be prepared the society should target this societal dimension of emerging diseases and organize accordingly. Unfortunately, the society is not organized that way and is still unprepared and vulnerable.

Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia.

BACKGROUND: Plasmodium falciparum malaria is one of the most widespread parasitic infections in humans and remains a leading global health concern. Malaria elimination efforts are threatened by the emergence and spread of resistance to artemisinin-based combination therapy, the first-line treatment of malaria. Promising molecular markers and pathways associated with artemisinin drug resistance have been identified, but the underlying molecular mechanisms of resistance remains unknown. The genomic data from early period of emergence of artemisinin resistance (2008-2011) was evaluated, with aim to define k13 associated genetic background in Cambodia, the country identified as epicentre of anti-malarial drug resistance, through characterization of 167 parasite isolates using a panel of 21,257 SNPs. RESULTS: Eight subpopulations were identified suggesting a process of acquisition of artemisinin resistance consistent with an emergence-selection-diffusion model, supported by the shifting balance theory. Identification of population specific mutations facilitated the characterization of a core set of 57 background genes associated with artemisinin resistance and associated pathways. The analysis indicates that the background of artemisinin resistance was not acquired after drug pressure, rather is the result of fixation followed by selection on the daughter subpopulations derived from the ancestral population. CONCLUSIONS: Functional analysis of artemisinin resistance subpopulations illustrates the strong interplay between ubiquitination and cell division or differentiation in artemisinin resistant parasites. The relationship of these pathways with the P. falciparum resistant subpopulation and presence of drug resistance markers in addition to k13, highlights the major role of admixed parasite population in the diffusion of artemisinin resistant background. The diffusion of resistant genes in the Cambodian admixed population after selection resulted from mating of gametocytes of sensitive and resistant parasite populations.

Valine/isoleucine variants drive selective pressure in the VP1 sequence of EV-A71 enteroviruses.

BACKGROUND: In 2011-2012, Northern Vietnam experienced its first large scale hand foot and mouth disease (HFMD) epidemic. In 2011, a major HFMD epidemic was also reported in South Vietnam with fatal cases. This 2011-2012 outbreak was the first one to occur in North Vietnam providing grounds to study the etiology, origin and dynamic of the disease. We report here the analysis of the VP1 gene of strains isolated throughout North Vietnam during the 2011-2012 outbreak and before. METHODS: The VP1 gene of 106 EV-A71 isolates from North Vietnam and 2 from Central Vietnam were sequenced. Sequence alignments were analyzed at the nucleic acid and protein level. Gene polymorphism was also analyzed. A Factorial Correspondence Analysis was performed to correlate amino acid mutations with clinical parameters. RESULTS: The sequences were distributed into four phylogenetic clusters. Three clusters corresponded to the subgenogroup C4 and the last one corresponded to the subgenogroup C5. Each cluster displayed different polymorphism characteristics. Proteins were highly conserved but three sites bearing only Isoleucine (I) or Valine (V) were characterized. The isoleucine/valine variability matched the clusters. Spatiotemporal analysis of the I/V variants showed that all variants which emerged in 2011 and then in 2012 were not the same but were all present in the region prior to the 2011-2012 outbreak. Some correlation was found between certain I/V variants and ethnicity and severity. CONCLUSIONS: The 2011-2012 outbreak was not caused by an exogenous strain coming from South Vietnam or elsewhere but by strains already present and circulating at low level in North Vietnam. However, what triggered the outbreak remains unclear. A selective pressure is applied on I/V variants which matches the genetic clusters. I/V variants were shown on other viruses to correlate with pathogenicity. This should be investigated in EV-A71. I/V variants are an easy and efficient way to survey and identify circulating EV-A71 strains.

Subtelomere organization in the genome of the microsporidian Encephalitozoon cuniculi: patterns of repeated sequences and physicochemical signatures.

BACKGROUND: The microsporidian Encephalitozoon cuniculi is an obligate intracellular eukaryotic pathogen with a small nuclear genome (2.9 Mbp) consisting of 11 chromosomes. Although each chromosome end is known to contain a single rDNA unit, the incomplete assembly of subtelomeric regions following sequencing of the genome identified only 3 of the 22 expected rDNA units. While chromosome end assembly remains a difficult process in most eukaryotic genomes, it is of significant importance for pathogens because these regions encode factors important for virulence and host evasion. RESULTS: Here we report the first complete assembly of E. cuniculi chromosome ends, and describe a novel mosaic structure of segmental duplications (EXT repeats) in these regions. EXT repeats range in size between 3.5 and 23.8 kbp and contain four multigene families encoding membrane associated proteins. Twenty-one recombination sites were identified in the sub-terminal region of E. cuniculi chromosomes. Our analysis suggests that these sites contribute to the diversity of chromosome ends organization through Double Strand Break repair mechanisms. The region containing EXT repeats at chromosome extremities can be differentiated based on gene composition, GC content, recombination sites density and chromosome landscape. CONCLUSION: Together this study provides the complete structure of the chromosome ends of E. cuniculi GB-M1, and identifies important factors, which could play a major role in parasite diversity and host-parasite interactions. Comparison with other eukaryotic genomes suggests that terminal regions could be distinguished precisely based on gene content, genetic instability and base composition biais. The diversity of processes assciated with chromosome extremities and their biological consequences, as they are presented in the present study, emphasize the fact that great effort will be necessary in the future to characterize more carefully these regions during whole genome sequencing efforts.

Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia.

BACKGROUND: Western Cambodia is recognized as the epicentre of emergence of Plasmodium falciparum multi-drug resistance. The emergence of artemisinin resistance has been observed in this area since 2008-2009 and molecular signatures associated to artemisinin resistance have been characterized in k13 gene. At present, one of the major threats faced, is the possible spread of Asian artemisinin resistant parasites over the world threatening millions of people and jeopardizing malaria elimination programme efforts. To anticipate the diffusion of artemisinin resistance, the identification of the P. falciparum population structure and the gene flow among the parasite population in Cambodia are essential. METHODS: To this end, a mid-throughput PCR-LDR-FMA approach based on LUMINEX technology was developed to screen for genetic barcode in 533 blood samples collected in 2010-2011 from 16 health centres in malaria endemics areas in Cambodia. RESULTS: Based on successful typing of 282 samples, subpopulations were characterized along the borders of the country. Each 11-loci barcode provides evidence supporting allele distribution gradient related to subpopulations and gene flow. The 11-loci barcode successfully identifies recently emerging parasite subpopulations in western Cambodia that are associated with the C580Y dominant allele for artemisinin resistance in k13 gene. A subpopulation was identified in northern Cambodia that was associated to artemisinin (R539T resistant allele of k13 gene) and mefloquine resistance. CONCLUSIONS: The gene flow between these subpopulations might have driven the spread of artemisinin resistance over Cambodia.

Tuberculosis Prevalence Trends from a Predictive Modelling Study - 10 High-Burden Countries, 1980-2035.

What is already known about this topic?: Given the challenges presented by drug-resistant strains of tuberculosis (TB) and the rising mobility of the population, achieving the objective of eradicating TB appears uncertain. What is added by this report?: The examination of TB incidence trends in 10 high-burden countries (HBCs) indicated a steady rise in cases, with India and China jointly accounting for nearly 70% of the burden. Projections for the future show diverse trajectories in these countries, with potential difficulties in reaching the TB elimination target, especially in Nigeria, Congo, and South Africa. What are the implications for public health practice?: The number of TB cases is on the rise. It is crucial to learn from successful strategies to improve TB prevention and control worldwide through collaborative efforts.

A regressive analysis of the main environmental risk factors of human echinococcosis in 370 counties in China.

BACKGROUND: Echinococcosis is a natural focal, highly prevalent disease in China. Factors influencing the spread of echinococcosis are not only related to personal exposure but also closely related to the environment itself. The purpose of this study was to explore the influence of environmental factors on the prevalence of human echinococcosis and to provide a reference for prevention and control of echinococcosis in the future. METHODS: Data were collected from 370 endemic counties in China in 2018. By downloading Modis, DEM and other remote-sensing images in 2018. Data on environmental factors, i.e., elevation, land surface temperature (LST) and normalized difference vegetation index (NDVI) were collected. Rank correlation analysis was conducted between each environmental factor and the prevalence of echinococcosis at the county level. Negative binomial regression was used to analyze the impact of environmental factors on the prevalence of human echinococcosis at the county level. RESULTS: According to rank correlation analysis, the prevalence of human echinococcosis in each county was positively correlated with elevation, negatively correlated with LST, and negatively correlated with NDVI in May, June and July. Negative binomial regression showed that the prevalence of human echinococcosis was negatively correlated with annual LST and summer NDVI, and positively correlated with average elevation and dog infection rate. The prevalence of human cystic echinococcosis was inversely correlated with the annual average LST, and positively correlated with both the average elevation and the prevalence rate of domestic animals. The prevalence of human alveolar echinococcosis was positively correlated with both NDVI in autumn and average elevation, and negatively correlated with NDVI in winter. CONCLUSION: The prevalence of echinococcosis in the population is affected by environmental factors. Environmental risk assessment and prediction can be conducted in order to rationally allocate health resources and improve both prevention and control efficiency of echinococcosis.