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Talaromycosis (penicilliosis) is an invasive mycosis that is endemic in tropical and subtropical Asia. Talaromycosis primarily affects individuals with advanced HIV disease and other immunosuppressive conditions, and the disease disproportionally affects people in low-income and middle-income countries, particularly agricultural workers in rural areas during their most economically productive years. Approximately 17 300 talaromycosis cases and 4900 associated deaths occur annually. Talaromycosis is highly associated with the tropical monsoon season, when flooding and cyclones can exacerbate the poverty-inducing potential of the disease. Talaromycosis can present as localised or disseminated disease, the latter causing cutaneous lesions that are disfiguring and stigmatising. Despite up to a third of diagnosed cases resulting in death, talaromycosis has received little attention and investment from regional and global funders, policy makers, researchers, and industry. Diagnostic and treatment modalities remain extremely insufficient, however control of talaromycosis is feasible with known public health strategies. This Viewpoint is a global call for talaromycosis to be recognised as a neglected tropical disease to alleviate its impact on susceptible populations., Competing Interests: Declaration of interests NPG reports grants from US National Institutes of Health, US Centers for Disease Control and Prevention, the CDC Foundation, the Bill & Melinda Gates Foundation, the UK Medical Research Council, and the South African National Health Laboratory Service Research Trust, outside the submitted work. JF-WC and K-YY have an issued patent on antibodies targeting T marneffei Mp1p proteins and their methods of use. JP reports grants from Merck, Astellas, Pfizer, Amplyx, and Minnetronix; and membership on advisory boards or consulting roles for Merck, Amplyx, Minnetronix, F2G, Scynexis, Ampili, and Matinas, outside the submitted work. TL reports research funding from Gilead Sciences, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Enteroviruses (EVs) species A are a major public health issue in the Asia-Pacific region and cause frequent epidemics of hand, foot and mouth disease (HFMD) in China. Mild infections are common in children; however, HFMD can also cause severe illness that affects the central nervous system. To molecularly characterize EVs, a prospective HFMD virological surveillance program was performed in China between 2013 and 2016. Throat swabs, rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals. EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions (RT-PCRs). Then, the complete VP1 regions of enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16) and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny. Of the 2836 enrolled HFMD patients, 2,517 (89%) were EV positive. The most frequently detected EVs were CVA16 (32.5%, 819), CVA6 (31.2%, 785), and EV-A71 (20.4%, 514). The subgenogroups CVA16_B1b, CVA6_D3a and EV-A71_C4a were predominant in China and recombination was not observed in the VP1 region. Sequence analysis revealed amino acid variations at the 30, 29 and 44 positions in the VP1 region of EV-A71, CVA16 and CVA6 (compared to the respective prototype strains BrCr, G10 and Gdula), respectively. Furthermore, in 21 of 24 (87.5%) identified EV-A71 samples, a known amino acid substitution (D31N) that may enhance neurovirulence was detected. Our study provides insights about the genetic characteristics of common HFMD-associated EVs. However, the emergence and virulence of the described mutations require further investigation.

Bats are a unique group of mammals of the order Chiroptera . They are highly diversified and are the group of mammals with the second largest number of species. Such highly diversified cell types and receptors facilitate them to be potential hosts of a large variety of viruses. Bats are the only group of mammals capable of sustained flight, which enables them to disseminate the viruses they harbor and enhance the chance of interspecies transmission. This article aims at reviewing the various aspects of the global epidemiology of bat coronaviruses (CoVs). Before the SARS epidemic, bats were not known to be hosts for CoVs. In the last 15 years, bats have been found to be hosts of >30 CoVs with complete genomes sequenced, and many more if those without genome sequences are included. Among the four CoV genera, only alphaCoVs and betaCoVs have been found in bats. As a whole, both alphaCoVs and betaCoVs have been detected from bats in Asia, Europe, Africa, North and South America and Australasia; but alphaCoVs seem to be more widespread than betaCoVs, and their detection rate is also higher. For betaCoVs, only those from subgenera Sarbecovirus , Merbecovirus , Nobecovirus and Hibecovirus have been detected in bats. Most notably, horseshoe bats are the reservoir of SARS-CoV, and several betaCoVs from subgenus Merbecovirus are closely related to MERS-CoV. In addition to the interactions among various bat species themselves, bat⁻animal and bat⁻human interactions, such as the presence of live bats in wildlife wet markets and restaurants in Southern China, are important for interspecies transmission of CoVs and may lead to devastating global outbreaks.

Populations of seasonal influenza virus experience strong annual bottlenecks that pose a considerable extinction risk. It has been suggested that an influenza source population located in tropical Southeast or East Asia seeds annual temperate epidemics. Here we investigate the seasonal dynamics and migration patterns of influenza A H3N2 virus by analysis of virus samples obtained from 2003 to 2006 from Australia, Europe, Japan, New York, New Zealand, Southeast Asia, and newly sequenced viruses from Hong Kong. In contrast to annual temperate epidemics, relatively low levels of relative genetic diversity and no seasonal fluctuations characterized virus populations in tropical Southeast Asia and Hong Kong. Bayesian phylogeographic analysis using discrete temporal and spatial characters reveal high rates of viral migration between urban centers tested. Although the virus population that migrated between Southeast Asia and Hong Kong persisted through time, this was dependent on virus input from temperate regions and these tropical regions did not maintain a source for annual H3N2 influenza epidemics. We further show that multiple lineages may seed annual influenza epidemics, and that each region may function as a potential source population. We therefore propose that the global persistence of H3N2 influenza A virus is the result of a migrating metapopulation in which multiple different localities may seed seasonal epidemics in temperate regions in a given year. Such complex global migration dynamics may confound control efforts and contribute to the emergence and spread of antigenic variants and drug-resistant viruses.

Geographical separation of host species has shaped the avian influenza A virus gene pool into independently evolving Eurasian and American lineages, although phylogenetic evidence for gene flow and reassortment indicates that these lineages also mix on occasion. While the evolutionary dynamics of the avian influenza gene pool have been described, the consequences of gene flow on virus evolution and population structure in this system have not been investigated. Here we show that viral gene flow from Eurasia has led to the replacement of endemic avian influenza viruses in North America, likely through competition for susceptible hosts. This competition is characterized by changes in rates of nucleotide substitution and selection pressures. However, the discontinuous distribution of susceptible hosts may produce long periods of co-circulation of competing virus strains before lineage extinction occurs. These results also suggest that viral competition for host resources may be an important mechanism in disease emergence.

The highly pathogenic Asian H5N1 influenza virus that was first detected in Guangdong in the People's Republic of China (China) in 1996 is unique in having spread to humans and other mammalian species. To date, this virus has not consistently transmitted between any mammalian species but the continued spread and evolution of these viruses in domestic poultry across Eurasia presents a continuing pandemic threat. These viruses have caused devastation in domestic poultry and have killed over 60% of infected humans. The H5N1 viruses are unique in having evolved into multiple clades and subclades by reassortment with other influenza viruses in the epicentre of southern China, and accumulation of point mutations has resulted in antigenic differences between the clades. Three waves of spread have occurred, wave one to East Asia and Southeast Asia, wave two through Qinghai Lake, China, to Europe, India and Africa, and wave three to Southeast Asia again. This paper deals with the molecular epidemiology of the evolution of the multiplicity of H5N1 clades. The continuing evolution of these H5N1 viruses and the possible establishment of secondary epicentres in Indonesia, Egypt and Nigeria present a continuing threat to poultry and people globally.

Antigenic profiles of post-2002 H5N1 viruses representing major genetic clades and various geographic sources were investigated using a panel of 17 monoclonal antibodies raised from five H5N1 strains. Four antigenic groups from seven clades of H5N1 virus were distinguished and characterized based on their cross-reactivity to the monoclonal antibodies in hemagglutination inhibition and cell-based neutralization assays. Genetic polymorphisms associated with the variation of antigenicity of H5N1 strains were identified and further verified in antigenic analysis with recombinant H5N1 viruses carrying specific mutations in the hemagglutinin protein. Modification of some of these genetic variations produced marked improvement to the immunogenicity and cross-reactivity of H5N1 strains in assays utilizing monoclonal antibodies and ferret antisera raised against clade 1 and 2 H5N1 viruses, suggesting that these sites represent antigenically significant amino acids. These results provide a comprehensive antigenic profile for H5N1 virus strains circulating in recent years and will facilitate the recognition of emerging antigenic variants of H5N1 virus and aid in the selection of vaccine strains.

Avian influenza infections by high and low pathogenicity H7 influenza viruses have caused several outbreaks in European poultry in recent years, also resulting in human infections. Although in some cases the source of H7 strains from domestic poultry was shown to be the viruses circulating in the wild bird reservoir, a thorough characterization of the entire genome of H7 viruses from both wild and domestic Eurasian birds, and their evolutionary relationships, has not been conducted. In our study, we have analysed low pathogenicity H7 influenza strains isolated from wild and domestic ducks in Italy and southern China and compared them with those from reared terrestrial poultry such as chicken and turkey. Phylogenetic analysis demonstrated that the H7 haemagglutinin genes were all closely related to each other, whereas the remaining genes could be divided into two or more phylogenetic groups. Almost each year different H7 reassortant viruses were identified and in at least two different years more than one H7 genotype co-circulated. A recent precursor in wild waterfowl was identified for most of the gene segments of terrestrial poultry viruses. Our data suggest that reassortment allows avian influenza viruses, in their natural reservoir, to increase their genetic diversity. In turn this might help avian influenza viruses colonize a wider range of hosts, including domestic poultry.

We examined the distribution of genetic mutations associated with resistance to the M2 ion channel-blocking adamantane derivatives, amantadine and rimantadine, among H5N1 viruses isolated in Vietnam, Thailand, Cambodia, Indonesia, Hong Kong, and China. More than 95% of the viruses isolated in Vietnam and Thailand contained resistance mutations, but resistant mutants were less commonly isolated in Indonesia (6.3% of isolates) and China (8.9% of isolates), where human infection was recently reported. The dual mutation motif Leu26Ile-Ser31Asn (leucine-->isoleucine at aa 26 and serine-->asparagine at aa 31) was found almost exclusively in all resistant isolates from Vietnam, Thailand, and Cambodia, suggesting the biological selection of these mutations.