[Show abstract][Hide abstract] ABSTRACT: The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence.
[Show abstract][Hide abstract] ABSTRACT: It is currently unclear whether changes in viral communities will ever be predictable. Here we investigate whether viral communities in wildlife are inherently structured (inferring predictability) by looking at whether communities are assembled through deterministic (often predictable) or stochastic (not predictable) processes. We sample macaque faeces across nine sites in Bangladesh and use consensus PCR and sequencing to discover 184 viruses from 14 viral families. We then use network modelling and statistical null-hypothesis testing to show the presence of non-random deterministic patterns at different scales, between sites and within individuals. We show that the effects of determinism are not absolute however, as stochastic patterns are also observed. In showing that determinism is an important process in viral community assembly we conclude that it should be possible to forecast changes to some portion of a viral community, however there will always be some portion for which prediction will be unlikely.
[Show abstract][Hide abstract] ABSTRACT: Macacine herpesvirus 1 (MaHV1; B virus) naturally infects macaques (Macaca spp.) and can cause fatal encephalitis in humans. In Peninsular Malaysia, wild macaques are abundant, and translocation is used to mitigate human-macaque conflict. Most adult macaques are infected with MaHV1, although the risk for transmission to persons who handle them during capture and translocation is unknown. We investigated MaHV1 shedding among 392 long-tailed macaques (M. fascicularis) after capture and translocation by the Department of Wildlife and National Parks in Peninsular Malaysia, during 2009-2011. For detection of MaHV1 DNA, PCR was performed on urogenital and oropharyngeal swab samples. Overall, 39% of macaques were shedding MaHV1 DNA; rates of DNA detection did not differ between sample types. This study demonstrates that MaHV1 was shed by a substantial proportion of macaques after capture and transport and suggests that persons handling macaques under these circumstances might be at risk for exposure to MaHV1.
[Show abstract][Hide abstract] ABSTRACT: HCV genotype 4 is prevalent in many African countries, yet little is known about the genotype׳s epidemic history on the continent. We present a comprehensive study of the molecular epidemiology of genotype 4. To address the deficit of data from the Democratic Republic of the Congo (DRC) we PCR amplified 60 new HCV isolates from the DRC, resulting in 33 core- and 48 NS5B-region sequences. Our data, together with genotype 4 database sequences, were analysed using Bayesian phylogenetic approaches. We find three well-supported intra-genotypic lineages and estimate that the genotype 4 common ancestor existed around 1733 (1650–1805). We show that genotype 4 originated in central Africa and that multiple lineages have been exported to north Africa since ~1850, including subtype 4a which dominates the epidemic in Egypt. We speculate on the causes of the historical intra-continental spread of genotype 4, including population movements during World War 2.
[Show abstract][Hide abstract] ABSTRACT: Zoonotic transmission of lethal henipaviruses (HNVs) from their natural fruit bat reservoirs to humans has only been reported in Australia and South/Southeast Asia. However, a recent study discovered numerous HNV clades in African bat samples. To determine the potential for HNV spillover events among humans in Africa, here we examine well-curated sets of bat (Eidolon helvum, n=44) and human (n=497) serum samples from Cameroon for Nipah virus (NiV) cross-neutralizing antibodies (NiV-X-Nabs). Using a vesicular stomatitis virus (VSV)-based pseudoparticle seroneutralization assay, we detect NiV-X-Nabs in 48% and 3-4% of the bat and human samples, respectively. Seropositive human samples are found almost exclusively in individuals who reported butchering bats for bushmeat. Seropositive human sera also neutralize Hendra virus and Gh-M74a (an African HNV) pseudoparticles, as well as live NiV. Butchering bat meat and living in areas undergoing deforestation are the most significant risk factors associated with seropositivity. Evidence for HNV spillover events warrants increased surveillance efforts.
[Show abstract][Hide abstract] ABSTRACT: Background
Foamy viruses (FVs) are a unique subfamily of retroviruses that are widely distributed in mammals. Owing to the availability of sequences from diverse mammals coupled with their pattern of codivergence with their hosts, FVs have one of the best-understood viral evolutionary histories ever documented, estimated to have an ancient origin. Nonetheless, our knowledge of some parts of FV evolution, notably that of prosimian and afrotherian FVs, is far from complete due to the lack of sequence data.
Here, we report the complete genome of the first extant prosimian FV (PSFV) isolated from a lorisiforme galago (PSFVgal), and a novel partial endogenous viral element with high sequence similarity to FVs, present in the afrotherian Cape golden mole genome (ChrEFV). We also further characterize a previously discovered endogenous PSFV present in the aye-aye genome (PSFVaye). Using phylogenetic methods and available FV sequence data, we show a deep divergence and stable co-evolution of FVs in eutherian mammals over 100 million years. Nonetheless, we found that the evolutionary histories of bat, aye-aye, and New World monkey FVs conflict with the evolutionary histories of their hosts. By combining sequence analysis and biogeographical knowledge, we propose explanations for these mismatches in FV-host evolutionary history.
Our discovery of ChrEFV has expanded the FV host range to cover the whole eutherian clade, and our evolutionary analyses suggest a stable mammalian FV-host co-speciation pattern which extends as deep as the exafroplacentalian basal diversification. Nonetheless, two possible cases of host switching were observed. One was among New World monkey FVs, and the other involves PSFVaye and a bat FV which may involve cross-species transmission at the level of mammalian orders. Our results highlight the value of integrating multiple sources of information to elucidate the evolutionary history of viruses, including continental and geographical histories, ancestral host locations, in addition to the natural history of host and virus.
Electronic supplementary material
The online version of this article (doi:10.1186/1742-4690-11-61) contains supplementary material, which is available to authorized users.
[Show abstract][Hide abstract] ABSTRACT: Non-primate hepacivirus (NPHV), equine pegivirus (EPgV) and Theiler's disease associated virus (TDAV) are newly discovered members of two genera in the Flaviviridae family, Hepacivirus and Pegivirus respectively, that include human hepatitis C virus (HCV) and human pegivirus (HPgV). To investigate their epidemiology, persistence and clinical features of infection, large cohorts of horses and other mammalian species were screened for NPHV, EPgV and TDAV viraemia and for past exposure through serological assays for NPHV and EPgV-specific antibodies. NPHV antibodies were detected in 43% of 328 horses screened for antibodies to NS3 and core antibodies, of which three were viraemic by PCR. All five horses that were stablemates of a viraemic horse were seropositive, as was a dog on the same farm. With this single exception, all other species were negative for NPHV antibodies and viraemia (donkeys (n=100), dogs (n=112), cats (n=131), non-human primates (n=164) and humans (n=362). EPgV antibodies to NS3 were detected in 66.5% of horses, including 11 of the 12 horses that had EPgV viraemia. All donkey samples were negative for EPgV antibody and RNA. All horse and donkey samples were negative for TDAV RNA. By comparing viraemia frequencies in horses with and without liver disease, no evidence was obtained that supported an association between active NPHV and EPgV infections with hepatopathy. The study demonstrates that NPHV and EPgV infections are widespread and enzootic in the study horse population and confirms that NPHV and potentially EPgV have higher frequencies of viral clearance than HCV and HPgV infections in humans.
Journal of General Virology 05/2014; 95(Pt_8). DOI:10.1099/vir.0.065094-0 · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa.
[Show abstract][Hide abstract] ABSTRACT: Monkeypox virus is a zoonotic virus endemic to Central Africa. Although active disease surveillance has assessed monkeypox disease prevalence and geographic range, information about virus diversity is lacking. We therefore assessed genome diversity of viruses in 60 samples obtained from humans with primary and secondary cases of infection from 2005 through 2007. We detected 4 distinct lineages and a deletion that resulted in gene loss in 10 (16.7%) samples and that seemed to correlate with human-to-human transmission (p = 0.0544). The data suggest a high frequency of spillover events from the pool of viruses in nonhuman animals, active selection through genomic destabilization and gene loss, and increased disease transmissibility and severity. The potential for accelerated adaptation to humans should be monitored through improved surveillance.
[Show abstract][Hide abstract] ABSTRACT: Of the seven known species of human retroviruses only one, human T-cell lymphotropic virus type 4 (HTLV-4), lacks a known animal reservoir. We report the largest screening for simian T-cell lymphotropic virus (STLV-4) to date in a wide range of captive and wild non-human primate (NHP) species from Cameroon. Among the 681 wild and 426 captive NHPs examined, we detected STLV-4 infection only among gorillas by using HTLV-4-specific quantitative polymerase chain reaction. The large number of samples analyzed, the diversity of NHP species examined, the geographic distribution of infected animals relative to the known HTLV-4 case, as well as detailed phylogenetic analyses on partial and full genomes, indicate that STLV-4 is endemic to gorillas, and that rather than being an ancient virus among humans, HTLV-4 emerged from a gorilla reservoir, likely through the hunting and butchering of wild gorillas. Our findings shed further light on the importance of gorillas as keystone reservoirs for the evolution and emergence of human infectious diseases and provide a clear course for preventing HTLV-4 emergence through management of human contact with wild gorillas, the development of improved assays for HTLV-4/STLV-4 detection and the ongoing monitoring of STLV-4 among gorillas and for HTLV-4 zoonosis among individuals exposed to gorilla populations.
[Show abstract][Hide abstract] ABSTRACT: Climate change is predicted to result in changes in the geographic ranges and local prevalence of infectious diseases, either through direct effects on the pathogen, or indirectly through range shifts in vector and reservoir species. To better understand the occurrence of monkeypox virus (MPXV), an emerging Orthopoxvirus in humans, under contemporary and future climate conditions, we used ecological niche modeling techniques in conjunction with climate and remote-sensing variables. We first created spatially explicit probability distributions of its candidate reservoir species in Africa's Congo Basin. Reservoir species distributions were subsequently used to model current and projected future distributions of human monkeypox (MPX). Results indicate that forest clearing and climate are significant driving factors of the transmission of MPX from wildlife to humans under current climate conditions. Models under contemporary climate conditions performed well, as indicated by high values for the area under the receiver operator curve (AUC), and tests on spatially randomly and non-randomly omitted test data. Future projections were made on IPCC 4(th) Assessment climate change scenarios for 2050 and 2080, ranging from more conservative to more aggressive, and representing the potential variation within which range shifts can be expected to occur. Future projections showed range shifts into regions where MPX has not been recorded previously. Increased suitability for MPX was predicted in eastern Democratic Republic of Congo. Models developed here are useful for identifying areas where environmental conditions may become more suitable for human MPX; targeting candidate reservoir species for future screening efforts; and prioritizing regions for future MPX surveillance efforts.
PLoS ONE 07/2013; 8(7):e66071. DOI:10.1371/journal.pone.0066071 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As part of a virus discovery investigation using a metagenomic approach, a highly divergent novel Human papillomavirus type was identified in pooled convenience nasal/oropharyngeal swab samples collected from patients with febrile respiratory illness. Phylogenetic analysis of the whole genome and the L1 gene reveals that the new HPV identified in this study clusters with previously described gamma papillomaviruses, sharing only 61.1% (whole genome) and 63.1% (L1) sequence identity with its closest relative in the Papillomavirus episteme (PAVE) database. This new virus was named HPV_SD2 pending official classification. The complete genome of HPV-SD2 is 7,299 bp long (36.3% G/C) and contains 7 open reading frames (L2, L1, E6, E7, E1, E2 and E4) and a non-coding long control region (LCR) between L1 and E6. The metagenomic procedures, coupled with the bioinformatic methods described herein are well suited to detect small circular genomes such as those of human papillomaviruses.
PLoS ONE 03/2013; 8(3):e58404. DOI:10.1371/journal.pone.0058404 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevalence and genetic diversity of hepatitis C virus (HCV) and human pegivirus (HPgV) in many regions of sub-Saharan Africa is poorly characterized, including in the Democratic Republic of Congo - the largest country in the region and one of the most populous. To address this situation we conducted a molecular epidemiological survey of HCV and HPgV (previously named GB Virus C or hepatitis G virus) in samples collected in 2007 from 299 males from the DRC, whose ages ranged from 21 to 71years old. Samples were tested for the presence of HCV antibodies by ELISA reactive samples were subsequently tested for HCV RNA using RT-PCR in which both the HCV Core and NS5B genome regions were amplified. Remaining samples were tested for HPgV RNA and the HPgV NS3 genome region of positive samples was amplified. For HCV, 13.7% of the samples were seropositive (41/299) but only 3.7% were viremic (11/299). HPgV RNA was found in 12.7% (33/259) of samples. HCV viremia was strongly associated with age; the percentage of samples that contained detectable HCV RNA was ∼0.5% in those younger than 50 and 13% in those older than 50. Our study represents the first systematic survey of HCV genetic diversity in the DRC. HCV sequences obtained belonged to diverse lineages of genotype 4, including subtypes 4c, 4k, 4l and 4r, plus one unclassified lineage that may constitute a new subtype. These data suggest that HCV in the DRC exhibits an age 'cohort effect', as has been recently reported in neighbouring countries, and are consistent with the hypothesis that HCV transmission rates were higher in the mid-twentieth century, possibly as a result of parenteral, iatrogenic, or other unidentified factors. Different HCV subtypes were associated with individuals of different ages, implying that HCV infection in the DRC may have arisen through multiple separate HCV epidemics with different causes.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 02/2013; 19. DOI:10.1016/j.meegid.2013.01.021 · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Zoonotic transmission of simian retroviruses in Central Africa is ongoing and can result in pandemic human infection. While simian foamy virus (SFV) infection was reported in primate hunters in Cameroon and Gabon, little is known about the distribution of SFV in Africa and whether human-to-human transmission and disease occur. We screened 3,334 plasmas from persons living in rural villages in central Democratic Republic of Congo (DRC) using SFV-specific EIA and Western blot (WB) tests. PCR amplification of SFV polymerase sequences from DNA extracted from buffy coats was used to measure proviral loads. Phylogenetic analysis was used to define the NHP species origin of SFV. Participants completed questionnaires to capture NHP exposure information.
Sixteen (0.5%) samples were WB-positive; 12 of 16 were from women (75%, 95% confidence limits 47.6%, 92.7%). Sequence analysis detected SFV in three women originating from Angolan colobus or red-tailed monkeys; both monkeys are hunted frequently in DRC. NHP exposure varied and infected women lived in distant villages suggesting a wide and potentially diverse distribution of SFV infections across DRC. Plasmas from 22 contacts of 8 WB-positive participants were all WB negative suggesting no secondary viral transmission. Proviral loads in the three women ranged from 14 – 1,755 copies/105 cells.
Our study documents SFV infection in rural DRC for the first time and identifies infections with novel SFV variants from Colobus and red-tailed monkeys. Unlike previous studies, women were not at lower risk for SFV infection in our population, providing opportunities for spread of SFV both horizontally and vertically. However, limited testing of close contacts of WB-positive persons did not identify human-to-human transmission. Combined with the broad behavioral risk and distribution of NHPs across DRC, our results suggest that SFV infection may have a wider geographic distribution within DRC. These results also reinforce the potential for an increased SFV prevalence throughout the forested regions of Africa where humans and simians co-exist. Our finding of endemic foci of SFV infection in DRC will facilitate longitudinal studies to determine the potential for person-to-person transmissibility and pathogenicity of these zoonotic retroviral infections.
[Show abstract][Hide abstract] ABSTRACT: Although the origin of hepatitis C virus (HCV) remains undetermined, a close homolog of HCV found in dogs, canine hepacivirus (CHV), provides evidence for a wider distribution of hepaciviruses in mammals in a study that determined frequencies of active infection among dogs and other mammals in the United Kingdom. Samples from dogs (46 respiratory, 99 plasma, 45 autopsy samples) were uniformly PCR negative for CHV. Wider screening of 362 samples from cats, horses, donkeys, rodents, and pigs identified 142 positive results; 3 (2%) of those were from horses. These samples were genetically divergent from CHV and nonprimate hepaciviruses (NPHVs) that horses were infected with during 2012 in New York State, United States. Investigation of infected horses demonstrated NPHV persistence, high viral loads (105–107 RNA copies/mL) in plasma, and frequently normal liver function tests, although several values were in the upper normal or mildly elevated range. Disease associations and host range of NPHVs require further investigatio
[Show abstract][Hide abstract] ABSTRACT: TO THE EDITOR: Bats are hosts for various emerging viruses, including the zoonotic paramyxoviruses Hendra virus and Nipah virus, which occur in Australia and Southeast Asia, respectively, and cause severe disease outbreaks among humans and livestock (1). Antibodies and henipavirus-related RNA have also been found in the straw-colored fruit bat, Eidolon helvum, in Ghana, West Africa (2,3). These bats are a chief protein source for humans in sub-Saharan Africa and are therefore targeted by hunters (4,5). This practice raises special concern about the risk for virus transmission from bats to humans.
[Show abstract][Hide abstract] ABSTRACT: Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09×10(6) RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ∼140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of >1∶1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa.