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Male lower urinary tract symptoms (LUTS) comprise a common syndrome of aging that negatively impacts quality of life. The etiology of LUTS is multifactorial, involving benign prostatic hyperplasia, smooth muscle and neurologic dysfunction, inflammation, sexually transmitted infections, fibrosis, and potentially dysbiosis, but this aspect remains poorly explored. We investigated whether the presence of infectious agents in urine might be associated with LUTS by combining next-generation DNA sequencing for virus discovery, microbiome analysis for characterization of bacterial communities, and mass spectrometry-based metabolomics. In urine from 29 LUTS cases and 9 controls from Wisconsin, we found a statistically significant association between a diagnosis of LUTS and the presence of JC virus (JCV), a common neurotropic human polyomavirus (Polyomaviridae,Betapolyomavirus) linked to severe neurologic disease in rare cases. This association (based on metagenomics) was not borne out when specific polymerase chain reaction (PCR) testing was applied to this set of samples, likely due to the greater sensitivity of PCR. Interestingly, urine metabolomics analysis identified dysregulation of metabolites associated with key LUTS processes. Microbiome analysis found no evidence of microbial community dysbiosis in LUTS cases, but JCV-positive samples contained moreAnaerococcusspecies, which are involved in polymicrobial infections of the urinary tract. Neither age nor body mass index were significantly associated with the presence of urinary JCV—in the initial group or in an additional, regionally distinct group. These data provide preliminary support the hypothesis that viruses such as JCV may play a role in the development or progression of LUTS, together with other infectious agents and host metabolic responses.

Syndromic surveillance, the collection of symptom data from individuals prior to or in the absence of diagnosis, is used throughout the developed world to provide rapid indications of outbreaks and unusual patterns of disease. However, the low cost of syndromic surveillance also makes it highly attractive for the developing world. We present a case study of electronic participatory syndromic surveillance, using participant-mobile phones in a rural region of Western Uganda, which has a high infectious disease burden, and frequent local and regional outbreaks. Our platform uses text messages to encode a suite of symptoms, their associated durations, and household disease burden, and we explore the ability of participants to correctly encode their symptoms, with an average of 75.2% of symptom reports correctly formatted between the second and 11th reporting timeslots. Concomitantly we identify divisions between participants able to rapidly adjust to this unusually participatory style of data collection, and those few for whom the study proved more challenging. We then perform analyses of the resulting syndromic time series, examining the clustering of symptoms by time and household to identify patterns such as a tendency towards the within-household sharing of respiratory illness.

Key biological properties such as high genetic diversity and high evolutionary rate enhance the potential of certain RNA viruses to adapt and emerge. Identifying viruses with these properties in their natural hosts could dramatically improve disease forecasting and surveillance. Recently, we discovered two novel members of the viral family Arteriviridae: simian hemorrhagic fever virus (SHFV)-krc1 and SHFV-krc2, infecting a single wild red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. Nearly nothing is known about the biological properties of SHFVs in nature, although the SHFV type strain, SHFV-LVR, has caused devastating outbreaks of viral hemorrhagic fever in captive macaques. Here we detected SHFV-krc1 and SHFV-krc2 in 40% and 47% of 60 wild red colobus tested, respectively. We found viral loads in excess of 1x10^6-1x10^7 RNA copies per milliliter of blood plasma for each of these viruses. SHFV-krc1 and SHFV-krc2 also showed high genetic diversity at both the inter- and intra-host levels. Analyses of synonymous and non-synonymous nucleotide diversity across viral genomes revealed patterns suggestive of positive selection in SHFV open reading frames (ORF) 5 (SHFV-krc2 only) and 7 (SHFV-krc1 and SHFV-krc2). Thus, these viruses share several important properties with some of the most rapidly evolving, emergent RNA viruses.

Substantial research has shown that while some parasite infections can be fatal to hosts, most infections are sub-clinical and non-lethal. Such sub-clinical infections can nonetheless have negative consequences for the long-term fitness of the host such as reducing juvenile growth and the host's ability to compete for food and mates. With such effects, infected individuals are expected to exhibit behavioural changes. Here we use a parasite removal experiment to quantify how gastrointestinal parasite infections affect the behaviour of vervet monkeys (Chlorocebus aethiops) at Lake Nabugabo, Uganda. Behavioural profiles and the structure of nearest neighbour relationships varied significantly. As predicted, after deworming the duration of the resting events decreased, which is consistent with the idea that parasite infections are energetically costly. In contrast to what was predicted, we could not reject the null hypothesis and we observed no change in either the frequency or duration of grooming, but we found that the duration of travel events increased. A network analysis revealed that after deworming, individuals tended to have more nearest neighbours and hence probably more frequent interactions, with this effect being particularly marked for juveniles. The heightened response by juveniles may indicate that they are avoiding infected individuals more than other age classes because it is too costly to move energy away from growth. We consider that populations with high parasite burden may have difficulties developing social networks and behaviours that could have cascading effects that impact the population in general.

Simian hemorrhagic fever (SHF) is an often lethal disease of Asian macaques. Simian hemorrhagic fever virus (SHFV) is one of at least three distinct simian arteriviruses that can cause SHF, but pathogenesis studies using modern methods have been scarce. Even seemingly straightforward studies, such as examining viral tissue and cell tropism in vivo, have been difficult to conduct due to the absence of standardized SHFV-specific reagents. Here we report the establishment of an in situ hybridization assay for the detection of SHFV and distantly related Kibale red colobus virus 1 (KRCV-1) RNA in cell culture. In addition, we detected SHFV RNA in formalin-fixed, paraffin-embedded tissues from an infected rhesus monkey (Macaca mulatta). The assay is easily performed and can clearly distinguish between SHFV and KRCV-1. Thus, if further developed, this assay may be useful during future studies evaluating the mechanisms by which a simian arterivirus with a restricted cell tropism can cause a lethal nonhuman primate disease similar in clinical presentation to human viral hemorrhagic fevers.

Background Simian hemorrhagic fever virus (SHFV) has caused lethal outbreaks of hemorrhagic disease in captive primates, but its distribution in wild primates has remained obscure. Here, we describe the discovery and genetic characterization by direct pyrosequencing of two novel, divergent SHFV variants co-infecting a single male red colobus monkey from Kibale National Park, Uganda. Methodology/Principal Findings The viruses were detected directly from blood plasma using pyrosequencing, without prior virus isolation and with minimal PCR amplification. The two new SHFV variants, SHFV-krc1 and SHFV-krc2 are highly divergent from each other (51.9% nucleotide sequence identity) and from the SHFV type strain LVR 42-0/M6941 (52.0% and 51.8% nucleotide sequence identity, respectively) and demonstrate greater phylogenetic diversity within SHFV than has been documented within any other arterivirus. Both new variants nevertheless have the same 3′ genomic architecture as the type strain, containing three open reading frames not present in the other arteriviruses. Conclusions/Significance These results represent the first documentation of SHFV in a wild primate and confirm the unusual 3′ genetic architecture of SHFV relative to the other arteriviruses. They also demonstrate a degree of evolutionary divergence within SHFV that is roughly equivalent to the degree of divergence between other arterivirus species. The presence of two such highly divergent SHFV variants co-infecting a single individual represents a degree of within-host viral diversity that exceeds what has previously been reported for any arterivirus. These results expand our knowledge of the natural history and diversity of the arteriviruses and underscore the importance of wild primates as reservoirs for novel pathogens.

Background: Host-associated microbes comprise an integral part of animal digestive systems and these interactions have a long evolutionary history. It has been hypothesized that the gastrointestinal microbiome of humans and other non-human primates may have played significant roles in host evolution by facilitating a range of dietary adaptations. We have undertaken a comparative sequencing survey of the gastrointestinal microbiomes of several non-human primate species, with the goal of better understanding how these microbiomes relate to the evolution of non-human primate diversity. Here we present a comparative analysis of gastrointestinal microbial communities from three different species of Old World wild monkeys. Methodology/Principal Findings: We analyzed fecal samples from three different wild non-human primate species (blackand-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and red-tailed guenon [Cercopithecus ascanius]). Three samples from each species were subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast majority of the phyla in each sample. Other phyla represented were Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia, Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. BrayCurtis similarity analysis of these microbiomes indicated that microbial community composition within the same primate species are more similar to each other than to those of different primate species. Comparison of fecal microbiota from nonhuman primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny. Conclusion/Significance: Our analysis provides evidence that the fecal microbiomes of wild primates co-vary with their hosts, and that this is manifested in higher intraspecies similarity among wild primate species, perhaps reflecting species specificity of the microbiome in addition to dietary influences. These results contribute to the limited body of primate microbiome studies and provide a framework for comparative microbiome analysis between human and non-human primates as well as a comparative evolutionary understanding of the human microbiome. Citation: Yildirim S, Yeoman CJ, Sipos M, Torralba M, Wilson BA, et al. (2010) Characterization of the Fecal Microbiome from Non-Human Wild Primates Reveals

Within the Flaviviridae, the recently designated genus Pegivirus has expanded greatly due to new discoveries in bats, horses, and rodents. Here we report the discovery and characterization of three simian pegiviruses (SPgV) that resemble human pegivirus (HPgV) and infect red colobus monkeys (Procolobus tephrosceles), red-tailed guenons (Cercopithecus ascanius) and an olive baboon (Papio anubis). We have designated these viruses SPgVkrc, SPgVkrtg and SPgVkbab, reflecting their host species' common names, which include reference to their location of origin in Kibale National Park, Uganda. SPgVkrc and SPgVkrtg were detected in 47% (28/60) of red colobus and 42% (5/12) red-tailed guenons, respectively, while SPgVkbab infection was observed in 1 of 23 olive baboons tested. Infections were not associated with any apparent disease, despite the generally high viral loads observed for each variant. These viruses were monophyletic and equally divergent from HPgV and pegiviruses previously identified in chimpanzees (SPgVcpz). Overall, the high degree of conservation of genetic features among the novel SPgVs, HPgV and SPgVcpz suggests conservation of function among these closely related viruses. Our study describes the first primate pegiviruses detected in Old World monkeys, expanding the known genetic diversity and host range of pegiviruses and providing insight into the natural history of this genus.

The influence of host diversity on multi-host pathogen transmission and persistence can be confounded by the large number of species and biological interactions that can characterize many transmission systems. For vector-borne pathogens, the composition of host communities has been hypothesized to affect transmission; however, the specific characteristics of host communities that affect transmission remain largely unknown. We tested the hypothesis that vector host use and force of infection (i.e., the summed number of infectious mosquitoes resulting from feeding upon each vertebrate host within a community of hosts), and not simply host diversity or richness, determine local infection rates of West Nile virus (WNV) in mosquito vectors. In suburban Chicago, Illinois, USA, we estimated community force of infection for West Nile virus using data on Culex pipiens mosquito host selection and WNV vertebrate reservoir competence for each host species in multiple residential and semi-natural study sites. We found host community force of infection interacted with avian diversity to influence WNV infection in Culex mosquitoes across the study area. Two avian species, the American robin (Turdus migratorius) and the house sparrow (Passer domesticus), produced 95.8% of the infectious Cx. pipiens mosquitoes and showed a significant positive association with WNV infection in Culex spp. mosquitoes. Therefore, indices of community structure, such as species diversity or richness, may not be reliable indicators of transmission risk at fine spatial scales in vector-borne disease systems. Rather, robust assessment of local transmission risk should incorporate heterogeneity in vector host feeding and variation in vertebrate reservoir competence at the spatial scale of vector-host interaction. La influencia de la diversidad de hospedadores en la transmisión y persistencia de patógenos de múltiples hospedadores puede verse confundida por el gran número de especies e interacciones biológicas que pueden caracterizar muchos sistemas de transmisión. En el caso de los patógenos transmitidos por vectores, se ha planteado la hipótesis de que la composición de las comunidades de hospedadores afecta a la transmisión; sin embargo, las características específicas de las comunidades de hospedadores que afectan a la transmisión siguen siendo en gran medida desconocidas. Hemos comprobado la hipótesis de que el uso de los hospedadores por parte de los vectores y la fuerza de infección (es decir, el número sumado de mosquitos infecciosos resultante de alimentarse de cada hospedador vertebrado dentro de una comunidad de hospedadores), y no simplemente la diversidad o riqueza de hospedadores, determinan las tasas locales de infección del virus del Nilo Occidental (VNO) en los mosquitos vectores. En los suburbios de Chicago, Illinois, EE.UU., estimamos la fuerza de infección comunitaria del virus del Nilo Occidental utilizando datos sobre la selección de hospedadores del mosquito Culex pipiens y la competencia de los reservorios vertebrados del VNO para cada especie de hospedador en múltiples lugares de estudio residenciales y seminaturales. Encontramos que la fuerza de infección de la comunidad de hospedadores interactuó con la diversidad aviar para influir en la infección del VNO en los mosquitos Culex en toda el área de estudio. Dos especies de aves, el petirrojo americano (Turdus migratorius) y el gorrión doméstico (Passer domesticus), produjeron el 95,8% de los mosquitos Cx. pipiens infecciosos y mostraron una asociación positiva significativa con la infección del VNO en los mosquitos Culex spp. Por lo tanto, los índices de la estructura de la comunidad, como la diversidad o la riqueza de especies, pueden no ser indicadores fiables del riesgo de transmisión a escalas espaciales finas en los sistemas de enfermedades transmitidas por vectores. Más bien, una evaluación sólida del riesgo de transmisión local debería incorporar la heterogeneidad en la alimentación del huésped vectorial y la variación en la competencia de los reservorios vertebrados a la escala espacial de la interacción entre el vector y el huésped. Universidad Nacional, Costa Rica. Escuela de Medicina Veterinaria