North American Prodrome Longitudinal Study (NAPLS 2) The Prodromal Symptoms

In studies describing the long-term follow-up up of youth at clinical high risk (CHR) of psychosis, little attention has been given to details of specific prodromal symptoms. In this paper, we describe the prodromal symptoms of 764 CHR participants recruited in the multi-site North American Prodrome Longitudinal Study (NAPLS). Symptoms were rated on the Scale of Prodromal Symptoms (SOPS) at baseline and 6-, 12-, 18-, and 24-month follow-ups. Clinical outcome at the 2-year assessment was categorized as psychotic, prodromal progression, symptomatic or in remission. Most of the CHR sample (92%) met criteria for the attenuated positive symptoms syndrome (APSS). Significant improvements in SOPS symptoms were observed over time. Unusual thought content, disorganized communication, and overall ratings on disorganized symptoms differentiated those who transitioned to psychosis from the other clinical outcome groups. Suspiciousness and total positive symptoms differentiated those in remission from the other clinical outcome groups

Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia

Avian influenza viruses (AIVs) periodically cross species barriers and infect humans. The likelihood that an AIV will evolve mammalian transmissibility depends on acquiring and selecting mutations during spillover, but data from natural infection is limited. We analyze deep sequencing data from infected humans and domestic ducks in Cambodia to examine how H5N1 viruses evolve during spillover. Overall, viral populations in both species are predominated by low-frequency (5% frequency within-host. However, short infection times, genetic drift, and purifying selection likely restrict their ability to evolve extensively during a single infection. Applying evolutionary methods to sequence data, we reveal a detailed view of H5N1 virus adaptive potential, and develop a foundation for studying host-adaptation in other zoonotic viruses

Influenza activity in Cambodia during 2006-2008

<p>Abstract</p> <p>Background</p> <p>There is little information about influenza disease among the Cambodian population. To better understand the dynamics of influenza in Cambodia, the Cambodian National Influenza Center (NIC) was established in August 2006. To continuously monitor influenza activity, a hospital based sentinel surveillance system for ILI (influenza like illness) with a weekly reporting and sampling scheme was established in five sites in 2006. In addition, hospital based surveillance of acute lower respiratory infection (ALRI) cases was established in 2 sites.</p> <p>Methods</p> <p>The sentinel sites collect weekly epidemiological data on ILI patients fulfilling the case definition, and take naso-pharyngeal specimens from a defined number of cases per week. The samples are tested in the Virology Unit at the Institut Pasteur in Phnom Penh. From each sample viral RNA was extracted and amplified by a multiplex RT-PCR detecting simultaneously influenza A and influenza B virus. Influenza A viruses were then subtyped and analyzed by hemagglutination inhibition assay. Samples collected by the ALRI system were tested with the same approach.</p> <p>Results</p> <p>From 2006 to 2008, influenza circulation was observed mainly from June to December, with a clear seasonal peak in October shown in the data from 2008.</p> <p>Conclusion</p> <p>Influenza activity in Cambodia occurred during the rainy season, from June to December, and ended before the cool season (extending usually from December to February). Although Cambodia is a tropical country geographically located in the northern hemisphere, influenza activity has a southern hemisphere transmission pattern. Together with the antigenic analysis of the circulating strains, it is now possible to give better influenza vaccination recommendation for Cambodia.</p

Transmission experiments support clade-level differences in the transmission and pathogenicity of Cambodian influenza A/H5N1 viruses

Influenza A/H5N1 has circulated in Asia since 2003 and is now enzootic in many countries in that region. In Cambodia, the virus has circulated since 2004 and has intermittently infected humans. During this period, we have noted differences in the rate of infections in humans, potentially associated with the circulation of different viral clades. In particular, a reassortant clade 1.1.2 virus emerged in early 2013 and was associated with a dramatic increase in infections of humans (34 cases) until it was replaced by a clade 2.3.2.1c virus in early 2014. In contrast, only one infection of a human has been reported in the 6 years since the clade 2.3.2.1c virus became the dominant circulating virus. We selected three viruses to represent the main viral clades that have circulated in Cambodia (clade 1.1.2, clade 1.1.2 reassortant, and clade 2.3.2.1c), and we conducted experiments to assess the virulence and transmissibility of these viruses in avian (chicken, duck) and mammalian (ferret) models. Our results suggest that the clade 2.3.2.1c virus is more “avian-like,” with high virulence in both ducks and chickens, but there is no evidence of aerosol transmission of the virus from ducks to ferrets. In contrast, the two clade 1 viruses were less virulent in experimentally infected and contact ducks. However, evidence of chicken-to-ferret aerosol transmission was observed for both clade 1 viruses. The transmission experiments provide insights into clade-level differences that might explain the variation in A/H5N1 infections of humans observed in Cambodia and other settings

Relation between cannabis use and subcortical volumes in people at clinical high risk of psychosis

Among people at genetic risk of schizophrenia, those who use cannabis show smaller thalamic and hippocampal volumes. We evaluated this relationship in people at clinical high risk (CHR) of psychosis. The Alcohol and Drug Use Scale was used to identify 132 CHR cannabis users, the majority of whom were non-dependent cannabis users, 387 CHR non-users, and 204 healthy control non-users, and all participants completed magnetic resonance imaging scans. Volumes of the thalamus, hippocampus and amygdala were extracted with FreeSurfer, and compared across groups. Comparing all CHR participants with healthy control participants revealed no significant differences in volumes of any ROI. However, when comparing CHR users to CHR non-users, a significant ROI × Cannabis group effect emerged: CHR users showed significantly smaller amygdala compared to CHR non-users. However, when limiting analysis to CHR subjects who reported using alcohol at a ‘use without impairment’ severity level, the amygdala effect was non-significant; rather, smaller hippocampal volumes were seen in CHR cannabis users compared to non-users. Controlling statistically for effects of alcohol and tobacco use rendered all results non-significant. These results highlight the importance of controlling for residual confounding effects of other substance use when examining the relationship between cannabis use and neural structure

Traumatic brain injury in individuals at clinical high risk for psychosis

Recent research suggests that a traumatic brain injury (TBI) can significantly increase the risk of later development of psychosis. However, it is unknown whether people at clinical high risk (CHR) of psychosis have experienced TBI at higher rates, compared to otherwise healthy individuals. This study evaluated the prevalence of mild TBI, whether it was related to past trauma and the relationship of mild TBI to later transition to psychosis

Diversity of A(H5N1) clade 2.3.2.1c avian Influenza viruses with evidence of reassortment in Cambodia, 2014-2016

In Cambodia, highly pathogenic avian influenza A(H5N1) subtype viruses circulate endemically causing poultry outbreaks and zoonotic human cases. To investigate the genomic diversity and development of endemicity of the predominantly circulating clade 2.3.2.1c A(H5N1) viruses, we characterised 68 AIVs detected in poultry, the environment and from a single human A(H5N1) case from January 2014 to December 2016. Full genomes were generated for 42 A(H5N1) viruses. Phylogenetic analysis shows that five clade 2.3.2.1c genotypes, designated KH1 to KH5, were circulating in Cambodia during this period. The genotypes arose through multiple reassortment events with the neuraminidase (NA) and internal genes belonging to H5N1 clade 2.3.2.1a, clade 2.3.2.1b or A(H9N2) lineages. Phylogenies suggest that the Cambodian AIVs were derived from viruses circulating between Cambodian and Vietnamese poultry. Molecular analyses show that these viruses contained the hemagglutinin (HA) gene substitutions D94N, S133A, S155N, T156A, T188I and K189R known to increase binding to the human-type α2,6-linked sialic acid receptors. Two A(H5N1) viruses displayed the M2 gene S31N or A30T substitutions indicative of adamantane resistance, however, susceptibility testing towards neuraminidase inhibitors (oseltamivir, zanamivir, lananmivir and peramivir) of a subset of thirty clade 2.3.2.1c viruses showed susceptibility to all four drugs. This study shows that A(H5N1) viruses continue to reassort with other A(H5N1) and A(H9N2) viruses that are endemic in the region, highlighting the risk of introduction and emergence of novel A(H5N1) genotypes in Cambodia

Dengue in Thailand and Cambodia: An Assessment of the Degree of Underrecognized Disease Burden Based on Reported Cases

Dengue is a major public health problem especially in tropical and subtropical countries of Asia and Latin-America. An effective dengue vaccine is not yet available, but several vaccine candidates are currently being evaluated in clinical trials. Accurate country-level incidence data are crucial to assess the cost-effectiveness of such vaccines and will assist policy-makers in making vaccine introduction decisions. Existing national surveillance systems are often passive and are designed to monitor trends and to detect disease outbreaks. Our analyses of data from prospectively followed cohorts with laboratory confirmation of dengue cases show that, in Thailand and Cambodia, dengue incidence is underrecognized by more than 8-fold. The magnitude of the outpatient burden caused by dengue is not assessed or reflected by the national surveillance data. We estimate that a median of more than 340,000 symptomatic dengue virus infections occurred annually in children less than 15 years of age in Thailand in Cambodia between 2003 and 2007