Antibiotic resistance is a major problem in
serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with ...the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel
Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR
Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the
extended-spectrum β-lactamase, and carrying the
fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of
Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally.
Typhoid fever is a severe disease caused by the Gram-negative bacterium
serovar Typhi. Antibiotic-resistant
Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR)
Typhi clone in Sindh, Pakistan. The XDR
Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in
Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR
Typhi to investigate the phylogenetic relationship between these isolates and a global collection of
Typhi isolates and to identify multiple genes linked to antibiotic resistance. This
Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in
Typhi observed here adds urgency to the need for typhoid prevention measures.
Pancreatic β cells are mostly post-mitotic, but it is unclear what locks them in this state. Perturbations including uncontrolled hyperglycemia can drive β cells into more pliable states with reduced ...cellular insulin levels, increased β cell proliferation, and hormone mis-expression, but it is unknown whether reduced insulin production itself plays a role. Here, we define the effects of ∼50% reduced insulin production in Ins1−/−:Ins2f/f:Pdx1CreERT:mTmG mice prior to robust hyperglycemia. Transcriptome, proteome, and network analysis revealed alleviation of chronic endoplasmic reticulum (ER) stress, indicated by reduced Ddit3, Trib3, and Atf4 expression; reduced Xbp1 splicing; and reduced phospho-eIF2α. This state was associated with hyper-phosphorylation of Akt, which is negatively regulated by Trib3, and with cyclinD1 upregulation. Remarkably, β cell proliferation was increased 2-fold after reduced insulin production independently of hyperglycemia. Eventually, recombined cells mis-expressed glucagon in the hyperglycemic state. We conclude that the normally high rate of insulin production suppresses β cell proliferation in a cell-autonomous manner.
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•Acute reduction of insulin production reverses baseline ER stress•Loss of insulin production reduces Trib3 and hyper-activates Akt•Reduced insulin production increases β cell proliferation cell autonomously•Insulin knockout induces glucagon mis-expression via hyperglycemia
Szabat et al. show that the normally high rate of insulin production acts as a brake on adult β cell proliferation in mice. Reducing this burden via acute deletion of the insulin gene relieves baseline ER stress, increases mitogenic signaling, and promotes cell-cycle progression in a cell-autonomous manner.
An outbreak of listeriosis was identified in South Africa in 2017. The source was unknown.
We conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to ...type
isolates. A case was defined as laboratory-confirmed
infection during the period from June 11, 2017, to April 7, 2018.
A total of 937 cases were identified, of which 465 (50%) were associated with pregnancy; 406 of the pregnancy-associated cases (87%) occurred in neonates. Of the 937 cases, 229 (24%) occurred in patients 15 to 49 years of age (excluding those who were pregnant). Among the patients in whom human immunodeficiency virus (HIV) status was known, 38% of those with pregnancy-associated cases (77 of 204) and 46% of the remaining patients (97 of 211) were infected with HIV. Among 728 patients with a known outcome, 193 (27%) died. Clinical isolates from 609 patients were sequenced, and 567 (93%) were identified as sequence type 6 (ST6). In a case-control analysis, patients with ST6 infections were more likely to have eaten polony (a ready-to-eat processed meat) than those with non-ST6 infections (odds ratio, 8.55; 95% confidence interval, 1.66 to 43.35). Polony and environmental samples also yielded ST6 isolates, which, together with the isolates from the patients, belonged to the same core-genome multilocus sequence typing cluster with no more than 4 allelic differences; these findings showed that polony produced at a single facility was the outbreak source. A recall of ready-to-eat processed meat products from this facility was associated with a rapid decline in the incidence of
ST6 infections.
This investigation showed that in a middle-income country with a high prevalence of HIV infection,
caused disproportionate illness among pregnant girls and women and HIV-infected persons. Whole-genome sequencing facilitated the detection of the outbreak and guided the trace-back investigations that led to the identification of the source.
We present the first global assessment of extinction risk for a major group of freshwater invertebrates, caridean shrimps. The risk of extinction for all 763 species was assessed using the IUCN Red ...List criteria that include geographic ranges, habitats, ecology and past and present threats. The Indo-Malayan region holds over half of global species diversity, with a peak in Indo-China and southern China. Shrimps primarily inhabit flowing water; however, a significant subterranean component is present, which is more threatened than the surface fauna. Two species are extinct with a further 10 possibly extinct, and almost one third of species are either threatened or Near Threatened (NT). Threats to freshwater shrimps include agricultural and urban pollution impact over two-thirds of threatened and NT species. Invasive species and climate change have the greatest overall impact of all threats (based on combined timing, scope and severity of threats).
Concerns regarding the clinical impact of meropenem instability in continuous infusion (CI) devices may contribute to inconsistent uptake of this method of administration across outpatient parenteral ...antimicrobial therapy (OPAT) services.
We retrospectively reviewed the clinical efficacy and safety of CIs of meropenem in two Australian tertiary hospitals and assessed its stability under simulated OPAT conditions including in elastomeric infusion devices containing 1% (2.4 g) or 2% (4.8 g) concentrations at either 'room temperature' or 'cooled' conditions. Infusate aliquots were assayed at different time-points over 24 hours.
Forty-one (82%) of 50 patients had clinical improvement or were cured. Adverse patient outcomes including hemato-, hepato- and nephrotoxicity were infrequent. Cooled infusers with 1% meropenem had a mean 24-hour recovery of 90.3%. Recoveries of 1% and 2% meropenem at room temperature and 2% under cooled conditions were 88%, 83% and 87%, respectively. Patients receiving 1% meropenem are likely to receive >95% of the maximum deliverable dose (MDD) over a 24-hour period whilst patients receiving 2% meropenem should receive 93% and 87% of the MDD under cooled and room temperature conditions, respectively.
Meropenem infusers are likely to deliver ∼95% MDD and maintain effective plasma concentrations throughout the dosing period. These data reflect our local favourable clinical experience with meropenem CIs.
Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. ...In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require <2 days of training to perform the assay. Further, given that the aim is to reduce inappropriate antimicrobial use as well as to deliver appropriate treatment for patients with bacterial infections, the group agreed on minimal diagnostic performance requirements of >90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result <10 min (but maximally <2 hrs); ii) storage conditions at 0-40°C, ≤90% non-condensing humidity with a minimal shelf life of 12 months; iii) operational conditions of 5-40°C, ≤90% non-condensing humidity; and iv) minimal sample collection needs (50-100μL, capillary blood). This expert approach to define assay requirements for a bacterial vs. non-bacterial assay should guide product development, and enable targeted and timely efforts by industry partners and academic institutions.
A morphological and genetic study of both newly collected and museum specimens of the east Australian freshwater shrimp genus Australatya indicates two genotypes and three morphotypes are present. ...One genotype and morphotype were of the known species, Australatya striolata (McCulloch McNeill 1923). The second genotype, comprising two morphotypes, is now described as a new species, Australatya hawkei sp. nov.. All Australian Australatya species and morphotypes currently have allopatric distributions. Australatya striolata is widespread along the south-eastern Australian seaboard, from Genoa River in Victoria to the Sunshine Coast in Queensland. The 'southern' morphotype of Australatya hawkei sp. nov. occurs in north Queensland, from near Mackay to about Cooktown, and its 'northern' morphotype is found on Cape York Peninsula, north from about Coen to the Iron Range, just north of Lockhart River. The once monotypic genus now includes two Australian species, Australatya striolata and A. hawkei sp. nov., and a third, A. obscura, recently described from Japan, Taiwan, and the Philippines.
Intensification of the use of natural resources is a world-wide trend driven by the increasing demand for water, food, fibre, minerals and energy. These demands are the result of a rising world ...population, increasing wealth and greater global focus on economic growth. Land use intensification, together with climate change, is also driving intensification of the global hydrological cycle. Both processes will have major socio-economic and ecological implications for global water availability. In this paper we focus on the implications of land use intensification for the conservation and management of freshwater ecosystems using Australia as an example. We consider this in the light of intensification of the hydrologic cycle due to climate change, and associated hydrological scenarios that include the occurrence of more intense hydrological events (extreme storms, larger floods and longer droughts). We highlight the importance of managing water quality, the value of providing environmental flows within a watershed framework and the critical role that innovative science and adaptive management must play in developing proactive and robust responses to intensification. We also suggest research priorities to support improved systemic governance, including adaptation planning and management to maximise freshwater biodiversity outcomes while supporting the socio-economic objectives driving land use intensification. Further research priorities include: i) determining the relative contributions of surface water and groundwater in supporting freshwater ecosystems; ii) identifying and protecting freshwater biodiversity hotspots and refugia; iii) improving our capacity to model hydro-ecological relationships and predict ecological outcomes from land use intensification and climate change; iv) developing an understanding of long term ecosystem behaviour; and v) exploring systemic approaches to enhancing governance systems, including planning and management systems affecting freshwater outcomes. A major policy challenge will be the integration of land and water management, which increasingly are being considered within different policy frameworks.
•This paper considers the impacts of land use and hydrological intensification on inland waters•Global issues are considered through the lens of Australian examples•Likely scenarios include wet regions becoming wetter, dry regions drier and storms more intense•The legacies of past land use change will need to be addressed•Proactive governance based on innovative science and adaptive management will be critical
Early data on pandemic 2009 influenza A(H1N1) suggest pregnant women are at increased risk of hospitalization and death.
To describe the severity of 2009 influenza A(H1N1) illness and the association ...with early antiviral treatment among pregnant women in the United States.
Surveillance of 2009 influenza A(H1N1) in pregnant women reported to the Centers for Disease Control and Prevention (CDC) with symptom onset from April through December 2009.
Severity of illness (hospitalizations, intensive care unit ICU admissions, and deaths) due to 2009 influenza A(H1N1) among pregnant women, stratified by timing of antiviral treatment and pregnancy trimester at symptom onset.
We received reports on 788 pregnant women in the United States with 2009 influenza A(H1N1) with symptom onset from April through August 2009. Among those, 30 died (5% of all reported 2009 influenza AH1N1 influenza deaths in this period). Among 509 hospitalized women, 115 (22.6%) were admitted to an ICU. Pregnant women with treatment more than 4 days after symptom onset were more likely to be admitted to an ICU (56.9% vs 9.4%; relative risk RR, 6.0; 95% confidence interval CI, 3.5-10.6) than those treated within 2 days after symptom onset. Only 1 death occurred in a patient who received treatment within 2 days of symptom onset. Updating these data with the CDC's continued surveillance of ICU admissions and deaths among pregnant women with symptom onset through December 31, 2009, identified an additional 165 women for a total of 280 women who were admitted to ICUs, 56 of whom died. Among the deaths, 4 occurred in the first trimester (7.1%), 15 in the second (26.8%), and 36 in the third (64.3%);
Pregnant women had a disproportionately high risk of mortality due to 2009 influenza A(H1N1). Among pregnant women with 2009 influenza A(H1N1) influenza reported to the CDC, early antiviral treatment appeared to be associated with fewer admissions to an ICU and fewer deaths.
The Viviparidae, commonly known as River Snails, is a dominant group of freshwater snails with a nearly worldwide distribution that reaches its highest taxonomic and morphological diversity in ...Southeast Asia. The rich fossil record is indicative of a probable Middle Jurassic origin on the Laurasian supercontinent where the group started to diversify during the Cretaceous. However, it remains uncertain when and howthe biodiversity hotspot in Southeast Asiawas formed. Here,we used a comprehensive genetic data set containing both mitochondrial and nuclear markers and comprising species representing 24 out of 28 genera from throughout the range of the family. To reconstruct the spatiotemporal evolution of viviparids on a global scale, we reconstructed a fossil-calibrated phylogeny. We further assessed the roles of cladogenetic and anagenetic events in range evolution. Finally, we reconstructed the evolution of shell features by estimating ancestral character states to assess whether the appearance of sculptured shell morphologies was driven by major habitat shifts. The molecular phylogeny supports the monophyly of the three subfamilies, the Bellamyinae, Lioplacinae, and Viviparinae, but challenges the currently accepted genus-level classification in several cases. The almost global distribution of River Snails has been influenced both by comparatively ancient vicariance and more recent founder events. In Southeast Asia, Miocene dispersal was a main factor in shaping the modern species distributions. A recurrent theme across different viviparid taxa is that many species living in lentic waters exhibit sculptured shells, whereas only one strongly sculptured species is known from lotic environments. We show that such shell sculpture is habitat-dependent and indeed evolved several times independently in lentic River Snails. Considerably high transition rates between shell types in lentic habitats probably caused the co-occurrence of morphologically distinct shell types in several lakes. In contrast, directional evolution toward smooth shells in lotic habitats, as identified in the present analyses, explains why sculptured shells are rarely found in these habitats. However, the specific factors that promoted changes in shell morphology require further work.
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