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Concept: Infection

223

Multidrug-resistant organism (MDRO) infections are associated with high mortality and readmission rates. Infectious diseases (ID) consultation improves clinical outcomes for drug-resistantStaphylococcus aureusbloodstream infections. Our goal was to determine the association between ID consultation and mortality following various MDRO infections.

Concepts: Immune system, Medicine, Epidemiology, Disease, Infectious disease, Death, Infection, The Association

218

Human rhinoviruses (HRVs) are the most common cause of viral respiratory tract infections, and are associated with significant morbidity and mortality in immunocompromised individuals and patients with pre-existing pulmonary conditions. The therapeutic options available are extremely limited and therefore novel therapeutics for HRV infections are of significant interest. Cathelicidins have been shown to have potent antiviral activity against a range of pathogens and are known to be key immunomodulatory mediators during infection. We therefore assessed the antiviral potential of cathelicidins from humans and other mammalian species against HRV, together with the potential for the human cathelicidin to modulate apoptotic pathways and alter cell viability during HRV infection. We demonstrate that LL-37, the porcine cathelicidin Protegrin-1, and the ovine cathelicidin SMAP-29 display potent antiviral activity towards HRV and that this activity is visible when either the virus is exposed to the peptides prior to cell infection or after cells have been infected. We further demonstrate that, in contrast to established findings with bacterial infection models, LL-37 does not induce apoptosis or necrosis in HRV-infected lung epithelial cells at physiological or superphysiological concentrations, but does reduce the metabolic activity of infected cells compared to uninfected cells treated with similar peptide concentrations. Collectively, the findings from this study demonstrate that the mechanism of action of cathelicidins against rhinovirus is by directly affecting the virus and we propose that the delivery of exogenous cathelicidins, or novel synthetic analogues, represent an exciting and novel therapeutic strategy for rhinovirus infection.

Concepts: Immune system, Protein, Human, Bacteria, Organism, Virus, Infection, Apoptosis

218

The most cost-effective intervention for certain infectious diseases is to eliminate them entirely. This article reviews the characteristics of potentially eradicable diseases and surveys current eradication methods.

Concepts: Epidemiology, Disease, Infectious disease, Malaria, Infection

212

There has not previously been a systematic comparison of awards for research funding in infectious diseases by sex. We investigated funding awards to UK institutions for all infectious disease research from 1997 to 2010, across disease categories and along the research and development continuum.

Concepts: Epidemiology, Disease, Infectious disease, Infection

210

Simon Hay and colleagues discuss the potential and challenges of producing continually updated infectious disease risk maps using diverse and large volume data sources such as social media.

Concepts: Epidemiology, Disease, Infectious disease, Infection, Clinical surveillance, Disease surveillance

198

Zika virus is an emerging mosquito-borne flavivirus that typically causes an asymptomatic infection or mild illness, although infection during pregnancy is a cause of microcephaly and other serious brain abnormalities. Guillain-Barré syndrome and other neurologic complications can occur in adults after Zika virus infection. However, there are few published reports describing postnatally acquired Zika virus disease among children. During January 2015-July 2016, a total of 158 cases of confirmed or probable postnatally acquired Zika virus disease among children aged <18 years were reported to CDC from U.S. states. The median age was 14 years (range = 1 month-17 years), and 88 (56%) were female. Two (1%) patients were hospitalized; none developed Guillain-Barré syndrome, and none died. All reported cases were travel-associated. Overall, 129 (82%) children had rash, 87 (55%) had fever, 45 (29%) had conjunctivitis, and 44 (28%) had arthralgia. Health care providers should consider a diagnosis of Zika virus disease in children who have an epidemiologic risk factor and clinically compatible illness, and should report cases to their state or local health department.

Concepts: Health care, Medicine, Health, Epidemiology, Infectious disease, Death, Infection, Illness

196

ABSTRACT A new human coronavirus (hCoV-EMC) has emerged very recently in the Middle East. The clinical presentation resembled that of the severe acute respiratory syndrome (SARS) as encountered during the epidemic in 2002/2003. In both cases, acute renal failure was observed in humans. HCoV-EMC is a member of the same virus genus as SARS-CoV but constitutes a sister species. Here we investigated whether it might utilize angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Knowledge of the receptor is highly critical because the restriction of the SARS receptor to deep compartments of the human respiratory tract limited the spread of SARS. In baby hamster kidney (BHK) cells, lentiviral transduction of human ACE2 (hACE2) conferred permissiveness and replication for SARS-CoV but not for hCoV-EMC. Monkey and human kidney cells (LLC-MK2, Vero, and 769-P) and swine kidney cells were permissive for both viruses, but only SARS-CoV infection could be blocked by anti-hACE2 antibody and could be neutralized by preincubation of virus with soluble ACE2. Our data show that ACE2 is neither necessary nor sufficient for hCoV-EMC replication. Moreover, hCoV-EMC, but not SARS-CoV, replicated in cell lines from Rousettus, Rhinolophus, Pipistrellus, Myotis, and Carollia bats, representing four major chiropteran families from both suborders. As human CoV normally cannot replicate in bat cells from different families, this suggests that hCoV-EMC might use a receptor molecule that is conserved in bats, pigs, and humans, implicating a low barrier against cross-host transmission. IMPORTANCE  A new human coronavirus (hCoV) emerged recently in the Middle East. The disease resembled SARS (severe acute respiratory syndrome), causing a fatal epidemic in 2002/2003. Coronaviruses have a reservoir in bats and because this novel virus is related to SARS-CoV, we investigated whether it might replicate in bat cells and use the same receptor (angiotensin-converting enzyme 2 [ACE2]). This knowledge is highly critical, because the SARS-CoV receptor influenced pathology, and its localization in the deep respiratory tract is thought to have restricted the transmissibility of SARS. Our data show that hCoV-EMC does not need the SARS-CoV receptor to infect human cells. Moreover, the virus is capable of infecting human, pig, and bat cells. This is remarkable, as human CoVs normally cannot replicate in bat cells as a consequence of host adaptation. Our results implicate that the new virus might use a receptor that is conserved between bats, pigs and humans suggesting a low barrier against cross-host transmission.

Concepts: Protein, Virus, Infection, Severe acute respiratory syndrome, Mammal, Primate, Bat, Coronavirus

194

Simultaneous infection by multiple parasite species (viruses, bacteria, helminths, protozoa or fungi) is commonplace. Most reports show co-infected humans to have worse health than those with single infections. However, we have little understanding of how co-infecting parasites interact within human hosts. We used data from over 300 published studies to construct a network that offers the first broad indications of how groups of co-infecting parasites tend to interact. The network had three levels comprising parasites, the resources they consume and the immune responses they elicit, connected by potential, observed and experimentally proved links. Pairs of parasite species had most potential to interact indirectly through shared resources, rather than through immune responses or other parasites. In addition, the network comprised 10 tightly knit groups, eight of which were associated with particular body parts, and seven of which were dominated by parasite-resource links. Reported co-infection in humans is therefore structured by physical location within the body, with bottom-up, resource-mediated processes most often influencing how, where and which co-infecting parasites interact. The many indirect interactions show how treating an infection could affect other infections in co-infected patients, but the compartmentalized structure of the network will limit how far these indirect effects are likely to spread.

Concepts: Immune system, Inflammation, Infectious disease, Bacteria, Infection, Fungus, Parasitism, Antiseptic

193

In the third millennium B.C., the Indus Civilization flourished in northwest India and Pakistan. The late mature phase (2200-1900 B.C.) was characterized by long-distance exchange networks, planned urban settlements, sanitation facilities, standardized weights and measures, and a sphere of influence over 1,000,000 square kilometers of territory. Recent paleoclimate reconstructions from the Beas River Valley demonstrate hydro-climatic stress due to a weakened monsoon system may have impacted urban centers like Harappa by the end of the third millennium B.C. the impact of environmental change was compounded by concurrent disruptions to the regional interaction sphere. Climate, economic, and social changes contributed to the disintegration of this civilization after 1900 B.C. We assess evidence for paleopathology to infer the biological consequences of climate change and socio-economic disruption in the post-urban period at Harappa, one of the largest urban centers in the Indus Civilization. Bioarchaeological evidence demonstrates the prevalence of infection and infectious disease increased through time. Furthermore, the risk for infection and disease was uneven among burial communities. Corresponding mortuary differences suggest that socially and economically marginalized communities were most vulnerable in the context of climate uncertainty at Harappa. Combined with prior evidence for increasing levels of interpersonal violence, our data support a growing pathology of power at Harappa after 2000 B.C. Observations of the intersection between climate change and social processes in proto-historic cities offer valuable lessons about vulnerability, insecurity, and the long-term consequences of short-term strategies for coping with climate change.

Concepts: Disease, Infectious disease, Infection, India, Pakistan, Indus River, Punjab, Indus Valley Civilization

193

On 9 June 2008, the UK’s largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06∶30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a “two-stage process” where a group of normally pelagic dolphins entered Falmouth Bay and, after 3-4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE.

Concepts: Disease, Infectious disease, Causality, Pathology, Infection, Toxin, Dolphin, Porpoise