Abstract Background There is little research on laypersons’ perceptions regarding common cold and influenza, their symptomatic distinction and considerations of risk. This study investigates understanding of pathogenesis across three European countries and provides a knowledge base from which adequate prevention recommendations and treatment advice can be derived. Methods This is a qualitative research study. Semi-structured face-to-face interviews were conducted with 85 participants from three European countries (Austria n = 31, Belgium n = 30, Croatia n = 24) about their experiences, perceptions and risk considerations regarding the common cold and influenza. We performed a qualitative thematic content analysis. Results Three main themes were identified: common cold as harmless with individualistic symptoms; influenza as mainly distinguishable by fever, confinement to bed and severity of symptoms, but description about onset and duration are diverse; and views on pathogenesis contain references to disease causing agents and circumstances. Overall we found that risk perception is based largely on personal experience and risk is assumed moderate for both diseases. Conclusions Study participants possessed a fairly good understanding of symptoms, differences and pathogenesis of common cold and influenza; but explanations integrated misconceptions, such as misinterpretation of fever, disease continuums, diverse onset ideas etc. Perceptions were largely based on lived experiences and interventions for prevention and treatment should be led by health care workers and focus on these issues. Basic consultations, awareness raising activities and other knowledge disseminations strategies should include aspects of communicableness and the self-limiting nature of both diseases. An informed understanding of both infectious diseases is crucial and may also increase influenza vaccination coverage in the three respective countries effectively.…

Darren W Westphal, Ashley Eastwood, Avram Levy, Jane Davies, Clare Huppatz, Marisa Gilles, Heather Lyttle, Stephanie A Williams, Gary K Dowse

The number of mumps outbreaks reported in recent years among highly vaccinated populations, including Indigenous populations, has been growing. More widespread and pre-emptive use of the third dose of measles, mumps, and rubella vaccine might be required to control and prevent future outbreaks in high-risk populations. Research should explore the benefit of increasing the intervals between vaccine doses to strengthen the durability of vaccine protection.

Alessandro Pini, Magnus Stenbeck, Ilias Galanis, Henrik Kallberg, Kostas Danis, Anders Tegnell, Anders Wallensten

These findings indicate persistent socioeconomic inequalities in infectious diseases in an egalitarian high-income country with universal health care. We recommend using these findings to identify priority interventions and as a baseline to monitor programmes addressing socioeconomic inequalities in health.

Agostino Colli, Alessandra Berzuini, Daniele Prati

A 19-year-old man presented to our emergency department with abdominal pain and jaundice. He had emigrated from Senegal during infancy. He was found to be a carrier of hepatitis B virus, with a hepatitis B surface antigen serum DNA concentration persistently below 2000 IU/mL. He was negative for hepatitis B e antigen and positive for anti-hepatitis B e antibodies.

The Lancet

Human Rights Day is recognised annually on Dec 10, and this year is especially important since it is the 70th anniversary of the day that the UN General Assembly adopted the Universal Declaration of Human Rights. The Declaration, through its 30 Articles, proclaims the rights that everyone is entitled to as a human being, regardless of race, colour, religion, sex, language, political or other opinion, national or social origin, property, birth, or other status. Today, Lawrence Gostin and colleagues, including the director-general of WHO, look back at the evolution of human rights in global health over the past 70 years and outline key messages for the future of health as a human right.

Margaret McCartney

Silicon Valley is a crucible of contemporary power. Technology parks burgeon with purposeful startups. Sometimes the Silicon Valley dare pays back handsomely with successes such as Apple, Google, and Airbnb. Sometimes the bite back comes after years of success—like Facebook and the scandals of fake news and data handling. Then there are companies like Tesla with an enormous idea and investment but little financial return as yet. And then there is Theranos, a medical technology company whose story serves as a surreal parable for how not to do it.

Julian S Peters, Jason R Andrews, Mark Hatherill, Sabine Hermans, Leonardo Martinez, Erwin Schurr, Yuri van der Heijden, Robin Wood, Roxana Rustomjee, Bavesh D Kana

Tuberculosis claims more human lives than any other infectious disease. This alarming epidemic has fuelled the development of novel antimicrobials and diagnostics. However, public health interventions that interrupt transmission have been slow to emerge, particularly in HIV-endemic settings. Transmission of tuberculosis is complex, involving various environmental, bacteriological, and host factors, among which concomitant HIV infection is important. Preventing person-to-person spread is central to halting the epidemic and, consequently, tuberculosis transmission is now being studied with renewed interest.

Patrick G T Cudahy, Jason R Andrews, Alyssa Bilinski, David W Dowdy, Barun Mathema, Nicolas A Menzies, Joshua A Salomon, Sourya Shrestha, Ted Cohen

As the leading infectious cause of death worldwide and the primary proximal cause of death in individuals living with HIV, tuberculosis remains a global concern. Existing tuberculosis control strategies that rely on passive case-finding appear insufficient to achieve targets for reductions in tuberculosis incidence and mortality. Active case-finding strategies aim to detect infectious individuals earlier in their infectious period to reduce onward transmission and improve treatment outcomes. Empirical studies of active case-finding have produced mixed results and determining how to direct active screening to those most at risk remains a topic of intense research.

Palwasha Y Khan, Tom A Yates, Muhammad Osman, Robin M Warren, Yuri van der Heijden, Nesri Padayatchi, Edward A Nardell, David Moore, Barun Mathema, Neel Gandhi, Vegard Eldholm, Keertan Dheda, Anneke C Hesseling, Valerie Mizrahi, Roxana Rustomjee, Alexander Pym

The emergence and expansion of the multidrug-resistant tuberculosis epidemic is a threat to the global control of tuberculosis. Multidrug-resistant tuberculosis is the result of the selection of resistance-conferring mutations during inadequate antituberculosis treatment. However, HIV has a profound effect on the natural history of tuberculosis, manifesting in an increased rate of disease progression, leading to increased transmission and amplification of multidrug-resistant tuberculosis. Interventions specific to HIV-endemic areas are urgently needed to block tuberculosis transmission.

John Zarocostas

Funding for victim assistance has been cut back to just 2% of international support funding needed despite high casualty numbers, John Zarocostas reports.

Bassirou Diarra, Mahamadou Kone, Antieme Combo Georges Togo, Yeya dit Sadio Sarro, Aissata Boubakar Cisse, Amadou Somboro, Boureima Degoga, Mohamed Tolofoudie, Bourahima Kone, Moumine Sanogo, Bocar Baya, Ousmane Kodio, Mamoudou Maiga, Michael Belson, Susan Orsega, Meryam Krit, Sounkalo Dao, Ibrahim Izétiegouma Maiga, Robert L. Murphy, Leen Rigouts, Seydou Doumbia, Souleymane Diallo, Bouke Catherine de Jong

by Bassirou Diarra, Mahamadou Kone, Antieme Combo Georges Togo, Yeya dit Sadio Sarro, Aissata Boubakar Cisse, Amadou Somboro, Boureima Degoga, Mohamed Tolofoudie, Bourahima Kone, Moumine Sanogo, Bocar Baya, Ousmane Kodio, Mamoudou Maiga, Michael Belson, Susan Orsega, Meryam Krit, Sounkalo Dao, Ibrahim Izétiegouma Maiga, Robert L. Murphy, Leen Rigouts, Seydou Doumbia, Souleymane Diallo, Bouke Catherine de Jong Objective Ancestral M. tuberculosis complex lineages such as M. africanum are underrepresented among retreatment patients and those with drug resistance. To test the hypothesis that they respond faster to TB treatment, we determined the rate of smear conversion of new pulmonary tuberculosis patients in Bamako, Mali by the main MTBc lineages. Methods Between 2015 and 2017, we conducted a prospective cohort study of new smear positive pulmonary tuberculosis patients in Bamako. Confirmed MTBc isolates underwent genotyping by spoligotyping for lineage classification. Patients were followed at 1 month (M), 2M and 5M to measure smear conversion in auramine (AR) and Fluorescein DiAcetate (FDA) vital stain microscopy. Result All the first six human MTBc lineages were represented in the population, plus M. bovis in 0.8% of the patients. The most widely represented lineage was the modern Euro-American lineage (L) 4, 57%, predominantly the T family, followed by L6 (M. africanum type 2) in 22.9%. Ancestral lineages 1, 5, 6 and M. bovis combined amounted to 28.8%. Excluding 25 patients with rifampicin resistance, smear conversion, both by AR and FDA, occurred later in L6 compared to L4 (HR 0.80 (95% CI 0.66–0.97) for AR, and HR 0.81 (95%CI 0.68–0.97) for FDA). In addition we found that HIV negative status, higher BMI at day 0, and patients with smear grade at baseline ≤ 1+ were associated with earlier smear conversion. Conclusion The six major human lineages of the MTBc all circulate in Bamako. Counter to our hypothesis, we found that patients diseased with modern M. tuberculosis complex L4 respond faster to TB treatment than those with M. africanum L6.…

Abstract Reaching the overall goal of eliminating malaria requires halting disease transmission. One approach to blocking transmission is to prevent passage of the parasite to a mosquito, by preventing formation or transmission of gametocytes. An alternative approach, pioneered in the veterinary field, is to use endectocides, which are molecules that render vertebrate blood meals toxic for the mosquito vector, also killing the parasite. Field studies and modelling suggest that reducing the lifespan of the mosquito may significantly reduce transmission, given the lengthy maturation process of the parasite. To guide the development of new endectocides, or the reformulation of existing molecules, it is important to construct a framework of the required attributes, commonly called the target candidate profile. Here, using a combination of insights from current endectocides, mathematical models of the malaria transmission dynamics, and known impacts of vector control, a target candidate profile (TCP-6) and a regulatory strategy are proposed for a transmission reducing agent. The parameters chosen can be used to assess the potential of a new medicine, independent of whether it has classical endectocide activity, reduces the insect and parasite lifespan or any combination of all three, thereby constituting an ‘endectocidal transmission blocking’ paradigm.…

Xiaoyun Wang

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 12, Page 1500-1518, December 15, 2018. …

Lauriane Sollelis, Matthias Marti

Trypanosoma brucei stumpy forms are the only stage that can transmit from human to tsetse fly. Stumpy formation is regulated by a quorum sensing mechanism that depends on parasite density and an unknown stumpy induction factor (SIF). Recently, an elegant study by Matthews and colleagues (Cell 176, 1–12) has identified several crucial components of this pathway, including the putative SIF and its receptor.

Elie Azoulay

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 12, Page 1519-1526, December 15, 2018. …

Chan, W.-Y., Entwisle, C., Ercoli, G., Ramos-Sevillano, E., McIlgorm, A., Cecchini, P., Bailey, C., Lam, O., Whiting, G., Green, N., Goldblatt, D., Wheeler, J. X., Brown, J. S.

Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes, and has led to non-vaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp, thought to be immune adjuvants). Proteomics and immunoblots demonstrated that compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognised protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including non-pneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonised after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, whilst passive transfer of rabbit serum from MAV vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat-shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae.…

Dubé M, Chan E, Lake J, et al.

AbstractBackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to their glucoregulatory actions. We evaluated inflammation and immune markers in suppressed HIV infection during treatment with the DPP-4 inhibitor sitagliptin.MethodsVirologically suppressed adults with HIV without diabetes mellitus on stable ART with ≥100/mm 3 CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/d vs. placebo in a multicenter trial. The primary endpoint was the change in plasma soluble CD14 (sCD14) from baseline to week 15/16. Additional soluble biomarkers, and lymphocyte and monocyte activation were assessed.ResultsNinety participants were randomized, and 42 from each arm were included in per-protocol analyses. Evaluable participants were 45% non-Hispanic white, 38% non-Hispanic black, 15% Hispanic, median age of 51 years, 83% male, with median CD4 count 602 cells/mm 3. At week 15/16, there was no difference in sCD14 change between the two arms (p=0.69). Relative to placebo, the sitagliptin arm had 47% greater decline in CXCL10 (95% CI:-57,-35) at week 15 (p

Abstract Background Nontuberculous mycobacteria (NTM) lung diseases are increasingly recognized as chronic opportunistic infections, occurring in individuals with a wide variety of underlying conditions. In the absence of systemic immunodeficiency, decision of NTM lung disease treatment must relies on a careful risk/benefit assessment, given the requirement of long-term administration of multidrug therapies supported by limited evidence. The primary objective was to identify the factors associated with anti-NTM treatment initiation. Clinical and radiological outcome upon treatment were studied. Methods This retrospective, single center study (2013–2016, 45 months) addressed the criteria supporting treatment decision among adults with NTM lung disease without systemic immunodeficiency at our institution, with the assigned goal to harmonize the practice. All patients matched the current international definitions of NTM lung disease according to the American Thoracic Society criteria. Factors associated with anti-NTM treatment were investigated by conditional logistic regression. Clinical and radiological outcomes of treated and untreated NTM-disease cases were examined. Mortality rate was assessed. An expert radiologist conducted a blinded computed tomography (CT)-scan review of the treated and untreated patients. Results Among 51 cases of NTM lung diseases, 25 (49%) received anti-NTM treatment. In univariate analysis, a body mass index (BMI) 

Koh HK, Kerlikowske R, Botticelli MP.

Since the United States first declared a war on drugs more than 40 years ago, the nation’s criminal justice system has largely implemented traditional strategies, including arrest, drug seizure, and incarceration. But the failure of such approaches alone has prompted an intense search for alternatives. One emerging approach explores having law enforcement officials collaborate more closely with health professionals to provide care and treatment.

Abstract Background Geographic differences in HIV, syphilis and condomless sex among men who have sex with men in China remained unknown. We aimed to elucidate these spatiotemporal changing patterns in China. Methods We conducted a spatiotemporal meta-analysis. We searched four databases for studies conducted between 2001 and 2015. We included studies that reported original data of HIV/syphilis prevalence in China, the study’s area/province, and period of data collection. We grouped studies into six regions and four time periods. We examined the changing patterns of national and regional prevalence of HIV, syphilis and condomless sex. Results Search results yielded 2119 papers, and 272 were included in the meta-analysis. The sample sizes of the studies ranged from 19 to 47,231. National HIV prevalence increased from 3.8% (95% CI 3.0–4.8) in 2001–07 to 6.6% (5.6–7.7) in 2013–15. In most regions, the rise occurred before 2010 and the HIV prevalence remained relatively stable afterwards, except for the Northwest which showed a considerable increase since 2008. National syphilis prevalence decreased from 12.3% (10.2–14.9) in 2001–07 to 7.1% (5.6–8.9) in 2013–15. Conclusions The trends of HIV and syphilis infections have been effectively curbed in MSM in most regions of China. Continuous efforts, particularly promotion of condom use, are needed to further reduce these infections.…

Sims, Charles R.; Warner, Matthew A.; Stelfox, Henry Thomas; Hyder, Joseph A.

Objectives: We examined recommendations within critical care guidelines to describe the pairing patterns for strength of recommendation and quality of evidence. We further identified recommendations where the reported strength of recommendation was strong while the reported quality of evidence was not high/moderate and then assessed whether such pairings were within five paradigmatic situations offered by Grading of Recommendations Assessment, Development and Evaluation methodology to justify such pairings. Data Sources and Extraction: We identified all clinical critical care guidelines published online from 2011 to 2017 by the Society of Critical Care Medicine along with individual guidelines published by Surviving Sepsis Campaign, Kidney Disease Improving Global Outcomes, American Society for Parenteral and Enteral Nutrition, and the Infectious Disease Society of America/American Thoracic Society. Data Synthesis: In all, 15 documents specifying 681 eligible recommendations demonstrated variation in strength of recommendation (strong n = 215 [31.6%], weak n = 345 [50.7%], none n = 121 [17.8%]) and in quality of evidence (high n = 41 [6.0%], moderate n = 151 [22.2%], low/very low n = 298 [43.8%], and Expert Consensus/none n = 191 [28.1%]). Strength of recommendation and quality of evidence were positively correlated (ρ = 0.66; p < 0.0001). Of 215 strong recommendations, 69 (32.1%) were discordantly paired with evidence other than high/moderate. Twenty-two of 69 (31.9%) involved Strong/Expert Consensus recommendations, a category discouraged by Grading of Recommendations Assessment, Development and Evaluation methodology. Forty-seven of 69 recommendations (68.1%) were comprised of Strong/Low or Strong/Very Low variation requiring justification within five paradigmatic scenarios. Among distribution in the five paradigmatic scenarios of Strong/Low and Strong/Very Low recommendations, the most common paradigmatic scenario was life threatening situation (n = 20/47; 42.6%). Four Strong/Low or Strong/Very Low recommendations (4/47; 8.5%) were outside Grading of Recommendations Assessment, Development and Evaluation methodology. Conclusions: Among a large, diverse assembly of critical care guideline recommendations using Grading of Recommendations Assessment, Development and Evaluation methodology, the strength of evidence of a recommendation was generally associated with the quality of evidence. However, strong recommendations were not infrequently made in the absence of high/moderate quality of evidence. To improve clarity and uptake, future guideline statements may specify why such pairings were made, avoid such pairings when outside of Grading of Recommendations Assessment, Development and Evaluation criteria, and consider separate language for Expert Consensus recommendations (good practice statements). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (httpm://journals.lww.com/ccmjournal). This work was performed without extramural funding. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: sims.charles@mayo.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Raquel Quatrini, D. Barrie Johnson

Acidithiobacillus ferrooxidans is by far the most widely studied of all extremely acidophilic prokaryotes. While it is found in many types of natural low-pH environments in a variety of geoclimatic contexts, it has been more widely cited in anthropogenic (mostly mine-impacted) environments. It is responsible for accelerating the oxidative dissolution of sulfide minerals, causing the generation of polluting acidic metal-rich drainage waters but also facilitating the recovery of base and precious metals from mineral leachates.

Derek W. Russell

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 12, Page 1465-1466, December 15, 2018. …

Charles L. Daley

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 12, Page 1473-1475, December 15, 2018. …

David E. Griffith

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 12, Page 1559-1569, December 15, 2018. …

Yvonne S. Eisele

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 12, Page 1475-1476, December 15, 2018. …

Dong, N., Liu, L., Zhang, R., Chen, K., Xie, M., Chan, E. W. C., Chen, S.

Completed sequences of three plasmids from a carbapenem-resistant, hypervirulent Klebsiella pneumoniae isolate, SH9, were obtained. In addition to the a pLVPK-like virulence-conferring plasmid (pVir-CR-HvKP_SH9), the two MDR plasmids (pKPC-CR-HvKP4_SH9 and pCTX-M-CR-HvKP4_SH9) were predicted to originate from a single pKPC-CR-HvKP4-like multi-replicon plasmid through homologous recombination. Interestingly, blaKPC-2 gene was detectable in five tandem repeats exhibiting the format of a NTEKPC-Id-like transposon (IS26-Tn3-ISKpn8-blaKPC-2-ISKpn6-korC-orf-IS26). The data suggested the important role of DNA recombination on mediating active plasmid evolution.…

Alexander Sprygin, Yurii Babin, Yana Pestova, Svetlana Kononova, David B. Wallace, Antoinette Van Schalkwyk, Olga Byadovskaya, Vyacheslav Diev, Dmitry Lozovoy, Alexander Kononov

by Alexander Sprygin, Yurii Babin, Yana Pestova, Svetlana Kononova, David B. Wallace, Antoinette Van Schalkwyk, Olga Byadovskaya, Vyacheslav Diev, Dmitry Lozovoy, Alexander Kononov Wide spread incidences of vaccine-like strains of lumpy skin disease virus (LSDV) have recently been reported in a Russian region with a neighboring country that actively vaccinate with a live attenuated LSD vaccine. The use of live-attenuated viruses (LAVs) as vaccines during an active outbreak, creates potential ground for coinfection of hosts and emergence of a strain combining genetic fragments of both parental vaccine and field strains. In this study, we analyse the vaccine-like strain LSDV RUSSIA/Saratov/2017 detected in Saratovskaya oblast, a region sharing border with Kazakhstan. To gain insight into possible recombination signals, a full-genome next-generation sequencing of the viral genome was performed using the Illumina platform. The genome contains the backbone of a live-attenuated vaccine with a patchwork of wild-type field virus DNA fragments located throughout. A total of 27 recombination events were identified. The average distance between the recombination sites was 3400 base pairs (bp). The impact of the recombination events on the virulence and transmission capacity of the identified virus remains to be clarified. These findings provide evidence for the first time of genetic exchanges between closely related strains of capripoxviruses in the field and a vaccine strain, and prompt a revisiting of the vaccination issue for a safe and efficacious prevention and control strategy of LSD.

Halberstadt C.

The molted wild feathers on my walls…

Priyanka Jain, Sudhanthiramani Sudhanthirakodi, Goutam Chowdhury, Sangeeta Joshi, Shalini Anandan, Ujjwayni Ray, Asish Mukhopadhyay, Shanta Dutta

by Priyanka Jain, Sudhanthiramani Sudhanthirakodi, Goutam Chowdhury, Sangeeta Joshi, Shalini Anandan, Ujjwayni Ray, Asish Mukhopadhyay, Shanta Dutta Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common serovar associated with non-typhoidal salmonellosis globally. However, there is insufficient data on molecular characterization of S. Typhimurium isolates from India. This study was undertaken to determine the antimicrobial resistance (AMR), plasmid, virulence profiles and molecular subtypes of S. Typhimurium Indian isolates (n = 70) of clinical and environmental origin isolated during 2010–2017. Antimicrobial susceptibility and minimum inhibitory concentrations were determined by disc diffusion and E-test methods respectively. Plasmid extraction was done following standard protocol. AMR genes, virulence genes and plasmid incompatibility types were detected by PCR; Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used for molecular subtyping. Majority (57%) of the study isolates was pan susceptible; five AMR profiles were observed among the resistant (43%) isolates. AMR was significantly (p = 0.004) associated with extra-intestinal isolates than intestinal isolates.The class 1 integron and plasmid-mediated quinolone resistance genes (qnrB1, qnrS1) in the resistant isolates were transferable by conjugation. Plasmids (≥1) ranging from 1.9 to 254kb size and of IncFIIS and/or FIB type were found in most isolates. A total of 39 pulsotypes by PFGE and four sequence types by MLST like ST36 (55.7%), ST19 (32.9%), ST313 (10%) and ST213 (1.4%) were observed. ST36 and ST19 were found circulating in both clinical and environmental host, while ST313 isolates had an exclusive clinical origin. All ST19 isolates (100%) were drug-resistant, while isolates belonging to ST313 (100%), ST213 (100%) and ST36 (82%) were pan susceptible. The virulence plasmid (VP) genes (spvB- spvC) were present in all genotypes except ST36. The VP was significantly (p…

Abstract Background A mosquito-based arbovirus surveillance system was set up at Barkedji, Senegal after the first outbreak of Rift valley fever in West Africa in 1988. This system was recently updated using more sampling methods and collecting in greater number of ponds and villages sites. Methods For the current study, mosquitoes were sampled biweekly between July and December 2012 and 2013 using CDC+CO2 light traps set at ground and canopy level, mosquito nets baited with goat, sheep, human or chicken, light traps baited with goat, sheep and chicken; bird-baited traps using pigeons or chickens placed either at the ground or canopy level. Collected mosquitoes were identified, pooled and screened for arboviruses. Results A total of 42,969 mosquitoes in 4,429 pools were processed for virus isolation. Ten virus species were identified among 103 virus isolates. West Nile virus (WNV; 31 isolates), Barkedji virus (BARV; 18), Sindbis virus (SINV; 13), Usutu virus (USUV; 12), Acado virus (ACAV; 8), Ndumu virus (NDUV; 9), Sanar virus (SANV; 7), Bagaza virus (BAGV; 3), Rift valley fever virus (RVFV; 1), and Yaounde virus (YAOV; 1) were isolated from 9 ponds (91 strains) and 7 villages (12 strains). Only 3 virus species (WNV, NDU and SINV) were isolated from villages. The largest numbers of isolates were collected in October (29.1% of total isolates) and November (50.5%). Viruses were isolated from 14 mosquito species including Cx. neavei (69.9% of the strains), Cx. antennatus (9.7%), and Ma. uniformis (4.8%). NDUV, ACAV, and SINV are herein reported for the first time in the Barkedji area. Isolation of ACAV and SANV from a pool of male Ma. uniformis and USUV and BARV from a pool of male Cx. neavei, are reported for the first time to our knowledge. Conclusion Our data indicate that the Barkedji area is characterized by a high diversity of viruses of medical, veterinary and unknown importance. Arboviruses were first detected in July at the beginning of the rainy season and peaked in abundance in October and November. The Barkedji area, an enzootic focus of several potentially emerging arboviruses, should be surveilled annually to be prepared to deal with future disease emergence events.…

Abbasi J.

Researchers at Imperial College London are developing an artificial intelligence (AI) agent to help physicians select optimal fluid and vasopressor doses for adult patients with sepsis in intensive care units (ICUs).

Abstract Background Liver transplant recipients are at high risk of developing invasive aspergillosis and in particular by Aspergillus fumigatus which is the most commonly encountered species in this population. Other non-fumigatus Aspergillus species with reduced susceptibility to antifungal drugs can also be involved. Accurate identification associated to antifungal susceptibility testing is essential for therapy adjustment. We report a case of invasive pulmonary aspergillosis due to Aspergillus pseudodeflectus in a liver transplant recipient. To our knowledge, this is the first reported case of invasive aspergillosis due to this species with a reduced susceptibility to azoles. Case presentation A 64 year-old woman with drug-induced fulminant hepatitis underwent liver transplantation. Prophylactic treatment with caspofungin was introduced due to aspergillosis risk factors consisting in hemodialysis and fulminant hepatitis. Six weeks after transplantation, CT scan showed a right pulmonary opacity associated with an increase of galactomannan (index 5.4). Culture of BAL grew with several colonies of Aspergillus sp. The diagnosis of invasive aspergillosis was probable according to the EORTC criteria. The antifungal susceptibility tests (Etest®) revealed low MICs to echinocandins and amphotericin B) but high MICs to azoles. After these results, voriconazole was switched to liposomal amphotericin B. The patient died one month after diagnosis from a refractory septic shock with multiple organ failure. A molecular identification of isolate, based on partial β-tubulin and calmodulin genes, was performed and identified A. pseudodeflectus. Conclusions Our case raises the question of pathogenicity of this species, which belongs to Aspergillus section Usti and is genetically and morphologically very close to Aspergillus calidoustus that was previously reported in human transplant recipients.…

Choi S, Weng L, Roselli C, et al.

This nested case-control study of patients with early-onset atrial fibrillation (AF) used large-scale, deep-coverage whole-genome sequencing to identify a loss-of-function variant in TTN, the gene encoding the rare nerve protein titin, as a genetic risk factor for early AF.

Osama Mahmoud

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 12, Page 1539-1548, December 15, 2018. …

Watson, Paula L.; Pandharipande, Pratik; Gehlbach, Brian K.; Thompson, Jennifer L.; Shintani, Ayumi K.; Dittus, Bob S.; Bernard, Gordon R.; Malow, Beth A.; Ely, E. Wesley

Objectives: Standard sleep scoring criteria may be unreliable when applied to critically ill patients. We sought to quantify typical and atypical polysomnographic findings in critically ill patients and to begin development and reliability testing of methodology to characterize the atypical polysomnographic tracings that confound standard sleep scoring criteria. Design: Prospective convenience sample. Setting: Two academic, tertiary care medical centers. Patients: Thirty-seven critically ill, mechanically ventilated, medical ICU patients. Interventions: None. Measurements and Main Results: Mechanically ventilated subjects were monitored by continuous polysomnography. After noting frequent atypical polysomnographic findings (i.e., lack of stage N2 markers, the presence of polymorphic delta, burst suppression, or isoelectric electroencephalography), attempts to use standard sleep scoring criteria alone were abandoned. Atypical polysomnographic findings were characterized and used to develop a modified scoring system. Polysomnographic data were scored manually via this revised scoring scheme. Of 7 medical ICU patients enrolled, 6 experienced atypical sleep, which accounted for 85% of all recorded data, with 5.1% normal sleep and 9.4% wake. Coupling observed patient arousal levels with polysomnographic characteristics revealed that standard polysomnographic staging criteria did not reliably determine the presence or absence of sleep. Rapid eye movement occurred in only five patients (14%). The revised scoring system incorporating frequently seen atypical characteristics yielded very high interrater reliability (weighted κ = 0.80; bootstrapped 95% CI, [0.48, 0.89]). Conclusions: Analysis of polysomnographic data revealed profound deficiencies in standard scoring criteria due to a predominance of atypical polysomnographic findings in ventilated patients. The revised scoring scheme proved reliable in sleep staging and may serve as a building block in future work. This work was performed in Vanderbilt University Medical Center and University of Chicago. Dr. Watson received support from the National Institutes of Health (MO1 RR-00095) and the Vanderbilt CTSA grant UL1 RR024975-01 from NCRR/NIH. Dr. Gehlbach received support from the National Institutes of Health (K2 HL088020), the Brain Research Foundation, the Institute for Translational Medicine (CTSA grant number UL1 RR024999), and the Department of Medicine at the University of Chicago. Dr. Pandharipande is supported by a VA Career Development Award (CSRD). Dr. Bernard is supported by NIH/NCRR UL1RR024975-0S5. Dr. Malow is supported by the Vanderbilt CTSA grant UL1 RR024975-01 from NCRR/NIH. Dr. Ely is supported by the National Institutes of Health (R01AG027472 and R01AG05117) and the VA Clinical Science Research and Developmental (VA Merit Review Award). Dr. Watson has received an unrestricted research grant for an investigator-initiated study from Aspect Medical Systems, Inc. and honorarium from Hospira Inc. Dr. Pandharipande has received a research grant from Hospira Inc. and honoraria from Hospira Inc. and Orion Pharma. Dr. Ely has received grants from Aspect Medical Systems, Eli Lily, and honoraria from Hospira, Abbott, and Masimo.The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: paula.l.watson@vanderbilt.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Patel K, Johnson J, Reece R, et al.

AbstractBackgroundSpontaneous splenic rupture is an increasingly reported complication of babesiosis and has been described as a severe complication.MethodsWe performed a retrospective chart review in a high prevalence area to identify seven cases of babesiosis-related splenic rupture between 2014 – 2016.ResultsSplenic rupture occurred in approximately 1% of babesiosis cases. Compared to cases without splenic rupture, these patients were younger (by >10 years), healthier (most with ≤1 comorbidity), had a lower degree of parasitemia (

Kazumi Yamasaki, Junko Tanaka, Akemi Kurisu, Tomoyuki Akita, Masayuki Ohisa, Kazuaki Sakamune, Ko Ko, Aya Sugiyama, Takahiro Yasaka, Satoshi Shirahama

Cover Caption: The cover image is based on the Research Article Analytical performance of a low-cost multiplex polymerase chain reaction human papillomavirus genotyping assay for use in Sub‐Saharan Africa, by Kandali Samwel et al., DOI 10.1002/jmv.25329.

McGlothlin AE, Viele K.

This JAMA Guide to Statistics and Methods discusses the use, limitations, and interpretation of Bayesian hierarchical modeling, a statistical procedure that integrates information across multiple levels and uses prior information about likely treatment effects and their variability to estimate true vs random treatment effects.

Abstract Background Lassa fever has been a public health concern in the West African sub-region where it is endemic and a latent threat to the world at large. We investigated the trend in Lassa fever research using bibliometric approach. Methods We used the SCOPUS database employing “Lassa fever” as search descriptor. The most common bibliometric indicators were applied for the selected publications. Results The number of scientific research articles retrieved for Lassa fever research from 1970 to 2017 was 1101. The growth of publications was more linear (r = 0.67) than exponential (r = 0.53). The duplication time of the scientific articles was 9.19 years. Small number of authors were responsible for bulk of the article production (transience index of 78.89%). The collaboration index was 4.59 per paper. The Bradford core consisted of 19 journals in which Journal of Virology was at the top (4.6%). Majority of the output were from USA government agencies. United States was the most productive country. Joseph B. McCormick was the most productive author, while New England Journal of Medicine published the two most cited articles. Conclusion The growth of scientific Literature on Lassa fever was of linear pattern with high transient authors indicating low productivity and non-specialized authors from other related areas publishing sporadically. This study provides a helpful reference for medical virologists, epidemiologist, policy decision makers, academics and Lassa fever researchers.…

Turan, Bulent; Crockett, Kaylee B.; Buyukcan-Tetik, Asuman; Kempf, Mirjam-Colette; Konkle-Parker, Deborah; Wilson, Tracey E.; Tien, Phyllis C.; Wingood, Gina; Neilands, Torsten B.; Johnson, Mallory O.; Weiser, Sheri D.; Turan, Janet M.

Background: One mechanism through which social stigma of HIV affects health outcomes for people living with HIV (PLWH) is via internalization of stigma. However, this transformation of social stigma in the community into internalized stigma may not be of the same magnitude for all PLWH. We examined the moderating effects of 3 personality traits—fear of negative social evaluation, attachment-related anxiety, and dispositional resilience—in transforming perceived stigma in the community into internalized stigma. Furthermore, we investigated downstream effects of these moderated associations on depressive symptoms and antiretroviral treatment (ART) adherence. Setting/Methods: In Study 1, data from 203 PLWH in the southeast US were analyzed controlling for age, sex, education, race, and time on ART. In Study 2, data from 453 women in a multi-site study were analyzed controlling for age, education, race, time on ART, and substance use. Results: In both studies, fear of negative evaluation and attachment-related anxiety moderated the effect of perceived HIV stigma in the community on internalized HIV stigma: People higher on those moderating variables had stronger associations between perceived stigma in the community and internalized stigma. In study 2, resilience was assessed, and also moderated the effect of perceived HIV stigma in the community on internalized stigma. In moderated mediation models, fear of negative evaluation, attachment-related anxiety, and resilience moderated the indirect effect of perceived HIV stigma in the community on ART adherence and depression through internalized stigma. Conclusions: Interventions to assuage internalization of HIV stigma should focus on bolstering attachment-related security, social competence, and resilience. Corresponding Author (requests for reprints should also be made to): Bulent Turan Email address: bturanb@uab.edu; bturanb@gmail.com Telephone: (650) 387 0251 Address: 415 Campbell Hall, Dept. of Psychology, University of Alabama at Birmingham, Birmingham, AL 35294-1170 * Bulent Turan and Kaylee B. Crockett contributed equally to this manuscript. The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Duncan Wilson

Pathogens often face zinc restriction due to the action of nutritional immunity – host processes which restrict microbial access to key micronutrients such as zinc and iron. Candida albicans scavenges environmental zinc via two pathways. The plasma membrane transporter Zrt2 is essential for zinc uptake and growth in acidic environments. Neutralisation to pH 7 severely decreases the solubility of ionic Zn2+; this increase in pH triggers expression and activity of a second zinc scavenging system, the zincophore.

Jores J, Schieck E, Liljander A, et al.

AbstractCapsular polysaccharides have been confirmed to be an important virulence trait in many different Gram-positive and Gram-negative bacteria. Similarly, they are proposed to be virulence traits in minimal Mycoplasma that cause disease in humans and animals. In this study, goats were infected with the caprine pathogen Mycoplasma mycoides subsp. capri or an engineered mutant lacking the capsular polysaccharide, galactofuranose. Goats infected with the mutant strain showed only transient fever. In contrast, five out of eight goats infected with the parental strain reached endpoint criteria after infection. This work confirms that galactofuranose is a virulence factor in Mycoplasma mycoides.

Abstract Background Congenital malaria is usually defined as the detection of asexual forms of Plasmodium spp. in a blood sample of a neonate during perinatal age if there is no possibility of postpartum infection by a mosquito bite. The incidence of congenital malaria is highly variable and seems related to several factors, such as different diagnostic methods for Plasmodium spp. detection, and area in which the epidemiologic analyses are performed. In non-endemic countries, cases of congenital malaria are rare. Hereby, a case of a congenital malaria in an HIV exposed child is reported. Case presentation A 2-month-old male child was admitted to Bambino Gesù Children’s Hospital due to anaemia and exposure to HIV. He was born prematurely in Italy by cesarean section at 34 weeks’ gestation after a bicorial, biamniotic pregnancy by a migrant woman from Nigeria. He was the first of non-identical twins. Combined with anaemia, spleen and liver enlargement was noted, malaria was hypothesized. Malaria laboratory panel was performed on the newborn, mother and other twin blood samples, as follows: (i) malaria rapid diagnostic test (RDT); (ii) Giemsa-stained thick and thin blood smears for Plasmodium spp. identification and parasitaemia titration; (iii) molecular screening and typing of Plasmodium spp. by multiplex qualitative PCR assay based on 18S rRNA gene. Genotyping of Plasmodium falciparum isolates from mother and child was performed by neutral microsatellite and highly polymorphic marker amplification. Conclusions The maternal RDT sample was negative, while the infant RDT was positive; in both cases microscopy of blood smears and PCR showed infection with P. falciparum. Two of the genotypic molecular markers displayed different allelic variants between the two samples. This difference could imply infection multiplicity of the mother during the pregnancy, possibly harbouring more than one isolate, only one of them being transmitted to the newborn while the other persisting in the mother’s blood. Because of the increasing number of pregnant women coming from endemic areas for malaria, an accurate anamnesis of infant’s mother, and the inclusion of Plasmodium spp. research into TORCH screenings for mother-infant pair at birth, aiming at reducing morbidity and mortality associated to the disease might be suitable.…

Chin Man Poon, Ngai Sze Wong, Tsz Ho Kwan, Horas Tze Hoo Wong, Kenny Chi Wai Chan, Shui Shan Lee

by Chin Man Poon, Ngai Sze Wong, Tsz Ho Kwan, Horas Tze Hoo Wong, Kenny Chi Wai Chan, Shui Shan Lee Background While HIV incidence among men who have sex with men (MSM) is increasing in Hong Kong, unprotected sex apparently remains prevalent among those infected but virally non-suppressed. Little is known about how sexual behaviours and sexual connections may change among MSM along their HIV care continuum. Methods In this retrospective cross-sectional study, HIV-positive MSM attending the largest HIV specialist clinic in Hong Kong between October and December 2014 were invited to complete a self-administrated structured questionnaire. Their behavioural profile and partner sourcing patterns during the one-year period respectively (a) before HIV diagnosis, (b) after HIV diagnosis, (c) after initiation of antiretroviral treatment and (d) preceding the survey were examined. Results Of 345 recruited MSM, 304 (88.1%) had treatment initiated and 272 (78.8%) had viral load suppressed. In the first year after HIV diagnosis, the proportion reporting inconsistent condom use dropped from 47.0% to 17.5% (p

Abstract Background The most prevalent strains of Mycobacterium tuberculosis (M.tb) in Beijing belong to the Beijing genotype family. The influence of Beijing genotype prevalence on the development of drug resistance, and the association of infection with Beijing genotype M.tb with population characteristics, in Beijing, however, are still unclear. Methods In this retrospective study, 1189 isolates were subjected to drug susceptibility testing (DST) and molecular epidemiological analysis, and differences in the percentage of drug resistance between Beijing and non-Beijing genotype strains were compared. The association between the occurrence of drug resistance and the prevalence of Beijing genotype M.tb was analyzed using statistical methods. Results The Beijing genotype family was the dominant genotype (83.3%) among the 1189 M.tb isolates. Beijing genotype M.tb strains were more likely to spread among males [p = 0.018, OR (95% CI):1.127(1.004–1.264)] and people in the 45–64 age group [p = 0.016, OR (95% CI): 1.438 (1.027–2.015)]. On the contrary, non-Beijing genotype M.tb strains were more probably disseminated among the over 65 [p = 0.005, OR (95% CI):0.653 (0.474–0.9)] and non-resident population [p = 0.035, OR (95% CI):1.185(0.985–1.427)]. DST results showed that 849 (71.4%) strains were fully sensitive to first-line drugs, while 340 (28.6%) strains were resistant to at least one drug, and 9% (107/1189) were MDR-TB. The frequency of INH-resistance among Beijing genotype strains was significantly lower than that among non-Beijing genotype strains (p = 0.032). In addition, the Beijing genotype family readily formed clusters. Conclusions Our findings indicate that male and middle-aged people were more probably be infected by Beijing genotype M.tb, older people and non-residents were more probably be infected by non-Beijing genotype M.tb. The high percentage of resistance to INH occurring in non-Beijing genotype strains suggested that non-Beijing genotype strains should be given much more interest in Beijing.…

Magudia K, Bick A, Cohen J, et al.

This study describes childbearing and family leave at 15 graduate medical education (GME)–sponsoring institutions affiliated with 12 US medical schools on top 10 lists for funding or ranking.

Sonja E. van Roeden, Peter C. Wever, Linda M. Kampschreur, Paul Gruteke, Wim van der Hoek, Andy I.M. Hoepelman, Chantal P. Bleeker-Rovers, Jan Jelrik Oosterheert

Chronic infection with Coxiella burnetii (chronic Q fever) can cause life threatening conditions such as endocarditis, infected vascular prostheses and infected arterial aneurysms. We aimed to assess prognosis of chronic Q fever patients in terms of complications and mortality.

Minh Tu Van Hoang, To Anh Nguyen, Tan Thanh Tran, Thi Ty Hang Vu, Nguyen Truc Nhu Le, Thi Han Ny Nguyen, Thanh Hoang Nhat Le, Thi Thu Hong Nguyen, Thanh Hung Nguyen, Nguyen Thanh Nhan Le, Huu Khanh Truong, Tuan Quy Du, Manh Tuan Ha, Lu Viet Ho, Chau Viet Do, Tran Nam Nguyen, Thi My Thanh Nguyen, Saraswathy Sabanathan, Tu Qui Phan, Vinh Chau Nguyen Van, Guy E. Thwaites, Bridget Wills, C. Louise Thwaites, Van Tan Le, H. Rogier van Doorn

Abstract Background Bacterial co-infection of patients suffering from influenza pneumonia is a key element that increases morbidity and mortality. The occurrence of Acinetobacter baumannii co-infection in patients with avian influenza A (H7N9) virus infection has been described as one of the most prevalent bacterial co-infections. However, the clinical and laboratory features of this entity of H7N9 and A. baumannii co-infection have not been systematically investigated. Methods We collected clinical and laboratory data from laboratory-confirmed H7N9 cases co-infected by A. baumannii. H7N9 patients without bacterial co-infection and patients with A. baumannii-related pneumonia in the same hospital during the same period were recruited as controls. The antibiotic resistance features and the corresponding genome determinants of A. baumannii and the immune responses of the patients were tested through the respiratory and peripheral blood specimens. Results Invasive mechanical ventilation was the most significant risk factor for the nosocomial A. baumannii co-infection in H7N9 patients. The co-infection resulted in severe clinical manifestation which was associated with the dysregulation of immune responses including deranged T-cell counts, antigen-specific T-cell responses and plasma cytokines. The emergence of genome variations of extensively drug-resistant A. baumannii associated with acquired polymyxin resistance contributed to the fatal outcome of a co-infected patient. Conclusions The co-infection of H7N9 patients by extensively drug-resistant A. baumannii with H7N9 infection is an important issue which deserves attention. The dysfunctions of immune responses were associated with the co-infection and were correlated with the disease severity. These data provide useful reference for the diagnosis and treatment of H7N9 infection.…