Abstract Introduction Staphylococcus aureus frequently causes infections in outpatient and hospital settings and can present as a highly variable entity. Typical manifestations are endocarditis, osteoarticular infections or infection of implanted prostheses, intravascular devices or foreign bodies. A thorough diagnostic evaluation with early focus identification is mandatory to improve patient outcome. Case report We report a case of a 68-year old patient with a history of double allogeneic stem cell transplant for acute myeloid leukemia who developed a S. aureus bacteremia with dissemination, severe sepsis and lethal outcome due to nasal handkerchief packing after nose bleeding. Conclusion A thorough medical examination with further diagnostic work-up is most important in S. aureus blood stream infection to identify and eradicate the portal(s) of entry, to rule out endocarditis, to search for spinal abscesses, osteomyelitis or spondylodiscitis. Adherence to management guides for clinicians must be of major importance to achieve optimal quality of clinical care, and thus improve patient outcome.

Folusho Balogun, Olayemi Omotade

by Folusho Balogun, Olayemi Omotade Background Human Papilloma virus (HPV) vaccines for adolescents are pivotal in the control of cervical cancer, the commonest women specific malignancy in sub-Saharan Africa. Knowledge about cervical cancer have been reported to be low in Africa but expressed acceptability for HPV vaccines have been high. The reason for this mismatch is not clear. An understanding of the interpretation of cervical cancer and views about HPV vaccine are important as they can affect actual decision making regarding adolescents’ uptake of HPV vaccine. This study explored contextual interpretations of stakeholders regarding cervical cancer and HPV vaccines for adolescents in five selected communities in Ibadan, Nigeria. Methods Qualitative data were collected through twenty focus group discussions among parents of adolescents, religious and traditional leaders, school teachers and adolescents; and four key informant interviews with the identified traditional healers in the selected communities. Constant comparison analysis was done after transcription. Results Almost every group had at least one person who had seen a cervical cancer patient. Cervical cancer was widely viewed as being caused by promiscuity of women while older participants believed that the alteration of lifestyle by civilization was a major contributory factor. There was also a general notion that it was due to a curse. The role of HPV was generally not known. Most participants were favourable towards HPV immunization for adolescents but traditional healers and some religious leaders were not. The high cost of the vaccines and possibility of side effects where the main concerns about the introduction of HPV vaccine. Decision to take the vaccine rest with the fathers whose views were heavily influenced by traditional and religious leaders. Conclusions Awareness about cervical cancer may not be as low as earlier reported and there were many misconceptions about cervical cancer in the study communities. It is important to address these misconceptions to ensure successful introduction of HPV vaccine for adolescents in future.

GBD 2016 Diarrhoeal Disease Collaborators

Substantial progress has been made globally in reducing the burden of diarrhoeal diseases, driven by decreases in several primary risk factors. However, this reduction has not been equal across locations, and burden among adults older than 70 years requires attention.

Elshad Hasanov, Elmira Vaziri Fard, Abin Puravath, Jason S Johnston, Shareez Peerbhai, Cristhiam M Rojas-Hernandez

A 64-year-old man was referred for evaluation of neutropenia. The patient complained of bilateral symmetrical pain and morning stiffness in multiple joints, and weight loss, fevers, increased sweating, and fatigue—all of which had been present for 2 months. Physical examination showed bilateral synovitis in the elbow, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. There was no lymphadenopathy or splenomegaly.

The Lancet

On Sept 12, the International Agency for Research on Cancer published the GLOBOCAN 2018 estimates of worldwide incidence and mortality for 36 cancers and cancer overall. Behind the data, gathered from local registries representing 185 countries, are the stories of 18·1 million people diagnosed with cancer in 2018 and the sorrow of 9·6 million deaths.

The Lancet

One of the most powerful forces to emerge from the MDG era has been the idea of accountability. At its most elementary level, accountability means holding those with responsibility for health accountable for their commitments. It is a controversial concept. Few governments wish to be judged by their actions. Global health is replete with pledges, agreements, and declarations guaranteeing outcomes. A Marshall Plan for west Africa after Ebola? Financial assistance to deliver universal health coverage? Scaling up human resources for health? Empty promises.

NCD Countdown 2030 collaborators

The third UN High-Level Meeting on Non-Communicable Diseases (NCDs) on Sept 27, 2018, will review national and global progress towards the prevention and control of NCDs, and provide an opportunity to renew, reinforce, and enhance commitments to reduce their burden. NCD Countdown 2030 is an independent collaboration to inform policies that aim to reduce the worldwide burden of NCDs, and to ensure accountability towards this aim. In 2016, an estimated 40·5 million (71%) of the 56·9 million worldwide deaths were from NCDs.

Simon Shorvon, Linda Luxon

The Royal College of Physicians (RCP) celebrates its 500th anniversary on Sept 23, 2018. Few organisations have been in continual existence for longer in the field of medicine and to be able to celebrate a quincentenary is a remarkable achievement. Over 500 years, the RCP has assumed different functions as a consequence of the many changes in British sociopolitical history and British medicine. Here, we reflect on some of these changing roles and challenges to the current roles of the College.

Talha Burki

Hundreds more cases of West Nile virus have been recorded in Europe this year compared with the 2017 season, which experts think might be a consequence of the hot summer. Talha Burki reports.

Ranzani, Otavio T.; Shankar-Hari, Manu; Harrison, David A.; Rabello, Lígia S.; Salluh, Jorge I. F.; Rowan, Kathryn M.; Soares, Marcio

Objectives: To test whether differences in both general and sepsis-specific patient characteristics explain the observed differences in sepsis mortality between countries, using two national critical care (ICU) databases. Design: Cohort study. Setting: We analyzed 62 and 164 ICUs in Brazil and England, respectively. Patients: Twenty-two–thousand four-hundred twenty-six adult ICU admissions from January 2013 to December 2013. Interventions: None. Measurements and Main Results: After harmonizing relevant variables, we merged the first ICU episode of adult medical admissions from Brazil (ORganizational CHaractEeriSTics in cRitical cAre study) and England (Intensive Care National Audit & Research Centre Case Mix Programme). Sepsis-3 definition was used, and the primary outcome was hospital mortality. We used multilevel logistic regression models to evaluate the impact of country (Brazil vs England) on mortality, after adjustment for general (age, sex, comorbidities, functional status, admission source, time to admission) and sepsis-specific (site of infection, organ dysfunction type and number) patient characteristics. Of medical ICU admissions, 13.2% (4,505/34,150) in Brazil and 30.7% (17,921/58,316) in England met the sepsis definition. The Brazil cohort was older, had greater prevalence of severe comorbidities and dependency compared with England. Respiratory was the most common infection site in both countries. The most common organ dysfunction was cardiovascular in Brazil (41.2%) and respiratory in England (85.8%). Crude hospital mortality was similar (Brazil 41.4% vs England 39.3%; odds ratio, 1.12 [0.98–1.30]). After adjusting for general patient characteristics, there was an important change in the point-estimate of the odds ratio (0.88 [0.75–1.02]). However, after adjusting for sepsis-specific patient characteristics, the direction of effect reversed again with Brazil having higher risk-adjusted mortality (odds ratio, 1.22 [1.05–1.43]). Conclusions: Patients with sepsis admitted to ICUs in Brazil and England have important differences in general and sepsis-specific characteristics, from source of admission to organ dysfunctions. We show that comparing crude mortality from sepsis patients admitted to the ICU between countries, as currently performed, is not reliable and that the adjustment for both general and sepsis-specific patient characteristics is essential for valid international comparisons of mortality amongst sepsis patients admitted to critical care units. Drs. Rowan and Soares are senior authors. † In memoriam. The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health. Drs. Ranzani and Shankar-Hari are equal contributors. Dr. Ranzani did data analyses. Drs. Ranzani and Shankar-Hari wrote the first draft of the article. Drs. Harrison, Rabello, Salluh, Rowan, and Soares led data collection. Dr. Rabello died during the peer-review process of this article. All authors unanimously agreed on her fundamental contribution for this study. All authors conceptualized and designed the study, interpreted data, and critically revised the article. 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 (http://journals.lww.com/ccmjournal). The original ORganizational CHaractEeriSTics in cRitical cAre study was supported by the National Council for Scientific and Technological Development (Grant number 304240/2014-1), Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro and by departmental funds from the D’Or Institute for Research and Education. The Case Mix Programme is a subscription-based, national quality assessment program. The current study was funded internally by Intensive Care National Audit & Research Centre. The funding sources had no role in the design, conduct or analyses of the study. Dr. Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (NIHR-CS-2016-16-011). Dr. Soares disclosed that he is founder and equity shareholder at Epimed Solutions. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: otavioranzani@usp.br Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Dian, S., Yunivita, V., Ganiem, A. R., Pramaesya, T., Chaidir, L., Wahyudi, K., Achmad, T. H., Colbers, A., te Brake, L., van Crevel, R., Ruslami, R., Aarnoutse, R.

High doses of rifampicin may help tuberculous meningitis (TBM) patients to survive. Pharmacokinetic-pharmacodynamic evaluations suggested that rifampicin doses higher than 13 mg/kg intravenously or 20 mg/kg orally (as previously studied) are warranted to maximize treatment response. In a double-blinded, randomised, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg or 1350 mg (10, 20 and 30 mg/kg) oral rifampicin combined with other TB drugs for 30 days. Endpoints included pharmacokinetic measures, adverse events and survival. A double and triple dose of oral rifampicin led to three and five-fold higher geometric mean total exposures in plasma in the critical early days (2±1) of treatment (AUC0-24h: 53·5 mg.h/L vs 170·6 mg.h/L vs. 293·5 mg.h/L, p

Jing Zhang , Xun Gui , Qingbing Zheng , Yixin Chen , Shengxiang Ge , Jun Zhang , Ningshao Xia

Abstract Rapid and sensitive diagnosis of influenza is urgently needed to address the limitations of low sensitivity associated with current rapid tests available for clinics and on‐site monitoring. A novel horseradish peroxidase (HRP)‐labeled lateral flow immunoassay strip (HRP‐LFIA) for rapid simultaneous detection and differentiation of influenza A (INF A) and influenza B (INF B) viruses was developed. This immunoassay was based on the signal amplification by the HRP‐catalyzed oxidation of 3, 3,’ 5, 5’‐tetramethylbenzidine (TMB) forming colored insoluble product which was proportional to the analyte concentration. Compared to conventional gold‐colloidal based strips, an analytical sensitivity enhancement of more than one order of magnitude for seven INF virus isolates was observed. A total of 1487 swabs obtained from persons with influenza‐like illnesses (ILIs) were tested for the presence of INF A and B viruses using real‐time reverse transcription polymerase chain reaction (rRT‐PCR) as reference criterion. The overall sensitivities of HRP‐LFIA were 77.5% (100/129) and 71.2% (116/163) for INF A and INF B, respectively. The overall specificities were 99.8% (1144/1146) and 99.8% (918/920) respectively. The nasopharyngeal sampling method yielded higher sensitivity rates of 90.2% (55/61) and 82.6% (71/86). In conclusion, this user‐friendly assay could be a promising rapid detection method for rapid screening for INF A and INF B viruses. This article is protected by copyright. All rights reserved.

Zhao, C., Lv, Y., Wei, M., Li, X., Hou, F., Wang, J., Ma, X., Kang, Z., Wei Mao, , Liu, Y., Xia, Y., Tian, J.

Chinfloxacin hydrochloride is a novel tricyclic fluorinated quinolone in development for treatment of conventional and biothreat infections. This first-in-human randomized study in Chinese healthy subjects was divided into 5 parts. Part A was a single ascending dose study to assess safety and tolerability of chinfloxacin. The single dose pharmacokinetic study, food effect study and a multiple dose pharmacokinetics study was conducted in Part B, Part C and Part D, respectively. Part E was a randomized, placebo- and positive-controlled single-dose, crossover study to evaluate the effect of chinfloxacin on thorough electrocardiographic QT/QTc interval. The results suggest that single and multiple oral administration of chinfloxacin were well tolerated. The observed adverse events (AEs) were dizziness, nausea, weakness, photosensitive dermatitis and increased frequency of defecation. All AEs were mild and were resolved spontaneously without any treatment. The time to Cmax (Tmax) was about 2 h and T1/2 was 14-16 h. Food slightly affected the drug’s rate and extent of absorption, increasing the Tmax from 1.60 to 2.59 h and reducing the Cmax by 13.6% and AUC by 8.95%, respectively. Chinfloxacin 400 mg had no effect on prolongation of QT/QTc intervals. Although chinfloxacin 600 mg caused mild effect on prolongation of QT/QTc interval, the effect was less pronounced than that of the positive control, moxifloxacin 400 mg. The pharmacokinetics and safety profiles of chinfloxacin in healthy Chinese volunteers support its once-daily dosing in future clinical investigations. (This study has been registered at ChiCTR.org.cn. Identifier of Part A to Part D: ChiCTR-TRC-10001619; Identifier of the Part E: ChiCTR1800015906.)…

Lee, Albert H.; Ledderose, Carola; Li, Xiaoou; Slubowski, Christian J.; Sueyoshi, Koichiro; Staudenmaier, Laura; Bao, Yi; Zhang, Jingping; Junger, Wolfgang G.

Objectives: Monocytes and macrophages produce interleukin-1β by inflammasome activation which involves adenosine triphosphate release, pannexin-1 channels, and P2X7 receptors. However, interleukin-1β can also be produced in an inflammasome-independent fashion. Here we studied if this mechanism also involves adenosine triphosphate signaling and how it contributes to inflammasome activation. Design: In vitro studies with human cells and randomized animal experiments. Setting: Preclinical academic research laboratory. Subjects: Wild-type C57BL/6 and pannexin-1 knockout mice, healthy human subjects for cell isolation. Interventions: Human monocytes and U937 macrophages were treated with different inhibitors to study how purinergic signaling contributes to toll-like receptor-induced cell activation and interleukin-1β production. Wild-type and pannexin-1 knockout mice were subjected to cecal ligation and puncture to study the role of purinergic signaling in interleukin-1β production and host immune defense. Measurements and Main Results: Toll-like receptor agonists triggered mitochondrial adenosine triphosphate production and adenosine triphosphate release within seconds. Inhibition of mitochondria, adenosine triphosphate release, or P2 receptors blocked p38 mitogen-activated protein kinase and caspase-1 activation and interleukin-1β secretion. Mice lacking pannexin-1 failed to activate monocytes, to produce interleukin-1β, and to effectively clear bacteria following cecal ligation and puncture. Conclusions: Purinergic signaling has two separate roles in monocyte/macrophage activation, namely to facilitate the initial detection of danger signals via toll-like receptors and subsequently to regulate nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 inflammasome activation. Further dissection of these mechanisms may reveal novel therapeutic targets for immunomodulation in critical care patients. 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 (http://journals.lww.com/ccmjournal). Supported, in part, by grants from the National Institutes of Health, GM-51477, GM-60475, GM-116162, AI-080582, and T32 GM-103702. Drs. Lee, Zhang, and Junger received support for article research from the National Institutes of Health. Dr. Li received support for article research from National Natural Science Foundation of China No. 81701564. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: wjunger@bidmc.harvard.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Background Viet Nam has made tremendous progress towards reducing mortality and morbidity associated with malaria in recent years. Despite the success in malaria control, there has been a recent increase in cases in some provinces. In order to understand the changing malaria dynamics in Viet Nam and measure progress towards elimination, the aim of this study was to describe and quantify spatial and temporal trends of malaria by species at district level across the country. Methods Malaria case reports at the Viet Nam National Institute of Malariology, Parasitology, and Entomology were reviewed for the period of January 2009 to December 2015. The population of each district was obtained from the Population and Housing Census-2009. A multivariate (insecticide-treated mosquito nets [ITN], indoor residual spraying [IRS], maximum temperature), zero-inflated, Poisson regression model was developed with spatial and spatiotemporal random effects modelled using a conditional autoregressive prior structure, and with posterior parameters estimated using Bayesian Markov chain Monte Carlo simulation with Gibbs sampling. Covariates included in the models were coverage of intervention (ITN and IRS) and maximum temperature. Results There was a total of 57,713 Plasmodium falciparum and 32,386 Plasmodium vivax cases during the study period. The ratio of P. falciparum to P. vivax decreased from 4.3 (81.0% P. falciparum; 11,121 cases) in 2009 to 0.8 (45.0% P. falciparum; 3325 cases) in 2015. Coverage of ITN was associated with decreased P. falciparum incidence, with a 1.1% (95% credible interval [CrI] 0.009%, 1.2%) decrease in incidence for 1% increase in the ITN coverage, but this was not the case for P. vivax, nor was it the case for IRS coverage. Maximum temperature was associated with increased incidence of both species, with a 4% (95% CrI 3.5%, 4.3%) and 1.6% (95% CrI 0.9%, 2.0%) increase in P. falciparum and P. vivax incidence for a temperature increase of 1 °C, respectively. Temporal trends of P. falciparum and P. vivax incidence were significantly higher than the national average in Central and Central-Southern districts. Conclusion Interventions (ITN distribution) and environmental factors (increased temperature) were associated with incidence of P. falciparum and P. vivax during the study period. The factors reviewed were not exhaustive, however the data suggest distribution of resources can be targeted to areas and times of increased malaria transmission. Additionally, changing distribution of the two predominant malaria species in Viet Nam will require different programmatic approaches for control and elimination.

Forthal, Donald N.; Finzi, Andrés

No abstract available…

Sader, H. S., Flamm, R. K., Carvalhaes, C. G., Castanheira, M.

P. aeruginosa isolates (n = 1,909) were collected from 70 United Sates medical centers and susceptibility tested by broth microdilution method. Ceftazidime-avibactam (MIC50/90, 2/8 mg/liter) and ceftolozane-tazobactam (MIC50/90, 0.5/2 mg/liter) were the most active (highest susceptibility rates) compounds after colistin, with national susceptibility rates of 96.9% and 97.5%, respectively. Overall, piperacillin-tazobactam (MIC50/90, 4/128 mg/liter) and meropenem (MIC50/90, 0.5/16 mg/liter) were active against 77.5% and 76.0%, respectively. Susceptibility variations across census divisions were documented for many antimicrobials.

Clotilde Allavena, Matthieu Hanf, David Rey, Claudine Duvivier, Firouze BaniSadr, Isabelle Poizot-Martin, Christine Jacomet, Pascal Pugliese, Pierre Delobel, Christine Katlama, Véronique Joly, Christian Chidiac, Nathalie Dournon, Dominique Merrien, Thierry May, Jacques Reynes, Amandine Gagneux-Brunon, Catherine Chirouze, Thomas Huleux, André Cabié, François Raffi, the Dat’AIDS study group

by Clotilde Allavena, Matthieu Hanf, David Rey, Claudine Duvivier, Firouze BaniSadr, Isabelle Poizot-Martin, Christine Jacomet, Pascal Pugliese, Pierre Delobel, Christine Katlama, Véronique Joly, Christian Chidiac, Nathalie Dournon, Dominique Merrien, Thierry May, Jacques Reynes, Amandine Gagneux-Brunon, Catherine Chirouze, Thomas Huleux, André Cabié, François Raffi, the Dat’AIDS study group As HIV-infected adults on successful antiretroviral therapy (ART) are expected to have close to normal lifespans, they will increasingly develop age-related comorbidities. The objective of this cross-sectional study was to compare in the French Dat’AIDS cohort, the HIV geriatric population, aged 75 years and over, to the elderly one, aged from 50 to 74 years. As of Dec 2015, 16,436 subjects (43.8% of the French Dat’AIDS cohort) were aged from 50 to 74 (elderly group) and 572 subjects (1.5%) were aged 75 and over (geriatric group). Durations of HIV infection and of ART were slightly but significantly different, median at 19 and 18 years, and 15 and 16 years in the elderly and geriatric group, respectively. The geriatric group was more frequently at CDC stage C and had a lower nadir CD4. This group had been more exposed to first generation protease inhibitors and thymidine analogues. Despite similar virologic suppression, type of ART at the last visit significantly differed between the 2 groups: triple ART in 74% versus 68.2%, ART ≥ 4 drugs in 4.7% versus 2.7%; dual therapy in 11.6% versus 16.4% in the elderly group and the geriatric group, respectively. In the geriatric group all co-morbidities were significantly more frequent, except dyslipidemia, 4.3% of the elderly group had ≥4 co-morbidities versus18.4% in the geriatric group. Despite more co-morbidities and more advanced HIV infection the geriatric population achieve similar high rate of virologic suppression than the elderly population. A multidisciplinary approach should be developed to face the incoming challenge of aging HIV population.

Abstract Background Most guidelines recommend 6 to 12 weeks of parenteral antibiotic treatment for pyogenic spondylodiscitis. When surgical debridement is adequately performed, further intravenous antibiotic treatment duration can be reduced than that of conservative treatment alone theoretically. However, the appropriate duration of post-surgical parenteral antibiotic treatment is still unknown. This study aimed to identify the risk factors of recurrence and evaluate the appropriate duration after surgical intervention. Methods This 3-year retrospective review included 102 consecutive patients who were diagnosed with pyogenic spondylodiscitis and underwent surgical intervention. Recurrence was defined as recurrent signs and symptoms and the need for another unplanned parenteral antibiotic treatment or operation within one year. This study included two major portions. First, independent risk factors for recurrence were identified by multivariable analysis, using the database of demographic information, pre-operative clinical signs and symptoms, underlying illness, radiographic findings, laboratory tests, intraoperative culture results, and treatment. Patients with any one of the risk factors were considered high-risk; those with no risk factors were considered low-risk. Recurrence rates after short-term (≤3 weeks) and long-term (> 3 weeks) parenteral antibiotic treatment were compared between the groups. Results Positive blood culture and paraspinal abscesses were identified as independent risk factors of recurrence. Accordingly, 59 (57.8%) patients were classified as low-risk and 43 (42.2%) as high-risk. Among the high-risk patients, a significantly higher recurrence rate occurred with short-term than with long-term antibiotic therapy (56.2% vs. 22.2%, p = 0.027). For the low-risk patients, there was no significant difference between short-term and long-term antibiotic therapy (16.0% vs. 20.6%, p = 0.461). Conclusions The appropriate duration of parenteral antibiotic treatment in patients with pyogenic spondylodiscitis after surgical intervention could be guided by the risk factors. The duration of postoperative intravenous antibiotic therapy could be reduced to 3 weeks for patients without positive blood culture or abscess formation.

Ndeye Fatou Ngom, Mame Awa Faye, Kiné Ndiaye, Aminata Thiam, Cheikh Tidiane Ndour, Jean-François Etard, Papa Salif Sow, Moussa Seydi, Eric Delaporte, Amandine Cournil

by Ndeye Fatou Ngom, Mame Awa Faye, Kiné Ndiaye, Aminata Thiam, Cheikh Tidiane Ndour, Jean-François Etard, Papa Salif Sow, Moussa Seydi, Eric Delaporte, Amandine Cournil Objective To examine how patient characteristics combined with ART eligibility expansions affect the initiation of antiretroviral therapy (ART) among eligible patients attending a referral center in Senegal from 1998 to 2015. Methods This is a retrospective observational study carried out at the outpatient treatment Centre (Centre de Traitement Ambulatoire) in Dakar, Senegal, based on computerized medical records, gathered from 1998 to 2015, of ART-naïve patients over 15 years of age. ART eligibility was defined as (CD4 count below 200) or as (WHO stage 4) or as (WHO stage 3 with (CD4 count below 350 or with unavailable CD4 count)) in 1998–2010; as (CD4 count below 350) or as (WHO stage 3 or 4) in 2011–2013; as (CD4 count below 500) or as (WHO stage 3 or 4) in 2014–2015. Four periods were defined according to ART eligibility expansions and Senegal’s HIV care history: 1998–2003 (P 1), 2004–2010 (P 2), 2011–2013 (P3), and 2014–2015 (P4). Patients were expected to participate financially in their treatment during the first period (P1). Results A total of 3651 patient records were included. The median patient age was 40 years (IQR: 32–48). Women represented 56% of the population. The median CD4 count was 183 cells/mm3. Overall, 53% of patients had CD4 < 200 cells/mm3 at entry. This proportion reached 45% in 2014–2015. 2535 patients (69%) were eligible for therapy, including 1503 (41%) who started ART. The proportion of treated patients among those who were eligible at entry or later increased steadily from 25%, 47%, 75% to 82% in the four periods, respectively. The median time to treatment decreased from 5.6 months (IQR: 3–11) in P1 to 0.8 months (IQR: 0–2) in P4. Eligible patients with more advanced disease (CD4…

David Hendrickx, Asha C. Bowen, Julie A. Marsh, Jonathan R. Carapetis, Roz Walker

by David Hendrickx, Asha C. Bowen, Julie A. Marsh, Jonathan R. Carapetis, Roz Walker Infectious diseases contribute a substantial burden of ill-health in Australia’s Aboriginal children. Skin infections have been shown to be common in remote Aboriginal communities, particularly in the Northern Territory, Australia. However, primary care data on skin and other infectious diseases among Aboriginal children living in remote areas of Western Australia are limited. We conducted a retrospective review of clinic presentations of all children aged 0 to 5 years presenting to four clinics located in the Western Desert region of Western Australia between 2007 and 2012 to determine this burden at a local level. Infectious diseases accounted for almost 50% of all clinic presentations. Skin infections (sores, scabies and fungal infections) were the largest proportion (16%), with ear infections (15%) and upper respiratory infections (13%) also high. Skin infections remained high in all age groups; 72% of children presented at least once with skin infections. Scabies accounted for only 2% of all presentations, although one-quarter of children presented during the study for management of scabies. Skin sores accounted for 75% of the overall burden of skin infections. Improved public health measures targeting bacterial skin infections are needed to reduce this high burden of skin infections in Western Australia.

Abstract Background The extent to which reproductive tract infections (RTIs) are associated with poor menstrual hygiene management (MHM) practices has not been extensively studied. We aimed to determine whether poor menstrual hygiene practices were associated with three common infections of the lower reproductive tract; Bacterial vaginosis (BV), Candida, and Trichomonas vaginalis (TV). Methods Non-pregnant women of reproductive age (18–45 years) and attending one of two hospitals in Odisha, India, between April 2015 and February 2016 were recruited for the study. A standardized questionnaire was used to collect information on: MHM practices, clinical symptoms for the three infections, and socio-economic and demographic information. Specimens from posterior vaginal fornix were collected using swabs for diagnosis of BV, Candida and TV infection. Results A total of 558 women were recruited for the study of whom 62.4% were diagnosed with at least one of the three tested infections and 52% presented with one or more RTI symptoms. BV was the most prevalent infection (41%), followed by Candida infection (34%) and TV infection (5.6%). After adjustment for potentially confounding factors, women diagnosed with Candida infection were more likely to use reusable absorbent material (aPRR = 1.54, 95%CI 1.2–2.0) and practice lower frequency of personal washing (aPRR = 1.34, 95%CI 1.07–1.7). Women with BV were more likely to practice personal washing less frequently (aPRR = 1.25, 95%CI 1.0–1.5), change absorbent material outside a toilet facility (aPRR = 1.21, 95%CI 1.0–1.48) whilst a higher frequency of absorbent material changing was protective (aPRR = 0.56, 95%CI 0.4–0.75). No studied factors were found to be associated with TV infection. In addition, among women reusing absorbent material, Candida but not BV or TV - infection was more frequent who dried their pads inside their houses and who stored the cloth hidden in the toilet compartment. Conclusion The results of our study add to growing number of studies which demonstrate a strong and consistent association between poor menstrual hygiene practices and higher prevalence of lower RTIs.

If current trends persist, one in six U.S. men who have sex with men will be infected with human immunodeficiency virus (HIV) in their lifetime, according to the Centers for Disease Control and Prevention (CDC). This prediction highlights the long road ahead if we are to end the spread of HIV in……

Kwong, J. C., Urbancic, K., Trubiano, J. A.

Beta-lactam therapy for severe staphylococcal infections is associated with superior outcomes when compared to non-beta-lactam therapy. In patients with immediate hypersensitivity to beta-lactams, desensitization has been widely employed to allow beta-lactam therapy, but published protocols for anti-staphylococcal beta-lactams such as flucloxacillin are lacking. Here, we report a case and the desensitization protocol successfully used for a patient with isolated flucloxacillin immediate hypersensitivity, where a penicillin desensitization protocol would likely have resulted in an adverse drug reaction.

Abeni Beshiru, Isoken H. Igbinosa, Etinosa O. Igbinosa

by Abeni Beshiru, Isoken H. Igbinosa, Etinosa O. Igbinosa Salmonella species is an important foodborne pathogen with the non-typhoidal serovars such as Enteritidis and Typhimurium as the most predominant strains. This study examines the biofilm formation, phenotypic virulence factors and cell surface characteristics of Salmonella strains from ready-to-eat shrimps. The ready-to-eat shrimps were obtained from open markets between November 2016 and October 2017 in Edo and Delta States, Nigeria. The occurrence of Salmonella strains in this study was 210/1440 (14.58%) of the ready-to-eat shrimp’s samples. The identified strains comprise of Salmonella Enteritidis 11, Salmonella Typhimurium 14 and other Salmonella spp. 20. The 45 identified Salmonella strains revealed the following virulence properties: swimming and swarming motility 45(100%); S-layer 39(86.67%); haemolytic activity 40(88.89%); lipase activity 43(95.56%); protease activity 43(95.56%); gelatinase production 43(95.56%); and DNA degrading activity 41(91.11%). The variation in the formation of biofilm-based on the diversity of Salmonella species was observed with higher percentage of Salmonella Typhimurium strains as strong biofilms producers under different environmental conditions. For surface hydrophobicity using bacterial adherence to hydrocarbons, 25(55.56%) were hydrophilic while 20(44.44%) were moderately hydrophobic from the 45 Salmonella isolates. Using salting aggregation test for surface hydrophobicity, all selected isolates 45(100%) was hydrophilic. Autoaggregation index for the 12 selected Salmonella isolates ranged from 15.2–47.2%, while the autoaggragation index for the 12 selected test bacteria ranged from 26.2–71.3%. Coaggragation between the 12 selected test bacteria and 12 Salmonella isolates ranged from 12.5–81.0%. The occurrence of pathogenic species of Salmonella from ready-to-eat shrimps could be detrimental to the consumers. Findings on the physiological conditions of biofilms formed by the foodborne pathogenic Salmonella and the cell surface characteristics therein are crucial for the advancement of methods for controlling Salmonella from ready-to-eat foods.

Tisungane Mvalo, Brian Eley, Colleen Bamford, Christopher Stanley, Maganizo Chagomerana, Marc Hendricks, Ann Van Eyssen, Alan Davidson

Chakraborty, R., Lam, V., Kommineni, S., Stromich, J., Hayward, M., Kristich, C. J., Salzman, N. H.

Enterococci are Gram-positive commensals of the mammalian intestinal tract and harbor intrinsic resistance to broad-spectrum cephalosporins. Disruption of colonization resistance in humans by antibiotics allow enterococci to proliferate in the gut and cause disseminated infections. In this study, we used Enterococcus faecalis (EF) colonized mice to study the dynamics of enterococci, commensal microbiota and host in response to systemic ceftriaxone administration. We found that the mouse model recapitulates intestinal proliferation and dissemination of enterococci seen in humans. Employing a ceftriaxone-sensitive strain of enterococci (EFJL308), we showed that increased intestinal abundance is critical for the systemic dissemination of enterococci. Investigation of the impact of ceftriaxone on the mucosal barrier defenses and integrity suggested that translocation of enterococci across the intestinal mucosa was not associated with intestinal pathology or increased permeability. Ceftriaxone-induced alteration of intestinal microbial composition was associated with transient increase in the abundance of multiple bacterial Operational Taxonomic Units (OTUs) in addition to enterococci, for example, lactobacilli, which also disseminated to the extra-intestinal organs. Collectively, these results emphasize that ceftriaxone-induced disruption of colonization resistance and alteration of mucosal homeostasis, facilitate increased intestinal abundance of a limited number of commensals along with enterococci, allowing their translocation and systemic dissemination in a healthy host.

Sarah Tschudin-Sutter, Nicole Fosse, Reno Frei, Andreas F. Widmer

by Sarah Tschudin-Sutter, Nicole Fosse, Reno Frei, Andreas F. Widmer Objectives Management of bloodstream infections (“BSIs”) caused by Pseudomonas aeruginosa remains controversial as data supporting the use of definite combination treatment for severe P. aeruginosa infections remain conflicting. We aimed to determine differences in mortality between patients treated with definite combination therapy and monotherapy in a large 11-year cohort. Methods All consecutive patients with P. aeruginosa BSI hospitalized at the University Hospital Basel, Switzerland, a tertiary academic care center, from January 2003 to December 2013 were included. Pertinent clinical data was assessed. Patients with and without definite combination therapy were compared and hazard ratios for death were calculated. Results During the study period, 187 patients with P. aeruginosa BSI were identified. Definite combination therapy was administered in 42.8% (80/187) of all patients, of which 76% (61/80) received a combination of a betalactam with an aminoglycoside and 24% (19/80) received a combination of a betalactam with a quinolone. The remaining 57.2% (107/187) were treated with betalactam monotherapy. Median treatment duration was 15 days (interquartile range 12–20 days). Mortality was lower in patients receiving definite combination therapy in univariable and multivariable cox regression analyses (HR 0.26, 95% CI 0.11–0.60, p = 0.002 and HR 0.30, 95% CI 0.13–0.71, p = 0.006, respectively), the latter adjusting for age, neutropenia at diagnosis, PITT bacteremia score, and inadequate empirical treatment. Conclusions Combination therapy (i.e. betalactam-aminoglycoside or betalactam-quinolone combinations) may improve survival of P. aeruginosa BSI, independent of potential confounders such as age, neutropenia, PITT bacteremia score, and inadequate empirical treatment.

Tan, D., Htun, H. L., Koh, J., Kanagasabai, K., Lim, J.-W., Hon, P.-Y., Ang, B., Chow, A.

Vancomycin-resistant enterococci (VRE) is an important cause of nosocomial infections in acute care hospitals (ACHs), intermediate- (ITCFs) and long-term care facilities (LTCFs). This study contemporaneously compared the epidemiology and risk factors for VRE colonization in different care settings in a healthcare network. We conducted a serial cross-sectional study in a 1700-bed ACH and its six closely-affiliated ITCFs and LTCFs in June-July, 2014–2016. Rectal swabs or stool were cultured for VRE. Multivariable logistic regression was used to assess for independent risk factors associated with VRE colonization. Of 5357 participants, 523 (9.8%) were VRE-colonized. VRE prevalence was higher in ACH (14.2%) than ITCFs (7.6%) and LTCFs (0.8%). Common risk factors between ACH and ITCFs included prior VRE carriage; a longer duration of antibiotic therapy; surgery in the preceding 90 days and presence of skin ulcer. Independent risk factors specific to ACH-admitted patients were prior MRSA carriage; a higher number of beds per room; prior proton pump inhibitors use and length of stay >14 days. For ITCFs, length of stay >14 days was inversely associated with VRE colonization. Similarities and differences in risk factors for VRE colonization were observed between healthcare settings. VRE prevention efforts should target the respective high-risk patients.

Benefield, R. J., Slechta, E. S., Gast, C. M., Spivak, E. S., Hanson, K. E., Alexander, D. P.

We evaluated the effect of rifampin co-administration and MDR1 single nucleotide polymorphisms on the disposition of daptomycin in twelve healthy adults. There were no significant changes from baseline in clearance (0.53 vs 0.55 L/hr, P = 1.00), volume of distribution (7.0 vs 7.2 L, P = 0.62), or half-life (9.7 vs 9.6 hrs, P = 0.89) of daptomycin after exposure to rifampin. The tested MDR1 polymorphisms were not associated with significant differences in daptomycin disposition.

Yulong Cao, Zhizhong Gong, Jiao Shan, Yan Gao

Abstract Background Malaria in Equatorial Guinea remains a major public health problem. The country is a holo-endemic area with a year-round transmission pattern. In 2016, the prevalence of malaria was 12.09% and malaria caused 15% of deaths among children under 5 years. In the Continental Region, 95.2% of malaria infections were Plasmodium falciparum, 9.5% Plasmodium vivax, and eight cases mixed infection in 2011. The main strategy for malaria control is quick and accurate diagnosis followed by effective treatment. Early and accurate diagnosis of malaria is essential for both effective disease management and malaria surveillance. The quality of malaria diagnosis is important in all settings, as misdiagnosis can result in significant morbidity and mortality. Microscopy and RDTs are the primary choices for diagnosing malaria in the field. However, false-negative results may delay treatment and increase the number of persons capable of infecting mosquitoes in the community. The present study analysed the performance of microscopy and RDTs, the two main techniques used in Equatorial Guinea for the diagnosis of malaria, compared to semi-nested multiplex PCR (SnM-PCR). Results A total of 1724 samples tested by microscopy, RDT, and SnM-PCR were analysed. Among the negative samples detected by microscopy, 335 (19.4%) were false negatives. On the other hand, the negative samples detected by RDT, 128 (13.3%) were false negatives based on PCR. This finding is important, especially since it is a group of patients who did not receive antimalarial treatment. Conclusions Owing to the high number of false negatives in microscopy, it is necessary to reinforce training in microscopy, the “Gold Standard” in endemic areas. A network of reference centres could potentially support ongoing diagnostic and control efforts made by malaria control programmes in the long term, as the National Centre of Tropical Medicine currently supports the National Programme against Malaria of Equatorial Guinea to perform all of the molecular studies necessary for disease control. Taking into account the results obtained with the RDTs, an exhaustive study of the deletion of the hrp2 gene must be done in EG to help choose the correct RDT for this area.

Tomislav Bedeković, Ivana Lohman Janković, Ivana Å�imić, Nina KreÅ�ić, Ivana Lojkić, Ivica Sučec, Emmanuelle Robardet, Florence Cliquet

by Tomislav Bedeković, Ivana Lohman Janković, Ivana Å�imić, Nina KreÅ�ić, Ivana Lojkić, Ivica Sučec, Emmanuelle Robardet, Florence Cliquet Despite the implementation of control measures (preventive dog vaccination), rabies has become endemic in Croatia, with red foxes being the main reservoir species. Oral rabies vaccination (ORV) campaigns supported by the European Commission have been conducted twice a year since the spring of 2011. The first campaigns were limited to the northern and eastern parts of the country, and from the autumn of 2012, the program was extended to the entire country. The Lysvulpen vaccine containing the SAD Bern strain was used for ORV. Following the vaccination campaigns, the number of rabies cases decreased, and the last positive case was recorded in February 2014. The bait uptake ranged from 24.86% to 84.62% and the immunisation rate from 11.24% to 35.64%.

Following publication of the original article [1], it was flagged by one of the authors that the name of the P. falciparum gene marker of artemisinin resistance ‘pfkelch13’ was (incorrectly) written as “pfketch13”, which was repeated seven times in different parts of the published paper.

The original version of this article unfortunately contained mistakes.

Ana Patricia Ortiz, Karen J. Ortiz-Ortiz, Moraima Ríos, José Laborde, Amit Kulkarni, Matthew Pillsbury, Andreas Lauschke, Homero A. Monsanto, Cecile Marques-Goyco

by Ana Patricia Ortiz, Karen J. Ortiz-Ortiz, Moraima Ríos, José Laborde, Amit Kulkarni, Matthew Pillsbury, Andreas Lauschke, Homero A. Monsanto, Cecile Marques-Goyco…

Jehangir Khan, Abdul Ghaffar, Shujaat Ali Khan

by Jehangir Khan, Abdul Ghaffar, Shujaat Ali Khan…

Elizabeth R. Stevens, Lingfeng Li, Kimberly A. Nucifora, Qinlian Zhou, Margaret L. McNairy, Averie Gachuhi, Matthew R. Lamb, Harriet Nuwagaba-Biribonwoha, Ruben Sahabo, Velephi Okello, Wafaa M. El-Sadr, R. Scott Braithwaite

by Elizabeth R. Stevens, Lingfeng Li, Kimberly A. Nucifora, Qinlian Zhou, Margaret L. McNairy, Averie Gachuhi, Matthew R. Lamb, Harriet Nuwagaba-Biribonwoha, Ruben Sahabo, Velephi Okello, Wafaa M. El-Sadr, R. Scott Braithwaite Introduction Link4Health, a cluster-RCT, demonstrated the effectiveness of a combination strategy targeting barriers at various HIV continuum steps on linkage to and retention in care; showing effectiveness in achieving linkage to HIV care within 1 month plus retention in care at 12 months after HIV testing for people living with HIV (RR 1.48, 95% CI 1.19–1.96, p = 0.002). In addition to standard of care, Link4Health included: 1) Point-of-care CD4+ count testing; 2) Accelerated ART initiation; 3) Mobile phone appointment reminders; 4) Care and prevention package including commodities and informational materials; and 5) Non-cash financial incentive. Our objective was to evaluate the cost-effectiveness of a scale-up of the Link4Health strategy in Swaziland. Methods and findings We incorporated the effects and costs of the Link4Health strategy into a computer simulation of the HIV epidemic in Swaziland, comparing a scenario where the strategy was scaled up to a scenario with no implementation. The simulation combined a deterministic compartmental model of HIV transmission with a stochastic microsimulation of HIV progression calibrated to Swaziland epidemiological data. It incorporated downstream health costs potentially saved and infections potentially prevented by improved linkage and treatment adherence. We assessed the incremental cost-effectiveness ratio of Link4Health compared to standard care from a health sector perspective reported in US$2015, a time horizon of 20 years, and a discount rate of 3% in accordance with WHO guidelines.[1] Our results suggest that scale-up of the Link4Health strategy would reduce new HIV infections over 20 years by 11,059 infections, a 7% reduction from the projected 169,019 cases and prevent 5,313 deaths, an 11% reduction from the projected 49,582 deaths. Link4Health resulted in an incremental cost per infection prevented of $13,310 and an incremental cost per QALY gained of $3,560/QALY from the health sector perspective. Conclusions Using a threshold of…

Suparna Das, Jenevieve Opoku, Adam Allston, Michael Kharfen

by Suparna Das, Jenevieve Opoku, Adam Allston, Michael Kharfen Background People with HIV infection in the United States are often affected by chronic viral hepatitis. These coinfected people with either HBV or HCV are at increased risk for serious, life-threatening complications. Coinfections with viral hepatitis may also complicate the delivery of anti-retroviral therapy (ART) by escalating the risk of drug-related hepatoxicity. According to the Centers for Disease Control and Prevention (CDC), approximately 10 percent of people with HIV in the United States also have HBV, and 25 percent also have HCV coinfection. With the advent of highly active antiretroviral therapy (HAART) and the increased life-expectancy of HIV patients, clinicians are more likely to be confronted with issues related to co-infection and the management challenges that they present, especially in resource-limited settings. The purpose of this analysis was to identify geographical clusters of HIV- (HBV/HCV) co-infection and compared to the geographical clusters of not co-infected using DC, Department of Health surveillance data. The results of the analysis will be used to target resources to areas at risk. Methods HIV and Hepatitis surveillance data were matched among cases diagnosed between 1980 and 2016. HIV-hepatitis co-infected and the not co-infected spatial clusters were detected using discrete Poisson model. Kulldorff’s spatial scan statistic method was implemented in the free software tool called SaTScan which has been widely adopted for detecting disease cluster. The analysis was conducted by tracts, but for visualization, ease of interpretation and assist in policy making the tract map was overlaid with the ward map using ArcGIS 10.5.1. Results Between 1980 and 2016, there were 12,965 diagnosed cases of HIV, of which 2,316 HIV/Hepatitis matches were identified. Of the 2316 co-infected people living in DC, 25 percent (N = 590) of people had HBV, and 75 percent (N = 1,726) had HCV. Out of 12,965 diagnosed cases, remaining 10,649 did not have any co-infections (not co-infected). IDU (27.16 percent) and MSM (32.86 percent) were the highest mode of transmission for co-infected population. African-American were reported 83.64 percent (N = 1,937) among co-infection population. Three clusters were identified for both co-infected population in DC. The largest cluster radius for co-infected analysis covers wards 6, 7 and 8 as well as large parts of 2 and 5 (p < 0.001). Multiple clusters were identified for not co-infected population (p < 0.001). IDU (n = 450) was the highest mode of transmission for the co-infected clusters. For all clusters combined of not co-infected population highest mode of transmission were MSM (n = 2,534). This analysis also showed racial disparity, economic deprivation and lack of education were prominent in the co-infected clusters. Conclusion We identified locations of high risk clusters where enhanced hepatitis and HIV prevention, treatment, and care can help combat the epidemic. The clusters radius expands into the neighboring state of Maryland as well. The findings from this analysis will be used to target area based public health policy and healthcare interventions for HIV-hepatitis. It is recommended based on the analysis that needle exchange programs can successfully control new HIV infections as well as hepatitis co-infections.

Thayara Morais Portal , Tammy Kathlyn Amaral Reymão , Germano Alves Quinderé Neto , Mercedes Kamila da C Fiuza , Dielle Monteiro Teixeira , Ian Carlos Gomes Lima , Edivaldo Costa Sousa Júnior , Renato da Silva Bandeira , Danielle Rodrigues de Deus , Maria Cleonice A Justino , Alexandre da Costa Linhares , Luciana Damascena da Silva , Hugo Reis Resque , Yvone Benchimol Gabbay

ABSTRACT Enteric adenovirus (AdV), sapovirus (SaV), and human astrovirus (HAstV) are important pathogens involved in the gastroenteritis etiology. In this study, a total of 219 fecal samples and sera were collected from children hospitalized for acute gastroenteritis (AGE) in two large pediatric hospitals in Belém, from March 2012 to April 2015. The samples were analyzed by polymerase chain reaction (PCR) for adenovirus (AdV) and HAstV (astrovirus) detection, and Nested‐PCR and qPCR for sapovirus (SaV) detection. AdV was detected in 50.2% (110/219) of the cases, with 42.7% (47/110) being sequenced and classified as: species F (63.9% ‐ 30/47), A (4.2% ‐ 2/47), B (6.4% ‐ 3/47), C (17.1% ‐ 8/47), D (4.2% ‐ 2/47), and E (4.2% ‐ 2/47). Of the 110 AdV‐positive faeces samples, 80 paired sera presented sufficient amounts and were also tested for this virus, of which 51 (63.7%) showed positive results and 26 (70.3%) pairs (feces plus sera) presented concordant results after sequencing being classified as: species F (21/26; 80.8%), A (1/26; 3.8%), B (1/26; 3.8%), and C (3/26; 11.5%). Overall, HAstV rate in the feces samples was 1.8% (4/219), including both HAstV‐1a (2/4; 50%) and HAstV‐2c (2/4; 50%). SaV was detected in 4.6% (10/219) of the fecal samples, out of which 50% (5/10) of the positive samples were characterized into the genogroups GI.1 (1), GI.2 (2), and GII.4 (2). These findings highlighted the important contributions of AdV, HAstV, and SaV in the enteric virus spectrum in our region and showed the high genetic diversity of AdV. In addition, it demonstrated for the first time in Brazil, the circulation of AdV in the serum of hospitalized children with AGE. This article is protected by copyright. All rights reserved.

Landahl J, Bockmann J, Scheurich C, et al.

AbstractBackgroundThis study aimed to comprehensively define the breadth and specificity of the HDV-specific T-cell response in patients at different stages of chronic co-infection with hepatitis B (HBV) and delta virus (HDV).MethodsFollowing in vitro stimulation with an overlapping set of 21 HDV-specific 20mer peptides and exogenous IL-2, HDV-specific CD4+ and CD8+ T-cell response of 32 HDV-infected patients were analyzed by ELISpot and intracellular cytokine staining for interferon-γ production on a single peptide level. Additionally, HLA binding studies both in silico and in vitro were performed.ResultsWe were able to detect one or more T-cell response in more than 50% our patients. Interestingly, there was no significant difference between the breadth of response in HDV PCR+ versus PCR- patients. HDV-specific T-cell responses focused on three distinct HDV-specific epitopes that were each detected by 12-21% of patients – two HLA class II restricted (aa11-30, aa41-60) as well as one MHC class I restricted epitope (aa191-210). In in vitro HLA binding assays, the two CD4 + T-cell specificities (aa11-30, aa41-60) showed promiscuous binding to multiple HLA-DR molecules.ConclusionsThis comprehensive characterization of HDV T-cell epitopes provides important information that will facilitate further studies of HDV immunopathogenesis.

Hye-young Wang, Hyunil Kim, Kwang Hwa Park

Pap smear and high-risk human papillomavirus (HR-HPV) DNA testing are the most widely applied methods for cervical cancer screening, but both methods are limited by their low specificity and lack of association with the patients’ prognoses. The aim of the study was to compare the clinical and prognostic significance of HPV E6/E7 mRNA as an early biomarker with cytology and HPV DNA detection in cervical cancer screening.

Tara D. Sutherland, Alagacone Sriskantha, Trevor D. Rapson, Benjamin D. Kaehler, Gavin A. Huttley

by Tara D. Sutherland, Alagacone Sriskantha, Trevor D. Rapson, Benjamin D. Kaehler, Gavin A. Huttley Many of the challenges we currently face as an advanced society have been solved in unique ways by biological systems. One such challenge is developing strategies to avoid microbial infection. Social aculeates (wasps, bees and ants) mitigate the risk of infection to their colonies using a wide range of adaptations and mechanisms. These adaptations and mechanisms are reliant on intricate social structures and are energetically costly for the colony. It seems likely that these species must have had alternative and simpler mechanisms in place to ensure the maintenance of hygienic domicile conditions prior to the evolution of these complex behaviours. Features of the aculeate coiled-coil silk proteins are reminiscent of those of naturally occurring α-helical antimicrobial peptides (AMPs). In this study, we demonstrate that peptides derived from the aculeate silk proteins have antimicrobial activity. We reconstruct the predicted ancestral silk sequences of an aculeate ancestor that pre-dates the evolution of sociality and demonstrate that these ancestral sequences also contained peptides with antimicrobial properties. It is possible that the silks evolved as an antifouling material and facilitated the evolution of sociality. These materials serve as model materials for consideration in future biomaterial development.

Abstract Background Legionellosis is a well-known cause of pneumonia. Primary cutaneous and subcutaneous infection caused by Legionella pneumophila is rare and the diagnosis is challenging. Case presentation A 38-year-old Thai woman with systemic lupus erythematosus and myasthenia gravis treated with prednisolone and azathioprine presented to our hospital with low-grade fever, diarrhea, and indurated skin lesions on both thighs. Initial examination showed plaques on both inner thighs. Magnetic resonance imaging showed myositis and swelling of the skin and subcutaneous tissue. Diagnosis of panniculitis due to L. pneumophila was carried out by histopathology, Gram stain, and 16S rRNA gene sequencing method of tissue biopsy from multiple sites on both thighs. Myocarditis was diagnosed by echocardiography. The final diagnosis was disseminated extrapulmonary legionellosis. Treatment comprised intravenous azithromycin for 3 weeks and the skin lesions, myositis and myocarditis resolved. Oral azithromycin and ciprofloxacin were continued for 3 months to ensure eradication of the organism. The patient’s overall condition improved. Conclusions To our knowledge, we report the first case of L. pneumophila infection manifesting with panniculitis, possible myositis, and myocarditis in the absence of pneumonia. The diagnosis of extrapulmonary Legionella infection is difficult, especially in the absence of pneumonia. A high index of suspicion and appropriate culture with special media or molecular testing are required. Initiation of appropriate treatment is critical because delaying therapy was associated with progressive infection in our patient.

SupitchaWanvimonsuk , PichayaThitiwanichpiwong , SomboonKeelawat , ApiwatMutirangura , NakarinKitkumthorn

Abstract The Epstein‐Barr virus (EBV) is one of the infectious agents found in stomach tissue. Recently, EBV associated gastric carcinoma (EBVaGC) was classified as a new subtype of gastric carcinoma. To date, there is a lack of knowledge about the distribution and prevalence of EBV infection in both the normal stomach and various gastric lesions, including EBVaGC, in the Thai population. In this study, we detected EBV in the normal stomach (NS; n=19), chronic gastritis (CG; n=36), intestinal metaplasia (IM; n=40), gastric dysplasia (GD; n=15), and gastric adenocarcinoma (GC; n=33) by polymerase chain reaction (PCR) amplification of the latent membrane protein (LMP1) gene of EBV. EBV‐PCR amplification was positive in 42.1%, 36.1%, 22.5%, 13.3%, and 33.3% of NS, CG, IM, GD, and GC, respectively. For further clarification in EBVaGC, we performed EBV‐encoded small RNA in situ hybridization (EBER‐ISH) in PCR positive cases of GD and GC. Four GC cases were EBER‐ISH positive (12.1%), while both GD cases were EBER‐ISH negative. In addition, we determined the distribution of the EBV strain (type A or B) based on EBNA3C sequence and EBV variants based on LMP1 variation (wild‐type and 30 bp‐deletion variants; wt‐LMP1 or del‐LMP1). The results showed that type A and wt‐LMP1 were the most prevalent in all lesions. In conclusion, EBV is common in both the normal stomach and gastric lesions and the frequency of EBVaGC was 12.1% in Thai patients. This article is protected by copyright. All rights reserved.

Harter, Zachery J.; Agarwal, Stuti; Dalvi, Pranjali; Voelkel, Norbert F.; Dhillon, Navneet K.

Improved survival among HIV-1 infected individuals with the advent of antiretroviral therapy has clearly led to a greater prevalence of non-infectious complications. One of the most devastating sequelae in these individuals is the development of pulmonary arterial hypertension (PAH). Various epidemiological studies suggest a worse survival of HIV-PAH patients when compared to other forms of PAH. Given that only a subset and not all HIV-infected individuals develop HIV-PAH, suggests that an additional second hit of genetic or environmental triggers is needed for the development of PAH. In this context, it has been well documented that HIV patients who abuse illicit drugs such as stimulants, opioids etc. are more susceptible to develop PAH. In this review, we highlight the studies that support the significance of a double hit of HIV and drug abuse in the incidence of PAH and focus on the research that has been undertaken to unravel the pathobiology and vascular remodeling mechanisms underlying the deleterious synergy between HIV infection and drugs of abuse in orchestrating the development of PAH. Correspondence to Navneet K. Dhillon, Division of Pulmonary and Critical care, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160. Tel: +913 945 6018; e-mail: ndhillon@kumc.edu Received 11 May, 2018 Accepted 27 July, 2018 Copyright © 2018 Wolters Kluwer Health, Inc.

Schaltz-Buchholzer F, Biering-Sørensen S, Lund N, et al.

AbstractObjectiveTo examine effects of early Bacille Calmette-Guérin (BCG) vaccination on the risk, cause and severity of infant hospitalizations. DesignAnalysis of three trials randomizing low-weight neonates to early-BCG(intervention) versus no-BCG(usual practice in low-weight neonates, control), with hospitalizations as secondary outcome. MethodsHospitalization data was collected at the pediatric ward of the National Hospital. Effects of BCG on hospitalization risk were assessed in Cox-models providing overall and major disease-group incidence rate ratios(IRRs). Severity was assessed by in-hospital case-fatality rates and compared by group as cohort study risk ratios(RRs). ResultsAmong 6,583 infants (3,297 BCG; 3,286 controls), there were 908 infant hospitalizations (450 BCG; 458 controls) and 135 in-hospital deaths (56 BCG; 79 controls). The neonatal(28days), 6-week and infant(1year) BCG versus control hospitalization IRRs were 0.97(95% CI 0.72-1.31), 0.95(0.73-1.24) and 0.96(0.84-1.10). Corresponding BCG versus control case-fatality RRs were 0.58(0.35-0.94), 0.56(0.35-0.90) and 0.72(0.53-0.99). BCG tended to reduce neonatal and infant sepsis hospitalization rates, IRRs being 0.75(0.50-1.13) and 0.78(0.55-1.11), and reduced in-hospital neonatal sepsis mortality, RR=0.46(0.22-0.98). There were no confirmed tuberculosis hospitalizations.ConclusionBCG did not affect hospitalization rates but reduced in-hospital mortality significantly, primarily by preventing fatal cases of sepsis. The observed beneficial effects of BCG on in-hospital mortality were entirely non-specific.

Abstract Background Community-acquired pneumonia (CAP) is a common condition with high mortality, morbidity and healthcare costs. This study aimed to determine whether clinical pathway (CP) implementation in different hospitals in China increased antibiotic compliance with the national CP in inpatients with CAP. Methods Chart reviews of CAP cases were conducted in 18 public hospitals from 3 different regions of China in 2015. Chi-square tests and the t-test were used to compare differences between hospitals that implemented CP (CP group) and those that did not (non-CP group). Multivariate logistic analysis was adopted to test whether CP implementation for CAP in hospitals affected their overall antibiotic use compliance rates with the national CP for CAP. Results The overall compliance rate with the national CP for inpatients with CAP was 43.69%. The compliance rates for timely initial antibiotic use, recommended antibiotic use and use of the recommended combination of antibiotics and the overall compliance rate were substantially higher in the CP group than in the non-CP group. A multivariate logistic model for overall compliance in inpatients with CAP showed that the hospitals in the CP group had greater overall compliance than those in the non-CP group (odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.16–2.71) after controlling for hospital and inpatient characteristics. Conclusion In China, the overall compliance rate with the national CP for inpatients with CAP was low, but inpatients with CAP in the hospitals in the CP group received antibiotics more concordantly with the national CP. Since adherence to evidence-based care has been shown to improve clinical outcomes, internal and external support from hospitals is required to facilitate CP implementation for inpatients with CAP. Additionally, governmental commitment, hospital input and population involvement are required to improve antibiotic utilization.

Yang, Jin; Xiao, Yan; Quan, Eugenie Y.; Hu, Zhangle; Guo, Qinyue; Miao, Changqing; Bradley, Jennifer L.; Peberdy, Mary A.; Ornato, Joseph P.; Mangino, Martin J.; Tang, Wanchun

Objectives: Polyethylene glycol-20k is a hybrid cell impermeant that reduces ischemia injury and improves microcirculatory flow during and following low flow states through nonenergy-dependent water transfer in the microcirculation. We investigated the effects of polyethylene glycol-20k on postresuscitation microcirculation, myocardial and cerebral function, and duration of survival in a rat model of cardiopulmonary resuscitation. Design: Ventricular fibrillation was induced in 20 male Sprague Dawley rats and untreated for 6 minutes. Animals were randomized into two groups (n = 10 for each group): polyethylene glycol-20k and control. Polyethylene glycol-20k (10% solution in saline, 10% estimated blood volume) and vehicle (saline) were administered at the beginning of cardiopulmonary resuscitation by continuous IV infusion. Resuscitation was attempted after 8 minutes of cardiopulmonary resuscitation. Setting: University-Affiliated Research Laboratory. Subjects: Sprague Dawley Rats. Interventions: Polyethylene glycol-20k. Measurements and Main Results: Buccal microcirculation was measured at baseline, 1, 3, and 6 hours after return of spontaneous circulation using a side-stream dark-field imaging device. Myocardial function was measured by echocardiography at baseline and every hour postresuscitation for 6 hours. The animals were then returned to their cage and observed for an additional 72 hours. Neurologic Deficit Scores were recorded at 24, 48, and 72 hours after resuscitation. Postresuscitation ejection fraction, cardiac output, and myocardial performance index were significantly improved in animals treated with polyethylene glycol-20k (p < 0.05). Perfused buccal vessel density and microcirculatory flow index values were significantly higher at all time points in the polyethylene glycol-20k group compared with the control group. Postresuscitation cerebral function and survival rate were also significantly improved in animals that received polyethylene glycol-20k. Conclusions: Administration of polyethylene glycol-20k following cardiopulmonary resuscitation improves postresuscitation myocardial and cerebral function, buccal microcirculation, and survival in a rat model of cardiopulmonary resuscitation. Drs. Yang and Xiao contributed equally to this work. All work was performed at the Weil Institute of Emergency and Critical Care Research at Virginia Commonwealth University. Supported, in part, by the project of Leading Talents in Pearl River Talent Plan of Guangdong Province, China (Number 81000-42020004), and by the Weil Family Foundation, California. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: wanchun.tang@vcuhealth.org Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Purpose Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with hematological malignancies, even in case of resolved infection. Prophylaxis of HBV reactivation is universally recommended in stem cell transplant (SCT) recipients and patients treated with anti-CD20 agents (i.e., rituximab). Despite its well-established favorable safety profile, lamivudine (LAM) use in prophylaxis has been debated because of the possible emergence of resistant viral strains. The aim of this study was to investigate the efficacy of LAM in preventing HBV reactivation in allogeneic SCT recipients with a resolved HBV infection. Methods Patients who received first allogeneic SCT in years 2009–2016 were evaluated. Sixty-three patients with resolved infection received LAM prophylaxis and were included in the study. Baseline and post-SCT characteristics were recorded, including rituximab exposure, length of LAM prophylaxis, and time from transplant to the last clinical and virological follow-up. Results Overall, 39 patients (62%) were male, 39 (62%) had acute myeloid leukemia, 38 (60%) received transplant from haploidentical donor, 29 (53%) received myeloablative conditioning, and 15 (24%) received rituximab post-transplant. Median clinical follow-up was 24 months after SCT (range 0.3–97); median virological follow-up 16 months (range 0.3–78), and median length of LAM prophylaxis of 14.5 months (range 0.3–78). No patient experienced HBV reactivation while on LAM prophylaxis. One patient experienced reactivation 8 months after discontinuing prophylaxis. Conclusions In this high-risk population, LAM prophylaxis was effective in preventing HBV reactivation in patients with resolved infection. It should be considered a reasonable first-line prophylactic agent to be administered in this setting.