Wendelin Moser, Somphou Sayasone, Syda Xayavong, Bangon Bounheuang, Maxim Puchkov, Jörg Huwyler, Jan Hattendorf, Jennifer Keiser

TDT with albendazole, pyrantel pamoate, and oxantel pamoate could make a difference, in particular in the context of soil-transmitted helminth elimination. Pyrantel pamoate might be a useful alternative to prevent benzimidazole resistance; however, larger trials are needed to confirm this finding.

Chongguang Yang, Liping Lu, Joshua L Warren, Jie Wu, Qi Jiang, Tianyu Zuo, Mingyu Gan, Mei Liu, Qingyun Liu, Kathryn DeRiemer, Jianjun Hong, Xin Shen, Caroline Colijn, Xiaoqin Guo, Qian Gao, Ted Cohen

The primary mechanism driving local incidence of tuberculosis in urban centres is local transmission between both migrants and residents. Combined analysis of epidemiological, genomic, and spatial data contributes to a richer understanding of local transmission dynamics and should inform the design of more effective interventions.

Nazir Ahmed Ismail, Lindiwe Mvusi, Ananta Nanoo, Andries Dreyer, Shaheed V Omar, Sanni Babatunde, Thabo Molebatsi, Martie van der Walt, Adeboye Adelekan, Varough Deyde, Chikwe Ihekweazu, Shabir A Madhi

The overall prevalence of MDR tuberculosis in South Africa in 2012–14 was similar to that in 2001–02; however, prevalence of rifampicin-resistant tuberculosis almost doubled among new cases. Furthermore, the high prevalence of isoniazid mono-resistant tuberculosis, not routinely screened for, and resistance to second-line drugs has implications for empirical management.

Robert Mash, Akye Essuman, Innocent Besigye, Olayinka Ayankogbe, Per Kallestrup, Jan De Maeseneer

In their Commission, Irene Agyepong and colleagues (Dec 23, 2017, p 2803)1 provide a comprehensive report on the pathway to healthier lives for all Africans by 2030. As highlighted in the Commission, we have been involved in training family physicians in Africa for the past 20 years within the framework of the Primary Care and Family Medicine Education (Primafamed) network, a South–South cooperation that brings together family medicine, primary care, and public health in more than 20 African countries.

Tetsuji Fujita

In the 2-year follow-up of the PRIMA (PRImary Mesh closure of Abdominal midline wounds) trial (Aug 5, 2017, p 567),1 prophylactic onlay mesh augmentation for midline abdominal closure significantly reduced the risk of incisional hernia, with similar risks of surgical site infection compared with primary closure. Consequently, An Jairam and colleagues1 conclude that onlay mesh augmentation has the potential to become the standard treatment for patients at high risk of incisional hernia.

Mika Kivimäki, Archana Singh-Manoux

The report by Gill Livingston and colleagues (Dec 16, 2017 p 2673)1 is a valuable collation of a large body of medical research evidence that aims to combat the dementia epidemic, the greatest global challenge for health and social care in the 21st century. One of the key messages of the Commission is the need to be ambitious in terms of prevention. Using population attributable fractions (PAF), the authors estimate that as much as 35% of dementia cases could be prevented by targeting nine modifiable risk factors.

Manuel Jakob, Guido Beldi

The conclusions of the PRIMA (PRImary Mesh closure of Abdominal midline wounds) trial1 (Aug 5, 2017, p 567) need to be taken with caution for several reasons. The rate of 18% of incisional hernia in patients receiving prophylactic sublay mesh implantation is very high compared with frequencies below 5% in many other reports.2,3 Furthermore, most series report a lower recurrence rate after sublay than onlay mesh implantation in the repair of incisional hernia.4,5 Therefore, the technical problems or insufficient training with the sublay group does not allow the conclusion that onlay mesh reinforcement has the potential to become the standard treatment for high-risk patients having elective midline laparotomy.

Badri M Shrestha

The PRIMA (PRImary Mesh closure of Abdominal midline wounds) trial by An Jairam and colleagues (Aug 5, 2017, p 567),1 provides relevant information on the outcomes of prophylactic repair of midline laparotomies for the prevention of incisional hernia. The trial shows significant reduction in the incidence of incisional hernia with onlay and sublay mesh reinforcement compared with primary suture only repair in patients with abdominal aortic aneurysm, but not in patients with a body mass index (BMI) greater than 27 kg/m2, contrary to the claim made by the authors of the PRIMA trial (ie, superior outcome of onlay mesh repair in patients with BMI greater than 27 kg/m2).

Abi Beane, Duncan Wagstaff, Anuja Abayadeera, David Walker, Rashan Haniffa

We congratulate the African Surgical Outcomes Study team, led by investigators from low-income and middle-income countries, for quantifying the scale of global inequality in surgical care, and for providing measurable goals for future improvement efforts (April 21, p 1589).1 This work also highlights the poor availability of the detailed information necessary to translate these inequalities into potential solutions.2,3 Continuous surveillance systems or registries could provide such information but are notoriously challenging; disparate paper-based systems, inadequate resources, and overburdened staff are seemingly insurmountable problems.

David S Hui, Esam I Azhar, Yae-Jean Kim, Ziad A Memish, Myoung-don Oh, Alimuddin Zumla

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonosis that causes death in 35·7% of cases. As of Feb 28, 2018, 2182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide, with most being reported in Saudi Arabia (1807 cases with 705 deaths). MERS-CoV features prominently in the WHO blueprint list of priority pathogens that threaten global health security. Although primary transmission of MERS-CoV to human beings is linked to exposure to dromedary camels (Camelus dromedarius), the exact mode by which MERS-CoV infection is acquired remains undefined.

Paul Joseph Brown

John J Jackson greeted me warmly when I arrived at the door of his top floor apartment in city-subsidised low-income housing. He had recently moved from a dangerous, crime-ridden part of downtown Seattle to a much safer neighbourhood. His small apartment was crammed with photographs and mementos of an exceptionally full life and the equipment and medications that he now needs to treat his chronic obstructive pulmonary disease (COPD). He was diagnosed with the disease in 2006 and it has completely changed his life.

Sohee Son, Visanu Thamlikitkul, Kulkanya Chokephaibulkit, Jennifer Perera, Kushlani Jayatilleke, Po-Ren Hsueh, Chun-Yi Lu, Veeraraghavan Balaji, Hiroyuki Moriuchi, Yumiko Nakashima, Min Lu, Yonghong Yang, Kaihu Yao, So Hyun Kim, Jae Hoon Song, Seonwoo Kim, Min-Ji Kim, Ulrich Heininger, Cheng-Hsun Chiu, Yae-Jean Kim

Bordetella pertussis continues to cause outbreaks worldwide. To assess the role of children and adolescent in transmission of pertussis in Asia, we performed a multinational serosurveillance study.

Sifuna, Peter; Otieno, Lucas; Andagalu, Ben; Oyieko, Janet; Ogutu, Bernhards; Singoei, Valentine; Owuoth, John; Ogwang, Sheila; Cowden, Jessica; Otieno, Walter

Background: Reliable data on the HIV epidemic is critical for the measurement of the impact of HIV response and for the implementation of further interventions. Methods: We used mortality data from the Kombewa Health and Demographic Surveillance Systems (HDSS) from 1st January 2011–31st December 2015 to examine the space-time pattern of HIV-associated mortality. HIV mortality rate was calculated per 1,000 PLHV (for comparison with regional and national averages) and per 1,000 person-years (p-y) for comparison with other HDSS sites. We used the Optimized Hot Spot Analysis to examine whether HIV-associated deaths would form statistically significant local aggregation in the five-year period. P-value of…

Abstract Background Non-hospital residential facilities are important reservoirs for MRSA transmission. However, conclusions and public health implications drawn from the many mathematical models depicting nosocomial MRSA transmission may not be applicable to these settings. Therefore, we reviewed the MRSA transmission dynamics studies in defined non-hospital residential facilities to: (1) provide an overview of basic epidemiology which has been addressed; (2) identify future research direction; and (3) improve future model implementation. Methods A review was conducted by searching related keywords in PUBMED without time restriction as well as internet searches via Google search engine. We included only articles describing the epidemiological transmission pathways of MRSA/community-associated MRSA within and between defined non-hospital residential settings. Results Among the 10 included articles, nursing homes (NHs) and correctional facilities (CFs) were two settings considered most frequently. Importation of colonized residents was a plausible reason for MRSA outbreaks in NHs, where MRSA was endemic without strict infection control interventions. The importance of NHs over hospitals in increasing nosocomial MRSA prevalence was highlighted. Suggested interventions in NHs included: appropriate staffing level, screening and decolonizing, and hand hygiene. On the other hand, the small population amongst inmates in CFs has no effect on MRSA community transmission. Included models ranged from system-level compartmental models to agent-based models. There was no consensus over the course of disease progression in these models, which were mainly featured with NH residents /CF inmates/ hospital patients as transmission pathways. Some parameters used by these models were outdated or unfit. Conclusions Importance of NHs has been highlighted from these current studies addressing scattered aspects of MRSA epidemiology. However, the wide variety of non-hospital residential settings suggest that more work is needed before robust conclusions can be drawn. Learning from existing work for hospitals, we identified critical future research direction in this area from infection control, ecological and economic perspectives. From current model deficiencies, we suggest more transmission pathways be specified to depict MRSA transmission, and further empirical studies be stressed to support evidence-based mathematical models of MRSA in non-hospital facilities. Future models should be ready to cope with the aging population structure.

Eron, Joseph J.; Orkin, Chloe; Gallant, Joel; Molina, Jean-Michel; Negredo, Eugenia; Antinori, Andrea; Mills, Anthony; Reynes, Jacques; Van Landuyt, Erika; Lathouwers, Erkki; Hufkens, Veerle; Jezorwski, John; Vanveggel, Simon; Opsomer, Magda; on behalf of the AMBER study group

Objectives: To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naïve, HIV-1-infected adults. Design: Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247). Methods: Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin). Results: At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load…

Katarzyna Kry�ciak, Joanna Majerczak, Jakub Kry�ciak, Dawid �ochy�ski, Dominik Kaczmarek, Hanna Drzyma�a-Celichowska, Piotr Krutki, Anna Gawedzka, Magdalena Guzik, Micha� Korostynski, Zbigniew Szkutnik, El�bieta Pyza, Wies�awa Jarmuszkiewicz, Jerzy A. Zoladz, Jan Celichowski

by Katarzyna KryÅ�ciak, Joanna Majerczak, Jakub KryÅ�ciak, Dawid Å�ochyÅ�ski, Dominik Kaczmarek, Hanna DrzymaÅ�a-Celichowska, Piotr Krutki, Anna Gawedzka, Magdalena Guzik, MichaÅ� Korostynski, Zbigniew Szkutnik, ElÅ�bieta Pyza, WiesÅ�awa Jarmuszkiewicz, Jerzy A. Zoladz, Jan Celichowski This study aimed at investigating the effects of 2, 4 and 8 weeks of endurance training on the contractile properties of slow (S), fast fatigue resistant (FR) and fast fatigable (FF) motor units (MUs) in rat medial gastrocnemius (MG) in relation to the changes in muscle mitochondrial biogenesis. The properties of functionally isolated MUs were examined in vivo. Mitochondrial biogenesis was judged based on the changes in mitochondrial DNA copy number (mtDNA), the content of the electron transport chain (ETC) proteins and PGC-1α in the MG. Moreover, the markers of mitochondria remodeling mitofusins (Mfn1, Mfn2) and dynamin-like protein (Opa1) were studied using qPCR. A proportion of FR MUs increased from 37.9% to 50.8% and a proportion of FF units decreased from 44.7% to 26.6% after 8 weeks of training. The increased fatigue resistance, shortened twitch duration, and increased ability to potentiate force were found as early as after 2 weeks of endurance training, predominantly in FR MUs. Moreover, just after 2 weeks of the training an enhancement of the mitochondrial network remodeling was present as judged by an increase in expression of Mfn1, Opa1 and an increase in PGC-1α in the slow part of MG. Interestingly, no signs of intensification of mitochondrial biogenesis assessed by ETC proteins content and mtDNA in slow and fast parts of gastrocnemius were found at this stage of the training. Nevertheless, after 8 weeks of training an increase in the ETC protein content was observed, but mainly in the slow part of gastrocnemius. Concluding, the functional changes in MUs’ contractile properties leading to the enhancement of muscle performance accompanied by an activation of signalling that controls the muscle mitochondrial network reorganisation and mitochondrial biogenesis belong to an early muscle adaptive responses that precede an increase in mitochondrial ETC protein content.

Beatriz Vidondo

by Beatriz Vidondo The popularly known 20–80 rule or Pareto rule states that 20% of efforts leads to 80% of results. This rule has been applied to the study of infection transmission in contact networks, and specifically, contact networks between cattle farms. Woolhouse and collaborators showed that targeting interventions for disease control and prevention to the 20% of the farms that contribute the most to the basic reproduction number (Ro), could reduce it by 80%. The rule results from the number of incoming and outgoing contacts per farm being highly heterogeneous. Besides, Woolhouse and collaborators showed that this high contact heterogeneity, together with a high positive correlation between the number of incoming and outgoing animal movements per farm leads to an amplification in the Ro. Two previous studies carried out with Scottish cattle transport data found either no correlation or only a weak correlation (rho up to 0.33) when using weighted data. Using data from the contacts between Swiss cattle farms in 2015, we found that the 20–80 rule applies with respect to Ro, although the proportion of highly active farms is smaller (11%). Besides, a positive strong correlation (rho = 0.64, weighted data) between the incoming and outgoing contacts of farms exists. This means that the amplification of Ro (due to the contact heterogeneities and the existing correlation) in cattle contact networks can be much higher than known until now. Our results highlight the importance of an effective active surveillance, more so than in other countries were these amplification mechanisms are absent.

Jerry Hella, Colin I. Cercamondi, Francis Mhimbira, Mohamed Sasamalo, Nicole Stoffel, Marcel Zwahlen, Thomas Bodmer, Sebastien Gagneux, Klaus Reither, Michael B. Zimmermann, Lorenz Risch, Lukas Fenner

by Jerry Hella, Colin I. Cercamondi, Francis Mhimbira, Mohamed Sasamalo, Nicole Stoffel, Marcel Zwahlen, Thomas Bodmer, Sebastien Gagneux, Klaus Reither, Michael B. Zimmermann, Lorenz Risch, Lukas Fenner Background Tuberculosis (TB) induces a systemic inflammatory state affecting iron homeostasis. Patients with TB often have additional comorbidities such as anemia which can result in poorer treat outcomes. We studied the contribution of anemia and the role of the iron regulatory hormone hepcidin among TB patients and household contacts. Methods We analyzed serum samples from 102 TB cases and 98 controls without TB, matched by age/sex, for hepcidin, iron, and inflammation parameters. Five controls developed TB within 12 months. We used linear regression to assess associations. Results Anemia of chronic disease (ACD) was more frequent among cases than controls (59.8% vs. 26.1%), but iron-deficiency anemia more frequent in controls (10% vs. 1%). The median hepcidin level was higher in cases than controls (63.7 vs. 14.2 ng/mL), but coinfections with HIV, helminths, and respiratory pathogens did not show cumulative effects. Hepcidin was associated with more severe TB symptom scoring (coefficient 0.8, 95% confidence interval [CI] 0.5–1.2) and higher mycobacterial load (0.7, 95% CI 0.4–1.0). Hepcidin was higher in TB cases and controls who developed TB compared to controls without TB (p

Stevens M, Rusch S, DeVincenzo J, et al.

AbstractBackgroundRespiratory syncytial virus (RSV) disease has no effective treatment. JNJ-53718678 is a fusion inhibitor with selective activity against RSV.MethodsAfter confirmation of RSV infection or 5 days post inoculation with RSV, participants (n=69) were randomized to JNJ-53718678 75 mg (n=15), 200 mg (n=17), 500 mg (n=18), or placebo (n=17), orally once-daily for 7 days. Antiviral effects were evaluated by assessing RSV RNA viral load (VL) area-under-the-curve (AUC) from baseline (prior to the first dose) until discharge, time-to-peak VL, duration of viral shedding, clinical symptoms, and quantity of nasal secretions.ResultsMean VL AUC was lower for individuals treated with different doses of JNJ-53718678 vs placebo (203.8–253.8 versus 432.8 log10 PFUe.hour mL). Also, mean peak VL, time-to-peak VL, duration of viral shedding, mean overall symptom score and nasal secretion weight were lower in each JNJ-53718678-treated group versus placebo. No clear exposure-response relationship was observed. Three participants discontinued due to treatment-emergent adverse events of Grade 2 and 1 ECG change (JNJ53718678 75 mg and 200 mg, respectively) and Grade 2 urticaria (placebo).ConclusionsJNJ-53718678 at all three doses substantially reduced VL and clinical disease severity, thus establishing clinical proof-of-concept and the compound’s potential as a novel RSV treatment.

Abstract Background GSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children. Methods The Phase III, randomized, double-blind, multinational study included three cohorts: adults (18–49 years; N = 120), children (3–17 years; N = 821), and infants (6–35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 μg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine. Results The primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786). Conclusions The study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process. Trial registration ClinicalTrials.gov: NCT02207413; trial registration date: August 4, 2014.

Soo Jung Kim, Shinhee Ye, Eunhee Ha, Eun Mi Chun

by Soo Jung Kim, Shinhee Ye, Eunhee Ha, Eun Mi Chun Introduction Overweight or obesity might be protective factors of tuberculosis (TB), but the evidence is inconclusive. The objective of study was to evaluate association between BMI and incident TB. Methods The National Health Insurance database was used. Eligible participants were individuals aged 20–89 years without history of TB before 2007, and who underwent national health examinations between January 2002 and December 2006. The latest record of BMI was used as the exposure and categorized as follows: 30 kg/m2 did not show protective effect of TB in female under 50 years. Additionally, BMI >30 kg/m2 did not decrease incident TB in diabetics. Conclusion Our study suggests that high BMI might be associated with decreased risk of TB. However, very high BMI did not reduce the risk of TB in young females or diabetics participants with in Korean population.

Liang Wang, Shuo Su, Yuhai Bi, Gary Wong, George F. Gao

Infections with bat-origin coronaviruses have caused severe illness in humans by ‘host jump’. Recently, novel bat-origin coronaviruses were found in pigs. The large number of mutations on the receptor-binding domain allowed the viruses to infect the new host, posing a potential threat to both agriculture and public health.

Kong, Chung Yin; Sigel, Keith; Criss, Steven D.; Sheehan, Deirdre F.; Triplette, Matthew; Silverberg, Michael J.; Henschke, Claudia I.; Justice, Amy; Braithwaite, R. Scott; Wisnivesky, Juan; Crothers, Kristina

Objective: Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung cancer screening is unknown. Our objective was to determine the benefits and harms of lung cancer screening among HIV-infected individuals. Design: We modified an existing simulation model, the Lung Cancer Policy Model, for HIV-infected patients. Data sources: Veterans Aging Cohort Study, Kaiser Permanente Northern California HIV Cohort, and medical literature. Setting: Target population: HIV-infected current and former smokers. Time horizon: Lifetime. Perspective: Population. Intervention: Annual LDCT screening from ages 45, 50, or 55 until ages 72 or 77 years. Main outcome measures: Benefits assessed included lung cancer mortality reduction and life-years gained; harms assessed included numbers of LDCT examinations, false-positive results, and overdiagnosed cases. Results of base-case analysis: For HIV-infected patients with CD4+ at least 500 and 100% antiretroviral therapy adherence, screening using the Centers for Medicare & Medicaid Services criteria (age 55–77, 30 pack-years of smoking, current smoker or quit within 15 years of screening) would reduce lung cancer mortality by 18.9%, similar to the mortality reduction of uninfected individuals. Alternative screening strategies utilizing lower screening age and/or pack-years criteria increase mortality reduction, but require more LDCT examinations. Limitations: Strategies assumed 100% screening adherence. Conclusion: Lung cancer screening reduces mortality in HIV-infected patients with CD4+ at least l500, with a number of efficient strategies for eligibility, including the current Centers for Medicare & Medicaid Services criteria. Correspondence to Chung Yin Kong, PhD, Institute for Technology Assessment, Massachusetts General Hospital, 101 Merrimac Street, 10th floor, Boston, MA 02114, USA. Tel: +1 617 726 5311; fax: +1 617 726 9414. e-mail: joey@mgh-ita.org. Received 20 September, 2017 Revised 23 January, 2018 Accepted 26 January, 2018 Copyright © 2018 Wolters Kluwer Health, Inc.

To the Editor: ECHELON-1, the trial reported by Connors et al. (Jan. 25 issue), shows advancement in the treatment of Hodgkin’s lymphoma and introduces an effective regimen for patients who are unable to receive bleomycin. However, clinically meaningful outcomes in patients with curable cancers are……

Solomon Kibret, G. Glenn Wilson, Darren Ryder, Habte Tekie, Beyene Petros

by Solomon Kibret, G. Glenn Wilson, Darren Ryder, Habte Tekie, Beyene Petros Background Water level management has been suggested as a potential tool to reduce malaria around large reservoirs. However, no field-based test has been conducted to assess the effect of water level management on mosquito larval abundance in African settings. The objective of the present study is to evaluate the effects of water level drawdown rates on mosquito larval abundance. Methods Twelve experimental dams were constructed on the foreshore of the Koka Dam in Ethiopia. These were grouped into four daily water drawdown treatments, each with three replicates: no water-level drawdown (Group 1; Control), 10 mm.d-1 (Group 2), 15 mm.d-1 (Group 3) and 20 mm.d-1 (Group 4). Larval sampling was conducted weekly for a period of 6 weeks each in the main malaria transmission season (October to November 2013) and subsequent dry season (February to March 2014). Larval densities were compared among treatments over time using repeated measures Analysis of Variance (ANOVA). Results A total of 284 Anopheles mosquito larvae were collected from the experimental dams during the study period. Most (63.4%; n = 180) were collected during the main malaria transmission season while the remaining (36.6%; n = 104) were collected during the dry season. Larvae comprised four Anopheles species, dominated by Anopheles arabiensis (48.1% of total larval samples; n = 136) and An. pharoensis (33.2%; n = 94). Mean larval density was highest in control treatment dams with stable water levels throughout the study, and decreased significantly (P < 0.05) with increasing water drawdown rates in both seasons. During the main transmission season, anopheline larval density was generally lower by 30%, 70% and 84% in Groups 2, Group 3 and Group 4, respectively, compared with the control dams (Group 1). In the dry season, larval density was reduced by 45%, 70% and 84% in Groups 2, Group 3 and Group 4, respectively, when compared to the control dams. Conclusion Increased water drawdown rates were associated with lower mosquito larval abundance. Water level management could thus serve as a potential control measure for malaria vectors around reservoirs by regulating the persistence of shallow shoreline breeding habitats. Dam operators and water resource managers should consider incorporating water level management as a malaria control mechanism into routine dam operations to manage the risk of malaria transmission to human populations around reservoirs.

Agot, Kawango; Masters, Samuel H.; Wango, Gift-Noelle; Thirumurthy, Harsha

No abstract available…

Presentation of Case. Dr. Emily C. Cleveland (Emergency Medicine): A 30-year-old woman was brought to the emergency department of this hospital because of cardiac arrest. On the morning of this presentation, the patient was found unresponsive in her bedroom. Her mother called emergency medical……

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease. Haemophysalis longicornis ticks have been considered the vector of severe fever with thrombocytopenia syndrome virus (SFTSV). However, clear data on the transmission of SFTS from ticks to humans are limited. Case presentation We report an 84-year-old woman who presented with fever and altered mentality, which was confirmed as SFTS with encephalopathy by reverse-transcription polymerase chain reaction in blood and cerebrospinal fluid. The SFTSV was also identified in the tick that bit her, H. longicornis. Phylogenetic analyses indicated that the SFTSV from the patient and the tick was identical. The patient gradually recovered with treatments of corticosteroids and immunoglobulin. Conclusion These findings provide further evidence of SFTS viral transmission from H. longicornis to human.

Plass, M., Solana, J., Wolf, F. A., Ayoub, S., Misios, A., Glazar, P., Obermayer, B., Theis, F. J., Kocks, C., Rajewsky, N.

Flatworms of the species Schmidtea mediterranea are immortal—adult animals contain a large pool of pluripotent stem cells that continuously differentiate to all adult cell types. Therefore, single-cell transcriptome profiling of adult animals should reveal mature and progenitor cells. By combining perturbation experiments, gene expression analysis, a computational method that predicts future cell states from the transcriptional changes, and a lineage reconstruction method, we placed all major cell types onto a single lineage tree that connects all cells to a single stem cell compartment. We characterize gene expression changes during differentiation and discover cell types important for regeneration. Our results demonstrate the importance of single-cell transcriptome analysis for mapping and reconstructing fundamental processes of developmental and regenerative biology at high resolution.

Fincher, C. T., Wurtzel, O., de Hoog, T., Kravarik, K. M., Reddien, P. W.

The transcriptome of a cell dictates its unique cell-type biology. We used single-cell RNA sequencing to determine the transcriptomes for essentially every cell type of a complete animal: the regenerative planarian Schmidtea mediterranea. Planarians contain a diverse array of cell types, possess lineage progenitors for differentiated cells (including pluripotent stem cells), and constitutively express positional information, making them ideal for this undertaking. We generated data for 66,783 cells, defining transcriptomes for known and many previously unknown planarian cell types and for putative transition states between stem and differentiated cells. We also uncovered regionally expressed genes in muscle, which harbors positional information. Identifying the transcriptomes for potentially all cell types for many organisms should be readily attainable and is a powerful new approach to metazoan biology.

Udeme E. Ekrikpo, Andre P. Kengne, Aminu K. Bello, Emmanuel E. Effa, Jean Jacques Noubiap, Babatunde L. Salako, Brian L. Rayner, Giuseppe Remuzzi, Ikechi G. Okpechi

by Udeme E. Ekrikpo, Andre P. Kengne, Aminu K. Bello, Emmanuel E. Effa, Jean Jacques Noubiap, Babatunde L. Salako, Brian L. Rayner, Giuseppe Remuzzi, Ikechi G. Okpechi Introduction The widespread use of antiretroviral therapies (ART) has increased life expectancy in HIV patients, predisposing them to chronic non-communicable diseases including Chronic Kidney Disease (CKD). We performed a systematic review and meta-analysis (PROSPERO registration number CRD42016036246) to determine the global and regional prevalence of CKD in HIV patients. Methods We searched PubMed, Web of Science, EBSCO and AJOL for articles published between January 1982 and May 2016. CKD was defined as estimated glomerular filtration rate (eGFR)…

George, Varghese K.; Pallikkuth, Suresh; Pahwa, Rajendra; de Armas, Lesley; Rinaldi, Stefano; Pan, Li; Pahwa, Savita

Objective: Antibody responses are often impaired in old age and in HIV+ infection despite virologic control with antiretroviral therapy but innate immunologic determinants are not well understood. Design: Monocytes and natural killer cells were examined for relationships to age, HIV infection and influenza vaccine responses. Methods: Virologically suppressed HIV+ (n = 139) and HIV− (n = 137) participants classified by age as young (18–39 years), middle-aged (40–59 years) and old (≥60 years) were evaluated preinfluenza and postinfluenza vaccination. Results: Prevaccination frequencies of inflammatory monocytes were highest in old HIV+ and HIV−, with old HIV+ exhibiting higher frequency of integrin CD11b on inflammatory monocytes that was correlated with age, expression of C-C chemokine receptor-2 (CCR2) and plasma soluble tumor necrosis factor receptor-1 (sTNFR1), with inverse correlation with postvaccination influenza H1N1 antibody titers. Higher frequencies of CD11b+ inflammatory monocytes (CD11bhi, >48.4%) compared with low frequencies of CD11b+ inflammatory monocytes (…

L. Leibovici

Violetta SulÅ�yc-Bielicka, Lidia KoÅ�odziejczyk, Sylwia Jaczewska, Dariusz Bielicki, Krzysztof Safranow, PaweÅ� Bielicki, Józef KÅ�adny, Wojciech Rogowski

by Violetta SulÅ�yc-Bielicka, Lidia KoÅ�odziejczyk, Sylwia Jaczewska, Dariusz Bielicki, Krzysztof Safranow, PaweÅ� Bielicki, Józef KÅ�adny, Wojciech Rogowski Transient or constant impaired immunity is often associated with neoplastic disease or oncological treatment. Among the most common pathogens found in patients with HIV or patients undergoing chemotherapy are protozoans of the Cryptosporidium genus, which cause diarrhea in humans and animals. The present study determined the frequency of Cryptosporidium spp. infections in patients with colorectal cancer (N = 108; 42 women; 66 men; median age, 65 years), before beginning oncological treatment, compared to a control group (N = 125; 56 women, 69 men; median age, 63 years) without colorectal cancer or a history of oncological disease. We also assessed whether Cryptosporidium spp. infections were associated with age, gender, cancer stage (based on Astler-Coller or TNM classification), histological grade, or cancer location. Patients were treated at the Pomeranian Medical University, in 2009–2014. The presence of Cryptosporidium spp. antigen was determined in stool samples, analyzed with a commercial immunoenzymatic test. Cryptosporidium spp. infections occurred significantly more often (p = 0.015) in patients (13%) compared to controls (4%). The patient group showed no significant relationship between Cryptosporidium spp. infection and sex, age, tumor location, cancer grade, or stage. A multivariate logistic regression analysis adjusted for age and sex that included all subjects (patient + control groups, n = 233) showed that the odds of a Cryptosporidium spp. infection were more than three-fold higher in patients than in controls, and more than six-fold higher among men than among women. Conclusions: 1) Cryptosporidium spp. infections occurred significantly more frequently in patients with colorectal cancer (before oncological treatment) compared to controls, independent of age and sex. 2) Cryptosporidium spp. infections were not associated with the colorectal cancer stage, grade, or location or with patient age. 3) Male gender was significantly related to the frequency of Cryptosporidium spp. infections, independent of age and the presence of colorectal cancer.

Chamie, Gabriel; Schaffer, Elisabeth M.; Ndyabakira, Alex; Emperador, Devy M.; Kwarisiima, Dalsone; Camlin, Carol S.; Havlir, Diane V.; Kahn, James G.; Kamya, Moses R.; Thirumurthy, Harsha

Objective: To assess the comparative effectiveness of alternative incentive-based interventions to promote HIV testing among men. Design: Randomized clinical trial. Methods: We enumerated four Ugandan parishes and enrolled men at least 18 years. Participants were randomized to six groups that received incentives of varying type and amount for HIV testing at a 13-day community health campaign. Incentive types were: gain-framed (control): participants were told they would receive a prize for testing; loss-framed: participants were told they had won a prize, shown several prizes, asked to select one, then told they would lose the prize if they did not test; lotteries: those who tested had a chance to win larger prizes. Each incentive type had a low and high amount (∼US$1 and US$5/participant). The primary outcome was HIV-testing uptake at the community health campaign. Results: Of 2532 participants, 1924 (76%) tested for HIV; 7.6% of those tested were HIV-positive. There was no significant difference in testing uptake in the two lottery groups (78%; P = 0.076) or two loss-framed groups (77%; P = 0.235) vs. two gain-framed groups (74%). Across incentive types, testing did not differ significantly in high-cost (76%) vs. low-cost (75%; P = 0.416) groups. Within low-cost groups, testing uptake was significantly higher in the lottery (80%) vs. gain-framed (72%; P = 0.009) group. Conclusion: Overall, neither offering incentives via lotteries nor framing incentives as losses resulted in significant increases in HIV testing compared with standard gain-framed incentives. However, when offering low-cost incentives to promote HIV testing, providing lottery-based rewards may be a better strategy than gain-framed incentives. Correspondence to Gabriel Chamie, MD, MPH, University of California, Box 0874, 995 Potrero Avenue, San Francisco, California, USA. Tel: +1 415 476 4082 x445; e-mail: Gabriel.chamie@ucsf.edu Received 13 December, 2017 Revised 13 March, 2018 Accepted 17 March, 2018 Copyright © 2018 Wolters Kluwer Health, Inc.

Connecting the Dots (Clinical Problem-Solving, N Engl J Med 2017;377:978-984). Connecting the Dots (N Engl J Med 2017;377:978-84). In the first sentence of the boldface paragraph beginning "MRI of the brain" (page 979), "hyperdense" should have been "hyperintense." In Figure 1 (page 981), Panel A……

Abstract Background Nosocomial, or healthcare-associated infections (HAI), exact a high medical and financial toll on patients, healthcare workers, caretakers, and the health system. Interpersonal contact patterns play a large role in infectious disease spread, but little is known about the relationship between health care workers’ (HCW) movements and contact patterns within a heath care facility and HAI. Quantitatively capturing these patterns will aid in understanding the dynamics of HAI and may lead to more targeted and effective control strategies in the hospital setting. Methods Staff at 3 urban university-based tertiary care hospitals in Canada completed a detailed questionnaire on demographics, interpersonal contacts, in-hospital movement, and infection prevention and control practices. Staff were divided into categories of administrative/support, nurses, physicians, and “Other HCWs” - a fourth distinct category, which excludes physicians and nurses. Using quantitative network modeling tools, we constructed the resulting HCW “co-location network” to illustrate contacts among different occupations and with locations in hospital settings. Results Among 3048 respondents (response rate 38%) an average of 3.79, 3.69 and 3.88 floors were visited by each HCW each week in the 3 hospitals, with a standard deviation of 2.63, 1.74 and 2.08, respectively. Physicians reported the highest rate of direct patient contacts (> 20 patients/day) but the lowest rate of contacts with other HCWs; nurses had the most extended (> 20 min) periods of direct patient contact. “Other HCWs” had the most direct daily contact with all other HCWs. Physicians also reported significantly more locations visited per week than nurses, other HCW, or administrators; nurses visited the fewest. Public spaces such as the cafeteria had the most staff visits per week, but the least mean hours spent per visit. Inpatient settings had significantly more HCW interactions per week than outpatient settings. Conclusions HCW contact patterns and spatial movement demonstrate significant heterogeneity by occupation. Control strategies that address this diversity among health care workers may be more effective than “one-strategy-fits-all” HAI prevention and control programs.

Courtney L. Davis, Rezwanul Wahid, Franklin R. Toapanta, Jakub K. Simon, Marcelo B. Sztein

by Courtney L. Davis, Rezwanul Wahid, Franklin R. Toapanta, Jakub K. Simon, Marcelo B. Sztein…

The PLOS ONE Staff

by The PLOS ONE Staff …

Mesay Hailu Dangisso, Endrias Markos Woldesemayat, Daniel Gemechu Datiko, Bernt Lindtjørn

by Mesay Hailu Dangisso, Endrias Markos Woldesemayat, Daniel Gemechu Datiko, Bernt Lindtjørn…

Juan M. Pericàs, Carlos Cervera, Asunción Moreno, Cristina Garcia-de-la-Mària, Manel Almela, Carles Falces, Eduard Quintana, Bàrbara Vidal, Jaume Llopis, David Fuster, Carlos A. Mestres, Francesc Marco, Jose M. Miró, on behalf of the Hospital Clinic Endocarditis Study Group

by Juan M. Pericàs, Carlos Cervera, Asunción Moreno, Cristina Garcia-de-la-Mària, Manel Almela, Carles Falces, Eduard Quintana, Bàrbara Vidal, Jaume Llopis, David Fuster, Carlos A. Mestres, Francesc Marco, Jose M. Miró, on behalf of the Hospital Clinic Endocarditis Study Group …

Jia Hui Chai, Chun Kiat Lee, Hong Kai Lee, Nicholas Wong, Kahwee Teo, Chuen Seng Tan, Praveen Thokala, Julian Wei-Tze Tang, Paul Anantharajah Tambyah, Vernon Min Sen Oh, Tze Ping Loh, Joanne Yoong

by Jia Hui Chai, Chun Kiat Lee, Hong Kai Lee, Nicholas Wong, Kahwee Teo, Chuen Seng Tan, Praveen Thokala, Julian Wei-Tze Tang, Paul Anantharajah Tambyah, Vernon Min Sen Oh, Tze Ping Loh, Joanne Yoong Pyrexia of unknown origin (PUO) is defined as a temperature of >38.3°C that lasts for >3 weeks, where no cause can be found despite appropriate investigation. Existing protocols for the work-up of PUO can be extensive and costly, motivating the application of recent advances in molecular diagnostics to pathogen testing. There have been many reports describing various analytical methods and performance of metagenomic pathogen testing in clinical samples but the economics of it has been less well studied. This study pragmatically evaluates the feasibility of introducing metagenomic testing in this setting by assessing the relative cost of clinically-relevant strategies employing this investigative tool under various cost and performance scenarios using Singapore as a demonstration case, and assessing the price and performance benchmarks, which would need to be achieved for metagenomic testing to be potentially considered financially viable relative to the current diagnostic standard. This study has some important limitations: we examined only impact of introducing the metagenomic test to the overall diagnostic cost and excluded costs associated with hospitalization and makes assumptions about the performance of the routine diagnostic tests, limiting the cost of metagenomic test, and the lack of further work-up after positive pathogen detection by the metagenomic test. However, these assumptions were necessary to keep the model within reasonable limits. In spite of these, the simplified presentation lends itself to the illustration of the key insights of our paper. In general, we find the use of metagenomic testing as second-line investigation is effectively dominated, and that use of metagenomic testing at first-line would typically require higher rates of detection or lower cost than currently available in order to be justifiable purely as a cost-saving measure. We conclude that current conditions do not warrant a widespread rush to deploy metagenomic testing to resolve any and all uncertainty, but rather as a front-line technology that should be used in specific contexts, as a supplement to rather than a replacement for careful clinical judgement.

De Oliveira, Fabienne; Cappy, Pierre; Lemée, Véronique; Moisan, Alice; Pronier, Charlotte; Bocket, Laurence; Bouvier-Alias, Magali; Chaix, Marie-Laure; Gault, Elyanne; Morvan, Odile; Poveda, Jean-Dominique; Schneider, Véronique; Wirden, Marc; Alessandri-Gradt, Elodie; Mourez, Thomas; Plantier, Jean-Christophe

Background: The broad genetic divergence of HIV-1/O relative to HIV-1/M has important implications for diagnosis, monitoring and treatment. Despite this divergence, some HIV-1/M+O dual infections and HIV-1/MO recombinant forms have been reported, mostly in Cameroon, where both groups are prevalent. Here, we describe the characteristics of such infections detected in France in 10 new patients, and discuss their implications for biological and clinical practice, owing to the presence of group O species. Methods: The French National Reference Centre for HIV received samples within the framework of mandatory notification of HIV infections, and for expert analysis. A strategy combining serotyping, viral quantification, group-specific molecular amplification and whole-genome sequencing was used for strain characterization and complementary investigations. Results: We identified one patient with M+O infection, three patients with M+O infection associated with MO recombinant, and six patients with only an MO recombinant. These atypical infections were detected upon strain characterization (n = 4) or because of anomalies during patient monitoring (n = 6). We identified eight new URF_MO, all but one originating from Cameroon. Interestingly, two distinct recombinant strains were found in two unrelated patients, representing possible precursors of a CRF_MO. Conclusion: Our work highlights the fact that the continuous evolution of HIV can hinder diagnosis and complicate clinical practice. We stress that unexpected results during diagnosis or monitoring necessitate further serological and molecular exploration, these atypical infections influence biological and therapeutic management and necessitate appropriate tools, and specific surveillance is necessary, especially as the frequency of such infections may be underestimated. Correspondence to Professor Jean-Christophe Plantier, PhD, PharmD, Laboratoire de Virologie, Institut de Biologie Clinique, CHU Charles Nicolle, 76031 Rouen Cedex, France. E-mail: jc.plantier@chu-rouen.fr; Dr Pierre Cappy, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015 Paris, France. E-mail: pcappy@ints.fr Received 19 December, 2017 Revised 28 February, 2018 Accepted 13 March, 2018 Copyright © 2018 Wolters Kluwer Health, Inc.

Wei Wu, Meifang Yang, Min Xu, Cheng Ding, Yongtao Li, Kaijin Xu, Jifang Shen, Lanjuan Li

by Wei Wu, Meifang Yang, Min Xu, Cheng Ding, Yongtao Li, Kaijin Xu, Jifang Shen, Lanjuan Li TB infection in patients after kidney transplantation remains a concern in a successful long-term outcome. This retrospective, descriptive study was performed on tuberculosis infection after kidney transplantation in the Department of Infectious Disease of the First Affiliated Hospital of Zhejiang University, a tertiary care hospital in China, from January 2011 to April 2017, with the aim to explain the clinical features of active tuberculosis after kidney transplantation and explore the correlated factors for diagnostic delay and mortality. It included 48 cases. All these cases were followed up for at least 12 months after anti-tuberculosis therapy, except the ones who died during this period. The median time of transplantation to active tuberculosis of these 48 patients was about 5.4 years. The time from a first hospital visit to the diagnosis (diagnostic delay) of 12 (25%) cases was more than 30 days. The correlated factors for the diagnostic delay more than 30 days were a fever for more than 2 weeks and antibiotic use for more than 2 weeks. Nine (18.8%) cases died during the anti-tuberculosis therapy or following-up period due to TB relapse. The risk factors for mortality were severe complications, such as encephaledema, severe pneumonia, intestinal perforation, liver function failure, and the following multiple-organ failure. In conclusion, the possibility of tuberculosis infection should be carefully assessed and sometimes diagnostic anti-tuberculosis therapy may be required for patients who had a fever for more than 2 weeks or used antibiotics for more than 2 weeks after kidney transplantation. Severe complications and the following multiple-organ failure might increase the mortality among these patients.

Abstract Background Efavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens. Methods HIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz-containing ART starting between 15 days prior to, during, or within 90 days after starting tuberculosis treatment, (efavirenz group), or other ART regimens (non-efavirenz group). Patients who started ART more than 90 days after initiation of TB treatment, or who experienced ART interruption of more than 15 days during TB treatment were excluded. We describe rates and factors associated with death, virological suppression, and loss to follow up at 12 months using univariate, multivariate Cox, and marginal structural models to compare the two groups of patients. Results Of 965 patients (647 receiving efavirenz-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE: rates of virological suppression ranged from 21% in EE to 61% in WE. After adjusting for potential confounders, rates of death (adjusted Hazard Ratio; aHR, 95%CI: 1.13, 0.72–1.78), virological suppression (aHR, 95%CI: 0.97, 0.76–1.22), and loss to follow up (aHR, 95%CI: 1.17, 0.81–1.67), were similar in patients treated with efavirenz and non-efavirenz containing ART regimens. Conclusion In this large, prospective cohort, the response to ART varied significantly across geographical regions, whereas the ART regimen (efavirenz or non-efavirenz containing) did not impact on the proportion of patients who were virologically-suppressed, lost to follow up or dead at 12 months.

Toshie Mashiba, Kouji Joko, Masayuki Kurosaki, Hironori Ochi, Yukio Osaki, Yuji Kojima, Ryo Nakata, Tohru Goto, Akahane Takehiro, Hiroyuki Kimura, Akeri Mitsuda, Chiharu Kawanami, Yasushi Uchida, Chikara Ogawa, Atsunori Kusakabe, Ryuichi Narita, Yasushi Ide, Takehiko Abe, Keiji Tsuji, Tadashi Kitamura, Kazuhiko Okada, Tetsuro Sohda, Masaya Shigeno, Takashi Satou, Namiki Izumi

by Toshie Mashiba, Kouji Joko, Masayuki Kurosaki, Hironori Ochi, Yukio Osaki, Yuji Kojima, Ryo Nakata, Tohru Goto, Akahane Takehiro, Hiroyuki Kimura, Akeri Mitsuda, Chiharu Kawanami, Yasushi Uchida, Chikara Ogawa, Atsunori Kusakabe, Ryuichi Narita, Yasushi Ide, Takehiko Abe, Keiji Tsuji, Tadashi Kitamura, Kazuhiko Okada, Tetsuro Sohda, Masaya Shigeno, Takashi Satou, Namiki Izumi Background and aim This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort. Methods This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively. Results AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients. Conclusions There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

Voelker R.

The FDA has warned 3 duodenoscope manufacturers that they’ve failed to comply with a federal requirement to assess whether current cleaning and disinfecting methods effectively reduce infection risk.

Hoshino A, Takashima T, Yoshida K, et al.

AbstractBackgroundSome patients with genetic defects develop Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD)/lymphoma as the main feature. Hypomophic mutations can cause different clinical and laboratory manifestations from null mutations in the same genes.MethodsWe sought to describe the clinical and immunologic phenotype of a 21-month-old boy having EBV-associated LPD who was in good health till then. A genetic and immunologic analysis was performed.ResultsWhole exome sequencing identified a novel compound heterozygous mutation of ZAP70 c.703-1G>A and c.1674G>A. A small amount of the normal transcript was observed. Unlike ZAP70 deficiency which is previously described as severe combined immunodeficiency with non-functional CD4+ T cells and absent CD8+ T cells, the patient had slightly low numbers of CD8+ T cells and a small amount of functional T cells. EBV-specific CD8+ T cells and invariant NKT (iNKT) cells were absent. The T-cell receptor repertoire using next generation sequencing was significantly restricted.ConclusionsOur patient shows that a hypomorphic mutation of ZAP70 can lead to EBV-associated LPD and that EBV-specific CD8+ T cells and iNKT cells are critically involved in immune response against EBV infection.

A 36-year-old man presented to the emergency department with substernal chest tightness of 6 hours’ duration. The chest tightness was initially intermittent but became persistent 1 hour before presentation. He was a current smoker with a smoking history of 10 pack-years. An electrocardiogram (ECG;……

Huttner A, Kowalczyk A, Turjeman A, et al.

This randomized clinical trial compares the clinical and microbiologic efficacy of 5-day nitrofurantoin vs single-dose fosfomycin in women with uncomplicated urinary tract infection (UTI).