Lei Gao, Xiangwei Li, Jianmin Liu, Xinhua Wang, Wei Lu, Liqiong Bai, Henan Xin, Haoran Zhang, Hengjing Li, Zongde Zhang, Yu Ma, Mufei Li, Boxuan Feng, Jiang Du, Hongtao Sui, Rong Zhao, Haoxiang Su, Shouguo Pan, Ling Guan, Fei Shen, Jian He, Shumin Yang, Hongyan Si, Xu Cheng, Zuhui Xu, Yunhong Tan, Tianzhu Chen, Weiguo Xu, Hong Peng, Zhijian Wang, Tao Zhu, Xiaoyou Chen, Xinhua Zhou, Xueling Guan, Qi Jin, LATENTTB-NSTM study team

Our results suggest that high-risk populations in communities in rural China, such as individuals at a high risk of disease reactivation from previous tuberculosis, should be targeted for latent infection screening and treatment with an interferon-? releasing assay rather than a TST.

Qifang Bi, Eva Ferreras, Lorenzo Pezzoli, Dominique Legros, Louise C Ivers, Kashmira Date, Firdausi Qadri, Laura Digilio, David A Sack, Mohammad Ali, Justin Lessler, Francisco J Luquero, Andrew S Azman, Oral Cholera Vaccine Working Group of The Global Task Force on Cholera Control

Two kOCV doses provide protection against cholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control.

Jean-Pierre Zellweger

Screening people at risk of developing tuberculosis because of latent infection and offering preventive treatment to those with positive results is now regarded as one of the components of the WHO End TB Strategy.1 In The Lancet Infectious Diseases, Lei Gao and colleagues2 present the results of a 2-year follow-up study in four rural regions of China, assessing patients with latent tuberculosis infection, defined by a positive tuberculin skin test (TST) or a positive interferon-? release assay (IGRA) QuantiFERON-TB Gold In-Tube (QFT), which has been described in previous publications.

Suman Kanungo, Pranab Chatterjee

The development of a cheap and effective oral cholera vaccine (OCV) is a remarkable achievement in the field of cholera prevention. A meta-analysis on the efficacy and effectiveness of OCVs by Qifang Bi and colleagues1 updates the estimates of the 2011 Cochrane review.2 Their analysis includes additional studies published since 2011, yet provides estimates that are almost the same.

Chikwari, Chido Dziva; Ferrand, Rashida A.; Simms, Victoria

No abstract available…

Rolle, Charlotte-Paige; Rosenberg, Eli S.; Siegler, Aaron J.; Sanchez, Travis H.; Luisi, Nicole; Weiss, Kevin; Cutro, Scott; Rio, Carlos del; Sullivan, Patrick S.; Kelley, Colleen F.

Background: HIV incidence among US young, black MSM (YBMSM) is high, and structural barriers (e.g. lack of health insurance) may limit access to Pre-Exposure Prophylaxis (PrEP). Research studies conducted with YBMSM must ensure access to the best available HIV prevention methods, including PrEP. Methods: We implemented an optional, non-incentivized PrEP program in addition to standard HIV prevention services in a prospective, observational cohort of HIV-negative YBMSM in Atlanta, GA. Provider visits and lab costs were covered; participant insurance plans and/or the manufacturer assistance program were used to obtain drug. Factors associated with PrEP initiation were assessed with prevalence ratios and time to PrEP initiation with Kaplan-Meier methods. Results: Of 192 enrolled YBMSM, 4% were taking PrEP at study entry. Of 184 eligible men, 63% indicated interest in initiating PrEP, 10% reported no PrEP interest, and 27% wanted to discuss PrEP again at a future study visit. Of 116 interested men, 46% have not attended a PrEP initiation appointment. Sixty-three men (63/184; 34%) initiated PrEP; 11/63 (17%) subsequently discontinued PrEP. The only factor associated with PrEP initiation was reported STI in the prior year (PR 1.50, 95%CI 1.002-2.25). Among interested men, median time to PrEP initiation was 16 weeks (95% CI 7-36). Conclusions: Despite high levels of interest, PrEP uptake may be suboptimal among YBMSM in our cohort even with amelioration of structural barriers that can limit use. PrEP implementation as standard of HIV prevention care in observational studies is feasible; however, further research is needed to optimize uptake for YBMSM. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

Helina Fikre, Rezika Mohammed, Saba Atinafu, Johan Griensven, Ermias Diro

Objective Cutaneous leishmaniasis (CL) receives far less attention than visceral leishmaniasis. Nevertheless, CL is predominantly caused by a unique species in Ethiopia (L aethiopica), which is known to cause severe forms such as diffuse (DCL) and mucocutaneous leishmaniasis (MCL). We report on the number and type of CL cases diagnosed, the clinical features, the treatments and treatment outcomes in North-West Ethiopia. Methods This is a retrospective chart record analysis of CL patients treated at the Leishmania Research and Treatment Center (LRTC) of the University of Gondar, Ethiopia. Results From 178 CL patients seen between Jan 2014 and Dec 2015, a total of 154 chart records were retrieved. These included 80 localized CL (LCL), 7 DCL and 67 MCL. The median age was 23 years; 71.4% were male. Most (n=121, 78.6%) of the lesions were on the face. The median time since onset was 12 months (6-24 months) and 28.6% presented after a trial of traditional medicine. The treatment of all forms of CL mainly consisted of 30 days of IM antimonial injections. Of these, 51/133 (38.3%) required treatment extension or change due to non-response. Three cases were treated with liposomal amphotericin B or miltefosine (two received the combination), of which two responded well. Conclusion CL was found to be complicated and difficult to treat. MCL was common, and patients presented after long delays. There is an urgent need to look for better treatment options for CL and improve access to care. This article is protected by copyright. All rights reserved.

Chen, Meiling; Dou, Zhihui; Wang, Liming; Wu, Yasong; Zhao, Decai; Gan, Xiumin; Ran, Hu; Ma, Ye; Fujie, Zhang

Backgroud: Women now account for about half of all people living with HIV worldwide, but researchers lack clear information and large population-based study about gender differences in treatment outcomes. Methods: A nationwide retrospective observational cohort study with data from the China National Free Antiretroviral Treatment Program was carried out. Antiretroviral-naive patients older than 18 years initiating standard antiretroviral therapy between January 1, 2010 and December 31, 2011 were included and followed up to Dec 31, 2015. We used modified Poisson regression models to estimate the impact of gender on virological suppression and retention in treatment, and Kaplan-Meier analysis and Cox proportional hazard models to evaluate gender difference in mortality. Results: 68646 patients (46083 (67.1%) men and 22563 (32.9%) women) with HIV met eligibility criteria. Women were significantly more likely to achieve virological suppression than men both at 12 months (adjusted relative risk [aRR] 1.02, 95%CI 1.01-1.03, p<0.001) and 48 months (aRR 1.01, 95%CI 1.00-1.02,p=0.005) after initiating antiretroviral treatment. Women were also more likely to remain in treatment at 12 months (aRR 1.02, 95%CI 1.01-1.02,p<0.001) and 48 months (aRR 1.04, 95%CI 1.03-1.05,p<0.001), although the difference became insignificant in alive patients. All-cause mortality was lower in women than in men (2.34 vs. 4.03 deaths/100PY, adjusted hazard ratio 0.72, 95%CI 0.67-0.77, p<0.001). Conclusions: In China, women are more likely to achieve virological suppression, remain in treatment and have a significantly lower risk of death than men. Future studies could take both biological and socio-behavioral factors into analysis to clarify the influence factors. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

Jiamsakul, Awachana; Kariminia, Azar; Althoff, Keri N; Cesar, Carina; Cortes, Claudia P; Davies, Mary-Ann; Do, Viet Chau; Eley, Brian; Gill, John; Kumarasamy, Nagalingeswaran; Machado, Daisy Maria; Moore, Richard; Prozesky, Hans; Zaniewski, Elizabeth; Law, Matthew

Background: Having 90% of patients on antiretroviral therapy (ART) and achieving an undetectable viral load (VL) is one of the 90:90:90 by 2020 targets. In this global analysis, we investigated the proportions of adult and paediatric patients with VL suppression in the first three years after ART initiation. Methods: Patients from the IeDEA cohorts who initiated ART between 2010 and 2014 were included. Proportions with VL suppression (…

M.S. Joshi, N.N. Ganorkar, S.S. Ranshing, A. Basu, N.A. Chavan, V. Gopalkrishna

Acute gastroenteritis outbreak occurred at Pargaon, Maharashtra, India in 1789 cases with an attack rate of 32.5% between November to December 2015. The stool specimens (n = 32) were investigated for different enteric viral agents using conventional methods. Transmission electron microscopy and RNA polyacrylamide gel electrophoresis respectively identified morphologically distinct rotavirus particles in 28% and RNA migration pattern of Group B Rotavirus (GBR) in 72% of the specimens. Reverse transcription polymerase chain reaction and nucleotide sequencing confirmed presence of GBR in 97% of the samples analyzed. The predominance of GBR infections and absence or insignificant presence of other agents confirmed GBR as an etiological agent of the gastroenteritis outbreak occurred in Maharashtra, India. This article is protected by copyright. All rights reserved …

Powderly WG, Naggie S, Kim AY, et al.

Oliver SE, Barry Cope A, Rinsky JL, et al.

AbstractBackground:Ocular syphilis is an inflammatory eye disease due to Treponema pallidum infection. In the United States, syphilis rates have increased since 2000; clusters of ocular syphilis were reported in 2015. We investigated ocular syphilis in North Carolina to describe the epidemiology and clinical course of disease.Methods:We reviewed syphilis cases reported to North Carolina during 2014-2015 and abstracted information from health department interviews for cases with ocular symptoms and no other defined etiology. To assess duration and severity of ocular symptoms, we also reviewed medical records and conducted structured interviews. We compared the prevalence of ocular manifestations among reported syphilis cases by demographic and clinical characteristics.Results:Among 4,232 syphilis patients, 63 (1.5%) had ocular syphilis: 21 in 2014 and 42 in 2015, a 100% increase. Total syphilis cases increased 35% through 2015. No patient with ocular syphilis named another ocular syphilis patient as a sex partner. Patients presented in all syphilis stages; 24 (38%) were diagnosed in primary or secondary syphilis. Ocular manifestations were more prevalent among syphilis patients who were male, aged >=40 years, white, and HIV-infected. No risk behaviors were associated with ocular syphilis. Among 39 interviewed patients, 34 (87%) reported reduced vision during infection; 12 (31%) reported residual visual symptoms post-treatment.Conclusion:In North Carolina, ocular syphilis increased from 2014 to 2015 and may be due to increased recognition of ocular manifestations, or a true increase in ocular syphilis. Many ocular syphilis patients experienced vision loss; however, most improved post-treatment.

Suzanne Filteau, G. PrayGod, S. L. Woodd, Henrik Friis, D. C. Heimburger, J. R. Koethe, P. Kelly, L. Kasonka, Andrea M. Rehman

Objectives Low grip strength is a marker of frailty and a risk factor for mortality among HIV patients and other populations. We investigated factors associated with grip strength in malnourished HIV patients at referral to ART, and at 12 weeks and 2-3 years after starting ART. Methods The study involved HIV-infected Zambian and Tanzanian participants recruited to the NUSTART trial when malnourished (body mass index …

Killpack, T. L., Ballesteros, M., Bunnell, S. C., Bedugnis, A., Kobzik, L., Hu, L. T., Petnicki-Ocwieja, T.

Phagocytosis of the Lyme disease causing pathogen Borrelia burgdorferi has been shown to be important in generating an inflammatory response to the pathogen. As a result, understanding the mechanisms of phagocytosis has been an area of great interest in the field of Lyme disease. Several cell surface receptors that participate in B. burgdorferi phagocytosis have been reported, including scavenger receptor MARCO and integrin α3β1. We sought to define the mechanisms by which these receptors mediated phagocytosis and to identify signaling pathways activated downstream of these receptors upon contact with B. burgdorferi. We identified both Syk and Src signaling pathways as ones that participate in B. burgdorferi phagocytosis and resulting cytokine activation. In our studies we found that MARCO and integrin β1 both play a role in the activation of the Src kinase pathway. However, only integrin β1 participates in the activation of Syk. Interestingly, the integrin activates Syk without the help of signaling adaptors Dap12 or FcR. Thus, we report that multiple pathways participate in B. burgdorferi internalization and different cell surface receptors act simultaneously in cooperation and independently to mediate phagocytosis.

Manchala Nageswar Reddy, Ranjeet Dungdung, Rajendra Pilankatta

Objectives Human serum protein profiling of the individual infected with multiple dengue virus serotypes for identifying the potential biomarkers and to investigate the cause for the severity of dengue virus infection. Methods Dengue virus NS1 positive serum samples were pooled into two groups (S2 and S3) based on the molecular serotyping and number of heterotypic infections. The pooled serum samples were subjected to two dimensional gel electrophoresis (2DGE) to identify the differentially expressed proteins. The peptide masses of up regulated protein were detected by matrix-assisted laser desorption ionization time-of-flight MALDI-TOF mass spectrometry and analyzed by MASCOT search engine. The results were compared with the control group (S1). The commonly upregulated protein was validated by quantitative ELISA and compared with control as well as single serotypic infected samples. Results Based on 2DGE, total thirteen proteins were differentially upregulated in S2 and S3 groups as compared to control. Some of the upregulated proteins were involved in mediating the complement activation of immune response. The Apolipoprotein A-1 (APO A-1) was upregulated in S2 and S3 groups. Upon validation, APO A-1 levels were increased in line with the number of heterotypic infection of dengue viruses. Conclusion Heterotypic infection of dengue viruses upregulate the serum proteins involved in the complement pathway in the early phase of infection. There was a significant increase in the level of APO A-1 in three different serotypic infections of dengue virus as compared to control. Further, the role of APO-A1 can be explored in elucidating the mechanism of dengue pathogenesis. This article is protected by copyright. All rights reserved.

Camus Nimmo, Ronan Doyle, Carrie Burgess, Rachel Williams, Rebecca Gorton, Timothy D. McHugh, Mike Brown, Stephen Morris-Jones, Helen Booth, Judith Breuer

Malte H. Wehmeyer, Patrick Ingiliz, Stefan Christensen, Dietrich Hueppe, Thomas Lutz, Karl Georg Simon, Knud Schewe, Christoph Boesecke, Axel Baumgarten, Heiner Busch, Juergen Rockstroh, Guenther Schmutz, Torben Kimhofer, Florian Berger, Stefan Mauss, Julian Schulze zur Wiesch

There are limited data regarding the real world effectiveness of direct acting antivirals (DAA) for the therapy of chronic genotype 3 hepatitis C virus (HCV) infection. All HCV genotype 3 infected patients from the German hepatitis C cohort (GECCO), which is a prospective database of nine German hepatitis C treatment centers, were included in the study. 342 chronically infected HCV genotype 3 patients were analyzed (253 males [74.0%], mean age 47.3 years, 127 cirrhotic patients [37.1%] mostly with Child A cirrhosis, 113 treatment experienced patients [37.1%], 38 HCV/HIV co-infected patients [11.1%]). SVR12 rates in the "intention-to-treat" analysis were as follows: sofosbuvir/ribavirin 69.4% (75/108), sofosbuvir/peginterferon/ribavirin 80.6% (58/72), sofosbuvir/daclatasvir ± ribavirin for 12 weeks 88.3% (53/63), sofosbuvir/daclatasvir ± ribavirin for 24 weeks 79.3% (23/29), sofosbuvir/ledipasvir ± ribavirin for 12 weeks 71.4% (10/14) and sofosbuvir/ledipasvir ± ribavirin for 24 weeks 86.7% (26/30). Forty patients were lost to follow-up, 23 patients had a relapse, 4 patients stopped treatment prematurely and 1 patient died. Female sex (P = 0.038) and treatment with two different DAAs (P = 0.05) were predictors for SVR12 in the multivariate analysis. In conclusion, sofosbuvir/daclatasvir ± ribavirin for 12 weeks and sofosbuvir/ledipasvir ± ribavirin for 24 weeks are effective for the treatment of HCV genotype 3 infected patients including cirrhotic, treatment-experienced or HIV/HCV co-infected patients. This article is protected by copyright. All rights reserved …

Calcagno, A; Piconi, S; Focà, E; Nozza, S; Carli, F; Montrucchio, C; Cattelan, AM; Orofino, G; Celesia, BM; Morena, V; De Socio, GV; Guaraldi, G; for the GEPPO (GEriatric Patients living with HIV/AIDS: a Prospective Multidimensional cOhort) Study Group

Background: Adults aging with HIV are at greater risk for several comorbidities. The CD4+ cell count and CD4+/CD8+ ratio often fail to normalize in elderly patients despite prolonged antiretroviral therapy; this has been associated with concomitant diseases and poor prognosis. Methods: A cross-sectional analysis in antiretroviral-treated HIV-positive patients aged >=65 years. Aim of the study was to describe the predictors of normalized T cell subsets ("nT", CD4+/CD8+ ratio >=1 and CD4+ >=500 cells/uL) in a cohort of geriatric HIV-positive patients and its association with HIV-associated non-AIDS conditions (HANA). Results: 1092 patients were included: nT was observed in 340 patients (31.1%). Multivariate binary logistic analysis showed that plasma HIV RNA …

Septimus E, Coopersmith C, Whittle J, et al.

AbstractThe Center for Medicare and Medicaid Services (CMS) adopted the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital Inpatient Quality Reporting (IQR) Program in July 2015 to help address the high mortality and high cost associated with sepsis. The SEP-1 performance measure requires, among other critical interventions, timely administration of antibiotics to patients with sepsis or septic shock. The multi-stakeholder work group recognizes the need for SEP-1, however, the work group strongly believes that multiple antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the use of these antibiotics, as called for in the SEP-1 measure, are not in alignment with prudent antimicrobial stewardship. To promote the appropriate use of antimicrobials and combat antimicrobial resistance, the work group provides recommendations for appropriate antibiotics for the treatment of sepsis.

Kuipers, K., Jong, W. S. P., van der Gaast-de Jongh, C. E., Houben, D., van Opzeeland, F., Simonetti, E., van Selm, S., de Groot, R., Koenders, M. I., Azarian, T., Pupo, E., van der Ley, P., Langereis, J. D., Zomer, A., Luirink, J., de Jonge, M. I.

Serotype-specific protection against a Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission and limit emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of LPS-detoxified outer membrane vesicles (OMVs) from Salmonella Typhimurium displaying the variable N-terminus of PspA (α1α2) for intranasal vaccination, which induced strong Th17 immunity associated with substantial reduction of pneumococcal colonization. Despite the variable nature of this protein a common MHCII epitope was identified, based on in silico prediction combined with ex vivo screening, and was essential for the IL17A-mediated cross-reactivity and associated with cross-protection. Based on 1352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single α1α2 type was estimated to cover 19.1% strains, illustrating the potential of Th17-mediated cross protection.

Cristina Barroso Hofer, Matthias Egger, Mary-Ann Davies, Ana Cristina Cisne Frota, Ricardo Hugo de Oliveira, Thalita Fernandes Abreu, Lúcia Evangelista Araújo, Bernardo Bastos Witthlin, Alice Weber Carvalho, Janaína Rivas Cordeiro, Giulia Pasqualini Lima, Olivia Keiser

Objective To describe the cascade of care to HIV mother-to-child-transmission (PMTCT) in a Rio de Janeiro reference pediatric clinic, and evaluate the main factors possibly associated with HIV transmission. Methods Data on antenatal care, perinatal and neonatal assistance to HIV-infected and HIV-exposed but uninfected children assisted in the clinic from 1996-2013 were collected. The cascade of care was graphically demonstrated, and possible factors associated with HIV infection were described using regression models for bivariate and multivariate analysis. We imputed missing values of explanatory variables for the final model. Results 989 children were included in the analysis: 211were HIV and 778 HEU. Graphically the HIV PMTCT cascade of care improved from 1996/2000 to the later periods, but not from 2001/2006 to 2007/2013. The main factor independently associated with the HIV infection over time was breastfeeding. In the period 1996/2000 the lack of antiretroviral use during labor was associated HIV transmission. While in 2001/2007, other modes of delivery but elective cesarean section, and lack of maternal antiretroviral use during antenatal care were associated with HIV transmssion. In the last period, the main factor associated with transmission was the lack of maternal antenatal care. Conclusions The HIV PMTCT cascade improved over time, but HIV vertical transmission remains a problem, and better access to antenatal care is needed. This article is protected by copyright. All rights reserved.

Bulger, J., MacDonald, U., Olson, R., Beanan, J., Russo, T. A.

Hypervirulent Klebsiella pneumoniae (hvKP) is an emerging pathotype that is capable of causing tissue-invasive, organ and life threatening infections in healthy individuals from the community. Knowledge on the virulence factors specific to hvKP is limited. In this report we describe a new factor (PEG344) that increases the virulence of the hvKP strain hvKP1. peg344 is present on the hvKP1 virulence plasmid, is broadly prevalent among hvKP strains, and has increased RNA abundance when grown in human ascites. An isogenic derivative of hvKP1 (hvKP1peg344) was constructed and compared with its wild-type parent in in vitro, ex vivo, and infection model studies. Both survival and competition experiments with outbred CD1 mice demonstrated that PEG344 was required for full virulence after pulmonary challenge, but interestingly, not after subcutaneous challenge. In silico analysis suggested that PEG344 serves as an inner membrane transporter. Compared to hvKP1, a small, but significantly significant decrease in growth/survival of hvKP1peg344 was observed in human ascites, but resistance to the bactericidal activity of complement was similar. These data suggested that PEG344 may transport an unidentified growth factor present in ascites. The data presented are important since it expands our limited knowledge base on virulence factors unique to hvKP, which is needed to lay the groundwork for translational approaches to prevent or treat these devastating infections.

Sule, N., Pasupuleti, S., Kohli, N., Menon, R., Dangott, L. J., Manson, M. D., Jayaraman, A.

Enterohemorrhagic E. coli (EHEC) is a commonly occuring foodborne pathogen responsible for numerous multistate outbreaks in the US. It is known to infect the host gastrointestinal tract, specifically in locations associated with lymphoid tissue. These niches serve as sources of enteric neurotransmitters such as epinephrine and norepinephrine that are known to increase virulence in several pathogens, including enterohemorrhagic E. coli. The mechanisms that allow pathogens to target these niches are poorly understood. We previously reported that 3,4-dihydroxymandelic acid (DHMA), a metabolite of norepinephrine produced by E. coli, is a chemoattractant for the non-pathogenic E. coli RP437 strain. Here we report that DHMA is also a chemoattractant for EHEC. In addition, DHMA induces the expression of EHEC virulence genes and increases attachment to intestinal epithelial cells in vitro in a QseC-dependent manner. We also show that DHMA is present in murine gut fecal contents and that its production requires the presence of the commensal microbiota. Based on its ability to both attract and induce virulence gene expression in EHEC, we propose that DHMA acts as a "molecular beacon" to target pathogens to their preferred sites of infection in vivo.IMPORTANCE Enterohemorrhagic E. coli (EHEC) is one of several foodborne pathogens that affect millions of people every year. Such pathogens infect the gut, preferring specific sites such as the gut-associated lymphoid tissue to initiate infection. Previous evidence has shown that norepinephrine, a stress hormone and the predominant neurotransmitter in the sympathetic nervous system that innervates the gut, exacerbates these infections by enhancing the virulence of the pathogens. Our research suggests metabolism of such host molecules by the gut microbiota may promote infections, offering promise of a new target for treatment of foodborne infections.

Ricardo Jorge Lopes, Antonio Muñoz Mérida, Miguel Carneiro

Genetic data generated by high-throughput sequencing and deposited in public databases are increasing exponentially. A substantial amount of these data is generated from wild animals, and can contain information from nontarget organisms, such as parasites. Methodologies that leverage this available information are warranted and can help to answer questions of general interest in parasitology.