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In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade., Competing Interests: Declaration of interests KAM, AJM, NMM, JTO, MTO, and AKU declare receiving financial support for the completion of this Personal View from Wellcome (grant number 226538/Z/22/Z), payments were made to the University of Minnesota. ADTB is a member of the Vaccine Research, Development and Manufacturing Committee of the Coalition for Epidemic Preparedness Innovations (CEPI). DME is employed by FIND. RFG declares grants U01AI151812, U19AI135995, R01AI132223, R01AI132244, and U19AI142790, all awarded from the National Institute of Allergy and Infectious Diseases, LEAP4WA awarded by the European & Developing Countries Clinical Trials Partnership, and ESEP1904 and INTU1901, both awarded by CEPI; stocks in and royalties or licenses from Zalgen Labs; ownership of a monoclonal antibody patent (WO2018106712A1); and travel support from Wellcome to attend the workshop identified in this Personal View. SG declares financial support for this Personal View from WHO and Wellcome; the receipt of drugs for clinical trials from Toyama–Fujifilm; grants (all payments were made to SG's institutions) from the German Research Foundation (grants GU 883/4-2, GU 883/5-1, and GU 883/7-1), the European Commission (project 101103204—INTEGRATE), the German Government, Ministry of Health (projects ZMI1-2521WHO002 and ZMII2-2523GHP006), CEPI (framework agreement for implementing partner services); the Kirmser Foundation (donation of equipment); speaker honoraria for continuing medical education on viral haemorrhagic fevers; and support for attending meetings from WHO, Wellcome, and CEPI, including travel support from Wellcome to attend the workshop identified in this Personal View. LTM declares being a science consultant at FIND, for which she receives grants, contracts, and consulting fees; and travel support from Wellcome to attend the workshop identified in this Personal View. SAO declares a consulting contract with CEPI (payments made to SAO); is a member of the INTEGRATE consortium with grants from the European & Developing Countries Clinical Trials Partnership (payments made to SAO's institution); and support from CEPI and EDCTP funds (payments made to travel agencies and through SAO's institution). CR declares participation on a Data Safety Monitoring Board or Advisory Board (this advisory board was designated after CR's participation in the work leading to this Personal View). WKA is Executive Director of the African Vaccine Manufacturing Initiative, and Cheif Executive of National Vaccine Institute, Ghana. DAA, IMA, WKA, ADTB, DGB, EF-C, IdC, DSG, SBG, MJ, KAM, JTO, MTO, AKU, and CSS declare Wellcome supported for travel to attend the workshop identified in this Personal View. PCF, PJH, and JPG worked at Wellcome during the time that this Personal View was completed. All other authors declare no competing interests. No authors were paid by a pharmaceutical company or any other agency to write this Personal View. The authors alone are responsible for the views expressed in this Personal View and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Recent outbreaks of Ebola virus disease (EVD) and Marburg virus disease (MVD) in sub-Saharan Africa illustrate the need to better understand animal reservoirs, burden of disease, and human transmission of filoviruses. This protocol outlines a systematic literature review to assess the prevalence of filoviruses that infect humans in sub-Saharan Africa. A secondary aim is to qualitatively describe and evaluate the assays used to assess prevalence., Methods: The data sources for this systematic review include PubMed, Embase, and Web of Science. Titles, abstracts, and full texts will be reviewed for inclusion by a primary reviewer and then by a team of secondary reviewers, and data will be extracted using a pre-specified and piloted data extraction form. The review will include human cross-sectional studies, cohort studies, and randomized controlled trials conducted in sub-Saharan Africa up until March 13, 2024 that have been published in peer-reviewed scientific journals, with no language restrictions. Prevalence will be stratified by pathogen, population, assay, and sampling methodology and presented in forest plots with estimated prevalence and 95% confidence intervals. If there are enough studies within a stratum, I 2 statistics will be calculated (using R statistical software), and data will be pooled if heterogeneity is low. In addition, assays used to detect infection will be evaluated. All studies included in the review will be assessed for quality and risk of bias using the JBI Prevalence Critical Appraisal Tool and for certainty using the GRADE certainty ratings., Discussion: Accurately measuring the rate of exposure to filoviruses infecting humans in sub-Saharan Africa using prevalence provides an essential understanding of natural history, transmission, and the role of subclinical infection. This systematic review will identify research gaps and provide directions for future research seeking to improve our understanding of filovirus infections. Understanding the natural history, transmission, and the role of subclinical infection is critical for predicting the impact of an intervention on disease burden., Systematic Review Registration: In accordance with the guidelines outlined in the PRISMA-P methodology, this protocol was registered with PROSPERO on April 7, 2023 (ID: CRD42023415358)., (© 2024. The Author(s).)

Castor ( Ricinus communis L.) is an important nonedible industrial crop that produces oil, which is used in the production of medicines, lubricants, and other products. However, the quality and quantity of castor oil are critical factors that can be degraded by various insect pest attacks. The traditional method of identifying the correct category of pests required a significant amount of time and expertise. To solve this issue, automatic insect pest detection methods combined with precision agriculture can help farmers in providing adequate support for sustainable agriculture development. For accurate predictions, the recognition system requires a sufficient amount of data from a real-world situation, which is not always available. In this regard, data augmentation is a popular technique used for data enrichment. The research conducted in this investigation established an insect pest dataset of common castor pests. This paper proposes a hybrid manipulation-based approach for data augmentation to solve the issue of the lack of a suitable dataset for effective vision-based model training. The deep convolutional neural networks VGG16, VGG19, and ResNet50 are then adopted to analyze the effects of the proposed augmentation method. The prediction results show that the proposed method addresses the challenges associated with adequate dataset size and significantly improves overall performance when compared to previous methods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nitin, Gupta, Yadav, Bovand and Tyagi.)

Vaccines are needed to disrupt or prevent continued outbreaks of filoviruses in humans across Western and Central Africa, including outbreaks of Marburg virus (MARV). As part of a filovirus vaccine product development plan, it is important to investigate dose response early in preclinical development to identify the dose range that may be optimal for safety, immunogenicity, and efficacy, and perhaps demonstrate that using lower doses is feasible, which will improve product access. To determine the efficacious dose range for a manufacturing-ready live recombinant vesicular stomatitis virus vaccine vector (rVSV∆G-MARV-GP) encoding the MARV glycoprotein (GP), a dose-range study was conducted in cynomolgus macaques. Results showed that a single intramuscular injection with as little as 200 plaque-forming units (PFUs) was 100% efficacious against lethality and prevented development of viremia and clinical pathologies associated with MARV Angola infection. Across the vaccine doses tested, there was nearly a 2000-fold range of anti-MARV glycoprotein (GP) serum IgG titers with seroconversion detectable even at the lowest doses. Virus-neutralizing serum antibodies also were detected in animals vaccinated with the higher vaccine doses indicating that vaccination induced functional antibodies, but that the assay was a less sensitive indicator of seroconversion. Collectively, the data indicates that a relatively wide range of anti-GP serum IgG titers are observed in animals that are protected from disease implying that seroconversion is positively associated with efficacy, but that more extensive immunologic analyses on samples collected from our study as well as future preclinical studies will be valuable in identifying additional immune responses correlated with protection that can serve as markers to monitor in human trials needed to generate data that can support vaccine licensure in the future.

Background: To investigate a vaccine technology with potential to protect against coronavirus disease 2019 (COVID-19) and reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a single vaccine dose, we developed a SARS-CoV-2 candidate vaccine using the live vesicular stomatitis virus (VSV) chimeric virus approach previously used to develop a licensed Ebola virus vaccine., Methods: We generated a replication-competent chimeric VSV-SARS-CoV-2 vaccine candidate by replacing the VSV glycoprotein (G) gene with coding sequence for the SARS-CoV-2 Spike glycoprotein (S). Immunogenicity of the lead vaccine candidate (VSV∆G-SARS-CoV-2) was evaluated in cotton rats and golden Syrian hamsters, and protection from SARS-CoV-2 infection also was assessed in hamsters., Findings: VSV∆G-SARS-CoV-2 delivered with a single intramuscular (IM) injection was immunogenic in cotton rats and hamsters and protected hamsters from weight loss following SARS-CoV-2 challenge. When mucosal vaccination was evaluated, cotton rats did not respond to the vaccine, whereas mucosal administration of VSV∆G-SARS-CoV-2 was found to be more immunogenic than IM injection in hamsters and induced immunity that significantly reduced SARS-CoV-2 challenge virus loads in both lung and nasal tissues., Interpretation: VSV∆G-SARS-CoV-2 delivered by IM injection or mucosal administration was immunogenic in golden Syrian hamsters, and both vaccination methods effectively protected the lung from SARS-CoV-2 infection. Hamsters vaccinated by mucosal application of VSV∆G-SARS-CoV-2 also developed immunity that controlled SARS-CoV-2 replication in nasal tissue., Funding: The study was funded by Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA. Parts of this research was supported by the Biomedical Advanced Research and Development Authority (BARDA) and the Defense Threat Reduction Agency (DTRA) of the US Department of Defense., Competing Interests: Declaration of interests C.L.P., M.Y., M.B.F., A.J.B., A.S.E. are listed as inventors on a patent application submitted jointly by IAVI, NY, USA and Merck & Co., Inc., Rahway, NJ, USA (Vaccine Compositions for Preventing Coronavirus Disease). MBF holds stock in Merck Sharpe & Dohme, Corp. and is a consultant for Sanofi Pasteur. M.B.F. is a member of the board of directors at IAVI. No other potential conflicts of interest are declared. D.D.R., S.S., L.Z., A.J.B., M.C., A.S.E., G.H., T.K.M. and M.H. are employees of Merck Sharpe & Dohme, Corp., and division of Merck & Co., Inc., Rahway, NJ, USA and hold stock options in the Company. K.K., E.S., G.W., B.L. and F.L. are employees of Merck Sharpe & Dohme, Corp., and division of Merck & Co., Inc., Rahway, NJ, USA., (Copyright © 2022 Merck Sharp & Dohme LLC., a subsidiary Merck & Co., Inc., Rahway, NJ, USA, The Author(s). Published by Elsevier B.V. All rights reserved.)

Background Urticaria, a vascular reaction of the skin, is marked by the transient appearance of erythematous papules or plaques (wheals) of varying sizes that are blanchable and associated with severe pruritus which lasts from a few hours to days. The etiological factors for urticaria include food, drugs, bacterial foci, pollen, fungi, dust, worms, physical stimuli, stress, anxiety, insect stings, etc. Skin prick tests (SPTs) represent the cheapest and most effective method to diagnose immunoglobulin E-mediated type 1 allergic reactions such as urticaria. A history suggestive of clinical sensitivity supported by a positive test strongly implicates the allergen in the disease process. In this study, we aimed to detect the common allergens and correlate the findings of SPTs with various epidemiological characteristics of urticaria patients. Methodology A total of 100 patients with urticaria were included in this study. After receiving written and informed consent from patients, SPTs using a battery of 45 allergens were performed. Results In our study, SPT positivity was seen in 88 (88%) patients. The highest sensitization was noted toward Dermatophagoides pteronyssinus (house dust mite) (30%), followed by D. farinae , Cynodon dactylon , and peanuts (each comprising 24%), and Ailanthus excelsa (20%). Conclusions Finding the causative allergen in urticaria is often a difficult and long-drawn process, both for the physician and the patient. Our study identified an allergen in 88% of patients with urticaria, thereby showing that the SPT is a cost-effective, easy, and reliable tool for diagnosing and guiding treatments in urticaria patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Lote et al.)

Rapid industrialization and intensive agriculture activities have led to a rise in heavy metal contamination all over the world. Chhattisgarh (India) being an industrial state, the soil and water are thickly contaminated with heavy metals, especially from arsenic (As). In the present study, we isolated 108 arsenic-resistant bacteria (both from soil and water) from different arsenic-contaminated industrial and mining sites of Chhattisgarh to explore the bacterial gene pool. Further, we screened 24 potential isolates out of 108 for their ability to tolerate a high level of arsenic. The sequencing of the 16S rRNA gene of bacterial isolates revealed that all these samples belong to different diverse genera including Bacillus, Enterobacter, Klebsiella, Pantoea, Acinetobacter, Cronobacter, Pseudomonas and Agrobacterium. The metal tolerance ability was determined by amplification of arsB (arsenite efflux gene) and arsC (arsenate reductase gene) from chromosomal DNA of isolated RnASA11, which was identified as Klebsiella pneumoniae through in silico analysis. The bacterial strains RpSWA2 and RnASA11 were found to tolerate 600 mM As (V) and 30 mM As (III) but the growth of strain RpSWA2 was slower than RnASA11. Furthermore, atomic absorption spectroscopy (AAS) of the sample obtained from bioremediation assay revealed that Klebsiella pneumoniae RnASA11 was able to reduce the arsenic concentration significantly in the presence of arsenate (44%) and arsenite (38.8%) as compared to control., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Studies on the changes in the presentation and management of acute myocardial infarction (AMI) during the COVID-19 pandemic from low- and middle-income countries are limited. We sought to determine the changes in the number of admissions, management practices, and outcomes of AMI during the pandemic period in India., Methods & Results: In this two-timepoint cross-sectional study involving 187 hospitals across India, patients admitted with AMI between 15th March to 15th June in 2020 were compared with those admitted during the corresponding period of 2019. We included 41,832 consecutive adults with AMI. Admissions during the pandemic period (n = 16414) decreased by 35·4% as compared to the corresponding period in 2019 (n = 25418). We observed significant heterogeneity in this decline across India. The weekly average decrease in AMI admissions in 2020 correlated negatively with the number of COVID cases (r = -0·48; r 2  = 0·2), but strongly correlated with the stringency of lockdown index (r = 0·95; r 2  = 0·90). On a multi-level logistic regression, admissions were lower in 2020 with older age categories, tier 1 cities, and centers with high patient volume. Adjusted utilization rate of coronary angiography, and percutaneous coronary intervention decreased by 11·3%, and 5·9% respectively., Conclusions: The magnitude of reduction in AMI admissions across India was not uniform. The nature, time course, and the patient demographics were different compared to reports from other countries, suggesting a significant impact due to the lockdown. These findings have important implications in managing AMI during the pandemic., Competing Interests: Declaration of competing interest Nothing to declare for all the authors., (Copyright © 2021 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

In the present study, bacterial isolates were screened for arsenic resistance efficiency. Environmental isolates were isolated from arsenic-rich soil samples (i.e., from Rajnandgaon district of Chhattisgarh state, India). Amplification and sequencing of 16S rRNA gene revealed that the isolates were of Bacillus firmus RSN1, Brevibacterium senegalense RSN2, Enterobacter cloacae RSN3, Stenotrophomonas pavanii RSN6, Achromobacter mucicolens RSN7, and Ochrobactrum intermedium RSN10. Arsenite efflux gene (arsB) was successfully amplified in E. cloacae RSN3. Atomic absorption spectroscopy (AAS) analysis showed an absorption of 32.22% arsenic by the RSN3 strain. Furthermore, results of scanning electron microscopy (SEM) for morphological variations revealed an initial increase in the cell size at 1 mM sodium arsenate; however, it was decreased at 10 mM concentration in comparison to control. This change of the cell size in different metal concentrations was due to the uptake and expulsion of the metal from the cell, which also confirmed the arsenite efflux system.

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely - and at times uniquely - affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group - a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy - in consultation with a variety of external experts and stakeholders., Competing Interests: Conflict of interest disclosure RAK has received grants from the Bill and Melinda Gates Foundation and PATH as well as personal fees from MERCK, outside the submitted work. JSA served as the Chair of the Global Alliance for Vaccines and Immunizations (Gavi) Vaccine Investment Strategic (VIS) Steering Committee (June 2017 – present) as well as the Co-chair of the Vaccine Innovation Prioritization Strategy Alliance (Gavi, WHO, UNICEF, Gates and PATH) Steering Committee (July 2018 – present) during the conduct of this work. BGG is President, Global Immunization at the Sabin Vaccine Institute. Sabin receives support from the Bill and Melinda Gates Foundation, Gavi, the National Philanthropic Trust, and private philanthropy. In addition, Sabin receives project-specific support from GlaxoSmithKline, Merck & Co., Pfizer, Sanofi Pasteur, Takeda Vaccines, Inc. None of this support is related to the focus of the PREVENT Working Group or the published Guidance. DCK has grant support from the Bill and Melinda Gates Foundation for work outside the scope of this Guidance. DCK oversees PATH's Center for Vaccine Innovation and Access (CVIA), which has grants from by the Bill and Melinda Gates Foundation for related work, including Advancing Maternal Immunization. The other authors do not have conflicts of interest to declare., (Copyright © 2019 Pan American Health Organization. Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 pandemic has affected around 20million patients worldwide and 2.0 million cases from India. The lockdown was employed to delay the pandemic. However, it had an unintentional impact on acute cardiovascular care, especially acute myocardial infarction (AMI). Observational studies have shown a decrease in hospital admissions for AMI in several developed countries during the pandemic period. We aimed to evaluate the impact of COVID-19 on the AMI admissions patterns across India., Methods: In this multicentric, retrospective, cross-sectional study, we included all AMI cases admitted to participating hospitals during the study period 15th March to 15th June 2020 and compared them using a historical control of all cases of AMI admitted during the corresponding period in the year 2019. Major objective of the study is to analyze the changes inthe number of hospital admissions for AMI in hospitals across India. In addition, we intend to evaluate the impact of COVID-19 on the weekly AMI admission rates, and other performance measures like rates of thrombolysis/primary percutaneous interventions (PCI), window period, door to balloon time, and door to needle time. Other objectives include evaluation of changes in the major complications and mortality rates of AMI and its predictors during COVID-19 pandemic., Conclusions: This CSI-AMI study will provide scientific evidence about the impact of COVID-19 on AMI care in India. Based on this study, we may be able to suggest appropriate changes to the existing MI guidelines and to educate the public regarding emergency care for AMI during COVID-19 pandemic., Competing Interests: Declaration of competing interest The authors are solely responsible for the design of the study, the conduct of the study, drafting and editing of the paper, and its final contents., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Introduction: The Ebola epidemic in West Africa from 2014 to 2016 was unique in its size, location, and duration; this article reviews the experiences and lessons learned for one vaccine candidate developed during the outbreak and discusses critical gaps that still exist today which will need to be addressed for successful end to end emerging infectious disease vaccine product development in the future., Areas Covered: Through the formation of numerous international partnerships, the rVSVΔG-ZEBOV-GP vaccine advanced through Phase I/II/III clinical trials which resulted in favorable Phase III efficacy results. Key lessons learned that could be used to facilitate future vaccine development efforts include sufficient preclinical work in relevant animal models, innovative partnerships created to pool resources and expertise, and 'hyper' coordination and communication among partners to build trust and ensure an adequate regulatory package needed to license a vaccine., Expert Commentary: As evidenced by the 2014-2016 outbreak in West Africa as well as the two other most recent outbreaks in the Democratic Republic of the Congo in 2018, there is an urgent need to develop new models for emerging infection vaccine development where trusted partners come together and where the development of vaccines is a shared responsibility conducted in advance of the next crisis.

Background: Healthcare workers have a high risk of developing hand eczema., Objectives: To determine the prevalence and severity of dermatologist-determined hand eczema among healthcare workers, carry out patch testing, and correlate the findings with impairment in quality of life (QoL) and demographic and vocational factors., Methods: Seven hundred and ten healthcare workers (279 nurses, 246 cleaners, and 185 nursing auxiliaries) were screened for the presence of hand eczema. Severity of eczema was calculated with the Hand Eczema Severity Index (HECSI), and QoL was measured with the Dermatology Life Quality Index (DLQI). Individuals with hand eczema were also patch tested., Results: The point and 1-year prevalences of hand eczema were 7.2% and 18.9%, respectively. Hand eczema was significantly associated with atopic dermatitis. The mean HECSI score was 9.39; it was significantly higher in patients with atopic dermatitis and those with recurrent hand eczema. The mean DLQI score was 5.37. Cleaning staff had significantly greater impairment in QoL. HECSI and DLQI scores were positively correlated. Patch testing showed that thiuram mix, antibiotics and cleansers as sensitizers were over-represented in healthcare workers as compared with controls., Conclusions: Hand eczema was particularly common in hospital cleaners and staff with atopic dermatitis. Further studies are needed to address the burden of occupational hand eczema and develop guidelines for its management at a national level., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: It is possible to prevent deaths due to cervical cancer through screening and treatment. Cervical cytology which is a standard screening tool in developed countries fails as a screening method in low-resource countries due to financial and technical constraints., Objective: To determine the prevalence of pre-malignant lesions of the cervix by VIA and Pap smear test among rural married women and to find out association of socio demographic factors with positive screening test results., Method: A community based cross-sectional study was carried out among rural married women in the field practice area of a tertiary health care center. A pre-designed questionnaire was administered to collect information on socio-demographic characteristics from 550 women. They were tested for the presence of pre-malignant lesions of the cervix using VIA and Pap smear as screening tools., Results: Out of 550 study participants, total 37 patients were found positive, out of which 7, 17 & 13 patients were found positive by Pap smear alone, VIA test alone, and by both these tests respectively. Moderate agreement (k=0.498) was found between these two tests by applying Kappa statistics at 95% confidence interval. The VIA and Pap smear tests were positive among 5.5% and 3.6% study subjects respectively. The positivity rate was found to be more in the age group of >50 years, Hindu, SC/ST caste, joint family, professional and, upper class., Conclusion: The prevalence of pre-malignant lesions of the cervix by VIA test was 5.5% while 3.6% pre-malignant lesion was detected by Pap smear method. VIA and Pap smear positivity rates among rural married women., Competing Interests: There are no conflicts of interest.

BACKGROUND Predicting recurrent Clostridium difficile infection (rCDI) remains difficult., Methods: We employed a retrospective cohort design. Granular electronic medical record (EMR) data had been collected from patients hospitalized at 21 Kaiser Permanente Northern California hospitals. The derivation dataset (2007-2013) included data from 9,386 patients who experienced incident CDI (iCDI) and 1,311 who experienced their first CDI recurrences (rCDI). The validation dataset (2014) included data from 1,865 patients who experienced incident CDI and 144 who experienced rCDI. Using multiple techniques, including machine learning, we evaluated more than 150 potential predictors. Our final analyses evaluated 3 models with varying degrees of complexity and 1 previously published model. RESULTS Despite having a large multicenter cohort and access to granular EMR data (eg, vital signs, and laboratory test results), none of the models discriminated well (c statistics, 0.591-0.605), had good calibration, or had good explanatory power. CONCLUSIONS Our ability to predict rCDI remains limited. Given currently available EMR technology, improvements in prediction will require incorporating new variables because currently available data elements lack adequate explanatory power. Infect Control Hosp Epidemiol 2017;38:1196-1203.

Background: Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti-toxin A and anti-toxin B antibody levels., Methods: Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays., Results: A predictor of recurrence was age ≥65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI., Conclusions: Our findings demonstrate the importance of clinical as well as immunological risk factors in rCDI and provide more robust evidence for the protective effects of antibody to toxin B in the prevention of rCDI., Clinical Trials Registration: NCT00350298., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Despite a large increase in Clostridium difficile infection (CDI) severity, morbidity and mortality in the US since the early 2000s, CDI burden estimates have had limited generalizability and comparability due to widely varying clinical settings, populations, or study designs., Methods: A decision-analytic model incorporating key input parameters important in CDI epidemiology was developed to estimate the annual number of initial and recurrent CDI cases, attributable and all-cause deaths, economic burden in the general population, and specific number of high-risk patients in different healthcare settings and the community in the US. Economic burden was calculated adopting a societal perspective using a bottom-up approach that identified healthcare resources consumed in the management of CDI., Results: Annually, a total of 606,058 (439,237 initial and 166,821 recurrent) episodes of CDI were predicted in 2014: 34.3 % arose from community exposure. Over 44,500 CDI-attributable deaths in 2014 were estimated to occur. High-risk susceptible individuals representing 5 % of the total hospital population accounted for 23 % of hospitalized CDI patients. The economic cost of CDI was $5.4 billion ($4.7 billion (86.7 %) in healthcare settings; $725 million (13.3 %) in the community), mostly due to hospitalization., Conclusions: A modeling framework provides more comprehensive and detailed national-level estimates of CDI cases, recurrences, deaths and cost in different patient groups than currently available from separate individual studies. As new treatments for CDI are developed, this model can provide reliable estimates to better focus healthcare resources to those specific age-groups, risk-groups, and care settings in the US where they are most needed. (Trial Identifier ClinicaTrials.gov: NCT01241552).

Background: There is limited data regarding the demographics and type of cardiac implantable electronic device (CIED) in India., Aim: The aim of this survey was to define trends in CIED implants, which included permanent pacemakers (PM), intracardiac defibrillators (ICD), and cardiac resynchronization therapy pacemakers and defibrillators (CRT-P/D) devices in India., Methods: The survey was the initiative of the Indian Society of Electrocardiology and the Indian Heart Rhythm Society. The type of CIED used, their indications, demographic characteristics, clinical status and co-morbidities were collected using a survey form over a period of 1 year., Results: 2117 forms were analysed from 136 centers. PM for bradyarrhythmic indication constituted 80% of the devices implanted with ICD's and CRT-P/D forming approximately 10% each. The most common indication for PM implantation was complete atrio-ventricular block (76%). Single chamber (VVI) pacemakers formed 54% of implants, majority in males (64%). The indication for ICD implantation was almost equal for primary and secondary prevention. A single chamber ICD was most commonly implanted (65%). Coronary artery disease was the etiology in 58.5% of patients with ICD implants. CRT pacemakers were implanted mostly in patients with NYHA III/IV (82%), left ventricular ejection fraction <0.35 (88%) with CRT-P being most commonly used (57%)., Conclusion: A large proportion of CIED implants in India are PM for bradyarrhythmic indications, predominantly AV block. ICD's are implanted almost equally for primary and secondary prophylaxis. Most CRT devices are implanted for NYHA Class III. There is a male predominance for implantation of CIED., (Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Dengue causes more human morbidity globally than any other vector-borne viral disease. Recent research has led to improved epidemiological methods that predict disease burden and factors involved in transmission, a better understanding of immune responses in infection, and enhanced animal models. In addition, a number of control measures, including preventative vaccines, are in clinical trials. However, significant gaps remain, including the need for better surveillance in large parts of the world, methods to predict which individuals will develop severe disease, and immunologic correlates of protection against dengue illness. During the next decade, dengue will likely expand its geographic reach and become an increasing burden on health resources in affected areas. Licensed vaccines and antiviral agents are needed in order to effectively control dengue and limit disease., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Diabetes is associated with a significant risk of cardiovascular diseases (CVDs). Patients with diabetes are known to suffer from a disproportionately large burden of CVDs, in terms of higher risk, worse prognosis and more adverse outcomes. Acute coronary syndromes, including coronary artery disease, represent a large proportion of this burden and conventionally coronary artery bypass grafting (CABG) has been the mainstay of facilitating reperfusion in patients with diabetes. However, hyperglycaemia is an important factor which affects the outcomes of CABG and shows a grave impact on patients' well-being. Thus, it is important to appropriately manage hyperglycaemia in the peri-and intra-operative periods to assure the best possible outcomes in patients with diabetes. There is scant evidence to show that oral antidiabetic drugs (OADs) or non-insulin based therapies show considerable benefit in patients undergoing CABG. Even with the use of insulin-based therapies, appropriate glycaemic targets, accurately designed algorithm to achieve such targets and specific recommendations to facilitate the appropriate use of such algorithm are important considerations. However, current international guidelines are either country-specific or fail to address context-specific needs in individual countries. In view of the growing incidence of cardiovascular diseases and diabetes in India, as a result of changing lifestyles, it is imperative upon clinicians to formulate India-specific guidelines for effective management of (CVDs). It is the endeavour of the current guideline to present recommendations based on a firm evidentiary foundation coupled with context-specific inputs from experts' consensus opinion. These recommendations represent an effort to address the urgent need for such an exercise both in the academic as well as the clinical realm.

Background: Women diagnosed with cervical cancer report longer duration and more recent use of combined oral contraceptives (COCs). It is unclear how COC use impacts risk of cervical carcinogenesis., Methods: We estimated the risk of new human papillomavirus (HPV) DNA detection and persistence among 1135 human immunodeficiency virus (HIV)-negative women aged 20-37 years from Thailand who were followed for 18 months at 6-month intervals. Type-specific HPV DNA, demographic information, hormonal contraceptive use, sexual behavior, genital tract coinfection, and Papanicolaou test results were assessed at baseline and each follow-up., Results: Women who reported current COC use during follow-up were less likely to clear HPV infection compared with nonusers, independent of sexual behavior, and Papanicolaou test diagnosis (AHR: 0.67 [95% CI: .49-.93]). Similar associations were not observed among women reporting current use of depomedroxyprogesterone acetate (DMPA). Neither COC nor DMPA use was significantly associated with new HPV DNA detection., Conclusions: These data do not support the hypothesis that contraceptive use is associated with cervical cancer risk via increased risk of HPV acquisition. The increased risk of HPV persistence observed among current COC users suggests a possible influence of female sex hormones on host response to HPV infection.

Objective: Clinical trials of new agents to reduce the severity and impact of influenza require accurate assessment of the effect of influenza infection. Because there are limited high-quality adult influenza Patient Reported Outcomes (PRO) measures, the aim was to develop and validate a simple but comprehensive questionnaire for epidemiological research and clinical trials., Methods: Construct and item generation was guided by the literature, concept mapping, focus groups, and interviews with individuals with laboratory-confirmed influenza and expert physicians. Items were administered to 311 people with influenza-like illness (ILI) across 25 US sites. Analyses included classic psychometrics, structural equation modeling (SEM), and Rasch analyses., Results: Concept mapping generated 149 concepts covering the influenza experience and clustered into symptoms and impact on daily activities, emotions, and others. Items were drafted using simplicity and brevity criteria. Eleven symptoms from the literature underwent review by physicians and patients, and two were removed and one added. The symptoms domain factored into systemic and respiratory symptoms, whereas the impact domains were unidimensional. All domains displayed good internal consistency (Cronbach α ≥ 0.8) except the three-item respiratory domain (α = 0.48). A five-factor SEM indicated excellent fit where systemic, respiratory, and daily activities domains differentiated patients with ILI or confirmed influenza. All scales were responsive over time., Conclusions: Patient and clinician consultations resulted in an influenza PRO measure with high validity and good overall evidence of reliability and responsiveness. The Influenza Intensity and Impact Questionnaire (FluiiQ™) will improve the evaluation of existing and future agents designed to prevent or control influenza infection by increasing the breadth and depth of measurement in this field., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Women diagnosed with cervical cancer report longer duration and more recent use of combined oral contraceptives (COCs). It is unclear whether COC use is associated with upstream events of human papillomavirus (HPV) infection prior to development of clinical disease. The objective of our study was to assess the association of contraceptive use on the risk for prevalent HPV infection in a cohort of long-term hormonal contraceptive (HC) users. One thousand and seventy (n = 1,070) HIV-negative women aged 20-37 from Thailand enrolled in a prospective study of the natural history of HPV. Baseline HPV genotype information, recency and duration of HC use, sexual behavior, other sexually transmitted infection (STI) information and cervical cytology and histology were assessed. At enrollment, 19.8% and 11.5% of women were infected with any HPV or any high-risk (HR)-HPV, respectively. After adjustment for age, current and past sexual risk behaviors, STI history and cytology, the use of COCs for >6 years was found to be associated with an increased risk of infection with any HPV [prevalence ratio (PR): 1.88 (1.21, 2.90)] and any HR-HPV [PR: 2.68 (1.47, 4.88)] as compared to never users. Recent, long-term COC use was associated with an increased risk for prevalent HPV infection independent of sexual behavior and cervical abnormalities. No similar association was observed for recent or long duration use of progestin-only contraceptives (i.e., depomedroxyprogesterone acetate). These data suggest that COC use may impact early upstream events in the natural history of HPV infection., (Copyright © 2010 UICC.)

Introduction: While high HPV 16 viral load measured at a single time point is associated with cervical disease outcomes, few studies have assessed changes in HPV 16 viral load on viral clearance., Objective: To measure the association between changes in HPV 16 viral load and viral clearance in a cohort of Thai women infected with HPV 16., Study Design: Fifty women (n=50) between the ages of 18-35 years enrolled in a prospective cohort study were followed up every three months for two years. Women positive for HPV 16 DNA by multiplex TaqMan assay at two or more study visits were selected for viral load quantitation using a type-specific TaqMan based real-time PCR assay. The strength of the association of change in viral load between two visits and viral clearance at the subsequent visit was assessed using a GEE model for binary outcomes., Results: At study entry, HPV 16 viral load did not vary by infection outcome. A >2 log decline in viral load across two study visits was found to be strongly associated with viral clearance (AOR: 5.5, 95% CI: 1.4-21.3). HPV 16 viral load measured at a single time point was not associated with viral clearance., Conclusions: These results demonstrate that repeated measurement of HPV 16 viral load may be a useful predictor in determining the outcome of early endpoints of viral infection., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Replication-defective adenoviruses have been utilized as candidate HIV vaccine vectors. Few studies have described the international epidemiology of pre-existing immunity to adenoviruses. We enrolled 1904 participants in a cross-sectional serological survey at seven sites in Africa, Brazil, and Thailand to assess neutralizing antibodies (NA) for adenovirus types Ad5, Ad6, Ad26 and Ad36. Clinical trial samples were used to assess NA titers from the US and Europe. The proportions of participants that were negative were 14.8% (Ad5), 31.5% (Ad6); 41.2% (Ad26) and 53.6% (Ad36). Adenovirus NA titers varied by geographic location and were higher in non-US and non-European settings, especially Thailand. In multivariate logistic regression analysis, geographic setting (non-US and non-European settings) was statistically significantly associated with having higher Ad5 titers; participants from Thailand had the highest odds of having high Ad5 titers (adjusted OR=3.53, 95% CI: 2.24, 5.57). Regardless of location, titers of Ad5NA were the highest and Ad36 NA were the lowest. Coincident Ad5/6 titers were lower than either Ad5 or Ad6 titers alone. Understanding pre-existing immunity to candidate vaccine vectors may contribute to the evaluation of vaccines in international populations.

Human papillomavirus type 52 is highly prevalent in Asia and Africa and accounts for 2-3% of total cervical cancer burden worldwide. The Roche Molecular Systems HPV Linear Array (RMS-LA uses multiple type (i.e. mixed) probes to detect DNA from HPV 52 infection which limits the assay's ability to determine HPV 52 status in the presence of HPV 33, 35, or 58 infection. This report presents a simple to use and highly reproducible HPV 52 type-specific quantitative real-time PCR (RT-PCR) assay based on Taqman chemistry for detection and quantification of HPV 52 DNA from cervical swab specimens. Mixed probe positive cervical swab specimens collected from rural and urban women in Thailand (n=68) were used to determine assay agreement and differences in HPV 52 DNA viral load across cytological diagnosis. Forty-eight specimens were determined to be HPV 52 positive by RMS-LA with 94% (n=45) confirmed positive by Taqman assay (kappa: 0.86, 95% CI: 0.74, 0.99). Higher median viral load was observed among women with a Pap diagnosis of >=ASCUS vs. normal/inflammation (8510 copies/1000 cell equivalents vs. 279 copies/1000 cell equivalents, p<0.05). Accurate ascertainment of infection status is important in understanding HPV 52's role in the etiology of cervical cancer as well as for the development of type-specific vaccines.

Amyloidosis is an uncommon plasma cell dyscrasia affecting Multisystem, characterized by deposition of amyloid proteins in extracellular spaces and the tissues. Reported incidence of amyloidosis is 8 cases per million per year. Deposition of amyloid fibrils occurs in peripheral nerves in 20% of the cases in Primary Amyloidosis. Though. polyneuropathy is one of the presenting manifestations in cases of Primary Amyloidosis, pure autonomic failure without involving peripheral nerves is not a documented entity. Here, we present a case of Primary Amyloidosis presenting as Pure Autonomic Failure (Dysautonomia).

Emergency Medicine (EM) is a new discipline for India. As Medical Council of India (MCI) makes progress in recognizing the need to develop EM residency training programs in India it is important that there exist an established training model for future faculty, residents and medical students. This INDO-US white paper makes a serious attempt to recognize the opportunities and challenges in developing academic emergency medicine in India. The contents of this white paper address the overall scenario and are not targeted towards a person, physician, body, hospital or any other associated entity. This paper emphasizes the importance of MCI recognized training in Emergency Medicine for physicians in India.

Background: Sickle cell nephropathy (SCN) is an important cause of mortality in patients with sickle cell disease. SCA with systemic lupus erythematosus (SLE) is known in children and less common in adults, however diffuse proliferative lupus nephritis (DPLN) with SCN has rarely been reported in adults. It requires early diagnosis and aggressive management., Case Presentation: We present here a 35 years old lady with sickle cell disease who presented with edema, dyspnoea on exertion, pyuria and had raised s. creatinine of 7 mg%. Her biopsy revealed SCN with DPLN. She is on maintenance hemodialysis after 2 months of diagnosis., Conclusion: DPLN with SCN is a rare entity with poor prognosis, which may be overlooked and needs aggressive management.

Interest in estimating HIV-1 incidence using specimens obtained as part of cross-sectional surveys has led to the development of new methods to detect recent HIV-1 infection through the testing of a single anti-HIV-positive specimen. These assays are based on quantitative and qualitative differences in anti-HIV-1 antibodies between recent and long-standing infections. An ongoing vaccine preparedness study enrolled female sex workers in the Dominican Republic. Specimens from women found to be HIV positive at baseline were tested for recent HIV-1 infection using the detuned assay, avidity index, and BED-CEIA assay. An unweighted kappa statistic in pairwise comparisons was used to estimate the correlation of recent HIV-1 infection detection by the three methods. Nineteen (3.9%) of 482 women were positive for HIV-1 infection. The incidence of HIV infection was 1.4% [95% confidence interval (CI): 0.2, 5.3], 0.9%(95% CI: 0.1, 4.4), and 1.0%(95% CI: 0.1, 4.4) using detuned assay, avidity index, and BED-CEIA techniques, respectively. The overall agreement between both detuned assay and avidity index and detuned assay and BED-CEIA was 94%(kappa = 0.8, 95% CI; 0.3, 1.0). The correlation was highest between BED-CEIA and avidity index methods (100%; kappa = 1.0). All three methods performed similarly in detecting recent HIV-1 infection in this region dominated by clade B HIV-1 infection. Although incidence estimates were slightly higher using the detuned assay method, they were not significantly different. These assays may be of value in both clinical research and practice. The utility of individual assays for recent infection detection will depend upon operating characteristics, HIV-1 subtype limitations, and selection of appropriate assay cutoff values.

Immunofluorescence (IF) studies are important diagnostic tool in understanding pathogenesis involved in graft injury. Acute humoral rejection (AHR) associated with circulating donor-specific cytotoxic antibodies, is a poor prognosticator for graft survival. It can be diagnosed by staining for C4d antibody using indirect IF technique. C4d staining required to diagnose AHR was made mandatory for reporting renal allograft biopsies in 7th Banff conference. We present 2 years experience of IF studies using C4d polyclonal antibody on 546 renal allograft biopsies belonging to two groups of patients; 464 from group A (tolerance induction protocol) and 82 from group B (controls). We observed C4d focal positivity in 4 (0.9%) biopsies from group A and 4 (4.9%) from group B. We conclude that it is advisable to collect simultaneous core biopsy samples for IF studies and light microscopy to give better definition of allograft injury and thereby support in clinical management.

An effective vaccine for HIV is likely to require induction of T-cell-mediated immune responses, and the interferon-gamma (IFNgamma) enzyme-linked immunospot (ELISPOT) assay has become the most commonly used assay for measuring these responses in vaccine trials. We optimized and validated the HIV ELISPOT assay using an empirical method to establish positivity criteria that results in a < or =1% false-positive rate. Using this assay, we detected a broad range of HIV-specific ELISPOT responses to peptide pools of overlapping 20mers, 15mers, or 9mers in study volunteers receiving DNA- or adenovirus vector-based HIV vaccines and in HIV-seropositive donors. We found that 15mers generally had higher response magnitudes than 20mers and lower false-positive rates than 9mers. These studies show that our validated ELISPOT assay using 15mer peptide pools and the positivity criteria of > or =55 spots per 10(6) cells and > or =4-fold over mock (negative control) is a sensitive and specific assay for the detection of HIV vaccine-induced cell-mediated immunity.