#Lopinavir / #ritonavir #Combination #Therapy Amongst Symptomatic #Coronavirus Disease 2019 Patients in #India: Protocol for Restricted Public Health Emergency Use (Indian J Med Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Indian J Med Res 2020 Mar 11 [Online ahead of print]

Lopinavir/ritonavir Combination Therapy Amongst Symptomatic Coronavirus Disease 2019 Patients in India: Protocol for Restricted Public Health Emergency Use

Tarun Bhatnagar 1, Manoj V Murhekar 2, Manish Soneja 3, Nivedita Gupta 4, Sidhartha Giri 4, Naveet Wig 3, Raman Gangakhedkar 4

Affiliations: 1 School of Public Health, ICMR-National Institute of Epidemiology, Chennai, Tamil Nadu, India. 2 ICMR-National Institute of Epidemiology, Chennai, Tamil Nadu, India. 3 Department of Medicine, All India Institute of Medical Sciences, New Delhi, India. 4 Division of Epidemiology & Communicable Diseases, Indian Council of Medical Research, New Delhi, India.

PMID: 32202256 DOI: 10.4103/ijmr.IJMR_502_20



As of February 29, 2020, more than 85,000 cases of coronavirus disease 2019 (COVID-19) have been reported from China and 53 other countries with 2,924 deaths. On January 30, 2020, the first laboratory-confirmed case of COVID was reported from Kerala, India. In view of the earlier evidence about effectiveness of repurposed lopinavir/ritonavir against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as preliminary docking studies conducted by the ICMR-National Institute of Virology, Pune, the Central Drugs Standard Control Organization approved the restricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients detected in the country. Hospitalized adult patients with laboratory-confirmed SARS-CoV-2 infection with any one of the following criteria will be eligible to receive lopinavir/ritonavir for 14 days after obtaining written informed consent: (i) respiratory distress with respiratory rate ≥22/min or SpO2 of <94 per cent; (ii) lung parenchymal infiltrates on chest X-ray; (iii) hypotension defined as systolic blood pressure <90 mmHg or need for vasopressor/inotropic medication; (iv) new-onset organ dysfunction; and (v) high-risk groups – age >60 yr, diabetes mellitus, renal failure, chronic lung disease and immunocompromised persons. Patients will be monitored to document clinical (hospital length of stay and mortality at 14, 28 and 90 days), laboratory (presence of viral RNA in serial throat swab samples) and safety (adverse events and serious adverse events) outcomes. Treatment outcomes amongst initial cases would be useful in providing guidance about the clinical management of patients with COVID-19. If found useful in managing initial SARS-CoV-2-infected patients, further evaluation using a randomized control trial design is warranted to guide future therapeutic use of this combination.

Keywords: COVID-19; Coronavirus disease 2019; lopinavir/ritonavir; severe acute respiratory syndrome coronavirus 2; treatment outcome.

Conflict of interest statement: None

Keywords: SARS-CoV-2; COVID-19; Antivirals; Lopinavir; Ritonavir; India.


Detection of #TorqueTeno Virus (TTV) and TTV-Like #Minivirus in patients with presumed infectious #endophthalmitis in #India (PLOS One, abstract)

[Source: PLOS One, full page: (LINK). Abstract, edited.]


Detection of Torque Teno Virus (TTV) and TTV-Like Minivirus in patients with presumed infectious endophthalmitis in India

Poonam Naik, Vivek Pravin Dave, Joveeta Joseph


Published: January 7, 2020 / DOI: https://doi.org/10.1371/journal.pone.0227121



Human anelloviruses (Torque Teno Virus (TTV) and TTV Like Mini Virus (TLMV)) are now being reported at a high prevalence across the world, with a controversial disease-inducing potential. The aim of this study was to investigate the role of these anellovirus in vitreous of patients with presumed infectious endophthalmitis. After informed consent, vitreous fluid from patients with endophthalmitis (n = 103) and non-infectious pathologies (n = 102) were analyzed for the presence of TTV and TLMV DNA by qPCR with the limit of quantification defined as 100 copies per reaction. Among the patients clinically diagnosed with endophthalmitis, 29 of the 40 culture proven samples (72.5%) and 42 out of 63 (66.6%) of culture-negative samples were positive for presence of TTV/TLMV. Interestingly, 51 of the 102 (50%) samples in the control group were also positive for TTV/TLMV. Comparing the clinical outcome among patients diagnosed with endophthalmitis, we observed no significant association in the final visual acuity of patients who were positive for presence of TTV/TLMV, however, these patients had significantly higher repeat antibiotic injections (p = 0.03). Further evidence is however needed to correlate TTV / TLMV with a particular pathology or group of pathologies in the eye.


Citation: Naik P, Dave VP, Joseph J (2020) Detection of Torque Teno Virus (TTV) and TTV-Like Minivirus in patients with presumed infectious endophthalmitis in India. PLoS ONE 15(1): e0227121. https://doi.org/10.1371/journal.pone.0227121

Editor: Adriana Calderaro, Universita degli Studi di Parma, ITALY

Received: August 7, 2019; Accepted: December 11, 2019; Published: January 7, 2020

Copyright: © 2020 Naik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript.

Funding: This work was supported by a grant from the DST-SERB to Dr Joveeta Joseph (File Number: EMR/2016/002259) India.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Human Anellovirus; Torque Teno Virus; Minivirus; Endophthalmitis; India.


#Antibiotic #exposure among #children younger than 5 years in low-income and middle-income countries:… (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Disease, full page: (LINK). Abstract, edited.]

Antibiotic exposure among children younger than 5 years in low-income and middle-income countries: a cross-sectional study of nationally representative facility-based and household-based surveys

Günther Fink, PhD, Valérie D’Acremont, PhD, Hannah H Leslie, PhD, Jessica Cohen, PhD

Published: December 13, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30572-9




Antibiotic resistance is a major threat to global health. Although detailed information about antibiotic use in high-income countries is available, little is known regarding the use of antibiotics and cumulative exposure to antibiotics in low-income and middle-income countries (LMICs). We aimed to quantify antibiotic exposure in children younger than 5 years in LMICs.


We did a cross-sectional study in sick children younger than 5 years who attended a health-care facility in eight LMICs (Haiti, Kenya, Malawi, Namibia, Nepal, Senegal, Tanzania, and Uganda) between May, 2006, and December, 2016. Demographic and Health Surveys were used to estimate the cumulative number of illnesses related to a fever or cough and the cumulative number of visits to a health-care facility because of these illnesses for each country. We also used clinical observation data from nationally representative health-care facility-based Service Provision Assessment (SPA) surveys to estimate the proportion of children who were prescribed an antibiotic during a visit to a health-care facility and the number of antibiotic prescriptions issued that were unrelated to fever or respiratory problems. By combining these estimates, and using bootstrap analysis to compute uncertainty intervals, we estimated cumulative antibiotic exposure in children from birth up to age 5 years in each LMIC.


From SPA surveys, we identified 22 519 clinical observations of children younger than 5 years who visited a health-care facility because of an illness between July, 2007, and December, 2016. From DHS surveys, we identified 68 826 children younger than 5 years who visited a health-care facility between May, 2006, and November, 2016. 85·4% of health-care facility visits were related to either a fever or cough. Antibiotics were prescribed to 80·5% of children diagnosed with respiratory illness, 50·1% with diarrhoea, and 28·3% with malaria. The mean number of antibiotic prescriptions issued to children between birth and age 5 years across the eight LMICs was 24·5 (95% CI 22·6–26·7), ranging from 7·1 (6·3–7·9) in Senegal to 59·1 (54·1–64·6) in Uganda.


Between birth and age 5 years, children in LMICs are prescribed a remarkably high number of antibiotics. A large proportion of these prescriptions appear to be unnecessary. National and local efforts to reduce unnecessary prescription of antibiotics to children would likely improve both patient wellbeing (in terms of preventing side-effects) and reduce the global threat of antimicrobial resistance.



Keywords: Antibiotics; Pediatrics; India.


Srinivasa #Ramanujan: in #celebration of the #centenary of his election as #FRS (Phil Transact Roy Soc., summary)

[Source: Philosophical Transaction of the Royal Society, full page: (LINK). Summary, edited.]

Srinivasa Ramanujan: in celebration of the centenary of his election as FRS

Ken Ono

Published: 09 December 2019 / DOI: https://doi.org/10.1098/rsta.2019.0386

Citation: Ono Ken, Srinivasa Ramanujan: in celebration of the centenary of his election as FRS378Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Scienceshttp://doi.org/10.1098/rsta.2019.0386


Srinivasa Ramanujan, the so-called Man Who Knew Infinity, was one of the most influential, as well as most enigmatic, mathematicians in the recent history of mathematics. With a letter written to G. H. Hardy in 1913, the impoverished Hindu college dropout, self-taught in mathematics, reaching for worlds beyond the shores of India, introduced himself to the history of science.


Keywords: Mathematics.


#Evolution and #Global #Transmission of a #MDR, CA #MRSA #Lineage from the #Indian Subcontinent (MBio, abstract)

[Source: MBio, full page: (LINK). Abstract, edited.]

Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent

Eike J. Steinig, Sebastian Duchene, D. Ashley Robinson, Stefan Monecke, Maho Yokoyama, Maisem Laabei, Peter Slickers, Patiyan Andersson, Deborah Williamson, Angela Kearns, Richard V. Goering, Elizabeth Dickson, Ralf Ehricht, Margaret Ip, Matthew V. N. O’Sullivan, Geoffrey W. Coombs, Andreas Petersen, Grainne Brennan, Anna C. Shore, David C. Coleman, Annalisa Pantosti, Herminia de Lencastre, Henrik Westh, Nobumichi Kobayashi, Helen Heffernan, Birgit Strommenger, Franziska Layer, Stefan Weber, Hege Vangstein Aamot, Leila Skakni, Sharon J. Peacock, Derek Sarovich, Simon Harris, Julian Parkhill, Ruth C. Massey, Mathew T. G. Holden, Stephen D. Bentley, Steven Y. C. Tong

Paul J. Planet, Invited Editor, Victor J. Torres, Editor

DOI: 10.1128/mBio.01105-19



The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.



The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA; CA-MRSA; India; Bangladesh.


Laboratory-Confirmed #Avian #Influenza A(#H9N2) Virus #Infection, #India, 2019 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 12—December 2019 / Research Letter

Laboratory-Confirmed Avian Influenza A(H9N2) Virus Infection, India, 2019

Varsha Potdar  , Dilip Hinge, Ashish Satav, Eric F. Simões, Pragya D. Yadav, and Mandeep S. Chadha

Author affiliations: National Institute of Virology, Pune, India (V. Potdar, D. Hinge, P.D. Yadav, M.S. Chadha); Mahan Trust Melghat, Amravati, India (A. Satav); University of Colorado School of Medicine, Aurora, Colorado, USA (E.F. Simões)



A 17-month-old boy in India with severe acute respiratory infection was laboratory confirmed to have avian influenza A(H9N2) virus infection. Complete genome analysis of the strain indicated a mixed lineage of G1 and H732. The strain also was found to be susceptible to adamantanes and neuraminidase inhibitors.

Keywords: Avian Influenza; H9N2; Human; India.


#Filovirus-reactive #antibodies in #humans and #bats in Northeast #India imply zoonotic #spillover (PLOS Negl Trop Dis., abstract)

[Source: PLOS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]


Filovirus-reactive antibodies in humans and bats in Northeast India imply zoonotic spillover

Pilot Dovih, Eric D. Laing, Yihui Chen, Dolyce H. W. Low, B. R. Ansil, Xinglou Yang, Zhengli Shi, Christopher C. Broder, Gavin J. D. Smith, Martin Linster, Uma Ramakrishnan, Ian H. Mendenhall


Published: October 31, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007733



Bats are reservoirs for several zoonotic pathogens, including filoviruses. Recent work highlights the diversity of bat borne filoviruses in Asia. High risk activities at the bat-human interface pose the threat of zoonotic virus transmission. We present evidence for prior exposure of bat harvesters and two resident fruit bat species to filovirus surface glycoproteins by screening sera in a multiplexed serological assay. Antibodies reactive to two antigenically distinct filoviruses were detected in human sera and to three individual filoviruses in bats in remote Northeast India. Sera obtained from Eonycteris spelaea bats showed similar patterns of cross-reactivity as human samples, suggesting them as the species responsible for the spillover. In contrast, sera from Rousettus leschenaultii bats reacted to two different virus glycoproteins. Our results indicate circulation of several filoviruses in bats and the possibility for filovirus transmission from bats to humans.


Author summary

Focused virus surveillance at human-wildlife interfaces enables proactive detection of potentially epidemic pathogens. Filoviruses, including ebolaviruses and marburgviruses, are pathogens with epidemic potential. They were previously detected in bats and have caused disease outbreaks in humans with a high case fatality rate. Here, we tested sera obtained from bats and humans at a high-risk interface for the presence of filovirus reactive antibodies. Human participants were engaged in annual bat hunts, possibly exposing them to bat-borne viruses. We report the exposure of humans to filoviruses that were likely derived from the two sampled bat species. The bats contain antibodies raised to presumably three distinct filoviruses. Our findings suggest bats in South Asia act as a reservoir host of a diverse range of filoviruses and filovirus spillover occurs through human exposure to these bats.


Citation: Dovih P, Laing ED, Chen Y, Low DHW, Ansil BR, Yang X, et al. (2019) Filovirus-reactive antibodies in humans and bats in Northeast India imply zoonotic spillover. PLoS Negl Trop Dis 13(10): e0007733. https://doi.org/10.1371/journal.pntd.0007733

Editor: Eric Mossel, Center for Disease Control and Prevention, UNITED STATES

Received: April 17, 2019; Accepted: August 26, 2019; Published: October 31, 2019

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: All relevant data are within the manuscript and its Supporting Information files. Next generation sequencing files are available from the Sequence Read Archive at the National Center for Biotechnology Information (Accession Numbers: SAMN12359407, SAMN12359408).

Funding: This project was funded by a United States Department of Defense, Defense Threat Reduction Agency, Broad Agency Announcement grant for the project ‘Bat harvesting in India: Detection, characterization and mitigation of emerging infectious disease risk’ to IHM (HDTRA1-17-1-0028; PI: IHM); a Department of Atomic Energy, Government of India award (2012/21/06/BRNS) to UR; and funding from Biological Defense Research Directorate of the Naval Medical Research Center (HT9404-13-1-0021) to CCB; Component Project: Soluble Trimeric Filovirus Envelope Glycoproteins. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Filovirus; Serology; Bats; Human; India.