Pushpendra Singh

Bio: Pushpendra Singh is an academic researcher from Indian Council of Medical Research. The author has contributed to research in topics: Mycobacterium leprae & Leprosy. The author has an hindex of 20, co-authored 76 publications receiving 2169 citations. Previous affiliations of Pushpendra Singh include Louisiana State University & Sarojini Naidu Medical College.

Comparative genomic and phylogeographic analysis of Mycobacterium leprae

Abstract: Reductive evolution and massive pseudogene formation have shaped the 3.31-Mb genome of Mycobacterium leprae, an unculturable obligate pathogen that causes leprosy in humans. The complete genome sequence of M. leprae strain Br4923 from Brazil was obtained by conventional methods (6x coverage), and Illumina resequencing technology was used to obtain the sequences of strains Thai53 (38x coverage) and NHDP63 (46x coverage) from Thailand and the United States, respectively. Whole-genome comparisons with the previously sequenced TN strain from India revealed that the four strains share 99.995% sequence identity and differ only in 215 polymorphic sites, mainly SNPs, and by 5 pseudogenes. Sixteen interrelated SNP subtypes were defined by genotyping both extant and extinct strains of M. leprae from around the world. The 16 SNP subtypes showed a strong geographical association that reflects the migration patterns of early humans and trade routes, with the Silk Road linking Europe to China having contributed to the spread of leprosy.

Genome-wide comparison of medieval and modern Mycobacterium leprae

Abstract: Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. The ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution.

Probable Zoonotic Leprosy in the Southern United States

Abstract: Background In the southern region of the United States, such as in Louisiana and Texas, there are autochthonous cases of leprosy among native-born Americans with no history of foreign exposure. In the same region, as well as in Mexico, wild armadillos are infected with Mycobacterium leprae. Methods Whole-genome resequencing of M. leprae from one wild armadillo and three U.S. patients with leprosy revealed that the infective strains were essentially identical. Comparative genomic analysis of these strains and M. leprae strains from Asia and Brazil identified 51 single-nucleotide polymorphisms and an 11-bp insertion–deletion. We genotyped these polymorphic sites, in combination with 10 variable-number tandem repeats, in M. leprae strains obtained from 33 wild armadillos from five southern states, 50 U.S. outpatients seen at a clinic in Louisiana, and 64 Venezuelan patients, as well as in four foreign reference strains. Results The M. leprae genotype of patients with foreign exposure generally reflected thei...

Anti-tuberculosis activity of selected medicinal plants against multi-drug resistant Mycobacterium tuberculosis isolates.

Abstract: Background & objectives Emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains of Mycobacterium tuberculosis has further complicated the problem of tuberculosis (TB) control. Medicinal plants offer a hope for developing alternate medicines for the treatment of TB. The present study was done to evaluate in vitro anti-tubercular activity of five medicinal plants viz., Acalypha indica, Adhatoda vasica, Allium cepa, Allium sativum and Aloe vera. Methods Aqueous extracts of leaves of A. indica, A. vasica, bulbs of A. cepa, cloves of A. sativum and pure gel of A. vera leaves, were tested in vitro for their activity against two MDR isolates (DKU-156 and JAL-1236), reference susceptible strain M. tuberculosis H37Rv as well as rapid grower mycobacterial pathogen M. fortuitum (TMC-1529) using Lowenstein Jensen (L-J) medium and colorimetric BacT/ ALERT 3D system. Activity in L-J medium was evaluated by percentage inhibition which was calculated by mean reduction in number of colonies on extract containing as compared to extract free controls. Results Extracts of all the five plants A. indica, A. vasica, A. cepa, A. sativum and A. vera exhibited anti-tuberculosis activity in L-J medium, the proportion of inhibition of these plants extract in respect mentioned above is 95, 32, 37, 72, 32 per cent, respectively for MDR isolate DKU-156 and 68, 86, 79, 72, 85 per cent, respectively for another MDR isolate JAL-1236, while for sensitive M. tuberculosis H37Rv, inhibition was found to be 68, 70, 35, 63 and 41 per cent, at 4 per cent v/v concentration in L-J medium. There was no inhibition against rapid grower M. fortuitum (TMC-1529). In BacT/ALERT also, extracts of these plants showed significant inhibition against M. tuberculosis. Interpretation & conclusion Our findings showed that all these plants exhibited activity against MDR isolates of M. tuberculosis. While the anti-TB activity of A. vera, A. vasica and A. sativum against MDR isolates confirm earlier results, activity of the extracts of A. indica and A. cepa is reported for the first time. Further studies aimed at isolation and identification of active substances from the extracts which exhibited promising activities, need to be carried out.

SARS-CoV-2 antibody seroprevalence in India, August-September, 2020: findings from the second nationwide household serosurvey.

Abstract: BACKGROUND: The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May-June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0·73% (95% CI 0·34-1·13). We aimed to assess the more recent nationwide seroprevalence in the general population in India. METHODS: We did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. 3-5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys. FINDINGS: Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6·6% (95% CI 5·8-7·4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7·1% (6·2-8·2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74·3 million infections in the country by Aug 18, 2020, with 26-32 infections for every reported COVID-19 case. INTERPRETATION: Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country. FUNDING: Indian Council of Medical Research.

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Integrative Genomics Viewer

Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

An Introduction to Genetic Statistics

Abstract: A reviewer for the Journal of the Royal Statistical Society of England comments \"This is the first book covering in one volume all important topics in genetical statistics.\" Written to provide basic probability ideas in terms of genetic situations, since the theory of genetics is a probability theory; to give a definitive treatment of applications of these ideas to genetic theory; and to describe statistical methods appropriate to the data models that are developed.

Genetic Data Analysis II. Methods for Discrete Population Genentic Data

Abstract: ‘‘Gentlemen don’t need mistletoe’’ said the Christmas whiskey billboard I saw recently in Florida, a garish reminder of how much mistletoe lore is embedded in western society. Mistletoe The Genus Viscum, one in the series of medicinal and aromatic plants for industry and academic researchers, centers on the mistletoe in this advertisement, the common European mistletoe,Viscum album. There are helpful discussions on African, Asian, and Argentine mistletoes and their uses but the corpus of the book deals with V. album. Viscum album, considered sacred by the Druids, is no doubt the most widely used parasitic angiosperm for various health concoctions. As a result, much has been learned about its biochemistry and pharmaceutical potential. A great deal of the work on the culture and utilization ofV. album has been done by investigators at Institute Hiscia Center for Cancer Research in Switzerland where votaries of Rudolf Steiner’s distinct form of homeopathy have used mistletoe extracts (‘‘Iscador’’) for many years in cancer treatment. Mistletoe collected from less common hosts are considered to have greater efficacy in preparation of Iscador. As a result, there is a helpful chapter on culturing V. album which is not as difficult as might be imagined for an obligate parasite. Most of the chapters deal with the medicinal aspects of mistletoe including toxicology, clinical aspects, chemistry, and biochemistry emphasizing the lectins which are one of the more desirable compounds produced by the parasite. I found the treatment by Bu ̈ssing (Biological and pharmacological properties of Viscum album L.) helpful because it reviews the link between folk and modern medicine. However, several relevant papers were omitted which are included in a recent excellent review of mistletoes (Watson 2001). Like many books with a diversity of authors, the quality of chapters varies. Obviously produced as a reference volume, Mistletoe lacks an extensive index. Especially aggravating is the lack of an author’s index, limiting the value of the book for anyone looking for specific papers. These days, $70 for a hardbound monograph is reasonable. Color images are well-produced but some of the black and white figures are blurry in my copy. This volume will be of value to ethnobotanists, anyone interested in alternative medicines, and students of mistletoes and parasitic plants. LITERATURE CITED

Transforming clinical microbiology with bacterial genome sequencing

Abstract: Whole-genome sequencing of bacteria has recently emerged as a cost-effective and convenient approach for addressing many microbiological questions. Here, we review the current status of clinical microbiology and how it has already begun to be transformed by using next-generation sequencing. We focus on three essential tasks: identifying the species of an isolate, testing its properties, such as resistance to antibiotics and virulence, and monitoring the emergence and spread of bacterial pathogens. We predict that the application of next-generation sequencing will soon be sufficiently fast, accurate and cheap to be used in routine clinical microbiology practice, where it could replace many complex current techniques with a single, more efficient workflow.