Shreemanta K. Parida

Max Planck Institute for Infection Biology

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Stefan H. E. Kaufmann

Max Planck Institute for Infection Biology

Gerhard Walzl

Stellenbosch University

Gillian F. Black

Sustainable Livelihoods Foundation

Alimuddin Zumla

University College London

Tom H. M. Ottenhoff

Leiden University Medical Center

Markus Maeurer

Champalimaud Foundation

Hazel M. Dockrell

London School of Hygiene & Tropical Medicine

Kees L. M. C. Franken

Leiden University Medical Center

Michèl R. Klein

Leiden University Medical Center

Bernhard Ryffel

Université d'Orléans

Cooperative Institutions

University of Cape Town

South African Tuberculosis Vaccine Initiative

South African Medical Research Council

Stellenbosch University

London School of Hygiene & Tropical Medicine

University College London

TuBerculosis Vaccine Initiative

MRC Unit the Gambia

National Research Foundation

Stanford University

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Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients

Journal of Medical Virology (1997)

V. Ravi Shreemanta K. Parida Anita Desai A. Chandramuki M. Gourie‐Devi

To investigate the prognostic role of tumour necrosis factor (TNF) in Japanese encephalitis virus (JEV) infection, we measured the immunoreactive forms of TNF concentrations in the serum and cerebrospinal fluid (CSF) of 47 laboratory-confirmed cases of JE. It was observed that TNF levels were elevated (>15 pgm/ml) in all the 47 serum samples (range 19.4–923.8 pg/ml), while in 46/47 CSF samples TNF was elevated (range 10.8–376 pg/ml). The mean (SD) TNF levels in the serum of fatal cases was 234.34 pg/ml (304.40) as compared to the mean of 85.31 pg/ml (SD 153.92) in nonfatal cases. Similar observations were also made with respect to the TNF levels in the CSF; the mean of fatal cases was 69.39 pg/ml (SD 39.00) in contrast to the mean of 62.41 pg/ml (SD 75.25) of nonfatal cases. The increase in TNF levels did not show any correlation to the duration of illness. It was further observed that the mortality rate increased with increasing concentrations of TNF in the serum and CSF. Correlation of laboratory parameters to final outcome revealed that TNF concentrations above 50 pg/ml in serum correlated significantly (P = .05) with a fatal outcome, whilst high levels of JEV-IgM antibodies (>500 units) in the CSF correlated with a nonfatal outcome (P = .03). These results suggest that TNF can be used as a possible prognosticator of a fatal outcome in JEV infection. J Med Virol 51:132–136, 1997. © 1997 Wiley-Liss, Inc.

10.1002/(sici)1096-9071(199702)51:2<132::aid-jmv8>3.3.co;2-6

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Four-Gene Pan-African Blood Signature Predicts Progression to Tuberculosis

American Journal of Respiratory and Critical Care Medicine (2018)

Sara Suliman Ethan Thompson Jayne S. Sutherland January Weiner Martin O. C. Ota

Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk of infection with Mycobacterium tuberculosis and progression to disease.Objectives: We investigated biosignatures with predictive ability for incident TB.Methods: In a case–control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, PCR, and the pair ratio algorithm in a training/test set approach. Overall, 79 progressors who developed TB between 3 and 24 months after diagnosis of index case and 328 matched nonprogressors who remained healthy during 24 months of follow-up were investigated.Measurements and Main Results: A four-transcript signature derived from samples in a South African and Gambian training set predicted progression up to two years before onset of disease in blinded test set samples from South Africa, the Gambia, and Ethiopia with little population-associated variability, and it was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection. By contrast, published diagnostic or prognostic TB signatures were predicted in samples from some but not all three countries, indicating site-specific variability. Post hoc meta-analysis identified a single gene pair, C1QC/TRAV27 (complement C1q C-chain / T-cell receptor-α variable gene 27) that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events.Conclusions: Collectively, we developed a simple whole blood–based PCR test to predict TB in recently exposed household contacts from diverse African populations. This test has potential for implementation in national TB contact investigation programs.

10.1164/rccm.201711-2340oc

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ATMP cell therapy: Triumphs and constraints for unmet clinical needs

Journal of Vaccines & Vaccination (2017)

Shreemanta K. Parida

Immunopharmacology

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Closing the gaps in our understanding of the pathogenesis of tuberculosis

Shreemanta K. Parida

Pathogenesis

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Two distinct phospholipases C of Listeria monocytogenes induce ceramide generation, nuclear factor-kappa B activation, and E-selectin expression in human endothelial cells.

PubMed (1998)

Nicole Schwarzer Ralph Nöst Joachim Seybold Shreemanta K. Parida Oliver Fuhrmann

Infection of endothelial cells by Listeria monocytogenes is an essential step in the pathogenesis of listeriosis. We recently reported that L. monocytogenes induces up-regulation of E-selectin and other endothelial adhesion molecules and subsequent polymorphonuclear leukocyte (PMN) adhesion into cultured human endothelial cells. In the present study, we characterized the mechanisms of enhanced E-selectin expression using L. monocytogenes wild type (EGD), the isogenic in-frame deletion mutants for phosphatidylcholine (PC)- and phosphatidylinositol (PI)-specific phospholipases EGD delta plcA and EGD delta plcB, as well as the nonvirulent control strain Listeria innocua. Infection of endothelial cells with EGD delta plcA or EGD delta plcB for 6 h induced, as compared with EGD wild type, intermediate levels of E-selectin mRNA and protein as well as PMN rolling and adhesion at a shear rate of 1 dyne/cm2, indicating that both bacterial phospholipases are required for a maximal effect. Similarly, ceramide content and NF-kappa B activity were increased in L. monocytogenes-exposed endothelial cells, but only to intermediate levels for PC- or PI-phospholipase C (PLC)-deficient listerial mutants. Phospholipase effects could be mimicked by exogenously added ceramides or bacterial sphingomyelinase. The data presented indicate that PI-PLC and PC-PLC are important virulence factors for L. monocytogenes infections that induce accumulation of ceramides that in turn may act as second messengers to control host cell signal-transduction pathways leading to persistent NF-kappa B activation, increased E-selectin expression, and enhanced PMN rolling/adhesion. The ability of L. monocytogenes to stimulate PMN adhesion to endothelial cells may be an important mechanism in the pathogenesis of severe listeriosis.

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Biomarkers for tuberculosis disease activity, cure, and relapse

The Lancet Infectious Diseases (2010)

Robert S. Wallis Cunshan Wang T. Mark Doherty Phillip Onyebujoh Mahnaz Vahedi

10.1016/s1473-3099(10)70003-7

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A prognostic role for anti-phosphatidyl choline antibodies in human cerebral malaria

Clinical & Experimental Immunology (1996)

Bidyut Kumar Das Shreemanta K. Parida Balaraman Ravindran

SUMMARY Anti-phosphatidyl choline antibodies (αPC) have been measured in adult patients from Orissa, India with Plasmodium falciparum infection of varying clinical severity. Significantly raised levels of αPC were observed in infected individuals in comparison with controls. The IgG αPC were found to be generally more than IgM αPC in most cases. The IgG αPC levels were significantly more in those cases of cerebral malaria who recovered fully after quinine administration in comparison with fatal cases not responding to quinine therapy, indicating a role for αPC in prognosis of adult cerebral malaria. There was no significant difference in levels of αPC IgG between non-cerebral and fatal cerebral malaria patients, indicating an absence of a direct protective role in the development of cerebral manifestations. Subgroup typing of IgG with αPC activity indicated IgG3 to be the predominant type, followed by IgG2. IgG1 and IgG4. A significant inverse relationship between serum tumour necrosis factor-alpha (TNF-α) levels and IgG1 antibodies with αPC activity was found, emphasizing the importance of αPC in modifying disease severity. These observations appear to give credence to recent reports in the literature indicating that toxic malarial antigens consist of phospholipids and that antibodies to phospholipids (αPL) inhibit such antigens in experimental systems.

Cerebral Malaria

Quinine

10.1111/j.1365-2249.1996.tb08300.x

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Totally drug‐resistant tuberculosis and adjunct therapies

Journal of Internal Medicine (2014)

Shreemanta K. Parida Rebecca Axelsson‐Robertson Martin Rao Nidhi Singh Iqbal Master

The first cases of totally drug-resistant (TDR) tuberculosis (TB) were reported in Italy 10 years ago; more recently, cases have also been reported in Iran, India and South Africa. Although there is no consensus on terminology, it is most commonly described as 'resistance to all first- and second-line drugs used to treat TB'. Mycobacterium tuberculosis (M.tb) acquires drug resistance mutations in a sequential fashion under suboptimal drug pressure due to monotherapy, inadequate dosing, treatment interruptions and drug interactions. The treatment of TDR-TB includes antibiotics with disputed or minimal effectiveness against M.tb, and the fatality rate is high. Comorbidities such as diabetes and infection with human immunodeficiency virus further impact on TB treatment options and survival rates. Several new drug candidates with novel modes of action are under late-stage clinical evaluation (e.g., delamanid, bedaquiline, SQ109 and sutezolid). 'Repurposed' antibiotics have also recently been included in the treatment of extensively drug resistant TB. However, because of mutations in M.tb, drugs will not provide a cure for TB in the long term. Adjunct TB therapies, including therapeutic vaccines, vitamin supplementation and/or repurposing of drugs targeting biologically and clinically relevant molecular pathways, may achieve better clinical outcomes in combination with standard chemotherapy. Here, we review broader perspectives of drug resistance in TB and potential adjunct treatment options.

Bedaquiline

10.1111/joim.12264

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Single‐Use Bioreactors for Manufacturing of Immune Cell Therapeutics

Ralf Pörtner Christian Sebald Shreemanta K. Parida Hans Hoffmeister

This chapter provides an overview of more or less advanced technologies and devices available for manufacturing immune cell therapeutics. When manufacturing therapeutic doses of a personal immune cell advanced therapy medicinal product, it has to be considered that only some subsets of the total immune cell mixture taken from a patient sample is able to recognize mutated tumor cells or other disease-causing cells. Single-use devices are predominant in the production of immune cells at clinically relevant doses. The ZRP platform of Zellwerk and its bioreactor types provides sophisticated features not only for mass production of different immune cells but also for realizing isolation and culturing the cells in closed processes. Bioreactors of the ZRP system can be operated in the good manufacturing practice (GMP) breeder. The cell-cultivation platform's single-use bioreactors enable the manufacturing of large quantities of individual immune cell preparations under GMP conditions.

10.1002/9781119477891.ch30

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Field trials on the use ofMycobacterium wvaccine in conjunction with multidrug therapy in leprosy patients for immunotherapeutic and immunoprophylactic purposes

Leprosy Review (1993)

Rajat Walia K. G. Sarathchandra Richa Pandey Shreemanta K. Parida S. Zaheer

A do uble blind field trial was started with a candidate anti-leprosy vaccine, Mycobacterium III as an immunotherapeutic and immunoprophylactic agent against leprosy in a highly endemic region with a prevalence rate of over 18 per 1000 population.By 31 August 1992, 224 villages have been surveyed, covering a population of 307,98 1 (1981 census).A total of 979 MB patients and 2801 PB patients have been registered.A total of 19,453 household contacts of leprosy patients have been examined for clinical signs of disease, of which 16, 519 have received the initial do se while 10,434 have also received the booster dose of vaccine/placebo.The aims and objectives, study de sign of the trial, present status as well as the socio-cultural aspect involved are highlighted in this paper.A potential leprosy vaccine, based on a cultivable, rapid growing, non-pathogenic bacillus, Mycobacterium w (M.w), was proposed by Talwar et al. in 1978.1This bacillus was identified by its ability to elicit cell-mediated immune reactions similar to those evoked by M. leprae with cells from tuberculoid leprosy patients.2-5It had, in addition,

10.5935/0305-7518.19930034

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Citations (10)