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ASSIST

Comprehensive approach to understand streptococcal diseases and their sequelae to develop innovative strategies for diagnosis, therapy, prevention and control

Overview

The disease burden of group A streptococcal infections worldwide is extremely high. More than 600 million persons, mostly children, suffer from streptococcal pharyngitis each year. There are 600 thousand cases of invasive disease. More serious are the sequelae of these infections in the form of acute rheumatic fever and rheumatic heart disease. About 15 million children are suffering from rheumatic heart disease, out of these, 6 million in India alone. Streptococcal diseases can be considered as one of the most important groups of neglected
communicable diseases in India. There are many reasons for the inability to control GAS diseases in India. Besides poverty and living conditions, inadequate treatment and noncompliance with penicillin secondary prophylaxis after onset of rheumatic fever have all contributed to the high disease burden. The best perspective for controlling this disease is to develop a fast diagnostic test for rheumatogenic streptococci and to develop a regionspecific vaccine against group A streptococci. Prerequisite for diagnostic and vaccine development is in-depth understanding of streptococcal diseases in Indian scenario. Data on
the epidemiology of all GAS diseases, the characterization of the circulating strains in different regions of India, determination of genetic predisposition markers in different ethnic populations of India and immunological data to identify region-specific vaccine candidates are urgently needed. The major objective of this proposal is to pull together such information in a comprehensive way which will then form the basis of a novel diagnostic test for
rheumatogenic streptococci and for the identification of candidates to develop a regionspecific vaccine, using state-of-the-art technologies already established in Europe. This proposal is the first comprehensive approach to understand streptococcal diseases and would contribute towards solving a major health problem in India.

Project Objectives

The primary objective of this proposal is to apply a multi-disciplinary approach to understanding the spectrum of streptococcal diseases in India. A novel diagnostic test for rheumatogenic streptococci will be designed and candidates for development of region-specific group A streptococcal vaccines prototypes will be identified. A diagnostic test for rheumatogenic streptococci and development of an efficacious vaccine in India has never been attempted so far and is, therefore, a novel feature of this proposal. The specific objectives are:

Objective 1:

Epidemiological studies in defined areas in North and South India

Objective 2:

Genotyping of virulence strains obtained during the survey and expression profiling of representative strains

Objective 3:

Elucidation of nature and mechanisms of invasive diseases in India in comparison to European surveillance data

Objective 4:

Identification of genetic markers that contribute towards susceptibility to streptococcal infections in the two ethnically defined Indian populations

Objective 5:

Validation of the induction mechanisms of acute rheumatic fever in the Indian
scenario

Objective 6:

Rational design of a fast diagnostic test for the identification of streptococci capable of causing rheumatic fever based on the structural biology of collagen recognition

Objective 7:

Identification of candidates to develop region-specific vaccine

Objective 8:

Communication of relevant information, transfer of technology and knowledge on new biotechnological approaches to governments, decision makers, international agencies and health authorities

Objective 9:

Training of young Indian scientists in the modern methodology established at the European partners’ institutes

Partner

Helmholtz Centre for Infection Research

Tasks:

  • Coordination & project management
  • Virulence expression profiling of the isolates
  • design of protein arrays
  • identification of region-specific vaccine candidates and testing their efficacy

Project coordinator:

Prof. Dr. G. S. Chhatwal

Helmholtz Centre for Infection Research

Dept. Microbiology

Inhoffenstr. 7

D 38124 Braunschweig

Germany

e-mail: gsc@helmholtz-hzi.de

Team Members:

Dr. Andreas Nerlich, e-mail: Andreas.Nerlich@helmholtz-hzi.de

Dr. Vivek Sagar, e-mail: Vivek.Sagar@helmholtz-hzi.de

Rene Bergmann, e-mail: Rene.Bergmann@helmholtz-hzi.de

Post Graduate Insitute of Medical Education and Research

Tasks:

  • Setting up school-level survey for streptococcal carriage and pharyngitis in defined areas near Chandigarh, North India
  • Setting up surveillance for acute rheumatic fever and rheumatic heart disease in hospitals of survey area
  • Establishing of surveillance for invasive strep disease in tertiary care hospitals of Chandigarh

Project Participant:

Prof. Dr. K. K. Talwar

Dept. of Cardiology

Post Graduate Institute of Medical Education and Research (PGIMER)

Chandigarh - 160 012

India

Tel. 0091-172-274-5062

Fax 0091-172-274-4401

e-mail: kktalwar@sancharnet.in

Christian Medical College

Tasks:

  • Establishment of a school survey system for the isolation, identification and characterization of GAS strains causing throat and skin infections in a highly endemic community
  • Establishment of a Registry for GAS disease and the strains causing them in a highly endemic south Indian community of school going children
  • Establishment of a hospital based Registry for GAS invasive disease in South India to determine their prevalence and the nature of strains causing them

Project Participant:

Prof. K. Brahmadathan

Dept. of Microbiology

Christian Medical College (CMC)

Vellore – 632 004

India

Tel. 0091-416-228-3085

Fax 0091-416-223-2103

e-mail: knb1948@hotmail.com

Karolinska Institute

Tasks:

  • Comparison of the nature of invasive streptococcal disease in relation to European data
  • Determination of host-pathogen interplay at the local site of infection
  • Determination of host humoral immunity in relation to disease manifestation
  • Identification of molecular mechanisms of streptococcal invasive diseases in India

Project Participant:

Prof. Anna Norrby-Teglund

Dept. of Medicine

Karolinska Institutet (KI)

SE-14186 Stockholm

Sweden

Tel. 0046-858-87296

Fax 0046-8746-7637

e-mail: Anna.Norrby-Teglund@ki.se

All India Institute of Medical Sciences

Tasks:

  • Establishing parameters of disease susceptibility in two patient cohorts with different ethnic backgrounds
  • Comparison of the disease associated MHC haplotypes between invasive disease and patients with rheumatic fever/ rheumatic heart disease
  • Understanding molecular mechanisms of genetic predisposition in streptococcal disease in India

Project Participant:

Prof. Dr. N. K. Mehra

Dept. of Transplant Immunology and Immunogenetics

All India Institute of Medical Sciences (AIIMS)

Ansari Nagar

New Delhi – 110 029

India

Tel. 0091-11-265-88588

Fax 0091-11-265-88663

e-mail: narin98@hotmail.com

University of St. Andrews

Tasks:

  • Analysis of the interaction of collagens with streptococcal surface components to select candidates for structural studies
  • structural analysis of collagen binding to streptococcal peptides
  • design and development of a fast diagnostic prototype assay for rheumatogenic streptococci based on collagen aggregation

Project Participant:

Dr. U. Schwarz-Linek

Centre for Biomolecular Sciences

University of St. Andrews

St Andrews – KY16 9AJ

United Kingdom

Tel. 0044-1334-463401

e-mail: us6@st-andrews.ac.uk

 

Beteiligte Gruppen

Es gibt keine Ergebnisse

Koordinator

Helmholtz-Zentrum für Infektionsforschung

Homepage

www.helmholtz-hzi.de/assist/

Geldgeber / Förderer

EU - Europäische Union