Group A Beta Hemolytic Streptococcal (GAS) Infection Clinical Trial
Official title:
Epidemiological Surveillance in India of Group A Streptococcal Infections Including Pharyngitis and Impetigo Supported by Indo-US Vaccine Action Program
Information from this study is needed to plan an eventual trial of a GAS vaccine in India if
and when one is available. A GAS vaccine is currently a priority of the Indian Council for
Medical Research (ICMR), and this project has been approved by the Joint Working Group (US
and Indian Delegates) of the Vaccine Action Program, a joint effort of the ICMR and NIAID to
implement cooperative efforts between the two countries on mutual objectives in vaccine
development. Currently, several GAS vaccines are in development, supported by NIAID, and
other sources, and one candidate is in phase one clinical trial authorized by the FDA.
Information on the antigenic structure of GAS isolated in India will be needed for planning
vaccine composition. It is the view of the Indian Ministry of Health and Indian Council for
Medical Research that eventual prevention and control of rheumatic fever and rheumatic heart
disease in India, now a heavy burden on the children will require a GAS vaccine, which
requires both access to primary health care and a vaccine if and when it is available.
Information on incidence is needed to determine the size of a future vaccine cohort in order
to obtain a statistically significant result on vaccine efficacy. Although unrelated to
vaccine development, information on the incidence of GAS pharyngitis is needed in India to
implement primary and secondary acute rheumatic fever (ARF) and rheumatic heart disease (RHD)
prevention programs as were implemented in the USA and Europe forty years ago.
A vaccine trial is not part of this study, nor is there any intervention, other than
antibiotic treatment of all children volunteers who develop GAS pharyngitis or impetigo.
An additional point should be made about the importance of obtaining epidemiological data on
streptococcal disease in India, and on the emm types of GAS that cause infections. The
population of India is over one billion people, representing nearly twenty five percent of
the world's population. Information on GAS epidemiology from India is scant to say the least,
and it is sorely needed. We now know that streptococcal toxic shock syndrome and fasciitis
that have occurred in the U. S., Europe, Australia, and Japan, with greater frequency in
recent years are caused by several genetically similar emm types of GAS. The implication of
such genetic and epidemiologic data is that these genetically related strains have spread
worldwide, Current information from India is far too limited to know if these virulent
strains of GAS occur in India, and if they do, to what extent might they be the cause of
frequent invasive disease in hospitalized patients.
Equally important, we do not know if a potentially high virulent GAS strain is currently
emerging in some locale(s) in India, and what possible threat it might become, if it were to
be transported to other worldwide geographic regions. Although not a specific aim of this
proposal, the surveillance conducted to accomplish the aims of this protocol will provide
essential information on the possible emergence of an unexpected emm type with pathogenic
potential.
...
This is an epidemiological study on the incidence of Group A beta hemolytic streptococcal
(GAS) infections (both pharyngitis and impetigo) in school-age children in two rural area of
India: surveillance in four schools, in the north in the Punjab near Chandigarh conducted by
the medical staff of the Department of Community Medicine Post-graduate Institute for Medical
Research and Training (PGI); and in one school in the south in Tamil Nadu near Vellore
conducted by the medical staff of the Department of Community Medicine, Christian Medical
College (CMC).
Children and their teachers were questioned weekly for a history of GAS infection. On all
children suspected from the history of a streptococcal infection of the pharynx or the skin,
a physical examination of nose, throat, ears and skin was performed and throat culture and or
skin culture and blood sample were taken for subsequent antibody determination. The diagnosis
of GAS infection was made on the basis of established clinical criteria and the isolation of
GAS from throat and skin lesion cultures.
The surveillance of the children was completed in March '04 in Vellore, and in April '04 in
Chandigarh. For the next year, there will be extensive analysis of the clinical data;
analysis of the isolated GAS for emm type and other bacteriologic characteristics; and
epidemiologic analysis in a search for patterns of distribution of GAS infections by sex,
age, school and session.
The general objectives have been:
To establish population-based surveillance to determine the incidence of GAS infection in
school children age 7-11, to characterize the M protein of the newly isolated strains of GAS
by emm gene sequencing,
1. to identify surrogate markers of protective immunity relevant to vaccine development
such as serum antibody to the M type-specific peptides and cysteine protease, and
2. to define the molecular epidemiology of GAS in terms of those characteristics that are
relevant to vaccine-induced immunity.
Information from this study is needed to plan an eventual trial of a vaccine(s) if and when
one is available. Information on the antigenic structure of GAS isolated in India will be
needed for planning vaccine composition. Information on incidence is needed to determine the
size of a future cohort that will be needed to obtain a statistically significant result on
vaccine efficacy.
A vaccine trial is not part of this study, nor was there any intervention, other than
diagnostic procedures and antibiotic treatment of all who develop a GAS infection.
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