Virulence potential of group A streptococci isolated from throat cultures of children from north India

Background & objectives: Rheumatic fever (RF)/rheumatic heart disease (RHD) caused by Group A streptococcus (GAS) are more prevalent in north India as compared to the western world, where invasive diseases are common. This could be due to variation in the virulence of GAS in different geographic locations. Hence, we studied the virulence potential of GAS isolated from the throat of children from north India Methods: Fifty GAS isolated consecutively, from children with mild pharyngitis (20), severe pharyngitis (24) and asymptomatic pharyngeal carriers (6), were characterized by emm typing and opacity factor (OF). Adherence and internalization of GAS in HEp-2 cells and opsonophagocytosis in convalescent serum samples were studied. Results: Twenty emm types, six sequence types, and one non-typeable GAS were circulating in the community. emm type 74, 11, 68, StI129 and NS292 were most prevalent. Twenty seven (54%) GAS isolates were OF negative. Sixty five per cent of the most prevalent emm types were OF negative indicating their rheumatogenic potential. Adhesion of GAS ranged from 0.1 to 100 per cent. Forty eight per cent of GAS were highly adherent. Invasion of GAS in HEp-2 cells ranged between 0 to 30 per cent. Only 20 per cent isolates exhibited highest invasion. GAS were opsonophagocytosed with highly divergent efficiency ranging from 0 to 91.7 per cent. Nineteen GAS were not opsonophagocytosed and 15 multiplied during the assay. Isolates of the same emm type also varied in their virulence potential. Interpretation & conclusions: GAS isolates from the throat of children from north India belonged to several emm types, majority were OF negative, excellent adherents but poor invaders. This explains why throat infections in these children tend to lead to ARF/RHD rather than invasive diseases. A few isolates exhibiting high invasion efficiency indicate that GAS throat cultures can also lead to invasive diseases

Immune response against M protein-conserved region peptides from prevalent group A Streptococcus in a North Indian population

BackgroundGroup A streptococci (GAS) cause infections with a high prevalence in most developing countries. A GAS vaccine under trial that is based on the amino-terminus of the M protein provides type-specific immunity, and hence seems ineffective in India because of heterogeneous emm types. However, the conserved C-terminal region of the M protein protects against multiple serotypes. In this paper, the immune response generated against the conserved C-repeat region of the M protein was checked in an Indian population to establish their vaccine candidature.MethodsWhen screened for GAS, patients with pharyngitis, rheumatic fever/rheumatic heart disease (RF/RHD), and invasive disease showed heterogeneous emm types, out of which five prevalent types (1-2, 11, 49, 75 and 112) were selected for the study. The C-terminal region of their M proteins showed conserved C1-, C2-, and C3-repeats. The C1-repeat was more diverse and had two different J14-like sequences. Peptides to these C-terminal regions (J14.1 and J14-R6) were designed. Antibodies against these peptides were analyzed using the sera of 130 GAS-infected volunteers.ResultsSerum antibodies were significantly higher in patients with acute rheumatic fever, RHD, and invasive disease than in patients with pharyngitis or the healthy controls. The serum antibodies to these peptides was higher in teenagers and adults than in children.ConclusionResults showed an association between streptococcal disease progression and the age-related development of immunity to the conserved regions. Hence, these peptides could be considered protective in impeding streptococcal infections worldwide

Clinical and microbiologic characteristics of invasive Streptococcus pyogenes infections in north and south India.

The lack of epidemiologic data on invasive Streptococcus pyogenes infections in many developing countries is concerning, as S. pyogenes infections are commonly endemic in these areas. Here we present the results of the first prospective surveillance study of invasive Streptococcus pyogenes infections in India. Fifty-four patients with invasive S. pyogenes infections were prospectively enrolled at two study sites, one in the north and one in the south of India. Sterile-site isolates were collected, and clinical information was documented using a standardized questionnaire. Available acute-phase sera were tested for their ability to inhibit superantigens produced by the patient's own isolate using a cell-based neutralizing assay. The most common clinical presentations were bacteremia without focus (30%), pneumonia (28%), and cellulitis (17%). Only two cases of streptococcal toxic shock syndrome and no cases of necrotizing fasciitis were identified. Characterization of the isolates revealed great heterogeneity, with 32 different emm subtypes and 29 different superantigen gene profiles being represented among the 49 sterile-site isolates. Analyses of acute-phase sera showed that only 20% of the cases in the north cohort had superantigen-neutralizing activity in their sera, whereas 50% of the cases from the south site had neutralizing activity. The results demonstrate that there are important differences in both clinical presentation and strain characteristics between invasive S. pyogenes infections in India and invasive S. pyogenes infections in Western countries. The findings underscore the importance of epidemiologic studies on streptococcal infections in India and have direct implications for current vaccine developments