Streptococcal pharyngitis, rheumatic fever and rheumatic heart disease: Eight-year prospective surveillance in Rupnagar district of Punjab, India.

Background. Rheumatic fever (RF)/rheumatic heart disease (RHD) continue to be a neglected public health priority. We carried out a registry-based control project, prospective surveillance and sample surveys to estimate the burden of disease. Methods. We trained healthcare providers and established a surveillance system for the 1.1 million population of Rupnagar district in Punjab. In sample surveys conducted among schools, physicians examined the sampled children. Children with a cardiac murmur were investigated by echocardiography. Throat swabs were obtained from a sub-sample, and group A streptococci (GAS) were identified and emm typed by standard laboratory methods. We estimated the morbidity rates for RF/RHD from surveillance data and school surveys using a correction factor to account for under-registration of cases in the registry. Results. A total of 813 RF/RHD cases were registered from 2002 to 2009. Of the 203 RF and 610 RHD cases, respectively, 51.2% and 36.7% were males. In the age group of 5–14 years, RF was more common (80%) than RHD (27%). The prevalence of RF/RHD in 5–14-year-old students was 1.0/ 1000 (95% CI 0.8–1.3). The school survey indicated that about two-thirds of the RF/RHD cases were enrolled in the hospital-based registries. Based on the school survey, the prevalence of RF/RHD was estimated to be 143/100 000 population. In the registry, the annual incidence of acute RF was estimated to be at least 8.7/100 000 children in the age group of 5–14 years. The prevalence of GAS was 2% (13/656) in children with sore throat and 0.5% (14/2920) among those not having sore throat. Typing of 27 GAS revealed 16 emm types. We estimate that about 1000 episodes of GAS pharyngitis lead to one episode of acute RF. Conclusion. RF/RHD continue to be a public health problem in Punjab, India.

Cholera toxin: A paradigm of a multifunctional protein.

Cholera toxin (CT) was discovered exactly half a century ago by S.N. De. We have come a long way since this epoch-making discovery. Retrospectively, science had to wait a long time since Koch’s prediction of the existence of a toxin, and its actual discovery by De. CT is not just another enterotoxin that causes the signs and symptoms of the dreaded disease, cholera. It is unique in many respects, starting from its structure to its functions. CT is a multifunctional protein that is capable of influencing the immune system in many ways. It not only has remarkable adjuvant properties, but also acts as an anti-inflammatory agent, by modulating specific signal transduction pathways. Its immunomodulatory properties can be harnessed for treatment of various autoimmune disorders, and have shown great promise in the area of immunotherapeutics. CT can truly be considered as a paradigm of a multifunctional protein.

Genotyping of group A streptococcus by various molecular methods.

BACKGROUND & OBJECTIVE: Group A streptococcus (GAS) causes a wide variety of life threatening diseases in developing countries like India. Characterization of GAS is therefore necessary for prevention and control of the disease. Genotypic analysis of GAS is largely lacking from India, therefore an attempt was made to study the genotype distribution of north Indian GAS isolates. METHODS: Sixty clinical isolates of GAS, (52 collected from pharyngitis and 8 from RF/RHD patients) were genotyped by various molecular techniques like restriction enzyme analysis (REA), ribotyping, PCR-ribotyping and random amplification of polymorphic DNA (RAPD). A few isolates were also typed by emm gene sequencing for comparison. RESULTS: REA using Hind III digestion differentiated the isolates into six different patterns. The same isolates were grouped into three ribotypes when analyzed for PCR - ribotyping of 16S- 23S rRNA region. However, RAPD fingerprints generated higher level of discrimination by AP4 and AP5 primers showing 12 rapdemes, followed by AP3, AP2 and API producing 11, 9 and 6 rapdemes respectively. A total of 78 RAPD fragments or rapdemes were generated, of which 48 (62%) were shared and 30 (38%) were unique. These unique RAPD fragments could be used as a genetic marker for identification of GAS. Representative isolates that produced 12 different rapdemes by AP5, on further confirmation by emm typing showed 11 different emm types. INTERPRETATION & CONCLUSION: The finding of our study demonstrated the RAPD profiling to be the most discriminatory for genotyping of group A streptococcus isolates as well as comparable to the most commonly used sophisticated technique of emm typing.

Antioxidant status in children with homozygous thalassemia.

The status of enzymatic and non-enzymatic anti-oxidants was evaluated in 41 patients with transfusion dependent beta-thalassemia. An additional 20 age-matched children, with non-hemolytic anemia, served as controls. Fresh blood samples, obtained in the morning, were processed immediately. Plasma was stored at -80 degrees C. Levels of vitamins A and E were assayed simultaneously by HPLC. RBC vitamin A was not measurable in 29 (70.7%) thalassemics and in all the controls. Plasma vitamin A levels were lower in thalassemics than in controls (p<0.05). Vitamin E in RBCs was not measurable in 13 (31. 7%) cases. The mean level of RBC vitamin E was 3 times lower in thalassemics. Similarly, SOD enzyme activity in thalassemics, was at least 1.5 lower in comparison to the activity documented in controls (p<0. 05). The observations indicate that thalassemics have enhanced oxidative stress. Administration of selective antioxidants and a balanced diet may preclude oxidative damage.

Clinical score card for diagnosis of group A streptococcal sore throat.

OBJECTIVE: Group A beta hemolytic streptococcus (GAS) sore throat primarily occurs among children in 5-15 years age group, and if not treated appropriately causes rheumatic fever/rheumatic heart disease (RF/RHD). Present study was aimed at validation of a clinical scoring system for diagnosis of GAS. METHODS: Five hundred and thirty six children in 5-15 years age group were enrolled by systematic random selection of households from a peri-urban slum of Chandigarh. They were visited fortnightly at their home for one year to record signs and symptoms of cough and cold. Throat swabs were collected in 918 episodes, of which 123 (13.4%) were GAS culture positive. RESULT: Significant association of GAS was found with pain in the throat, enlarged tonsils, pharyngeal erythema and tender cervical lymphadenopathy. According to the percentage positivity of GAS culture, weighted scores were assigned to age of the child, season of occurrence, fever, size of tonsil, pharyngeal erythema and exudate, lymphadenopathy and pain in throat. Combinations of various symptoms and signs gave sensitivity of 86-89% and specificity of 83-89% whereas clinical score of 15 or more had 91% sensitivity and 98% specificity for diagnosis of GAS pharyngitis. CONCLUSION: As the level of clinical acumen and prevalence of GAS may differ in different primary care settings of the country, the proposed scoring system should be validated and adapted to suit local conditions before establishing it in the primary prophylaxis strategy to prevention of RF/RHD.