Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies

A community-based case–control study to investigate the role of iron deficiency in the persistence of goiter

Objectives: To find out the magnitude of iron deficiency anemia in the age group of 6–12 years and investigate the role of iron deficiency as a possible contributor to endemic goiter in school children in Ambala. Materials and Methods: The present study was conducted as a subset of a cross-sectional study among 2700 children from 6 to 12 years of age to find out the prevalence of goiter. All the subjects who were found to be suffering from goiter in the cross-sectional study were enrolled in the case–control study as cases and were compared with age- and sex-matched controls (children without goiter) from the same cohort. The study was conducted from February 2011 to January 2012. Results: Out of total, goiter was observed in 12.6% of the subjects. Urinary iodine excretion was found to be <100 μg/L in 57 (10.5%) children. Mean hemoglobin (Hb) level of the study population was 11.9 g/dL. It was noted that 71% of the goitrous children had anemia (Hb <12 g/dL) as compared to 63.7% of the control group. Serum ferritin (SF) was <15 ng/mL in 70% of the children. The mean ± standard deviation of SF in the goitrous and nongoitrous children was 19.65 ± 32.51 μg/L and 27.55 ± 21.07 μg/L, respectively (P = 0.012). Conclusion: The findings in the study suggest that iron deficiency anemia in children is contributing toward the persistence of goiter in the postiodization phase

Detection of Newcastle disease virus and assessment of associated relative risk in backyard and commercial poultry in Kerala, India

Abstract Background Newcastle disease (ND) is an economically important viral disease affecting the poultry industry. In Kerala, a state in South India, incidences of ND in commercial and backyard poultry have been reported. But a systematic statewide study on the prevalence of the disease has not been carried out. Objectives A cross‐sectional survey was performed to detect the presence of Newcastle disease virus (NDV) in suspect cases and among apparently healthy commercial flocks and backyard poultry, in the state and to identify risk factors for NDV infection. Methods Real‐time reverse transcription‐PCR (RT‐PCR) was used to detect the M gene of NDV in choanal swabs and tissue samples collected from live and dead birds, respectively and the results were statistically analysed. Results The predominant clinical signs of the examined birds included mild respiratory signs, huddling together and greenish diarrhoea. Nervous signs in the form of torticollis were noticed in birds in some of the affected flocks. On necropsy, many birds had haemorrhages in the proventriculus and caecal tonsils which were suggestive of ND. Of the 2079 samples tested, 167 (8.0%) were positive for the NDV M‐gene by RT‐PCR. Among 893 samples collected from diseased flocks, 129 (14.5%), were positive for M gene with pairwise relative risk (RR) of 15.6 as compared to apparently healthy flocks where 6 out of 650 (0.9%) samples were positive. All positive samples were from poultry; none of the ducks, pigeons, turkey and wild birds were positive. Commercial broilers were at higher risk of infection than commercial layers (RR: 4.5) and backyard poultry (RR: 4.9). Similarly, birds reared under intensive housing conditions were at a higher risk of being infected as compared to those reared under semi‐intensive (RR: 6.7) or backyard housing (RR: 2.1). Multivariable analysis indicated that significantly higher risk of infection exists during migratory season and during ND outbreaks occurring nearby. Further, lower risk was observed with flock vaccination and backyard or semi‐intensive housing when compared to intensive housing. When the M gene positive samples were tested by RT‐PCR to determine whether the detected NDV were mesogenic/velogenic, 7 (4.2%) were positive. Conclusions In Kerala, NDV is endemic in poultry with birds reared commercially under intensive rearing systems being affected the most. The outcome of this study also provides a link between epidemiologic knowledge and the development of successful disease control measures. Statistical analysis suggests that wild bird migration season and presence of migratory birds influences the prevalence of the virus in the State. Further studies are needed to genotype and sub‐genotype the detected viruses and to generate baseline data on the prevalence of NDV strains, design better detection strategies, and determine patterns of NDV transmission across domestic poultry and wild bird populations in Kerala