Background Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for diagnosis of pediatric tuberculosis. Methods We conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB. Multiplex assay was performed to examine the plasma CC and CXC levels of chemokines. Results Baseline levels of CCL1, CCL3, CXCL1, CXCL2 and CXCL10 were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics curve analysis revealed that CCL1, CXCL1 and CXCL10 could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 80%. In addition, combiROC exhibited more than 90% sensitivity and specificity in distinguishing confirmed and unconfirmed TB from unlikely TB. Finally, classification and regression tree models also offered more than 90% sensitivity and specificity for CCL1 with a cutoff value of 28 pg/ml, which clearly classify active TB from unlikely TB. The levels of CCL1, CXCL1, CXCL2 and CXCL10 exhibited a significant reduction following anti-TB treatment. Conclusion Thus, a baseline chemokine signature of CCL1/CXCL1/CXCL10 could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.

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Shiga toxin-producing Escherichia coli (STEC), Enteropathogenic E. coli (EPEC), and Enterotoxigenic E. coli (ETEC) make up an important group of pathogens causing major animal and public health concerns worldwide. The aim of this study was to determine the prevalence of different pathotypes of E. coli in captive wildlife. We analyzed 314 fresh fecal samples from captive wildlife, 30 stool swabs from animal caretakers, and 26 feed and water samples collected from various zoological gardens and enclosures in India for the isolation of E. coli , followed by pathotyping by multiplex PCR. The overall occurrence rate of E. coli was 74.05% (274/370). The 274 E. coli isolates were pathotyped by multiplex PCR targeting 6 genes. Of them, 5.83% were pathotyped as EPEC, 4.74% as STEC, and 1.09% as ETEC. The 16S rRNA genes from the selected isolates were amplified, sequenced, and a phylogenetic tree was constructed. The phylogenetic tree exhibited indiscriminate genetic profiling and some isolates from captive wild animals had 100% genetic identity with isolates from caretakers, suggesting that captive wildlife may serve as a reservoir for infection in humans and vice-versa. The present study demonstrates for the first time the prevalence of these E. coli pathotypes in captive wildlife in India. Our study suggests that atypical EPEC strains are more frequent than typical EPEC strains in captive wildlife. Discovering the implications of the prevalence of these pathotypes in wildlife conservation is a challenging topic to be addressed by further investigations.

Pediatric TB poses challenge in diagnosis due to the paucibacillary nature of the disease. We conducted a prospective diagnostic study to identify immune biomarkers of pediatric TB and controls (discovery cohort) and obtained a separate “validation” cohort of confirmed cases of pediatric TB and controls. Multiplex ELISA was performed to examine the plasma levels of cytokines. Discovery and validation cohorts revealed that baseline plasma levels of IFNγ, TNFα, IL-2, and IL-17A were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics (ROC) curve analysis revealed that IFNγ, IL-2, TNFα, and IL-17A (in the discovery cohort) and TNFα and IL-17A (in the validation cohort) could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 90%. In the discovery cohort, cytokines levels were significantly diminished following anti-tuberculosis treatment. In both the cohorts, combiROC models offered 100% sensitivity and 98% to 100% specificity for a three-cytokine signature of TNFα, IL-2, and IL-17A, which can distinguish confirmed or unconfirmed TB children from unlikely TB. Thus, a baseline cytokine signature of TNFα, IL-2, and IL-17A could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.

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BERA abnormalities are reversible in term neonates with hyperbilirubinemia.