Evaluation of the Universal Immunization Program and Challenges in Coverage of Migrant Children in Haridwar,Uttarakhand, India

Background:

Studies show that immunization among migrant children is poor. India has a dropout rate of 17.7% between Bacillus Calmette-Guιrin (BCG) and measles (District Level Household Survey (DLHS)-3). Haridwar district had the highest dropout rate of 27.4% from BCG to diphtheria, pertussis, and tetanus (DPT) 3 (DLHS-3) in Uttarakhand. We evaluated the Universal Immunization Programme (UIP) among migrants in Haridwar in two blocks.

Materials and Methods:

We developed input, process, and output indicators on infrastructure, human resources, and service delivery. A facility, session site and cross-sectional survey of 180 children were done and proportions for various indicators were estimated. We determined factors associated with not taking vaccination using multivariate analysis.

Results:

We surveyed 11 cold chain centers, 25 subcenters, 14 sessions, and interviewed 180 mothers. Dropouts were supposed to be tracked using vaccination card counterfoils and tracking registers. The dropout rate from BCG to DPT3 was 30%. Lack of knowledge (adjusted odds ratio (AOR) 6.6,95% confidence interval (CI) 2.6–16.7), mother not being decision maker (AOR 4.0,95%CI 1.7–9.2), lack of contact by Accredited Social Health Activist (ASHA; AOR 3.0,95%CI 1.1–7.7), not being given four post-vaccination messages (AOR 7.7, 95% CI 2.9–20.2), and longer duration of stay in Haridwar (AOR 3.0 95% 1.9–7.6) were risk factors for nonimmunization. The reasons stated by mothers included lack of awareness of session site location (67%) and belief that child should only be vaccinated in their resident district (43%).

Conclusions:

There was low immunization coverage among migrants within adequate supervision, poor cold chain maintenance, and improper tracking of dropouts. Mobile immunization teams, prelisting of migrant children, and change in incentives of ASHAs for child tracking were needed. A monitoring plan for sessions and cold chain needed enforcement.     

Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics

Purpose

Describe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic variation detected by next-generation sequencing (NGS) with comprehensive annotation and functional studies.

Methods

Seventy ST cases on clopidogrel identified from the PLATO trial (n =?58) and Mayo Clinic biorepository (n =?12) were matched 1:1 with controls for age, race, sex, diabetes mellitus, presentation, and stent type. NGS was performed to cover the entire CYP2C19 gene. Assessment of exonic variants involved measuring in vitro protein expression levels. Intronic variants were evaluated for potential splicing motif variations.

Results

Poor metabolizers (n =?4) and rare CYP2C19*8, CYP2C19*15, and CYP2C19*11 alleles were identified only in ST cases. CYP2C19*17 heterozygote carriers were observed more frequently in cases (n =?29) than controls (n =?18). Functional studies of CYP2C19 exonic variants (n =?11) revealed 3 cases and only 1 control carrying a deleterious variant as determined by in vitro protein expression studies. Greater intronic variation unique to ST cases (n =?169) compared with controls (n =?84) was observed with predictions revealing 13 allele candidates that may lead to a potential disruption of splicing and a loss-of-function effect of CYP2C19 in ST cases.

Conclusion

NGS detected CYP2C19 poor metabolizers and paradoxically greater number of so-called rapid metabolizers in ST cases. Rare deleterious exonic variation occurs in 4%, and potentially disruptive intronic alleles occur in 16% of ST cases. Additional studies are required to evaluate the role of these variants in platelet aggregation and clopidogrel metabolism.

     

An elaborative NMR based plasma metabolomics study revealed metabolic derangements in patients with mild cognitive impairment: a study on north Indian population

Metabolic Brain Disease - Mild cognitive impairment (MCI) is transition phase between cognitive decline and dementia. The current study aims to investigate altered metabolic pattern in plasma of...     

Association of Interleukin-1β-31C/T, -511T/C and -3954C/T Single Nucleotide Polymorphism and Their Blood Plasma Level in Acquired Aplastic Anemia

Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1β) gene polymorphisms, (IL-1β-31, IL-1β-511 and IL-1β-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR–RFLP) method and IL-1β plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1β was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1β-3954 genotype. IL-1β-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1β gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1β gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA.     

Neurological manifestations of hepatitis E virus infection: An overview

Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.     

Human and simian immunodeficiency retroviruses: activation and differential transactivation of gene expression

New West African human immunodeficiency viruses (HIV-2s) and simian immunodeficiency virus (SIV) contain functional transactivator (tat) gene and tat response elements. Their long terminal repeats (LTR) and tat genes are more related among themselves than to HIV-1 LTR and tat gene. The viral gene expression of HIV-2 as well as SIV can be stimulated by T cell activators, such as mitogens and phorbol esters. HIV-2 and SIV display a much broader transactivation response specificity than does HIV-1. The LTR-directed gene expression of HIV-2/SIV is not only transactivated by their own tat gene and by HIV-1 tat gene but also by factors in human T cell leukemia/lymphoma virus type I (HTLV-I) and simian virus 40 (SV40) infected cells, involving HTLV-I tat gene and SV40 T antigens, respectively. HIV-1 LTR-directed gene expression is much less transactivated by HIV-2/SIV tat genes and by factors in HTLV-I- and SV40-infected cells. Immune activation and heterologous transactivation of the LTR-directed gene expression may be relevant to the latency of virus infection and progression toward the acquired immunodeficiency syndrome (AIDS).     

Ablation of atrial fibrillation

Atrial fibrillation (AF) is a common arrhythmia, affecting an estimated 2 million people in the United States and its prevalence increases with age, reaching 10% in those > or = 80 years. AF confers a four- to fivefold increased risk of stroke compared to the general population and has been associated with a doubling of all-cause mortality. During the past decade, limited success rates of drug treatment stimulated an exploration of interventional treatment options for AF. As our knowledge on initiating triggers and perpetuating substrate of AF expanded, different potentially curative catheter ablation techniques have been developed. In this article we review the current patient selection criteria, methods, and the results of the catheter ablation of atrial fibrillation.