Vandana Choudhary

Genetic Variation in the Plasmodium falciparum Circumsporozoite Protein in India and Its Relevance to RTS,S Malaria Vaccine

RTS,S is the most advanced malaria vaccine candidate, currently under phase-III clinical trials in Africa. This Plasmodium falciparum vaccine contains part of the central repeat region and the complete C-terminal T cell epitope region (Th2R and Th3R) of the circumsporozoite protein (CSP). Since naturally occurring polymorphisms at the vaccine candidate loci are critical determinants of the protective efficacy of the vaccines, it is imperative to investigate these polymorphisms in field isolates. In this study we have investigated the genetic diversity at the central repeat, C-terminal T cell epitope (Th2R and Th3R) and N-terminal T cell epitope regions of the CSP, in P. falciparum isolates from Madhya Pradesh state of India. These isolates were collected through a 5-year prospective study aimed to develop a well-characterized field-site for the future evaluation of malaria vaccine in India. Our results revealed that the central repeat (63 haplotypes, n = 161) and C-terminal Th2R/Th3R epitope (24 haplotypes, n = 179) regions were highly polymorphic, whereas N-terminal non-repeat region was less polymorphic (5 haplotypes, n = 161) in this population. We did not find any evidence of the role of positive natural selection in maintaining the genetic diversity at the Th2R/Th3R regions of CSP. Comparative analysis of the Th2R/Th3R sequences from this study to the global isolates (n = 1160) retrieved from the GenBank database revealed two important points. First, the majority of the sequences (∼61%, n = 179) from this study were identical to the Dd2/Indochina type, which is also the predominant Th2R/Th3R haplotype in Asia (∼59%, n = 974). Second, the Th2R/Th3R sequences in Asia, South America and Africa are geographically distinct with little allele sharing between continents. In conclusion, this study provides an insight on the existing polymorphisms in the CSP in a parasite population from India that could potentially influence the efficacy of RTS,S vaccine in this region.

Comparison of higher order aberration profiles between normal and amblyopic eyes in children with idiopathic amblyopia

Aim:  To evaluate the higher order aberrations and resultant bilateral wavefront patterns in paediatric patients with idiopathic amblyopia.

Higher-order aberrations in young refractive surgery candidates in India: establishment of normal values and comparison with white and Chinese Asian populations.

PURPOSE: To establish normal values of higher‐order aberrations (HOAs) in young candidates in an Indian population and compare them with results in white and Asian (Chinese) populations. SETTING: Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. METHODS: This prospective trial comprised 206 consecutive candidates (412 eyes) for customized laser in situ keratomileusis. Exclusion criteria were previous ocular surgery, corneal ectasia, rigid gas‐permeable contact lens use, corneal scar, or cataract. Higher‐order aberrations were analyzed on a Zywave workstation (Bausch & Lomb Surgical). RESULTS: The mean age was 23.63 years ± 1.99 (SD); the mean refractive error, −2.97 ± 4.0 diopters (D) sphere and −1.73 ± 3.6 D cylinder; and the mean 6.0 mm HOA root mean square (RMS), 0.36 ± 0.26 μm. The most predominant HOAs were 3rd order (coma, trefoil). The summated RMS of the 3rd order was the most predominant (mean 0.23 ± 0.15 μm), followed by the 4th and 5th orders (P<.0001). The ratio between summated RMS means was 1:0.7:0.3, similar to that in white populations (1:0.7:0.3) and different than in Asian (Chinese) populations (1:∼0.8:0.002). Third‐ and 4th‐order aberrations were between 60% and 70% higher in Asian (Chinese) eyes. The difference between data in this study and those in others was less than 10% in 3rd and 4th order. CONCLUSION: The normative data for HOA in Indian eyes closely matched that in white populations but was different from that in Asian (Chinese) populations, which may provide help in nomogram modifications.

Interaction of Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 with Band 3 on Human Erythrocyte Surface Facilitates Parasite Growth.

Background: Plasmodium tryptophan-rich antigens are involved in host-parasite interaction. Results: Plasmodium vivax tryptophan-rich antigen PvTRAg38 interacts with three exofacial loops of Band 3 through its peptide domain KWVQWKNDKIRSWLSSEW to facilitate parasite growth. Conclusion: A novel receptor-ligand interaction between host and parasite has been defined. Significance:The study will help in understanding the host-parasite interaction and development of therapeutics for vivax malaria. Plasmodium tryptophan-rich proteins are involved in host-parasite interaction and thus potential drug/vaccine targets. Recently, we have described several P. vivax tryptophan-rich antigens (PvTRAgs), including merozoite expressed PvTRAg38, from this noncultivable human malaria parasite. PvTRAg38 is highly immunogenic in humans and binds to host erythrocytes, and this binding is inhibited by the patient sera. This binding is also affected if host erythrocytes were pretreated with chymotrypsin. Here, Band 3 has been identified as the chymotrypsin-sensitive erythrocyte receptor for this parasite protein. Interaction of PvTRAg38 with Band 3 has been mapped to its three different ectodomains (loops 1, 3, and 6) exposed at the surface of the erythrocyte. The binding region of PvTRAg38 to Band3 has been mapped to its sequence, KWVQWKNDKIRSWLSSEW, present at amino acid positions 197–214. The recombinant PvTRAg38 was able to inhibit the parasite growth in in vitro Plasmodium falciparum culture probably by competing with the ligand(s) of this heterologous parasite for the erythrocyte Band 3 receptor. In conclusion, the host-parasite interaction at the molecular level is much more complicated than known so far and should be considered during the development of anti-malarial therapeutics.

Change in the accommodative convergence per unit of accommodation ratio after bilateral laser in situ keratomileusis for myopia in orthotropic patients Prospective evaluation

PURPOSE: To analyze the effect of bilateral laser in situ keratomileusis (LASIK) on the accommodative convergence per unit of accommodation (AC/A) ratio in otherwise normal orthotropic myopic patients. SETTING: Cornea and refractive services of a tertiary‐care ophthalmic center. METHODS: This prospective clinical trial consisted of 61 myopic patients who had bilateral LASIK. Those with manifest tropia, previous squint surgery, amblyopia, or absent or impaired binocularity or those in whom monovision was planned were excluded. The preoperative examination included visual acuity, cycloplegic refraction, assessment of binocularity, a prism cover test, and evaluation of the stimulus AC/A ratio by the gradient method. All patients had LASIK using the Zyoptix platform (Bausch & Lomb). Postoperative evaluation included uncorrected and best corrected visual acuities, residual refraction, and the AC/A ratio. RESULTS: All patients had a follow‐up of 9 months. There was significant decrease in the mean AC/A ratio at the 1‐week and 1‐month follow‐ups. The AC/A progressively recovered to near preoperative values between 3 months and 9 months after surgery (analysis of variance test). There was a significant reduction in the number of symptomatic patients from the first month onward (chi square = 89.23; P<.001). CONCLUSIONS: The AC/A ratio varied after LASIK, stabilizing between 3 months and 9 months after surgery. This suggests that the maximum variation in the accommodation–convergence relationship after LASIK occurs in the first 3 months.

Extensive heterozygosity in flanking microsatellites of Plasmodium falciparum Na+/H+ exchanger (pfnhe-1) gene among Indian isolates.

Plasmodium falciparum Na(+)/H(+) exchanger-1 (pfnhe-1) gene has been proposed to be a possible marker for quinine resistance. Here, we describe the sequence analysis of the flanking microsatellites of the pfnhe-1 gene among 108 Indian P.falciparum isolates. Among the parasite population, a high degree of polymorphism was observed at all the 10 microsatellite loci within +/-40kb region of the pfnhe-1 gene where the number of alleles varied from 2 to 16 with a high expected heterozygosity ranging from 0.43 to 0.91 at these loci. Also, higher levels of heterozygosity have been observed in P.falciparum isolates collected from both low and high transmission and drug resistant areas. Furthermore, there was no association between QN resistance associated DNNND repeats in PFNHE-1 and the flanking microsatellite haplotypes. In conclusion, the observed high level of microsatellite polymorphism and absence of selective sweep in the flanking +/-40kb region of the pfnhe-1 gene could be an indication that there is no strong selection pressure on this target gene.

Review of Randomized Controlled Trials on Psychological Interventions in Child Sexual Abuse: Current Status and Emerging Needs in the Indian Context.

Child sexual abuse (CSA) is a critical, psychologically traumatic and sometimes life-threatening incident often associated with sequel of adverse physical, behavioral, and mental health consequences. Factors such as developmental age of the child, severity of abuse, closeness to the perpetrator, availability of medico-legal-social support network and family care, gender stereotypes in the community complicate the psychological trauma. Although the research on the effects of CSA as well as psychological intervention to reduce the victimization and promote the mental health of the child is in its infancy stage in India, the global research in the past three decades has progressed much ahead. A search was performed using MEDLINE, PubMed, PsycINFO, and Google Scholar from 1984 to 2015 and only 17 randomized controlled trials (RCTs) out of 96 potentially relevant studies were included. While nonspecific therapies covering a wide variety of outcome variables were prominent till 1999s, the trend changed to specific and focused forms of trauma-focused therapies in next one-and-half decades. Novel approaches to psychological interventions have also been witnessed. One intervention (non-RCT) study on effects on general counseling has been reported from India.

Nonpharmacological interventions for children with attention deficit hyperactivity disorder in India: A comprehensive and comparative research update

The nonpharmacological treatments for children with attention deficit hyperactivity disorder (ADHD) have witnessed a sea change from a rudimentary and haphazard psychosocial to cognitive interventions to social and behavioral skills to body oriented interventions to more sophisticated neurocognitive interventions. As the objective of each treatment varied, the method or procedure of each treatment also differed across studies. Indian research although not very rigorous, did witness changes emphasizing on exploring interventions in reducing symptoms and improving overall behavior. The research literature between 2005 and 2015 was searched using PubMed, Google Scholar, IndMED, MedIND, ResearchGate, and other indexed databases. Results of 110 studies were organized into five broad categories of themes of interventions such as psychosocial, body-focused, cognitive/neuro-cognitive, and cognitive behavioral. Effects of ADHD on cognitive, academic, and behavioral outcomes were also highlighted before the themes of intervention to establish linkage with discussion. However, a limited number (n = 9) of reported Indian studies focusing either on the impact of ADHD on the function of children or on interventions were found, suggesting a huge gap between global and Indian research in the area of children with ADHD. It also highlights the need for development and efficacy testing of indigenous intervention program in different areas of intervention for research and clinical practice.

Development of a multi-dimensional scale to measure trauma associated with child sexual abuse (MSCSA) and its ramifying impacts on children: A pilot study

BACKGROUND With the rising incidence of CSA in India and absence of culturally competent tool to assess the impact of trauma, there is a dire need for development of a comprehensive scale to assess the impact of trauma on children. Thus, the present study aims to develop a multi-dimensional CSA tool for children aged between 7 and 13 years. METHOD Qualitative research method of FGD/Key Interviews with 4 group participants (Parents, counsellors, mental health and medical professionals) and in-depth interview with children having history of CSA was conducted along with item pooling from existing scales. Scale domain and sub-constructs were identified through thematic analysis of the qualitative data and statements extracted through item pooling. Face and content validity was obtained followed by the administration of the scale on pilot sample of 30 children meeting selection criteria of the study. RESULTS 6 domains of the multi-dimensional impact of trauma was identified (i.e. Behavioral, Emotional, Cognition, Biological, Psychopathology and Social Functioning) which was constructed in the form of 85 scale statements across 6 domains and 48 sub-constructs on a 3-point Likert scale of response in both Hindi as well as English language. The scale was found to be having high reliability and average inter-item and inter-domain correlation. Modification of scale items based on pilot study findings and expert feedback analysis done to obtain a final scale containing 78 items. DISCUSSION Discussion done primarily in terms of scales psychometric properties, its clinical & research implications, especially focusing on cultural competency of the scale.

Tools to assess psychological trauma & its correlates in child sexual abuse: A review & current needs in Asia.

Absence of visible physical symptoms and limited capacity to express trauma directly, pose significant challenges in assessment of its exact nature of trauma and its correlates in child sexual abuse. There are numerous assessment tools however, deciding upon the appropriateness is often challenging in Asian socio-cultural and health care set up. A review would provide a ready reference to the practioner regarding the exact clinically utility of the tools and also would guide them in the direction of culture specific modifications. Computerized databases namely Medline, PsycINFO, Health and Psychosocial Instruments, and Social Sciences Citation Index were used. 52 scales were obtained and analysed in terms of scale characteristics, reference to theory and DSM, and cultural competency. Despite of a wide variety of methods, and newer instruments, many of the traditionally used techniques of childs internal thinking and emotional assessment appear outdated while reviewing the recent theories of CSA related psychological trauma. An integrated format, incroporating child-parent-clinicain rating, with multiple domain speciafic items and verbal and non-verbal tasks, is the current need in the Asian region.