Determinants of post discharge mortality among hospitalized COVID-19 patients.

Background & objectives: The post-acute effects of COVID-19 are continually being updated. This investigation was conducted to evaluate the determinants of post discharge mortality in hospitalized COVID-19 patients, especially 18-45 yr of age. Methods: A series of three nested case-control analyses was conducted on follow up data collected in the National Clinical Registry for COVID-19 between September 2020 and February 2023 from 31 hospitals. Matching (1:4) was done by the date of hospital admission ±14 days for the following comparisons: (i) case-patients reported as dead vs. controls alive at any contact within one year follow up; (ii) the same in the 18-45 yr age group and (iii) case-patients reported as dead between the first and one year of follow up vs. controls alive at one year post discharge. Results: The one year post discharge mortality was 6.5 per cent (n=942). Age [≤18 yr: adjusted odds ratio (aOR) (95% confidence interval [CI]): 1.7 (1.04, 2.9); 40-59 yr: aOR (95% CI): 2.6 (1.9, 3.6); ≥60 yr: aOR (95% CI): 4.2 (3.1, 5.7)], male gender [aOR (95% CI): 1.3 (1.1, 1.5)], moderate-to-severe COVID-19 [aOR (95% CI): 1.4 (1.2, 1.8)] and comorbidities [aOR (95%CI): 1.8 (1.4, 2.2)] were associated with higher odds of post-discharge one-year mortality, whereas 60 per cent protection was conferred by vaccination before the COVID-19 infection. The history of moderate-to-severe COVID-19 disease [aOR (95% CI): 2.3 (1.4, 3.8)] and any comorbidities [aOR (95% CI): 3 (1.9, 4.8)] were associated with post-discharge mortality in the 18-45-yr age bracket as well. Post COVID condition (PCC) was reported in 17.1 per cent of the participants. Death beyond the first follow up was associated with comorbidities [aOR (95%CI): 9.4 (3.4, 26.1)] and reported PCC [aOR (95% CI): 2.7 (1.2, 6)]. Interpretation & conclusions: Prior vaccination protects against post discharge mortality till one year in hospitalized COVID-19 patients. PCC may have long term deleterious effects, including mortality, for which further research is warranted.

Characterizing the third wave of COVID-19: An analysis from the National Clinical Registry of COVID-19.

Background & objectives: Data from the National Clinical Registry for COVID-19 (NCRC) were analyzed with an aim to describe the clinical characteristics, course and outcomes of patients hospitalized with COVID-19 in the third wave of the pandemic and compare them with patients admitted earlier. Methods: The NCRC, launched in September 2020, is a multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized COVID-19 patients were captured in an electronic data portal from 38 hospitals across India. Patients enrolled during December 16, 2021 to January 17, 2022 were considered representative of the third wave of COVID-19 and compared with those registered during November 15 to December 15, 2021, representative of the tail end of the second wave. Results: Between November 15, 2021 and January 17, 2022, 3230 patients were recruited in NCRC. Patients admitted in the third wave were significantly younger than those admitted earlier (46.7±20.5 vs. 54.6±18 yr). The patients admitted in the third wave had a lower requirement of drugs including steroids, interleukin (IL)-6 inhibitors and remdesivir as well as lower oxygen supplementation and mechanical ventilation. They had improved hospital outcomes with significantly lower in-hospital mortality (11.2 vs. 15.1%). The outcomes were better among the fully vaccinated when compared to the unvaccinated or partially vaccinated. Interpretation & conclusions: The pattern of illness and outcomes were observed to be different in the third wave compared to the last wave. Hospitalized patients were younger with fewer comorbidities, decreased symptoms and improved outcomes, with fully vaccinated patients faring better than the unvaccinated and partially vaccinated ones.

Usability of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency: a multi-country assessment of test label comprehension and results interpretation.

BACKGROUND: Point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing has the potential to make the use of radical treatment for vivax malaria safer and more effective. Widespread use of G6PD tests as part of malaria case management has been limited, in part due to due concerns regarding product usability, user training, and supervision. This study seeks to assess how well end users can understand the Standard™ G6PD Test (SD Biosensor, Suwon, South Korea) workflow, result output, and label after training. This will ultimately help inform test registration and introduction. METHODS: Potential G6PD test users who provide malaria case management at three sites in Brazil, Ethiopia, and India were trained on the use of the SD Biosensor Standard G6PD Test and assessed based on their ability to understand the test workflow and interpret results. The assessment was done through a questionnaire, designed to assess product usability against key technical product specifications and fulfill regulatory evidence requirements. Any participant who obtained 85% or above correct responses to the questionnaire was considered to adequately comprehend how to use and interpret the test. RESULTS: Forty-five participants, including malaria microscopists, laboratory staff, nurses, and community health workers took part in the study. Seventy-eight percent of all participants in the study (35/45) obtained passing scores on the assessment with minimal training. Responses to the multiple-choice questions indicate that most participants understood well the test intended use, safety claims, and warnings. The greatest source of error regarding the test was around the correct operating temperature. Most test results were also read and interpreted correctly, with the haemoglobin measurement being a more problematic output to interpret than the G6PD measurement. CONCLUSIONS: These data results show how a standardized tool can be used to assess a user's ability to run a point-of-care diagnostic and interpret results. When applied to the SD Biosensor Standard G6PD Test, this tool demonstrates that a range of users across multiple contexts can use the test and suggests improvements to the test instructions and training that can improve product usability, increase user comprehension, and ultimately contribute to more widespread effective use of point-of-care G6PD tests. TRIAL REGISTRATION: NCT04033640.

Limited-resource preparable chitosan magnetic particles for extracting amplification-ready nucleic acid from complex biofluids.

Extraction and concentration of pure nucleic acid from complex biofluids are the prerequisite for nucleic acid amplification test (NAAT) applications in pathogen detection, biowarfare prevention, and genetic diseases. However, conventional spin-column mediated nucleic acid extraction is constricted by the requirement for costly power-intensive centralized lab infrastructure, making it unsuitable for limited-resource settings. Significant progress in lab-on-a-chip devices or cartridges (e.g., Cepheid GeneXpert®) that integrate nucleic acid extraction and amplification has been made, but these approaches either require additional equipment or are costly. Similarly, their complexities make them difficult to fabricate in low-resource settings by the end-user themselves. The application of magnetic particles such as silica-coated iron oxide beads for nucleic acid extraction is relatively instrument-free, rapid, user-friendly, and amenable to automation. But, they rely on hazardous chaotropic salt chemistry and ethanol desalting that could limit their efficacy for downstream NAATs. Recent advances in several types of novel material (e.g., polyamine) coated magnetic bead-based chaotropic salt-free extraction methods offer a possible solution to this problem. However, these materials also involve multistep synthesis impermissible in limited-resource settings. To offer a possible instrument-free magnetic particle-based nucleic acid extraction doable at limited-resource settings, we investigated the nucleic acid capture ability of two chitosan-coated magnetic particles that are preparable by minimally trained personnel using only a water bath and a magnetic stirrer within 6-8 h. We quantitatively probed the efficiency of the passive (without any electrical shaking or vortex-aided) DNA magnetocapture (i.e., binding to chitosan magnetic particles, physical separation from its sample of origin, and release from the particles) using UV260. To explore their suitability towards clinically relevant sensitive downstream NAATs, 100-1000 copies (i.e., in the order of zeptomole) of Escherichia coli (E. coli) or human genomic DNA from aqueous solution, crude cell lysate, and fetal bovine serum were extracted by them and then successfully detected using quantitative real-time loop-mediated isothermal amplification (LAMP) or real-time polymerase chain reaction (PCR). Alongside, their suitability with gel-based LAMP, colorimetric LAMP, and in situ (on beads) LAMP was also probed. The required optimization of the amplification methods has been discussed. Overall, the turnaround time for the magnetocapture combined with NAAT was 1.5-2 h and is thus expected to aid in rapid clinical decision making. With the ease of preparation, reproducibility, and compatibility with downstream NAATs, we anticipate that these magnetic particles would facilitate the expansion and decentralization of nucleic acid-based diagnosis for limited-resource settings.

Role of direct antiglobulin test in anemia under evaluation: Its prevalence, laboratory workup, and significance in further patient management-a study from eastern India.

INTRODUCTION AND AIMS: The direct antiglobulin test (DAT) is an important diagnostic tool for immune hemolytic anemia (IHA). The present study was primarily aimed to identify the prevalence of DAT positivity in anemia patients along with its specificity . A three months follow up of the DAT positive patients were performed for the response during course of illness in terms of transfusion requirement, hemoglobin level, persistence of DAT. MATERIALS AND METHODS: This cross sectional study was performed at a government medical college on symptomatic anemia patients. At initial evaluation, complete blood count (CBC), blood grouping and DAT were performed in the EDTA blood. DAT positive blood samples were analyzed for their immunoglobulin specificity, auto or alloantibody type. Acid elution and red cell phenotyping were performed wherever applicable. Their clinical presentation, hematological and biochemical parameters of hemolysis were evaluated. Statistical analysis was performed on the results on SPSS (Version 23.0;.USA) and Graph pad Prism version 9. P value <0.05 was considered significant. RESULTS: DAT was present in 64 out of 501 patients with male female ratio 1: 4. Warm AIHA (WAIHA) was 93.7% with secondary WAIHA 60%. IgG was associated in 86% DAT positive samples, Only C3d was 14%. All the 4 cold AIHA (6.3%) had a higher antibody titre and thermal amplitude.DAT strength was directly proportional to the degree of hemolysis. During 3 months follow up, persistence of DAT and blood transfusion requirement was more in secondary WAIHA . Hemoglobin increment was more in primary WAIHA (75%). CONCLUSION: DAT played a significant role in the diagnosis as well as evaluation of AIHA.

Gastric volvulus through morgagni hernia: an easily overlooked emergency.

BACKGROUND: Intractable vomiting in an elderly patient is an emergency condition requiring prompt diagnosis and intervention. Acute gastric outlet obstruction due to gastric volvulus through Morgagni-type diaphragmatic hernia is an exceedingly rare cause of this nonspecific complaint. OBJECTIVE: Our aim was to highlight that Morgagni hernia, although rare in adults, should be suspected in the appropriate clinical setting, and that a clue toward diagnosis often comes from routine chest and abdominal x-ray studies. In addition, we emphasize the atypical radiological findings and importance of emergency surgical intervention in such a case. CASE REPORT: We describe the case of a 78-year-old woman who presented to the Emergency Department with a 4-day history of intractable vomiting, and with no definitive clue to the diagnosis on examination. Her routine chest and abdomen x-ray studies suggested abnormal air-fluid level at right hemithorax, which prompted a computed tomography (CT) scan of the abdomen and an upper gastrointestinal contrast study. Gastric volvulus through a foramen of Morgagni was diagnosed and transthoracic reduction of the contents was performed, along with repair of the defect. CONCLUSIONS: A symptomatic Morgagni hernia in adults, although rare, can present with a variety of symptoms ranging from nonspecific complaints of bloating and indigestion to the more severe complaint of intestinal obstruction. Gastric volvulus and obstructive features are less frequently reported as acute complications of these hernias, which need early identification and intervention.

Evaluation of indirect sequence-specific magneto-extraction-aided LAMP for fluorescence and electrochemical SARS-CoV-2 nucleic acid detection.

Nucleic acid amplification tests (NAATs) such as quantitative real-time reverse transcriptase PCR (qRT-PCR) or isothermal NAATs (iNAATs) such as loop-mediated isothermal amplification (LAMP) require pure nucleic acid free of any polymerase inhibitors as its substrate. This in turn, warrants the use of spin-column mediated extraction with centralized high-speed centrifuges. Additionally, the utilization of centralized real-time fluorescence readout and TaqMan-like molecular probes in qRT-PCR and real-time LAMP add cost and restrict their deployment. To circumvent these disadvantages, we report a novel sample-to-answer workflow comprising an indirect sequence-specific magneto-extraction (also referred to as magnetocapture, magneto-preconcentration, or magneto-enrichment) for detecting SARS-CoV-2 nucleic acid. It was followed by in situ fluorescence or electrochemical LAMP. After in silico validation of the approach's sequence selectivity against SARS-CoV-2 variants of concern, the comparative performance of indirect and direct magnetocapture in detecting SARS-CoV-2 nucleic acid in the presence of excess host nucleic acid or serum was probed. After proven superior, the sensitivity of the indirect sequence-specific magnetocapture in conjunction with electrochemical LAMP was investigated. In each case, its sensitivity was assessed through the detection of clinically relevant 102 and 103 copies of target nucleic acid. Overall, a highly specific nucleic acid detection method was established that can be accommodated for either centralized real-time SYBR-based fluorescence LAMP or portable electrochemical LAMP.

CardioSim: a PC-based cardiac signal simulator using segmental modeling of electrocardiogram.

Background: ECG modeling has wide application in signal representation, compression and synthetic ECG generation. Method: CardioSim generates synthetic ECG waveform in real-time using PC-based system. It provides dual facility of interface-based visualization with hardware-based waveform generation. It has two stages viz., development of reference model parameter database using Fourier model and generation of synthetic ECG waveform based on user defined parameters using normal and abnormal records (H, APC, PVC, LBBB, RBBB, P) from mitdb under PhysioNet. Result: It generates ten various ECG waveforms including one healthy and nine diseased rhythms from a single dynamic model with flexible user defined parameters. It gives higher reconstruction performance in terms of SNR and MSE. The mean SNR for different beat morphology is 89.2(H), 88.37(V), 86.32(A), 85.35(L), 97.22(P) and 83.3(R) and mean MSE is 2.45 × 10-6(H), 3.14 × 10-6(V), 8.98 × 10-6(A), 5.82 × 10-6(L), 0.43 × 10-6(P) and 0.25 × 10-6(R). Conclusion: It improves the performance parameters over published research work on ECG modeling and simulation. It can be used as a self-learning tool for entry level medical students.

Clinical performance validation of the STANDARD G6PD test: A multi-country pooled analysis.

INTRODUCTION: Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency. METHODS AND FINDINGS: Data from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with <30% activity and 77% (95% CI 66.8%-85.4%) for females with intermediate activity between 30%-70%. Specificity was 98.1% (95% CI 97.6%-98.5%) and 92.8% (95% CI 91.6%-93.9%) for G6PD deficient individuals and intermediate females, respectively. Out of 20 G6PD intermediate females with false normal results, 12 had activity levels >60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test. CONCLUSIONS: The STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

Deep phenotyping and genomic data from a nationally representative study on dementia in India.

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.

Post COVID sequelae among COVID-19 survivors: insights from the Indian National Clinical Registry for COVID-19.

INTRODUCTION: The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities. METHODS: Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020-October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting. RESULTS: Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30-60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6-7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03). CONCLUSION: Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality.

Evaluation of depression and coping skill among HIV-positive people in Kolkata, India.

The objectives of the present study were to evaluate depressive symptoms and coping strategy among HIV-positive women and men. This cross-sectional study was done among 164 newly diagnosed HIV-positive people through a structured questionnaire. Beck Depression Inventory (BDI) scale was used to measure depression. A 16-items coping scale, Coping with AIDS - Fleishman (CWAF) Instrument, was used to assess coping strategy. χ(2) test was used to compare proportions. Men had significantly higher mean BDI somatic score. Odds for being depressed were 3.6 times higher among men (P value .001, 95% C.I. 1.64-8.07). Analysis of the coping strategies showed that women had better coping skill. Significant correlation was observed between BDI score and emotion-focused coping score (correlation coefficient -0.258, P value .01). HIV-positive men had more depression. Gender-sensitive strategies needed to provide better care for them.

Utilization of therapeutic intervention to prevent mother to child transmission of HIV in a teaching hospital in Kolkata, India.

AIM: To assess the uptake of an HIV screening program and therapeutic intervention to minimize the risk of mother to child transmission. METHODS: This was a cross-sectional, observational study with retrospective data obtained from patient medical records. Pregnant women presenting to a tertiary care center in Kolkata, India, from 1 January 2004 - 31 December 2007 underwent HIV serology by rapid test after receiving group counseling. Care was administered using a standard national protocol by a multi-disciplinary team of health-care personnel. Main outcome measures were: acceptance of pretest counseling and HIV testing by pregnant women attending antenatal clinic services, post-test counseling rate, coverage rate of nevirapine to mother-child pairs, and averted HIV infection in children. RESULTS: Of the 52 127 new antenatal booking visits, 49 580 (95.11%) women attended pretest counseling and 47 506 (91.13%) women accepted HIV testing. Eighty-six women were found to be seropositive. The seroprevalence rate of HIV infection was 0.17%. Thirty-seven mothers (88%) and all newborn infants (100%) had received nevirapine prophylaxis. Overall nevirapine coverage rate was 48%. Twenty-four of the mother-infant pairs that we assessed had infants who were aged over 18 months by June 2008. Eleven (45.83%) of these women turned up with their babies for a blood test at 18 months. Three (27.27%) babies tested reactive. CONCLUSION: As uptake of testing is high and detection of HIV-infected women in pregnancy remains very low, a radical rethinking of policies on therapeutic intervention and their implementation now needs to be undertaken.

Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity.

Management of severe malaria remains a critical global challenge. In this study, using a multiplexed quantitative proteomics pipeline we systematically investigated the plasma proteome alterations in non-severe and severe malaria patients. We identified a few parasite proteins in severe malaria patients, which could be promising from a diagnostic perspective. Further, from host proteome analysis we observed substantial modulations in many crucial physiological pathways, including lipid metabolism, cytokine signaling, complement, and coagulation cascades in severe malaria. We propose that severe manifestations of malaria are possibly underpinned by modulations of the host physiology and defense machinery, which is evidently reflected in the plasma proteome alterations. Importantly, we identified multiple blood markers that can effectively define different complications of severe falciparum malaria, including cerebral syndromes and severe anemia. The ability of our identified blood markers to distinguish different severe complications of malaria may aid in developing new clinical tests for monitoring malaria severity.

Development of a scale for attitude toward condom use for migrant workers in India.

BACKGROUND: The propaganda for the use of condoms remains one of the mainstay for prevention of human immunodeficiency virus (HIV) transmission. In spite of the proven efficacy of condom, some moral, social and psychological obstacles are still prevalent, hindering the use of condoms. AIMS: The study tried to construct a short condom-attitude scale for use among the migrant workers, a major bridge population in India. SETTINGS AND DESIGN: The study was conducted among the male migrant workers who were 18-49 years old, sexually active and had heard about condoms and were engaged in nonformal jobs. We recruited 234 and 280 candidates for Phase 1 and Phase 2 respectively. MATERIALS AND METHODS: Ten items from the original 40-item Brown's ATC (attitude towards condom) scale were selected in Phase 1. After analysis of Phase 1 results, using principal component analysis six items were found appropriate for measuring attitude towards condom use. These six items were then administered in another group in Phase 2. Utilizing Pearson's correlations, scale items were examined in terms of their mean response scores and the correlation matrix between items. Cornbach's alpha and construct validity were also assessed for the entire sample. RESULTS: Study subjects were categorized as condom users and nonusers. The scale structure was explored by analyzing response scores with respect to the items, using principal component analysis followed by varimax rotation analysis. Principal component analysis revealed that the first factor accounted for 71% of the variance, with eigenvalue greater than one. Eigenvalues of the second factor was less than one. Application of screen test suggests only one factor was dominant. Mean score of six items among condom users was 20.45 and that among nonusers was 16.67, which was statistically significant (P<0.01). Cornbach's alpha coefficient was 0.92. CONCLUSION: This tailor-made attitude-toward-condom-use scale, targeted for most vulnerable people in India, can be included in any rapid survey for assessing the existing beliefs and attitudes toward condoms and also for evaluating efficacy of an intervention program.

A Proteogenomic Analysis of Haptoglobin in Malaria.

SCOPE: Haptoglobin (Hp), an acute phase inflammatory protein is associated with malaria pathogenesis in several proteomics and genomics studies. The Hp gene has two co-dominant alleles: Hp1 and Hp2 that produce three genotypes: Hp1/Hp1, Hp1/Hp2 and Hp2/Hp2. EXPERIMENTAL DESIGN: In this study, validation of the proteomics data with Multiple Reaction Monitoring Mass Spectroscopy (MRM-MS) is performed and the association of the Hp gene variants with severe, non-severe malaria and community (healthy) controls using genotyping PCRs and DNA sequencing is analysed. RESULTS: Highly significant values of Hp is observed in the MRM assay that show a correlation with severity of malaria and is clearly distinguished from another febrile disease, dengue. Moreover, the Hp2/Hp2 genotype is seen in high percentages in non-severe malaria patients (74%) and community controls (72%) whereas patients diagnosed with severe malaria show only (31%) of this genotype. Sequencing of the Hp promoter region reveals three SNPs along with 10 unique haplotypes, out of which five are associated with non-severe and three with severe malaria populations (χ2  = 130; df = 18; p < 0.0001). CONCLUSION AND CLINICAL RELEVANCE: This proteo-genomic study focuses on the correlation of the Hp protein and gene with malaria, thus highlighting the pivotal role of this acute phase immune gene in malaria pathogenesis.

Risk of HIV infection but not other sexually transmitted diseases is lower among homeless Muslim men in Kolkata.

OBJECTIVE: To compare the risk of HIV and sexually transmitted diseases (STD) among homeless Muslim (circumcised) and Hindu (uncircumcised) men in Kolkata, India. BACKGROUND: Many observational studies and clinical trials in Africa have demonstrated that male circumcision provides protection against HIV acquisition, but there are sparse data on circumcision and HIV in India, which has the largest number of HIV cases in the world. METHODS: Using a two-stage probability proportionate to size cluster design among homeless men aged 18-49 years in Kolkata, India, data were obtained on religion, behavioral risk factors, and HIV/STD prevalence, by administering an anonymous questionnaire. Rapid HIV tests and testing for syphilis were performed on blood, and urine samples were obtained to test for gonorrhea. RESULTS: The odds ratio for HIV among Muslims (circumcised) compared to Hindus (uncircumcised) was 0.43 (95% confidence interval 0.29-0.67). Despite Muslims having more partners and visits to commercial sex workers, the rates of syphilis and gonorrhea were similar. The results suggest that a biological effect of circumcision protects against HIV infection. CONCLUSION: The beneficial effect of circumcision should be communicated to high-risk groups, as well as to the general population.

Clinical Proteomics and Cytokine Profiling for Dengue Fever Disease Severity Biomarkers.

Dengue fever (DF) is a major global health burden with a pathophysiology that is still incompletely understood. Biomarkers that predict and explain susceptibility to DF and its progression to its more severe hemorrhagic form are much needed. DF is endemic in tropical and subtropical regions of the world, with a rapidly increasing incidence of disease severity. We conducted a clinical biomarker discovery study using both a case-control and longitudinal study design. Plasma proteome alterations in patients with DF (n = 12) and dengue hemorrhagic fever (DHF, n = 24) were analyzed in comparison to healthy controls (HCs, n = 16), using the isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics methodology (false discovery rate of 1%, ≥2 peptides). Several proteins such as the alpha-2 macroglobulin, angiotensinogen, apolipoprotein B-100, serotransferrin, and ceruloplasmin were upregulated (fold change >1.2) in all DHF cases, and downregulated in DF (fold change <0.83), compared with HCs. Plasma cytokine profiling (8 DF, 8 DHF, and 8 HC) on two consecutive time points, at day 0 (day of admission) and days 5-7, found significant elevation in IL-1RA, IL-7, TNF-α, MCP1-MCAF, and MIP-1ß levels, but only in the DHF cases, which is the severe disease, and not in DF, compared with HCs (p < 0.05). These new observations on changes in the plasma proteome and cytokine profiles in patients with dengue infection identify several putative molecular leads for future biomarker development and precision medicine in relation to forecasting DF disease severity.

Enteric Parasitic Infection Among Antiretroviral Therapy Naïve HIV-Seropositive People: Infection Begets Infection-Experience from Eastern India.

CONTEXT: Parasitic opportunistic infections (POIs) frequently occur in HIV/AIDS patients and affect the quality of life. AIMS: This study assessing the standard organisms in the stool of HIV-positive patients, their comparison with HIV-negative controls, their relation with various factors, is the first of its kind in the eastern part of India. SETTINGS AND DESIGN: hospital-based case-control study. MATERIALS AND METHODS: A total of 194 antiretroviral therapy naïve HIV-positive patients (18-60 years) were taken as cases and 98 age- and sex-matched HIV-negative family members as controls. Demographical, clinical, biochemical, and microbiological parameters were studied. STATISTICAL ANALYSIS USED: Odds ratio, 95% confidence interval, and P (< 0.05 is to be significant) were calculated using Epi Info 7 software. RESULTS: POI was significantly higher among HIV-seropositive cases (61.86%) (P < 0.001). Cryptosporidium was the most common POI in HIV-seropositive patients overall and without diarrhea; Entameba was the most common POI in patients with acute diarrhea, and Isospora was the most common POI in the patients having chronic diarrhea. Entameba was the most common POI in CD4 count <350 cells/µl while for CD4 count >350 cells/µl Cryptosporidium was the most common POI. Mean CD4 count was significantly (P < 0.001) lower among people having multiple infections. Male sex, hemoglobin <10 g/dl, WHO Clinical Stage 3 or 4, tuberculosis, absolute eosinophil count of more than 540/dl, CD4 count <350 cells/µl, and seroconcordance of spouses were significantly associated with HIV-seropositive cases having POI (P < 0.05). CONCLUSIONS: Physicians should advise HIV-infected patients to undergo routine evaluation for POI, and provision of chemoprophylaxis should be made in appropriate settings.

Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.

In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.