HLA-B∗57 and Gender Influence the Occurrence of Tuberculosis in HIV Infected People of South India

Background. Substantial evidence exists for HLA and other host genetic factors being determinants of susceptibility or resistance to infectious diseases. However, very little information is available on the role of host genetic factors in HIV-TB coinfection. Hence, a longitudinal study was undertaken to investigate HLA associations in a cohort of HIV seropositive individuals with and without TB in Bangalore, South India. Methods. A cohort of 238 HIV seropositive subjects were typed for HLA-A, B, and DR by PCR-SSP and followed up for 5 years or till manifestation of Tuberculosis. HLA data of 682 HIV Negative healthy renal donors was used as control. Results. The ratio of males and females in HIV cohort was comparable (50.4% and 49.6%). But the incidence of TB was markedly lower in females (12.6%,) than males (25.6%). Further, HLA-B*57 frequency in HIV cohort was significantly higher among females without TB (21.6%, 19/88) than males (1.7%, 1/59); P = 0.0046; OR = 38. CD4 counts also were higher among females in this cohort. Conclusion. This study suggests that HIV positive women with HLA-B*57 have less occurrence of TB as compared to males

HLA-B * 57 and Gender Influence the Occurrence of Tuberculosis in HIV Infected People of South India

Background. Substantial evidence exists for HLA and other host genetic factors being determinants of susceptibility or resistance to infectious diseases. However, very little information is available on the role of host genetic factors in HIV-TB coinfection. Hence, a longitudinal study was undertaken to investigate HLA associations in a cohort of HIV seropositive individuals with and without TB in Bangalore, South India. Methods. A cohort of 238 HIV seropositive subjects were typed for HLA-A, B, and DR by PCR-SSP and followed up for 5 years or till manifestation of Tuberculosis. HLA data of 682 HIV Negative healthy renal donors was used as control. Results. The ratio of males and females in HIV cohort was comparable (50.4% and 49.6%). But the incidence of TB was markedly lower in females (12.6%,) than males (25.6%). Further, HLA-B * 57 frequency in HIV cohort was significantly higher among females without TB (21.6%, 19/88) than males (1.7%, 1/59); P = 0.0046; OR = 38. CD4 counts also were higher among females in this cohort. Conclusion. This study suggests that HIV positive women with HLA-B * 57 have less occurrence of TB as compared to males

Common, Intermediate and Well-Documented HLA Alleles in World Populations: CIWD Version 3.0.0

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A study of centralized individual donor nucleic acid testing for transfusion transmitted infections to improve blood safety in Karnataka, India

Introduction: Karnataka state has a total of 176 blood banks, with a total collection of around 650,000 units annually. From January 2014, all units under the Department of Health and Family Welfare services are tested at NAT Lab established at the Central facility and from September 2014, standalone Regional Blood Transfusion Centre was included in the State Government project. Aim and Objective: The aim of the study is to analyze the nucleic acid testing (NAT) for our donor population and demonstrate consolidation of blood transfusion service through a centralized testing center for NAT and also to assess safety benefits of implementing individual donor NAT (IDNAT). Materials and Methods: We collect nearly 40,000 units annually from voluntary donors with 30% repeat donations. The donors undergo strict predonation counseling, donor questionnaire, and medical examination. The units collected are tested for human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) by ECI using VItros 3600. All the units are tested by NAT at Central NAT Lab, screened by Procleix® Panther System by Grifols. Results: From September 2014 to March 2016, total 50,903 samples tested for NAT. Of 50,903 samples, 588 samples (1.15%) were reactive by Chemiluminescence including 265 for HBV, 188 for HCV, and 135 for HIV. Total NAT reactive samples were 254, out of this 11 reactive for HIV-1 (0.02%), 2 reactive for HCV (0.003%), 235 (0.46%) reactive for HBV. There was one HIV and 10 HBV infection cases that were not detected by serology but reactive by NAT. The yield detected is 0.021% or one in 5000. Conclusion: The IDNAT project has helped in preventing window period infections thus reducing the treatment cost and burden on healthcare. It has added benefits in blood safety and should be considered along with the basic quality assured blood transfusion system such as volunteer base for blood donation, provision of donor self-deferral, donor notification, and quality assured sensitive serological methods

Luminex-Based Donor-Specific antibody crossmatching for renal transplant: A 3-Year experience in South India

Introduction: Although CDC has been the gold standard for many years, this assay is certainly not perfect and its use is associated with several problems. The Luminex anti-HLA antibody detection assay is reportedly more sensitive and specific. One of the test is Luminex DSA cross match which is more sensitive than CDC cross match. It is also considered cost effective tool to evaluate pre and post renal transplant cases. Material and Methods: We started Luminex based Donor specific antibody Cross Match tests (DSA Xm) with lysate by the end of 2009 along with CDC after standardization. This study is planned to evaluate the results of DSA Xm of last three years & also to observe antibody medicated rejections after renal transplant. Results: Total 3137 Luminex DSA Cross Match tests were done & 515 tests were positive cross match with negative CDC xm result. Out of 515 positive results 164 were positive for class I, 223 were positive for class II and 128 were positive for both class I & II. In the three years total 1129 renal transplants were done at various centers and total 42 cases of Antibody medicated rejections were reported. Out of 42 patients, 36 patients had pre transplant history of CDC negative & Luminex DSA xm positive. Conclusion: We evaluated our three year results of DSA Xm test and found a cost effective, sensitive and useful supplementary test to evaluate pre and post renal transplant cases

Red Blood Cell Alloimmunization in Multi - transfused Patients: A Bicentric Study in India

Background: It is well-known that alloimmunization to red blood cell antigens resulting from the genetic disparities between donor and recipient is one of the risks of blood transfusion. The antibody screening cells are used to detect unexpected antibodies. The risk of alloimmunization is higher in patients who have received multiple blood transfusions such as thalassemia, other hematological disorders, renal failure patients on dialysis who receive blood transfusions, and females with bad obstetric history. Antibody screening test using 2–3 cells panel is not a mandatory pretransfusion testing in India and is performed routinely in limited blood centers. Materials and Methods: This bicentric study has been carried out to look at prevalence of antibodies in multi-transfused patients who have higher risks of alloimmunization such as patients who have received multiple blood transfusions such as thalassemia, other hematological disorders, renal failure patients on dialysis who receive blood transfusions, and females with bad obstetric history in the North as well as South India. The study was conducted at two blood centers, one regional blood transfusion of North India and one at South India. Totally, 4569 cases were analyzed and 258 patients were selected for antibody screening and identification. Results: Of total 4569 patients, 258 multi-transfused patients were studied. Among these, seven patients (2.71%) were found alloimmunized. The risk of alloimmunization was 2.90% in thalassemia, 0% in chronic renal failure patients, 3.77% in pregnant females with bad obstetric history, and 2.78% in other multi-transfused patients like cancer. Discussion: Regular monitoring through antibody screening and transfusion of blood matched for minor erythrocyte antigens are recommended in these patients