Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Impact of antigenic exposures and role of molecular blood grouping in enhancing transfusion safety in chronically transfused thalassemics

Background: Red cell alloimmunization is an acknowledged complication of blood transfusion. Current transfusion practices for thalassemia do not cater to this risk. Serological phenotyping is usually not reliable in these cases unless performed before the first transfusion. Under such circumstances, molecular blood grouping is an effective alternative. Aim: To perform molecular blood group genotyping in chronically transfused thalassemia patients and assess the risk of antigenic exposure and incidence of alloimmunization with current transfusion protocols. Materials and Methods: Molecular blood group genotyping was performed for 47 chronically transfused thalassemia patients. Their 1-year transfusion records were retrieved to assess the antigenic exposure and the frequency thereof. Results: Of 47 patients, 6 were already alloimmunized (3 with anti-E and 3 with anti-K) and were receiving the corresponding antigen negative units. We observed that random selection of ABO and Rh D matched units resulted in 57.7% ±8.26% chance of Rh and Kell phenotype matching also. Forty-four patients had received one or more antigenic exposures at least once. The 6 already alloimmunized patients were further exposed to antigens other than the ones they were immunized to. During the study period, only one patient developed an alloantibody, anti-E with exposure to antigens C (92%) and/or E (32%) at each transfusion. Conclusion: Several factors apart from mere antigen exposure may influence the development of alloimmunization as most of our patients received antigenic exposures but not alloimmunized. Our data provide an impetus for future large-scale studies to understand the development of alloimmunization in such patients

Red cell alloimmunization and infectious marker status (human immunodeficiency virus, hepatitis B virus and hepatitis C virus) in multiply transfused thalassemia patients of North India

Background: Patients with thalassemia major are largely transfusion dependent and are thus exposed to a variety of risks such as transmission of infectious diseases, iron overload and alloimmunization. This study was performed to determine the prevalence of human immune deficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and red cell antibodies among multiple-transfused thalassemic patients in and around the national capital region. Materials and Methods: The Department of Transfusion Medicine, Indraprastha Apollo Hospitals, conducted this study in collaboration with the National Thalassemia Welfare Society over a period of 1 year starting February2011. Blood samples from the patients were tested for blood group, red cell alloantibody/ies, anti-HIV, anti-HCV and hepatitis B surface antigen (HBsAg) by ELISA and for the respective viral ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) by nucleic acid testing (NAT). Results: A total of 462 thalassemics which consists of 290 males and 172 females were tested. The overall alloimmunization rate was 4.1% and anti-Kell was the most common antibody identified. Thirteen cases (2.8%) were positive for HBsAg by ELISA, 107 (23.1%) were reactive for anti HCV and 11 (2.38%) for anti HIV antibodies. Further screening and discriminatory assays by NAT confirmed the presence of HBV DNA in 11 cases, HIV RNA in 7 cases and HCV RNA in 48 cases. Conclusion: In spite of advances in Immunohematology and infectious marker testing in recent years, the rates of alloimmunization and infectious marker positivity remains high among multiply transfused patients like thalassemics. Provision of safe and adequate blood supply to these patients is a key to improving their quality-of-life and longevity

Evaluation of bacterial inactivation in random donor platelets and single-donor apheresis platelets by the INTERCEPT blood system

Background: Blood transfusion of contaminated components is a potential source of sepsis by a wide range of known and unknown pathogens. Collection mechanism and storage conditions of platelets make them vulnerable for bacterial contamination. Several interventions aim to reduce the transfusion of contaminated platelet units; however, data suggest that contaminated platelet transfusion remains very common. Aim: A pathogen inactivation system, “INTERCEPT”, to inactivate bacteria in deliberately contaminated platelet units was implemented and evaluated. Materials and Methods: Five single-donor platelets (SDP) and five random donor platelets (RDP) were prepared after prior consent of donors. Both SDP and RDP units were deliberately contaminated by stable stock ATCC Staphylococcus aureus and Escherichia coli, respectively, with a known concentration of stock culture. Control samples were taken from the infected units and bacterial concentrations were quantified. The units were treated for pathogen inactivation with the INTERCEPT (Cerus Corporation, Concord, CA) Blood system for platelets (Amotosalen/UVA), as per the manufacturer's instructions for use. Post illumination, test samples were analyzed for any bacterial growth. Results: Post-illumination test samples did not result in any bacterial growth. A complete reduction of >6 log10S. aureus in SDP units and >6 log10Escherichia coli in RDP units was achieved. Conclusion: The INTERCEPT system has been shown to be very effective in our study for bacterial inactivation. Implementation of INTERCEPT may be used as a mitigation against any potential bacterial contamination in platelet components

A multivariate analysis to assess the effect of packed red cell transfusion and the unit age of transfused red cells on postoperative complications in patients undergoing cardiac surgeries

Background: Transfusion of blood components and age of transfused packed red cells (PRCs) are independent risk factors for morbidity and mortality in cardiac surgeries. Materials and Methods: We retrospectively examined data of patients undergoing cardiac surgery at our institute from January 1, 2012 to September 30, 2012. Details of transfusion (autologous and allogenic), postoperative length of stay (PLOS), postoperative complications were recorded along with other relevant details. The analysis was done in two stages, in the first both transfused and nontransfused individuals and in the second only transfused individuals were considered. Age of transfused red cells as a cause of morbidity was analyzed only in the second stage. Results: Of the 762 patients included in the study, 613 (80.4%) were males and 149 (19.6%) were females. Multivariate analysis revealed that factors like the number and age of transfused PRCs and age of the patient had significant bearing upon the morbidity. Morbidity was significantly higher in the patients transfused with allogenic PRCs when compared with the patients not receiving any transfusion irrespective of the age of transfused PRCs. Transfusion of PRC of over 21 days was associated with higher postoperative complications, but not with in-hospital mortality. Conclusion: In patients undergoing cardiac surgery, allogenic blood transfusion increases morbidity. The age of PRCs transfused has a significant bearing on morbidity, but not on in-hospital mortality. Blood transfusion services will therefore have to weigh the risks and benefits of providing blood older than 21 days in cardiac surgeries