Defective anticarbohydrate antibody responses to naturally occurring bacteria following bone marrow transplantation

AbstractThe long-term recipients of allogeneic bone marrow transplantation (BMT) are at an increased risk of death due to bacterial infections. We evaluated the anticarbohydrate antibody responses of BMT recipients to a naturally occurring bacterial carbohydrate, polyribose phosphate (PRP). The recipients of autologous BMT achieved protective anti-PRP levels (>100 ng/mL) by 3 years after transplantation, with a pattern consistent with a recapitulation of the ontogeny of anticarbohydrate antibody responses. None of the six recipients of unrelated BMT who were off immunosuppressive therapy had protective anti-PRP levels, though their response to a protein antigen (tetanus toxoid) was normal. Of 48 recipients of histocompatible BMT, 22 (46%) had protective anti-PRP antibody levels, whereas 13 (27%) recipients who were >3 years post-BMT did not have protective levels. Therefore, all unrelated recipients and a significant proportion of histocompatible recipients without clinical graft-vs.-host disease had persistent and prolonged defects in their capacity to produce antibodies to naturally occurring bacterial carbohydrate antigens. These results suggest that allogeneic BMT recipients should be longitudinally evaluated for their anticarbohydrate antibody responses and that patients with defective antibody responses should receive prophylactic antibiotics or replacement immunoglobulin therapy or both to reduce their risk of late bacterial infections.Biol Blood Marrow Transplant 1999;5(1):46-50

Genetic variation in histidine rich proteins among Indian Plasmodium falciparum population: possible cause of variable sensitivity of malaria rapid diagnostic tests

BACKGROUND: Rapid diagnostic tests (RDTs) have revolutionized the diagnosis of malaria. Among the various factors affecting RDTs sensitivity is genetic variation of the antigen used. The genetic variation in PfHRP2 and PfHRP3 proteins was studied among the Indian Plasmodium falciparum isolates. METHODS: One hundred and forty isolates of P. falciparum were collected from six geographical regions of India. Target genes encoding PfHRP2 and PfHRP3 antigens were sequenced to study genetic polymorphism. Minimum detection limit giving a positive rapid diagnostic test was also determined. RESULTS: Extensive variations were observed in amino acid repeat types of PfHRP2 and PfHRP3. PfHRP2 exhibited more polymorphism than PfHRP3. Significant relation was observed between type 2 and type 7 repeats and RDT detection rate as higher number of these repeats showed better sensitivity with RDTs. CONCLUSION: The results provide insights into the genetic diversity of Pfhrp2 and Pfhrp3 genes among Indian P. falciparum population and its relation to RDT sensitivity

Clinical and radiologic features of extraskeletal myxoid chondrosarcoma including initial presentation, local recurrence, and metastases

Background: The aim of the study was to evaluate the clinical and imaging features of extraskeletal myxoid chondrosarcoma (EMC) including initial presentation, recurrence, and metastases. Patients and methods. In this institutional review board-approved retrospective study, imaging features of 13 patients with pathologically proven EMC seen from August 1995 to December 2011 were analyzed. The group included 3 women and 10 men and the mean age was 54 years (range 29–73 years). Imaging studies were evaluated by two radiologists in consensus. Location, size, and imaging features of primary tumors were recorded as well as the presence of recurrent disease and location of metastases. Results: Among 13 patients, 3 died during the timeframe of this study. Nine patients had primary tumor in the lower extremity, and average tumor size was 9.3 cm (range 3.3–18 cm). On MRI, primary tumors were hyperintense on T2, isointense to muscle on T1, and demonstrated peripheral/septal enhancement. Three patients had local recurrence and 12 had metastatic disease, with lung involvement being the most common. Tumor density on contrast enhanced CT ranged from 8.2 to 82.9 Hounsfield unit (HU). FDG-PET/CT imaging was performed in 3 patients. One patient had no FDG avid disease and 2 patients had metastatic disease with standard uptake values (SUV) of 2.8 and 7.4. The patient with intense FDG uptake demonstrated more solid appearing tumor burden and had the shortest survival. Conclusions: EMC is a rare tumor that often occurs in the lower extremities and frequently metastasizes to the lungs. Increased tumor density and increased FDG uptake may be related to more aggressive disease

long term outcomes of pediatric patients with malignant and non malignant disorders receiving α β t cell depleted hla haploidentical hematopoietic stem cell transplantation hsct followed by infusion of bpx 501 t cells donor t cells transduced with ic9

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MOLECULAR DETECTION OF HUMAN RHINOVIRUS IN RESPIRATORY SAMPLES OF SWINE FLU NEGATIVE NORTH INDIAN CHILDREN WITH FLU-LIKE ILLNESS

Objectives: Flu-like illness may also be caused by different respiratory viruses other than influenza. Human rhinovirus (HRV) shows almost flu-likesymptoms. The purpose of this study is the molecular detection of HRV in throat swab of swine flu negative North Indian children during the years2012 and 2013. Reverse transcriptase (RT) - polymerase chain reaction (PCR) amplification of 5'non-coding region (NCR) was used for HRV detectionfollowed by cell culture isolation of HRV.Methods: PCR confirmed swine flu negative throat swab samples were collected from the Department of Microbiology, Sanjay Gandhi Post GraduateInstitute of Medical Sciences, Lucknow, Uttar Pradesh, India. The RNA isolation of samples was done using the QIAampViral RNA Mini Kit (Qiagen),followed by single step RT-PCR amplification (AgPath-ID, Life Technologies). All PCR positive HRV samples were cell cultured in HeLa and HEp-2 celllines for viral isolation.®Results: 135 swine flu negative throat swab samples were examined. Out of which 34 samples (25.2%) were found HRV positive by RT-PCR, while onlyfour samples (11.8%) were culture positive on HeLa cell line. Younger children (0-4 year) were found more susceptible to HRV infection. This studyindicated the highest prevalence of HRV (37.0%) during the months (September-October) of the Autumn season in 2012 and 57% in Winter-springseason (February-March) during 2013.Conclusion: HRV may be a cause of flu-like symptoms in swine flu suspected North Indian children with a higher rate during Autumn and Springseason. Molecular detection of HRV using RT-PCR is more sensitive than cell culture assay.Keywords: Human rhinovirus, Swine flu, Influenza-like illness, Lower respiratory tract infections

Administration of BPX-501 Cells Following Αβ T and B-Cell-Depleted HLA Haploidentical HSCT (haplo-HSCT) in Children with Acute Leukemias (AL)

Background Allogeneic HSCT is a well-established treatment for children with AL. For pts lacking a compatible matched related or unrelated donor, HLA-haplo-HSCT represents an alternative. Promising results were reported with selective depletion of αβ T and B cells (Locatelli, Blood 2017). PX-501 is an allogeneic product consisting of T cells modified to express the inducible caspase-9 (iC9) safety switch and truncated CD19 to allow monitoring and expansion of BPX-501 following transplant. BPX-501 provides broad virus and tumor-specific immunity; the safety switch provides the unique ability to promptly and durably resolve graft-versus-host disease (GvHD) symptoms following the administration of rimiducid. Aims Evaluate the safety and efficacy of BPX-501 in pediatric pts with AL by determining whether BPX-501 infusion can increase efficacy outcomes through an enhanced graft-versus-leukemic (GvL) effect, while maintaining a low risk of GvHD. Methods A subset of pts had high-risk ALs. BPX-501 was planned to be infused on day14±4 after the allograft with no post-transplant GvHD prophylaxis allowed. Pts who developed steroid-resistant GvHD could receive ≥1 dose of rimiducid. Results As of June 30, 2018, 100 pts with AL (described in Table 1) were efficacy evaluable. Median time for neutrophil and platelet engraftment was 16 and 12 days, respectively. Four pts (4.1%) experienced primary graft failure. Of 96 evaluable pts, 5 (3.1%) developed Grade III-IV aGvHD. Of 82 evaluable pts, 12 developed cGvHD (18.1%), with 3 moderate-severe. Rimiducid was administered to 10 pts. Best overall clinical response (CR/PR) post-rimiducid was 80% (8 pts). Among responding patients, 7 (87.5%) had a CR. Six (6.6%) pts died after transplantation. Efficacy outcomes in AL subsets are in Table 2. CD3+ and CD3+CD4+ T cells above 500 cells/ml were achieved by 180 and 270 days, respectively. IgA and IgM levels achieved normal values by 180 days. Conclusion BPX-501 following αβ-T and B-cell depleted haplo-HSCT represents a highly effective transplantation strategy for pediatric pts with AL. Rimiducid was an effective treatment for pts with steroid-resistant GvHD

The path to universal health coverage in five African and Asian countries: examining the association between insurance status and health-care use

Despite major efforts to achieve universal health coverage (UHC), progress has lagged in many African and Asian countries. A key strategy pursued by many countries is the use of health insurance to increase access and affordability. However, evidence on insurance coverage and on the association between insurance and UHC is mixed. We analysed nationally representative cross-sectional data collected between 2022 and 2023 in Ethiopia, Kenya, South Africa, India, and Laos. We described public and private insurance coverage by sociodemographic factors and used logistic regression to examine the associations between insurance status and seven health-care use outcomes. Health insurance coverage ranged from 25% in India to 100% in Laos. The share of private insurance ranged from 1% in Ethiopia to 13% in South Africa. Relative to the population with private insurance, the uninsured population had reduced odds of health-care use (adjusted odds ratio 0·68, 95% CI 0·50–0·94), cardiovascular examinations (0·63, 0·47–0·85), eye and dental examinations (0·54, 0·42–0·70), and ability to get or afford care (0·64, 0·48–0·86); private insurance was not associated with unmet need, mental health care, and cancer screening. Relative to private insurance, public insurance was associated with reduced odds of health-care use (0·60, 0·43–0·82), mental health care (0·50, 0·31–0·80), cardiovascular examinations (0·62, 0·46–0·84), and eye and dental examinations (0·50, 0·38–0·65). Results were highly heterogeneous across countries. Public health insurance appears to be only weakly associated with access to health services in the countries studied. Further research is needed to improve understanding of these associations and to identify the most effective financing strategies to achieve UHC

Population Preferences for Primary Care Models for Hypertension in Karnataka, India

IMPORTANCE Hypertension contributes to more than 1.6 million deaths annually in India, with many individuals being unaware they have the condition or receiving inadequate treatment. Policy initiatives to strengthen disease detection and management through primary care services in India are not currently informed by population preferences. OBJECTIVE To quantify population preferences for attributes of public primary care services for hypertension. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study involved administration of a household survey to a population-based sample of adults with hypertension in the Bengaluru Nagara district (Bengaluru City; urban setting) and the Kolar district (rural setting) in the state of Karnataka, India, from June 22 to July 27, 2021. A discrete choice experiment was designed in which participants selected preferred primary care clinic attributes from hypothetical alternatives. Eligible participants were 30 years or older with a previous diagnosis of hypertension or with measured diastolic blood pressure of 90mmHg or higher or systolic blood pressure of 140mmHg or higher. A total of 1422 of 1927 individuals (73.8%) consented to receive initial screening, and 1150 (80.9%) were eligible for participation, with 1085 (94.3%) of those eligible completing the survey. MAIN OUTCOMES AND MEASURES Relative preference for health care service attributes and preference class derived from respondents selecting a preferred clinic scenario from 8 sets of hypothetical comparisons based on wait time, staff courtesy, clinician type, carefulness of clinical assessment, and availability of free medication. RESULTS Among 1085 adult respondents with hypertension, the mean (SD) age was 54.4 (11.2) years; 573 participants (52.8%) identified as female, and 918 (84.6%) had a previous diagnosis of hypertension. Overall preferences were for careful clinical assessment and consistent availability of free medication; 3 of 5 latent classes prioritized 1 or both of these attributes, accounting for 85.1%of all respondents. However, the largest class (52.4%of respondents) hadweak preferences distributed across all attributes (largest relative utility for careful clinical assessment: β = 0.13; 95%CI, 0.06-0.20; 36.4%preference share). Two small classes had strong preferences; 1 class (5.4%of respondents) prioritized shorter wait time (85.1%preference share; utility, β = -3.04; 95%CI, -4.94 to -1.14); the posterior probability of membership in this class was higher among urban vs rural respondents (mean [SD], 0.09 [0.26] vs 0.02 [0.13]). The other class (9.5%of respondents) prioritized seeing a physician (the term doctor was used in the survey) rather than a nurse (66.2% preference share; utility, β = 4.01; 95%CI, 2.76-5.25); the posterior probability of membership in this class was greater among rural vs urban respondents (mean [SD], 0.17 [0.35] vs 0.02 [0.10]). CONCLUSIONS AND RELEVANCE In this study, stated population preferences suggested that consistent medication availability and quality of clinical assessment should be prioritized in primary care services in Karnataka, India. The heterogeneity observed in population preferences supports considering additional models of care, such as fast-track medication dispensing to reduce wait times in urban settings and physician-led services in rural areas.This study was supported by grant P30AG024409 from the National Institute on Aging of the National Institutes of Health (Program on the Global Demography of Aging, Harvard University) and grant INV-005254 from the Bill & Melinda Gates Foundation (Dr Kruk)

Population confidence in the health system in 15 countries: results from the first round of the People's Voice Survey

Population confidence is essential to a well functioning health system. Using data from the People's Voice Survey—a novel population survey conducted in 15 low-income, middle-income, and high-income countries—we report health system confidence among the general population and analyse its associated factors. Across the 15 countries, fewer than half of respondents were health secure and reported being somewhat or very confident that they could get and afford good-quality care if very sick. Only a quarter of respondents endorsed their current health system, deeming it to work well with no need for major reform. The lowest support was in Peru, the UK, and Greece—countries experiencing substantial health system challenges. Wealthy, more educated, young, and female respondents were less likely to endorse the health system in many countries, portending future challenges for maintaining social solidarity for publicly financed health systems. In pooled analyses, the perceived quality of the public health system and government responsiveness to public input were strongly associated with all confidence measures. These results provide a post-COVID-19 pandemic baseline of public confidence in the health system. The survey should be repeated regularly to inform policy and improve health system accountability