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

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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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)

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

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

A Rapid Assessment Scorecard to Identify Informal Settlements at Higher Maternal and Child Health Risk in Mumbai

The communities who live in urban informal settlements are diverse, as are their environmental conditions. Characteristics include inadequate access to safe water and sanitation, poor quality of housing, overcrowding, and insecure residential status. Interventions to improve health should be equity-driven and target those at higher risk, but it is not clear how to prioritise informal settlements for health action. In implementing a maternal and child health programme in Mumbai, India, we had conducted a detailed vulnerability assessment which, though important, was time-consuming and may have included collection of redundant information. Subsequent data collection allowed us to examine three issues: whether community environmental characteristics were associated with maternal and newborn healthcare and outcomes; whether it was possible to develop a triage scorecard to rank the health vulnerability of informal settlements based on a few rapidly observable characteristics; and whether the scorecard might be useful for future prioritisation. The City Initiative for Newborn Health documented births in 48 urban slum areas over 2 years. Information was collected on maternal and newborn care and mortality, and also on household and community environment. We selected three outcomes—less than three antenatal care visits, home delivery, and neonatal mortality—and used logistic regression and classification and regression tree analysis to test their association with rapidly observable environmental characteristics. We developed a simple triage scorecard and tested its utility as a means of assessing maternal and newborn health risk. In analyses on a sample of 10,754 births, we found associations of health vulnerability with inadequate access to water, toilets, and electricity; non-durable housing; hazardous location; and rental tenancy. A simple scorecard based on these had limited sensitivity and positive predictive value, but relatively high specificity and negative predictive value. The scorecard needs further testing in a range of urban contexts, but we intend to use it to identify informal settlements in particular need of family health interventions in a subsequent program

Measuring people's views on health system performance: design and development of the People's Voice Survey

Todd Lewis and co-authors discuss development and use of the People's Voice Survey for health system assessment

Cluster-randomised controlled trial of community mobilisation in Mumbai slums to improve care during pregnancy, delivery, postpartum and for the newborn

Background: The United Nations Millennium Development Goals look to substantial improvements in child and maternal survival. Morbidity and mortality during pregnancy, delivery and the postnatal period are prime obstacles to achieving these goals. Given the increasing importance of urban health to global prospects, Mumbai's City Initiative for Newborn Health aims to improve maternal and neonatal health in vulnerable urban slum communities, through a combination of health service quality improvement and community participation. The protocol describes a trial of community intervention aimed at improving prevention, care seeking and outcomes.Objective: To test an intervention that supports local women as facilitators in mobilising communities for better health care. Community women's groups will build an understanding of their potential to improve maternal and infant health, and develop and implement strategies to do so.Design: Cluster-randomized controlled trial.Methods: The intervention will employ local community-based female facilitators to convene groups and help them to explore maternal and neonatal health issues. Groups will meet fortnightly through a seven-phase process of sharing experiences, discussion of the issues raised, discovery of potential community strengths, building of a vision for action, design and implementation of community strategies, and evaluation.The unit of allocation will be an urban slum cluster of 1000-1500 households. 48 clusters have been randomly selected after stratification by ward. 24 clusters have been randomly allocated to receive the community intervention. 24 clusters will act as control groups, but will benefit from health service quality improvement. Indicators of effect will be measured through a surveillance system implemented by the project. Key distal outcome indicators will be neonatal mortality and maternal and neonatal morbidity. Key proximate outcome indicators will be home care practices, uptake of antenatal, delivery and postnatal care, and care for maternal and neonatal illness.Data will be collected through a vital registration system for births and deaths in the 48 study clusters. Structured interviews with families will be conducted at about 6 weeks after index deliveries. We will also collect both quantitative and qualitative data to support a process evaluation.Trial registration: Current controlled trials ISRCTN9625679