Ultrasensitive and Robust Point-of-Care Immunoassay for the Detection of Plasmodium falciparum Malaria.

Plasmodium falciparum malaria is widespread in the tropical and subtropical regions of the world. There is ongoing effort to eliminate malaria from endemic regions, and sensitive point-of-care (POC) diagnostic tests are required to support this effort. However, current POC tests are not sufficiently sensitive to detect P. falciparum in asymptomatic individuals. After extensive optimization, we have developed a highly sensitive and robust POC test for the detection of P. falciparum infection. The test is based on upconverting nanophosphor-based lateral flow (UCNP-LF) immunoassay. The developed UCNP-LF test was validated using whole blood reference panels containing samples at different parasite densities covering eight strains of P. falciparum from different geographical areas. The limit of detection was compared to a WHO-prequalified rapid diagnostic test (RDT). The UCNP-LF achieved a detection limit of 0.2-2 parasites/μL, depending on the strain, which is 50- to 250-fold improvement in analytical sensitivity over the conventional RDTs. The developed UCNP-LF is highly stable even at 40 °C for at least 5 months. The extensively optimized UCNP-LF assay is as simple as the conventional malaria RDTs and requires 5 μL of whole blood as sample. Results can be read after 20 min from sample addition, with a simple photoluminescence reader. In the absence of a reader device at the testing site, the strips after running the test can be transported and read at a central location with access to a reader. We have found that the test and control line signals are stable for at least 10 months after running the test. The UCNP-LF has potential for diagnostic testing of both symptomatic and asymptomatic individuals

Ultrasensitive and Robust Point-of-Care Immunoassay for the Detection of Plasmodium falciparum Malaria

Plasmodium falciparum malaria is widespread in the tropical and subtropical regions of the world. There is ongoing effort to eliminate malaria from endemic regions, and sensitive point-of-care (POC) diagnostic tests are required to support this effort. However, current POC tests are not sufficiently sensitive to detect P. falciparum in asymptomatic individuals. After extensive optimization, we have developed a highly sensitive and robust POC test for the detection of P. falciparum infection. The test is based on upconverting nanophosphor-based lateral flow (UCNP-LF) immunoassay. The developed UCNP-LF test was validated using whole blood reference panels containing samples at different parasite densities covering eight strains of P. falciparum from different geographical areas. The limit of detection was compared to a WHO-prequalified rapid diagnostic test (RDT). The UCNP-LF achieved a detection limit of 0.2-2 parasites/μL, depending on the strain, which is 50- to 250-fold improvement in analytical sensitivity over the conventional RDTs. The developed UCNP-LF is highly stable even at 40 °C for at least 5 months. The extensively optimized UCNP-LF assay is as simple as the conventional malaria RDTs and requires 5 μL of whole blood as sample. Results can be read after 20 min from sample addition, with a simple photoluminescence reader. In the absence of a reader device at the testing site, the strips after running the test can be transported and read at a central location with access to a reader. We have found that the test and control line signals are stable for at least 10 months after running the test. The UCNP-LF has potential for diagnostic testing of both symptomatic and asymptomatic individuals. </p

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Geography and prevalence of rickettsial infections in Northern Tamil Nadu, India: a cross-sectional study

Abstract Rickettsial infections and Q fever are a common cause of acute febrile illness globally. Data on the role of climate and altitude on the prevalence of these infections in lacking from Southern India. In this study, we determined the sero-prevalence of scrub typhus (ST), spotted fever (SF), murine typhus (MT) and Q Fever (QF) in 8 eight geographical regions of North Tamil Nadu by detecting IgG antibodies using ELISA. Totally we tested 2565 people from 86 localities. Among the 27.3% positives, approximately 5% were IgG positive for two or more infections. Sero-prevalence to rickettsioses and Q fever was highest for individuals from rural areas and increased with age (> 30 years). Those in the Nilgiris highlands (wetter and cooler) and Erode, which has the most land under irrigation, demonstrated the least exposure to rickettsioses and Q fever. Lowland plains (AOR: 8.4–22.9; 95% CI 3.1–55.3) and highland areas up to 1000 m (AOR: 6.1–10.3; 95% CI 2.4–23.9) showed the highest risk of exposure to scrub typhus. For spotted fever, the risk of exposure was highest in Jawadhi (AOR:10.8; 95% CI 2.6–44.3) and Kalrayan (AOR:16.6; 95% CI 4.1–66.2). Q fever positivity was most likely to be encountered in Salem (AOR: 5.60; 95% CI 1.01–31.08) and Kalrayan hills (AOR:12.3; 95% CI 2.9–51.6). Murine typhus risk was significant only in Tiruvannamalai (AOR:24.2; 95% CI 3.3–178.6). Our study suggests that prevalence of rickettsial infections and Q fever is low in areas which receive rainfall of ≥ 150 cm/year, with average minimum and maximum temperatures between 15 and 25 °C and elevation in excess of 2000 m. It is also less in well irrigated lowlands with dry climate. These preliminary findings need confirmation by active surveillance in these areas

Emerging trends of antimicrobial susceptibility and resistance in burn patients

Background: Burn wound infection is a dynamic entity that is one of the major determining factors of the patient’s hospital stay, mortality and morbidity. The analysis of the changing trends in the burn wounds microbiological profile will help deciding a more effective empirical therapy for burn wound infection. Objectives: To identify the changing trends of the organisms cultured from the burn wounds during the time of admission, and over a period of last 5 years in the burn unit and their antibiotic susceptibility profile. Methodology: Analysis of the burn wound culture sensitivity results sent to the microbiology lab on weekly basis and interpretation of the results. Results: The gram-positive organisms have become more common in 2017 in the first week of burn admission as compared to previous years. From the second week onwards the gram-negative organisms are the more prevalent organisms. Non-fermenting gram-negative bacilli, Pseudomonas aeruginosa and Staphylococci are the most commonly seen organisms. The patients with a rapid progression of sepsis with burn wound infected with Pseudomonas and non-fermenting gram-negative bacilli will benefit from starting of Colistin at an early stage. Similarly, those with Staphylococci growing in the burn wounds can benefit from Linezolid, Chloramphenicol. Keywords: Burn, Infection, Changing trends, Sensitivity, Resistanc

Polymerase Spiral Reaction (PSR) as a point-of-care diagnostic assay: A systematic review

The current systematic review aimed to collect and analyze the comprehensive evidence regarding Polymerase Spiral Reaction (PSR) and to estimate its diagnostic performance and usefulness as a point-of-care (PoC) assay. Literature was retrieved systematically from 2015 to 2023 from PubMed and Scopus. Studies were screened and selected against pre-determined inclusion and exclusion criteria. Quality assessment and risk of bias were critiqued using QUADAS-2. A systematic, qualitative narrative synthesis was employed to synthesize the data.  11 studies were selected for the systematic review, testing diseases in humans utilizing PSR. Only 2 studies clinically validated the test with a sample size > 150. 5 studies were of poor quality; 3 studies were of moderate quality and 3 studies were deemed to be of high quality. 3 studies quantified the diagnostic throughput and reported clinical sensitivity and specificity of PSR approaching to be > 92% and ~ 100%, respectively. Polymerase spiral reaction promises to be an optimistic isothermal assay; however, a huge research gap can be attributed to the lack of statistical and clinical evidence to validate the assay. Adequate research, focused on optimization, coupled with statistical and clinical validation, can help in estimating its true diagnostic potential and applicability. A detailed protocol of this review is registered and available in Prospero (registration number CRD42023406265).</p