Clinical performance validation of the STANDARD G6PD test: A multi-country pooled analysis.

INTRODUCTION: Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency. METHODS AND FINDINGS: Data from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with <30% activity and 77% (95% CI 66.8%-85.4%) for females with intermediate activity between 30%-70%. Specificity was 98.1% (95% CI 97.6%-98.5%) and 92.8% (95% CI 91.6%-93.9%) for G6PD deficient individuals and intermediate females, respectively. Out of 20 G6PD intermediate females with false normal results, 12 had activity levels >60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test. CONCLUSIONS: The STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol.

The coronavirus disease (COVID-19) pandemic has led to an unprecedented public health crisis. Insufficient testing continues to limit the effectiveness of the global response to the COVID-19 pandemic. Molecular testing methods such as reverse transcriptase polymerase chain reaction (RT-PCR) continue to be highly centralized and are a sub-optimal option for population surveillance. Rapid antigen tests (Ag-RDTs) offer multiple benefits including low costs, high flexibility to conduct tests in a wide variety of settings, and faster return of results. Self-test Ag-RDTs (STs) have gained approval in several markets and offer the possibility to expand testing, reaching at-risk populations. While STs have the potential to assist the COVID-19 response, test result integrity, reporting, and appropriate linkage to care continue to hinder the widespread implementation of self-testing programs. This protocol presents a mixed-methods pragmatic trial (ISRCTN91602092) to better understand the feasibility of self-testing as part of a contact tracing strategy within the Brazilian public health system. Approximately 604 close contacts of 150 index cases testing positive for COVID-19 will be enrolled. Index cases will be randomized for their close contacts to participate in either serial (daily) self-testing over a 10-day follow-up period or a more traditional approach to contact tracing with a professional Ag-RDT at one time point post-exposure. Usability workshops and focus group discussions will also be conducted. This study protocol presents a comprehensive plan to assess the effectiveness, operational feasibility, and stakeholder preferences of a serial self-testing strategy for contact tracing within the Brazilian public health system. Our results will contribute to better understanding of the feasibility of a self-testing strategy within the public sector. Potential risks and limitations are discussed. Our findings will have important implications as governments continue working to mitigate the impact of COVID-19, particularly in the context of where to direct limited resources for testing and healthcare infrastructure. Registration: This trial is registered at ISCTRN (ISRCTN91602092).

Antigen concentration, viral load, and test performance for SARS-CoV-2 in multiple specimen types.

The relationship between N-antigen concentration and viral load within and across different specimens guides the clinical performance of rapid diagnostic tests (RDT) in different uses. A prospective study was conducted in Porto Velho, Brazil, to investigate RDT performance in different specimen types as a function of the correlation between antigen concentration and viral load. The study included 214 close contacts with recent exposures to confirmed cases, aged 12 years and older and with various levels of vaccination. Antigen concentration was measured in nasopharyngeal swab (NPS), anterior nares swab (ANS), and saliva specimens. Reverse transcriptase (RT)-PCR was conducted on the NPS and saliva specimens, and two RDTs were conducted on ANS and one RDT on saliva. Antigen concentration correlated well with viral load when measured in the same specimen type but not across specimen types. Antigen levels were higher in symptomatic cases compared to asymptomatic/oligosymptomatic cases and lower in saliva compared to NPS and ANS samples. Discordant results between the RDTs conducted on ANS and the RT-PCR on NPS were resolved by antigen concentration values. The analytical limit-of-detection of RDTs can be used to predict the performance of the tests in populations for which the antigen concentration is known. The antigen dynamics across different sample types observed in SARS-CoV-2 disease progression support use of RDTs with nasal samples. Given lower antigen concentrations in saliva, rapid testing using saliva is expected to require improved RDT analytical sensitivity to achieve clinical sensitivity similar to rapid testing of nasal samples.

Assessing the Operational Feasibility of Integrating Point-of-Care G6PD Testing into Plasmodium vivax Malaria Management in Vietnam.

Plasmodium vivax cases represent more than 50% of a diminishing malaria case load in Vietnam. Safe and effective radical cure strategies could support malaria elimination by 2030. This study investigated the operational feasibility of introducing point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing into malaria case management practices. A prospective interventional study was conducted at nine district hospitals and commune health stations in Binh Phuoc and Gia Lai provinces in Vietnam over the period of October 2020 to October 2021. The STANDARD™ G6PD Test (SD Biosensor, Seoul, Republic of Korea) was incorporated to inform P. vivax case management. Case management data and patient and health care provider (HCP) perspectives, as well as detailed cost data were collected. The G6PD test results were interpreted correctly by HCP and the treatment algorithm was adhered to for the majority of patients. One HCP consistently ran the test incorrectly, which was identified during the monitoring and resulted in provision of refresher training and updating of training materials and patient retesting. There was wide acceptability of the intervention among patients and HCP albeit with opportunities to improve the counseling materials. Increasing the number of facilities to which the test was deployed and decreases in the malaria cases resulted in higher per patient cost for incorporating G6PD testing into the system. Commodity costs can be reduced by using the 10-unit kits compared to the 25 unit kits, particularly when the case loads are low. These results demonstrate intervention feasibility while also highlighting specific challenges for a country approaching malaria elimination.

Evaluation of a protein-to-creatinine dipstick diagnostic test for proteinuria screening in selected antenatal care clinics in three Districts in the Bono-East Region of Ghana.

BACKGROUND: Preeclampsia and eclampsia contribute significantly to maternal and newborn deaths worldwide. Early and accurate identification of pregnant women at risk can avert these deaths, but the necessary diagnostics are not widely available. A protein and creatinine ratio, rather than a measurement of protein alone, may provide better identification of proteinuria. The objective of this study was to assess the operational and performance characteristics of the LifeAssay Diagnostics (LAD) Test-it™ protein-to-creatinine ratio (PrCr) urinalysis dipstick test in a representative antenatal care setting (ANC). METHODS: Mixed methods were used to assess the operational and performance characteristics of the PrCr test, including a usability study with 25 participants, a prospective cross-sectional diagnostic accuracy study (N = 1483), and a targeted reassessment of discordant frozen samples (N = 200). Several other commonly used proteinuria tests were included for comparison. RESULTS: The test demonstrated improved clinical performance for detection of proteinuria over the current standard-of-care tests widely used in Ghana. The LAD PrCr test showed a sensitivity of 50.7% and specificity of 69.2% when run at the point of care. In contrast, the standard-of-care Accu-Tell® protein dipstick test was found to have a sensitivity of 32.4% and a specificity of 82.2%. The LAD test shows minor improvement over the tests currently used in Ghana to detect proteinuria. CONCLUSIONS: The PrCr test offers the potential for improved detection of proteinuria over the standard-of-care tests used in ANC. However, this test and the others evaluated for this study demonstrate limited performance, particularly among samples with a low level of proteinuria. Additional exploration in other clinical use cases, such as triage among high-risk populations, is warranted. The LAD test can also be considered a transition product, as health systems consider adopting next-generation biomarker tests when more readily available.

Screening for Severe Acute Respiratory Syndrome Coronavirus 2 in Close Contacts of Individuals With Confirmed Infection: Performance and Operational Considerations.

BACKGROUND: Point-of-care and decentralized testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to inform public health responses. Performance evaluations in priority use cases such as contact tracing can highlight trade-offs in test selection and testing strategies. METHODS: A prospective diagnostic accuracy study was conducted among close contacts of coronavirus disease 2019 (COVID-19) cases in Brazil. Two anterior nares swabs (ANS), a nasopharyngeal swab (NPS), and saliva were collected at all visits. Vaccination history and symptoms were assessed. Household contacts were followed longitudinally. Three rapid antigen tests and 1 molecular method were evaluated for usability and performance against reference reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swab specimens. RESULTS: Fifty index cases and 214 contacts (64 household) were enrolled. Sixty-five contacts were RT-PCR positive during ≥1 visit. Vaccination did not influence viral load. Gamma variants were most prevalent; Delta variants emerged increasingly during implementation. The overall sensitivity of evaluated tests ranged from 33% to 76%. Performance was higher among symptomatic cases and those with cycle threshold (Ct) values <34 and lower among oligosymptomatic or asymptomatic cases. Assuming a 24-hour time to results for RT-PCR, the cumulative sensitivity of an anterior nares swab rapid antigen test was >70% and almost 90% after 4 days. CONCLUSIONS: The near-immediate time to results for antigen tests significantly offsets lower analytical sensitivity in settings where RT-PCR results are delayed or unavailable.

Further evidence needed to change policy for the safe and effective radical cure of vivax malaria: Insights from the 2019 annual APMEN Vivax Working Group meeting.

New diagnostics and treatment options for the radical cure of Plasmodium vivax malaria are now available. At the 2019 annual meeting of the Vivax Working Group of the Asia Pacific Malaria Elimination Network, participants took part in a roundtable discussion to identify further evidence required to introduce these new tools into policy and practice. Key gaps identified were accuracy and reliability of glucose-6-phosphate-dehydrogenase deficiency tests, health system capacity, and feasibility and cost effectiveness of novel treatment strategies in routine clinical practice. As expected, there were differences in the priorities between country partners and researcher partners. To achieve the 2030 target for the regional elimination of malaria, evidence to address these issues should be generated as a matter of priority. Review of global guidelines alongside locally generated data will help to ensure the timely revision and optimisation of national treatment guidelines that will be vital to meet regional elimination goals.

Reference and point-of-care testing for G6PD deficiency: Blood disorder interference, contrived specimens, and fingerstick equivalence and precision.

Certain clinical indications and treatments such as the use of rasburicase in cancer therapy and 8-aminoquinolines for Plasmodium vivax malaria treatment would benefit from a point-of-care test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Three studies were conducted to evaluate the performance of one such test: the STANDARD™ G6PD Test (SD BIOSENSOR, South Korea). First, biological interference on the test performance was evaluated in specimens with common blood disorders, including high white blood cell (WBC) counts. Second, the test precision on fingerstick specimens was evaluated against five individuals of each, deficient, intermediate, and normal G6PD activity status. Third, clinical performance of the test was evaluated at three point-of-care settings in the United States. The test performed equivalently to the reference assay in specimens with common blood disorders. High WBC count blood samples resulted in overestimation of G6PD activity in both the reference assay and the STANDARD G6PD Test. The STANDARD G6PD Test showed good precision on multiple fingerstick specimens from the same individual. The same G6PD threshold values (U/g Hb) were applied for a semiquantitative interpretation for fingerstick- and venous-derived results. The sensitivity/specificity values (95% confidence intervals) for the test for G6PD deficiency were 100 (92.3-100.0)/97 (95.2-98.2) and 100 (95.7-100.0)/97.4 (95.7-98.5) for venous and capillary specimens, respectively. The same values for females with intermediate (> 30% to ≤ 70%) G6PD activity were 94.1 (71.3-99.9)/88.2 (83.9-91.7) and 82.4 (56.6-96.2)/87.6(83.3-91.2) for venous and capillary specimens, respectively. The STANDARD G6PD Test enables point-of-care testing for G6PD deficiency.

Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency, prevalent in many malaria-endemic countries. G6PD-deficient individuals are susceptible to hemolysis during oxidative stress, which can occur from exposure to certain medications, including 8-aminoquinolines used to treat Plasmodium vivax malaria. Accordingly, access to point-of-care (POC) G6PD testing in Brazil is critical for safe treatment of P. vivax malaria. METHODOLOGY/PRINCIPAL FINDINGS: This study evaluated the performance of the semi-quantitative, POC STANDARD G6PD Test (SD Biosensor, Republic of Korea). Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. G6PD and hemoglobin measurements were obtained from capillary samples at the POC using the STANDARD and HemoCue 201+ (HemoCue AB, Sweden) tests. A thick blood slide was prepared for malaria microscopy. At the laboratories, the STANDARD and HemoCue tests were repeated on venous samples and a quantitative spectrophotometric G6PD reference assay was performed (Pointe Scientific, Canton, MI). G6PD was also assessed by fluorescent spot test. In Manaus, a complete blood count was performed. Samples were analyzed from 1,736 participants. In comparison to spectrophotometry, the STANDARD G6PD Test performed equivalently in determining G6PD status in venous and capillary specimens under varied operating temperatures. Using the manufacturer-recommended reference value thresholds, the test's sensitivity at the <30% threshold on both specimen types was 100% (95% confidence interval [CI] venous 93.6%-100.0%; capillary 93.8%-100.0%). Specificity was 98.6% on venous specimens (95% CI 97.9%-99.1%) and 97.8% on capillary (95% CI 97.0%-98.5%). At the 70% threshold, the test's sensitivity was 96.9% on venous specimens (95% CI 83.8%-99.9%) and 94.3% on capillary (95% CI 80.8%-99.3%). Specificity was 96.5% (95% CI 95.0%-97.6%) and 92.3% (95% CI 90.3%-94.0%) on venous and capillary specimens, respectively. CONCLUSION/SIGNIFICANCE: The STANDARD G6PD Test is a promising tool to aid in POC detection of G6PD deficiency in Brazil. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (identifier: NCT04033640).

Usability of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency: a multi-country assessment of test label comprehension and results interpretation.

BACKGROUND: Point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing has the potential to make the use of radical treatment for vivax malaria safer and more effective. Widespread use of G6PD tests as part of malaria case management has been limited, in part due to due concerns regarding product usability, user training, and supervision. This study seeks to assess how well end users can understand the Standard™ G6PD Test (SD Biosensor, Suwon, South Korea) workflow, result output, and label after training. This will ultimately help inform test registration and introduction. METHODS: Potential G6PD test users who provide malaria case management at three sites in Brazil, Ethiopia, and India were trained on the use of the SD Biosensor Standard G6PD Test and assessed based on their ability to understand the test workflow and interpret results. The assessment was done through a questionnaire, designed to assess product usability against key technical product specifications and fulfill regulatory evidence requirements. Any participant who obtained 85% or above correct responses to the questionnaire was considered to adequately comprehend how to use and interpret the test. RESULTS: Forty-five participants, including malaria microscopists, laboratory staff, nurses, and community health workers took part in the study. Seventy-eight percent of all participants in the study (35/45) obtained passing scores on the assessment with minimal training. Responses to the multiple-choice questions indicate that most participants understood well the test intended use, safety claims, and warnings. The greatest source of error regarding the test was around the correct operating temperature. Most test results were also read and interpreted correctly, with the haemoglobin measurement being a more problematic output to interpret than the G6PD measurement. CONCLUSIONS: These data results show how a standardized tool can be used to assess a user's ability to run a point-of-care diagnostic and interpret results. When applied to the SD Biosensor Standard G6PD Test, this tool demonstrates that a range of users across multiple contexts can use the test and suggests improvements to the test instructions and training that can improve product usability, increase user comprehension, and ultimately contribute to more widespread effective use of point-of-care G6PD tests. TRIAL REGISTRATION: NCT04033640.

Optimizing G6PD testing for Plasmodium vivax case management and beyond: why sex, counseling, and community engagement matter.

Safe access to the most effective treatment options for  Plasmodium vivax malaria are limited by the absence of accurate point-of-care testing to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against  P. vivax hypnozoites. Until recently, only qualitative tests were available in most settings. These can identify patients with severe G6PD deficiency (mostly male) but not patients with intermediate G6PD deficiency (always female). This has led to and reinforced a gap in awareness in clinical practice of the risks and implications of G6PD deficiency in females-who, unlike males, can have a heterozygous genotype for G6PD. Increasing recognition of the need for radical cure of   P. vivax, first for patients' health and then for malaria elimination, is driving the development of new point-of-care tests for G6PD deficiency and their accessibility to populations in low-resource settings. The availability of user-friendly, affordable, and accurate quantitative point-of-care diagnostics for the precise classification of the three G6PD phenotypes can reduce sex-linked disparities by ensuring safe and effective malaria treatment, providing opportunities to develop supportive counseling to enhance understanding of genetic test results, and improving the detection of all G6PD deficiency phenotypes in newborns and their family members.

Potential new tool for anemia screening: An evaluation of the performance and usability of the TrueHb Hemometer.

In low- and middle-income countries, many women experience anemia during pregnancy due to insufficient dietary intake of key micronutrients, parasitic infections, hemoglobinopathies, and chronic infections. Maternal anemia increases perinatal risks for both mothers and infants, and slow progress to reduce the prevalence may be due in part to the lack of affordable tools to quantify hemoglobin levels in antenatal care (ANC) clinics. A simple, inexpensive, accurate, and robust diagnostic is needed to measure hemoglobin in ANC. This study evaluated the performance and usability of the TrueHb Hemometer. A cross-sectional diagnostic accuracy study was conducted to compare the accuracy of the TrueHb and the HemoCue® 201+ using capillary samples. Next, analytical performance (precision, coefficient of variation, R2) of the TrueHb was evaluated in varying environmental conditions using linearity panels with serial dilutions of venous blood samples. Lastly, the usability of the TrueHb Hemometer was assessed across three domains (effectiveness, efficiency, and satisfaction) by 20 ANC providers in Ghana. Capillary blood test results were not well correlated (R2 = 0.35) between the TrueHB and HemoCue201+, but 80% of TrueHb measurements were within +/-1.0 g/dl of the HemoCue® 201+ hemoglobin values. Precision tests indicated similar mean values across the three environmental conditions (CV<6%). At 21°C, the TrueHb follows a linear relationship (R2≥0.96) but does not generate accurate readings below 4.0 g/dl. At 30°C and 37°C, the TrueHb follows a linear relationship (R2 > 0.90) but begins to underestimate the hemoglobin concentration below 7.0 g/dl. The usability study identified potential failure modes due to inadequate instructions and device feedback. With some modifications, both to the product and to the instructions for use, the TrueHb may be suitable for use in ANC settings to help fill the diagnostic gap for anemia screening during pregnancy. Further testing is required with anemic populations in LMIC settings.

Malaria radical cure opportunity assessment in India: Discussing opportunities through stakeholder convening workshop and recommendation for improved access to malaria treatment.

India contributes to over 40% of the global Plasmodium vivax disease burden, and P. vivax contributes to approximately one-third of all malaria in India. Government of India has set goals to eliminate malaria by 2030. Doing so will require scaling up existing and new strategies, treatments and diagnostic tools. Access to appropriate diagnosis and treatment for P. vivax malaria is currently limited, and it is unclear how new tools will be rolled out. To support the government in its malaria elimination efforts, the current challenges associated with access to best clinical management of vivax malaria must be understood and mitigated to effectively deploy new tools and scale up existing solutions. The recent Food and Drug Administration (US-FDA) as well as Therapeutics Goods Administration (Australian TGA) approval of tafenoquine, developed by GSK GlaxoSmithKline and Medicines for Malaria Venture (MMV) as a new single-dose radical cure treatment for P. vivax malaria, and the commercial availability of new point-of-care glucose-6-phosphate dehydrogenase (G6PD) tests provide new opportunities to improve clinical management of vivax malaria in India. This report discusses the background, objectives, implementation strategies, and next steps that came out of the Stakeholder Workshop on Malaria Radical Cure in New Delhi, India on 4 February 2019. The focus was to understand the risks and opportunities associated with access to best clinical practices for managing vivax malaria in India. A key outcome was to propose a framework for articulating and segmenting important investment opportunities for improving access to best clinical practices for P. vivax radical cure in India.

Evaluating the use of job aids and user instructions to improve adherence for the treatment of childhood pneumonia using amoxicillin dispersible tablets in a low-income setting: a mixed-method study.

OBJECTIVES: We conducted a study to evaluate the use of job aids and simple user instructions to improve adherence for the treatment of childhood pneumonia with amoxicillin dispersible tablet (DT). DESIGN: A mixed-method study implemented in three phases between October 2015 and February 2016. SETTINGS: The study was implemented in two subdistricts of Bangladesh. PARTICIPANTS: Caregivers of children aged 2-59 months, health service providers and key stakeholders at national and district level. INTERVENTIONS: An intervention including training and job aids and user-friendly instructions was introduced in one subdistrict while standard amoxicillin DT packaging and instructions with no training served as the control in the comparison subdistrict. PRIMARY OUTCOME: Adherence behaviour of caregivers of children aged 2-59 months for the treatment of childhood pneumonia with amoxicillin DT. METHODS: We conducted a survey with 56 caregivers in the intervention subdistrict and 38 caregivers in the comparison subdistrict. We also conducted 44 in-depth interviews to evaluate the job aids and user-friendly instructions with healthcare providers and caregivers to assess the feasibility, usability and acceptability of the tools in intervention subdistrict. RESULTS: For 5-day treatment course, 32.1% (95% CI 23.1% to 41.1%) of caregivers in the intervention subdistrict and 2.6% (95% CI 0.3% to 7.8%) in the comparison subdistrict maintained full adherence to the amoxicillin DT treatment for pneumonia. More children under 12 months were given age-appropriate treatment than older children. Key stakeholders and healthcare providers considered the use and integration of the tools into the health system to be feasible and acceptable. CONCLUSIONS: The provision of tools for the treatment of childhood pneumonia with amoxicillin DT had a positive influence on adherence behaviours. These tools can help close information gaps and overcome the barriers posed by medical illiteracy and remembering instructions from providers.

Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group.

The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness.

Transdermal delivery of vitamin K using dissolving microneedles for the prevention of vitamin K deficiency bleeding.

Vitamin K deficiency within neonates can result in vitamin K deficiency bleeding. Ensuring that newborns receive vitamin K is particularly critical in places where access to health care and blood products and transfusions is limited. The World Health Organization recommends that newborns receive a 1 mg intramuscular injection of vitamin K at birth. Evidence from multiple surveillance studies shows that the introduction of vitamin K prophylaxis reduces the incidence of vitamin K deficiency bleeding. Despite these recommendations, coverage of vitamin K prophylactic treatment in low-resource settings is limited. An intramuscular injection is the most common method of vitamin K administration in neonates. In low- and middle-income countries, needle sharing may occur, which may result in the spread of bloodborne diseases. The objective of our study was to investigate the manufacture of microneedles for the delivery of vitamin K. Following microneedle fabrication, we performed insertion studies to assess the microneedle's mechanical properties. Results indicate that vitamin K in a microneedle array was successfully delivered in vitro across neonatal porcine skin with 1.80 ±â€¯0.08 mg delivered over 24 h. Therefore, this initial study shows that microneedles do have the potential to prevent vitamin K deficiency bleeding. Future work will assess delivery of vitamin K in microneedle array in vivo.

Current perspectives and practices of newborn vitamin K administration in low and middle income countries.

BACKGROUND: Vitamin K prophylaxis can prevent vitamin K deficiency bleeding (VKDB), and current global recommendations support universal prophylactic use in newborns. Data about access to and use of vitamin K in low and middle income countries (LMIC) are scarce. To address this gap, we explored current perspectives and practices of newborn vitamin K administration in LMIC in order to better understand the barriers to more widespread coverage of this lifesaving preventative treatment. METHODS: We conducted an online survey of stakeholders involved in newborn health. We sent the survey via e-mail to 109 individuals who were based primarily in LMIC and 23 responses were received, resulting in a response rate of 21%. Respondents were generally health or development professionals from sub-Saharan Africa and Asia. RESULTS: Incidence rates at the country level were mostly unknown or not supported by adequate data. Many respondents (17/23) indicated that vitamin K prophylaxis is included in their national newborn care guidelines and policies, while 12 respondents indicated that administration at birth was widely practiced. Around half of respondents reported that health workers were trained in the diagnosis and treatment of VKDB. The most frequently cited barriers to more widespread vitamin K prophylaxis were (in rank order) high rates of home birth (which preclude injections that must be given by skilled health workers), lack of access to and availability of vitamin K, perception that vitamin K prophylactic treatment is not a priority among health workers, lack of vitamin K formulations appropriate for infants, cultural practices suggesting that injection at birth is not acceptable to parents, and vitamin K not being included in national guidelines and policies. There was no consensus as to the ideal formulation, respondents preferring both the current intramuscular (IM) injection and oral formulation. Reported product attributes of IM and oral formulations are summarized. CONCLUSION: Prophylactic administration of vitamin K to newborns is relatively well integrated into policy at the global and country levels, but its practice is underutilized. Barriers to use are access, supply chain logistics, provider attitudes, and restrictions on the use of injections by providers at the community level. Technology innovation may offer some promise to mitigate these barriers, although advocacy and health system strengthening might be more likely to yield improved coverage. Further investigation using in-depth bottleneck analysis at the country level could help identify specific health system improvements.

Point-of-Care Testing for G6PD Deficiency: Opportunities for Screening.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked genetic disorder, is associated with increased risk of jaundice and kernicterus at birth. G6PD deficiency can manifest later in life as severe hemolysis, when the individual is exposed to oxidative agents that range from foods such as fava beans, to diseases such as typhoid, to medications such as dapsone, to the curative drugs for Plasmodium (P.) vivax malaria, primaquine and tafenoquine. While routine testing at birth for G6PD deficiency is recommended by the World Health Organization for populations with greater than 5% prevalence of G6PD deficiency and to inform P. vivax case management using primaquine, testing coverage is extremely low. Test coverage is low due to the need to prioritize newborn interventions and the complexity of currently available G6PD tests, especially those used to inform malaria case management. More affordable, accurate, point-of-care (POC) tests for G6PD deficiency are emerging that create an opportunity to extend testing to populations that do not have access to high throughput screening services. Some of these tests are quantitative, which provides an opportunity to address the gender disparity created by the currently available POC qualitative tests that misclassify females with intermediate G6PD activity as normal. In populations where the epidemiology for G6PD deficiency and P. vivax overlap, screening for G6PD deficiency at birth to inform care of the newborn can also be used to inform malaria case management over their lifetime.

Understanding user requirements to improve adoption of influenza diagnostics in clinical care within Metro Manila.

BACKGROUND AND AIM: Influenza diagnostics play a critical role informing in clinical management decisions and defining the global epidemiology of the disease to support public health responses. Use of influenza diagnostics within most low-income and middle-income countries remains limited, including in the Philippines, where they are currently used only for epidemiologic surveillance. The aim of this study was to define key considerations, including product characteristics, which may influence future adoption, uptake, and integration of influenza diagnostics into public and private clinical settings in this emerging Asian market. METHODS: Our study was conducted using a convenience sample of public and private hospital laboratories in Metro Manila. A usability assessment was conducted that included interviews with decision-makers and direct observation of laboratory end users using 2 platforms representative of emerging diagnostic products: (1) a point-of-care antigen-based rapid immunoassay diagnostic test paired with a reader and (2) a molecular diagnostic platform intended for decentralized use. Data were analyzed to assess user errors and device failure modes with each platform and to determine key considerations related to product adoption and uptake. RESULTS: The most difficult test step for most users on both platforms involved sample preparation. When deciding to adopt a new test, priority product attributes include performance, potential volume of demand from clinicians, equipment cost, and ease of use. Demand for new tests is likely going to be driven by clinicians, and policies and guidelines will be needed to support the introduction of new products. CONCLUSION: Adoption of influenza diagnostics in Metro Manila is feasible but will require affordable products capable of satisfying needs for use in both epidemiologic surveillance and clinical management.

Feasibility of utilizing the SD BIOLINE Onchocerciasis IgG4 rapid test in onchocerciasis surveillance in Senegal.

As effective onchocerciasis control efforts in Africa transition to elimination efforts, different diagnostic tools are required to support country programs. Senegal, with its long standing, successful control program, is transitioning to using the SD BIOLINE Onchocerciasis IgG4 (Ov16) rapid test over traditional skin snip microscopy. The aim of this study is to demonstrate the feasibility of integrating the Ov16 rapid test into onchocerciasis surveillance activities in Senegal, based on the following attributes of acceptability, usability, and cost. A cross-sectional study was conducted in 13 villages in southeastern Senegal in May 2016. Individuals 5 years and older were invited to participate in a demographic questionnaire, an Ov16 rapid test, a skin snip biopsy, and an acceptability interview. Rapid test technicians were interviewed and a costing analysis was conducted. Of 1,173 participants, 1,169 (99.7%) agreed to the rapid test while 383 (32.7%) agreed to skin snip microscopy. The sero-positivity rate of the rapid test among those tested was 2.6% with zero positives 10 years and younger. None of the 383 skin snips were positive for Ov microfilaria. Community members appreciated that the rapid test was performed quickly, was not painful, and provided reliable results. The total costs for this surveillance activity was $22,272.83, with a cost per test conducted at $3.14 for rapid test, $7.58 for skin snip microscopy, and $13.43 for shared costs. If no participants had refused skin snip microscopy, the total cost per method with shared costs would have been around $16 per person tested. In this area with low onchocerciasis sero-positivity, there was high acceptability and perceived value of the rapid test by community members and technicians. This study provides evidence of the feasibility of implementing the Ov16 rapid test in Senegal and may be informative to other country programs transitioning to Ov16 serologic tools.