Design and implementation of a web-based, respondent-driven sampling solution.

BACKGROUND: Respondent-driven sampling (RDS) refers both to a chain-referral sampling method and an analytical model for analysing sampled data. Web-based respondent-driven sampling (webRDS) uses internet-based recruitment coupled with an electronic survey to carry out RDS studies; there is currently no commercially available webRDS solution. We designed and developed a webRDS solution to support a research study aimed at estimating conflict-attributable mortality in Yemen. Our webRDS solution is composed of an existing survey platform (i.e. ODK) and a bespoke RDS system. The RDS system is designed to administer and manage an RDS survey cascade and includes: (1) an application programming interface, (2) a study participant client, and (3) an administrator interface. We report here on the design of the webRDS solution and its implementation. RESULTS: We consulted members of the Yemeni diaspora throughout the development of the solution. Technical obstacles were largely the result of: WhatsApp's policies on bulk messaging and automated messaging behaviour, the inherent constraints of SMS messaging, and SMS filtering behaviour. Language support was straight-forward yet time consuming. Survey uptake was lower than expected. Factors which may have impacted uptake include: our use of consumable survey links, low interest amongst the diaspora population, lack of material incentives, and the length and subject matter of the survey itself. The SMS/WhatsApp messaging integration was relatively complex and limited the information we could send potential participants. CONCLUSION: Despite lower-than expected survey uptake we believe our webRDS solution provides efficient and flexible means to survey a globally diverse population.

Glucose 6 Phosphate Dehydrogenase (G6PD) quantitation using biosensors at the point of first contact: a mixed method study in Cambodia.

BACKGROUND: Quantitative measurement of Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme activity is critical to decide on appropriate treatment and provision of radical cure regimens for vivax malaria. Biosensors are point-of-care semi-quantitative analysers that measure G6PD enzyme activity. The main objective of this study was to evaluate the operational aspects of biosensor deployment in the hands of village malaria workers (VMWs) in Cambodia over a year. METHODS: Following initial orientation and training at Kravanh Referral Hospital, each VMW (n = 28) and laboratory technician (n = 5) was provided a biosensor (STANDARD SD Biosensor, Republic of Korea) with supplies for routine use. Over the next 12 months VMWs convened every month for refresher training, to collect supplies, and to recalibrate and test their biosensors. A quantitative self-administered questionnaire was used to assess the skills necessary to use the biosensor after the initial training. Subsequently, VMWs were visited at their location of work for field observation and evaluation using an observer-administered questionnaire. All quantitative questionnaire-based data were analysed descriptively. Semi-structured interviews (SSIs) were conducted among all participants to explore their experience and practicalities of using the biosensor in the field. SSIs were transcribed and translated into English and underwent thematic analysis. RESULTS: A total of 33 participants completed the training and subsequently used the biosensor in the community. Quantitative assessments demonstrated progressive improvement in skills using the biosensor. VMWs expressed confidence and enthusiasm to use biosensors in their routine work. Providing G6PD testing at the point of first contact avoids a multitude of barriers patients have to overcome when travelling to health centres for G6PD testing and radical cure. Deploying biosensors in routine work of VMWs was also considered an opportunity to expand and strengthen the role of VMWs as health care providers in the community. VMWs reported practical concerns related to the use of biosensor such as difficulty in using two pipettes, difficulty in extracting the code chip from the machine, and the narrow base of buffer tube. CONCLUSIONS: VMWs considered the biosensor a practical and beneficial tool in their routine work. Providing VMWs with biosensors can be considered when followed by appropriate training and regular supervision. Providing community management of vivax malaria at the point of first contact could be key for elimination.

A Systematic Review of Methods for Estimating Productivity Losses due to Illness or Caregiving in Low- and Middle-Income Countries.

BACKGROUND: Productivity losses are often included in costing studies and economic evaluations to provide a comprehensive understanding of the economic burden of disease. Global guidance on estimating productivity losses is sparse, especially for low-and middle-income countries (LMICs) where informal and unpaid work remains dominant. This study aims to describe current practices for valuing productivity losses in LMICs. METHODS: We performed a systematic review of studies published before April 2022 using three databases, including PubMed, Cochrane Library and Web of Science Core Collection. We included any costing or economic evaluation study conducted in a LMIC that provided methodological details on how the monetary value for productivity losses was estimated. Two reviewers independently screened articles for inclusion, extracted data and assessed the quality of the studies. RESULTS: A total of 281 articles were included. While most studies did not specify the overall approach used to measure and value productivity losses (58%), the human capital approach was the most frequently used approach to measure productivity losses when this was clearly stated (39%). The most common methods to estimate a monetary value for productivity losses were market wages (51%), self-reported wages (28%) and macroeconomic measures (15%). CONCLUSION: Reporting standards for productivity losses in LMIC settings have room for improvement. While market wages were the most frequently used method to estimate the monetary value of productivity losses, this relies on context-specific data availability. Until a consensus is reached on if, when and how to include productivity losses in costing and economic evaluation studies, future studies could include a sensitivity analysis to explore the impact of different methods for estimating the monetary value of productivity losses.

Implementation of Glucose-6-Phosphate Dehydrogenase (G6PD) testing for Plasmodium vivax case management, a mixed method study from Cambodia.

Plasmodium vivax remains a challenge for malaria elimination since it forms dormant liver stages (hypnozoites) that can reactivate after initial infection. 8-aminoquinolone drugs kill hypnozoites but can cause severe hemolysis in individuals with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. The STANDARD G6PD test (Biosensor) is a novel point-of-care diagnostic capable of identifying G6PD deficiency prior to treatment. In 2021, Cambodia implemented the Biosensor to facilitate radical cure treatment for vivax malaria. To assess the Biosensor's implementation after its national rollout, a mixed-methods study was conducted in eight districts across three provinces in Cambodia. Interviews, focus group discussions, and observations explored stakeholders' experiences with G6PD testing and factors influencing its implementation. Quantitative data illustrative of test implementation were gathered from routine surveillance forms and key proportions derived. Qualitative data were analyzed thematically. The main challenge to implementing G6PD testing was that only 49.2% (437/888) of eligible patients reached health centers for G6PD testing following malaria diagnosis by community health workers. Factors influencing this included road conditions and long distances to the health center, compounded by the cost of seeking further care and patients' perceptions of vivax malaria and its treatment. 93.9% (790/841) of eligible vivax malaria patients who successfully completed referral (429/434) and directly presented to the health center (360/407) were G6PD tested. Key enabling factors included the test's acceptability among health workers and their understanding of the rationale for testing. Only 36.5% (443/1213) of eligible vivax episodes appropriately received primaquine. 70.5% (165/234) of female patients and all children under 20 kilograms never received primaquine. Our findings suggest that access to radical cure requires robust infrastructure and income security, which would likely improve referral rates to health centers enabling access. Bringing treatment closer to patients, through community health workers and nuanced community engagement, would improve access to curative treatment of vivax malaria.

A Review of the Current Status of G6PD Deficiency Testing to Guide Radical Cure Treatment for Vivax Malaria.

Plasmodium vivax malaria continues to cause a significant burden of disease in the Asia-Pacific, the Horn of Africa, and the Americas. In addition to schizontocidal treatment, the 8-aminoquinoline drugs are crucial for the complete removal of the parasite from the human host (radical cure). While well tolerated in most recipients, 8-aminoquinolines can cause severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. G6PD deficiency is one of the most common enzymopathies worldwide; therefore, the WHO recommends routine testing to guide 8-aminoquinoline based treatment for vivax malaria whenever possible. In practice, this is not yet implemented in most malaria endemic countries. This review provides an update of the characteristics of the most used G6PD diagnostics. We describe the current state of policy and implementation of routine point-of-care G6PD testing in malaria endemic countries and highlight key knowledge gaps that hinder broader implementation. Identified challenges include optimal training of health facility staff on point-of-care diagnostics, quality control of novel G6PD diagnostics, and culturally appropriate information and communication with affected communities around G6PD deficiency and implications for treatment.

Glucose-6-Phosphate Dehydrogenase (G6PD) Measurement Using Biosensors by Community-Based Village Malaria Workers and Hospital Laboratory Staff in Cambodia: A Quantitative Study.

Vivax malaria can relapse after an initial infection due to dormant liver stages of the parasite. Radical cure can prevent relapses but requires the measurement of glucose-6-phosphate dehydrogenase enzyme (G6PD) activity to identify G6PD-deficient patients at risk of drug-induced haemolysis. In the absence of reliable G6PD testing, vivax patients are denied radical curative treatment in many places, including rural Cambodia. A novel Biosensor, 'G6PD Standard' (SD Biosensor, Republic of Korea; Biosensor), can measure G6PD activity at the point of care. The objectives of this study were to compare the G6PD activity readings using Biosensors by village malaria workers (VMWs) and hospital-based laboratory technicians (LTs), and to compare the G6PD deficiency categorization recommended by the Biosensor manufacturer with categories derived from a locally estimated adjusted male median (AMM) in Kravanh district, Cambodia. Participants were enrolled between 2021 and 2022 in western Cambodia. Each of the 28 VMWs and 5 LTs received a Biosensor and standardized training on its use. The G6PD activities of febrile patients identified in the community were measured by VMWs; in a subset, a second reading was done by LTs. All participants were tested for malaria by rapid diagnostic test (RDT). The adjusted male median (AMM) was calculated from all RDT-negative participants and defined as 100% G6PD activity. VMWs measured activities in 1344 participants. Of that total, 1327 (98.7%) readings were included in the analysis, and 68 of these had a positive RDT result. We calculated 100% activity as 6.4 U/gHb (interquartile range: 4.5 to 7.8); 9.9% (124/1259) of RDT-negative participants had G6PD activities below 30%, 15.2% (191/1259) had activities between 30% and 70%, and 75.0% (944/1259) had activities greater than 70%. Repeat measurements among 114 participants showed a significant correlation of G6PD readings (rs = 0.784, p < 0.001) between VMWs and LTs. Based on the manufacturer's recommendations, 285 participants (21.5%) had less than 30% activity; however, based on the AMM, 132 participants (10.0%) had less than 30% activity. The G6PD measurements by VMWs and LTs were similar. With the provisions of training, supervision, and monitoring, VMWs could play an important role in the management of vivax malaria, which is critical for the rapid elimination of malaria regionally. Definitions of deficiency based on the manufacturer's recommendations and the population-specific AMM differed significantly, which may warrant revision of these recommendations.

Rapid Diagnostic Tests as a Source of Dengue Virus RNA for Envelope Gene Amplification: A Proof of Concept.

Molecular epidemiological data are key for dengue outbreak characterization and preparedness. However, sparse Dengue virus (DENV) molecular information is available in Laos because of limited resources. In this proof-of-concept study, we evaluated whether DENV1 RNA extracted from rapid diagnostic tests (RDTs) could be amplified and sequenced. The protocol for envelope gene amplification from RNA purified from RDTs was first assessed using viral isolate dilutions then conducted using 14 dengue patient sera. Envelope gene amplification was successful from patient sera with high virus titer, as was sequencing but with lower efficiency. Hence, based on our results, RDTs can be a source of DENV1 RNA for subsequent envelope gene amplification and sequencing. This is a promising tool for collecting molecular epidemiology data from rural dengue-endemic areas. However, further investigations are needed to improve assay efficiency and to assess this tool's level of efficacy on a larger scale in the field.