Technologies In Resource-limited Settings Research Articles

Integrating Genomic Data with the Development of CRISPR-Based Point-of-Care-Testing for Bacterial Infections

Abstract Purpose of Review Bacterial infections and antibiotic resistance contribute to global mortality. Despite many infections being preventable and treatable, the lack of reliable and accessible diagnostic tools exacerbates these issues. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based diagnostics has emerged as a promising solution. However, the development of CRISPR diagnostics has often occurred in isolation, with limited integration of genomic data to guide target selection. In this review, we explore the synergy between bacterial genomics and CRISPR-based point-of-care tests (POCT), highlighting how genomic insights can inform target selection and enhance diagnostic accuracy. Recent Findings We review recent advances in CRISPR-based technologies, focusing on the critical role of target sequence selection in improving the sensitivity of CRISPR-based diagnostics. Additionally, we examine the implementation of these technologies in resource-limited settings across Asia and Africa, presenting successful case studies that demonstrate their potential. Summary The integration of bacterial genomics with CRISPR technology offers significant promise for the development of effective point-of-care diagnostics.

Open-source spring-driven syringe pump with 3D-printed components for microfluidic applications

The operation of microfluidic devices requires precise and constant fluid flow. Microfluidic systems in low-resource settings require a portable, inexpensive, and electricity-free pumping approach due to the rising demand for microfluidics in point-of-care testing (POCT). Open-source alternatives, employing 3D printing and motors, offer affordability. However, using motors require electrical power, which often relies on external sources, hindering the on-site use of open-source pumps. This study introduces a spring-driven, 3D-printed syringe pump, eliminating the need for an external power source. The syringe pump is operated by the flat spiral spring’s torque. By manually winding up the mainspring, the syringe pump can be operated without electricity. Various flow rates can be achieved by utilizing different syringe sizes and choosing the right gear combinations. All the parts of the syringe pump can be fabricated by 3D printing, requiring no additional components that require electricity. It operates by winding a mainspring and is user-friendly, allowing flow rate adjustments by assembling gears that modulate syringe plunger pushing velocity. The fabrication cost is $25–30 and can be assembled easily by following the instructions. We expect that the proposed syringe pump will enable the utilization of microfluidic technologies in resource-limited settings, promoting the adoption of microfluidics. Detailed information and results are available in the original research paper (https://doi.org/10.1016/j.snb.2024.135289).

METB-11. HOW METHYLATION PROFILING HELPS IN DIAGNOSING AND TREATING PEDIATRIC BRAIN TUMORS IN INDONESIA

Abstract BACKGROUNDS Pediatric brain tumors (PBT) exhibit extensive heterogeneity, impacting treatment outcomes. While traditionally classified based on histopathological features, recent WHO classifications have integrated DNA methylation array profiling amongst other molecular characteristics, which improves diagnostic accuracy and thus treatment decisions. However, access to this technology is limited in low- and middle-income countries (LMICs) like Indonesia. As part of the MNP Outreach Consortium, we aimed to introduce methylation profiling in Indonesia to aid in diagnosing and stratifying PBT patients. METHODS In 2023, we conducted a case series involving seven challenging PBT cases from Cipto Mangunkusumo National General Hospital, re-assessing them with methylation profiling. RESULTS Through collaboration with the Institute of Neuropathology Heidelberg and the DKFZ, our centre adopted a discerning approach to re-evaluate histopathological samples from complex cases. This endeavour yielded notable results, reaffirming four initial diagnoses and altering three others Amongst the findings, one case initially diagnosed as anaplastic ependymoma, CNS WHO grade 3, was reclassified as a supratentorial ependymoma with YAP1 fusion gene, based on methylation class. Noteworthy within this latter group, one case initially categorized as low-grade pilocytic astrocytoma was reclassified as high-grade diffuse midline glioma, H3 K27 altered. Moreover identifying the copy number plot could indicate a KIAA1549::BRAF fusion to reclassify a case from diffuse pediatric glioma WHO grade 2 to pilocytic astrocytoma WHO grade 1. The recurrent pigmented neuroectodermal tumor of infancy (MNTI) was reclassified as Medulloblastoma, non-WNT/non-SHH, group 3 subtype II on methylation profiling, highlighting molecular similarities and potential treatment insights. These findings offer insights into genetic mechanisms and guide treatment strategies. CONCLUSION Accurate diagnosis, facilitated by advanced molecular profiling, enhances prognostication and enables personalized treatment plans, even in LMICs. This underscores the importance of expanding access to advanced diagnostic technologies in resource-limited settings.

Use of digital technologies for staff education and training programmes on newborn resuscitation and complication management: a scoping review

BackgroundPoor-quality care is linked to higher rates of neonatal mortality in low-income and middle-income countries (LMICs). Limited educational and upskilling opportunities for healthcare professionals, particularly those who work in remote...

Learning and clinical reasoning experience of second-year medical pharmacology students and teachers with virtual patients developed using OpenLabyrinth

<b>Objective: </b>To determine the perceived usefulness of a virtual case scenario developed and delivered through the OpenLabyrinth platform among medical students and teachers.<br /> <b>Methods: </b>20 second-year medical students and 12 teachers of pharmacology were invited to complete a virtual case scenario exercise. The participants accessed the case scenario using their laptops or mobile devices. Participants’ feedback was obtained using the electronic virtual patient consortium-developed questionnaire.<br /> <b>Results: </b>19 students and 12 teachers provided feedback. All the faculty members and 95% of students felt that they had to make the same decisions a doctor would have to make in real life; ‘authenticity of patient encounter’ received the highest percentage of positive responses and ‘the learning effect’ the least.<br /> <b>Conclusions: </b>The feedback obtained suggests that virtual case scenarios are likely to be well received by students and teachers. The availability of open-source software enables the use of this technology in resource-limited settings.

Remote Robotic Surgery and Virtual Education Platforms: How Advanced Surgical Technologies Can Increase Access to Surgical Care in Resource-Limited Settings.

Advanced surgical technologies consist of remote and virtual platforms that facilitate surgical care and education. It also includes the infrastructure necessary to utilize these platforms (e.g., internet access, robotic systems, and simulators). Given that 5 billion people lack access to safe and timely surgical care, the appeal of these technologies to the field of global surgery lies primarily in its ability to eliminate geographical barriers and address surgeon shortages. This article discusses the use of virtual and remote technologies in resource-limited settings, the potential applications of these technologies, the possible barriers to their integration, and the impact these technologies may have on access to surgical care and education. Specifically, it will explore how robotic surgery, telesurgery, virtual education platforms, and simulations have the potential to be instrumental in enhancing worldwide access to safe surgical care.

Predicting healthcare professionals’ acceptance towards electronic personal health record systems in a resource-limited setting: using modified technology acceptance model

ObjectivesPersonal health record systems allow users to manage their health information in a confidential manner. However, there is little evidence about healthcare providers’ intentions to use such technologies in resource-limited...

Intention to use wearable health devices and its predictors among diabetes mellitus patients in Amhara region referral hospitals, Ethiopia: Using modified UTAUT-2 model

IntroductionThe burden of diabetes mellitus is increasing in Africa. Wearables have a proven track record of combating chronic diseases. However, little is known about patients’ intentions to use such technologies in resource-limited settings. Therefore, this study aimed to assess DM patients' intentions to use wearable health devices and its predictors in Ethiopia. MethodsAn institutional-based cross-sectional study was conducted among 924 diabetes mellitus patients from May 19 to June 23, 2022, at referral hospitals in the Amhara regional state of Ethiopia. An interviewer-administered questionnaire was used to collect the data using the Kobo Collect app. A systematic random sampling technique was used to select the study participants. Descriptive statistics were done using SPSS version 25 software and presented using tables and pie charts. Structural equation modeling analysis with SPSS AMOS version 26 software was employed to identify predictors associated with the intention to use wearable health devices in Ethiopia. ResultsA total of 883 diabetes mellitus patients, with a 95.56% response rate, participated in the study. The proportion of intention to use wearable health devices was 47.1%, 95% CI (43.7–50.5). Effort expectancy (β = 0.543, P < 0.01), performance expectancy (β = 0.306, P < 0.01), facilitating condition (β = 0.131, P < 0.05), and habit (β = 0.093, P < 0.05) had a positive direct relationship with intention to use wearable health devices. Age (β = 0.439, p < 0.001) was moderate performance expectancy, while gender (β = 0.780, p < 0.001) had moderate effort expectancy to the intention to use wearable health devices. ConclusionsOverall, diabetes mellitus patients’ intentions to use wearable health devices were promising. The intention to use wearables was positively related to effort expectancy, performance expectancy, facilitating conditions, and habit. Thus, increasing patient intention to utilize it could be achieved through capacity building, access to technology, and technical support. In addition, implementers should prioritize improving the availability of devices, patients' abilities, encouraging customers, to utilize the product on a regular basis by actively fostering their relationship with them, and create awareness about usefulness of wearable health devices.

Hydrogel Stamping for Rapid, Multiplexed, Point-of-Care Immunostaining of Cells and Tissues.

In the era of precision oncology, multicolor fluorescence imaging has become a core technology for multiplexed molecular analysis of cellular and tissue specimens. However, conventional solution-based staining is labor-intensive and time-consuming and requires considerable expertise to yield optimal results, which creates difficulties for employing this technology in resource-limited settings. Here, we report a new immunostaining method based on hydrogel stamping, which is simple, fast, easy to use, and reproducible. We showed that a hydrophilic hydrogel stamp could effectively transfer fluorescent antibodies to targets and withdraw an excess solution when the reaction is completed, obviating the need for extra washing. This unique property allows for quality immunostaining in 5 min for cells using one-eighth of antibody consumption compared to the conventional solution-based method. Furthermore, we implemented fluorescence quenching and immunocycling with hydrogel staining for multiplexed analysis of 9 protein markers at a single cell level. Finally, we applied the immunocycling method to human breast cancer tissue samples and showed quality immunostaining over a large area (∼2 cm2) in 30 min for molecular subtyping of breast cancer. The hydrogel immunostaining could open new opportunities for rapid, automated, and multiplexed profiling in compact point-of-care systems for molecular cancer diagnosis.

Near Point-of-Care HIV Viral Load: Targeted Testing at Large Facilities.

Introduction:Point-of-care (POC) technologies in resource-limited settings can circumvent challenges of centralized laboratory testing, improving clinical management. However, higher device costs and uncertain indications for use have inhibited scaling up POC modalities. To address this gap, we investigated the feasibility and cost of targeted near-POC viral load (VL) testing in 2 large HIV clinics in Lilongwe, Malawi.Methods:VL testing using GeneXpert was targeted for patients suspected of treatment failure or returning to care after a previously elevated VL (>1000 copies/mL). Descriptive analysis of retrospective clinical and cost data is presented.Results:Two thousand eight hundred thirteen near-POC VL tests were conducted. One thousand five hundred eleven (54%) tests were for patients for whom results and reason for the test were documented: 57% (794/1389) of tests were to confirm a previously high VL, and 33% (462/1389) were due to clinical indications. Sixty-one percent (926/1511) of patients had a high VL, of whom 78% (719/926) had a recorded clinical action: 77% (557/719) switched to second line antiretroviral therapy, and 15% (194/719) were referred for intensive adherence counseling. Eighty-two percent (567/687) of patients received a clinical action on the same day as testing. The “all-in” cost was $33.71 for a valid POC VL test, compared with an international benchmark for a centralized VL test of $28.62.Conclusion:Targeted, near-POC VL testing was feasible and consistently enabled prompt clinical action. The difference between the “all-in” cost of near-POC VL and centralized testing of $5.09 could be further reduced in an optimized national program by combining targeted near-POC testing and centralized testing.

A Population-Specific Optimized GeneXpert Pooling Algorithm for Chlamydia trachomatis and Neisseria gonorrhoeae To Reduce Cost of Molecular Sexually Transmitted Infection Screening in Resource-Limited Settings.

The sexually transmitted infections (STIs) chlamydia (CT) and gonorrhea (NG) are often asymptomatic in women and undetected by syndromic management, leading to complications such as pelvic inflammatory disease, infertility, and ectopic pregnancy. Molecular testing, such as the GeneXpert CT/NG assay, is highly sensitive, but cost restraints preclude implementation of these technologies in resource-limited settings. Pooled testing is one strategy to reduce the cost per sample, but the extent of savings depends on disease prevalence. The current study describes a pooling strategy based on identification of sociodemographic and laboratory factors associated with CT/NG prevalence in a high-risk cohort of Zambian female sex workers and single mothers conducted from 2016 to 2019. Factors associated with testing positive for CT/NG via logistic regression modeling included city, younger age, lower education, long-acting reversible contraception usage, Trichomonas vaginalis infection, bacterial vaginosis, and incident syphilis infection. Based on these factors, the study population was stratified into high-, intermediate-, and low-prevalence subgroups and tested accordingly-individually, pools of 3, or pools of 4, respectively. The cost per sample was reduced from $18 to as low as $9.43 in the low-prevalence subgroup. The checklist tool and pooling approach described can be used in a variety of treatment algorithms to lower the cost per sample and increase access to molecular STI screening. This is particularly valuable in resource-limited settings to detect and treat asymptomatic CT/NG infections missed by traditional syndromic management.

Sustainability of high flow in a Peruvian PICU: A qualitative analysis.

To describe nurse and physician perspectives on enabling factors that promote sustainability of high flow use in resource-limited settings. Over 650000 children died from respiratory infections in 2016 globally. Many deaths could be prevented with access to advanced paediatric respiratory support, but sustainability of technology in resource-limited settings remains challenging. Local providers have expertise related to site-specific barriers to sustainability. Engaging local providers during implementation can identify strategies to promote ongoing technology use beyond initial deployment. This qualitative descriptive studywas conducted five focus groups with nineteen nurses and seven individual interviews with physicians in a Peruvian paediatric intensive care unit. Data were analysed using a realist thematic approach. Providers described five important factors for high flow sustainability: (i) Applying high flow to a broader patient population, including use outside the paediatric intensive care unit to increase opportunities for practice; (ii) Establishing a multidisciplinary approach to high flow management at all hours; (iii) Willingness of nurses and physicians to adopt standardization; (iv) Ongoing high flow leadership; (v) Transparency of high flow impact, including frequent reporting of clinical outcomes of high flow patients. Local providers described strategies to overcome barriers to sustainability of high flow in their clinical setting, many of which are generalizable to implementation projects in other resource-limited settings. These findings provide nursing, administrative leaders and policymakers with strategies to promote sustainability of new technology in resource-limited settings, including development of guidelines for appropriate clinical use, change management support, leadership development and clinical outcome reporting procedures. Administrative support and oversight are paramount to foster successful implementation in these settings.

422. Pooling Strategy for Chlamydia trachomatis and Neisseria gonorrhoeae Reduces Cost of GeneXpert Molecular STI Screening in Two Limited-Resource Clinics in Zambia

BackgroundRisk of heterosexual HIV-1 transmission is elevated in the presence of sexually transmitted infections (STIs) such as chlamydia (CT) and gonorrhea (NG). Syndromic management is a common, low-resource, approach to detecting STIs. However, CT and/or NG infections in women are often asymptomatic and therefore missed by syndromic management. Molecular testing for STIs is highly sensitive, but time and cost restraints preclude implementation of these technologies in resource-limited settings. Pooling samples for testing together in GeneXpert cartridges is one strategy for reducing the cost per individual tested.MethodsThis project describes the development of a pooling strategy based on social and demographic factors associated with CT/NG prevalence rates in a cohort of high-risk women in Zambia. Logistic regression modeling was used to predict the probability of a positive CT/NG test result in the presence of various factors. Data from a 2016 cross-sectional sub-study on intra-vaginal practices in 509 women was examined and an easy-to-use diagnostic screening checklist was created to categorize women by probability of testing positive on the GeneXpert. An algorithm considering cost of each test and prevalence of disease in each group determined the optimal pool size for each risk category.ResultsLogistic regression identified CT/NG to be associated with: city, age, education, long-acting reversible contraception usage, and laboratory results for bacterial vaginosis, Trichomonas vaginalis, and incident syphilis on the day of CT/NG testing. Signs and symptoms were not found to be associated. The overall prevalence of either CT and/or NG infection in this population was 17%. Low, middle, and high-risk groups could be separated based on checklist score with 7.52%, 18.30%, and 46.51% CT/NG prevalence, respectively.ConclusionPooling women with similar CT/NG predictive factors together, or testing those at highest risk individually, reduces the cost per test. Further implementation of this tool to guide presumptive treatment, in lieu of molecular testing, increases the cost-saving potential. The strategies described in this study are applicable to other low-resource clinical settings seeking to provide the accuracy of molecular testing with a reduced financial burden.Disclosures All authors: No reported disclosures.

The new frontier of diagnostics: Molecular assays and their role in infection prevention and control.

Recent advances in technology over the last decade have propelled the microbiology laboratory into a pivotal role in infection prevention and control. The rapid adaptation of molecular technologies to the field of clinical microbiology now greatly influences infectious disease management and significantly impacts infection control practices. This review discusses recent developments in molecular techniques in the diagnosis of infectious diseases. It describes the basic concepts of molecular assays, discusses their advantages and limitations, and characterizes currently available commercial assays with respect to cost, interpretive requirements, and clinical utility.

Rapid diagnostic point of care tests in resource limited settings

Abstract: One of the definitions of diagnostic point of care testing is provision of laboratory testing at or near the site of patient care. It has the potential to minimise the time to obtain the result of the test, which expedites the diagnosis and initiation of the treatment especially in resource-limited settings where health care infrastructure is weak and access to quality and timely medical care represents a challenge. It is estimated, that introduction of rapid, laboratory-independent diagnostic tests for four diseases (syphilis, malaria, tuberculosis and bacterial pneumonia) in developing countries could prevent more than 1.2 million deaths annually. In resource-limited settings, laboratory medicine is still one of the most neglected pillars of the health care. In such settings, primary health care services largely depend on diagnostic point of care testing; therefore the benefits need to overweight the costs. To optimise the diagnostic point-of-care, there is a need for strict evaluation focused on relevant clinical outcomes and operational costs and these evaluations differ from the conventional tests. However, there is no consistent, standardized approach to assess the point-of-care testing technologies in resource-limited settings. Diagnostic point-of-care testing possesses significant importance in infections like TB or HIV, because it eliminates the long turn-around times and delays and the resulting loss of patients from the testing and therapy pathway. An ideal rapid diagnostic point-of-care test used in resource-limited settings should fulfil the following criteria: allowing a quick clinical decision, can be used by a health care worker (possibly by a nonprofessional), affordable, rapid, acceptable test efficacy, and cost effectiveness.

CHALLENGES IN THE USE OF INFORMATION TECHNOLOGY IN PROCESSING OF HEALTH INFORMATION IN RESOURCE LIMITED SETTINGS: A COMPREHENSIVE SYSTEMATIC REVIEW

Information technology in processing and utilization of health information has significant health care outcomes. Its use in the assessment, diagnosis and management of health problems through access to relevant health information is crucial. The aim of this review was to identify the use of information technology in processing and utilization of health information in low resource settings. Method: a comprehensive systematic review focusing on resource limited settings were conducted. Results: the review identified the following challenges in the use of information technology in resource limited settings: lack of health information system and networking; limited knowledge and skills; information users’ participation; standardised health indicators and quality information processing. Conclusion: combining manual and technology assisted information processing system in less resource settings are essential in transforming and promoting the utilization of health information. The capacity development training; involvement of community professional nurses and midwives in the design and development of health information system for processing and utilization, and creating an enabling environment could overcome the challenges in the use of information technology in low resource settings.

Cell Phone-Based and Adherence Device Technologies for HIV Care and Treatment in Resource-Limited Settings: Recent Advances.

Numerous cell phone-based and adherence monitoring technologies have been developed to address barriers to effective HIV prevention, testing, and treatment. Because most people living with HIV and AIDS reside in resource-limited settings (RLS), it is important to understand the development and use of these technologies in RLS. Recent research on cell phone-based technologies has focused on HIV education, linkage to and retention in care, disease tracking, and antiretroviral therapy adherence reminders. Advances in adherence devices have focused on real-time adherence monitors, which have been used for both antiretroviral therapy and pre-exposure prophylaxis. Real-time monitoring has recently been combined with cell phone-based technologies to create real-time adherence interventions using short message service (SMS). New developments in adherence technologies are exploring ingestion monitoring and metabolite detection to confirm adherence. This article provides an overview of recent advances in these two families of technologies and includes research on their acceptability and cost-effectiveness when available. It additionally outlines key challenges and needed research as use of these technologies continues to expand and evolve.

The Global Burden of Pediatric Cryptosporidium Infections

Cryptosporidiosis has been identified as a leading cause of diarrhea in young children worldwide. Infection results in significant short-term morbidity as well as long-term sequelae. Recent advancements in molecular diagnostics used in large multicenter prospective studies have led to the discovery that burden of Cryptosporidium disease is higher than previously recognized; however, the implications of this discovery are not fully understood. Epidemiologic studies suggest infection impacts long-term growth; however, the mechanisms driving this vicious cycle have yet to be elucidated, and it remains to be seen why malnutrition renders such high susceptibility to Cryptosporidium. Whole-genome sequencing has refined classification of anthroponotic and zoonotic strains and may shed light on novel modes of transmission and species -specific pathogenicity. As Cryptosporidium has been recognized as a significant pathogen with implications on child health it challenges us to determine the mechanisms of pathogenesis for this difficult to study parasite and also enforces the need to continue advancing innovative technologies in resource-limited settings to curb the impact of this neglected tropical disease.

Are surveillance response systems enough to effectively combat and contain the Ebola outbreak?

The epidemic of the Ebola virus infection in West Africa in 2014 has become a worldwide concern. Due to the nature of the disease, which has an extremely high mortality potential, this outbreak has received much attention from researchers and public health workers. An article entitled "Need of surveillance response systems to combat Ebola outbreaks and other emerging infectious diseases in African countries," published in the journal Infectious Diseases of Poverty in August 2014, concluded that a good surveillance system to monitor disease transmission dynamics is essential and needs to be implemented to combat the outbreak. Issues regarding the limitation of the passive surveillance system have been raised by Professor Viroj Wiwanitkit, who emphasizes the need for an active disease detection system such as mass screening in this letter to editor. The different function between passive and active surveillance system in combating the disease outbreak has been agreed upon by Ernest Tambo et al. There have also been discussions between Wiwanitkit and Tambo et al. on the following issues: (i) the extreme resource limitations in outbreak areas, (ii) new technology to improve the available systems. Further recommendations echoed in this letter to editor by Wiwanitkit, who outlined the research priorities on the development of appropriate combined disease monitoring systems and good policy to allocate available tools and technology in resource-limited settings for epidemic scenarios. The journal’s editor, Professor Xiao-Nong Zhou, has therefore collated all parts of these discussions between authors in this letter to editor paper, in order to further promote research on a combined active and passive system to combat the present extending Ebola outbreak.Electronic supplementary materialThe online version of this article (doi:10.1186/2049-9957-4-7) contains supplementary material, which is available to authorized users.

Point-of-care ultrasound use over six-month training period in Rwandan district hospitals

Introduction Point-of-care ultrasound (POCUS) is an effective diagnostic technology in resource-limited settings. There is increasing interest in introducing ultrasound training in such environments, but few reports describing long-term follow-up and impact of a POCUS program in a resource-limited setting. We introduced a POCUS program in Rwanda, and sought to determine the number and type of ultrasounds performed, the impact of a remote quality assurance (QA) program, and the effect of POCUS on patient management. Methods Seventeen Rwandan physicians underwent a ten-day training course in POCUS in Kigali, Rwanda. Post-course, participants tracked the ultrasounds they performed using a cloud-based storage system, recorded clinical impressions, and received periodic QA with on-site proctoring over a six-month follow-up. Remote QA to evaluate image quality was performed by five emergency ultrasound fellowship-trained clinicians. Images were graded on a scale of 0–4. (0=no meaningful image, 2=adequate, 4=outstanding). Trainees also documented how POCUS changed clinical management. Results Over six months, 1158 ultrasounds were performed and logged by fifteen participants at eleven regional hospitals. 590 (50.9%) had matched images and interpretations available for review. Abdominal ultrasound was the most frequently performed application (19.7%), followed by liver (14.6%), obstetrics (14.5%), renal (12.4%), and spleen (11%). Across all applications, the mean score was 2.5 (SD±0.11, 95% confidence interval, 2.39–2.54). Ultrasound resulted in a management change in 84% of cases. Major changes in management related to medication choice (42.4%), admission (30%), transfer to a higher level of care (28.1%), and performance of procedures (23.3%). Conclusions During this six-month training program in Rwanda, participants used POCUS for a range of applications. The remote QA process captured 51% of ultrasounds performed. Of scans with QA, the average score was adequate to good. POCUS routinely changed clinical management. This study demonstrates the impact of POCUS in a resource-limited setting.