Managing Severe Acute Asthma Exacerbation in Pregnancy during the COVID-19 Pandemic: A Case Report from a Resource-limited Setting

BACKGROUND: One-third of pregnant women will experience worsening asthma requiring emergency hospitalization. However, no report comprehensively discussed the management of asthma attacks in pregnant women in impoverished settings. We attempt to illuminate what general practitioners can do to stabilize and improve the outcome of severe acute asthma exacerbations in primary care with resource limitations. CASE REPORT: A nulliparous 29-year-old woman in her 21st week of pregnancy presented severe acute asthma exacerbation in moderate persistent asthma with uncontrolled asthma status along with gestational hypertension, uncompensated metabolic acidosis with a high anion gap, anemia, respiratory infection, and asymptomatic bacteriuria, all of which influenced her exacerbations. This patient was admitted to our resource-limited subdistrict hospital in Indonesia during the COVID-19 pandemic for optimal stabilization. Crystalloid infusions, oxygen supplementation, nebulized beta-agonist with anticholinergic agents, inhaled corticosteroids, intravenous methylprednisolone, broad-spectrum antibiotics, subcutaneous terbutaline, mucolytics, magnesium sulphate, oral antihypertensives, and continuous positive airway pressure were used to treat her life-threatening asthma. After she was stabilized, we referred the patient to a higher-level hospital with more advanced pulmonary management under the supervision of a multidisciplinary team to anticipate the worst scenario of pregnancy termination. CONCLUSION(S): Limitations in primary care, including the lack of sophisticated intensive care units and laboratory panels, may complicate challenges in managing severe acute asthma exacerbation during pregnancy. To enhance maternal-fetal outcomes, all multidisciplinary team members should be well-informed about key asthma management strategies during pregnancy using evidence-based guidelines regarding the drug, rationale, and safety profile.Copyright © 2023 Muhammad Habiburrahman, Triya Damayanti, Mohammad Adya Firmansha Dilmy, Hariyono Winarto.

Three rare presentations of high-altitude pulmonary edema at a high-altitude clinic in the Everest region (4371 m): A case series.

Diagnosis of HAPE can be challenging when the presentation deviates from usual natural history. Point of care ultrasonography serves as a great diagnostic tool in such settings. An umbrella treatment could be beneficial during such scenarios.

Prognostication using SpO2/FiO2 in invasively ventilated ICU patients with ARDS due to COVID-19 - Insights from the PRoVENT-COVID study.

BACKGROUND: The SpO2/FiO2 is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO2/FiO2 for mortality in patients with ARDS due to COVID-19. METHODS: This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID-19. The primary endpoint was 28-day mortality. RESULTS: In 869 invasively ventilated patients, 28-day mortality was 30.1%. The SpO2/FiO2 on day 1 had no prognostic value. The SpO2/FiO2 on day 2 and day 3 had prognostic capacity for death, with the best cut-offs being 179 and 199, respectively. Both SpO2/FiO2 on day 2 (OR, 0.66 [95%-CI 0.46-0.96]) and on day 3 (OR, 0.70 [95%-CI 0.51-0.96]) were associated with 28-day mortality in a model corrected for age, pH, lactate levels and kidney dysfunction (AUROC 0.78 [0.76-0.79]). The measured PaO2/FiO2 and the PaO2/FiO2 calculated from SpO2/FiO2 were strongly correlated (Spearman's r = 0.79). CONCLUSIONS: In this cohort of patients with ARDS due to COVID-19, the SpO2/FiO2 on day 2 and day 3 are independently associated with and have prognostic capacity for 28-day mortality. The SpO2/FiO2 is a useful metric for risk stratification in invasively ventilated COVID-19 patients.

Challenges to sustainability of pediatric early warning systems (PEWS) in low-resource hospitals in Latin America.

Background: Sustainability, or continued use of evidence-based interventions for long-term patient benefit, is the least studied aspect of implementation science. In this study, we evaluate sustainability of a Pediatric Early Warning System (PEWS), an evidence-based intervention to improve early identification of clinical deterioration in hospitalized children, in low-resource settings using the Clinical Capacity for Sustainability Framework (CCS). Methods: We conducted a secondary analysis of a qualitative study to identify barriers and enablers to PEWS implementation. Semi-structured interviews with PEWS implementation leaders and hospital directors at 5 Latin American pediatric oncology centers sustaining PEWS were conducted virtually in Spanish from June to August 2020. Interviews were recorded, professionally transcribed, and translated into English. Exploratory thematic content analysis yielded staff perceptions on PEWS sustainability. Coded segments were analyzed to identify participant perception about the current state and importance of sustaining PEWS, as well as sustainability successes and challenges. Identified sustainability determinants were mapped to the CCS to evaluate its applicability. Results: We interviewed 71 staff including physicians (45%), nurses (45%), and administrators (10%). Participants emphasized the importance of sustaining PEWS for continued patient benefits. Identified sustainability determinants included supportive leadership encouraging ongoing interest in PEWS, beneficial patient outcomes enhancing perceived value of PEWS, integrating PEWS into the routine of patient care, ongoing staff turnover creating training challenges, adequate material resources to promote PEWS use, and the COVID-19 pandemic. While most identified factors mapped to the CCS, COVID-19 emerged as an additional external sustainability challenge. Together, these challenges resulted in multiple impacts on PEWS sustainment, ranging from a small reduction in PEWS quality to complete disruption of PEWS use and subsequent loss of benefits to patients. Participants described several innovative strategies to address identified challenges and promote PEWS sustainability. Conclusion: This study describes clinician perspectives on sustainable implementation of evidence-based interventions in low-resource settings, including sustainability determinants and potential sustainability strategies. Identified factors mapped well to the CCS, however, external factors, such as the COVID pandemic, may additionally impact sustainability. This work highlights an urgent need for theoretically-driven, empirically-informed strategies to support sustainable implementation of evidence-based interventions in settings of all resource-levels.

The impact of a "short-term" basic intensive care training program on the knowledge of nonintensivist doctors during the COVID-19 pandemic: An experience from a population-dense low- and middle-income country.

BACKGROUND: The utility of basic intensive care unit (ICU) training comprising a "1-day course" has been scientifically evaluated and reported in very few studies, with almost no such study from resource-limited settings. AIM: The study assessed the utility of basic ICU training comprising of a "1-day course" in increasing the knowledge of nonintensivist doctors. MATERIALS AND METHODS: This is an observational study conducted at a medical university in North India in 2020. The participants were nonintensivist doctors attending the course. The course was designed by intensivists, and it had four domains. The participants were categorised on the basis of their duration of ICU experience and broad speciality. Pretest and posttest was administered, which was analysed to ascertain the gain in the knowledge score. RESULTS: A total of 252 participants were included, of which the majority were from the clinical medicine speciality (85.3%) and had ICU experience of 1-6 months (47.6%). There was a significant improvement in the mean total score of the participants after training from 14/25 to 19/25, with a mean difference (MD) of 5.02 (p < 0.001). Based on ICU experience, in groups I (<1 month), II (1-6 months), and III (>6 months), there was a significant improvement in the total score of the participants after training with MD with 95% confidence interval (CI) limits of 5.27 (4.65-5.90), 4.70 (4.38-5.02), and 5.33 (4.89-5.78), respectively. In the clinical surgery specialty (n = 37), there was a significant improvement in the total score after training from 11/25 to 16.4/25 with an MD (95% CI limits) of 5.38 (4.4-6.3). Similarly, in the clinical medicine group (n = 215), the MD (95% CI limits) score after training was 4.95 (4.71-5.20), from 14.5/25 to 19.5/25. In feedback, more than half of the participants showed interest in joining ICU after training. CONCLUSIONS: Training nonintensivist doctors for 1 day can be useful in improving their knowledge, regardless of their prior ICU experience and speciality.

Evaluation of Various Alternative Economical and High Throughput SARS-CoV-2 Testing Methods within Resource-Limited Settings.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak posed a challenge for diagnostic laboratories worldwide, with low-middle income countries (LMICs) being the most affected. The polymerase chain reaction (PCR) is the gold standard method for detecting SARS-CoV-2 infection. However, the challenge with this method is that it is expensive, which has resulted in under-testing for SARS-CoV-2 infection in many LMICs. Hence, this study aimed to compare and evaluate alternative methods for the mass testing of SARS-CoV-2 infection in laboratories with limited resources to identify cost-effective, faster, and accurate alternatives to the internationally approved kits. A total of 50 residual nasopharyngeal swab samples were used for evaluation and comparison between internationally approved kits (Thermo Fisher PureLink™ RNA Isolation Kit and Thermo Fisher TaqPath™ COVID-19 Assay Kit) and alternative methods (three RNA extraction and four commercial SARS-CoV-2 RT-PCR assay kits) in terms of the cost analysis, diagnostic accuracy, and turnaround time. In terms of performance, all of the alternative RNA extraction methods evaluated were comparable to the internationally approved kits but were more cost-effective (Lucigen QuickExtract™ RNA Extraction Kit, Bosphore EX-Tract Dry Swab RNA Solution and Sonicator method) and four commercial SARS-CoV-2 RT-PCR assay kits (Nucleic Acid COVID-19 Test Kit (SARS-CoV-2), abTESTM COVID-19 qPCR I Kit, PCL COVID19 Speedy RT-PCR Kit, and PCLMD nCoV One-Step RT-PCR Kit) with a sensitivity range of 76-100% and specificity of 96-100%. The cost per sample was reduced by more than 50% when compared to internationally approved kits. When compared to the Thermo Fisher PureLink™ Kit and Thermo Fisher TaqPath™ COVID-19 Assay Kit, the alternative methods had a faster turnaround time, indicating that laboratories with limited resources may be able to process more samples in a day. The above-mentioned cost-effective, fast, and accurate evaluated alternative methods can be used in routine diagnostic laboratories with limited resources for mass testing for SARS-CoV-2 because these were comparable to the internationally approved kits, Thermo Fisher PureLink™ Kit and Thermo Fisher TaqPath™ COVID-19 Assay Kit. The implementation of alternative methods will be the most cost-effective option for testing SARS-CoV-2 infection in LMICs.

Designing and Piloting of a Mobile Learning Curriculum for Quality Point-Of-Care Diagnostics Services in Rural Clinics of KwaZulu-Natal, South Africa.

Background: The use of mobile technology has been reported to help improve access to education for people in remote areas. However, there is limited evidence of its adoption in resource-limited settings. The aim of this study was to utilize stakeholder generated ideas to design and pilot a mobile learning curriculum, with the purpose of facilitating training to improve the quality of point-of-care diagnostics services in KwaZulu-Natal (KZN) rural clinics. Methods: Nominal Group Technique was employed to enable collaboration with stakeholders in designing and piloting of a POC diagnostics curriculum. Stakeholders were selected from 11 KZN districts to participate in a clinic-based piloting of the curriculum using an online application. The application was designed in collaboration with a teacher training institute in Durban. Moodle was used as an established reliable online learning management system. During piloting, quantitative and qualitative data were generated and analyzed using descriptive statistics and content analysis. Findings and Conclusion: Guided by the Nominal Group Technique results, five delivery modes for curriculum content through Mobile Learning were generated. An interactive course page was created on the Moodle site, titled: Quality HIV Point of Care Diagnostics Curriculum Delivery for Nurses in Rural Areas. The course content consisted of three teaching units, activities, an online quiz and an online survey. An analytic-algorithm built into the online course enabled monitoring of participation and assessment outcomes automatically. At piloting, 64% of the invited representative clinics were able to access the course, with 47% meeting the course completion requirements. All the participants achieved the set pass mark of 75% with an average of 87%. The activity completion report showed that topics presented through images, videos and simple text were accessed more than those presented as attachments of national documents. Despite poor network coverage and limited access to mobile technology, exacerbated by Covid-19 related restrictions, Point of care diagnostics Mobile Learning curriculum was well-received in participating rural clinics. Recommendations relating to course improvement and access, included extending collaboration with specialists in eHealth systems development and with South African cell phone network providers.

Automated Recognition of Plasmodium falciparum Parasites from Portable Blood Levitation Imaging.

In many malaria-endemic regions, current detection tools are inadequate in diagnostic accuracy and accessibility. To meet the need for direct, phenotypic, and automated malaria parasite detection in field settings, a portable platform to process, image, and analyze whole blood to detect Plasmodium falciparum parasites, is developed. The liberated parasites from lysed red blood cells suspended in a magnetic field are accurately detected using this cellphone-interfaced, battery-operated imaging platform. A validation study is conducted at Ugandan clinics, processing 45 malaria-negative and 36 malaria-positive clinical samples without external infrastructure. Texture and morphology features are extracted from the sample images, and a random forest classifier is trained to assess infection status, achieving 100% sensitivity and 91% specificity against gold-standard measurements (microscopy and polymerase chain reaction), and limit of detection of 31 parasites per µL. This rapid and user-friendly platform enables portable parasite detection and can support malaria diagnostics, surveillance, and research in resource-constrained environments.

Portable Biosafety Barrier Innovations to Limit Transmissibility of Infectious Diseases during Patient Care in Resource-limited Settings during the COVID-19 Pandemic.

Background: The coronavirus disease-2019 (COVID-19) pandemic has brought about a change in healthcare practices that are likely to persist into the foreseeable future. In particular, is the exposure risk to the healthcare practitioners in the emergency department (ED) and the intensive care units. Mitigating this issue in a low-resource setting remains challenging, and in particular, in developing nations such as India, where ED patient flows can overwhelm a system and its human resources, breaking down processes and infecting healthcare workers (HCWs). Technique: To tackle this and the possible lack of appropriate personal protective equipment (PPE), we designed and built biosafety barrier devices using local resources for use in patient stabilization, transport, and continued care in the ED or the intensive care units. Results: Four biosafety devices bio-safe levels 1 and 2, ultra-ductile portable interface of interventions in infections, and tented transport trolley for transmissibility (4T) were tested for the feasibility of usage for patient care during the pandemic with simulation. Conclusion: We anticipate that with time it may be common practice for in situ isolation of patients in the emergency departments with a suspicion of an infectious disease. With the proof of concept, simulation, hospital infection control committee (HICC) approval, and trial run, we look to close the gaps that exist in these initial innovations. How to cite this article: Balakrishnan JM, Sirur FM, Prakash N, Bhat R, Wilson W, Angadi B, et al. Portable Biosafety Barrier Innovations to Limit Transmissibility of Infectious Diseases during Patient Care in Resource-limited Settings during the COVID-19 Pandemic. Indian J Crit Care Med 2022;26(9):1036-1038.

Challenge of managing hepatitis B virus and hepatitis C virus infections in resource-limited settings.

The global burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and coinfection represents a major public health concern, particularly in resource-limited settings. Elimination of HCV by 2030 has become foreseeable, with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries (LMICs). However, access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices. Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal. Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection, and with improved access to medications, the most significant barrier remains access to affordable diagnostics and preventive strategies. The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs, albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage. This review underpins the HBV and HCV management challenges in resource-limited settings, highlighting the current status and suggested future elimination strategies in some of these countries. Global efforts should continue to improve awareness and political commitment. Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.

A fast extraction-free isothermal LAMP assay for detection of SARS-CoV-2 with potential use in resource-limited settings.

BACKGROUND: To retain the spread of SARS-CoV-2, fast, sensitive and cost-effective testing is essential, particularly in resource limited settings (RLS). Current standard nucleic acid-based RT-PCR assays, although highly sensitive and specific, require transportation of samples to specialised laboratories, trained staff and expensive reagents. The latter are often not readily available in low- and middle-income countries and this may significantly impact on the successful disease management in these settings. Various studies have suggested a SARS-CoV-2 loop mediated isothermal amplification (LAMP) assay as an alternative method to RT-PCR. METHODS: Four previously published primer pairs were used for detection of SARS-CoV-2 in the LAMP assay. To determine optimal conditions, different temperatures, sample input and incubation times were tested. Ninety-three extracted RNA samples from St. George's Hospital, London, 10 non-extracted nasopharyngeal swab samples from Great Ormond Street Hospital for Children, London, and 92 non-extracted samples from Queen Elisabeth Central Hospital (QECH), Malawi, which have previously been tested for SARS-Cov-2 by quantitative reverse-transcription RealTime PCR (qRT-PCR), were analysed in the LAMP assay. RESULTS: In this study we report the optimisation of an extraction-free colourimetric SARS-CoV-2 LAMP assay and demonstrated that a lower limit of detection (LOD) between 10 and 100 copies/µL of SARS-CoV-2 could be readily detected by a colour change of the reaction within as little as 30 min. We further show that this assay could be quickly established in Malawi, as no expensive equipment is necessary. We tested 92 clinical samples from QECH and showed the sensitivity and specificity of the assay to be 86.7% and 98.4%, respectively. Some viral transport media, used routinely to stabilise RNA in clinical samples during transportation, caused a non-specific colour-change in the LAMP reaction and therefore we suggest collecting samples in phosphate buffered saline (which did not affect the colour) as the assay allows immediate sample analysis on-site. CONCLUSION: SARS-CoV-2 LAMP is a cheap and reliable assay that can be readily employed in RLS to improve disease monitoring and management.

Open Online Courses for Strengthening Laboratory-Based Detection of Antimicrobial Resistance in Pakistan.

Introduction: Quality-assured antimicrobial susceptibility testing (AST) depends upon the knowledge and skills of laboratory staff. In many low- and middle-income countries (LMICs), including Pakistan, such types of knowledge and skills are limited. Therefore, the objective of this study was to use openaccess online courses to improve the knowledge of laboratory staff involved in the detection and reporting of antimicrobial resistance (AMR). Methodology: Seven online modules comprising 22 courses aimed at strengthening the laboratory detection of Antimicrobial resistance (AMR) were developed. The courses were uploaded onto the website www.parn.org.pk. Participants had an option of selecting courses of their interest. Online registration and completion of a pre-course assessment (pre-test) were essential for enrolment. However, participation in post-course assessment (post-test) was optional. The number of registered participants and the proportion of participants who completed each course were computed. A paired t-test was used to assess the increase between mean pre- and post-test scores. The association between the participants working in public vs. private laboratories and course completion rates were determined using the chi-square test. Results: A total of 227 participants from Pakistan (March 2018 to June 2020) were registered. The largest number of registered participants and the highest completion rate were noted for AST and biosafety courses, while quality-related courses attracted a lower interest. A comparison of pre- and post-test performance using the paired mean score for the individual courses showed a statistically significant (the value of p < 0.05) improvement in 13/20 assessed courses. A higher course completion rate was observed in participants from public vs. private sector laboratories (56.8 vs. 30.8%, the value of p = 0.005). Conclusions: Our study suggests a promising potential for open online courses (OOCs) toward addressing knowledge gaps in laboratory practice in resource limited settings.

Conference proceedings from virtual 24th Bangkok International Symposium on HIV medicine

HIV-NAT has held the Bangkok International Symposium on HIV Medicine annually since 1998. It provides the latest advances in HIV medicine to professional healthcare workers in the Asia-Pacific region. This year's symposium (the 24th) was held virtually, from 19 to 21 January 2022. There were a total of 27 sessions divided over 3 days. The Symposium started in the afternoon following industrial symposia and ended at 18:00. Various topics were presented by experts from Australia, India, Malaysia, The Netherlands, Singapore, Switzerland, Thailand, UK and USA. COVID-19 has changed healthcare delivery and artificial intelligence is changing medical practice so sessions on these topics were included in the symposium.

The challenges of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in low-middle income countries and possible cost-effective measures in resource-limited settings.

Diagnostic testing for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains a challenge around the world, especially in low-middle-income countries (LMICs) with poor socio-economic backgrounds. From the beginning of the pandemic in December 2019 to August 2021, a total of approximately 3.4 billion tests were performed globally. The majority of these tests were restricted to high income countries. Reagents for diagnostic testing became a premium, LMICs either cannot afford or find manufacturers unwilling to supply them with expensive analytical reagents and equipment. From March to December 2020 obtaining testing kits for SARS-CoV-2 testing was a challenge. As the number of SARS-CoV-2 infection cases increases globally, large-scale testing still remains a challenge in LMICs. The aim of this review paper is to compare the total number and frequencies of SARS-CoV-2 testing in LMICs and high-income countries (HICs) using publicly available data from Worldometer COVID-19, as well as discussing possible interventions and cost-effective measures to increase testing capability in LMICs. In summary, HICs conducted more SARS-CoV-2 testing (USA: 192%, Australia: 146%, Switzerland: 124% and Canada: 113%) compared to middle-income countries (MICs) (Vietnam: 43%, South Africa: 29%, Brazil: 27% and Venezuela: 12%) and low-income countries (LICs) (Bangladesh: 6%, Uganda: 4% and Nigeria: 1%). Some of the cost-effective solutions to counteract the aforementioned problems includes using saliva instead of oropharyngeal or nasopharyngeal swabs, sample pooling, and testing high-priority groups to increase the number of mass testing in LMICs.

Impact of COVID-19 on Tuberculosis Case Detection and Treatment Outcomes in Sierra Leone.

The COVID-19 pandemic has adversely affected tuberculosis (TB) care delivery in high burden countries. We therefore conducted a retrospective study to assess the impact of COVID-19 on TB case detection and treatment outcomes at the Chest Clinic at Connaught Hospital in Freetown, Sierra Leone. Overall, 2300 presumptive cases were tested during the first three quarters of 2020 (intra-COVID-19) versus 2636 in 2019 (baseline), representing a 12.7% decline. Testing declined by 25% in women, 20% in children and 81% in community-initiated referrals. Notwithstanding, laboratory-confirmed TB cases increased by 37.0% and treatment success rate was higher in 2020 (55.6% vs. 46.7%, p = 0.002). Multivariate logistic regression analysis found that age < 55 years (aOR 1.74, 95% CI (1.80, 2.56); p = 0.005), new diagnosis (aOR 1.69, 95% CI (1.16, 2.47); p = 0.007), pulmonary TB (aOR 3.17, 95% CI (1.67, 6.04); p < 0.001), HIV negative status (aOR 1.60, 95%CI (1.24, 2.06); p < 0.001) and self-administration of anti-TB drugs through monthly dispensing versus directly observed therapy (DOT) (aOR 1.56, 95% CI (1.21, 2.03); p = 0.001) independently predicted treatment success. These findings may have policy implications for DOTS in this setting and suggest that more resources are needed to reverse the negative impact of the COVID-19 pandemic on TB program activities in Sierra Leone.

Chemoprophylaxis against COVID-19 among health-care workers using Ivermectin in low- and middle-income countries: A systematic review and meta-analysis.

Coronavirus disease-2019 (COVID-19) is a novel viral infectious disease that the World Health Organization (WHO) has announced to be a pandemic. This meta-analysis was aimed at providing evidence for the use of ivermectin to prevent COVID-19 among hospital workers in low-resource countries. Medical databases including African Journals online, Google Scholar, PubMed, Cochrane library, EMBASE, COVID-19 research database (WHO), Clinicaltrials.gov, and SCOPUS were searched for studies on Ivermectin as a chemoprophylactic drug against COVID-19 among hospital personnel in settings with limited resources. Preprint servers such as bioRxiv and medRxiv as well as the gray literature were also searched. Studies adjudged to be eligible were identified using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses algorithm. Statistical analyses were done using Stata version 14.3. Seven studies were selected for the meta-analysis. The total sample size was 2652. There were two randomized controlled trials and five nonrandomized studies. Some studies dosed Ivermectin daily while some dosed it weekly. However, one of the studies dosed it monthly. The studies reported variable clinical benefits. I2 statistic was 92%, and random effect model was used. The pooled odd ratio was 0.11 (95% confidence interval 0.09-0.13). This implies that 89% of the participants benefited from taking Ivermectin as a form of preexposure chemoprophylaxis. Ivermectin has a significant clinical benefit as a preventive drug against COVID-19 for hospital personnel in settings with limited resources.

A Scoping Review of Supply Chain Management Systems for Point of Care Diagnostic Services: Optimising COVID-19 Testing Capacity in Resource-Limited Settings.

BACKGROUND: Point of care (POC) testing has enabled rapid coronavirus disease 2019 (COVID-19) diagnosis in resource-limited settings with limited laboratory infrastructure and high disease burden. However, the accessibility of the tests is not optimal in these settings. This scoping review mapped evidence on supply chain management (SCM) systems for POC diagnostic services to reveal evidence that can help guide future research and inform the improved implementation of SARS-CoV-2 POC diagnostics in resource-limited settings. METHODOLOGY: This scoping review was guided by an adapted version of the Arksey and O'Malley methodological framework. We searched the following electronic databases: Medline Ovid, Medline EBSCO, Scopus, PubMed, PsychInfo, Web of Science and EBSCOHost. We also searched grey literature in the form of dissertations/theses, conference proceedings, websites of international organisations such as the World Health Organisation and government reports. A search summary table was used to test the efficacy of the search strategy. The quality of the included studies was appraised using the mixed method appraisal tool (MMAT) version 2018. RESULTS: We retrieved 1206 articles (databases n = 1192, grey literature n = 14). Of these, 31 articles were included following abstract and full-text screening. Fifteen were primary studies conducted in LMICs, and 16 were reviews. The following themes emerged from the included articles: availability and accessibility of POC diagnostic services; reasons for stockouts of POC diagnostic tests (procurement, storage, distribution, inventory management and quality assurance) and human resources capacity in POC diagnostic services. Of the 31 eligible articles, 15 underwent methodological quality appraisal with scores between 90% and 100%. CONCLUSIONS: Our findings revealed limited published research on SCM systems for POC diagnostic services globally. We recommend primary studies aimed at investigating the barriers and enablers of SCM systems for POC diagnostic services for highly infectious pathogens such SARS-CoV-2 in high disease-burdened settings with limited laboratory infrastructures.

Enhancing the Stability of COVID-19 Serological Assay through Metal-Organic Framework Encapsulation.

Enzyme-linked immunosorbent assay is widely utilized in serologic assays, including COVID-19, for the detection and quantification of antibodies against SARS-CoV-2. However, due to the limited stability of the diagnostic reagents (e.g., antigens serving as biorecognition elements) and biospecimens, temperature-controlled storage and handling conditions are critical. This limitation among others makes biodiagnostics in resource-limited settings, where refrigeration and electricity are inaccessible or unreliable, particularly challenging. In this work, metal-organic framework encapsulation is demonstrated as a simple and effective method to preserve the conformational epitopes of antigens immobilized on microtiter plate under non-refrigerated storage conditions. It is demonstrated that in situ growth of zeolitic imidazolate framework-90 (ZIF-90) renders excellent stability to surface-bound SARS-CoV-2 antigens, thereby maintaining the assay performance under elevated temperature (40 °C) for up to 4 weeks. As a complementary method, the preservation of plasma samples from COVID-19 patients using ZIF-90 encapsulation is also demonstrated. The energy-efficient approach demonstrated here will not only alleviate the financial burden associated with cold-chain transportation, but also improve the disease surveillance in resource-limited settings with more reliable clinical data.

A Multiplex and Colorimetric Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Sensitive and Rapid Detection of Novel SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major threat to public health. Rapid molecular testing for convenient and timely diagnosis of SARS-CoV-2 infections represents a challenge that could help to control the current pandemic and prevent future outbreaks. We aimed to develop and validate a multiplex and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using lyophilized LAMP reagents for sensitive and rapid detection of SARS-CoV-2. LAMP primers were designed for a set of gene targets identified by a genome-wide comparison of viruses. Primer sets that showed optimal features were combined into a multiplex RT-LAMP assay. Analytical validation included assessment of the limit of detection (LoD), intra- and inter-assay precision, and cross-reaction with other respiratory pathogens. Clinical performance compared to that of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was assessed using 278 clinical RNA samples isolated from swabs collected from individuals tested for COVID-19. The RT-LAMP assay targeting the RNA-dependent RNA polymerase (RdRp), membrane (M), and ORF1ab genes achieved a comparable LoD (0.65 PFU/mL, CT=34.12) to RT-qPCR and was 10-fold more sensitive than RT-qPCR at detecting viral RNA in clinical samples. Cross-reactivity to other respiratory pathogens was not observed. The multiplex RT-LAMP assay demonstrated a strong robustness and acceptable intra- and inter-assay precision (mean coefficient of variation, 4.75% and 8.30%). Diagnostic sensitivity and specificity values were 100.0% (95% CI: 97.4-100.0%) and 98.6% (95% CI: 94.9-99.8%), respectively, showing high consistency (Cohen's kappa, 0.986; 95% CI: 0.966-1.000; p<0.0001) compared to RT-qPCR. The novel one-step multiplex RT-LAMP assay is storable at room temperature and showed similar diagnostic accuracy to conventional RT-qPCR, while being faster (<45 min), simpler, and cheaper. The new assay could allow reliable and early diagnosis of SARS-CoV-2 infections in primary health care. It may aid large-scale testing in resource-limited settings, especially if it is integrated into a point-of-care diagnostic device.

Fast, Scalable, and Practical: An Alkaline DNA Extraction Pipeline for Emergency Microbiomics Biosurveillance.

Pandemics and environmental crises evident from the first two decades of the 21st century call for methods innovation in biosurveillance and early detection of risk signals in planetary ecosystems. In crises conditions, conventional methods in public health, biosecurity, and environmental surveillance do not work well. In addition, the standard laboratory amenities and procedures may become unavailable, irrelevant, or simply not feasible, for example, owing to disruptions in logistics and process supply chains. The COVID-19 pandemic has been a wakeup call in this sense to reintroduce point-of-need diagnostics with an eye to limited resource settings and biosurveillance solutions. We report here a methodology innovation, a fast, scalable, and alkaline DNA extraction pipeline for emergency microbiomics biosurveillance. We believe that the presented methodology is well poised for effective, resilient, and anticipatory responses to future pandemics and ecological crises while contributing to microbiome science and point-of-need diagnostics in nonelective emergency contexts. The alkaline DNA extraction pipeline can usefully expand the throughput in emergencies by deployment or to allow backup in case of instrumentation failure in vital facilities. The need for distributed public health genomics surveillance is increasingly evident in the 21st century. This study makes a contribution to these ends broadly, and for future pandemic preparedness in particular. We call for innovation in biosurveillance methods that remain important existentially on a planet under pressure from unchecked human growth and breach of the boundaries between human and nonhuman animal habitats.