Cost-effectiveness analysis of a multiplex lateral flow rapid diagnostic test for acute non-malarial febrile illness in rural Cambodia and Bangladesh.

Background: Multiplex lateral flow rapid diagnostic tests (LF-RDTs) may aid management of patients with acute non-malarial febrile illness (NMFI) in rural south and southeast Asia. We aimed to evaluate the cost-effectiveness in Cambodia and Bangladesh of a putative, as-yet-undeveloped LF-RDT capable of diagnosing enteric fever and dengue, as well as measuring C-reactive protein (CRP) to guide antibiotic prescription, in primary care patients with acute NMFI. Methods: A country-specific decision tree model-based cost-effectiveness analysis was conducted from a health system plus limited societal perspective considering the cost of antimicrobial resistance. Parameters were based on data from a large observational study on the regional epidemiology of acute febrile illness, published studies, and procurement price lists. Costs were expressed in US$ (value in 2022), and cost-effectiveness evaluated by comparing incremental cost-effectiveness ratios with conservative opportunity cost-based willingness-to-pay thresholds and the more widely used threshold of per capita gross domestic product (GDP). Findings: Compared to standard of care, LF-RDT-augmented clinical assessment was dominant in Cambodia, being more effective and cost-saving. The cost per disability-adjusted life year (DALY) averted in Bangladesh was US$482, slightly above the conservative opportunity cost-based willingness-to-pay threshold of US$388 and considerably lower than the GDP-based threshold of US$2687. The intervention remained dominant in Cambodia and well below the GDP-based threshold in Bangladesh when antimicrobial resistance costs were disregarded. Interpretation: These findings provide guidance for academic, industry, and policymaker stakeholders involved in acute NMFI diagnostics. While definitive conclusions cannot be made in the absence of established thresholds, our results suggest that similar results are highly likely in some target settings and possible in others. Funding: Wellcome Trust, UK Government, Royal Australasian College of Physicians, and Rotary Foundation.

Integrating climate change in Environmental Impact Assessment: A review of requirements across 19 EIA regimes.

The contribution of human activities to climate change is well understood. Yet the integration of climate change considerations into local decision making tools designed to govern activities affecting the environment, such as Environmental Impact Assessments (EIAs), remains underdeveloped and inconsistently applied for proposed policies, programs, plans and projects. This study reviews progress across a range of 19 EIA regimes and identifies and assesses regulations and guidelines that have been established to promote the integration of climate change considerations within EIAs. A typology of levels of integration is developed to guide analysis across multiple EIA regimes. The findings identify a global and growing requirement for climate change aspects to be considered within EIAs and describe the range of ways this is done across the regimes selected. Climate change is typically concerned with the mitigation of greenhouse gas emissions from proposed developments in EIAs. Fewer regimes are concerned with climate change adaptation, and in general, an integration deficit is identified for regimes where climate change is only partially considered. Examples of high integration indicate that EIA holds the potential to play a substantive role in climate change governance at project level decision making, suggesting the tools hold promise for local level climate governance. However, many domestic obstacles can militate against integration, including political, socio-technical, and economic imperatives, particularly for exemptions of sector and scope. Nevertheless, examples also indicate advances can be made through jurisprudence during the EIA review stage to establish new precedents of how climate should be considered in EIAs. Potential future research and practice directions are identified, and recommendations include the development of regulations and practice guidelines; inclusion of climate change adaptation; strengthening post-decision monitoring; application to all relevant sectors and activities; alignment with SEA; and integration across all stages of the EIA process.

Perceptions and priorities for the development of multiplex rapid diagnostic tests for acute non-malarial fever in rural South and Southeast Asia: An international modified e-Delphi survey.

BACKGROUND: Fever is a common presenting symptom in low- and middle-income countries (LMICs). It was previously assumed that malaria was the cause in such patients, but its incidence has declined rapidly. The urgent need to develop point-of-care tests for the most important causes of non-malarial acute febrile illness is hampered by the lack of robust epidemiological data. We sought to obtain expert consensus on analytes which should be prioritized for inclusion in fingerprick blood-based multiplex lateral flow rapid diagnostic tests (LF-RDTs) targeted towards four categories of patients with acute non-malarial fever in South and Southeast Asian LMICs, stratified by age (paediatric vs. adult) and care setting (primary vs. secondary care). METHODOLOGY/PRINCIPAL FINDINGS: We conducted a two-round modified e-Delphi survey. A total of 84 panellists were invited, consisting of seven each from 12 countries, divided into three regional panels (Mainland Southeast Asia, Maritime Southeast Asia, and South Asia). Panellists were asked to rank their top seven analytes for inclusion in LF-RDTs to be used in each patient category, justify their choices, and indicate whether such LF-RDTs should be incorporated into algorithm-based clinical decision support tools. Thirty-six panellists (43%) participated in the first round and 44 (52%) in the second. There was consensus that such LF-RDTs should be incorporated into clinical decision support tools. At a minimum, these LF-RDTs should be able to diagnose dengue and enteric fever in all patient categories. There was a clear preference to develop LF-RDTs for pathogens not readily detected by existing technologies, and for direct diagnosis through antigen detection. Pathogen biomarkers were prioritized over host inflammatory biomarkers, with CRP being the only one ranked consistently highly. CONCLUSIONS/SIGNIFICANCE: Our results provide guidance on prioritizing analytes for inclusion in context-specific multiplex LF-RDTs and similar platforms for non-malarial acute febrile illness, for which there is an urgent unmet need.

Climate drives the spatiotemporal dynamics of scrub typhus in China.

Scrub typhus is a climate-sensitive and life-threatening vector-borne disease that poses a growing public health threat. Although the climate-epidemic associations of many vector-borne diseases have been studied for decades, the impacts of climate on scrub typhus remain poorly understood, especially in the context of global warming. Here we incorporate Chinese national surveillance data on scrub typhus from 2010 to 2019 into a climate-driven generalized additive mixed model to explain the spatiotemporal dynamics of this disease and predict how it may be affected by climate change under various representative concentration pathways (RCPs) for three future time periods (the 2030s, 2050s, and 2080s). Our results demonstrate that temperature, precipitation, and relative humidity play key roles in driving the seasonal epidemic of scrub typhus in mainland China with a 2-month lag. Our findings show that the change of projected spatiotemporal dynamics of scrub typhus will be heterogeneous and will depend on specific combinations of regional climate conditions in future climate scenarios. Our results contribute to a better understanding of spatiotemporal dynamics of scrub typhus, which can help public health authorities refine their prevention and control measures to reduce the risks resulting from climate change.

Understanding responses to climate-related water scarcity in Africa.

Water scarcity is a global challenge, yet existing responses are failing to cope with current shocks and stressors, including those attributable to climate change. In sub-Saharan Africa, the impacts of water scarcity threaten livelihoods and wellbeing across the continent and are driving a broad range of adaptive responses. This paper describes trends of water scarcity for Africa and outlines climate impacts on key water-related sectors on food systems, cities, livelihoods and wellbeing, conflict and security, economies, and ecosystems. It then uses systematic review methods, including the Global Adaptation Mapping Initiative, to analyse 240 articles and identify adaptation characteristics of planned and autonomous responses to water scarcity across Africa. The most common impact drivers responded to are drought and participation variability. The most frequently identified actors responding to water scarcity include individuals or households (32%), local government (15%) and national government (15%), while the most common types of response are behavioural and cultural (30%), technological and infrastructural (27%), ecosystem-based (25%) and institutional (18%). Most planned responses target low-income communities (31%), women (20%), and indigenous communities (13%), but very few studies target migrants, ethnic minorities or those living with disabilities. There is a lack of coordination of planned adaptation at scale across all relevant sectors and regions, and lack of legal and institutional frameworks for their operation. Most responses to water scarcity are coping and autonomous responses that showed only minor adjustments to business-as-usual water practices, suggesting limited adaptation depth. Maladaptation is associated with one or more dimension of responses in almost 20% of articles. Coordinating institutional responses, carefully planned technologies, planning for projected climate risks including extension of climate services and increased climate change literacy, and integrating indigenous knowledge will help to address identified challenges of water scarcity towards more adaptive responses across Africa.

Detection of urinary microRNA biomarkers using diazo sulfonamide-modified screen printed carbon electrodes.

This paper describes a straightforward electrochemical method for rapid and robust urinary microRNA (miRNA) quantification using disposable biosensors that can discriminate between urine from diabetic kidney disease (DKD) patients and control subjects. Aberrant miRNA expression has been observed in several major human disorders, and we have identified a urinary miRNA signature for DKD. MiRNAs therefore have considerable promise as disease biomarkers, and techniques to quantify these transcripts from clinical samples have significant clinical and commercial potential. Current RT-qPCR-based methods require technical expertise, and more straightforward methods such as electrochemical detection offer attractive alternatives. We describe a method to detect urinary miRNAs using diazo sulfonamide-modified screen printed carbon electrode-based biosensors that is amenable to parallel analysis. These sensors showed a linear response to buffered miR-21, with a 17 fM limit of detection, and successfully discriminated between urine samples (n = 6) from DKD patients and unaffected control subjects (n = 6) by differential miR-192 detection. Our technique for quantitative miRNA detection in liquid biopsies has potential for development as a platform for non-invasive high-throughput screening and/or to complement existing diagnostic procedures in disorders such as DKD.

Electrochemical Detection and Quantification of Lithium Ions in Authentic Human Saliva Using LiMn2O4-Modified Electrodes.

We report an electrochemical sensor for the detection of lithium ions (Li+) in authentic human saliva at lithium manganese oxide (LiMn2O4)-modified glassy carbon electrodes (LMO-GCEs) and screen-printed electrodes (LMO-SPEs). The sensing strategy is based on an initial galvanostatic delithiation of LMO followed by linear stripping voltammetry (LSV) to detect the reinsertion of Li+ in the analyte. The process was investigated using powder X-ray diffraction and voltammetry. LSV measurements reveal a measurable lower limit of 50.0 µM in both LiClO4 aqueous solutions and synthetic saliva samples, demonstrating the applicability of the proposed analytical method down to low Li+ concentrations. Four different samples of authentic human saliva were then analyzed with the established sensing strategy using LMO-SPEs, showing good linearity over a concentration range up to 5.0 mM Li+ with high reproducibility (RSD < 7%) and applicability for routine monitoring purposes. The total time needed to analyze a sample is less than 3 min.

Magnetic resonance imaging of the brain in adults with severe falciparum malaria.

BACKGROUND: Magnetic resonance imaging (MRI) allows detailed study of structural and functional changes in the brain in patients with cerebral malaria. METHODS: In a prospective observational study in adult Bangladeshi patients with severe falciparum malaria, MRI findings in the brain were correlated with clinical and laboratory parameters, retinal photography and optic nerve sheath diameter (ONSD) ultrasound (a marker of intracranial pressure). RESULTS: Of 43 enrolled patients, 31 (72%) had coma and 12 (28%) died. MRI abnormalities were present in 79% overall with mostly mild changes in a wide range of anatomical sites. There were no differences in MRI findings between patients with cerebral and non-cerebral or fatal and non-fatal disease. Subtle diffuse cerebral swelling was common (n = 22/43), but mostly without vasogenic oedema or raised intracranial pressure (ONSD). Also seen were focal extracellular oedema (n = 11/43), cytotoxic oedema (n = 8/23) and mildly raised brain lactate on magnetic resonance spectroscopy (n = 5/14). Abnormalities were much less prominent than previously described in Malawian children. Retinal whitening was present in 36/43 (84%) patients and was more common and severe in patients with coma. CONCLUSION: Cerebral swelling is mild and not specific to coma or death in adult severe falciparum malaria. This differs markedly from African children. Retinal whitening, reflecting heterogeneous obstruction of the central nervous system microcirculation by sequestered parasites resulting in small patches of ischemia, is associated with coma and this process is likely important in the pathogenesis.