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On 17th March, ERGO's own Catrin Moore paid a visit to the budding scientists at Freeland School. There, pupils had the opportunity to learn about vectors and the diseases that they carry, getting a close look at specimens of ticks and mosquitos under a microscope.
Acceptability and feasibility of glucose-6-phosphate dehydrogenase (G6PD) testing using SD Biosensor by village malaria workers in Cambodia: a qualitative study
IntroductionPlasmodium vivaxis the predominant cause of malaria in the Greater Mekong Subregion. To ensure safe treatment with primaquine, point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing was rolled out in Cambodia at the health facility level, although most malaria patients are diagnosed in the community. The current study aims to explore the acceptability and feasibility of implementing community-level G6PD testing in Cambodia.MethodsSemistructured interviews and focus group discussions (FGD) were conducted. Across eight study sites in three provinces, 142 respondents, including policymakers, programme officers, healthcare providers and patients, participated in 67 interviews and 19 FGDs in 2022 and 2023. Data were analysed thematically using an adapted framework derived from Bowenet al’s feasibility framework and Sekhonet al’s acceptability framework.ResultsAll stakeholders attributed value to the intervention. Acknowledging an intervention’s different values can help discern policy implications for an intervention’s successful implementation. Building and maintaining confidence in the device, end users, infrastructure and health systems were found to be key elements of acceptability. In general, health centre workers and village malaria workers (VMWs) had confidence that VMWs could conduct the test and administer treatment given appropriate initial training, monthly refresher training and the test’s repeated use. More is required to build policymakers’ confidence, while some implementation challenges, including the test’s regulatory approval, stability above 30°C and cost, need to be overcome.ConclusionImplementation of G6PD testing at the community level in Cambodia is an acceptable and potentially feasible option but requires addressing implementation challenges and building and maintaining confidence among stakeholders.
"The traditional healer said, 'I had a genie that scared me in my eyes, and that is why I fall": An ethnographic study in Mahenge, Tanzania.
BackgroundIn many low-income countries, individuals with epilepsy often turn to traditional healers as their first source of treatment after the onset of seizures. However, their experiences with traditional healing practices remain poorly understood. This study examines the perceptions and experiences of people with epilepsy in relation to traditional healing in Mahenge, Tanzania.MethodsA culturally specific ethnographic approach, centred on oral history, was employed to capture rich, contextually grounded narratives. A total of 45 oral history interviews were conducted with individuals living with epilepsy from 21 villages in Mahenge. Participants were purposively selected based on the following criteria: being at least 18 years of age, having a diagnosis of epilepsy, and the ability to recount their experiences in Swahili, the primary language spoken in the region. Data were manually analysed using thematic analysis.ResultsTraditional healers often attribute epilepsy to supernatural causes, such as curses or witchcraft, linking seizure onset to past events believed to have triggered the condition. Their treatment practices are frequently accompanied by strict behavioural restrictions, which can be challenging for individuals with epilepsy to follow and are sometimes cited as reasons for treatment failure. Moreover, some participants reported experiences of physical, emotional, and even sexual harassment during their encounters with traditional healers.ConclusionThere is a strong reliance on traditional healing practices for epilepsy, where cultural beliefs and rituals can hinder accurate diagnosis and effective care. Raising awareness about epilepsy, its medical management, and the rights of people with epilepsy, both among traditional healers and the broader community, is essential to improve care and protect the well-being of those affected.
The relationship between lifetime trauma exposure and psychosis in a multi-country case-control study in Africa
Background: Exposure to traumatic events is a known risk factor for psychosis. Additionally, psychosis may be a risk factor for exposure to traumatic events. There are little data on the relationship between traumatic events and psychosis in sub-Saharan Africa, particularly in large, cross-country samples using the same instrument. Methods: In a case-control study, 21,606 adults were recruited with psychosis (cases) and 21,329 adults without any history of psychosis (controls) in Ethiopia, Kenya, South Africa, and Uganda from 2018 to 2023 (n = 42,935). Lifetime trauma exposure was assessed using the Life Events Checklist-5. Regression models included the: i) prevalence of any trauma exposure; ii) cumulative burden of trauma exposure; and iii) the odds of exposure to specific trauma types. Analyses were run by case-control status for the full sample and within each country; trauma types endorsed by cases and controls were further stratified by sex. Results: There was a modest increased odds of trauma among cases compared with controls. Cases had higher odds of reporting exposure to ≥1 trauma and ≥3 trauma types (adjusted odds ratio (AOR) = 1.23, 95 % CI: 1.18–1.28 and AOR = 1.19, 95 % CI: 1.15–1.23, respectively). The trauma types with the highest odds were sexual violence (AOR = 1.99, 95 % CI: 1.86–2.14), physical violence (AOR = 1.69, 95 % CI: 1.62–1.76), and network trauma (causing injury, harm, or death to someone else) (AOR = 1.52, 95 % CI: 1.38–1.67). Similar trends were seen within each country. Sexual violence and physical violence were most endorsed by female cases and male cases, respectively. Network trauma was most endorsed by male cases and particularly from South Africa. Conclusion: People in eastern and southern Africa report significant exposure to trauma with a slightly higher prevalence among individuals with psychosis. Special attention should be paid to potential trauma exposure including interpersonal violence when providing treatment for this population.
Socio-medical factors associated with neurodevelopmental disorders on the Kenyan coast.
Neurodevelopmental disorders (NDDs) are a group of conditions with their onset during the early developmental period and include conditions such as autism and intellectual disability. Occurrence of NDDs is thought to be determined by both genetic and environmental factors, but data on the role of environmental factors for NDD in Africa is limited. This study investigates environmental influences on NDDs in children from Kenya. This case-control study compared children with NDDs and typically developing children from two studies on the Kenyan coast. We included 172 study participants from the Kilifi Autism study and 151 from the NeuroDev study who had a diagnosis of at least one NDD and 112 and 73 with no NDD diagnosis from each study, respectively. Potential risk factors were identified using unadjusted univariable analysis and adjusted multivariable logistic regression. Univariable analysis in the Kilifi Autism study sample revealed hypoxic-ischaemic encephalopathy conferred the largest odds ratio (OR) 10.52 [95%CI: 4.04, 27.41] for NDDs, followed by medical complications during pregnancy (gestational hypertension & diabetes, eclampsia, maternal bleeding) (OR=3.17 [95%CI: 1.61, 6.23]). In the NeuroDev study sample, labour and birth complications (OR=7.30 [95%CI 2.17, 24.61]), neonatal jaundice (OR=5.49 [95%CI 1.61,18.72]) and infection during pregnancy (OR= 5.31 [95%CI 1.56, 18.11]) conferred the largest risk associated with NDDs. In the adjusted analysis, seizures before age 3 years in the Kilifi Autism study and labour and birth complications in the NeuroDev study conferred the largest increased risk. Higher parity, the child being older and delivery at home were associated with a reduced risk for NDDs. Recognition of important risk factors such as labour and birth complications could guide preventative interventions, developmental screening of at-risk children and monitoring progress of these children. Further studies examining the aetiology of NDDs in population-based samples, including investigating the interaction between genetic and environmental factors, are needed.
Development of an oral regimen of unithiol for the treatment of snakebite envenoming: a phase 1 open-label dose-escalation safety trial and pharmacokinetic analysis in healthy Kenyan adults.
BackgroundViperidae snakes are responsible for many of the 94,000 deaths caused by snakebite envenoming each year. The most pathological venom component of this globally diverse family of snakes are the zinc-dependent snake venom metalloproteinase (SVMP) enzymes, which can be inhibited by the metal chelator, unithiol. A short-course oral regimen, readily available and rapidly deployed ahead of hospital admission is needed.MethodsThis open-label, phase 1 clinical trial assessed the safety of single ascending oral, multiple ascending oral, and single ascending intravenous doses of unithiol in 64 healthy adult volunteers from Kilifi County, Kenya. The multiple dose stage was informed by an interim safety and pharmacokinetic analysis, and predefined target plasma concentrations. Plasma concentrations of unithiol were measured using high-performance liquid chromatography-mass spectrometry, and safety was described by full adverse event reporting.Findings175 individuals were screened, and 64 (median age 30 years, IQR 25-38 years) received the study drug. There were no dose limiting toxicities or serious adverse events. There were 61 solicited adverse events, 17 related unsolicited adverse events, and 53 laboratory adverse events, all of mild or moderate severity. The maximum oral dose of 1500 mg was well tolerated and associated with the following pharmacokinetic parameters: Cmax 14.7 μg/mL, Tmax 2.9 h, T1/2 18.4 h, and AUC0-∞ 204.5 μg.h/mL.InterpretationThe phase 2 recommended dose (1500 mg loading dose, followed by 900 mg doses at 6-h and 24-h) has no safety concerns, and has promising pharmacokinetic properties for clinical use. Unithiol is affordable, stable at room temperature, and has the potential to be given orally in remote rural clinics. Its further development for snakebite indication is warranted.FundingWellcome Trust, Bloomsbury Set, and Cures Within Reach.
Application of fluid dynamics in modeling the spatial spread of infectious diseases with low mortality rate: A study using MUSCL scheme
This study presents a comprehensive mathematical framework that applies fluid dynamics to model the spatial spread of infectious diseases with low mortality rates. By treating susceptible, infected, and treated population densities as fluids governed by a system of partial differential equations, the study simulates the epidemic's spatial dynamics. The Monotone Upwind Scheme for Conservation Laws is employed to enhance the accuracy of numerical solutions, providing a high-resolution approach for capturing disease transmission patterns. The model's analogy between fluid flow and epidemic propagation reveals critical insights into how diseases disperse geographically, influenced by factors like human mobility and environmental conditions. Numerical simulations show that the model can predict the evolution of infection and treatment population densities over time, offering practical applications for public health strategies. Sensitivity analysis of the reproduction number highlights the influence of key epidemiological parameters, guiding the development of more efficient disease control measures. This work contributes a novel perspective to spatial epidemiology by integrating principles of fluid dynamics, aiding in the design of targeted interventions for controlling disease outbreaks.
Safety and efficacy of single-dose primaquine to interrupt Plasmodium falciparum malaria transmission in children compared with adults: a systematic review and individual patient data meta-analysis.
BackgroundAdding a single dose of primaquine to artemisinin-based combination therapy (ACT) for the treatment of falciparum malaria can reduce the transmission of Plasmodium falciparum and could limit the spread of artemisinin partial resistance, including in Africa, where the disease burden is greatest. We aimed to compare the safety and efficacy of single-dose primaquine plus ACT between young children (aged <5 years) and older children (aged 5 years to <15 years) and adults (aged ≥15 years), and between low and moderate-to-high transmission areas.MethodsFor this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus, OpenGrey.eu, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform, from database inception to April 3, 2024, with no language restrictions. We included prospective studies on efficacy against falciparum malaria that enrolled at least one child younger than 15 years and involved a study group given a single dose of primaquine (≤0·75 mg/kg) plus ACT. Studies involving mass drug administration, healthy volunteers, or patients with severe malaria or mixed (with non-falciparum) infections were excluded. For inclusion in the efficacy analysis, data on transmission potential (as determined by gametocytaemia, infectivity, or both) at enrolment and follow-up (day 3, day 7, or day 14) were required; the safety analysis required data on haemoglobin concentrations or haematocrit values at enrolment and at one or more follow-up visits by day 7, any data on adverse events, or both. After independent screening of the search results by two reviewers, the investigators of eligible studies were invited to contribute individual patient data. We quantified day 7 gametocyte carriage, probability of infecting a mosquito, decreases (>25%) in haemoglobin concentration associated with anaemia, and adverse events until day 28 using regression analyses, with random study-site intercepts to account for clustered data. These analyses were registered with PROSPERO, CRD42021279363 (safety) and CRD42021279369 (efficacy).FindingsOf 5697 records identified by the search, 30 studies were eligible for analysis. Of these, individual patient data were shared for 23 studies, including 6056 patients from 16 countries: 1171 (19·3%) young children (aged <5 years), 2827 (46·7%) older children (aged 5 years to <15 years), and 2058 (34·0%) adults (aged ≥15 years). Adding a single low dose of primaquine (0·2-0·25 mg/kg) to ACTs reduced day 7 gametocyte positivity (adjusted odds ratio [aOR] 0·34, 95% CI 0·22-0·52; p<0·001) and infectivity to mosquitoes over time (aOR per day 0·02, 0·01-0·07, p<0·001). No difference was found in the effect of single low-dose primaquine both on gametocyte positivity in young children compared with older children (1·08, 0·52-2·23; p=0·84) and adults (0·50, 0·20-1·25; p=0·14) and between low-transmission and moderate-to-high transmission settings (1·07, 0·46-2·52; p=0·86), and on infectivity to mosquitoes in young children compared with older children (1·36, 0·07-27·71; p=0·84) and adults (0·31, 0·01-8·84; p=0·50) and between low-transmission and moderate-to-high transmission settings (0·18, 0·01-2·95; p=0·23). Gametocyte clearance was also similar for different ACTs (dihydroartemisinin-piperaquine vs artemether-lumefantrine) when combined with a primaquine target dose of 0·25 mg/kg (1·56, 0·65-3·79; p=0·32 at day 7). However, patients given a primaquine dose of less than 0·2 mg/kg with dihydroartemisinin-piperaquine were more likely to have gametocytaemia than those treated with artemether-lumefantrine (5·68, 1·38-23·48; p=0·016 at day 7). There was no increase in anaemia-associated declines in haemoglobin concentration (>25%) at a primaquine dose of 0·25 mg/kg, regardless of age group, transmission setting, and glucose-6-phosphate dehydrogenase status. The risks of adverse events of grade 2 or higher and of serious adverse events were similar between primaquine and no-primaquine groups, including in young children.InterpretationRegardless of malaria transmission intensity and age group, a single dose of 0·25 mg/kg primaquine is safe and efficacious for reducing P falciparum transmission. These findings underscore the need for primaquine formulations suitable for young children, and also provide supportive evidence to expand the use of single low-dose primaquine in regions with a moderate-to-high transmission rate that are threatened by artemisinin partial resistance.FundingThe EU and the Bill & Melinda Gates Foundation.
Defining and subphenotyping ARDS: insights from an international Delphi expert panel.
Although the definition of acute respiratory distress syndrome (ARDS) has undergone numerous revisions aimed at enhancing its diagnostic accuracy and clinical practicality, the usefulness and precision of these definitions remain matters of ongoing discussion. In this Position Paper, we report on a Delphi study to reach a consensus on the conceptual model of ARDS, specifically identifying its defining components within clinical, research, and educational contexts as well as exploring the potential role of subphenotyping. We did a four-round Delphi study, involving experts in ARDS research and management from a diverse range of geoeconomic regions and professional backgrounds. Consensus was achieved for the conceptual model of ARDS; key components to be included for an ARDS definition in the context of research, education, and patient management; and the need for further research in subphenotyping ARDS. Additionally, we highlight knowledge gaps and research priorities that could guide future investigations in this area. Our study builds on previous non-Delphi-based consensus processes (eg, the new global definition of ARDS and recent society-based guidelines) by using a rigorous Delphi method that ensured panellist anonymity and used clear quantitative criteria to mitigate potential peer pressure and group conformity. The findings underscore the need to refine the ARDS definition to better account for the heterogeneity of clinical presentations and underlying pathophysiology, and to improve diagnostic precision, including the use of subphenotyping where appropriate.
Use of the pragmatic-explanatory continuum indicator summary tool in low- and middle-income country settings: Systematic review.
ObjectiveTo systematically review and characterize the literature on using the PRagmatic-Explanatory Continuum Indicator Summary (PRECIS) tools in low- and middle-income countries (LMICs), focusing on successes, challenges, and potential improvements to enhance applicability across diverse settings.Study design and settingA systematic search of PubMed to identify peer-reviewed articles applying PRECIS tools to LMIC-based research. Data extraction focused on trial characteristics, modifications, and use of PRECIS tools. Narrative synthesis was used to outline successes, challenges, and recommendations.ResultsA total of 40 articles met the selection criteria. The PRECIS tools were mostly (n=39, 97.5%) used for purposes other than trial design. Significant variation was seen in methods of use and reporting. Most (n=32, 80%) used PRECIS-2, valued for its reliability, ability to quantify pragmatism, assess trial design, and identify research gaps. Challenges included the tools' subjectivity, absence of information needed for scoring, interpretation of scores, and application to non-Western contexts and multinational trials. Recommendations for improvement included refining scoring criteria, translating guidance, and developing additional educational resources.ConclusionThe PRECIS tools have successfully supported research globally and are perceived as reliable research tools with multiple strengths. Further guidance and refinement would enable consistent application and reporting, particularly as the tools have frequently been used for purposes other than their original intention. Most challenges were similar to high-income settings, however, translation and application of the tools to traditional medicine, international trials and research-naïve settings were highlighted as LMIC-focused issues requiring consideration.
The aetiologies, mortality, and disability of non-traumatic coma in African children: a systematic review and meta-analysis.
BackgroundNon-traumatic coma in African children is a common life-threatening presentation often leading to hospital attendance. We aimed to estimate the distribution of non-traumatic coma causes and outcomes, including disease-specific outcomes, for which evidence is scarce.MethodsWe systematically reviewed MEDLINE, Embase, and Scopus databases from inception to Feb 6, 2024. We included studies recruiting children (aged 1 month to 16 years) with non-traumatic coma (Blantyre Coma Scale score ≤2, ie deep coma or comparable alternative) from any African country. Disease-specific studies were included if outcomes were reported. Primary data were requested where required. We used a DerSimonian-Laird random effects model to calculate pooled estimates for prevalence of causes, mortality, and morbidity (in-hospital and post-discharge), including analysis of mortality by temporality. This study was registered with PROSPERO (CRD4202014193).FindingsWe screened 16 666 articles. 138 studies were eligible for analysis, reporting causes, outcome data, or both from 35 027 children with non-traumatic coma in 30 African countries. 114 (89%) of 128 studies were determined to be high quality. Among the causes, cerebral malaria had highest pooled prevalence at 58% (95% CI 48-69), encephalopathy of unknown cause was associated with 23% (9-36) of cases, and acute bacterial meningitis was the cause of 10% (8-12) of cases, with all other causes representing lower proportions of cases. Pooled overall case-fatality rates were 17% (16-19) for cerebral malaria, 37% (20-55) for unknown encephalopathy, and 45% (34-55) for acute bacterial meningitis. By meta-regression, there was no significant difference in cerebral malaria (p=0·98), acute bacterial meningitis (p=0·99), or all-cause coma (p=0·081) mortality by year of study. There was no substantial difference in deaths associated with cerebral malaria in-hospital compared with post-discharge (17% [16-19] vs (18% [16-20]). Mortality was higher post-discharge than in-hospital in most non-malarial comas, including acute bacterial meningitis (39% [26-52]) vs 53% [38-69]). Disability associated with cerebral malaria was 11% (9-12). Pooled disability outcomes associated with other non-malarial diseases were largely absent.InterpretationThe prevalence and outcomes of cerebral malaria and meningitis associated with non-traumatic coma were strikingly static across five decades. Enhanced molecular and radiological diagnostics, investment, policy making, community awareness, and health service provision are all required to facilitate earlier referral to specialist centres, to drive a step-change in diagnostic yield and treatment options to improve these outcomes.FundingWellcome Trust.TranslationsFor the Chichewa, French and Portuguese translations of the abstract see Supplementary Materials section.
Impact of the Global Fund Regional Artemisinin-resistance Initiative on malaria control and elimination in the Greater Mekong subregion of southeast Asia.
Responding to the emergence of Plasmodium falciparum partial resistance to artemisinins and partner drugs of artemisinin-based combination therapies in the Greater Mekong subregion (GMS) of southeast Asia, the Regional Artemisinin-resistance Initiative (RAI) was established in 2014 and has made remarkable progress in eliminating falciparum malaria. In Cambodia, Laos, and Viet Nam, the number of malaria cases has declined from hundreds of thousands in 2010 to 2313 cases in 2023, with only 246 caused by falciparum malaria. The key components of this success have been an effective package of interventions curbing malaria transmission, with an emphasis on early diagnosis and treatment in hard-to-reach populations through an extended and well organised network of community and mobile malaria workers; improved surveillance systems; and evidence-driven implementation of intensified approaches such as active case detection, chemoprevention in specific risk groups, and targeted drug administration. The RAI is funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria and governed by a closely collaborating Regional Steering Committee, including technical partners, key development partners, and stakeholders from ministries of health, national malaria control programmes, civil society organisations, the private sector, academia, and regional multilateral organisations. The RAI has brought the countries of the eastern GMS close to eliminating P falciparum, the deadliest malaria-causing Plasmodium species. Nonetheless, a worrying rise in malaria cases in Myanmar with cross-border spillover requires urgent action. Lessons learned from the RAI's approach to antimalarial drug resistance in the GMS can inform countries in sub-Saharan Africa, where artemisinin partial resistance has now also emerged.
Operational evaluation of the deployment of Malaria/CRP Duo and Dengue Duo rapid diagnostic tests for the management of febrile illness by village malaria workers in rural Cambodia
Abstract Introduction The decline in malaria cases in Cambodia has led to a relative increase in non-malarial febrile illness. In rural Cambodia, village malaria workers (VMWs) provide early diagnosis and treatment for malaria, but their role and relevance are diminishing as malaria cases decline. Expanding VMW roles would ensure continued utilisation of their services until malaria elimination is achieved and strengthen community health services. Methods A mixed methods operational research study was implemented to evaluate the use of two combination-RDTs (combo-RDTs) as an expansion of the VMW role, enabling VMWs in Cambodia to test for diseases other than malaria for the first time. VMWs in 78 villages in Battambang and Pailin Provinces were trained and provided with either a Malaria/CRP Duo or Dengue Duo RDT to assess febrile patients. Data were collected on VMW consultations, and combo-RDT usage and results. Focus group discussions (FGDs) and competency assessments of combo-RDT usage were conducted with VMWs. The main objectives were to determine whether VMWs could perform these combo-RDTs correctly and follow management algorithms, and whether deployment had an impact on VMW consultation rates. Perspectives concerning role expansion and the feasibility of conducting additional tests were also explored. Results Between June 2022, and May 2023, a total of 2,425 febrile patients were assessed with either a Malaria/CRP Duo or Dengue Duo RDT. Active dengue infection (NS1- and/or IgM-positive) was identified in 1.2% (11/915) of patients. Positive CRP results (> 20 mg/L) were found for 3.2% (48/1,510) of patients. Following deployment, there was an immediate mean increase of 4.4 VMW consultations per month, from 9.0 to 13.4 (p < 0.01). Competency assessments revealed that some VMWs had difficulty performing the Dengue Duo RDT, particularly in collecting the correct blood volume. This limitation may have led to false-negative dengue NS1 results. VMWs and community members were keen to broaden the skills and responsibilities of VMWs. Conclusions Deploying combo-RDTs to VMWs led to a higher utilization of their services. Difficulties performing some aspects of the Dengue Duo RDT, low positivity rates, and a lack of actionable outcomes within the existing context of VMW services suggest that alternative interventions may be better suited for VMW role expansion at this time. Overall, VMWs and community members were receptive to the expansion of the VMW role for a wider range of diseases other than malaria.
Optimization of heat inactivation protocols for Orientia and Rickettsia species.
Heat treatment, or thermal disinfection, is one of the simplest and most widely used methods for microbial inactivation. Proper heat inactivation protocols are essential to ensure the safe transportation and handling of infectious materials, particularly for organisms in risk group 3, such as Rickettsia and Orientia. In this study, we examined the inactivation of four bacterial species-Orientia tsutsugamushi, Rickettsia typhi, Rickettsia conorii, and Rickettsia honei-at temperatures of 56 °C, 80 °C, and 90 °C for durations of 5, 15, 30, and 60 min. Observations were made at 0, 1, 3, 7, 10, and 14 days post-infection (dpi) to assess bacterial infectivity by monitoring bacterial DNA copies in newly infected cells. Our results indicate that 56 °C for 5 min was the minimum temperature and time required to inactivate O. tsutsugamushi, R. typhi, R. conorii, and R. honei. O. tsutsugamushi exhibited a higher reduction factor at 56 °C compared to R. typhi, R. conorii, and R. honei. Additionally, a strong inverse correlation between incubation time and log10 reduction factor was observed for O. tsutsugamushi and R. typhi, underscoring the importance of both time and temperature in effective heat treatment. However, no such correlation was observed for R. conorii and R. honei. These findings highlight the variable responses of bacteria to heat, emphasizing the need for pathogen-specific approaches in inactivation protocols. Optimizing heat treatment strategies based on these insights is critical for enhancing biosafety and ensuring effective pathogen eradication.