Search results
Found 22102 matches for
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.
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.
Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial
Background Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use. Methods and findings Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507. Interpretation In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs. Trial registration ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947.
Hypertension in Sub-Saharan Africa: Burden, Barriers and Priorities for Improving Treatment Outcomes.
The burden of hypertension is rising rapidly in sub-Saharan Africa (SSA), posing significant health challenges and economic costs that hinder national development. Despite being well-studied in clinical medicine, the detection, treatment, and control of hypertension in SSA remain inadequate. This is due to barriers across the care continuum, including individual-, provider-, and system-level obstacles within the health system. A critical issue is the lack of contextualized mechanistic research to understand the mechanisms, phenotypes, and treatment responses in native SSA populations. Current treatment approaches are often based on data from diaspora Africans, particularly African Americans. Consequently, most guidelines do not recommend angiotensin system drugs as first-line agents for Black patients, a stance that should be reconsidered given some evidence of their effectiveness in native SSA populations. Addressing these barriers requires a comprehensive, multisectoral strategy that includes both preventative and clinical measures at the population and individual levels. Preventative approaches should encompass health and nutrition education, improving food supply quality, and implementing comprehensive transportation and environmental policies. In addition, strategies should be developed to increase the detection of undiagnosed cases through enhanced screening and treatment access to those not receiving care, and revisit current treatment approaches to ensure that they are more tailored to the specific populations and settings. In conclusion, innovative strategies are needed to identify and overcome barriers to hypertension diagnosis and management. A coordinated, multisectoral approach that includes a contextualized mechanistic research agenda, as well as task shifting and task sharing, will help prevent and reduce hypertension in SSA.
Use of minimally invasive tissue sampling to determine the contribution of diarrheal diseases to under-five mortality and associated co-morbidities and co-infections in children with fatal diarrheal diseases in Africa and Bangladesh.
Achieving the Sustainable Development Goal of reducing child mortality to <25 deaths per 1000 live births by 2030 requires strategies to prevent diarrheal disease-related morbidity and mortality. Accurate etiological diagnosis is essential. This study used postmortem diagnostics to investigate the contribution of diarrhea to under-5 mortality and examine co-morbidities and co-infections in Africa and South Asia. Child Health and Mortality Prevention Surveillance (CHAMPS) generates data on child deaths through minimally invasive tissue sampling, clinical record review, and verbal autopsies. Multidisciplinary panels assign cause(s) of death using WHO International Classification of Diseases. This analysis included deaths among children aged 1-59 months enrolled from 18 December 2016-31 December 2023 across six African sites (Ethiopia, Mali, Kenya, Sierra Leone, Mozambique, South Africa) and Bangladesh. Of 1517 deaths assessed, diarrhea was in the causal pathway in 240 (15.8%). The proportion of diarrhea-related deaths was highest in Ethiopia (41.0%, 34/83), followed by Bangladesh, (30.0%, 3/10), Mozambique (21.7%, 56/258), Mali (17.5%, 18/103), Kenya (13.9%, 51/366), Sierra Leone (12.8%, 46/358), and South Africa (9.4%, 32/339). Diarrhea was underlying cause in 44.2% (106/240) of cases and immediate/antecedent cause in 58.3% (140/240), with some deaths involving multiple roles in the causal chain. When diarrhea was underlying cause, sepsis (33.0%) and lower respiratory infections (25.5%) were common downstream conditions; when an antecedent/immediate cause, leading underlying causes were malnutrition (64.3%) and HIV (13.6%). No pathogen was identified in 49.6% (119/240) of diarrhea-related deaths; among these, diarrhea was underlying cause in 42.9%. Among the 121 pathogen-attributed deaths, the most frequent were EAEC (34.7%), typical EPEC (15.7%), Shigella/EIEC (14.0%), ST-ETEC (12.4%), rotavirus (26.4%), and adenovirus (non-40/41: 19.0%; 40/41: 5.0%). These pathogens were frequently identified as co-infections. Diarrheal disease accounted for a substantial share of child deaths across CHAMPS sites. Reducing mortality will require preventing diarrhea and addressing key contributors such as malnutrition and HIV.