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IDDO has launched a new global Chagas scientific collaboration with the Drugs for Neglected Diseases initiative (DNDi). The new platform will collate and standardise data to accelerate better treatments for the 6–7 million people worldwide with Chagas disease.
Hypothermia amongst neonatal admissions in Kenya: a retrospective cohort study assessing prevalence, trends, associated factors, and its relationship with all-cause neonatal mortality.
BackgroundReports on hypothermia from high-burden countries like Kenya amongst sick newborns often include few centers or relatively small sample sizes.ObjectivesThis study endeavored to describe: (i) the burden of hypothermia on admission across 21 newborn units in Kenya, (ii) any trend in prevalence of hypothermia over time, (iii) factors associated with hypothermia at admission, and (iv) hypothermia's association with inpatient neonatal mortality.MethodsA retrospective cohort study was conducted from January 2020 to March 2023, focusing on small and sick newborns admitted in 21 NBUs. The primary and secondary outcome measures were the prevalence of hypothermia at admission and mortality during the index admission, respectively. An ordinal logistic regression model was used to estimate the relationship between selected factors and the outcomes cold stress (36.0°C-36.4°C) and hypothermia (<36.0°C). Factors associated with neonatal mortality, including hypothermia defined as body temperature below 36.0°C, were also explored using logistic regression.ResultsA total of 58,804 newborns from newborn units in 21 study hospitals were included in the analysis. Out of these, 47,999 (82%) had their admission temperature recorded and 8,391 (17.5%) had hypothermia. Hypothermia prevalence decreased over the study period while admission temperature documentation increased. Significant associations were found between low birthweight and very low (0-3) APGAR scores with hypothermia at admission. Odds of hypothermia reduced as ambient temperature and month of participation in the Clinical Information Network (a collaborative learning health platform for healthcare improvement) increased. Hypothermia at admission was associated with 35% (OR 1.35, 95% CI 1.22, 1.50) increase in odds of neonatal inpatient death.ConclusionsA substantial proportion of newborns are admitted with hypothermia, indicating a breakdown in warm chain protocols after birth and intra-hospital transport that increases odds of mortality. Urgent implementation of rigorous warm chain protocols, particularly for low-birth-weight babies, is crucial to protect these vulnerable newborns from the detrimental effects of hypothermia.
Melioidosis in Patients with COVID-19 Exposed to Contaminated Tap Water, Thailand, 2021.
In September 2021, a total of 25 patients diagnosed with COVID-19 developed acute melioidosis after (median 7 days) admission to a COVID-19 field hospital in Thailand. Eight nonpotable tap water samples and 6 soil samples were culture-positive for Burkholderia pseudomallei. Genomic analysis suggested contaminated tap water as the likely cause of illness.
Blood culture versus antibiotic use for neonatal inpatients in 61 hospitals implementing with the NEST360 Alliance in Kenya, Malawi, Nigeria, and Tanzania: a cross-sectional study.
BackgroundThirty million small and sick newborns worldwide require inpatient care each year. Many receive antibiotics for clinically diagnosed infections without blood cultures, the current 'gold standard' for neonatal infection detection. Low neonatal blood culture use hampers appropriate antibiotic use, fuelling antimicrobial resistance (AMR) which threatens newborn survival. This study analysed the gap between blood culture use and antibiotic prescribing in hospitals implementing with Newborn Essential Solutions and Technologies (NEST360) in Kenya, Malawi, Nigeria, and Tanzania.MethodsInpatient data from every newborn admission record (July 2019-August 2022) were included to describe hospital-level blood culture use and antibiotic prescription. Health Facility Assessment data informed performance categorisation of hospitals into four tiers: (Tier 1) no laboratory, (Tier 2) laboratory but no microbiology, (Tier 3) neonatal blood culture use 50%.ResultsA total of 144,146 newborn records from 61 hospitals were analysed. Mean hospital antibiotic prescription was 70% (range = 25-100%), with 6% mean blood culture use (range = 0-56%). Of the 10,575 blood cultures performed, only 24% (95%CI 23-25) had results, with 10% (10-11) positivity. Overall, 40% (24/61) of hospitals performed no blood cultures for newborns. No hospitals were categorised as Tier 1 because all had laboratories. Of Tier 2 hospitals, 87% (20/23) were District hospitals. Most hospitals could do blood cultures (38/61), yet the majority were categorised as Tier 3 (36/61). Only two hospitals performed > 50% blood cultures for newborns on antibiotics (Tier 4).ConclusionsThe two Tier 4 hospitals, with higher use of blood cultures for newborns, underline potential for higher blood culture coverage in other similar hospitals. Understanding why these hospitals are positive outliers requires more research into local barriers and enablers to performing blood cultures. Tier 3 facilities are missing opportunities for infection detection, and quality improvement strategies in neonatal units could increase coverage rapidly. Tier 2 facilities could close coverage gaps, but further laboratory strengthening is required. Closing this culture gap is doable and a priority for advancing locally-driven antibiotic stewardship programmes, preventing AMR, and reducing infection-related newborn deaths.
Spatial Analysis of Drug-Susceptible and Multidrug-Resistant Cases of Tuberculosis, Ho Chi Minh City, Vietnam, 2020-2023.
We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.
Teledermatology to Improve Access to and Quality of Skin Care in Eastern Indonesia.
Skin diseases are a major public health concern in Indonesia, although access to specialized care in remote areas is limited. We initiated a low-cost teledermatology service in Sumba, a remote island in eastern Indonesia. Eighteen healthcare workers (HCWs) at five primary healthcare centers received training to manage common skin diseases and submit clinical cases beyond their expertise to an online platform. Submitted cases were reviewed by at least one dermatologist. Diagnostic agreement between HCWs and dermatologists was calculated. The HCWs participated in a satisfaction survey 2 years after project initiation. Since October 2020, of 10,384 patients presenting with skin complaints in a 24-month period, 307 (3%) were submitted for a teledermatology consultation. The most frequent skin diseases were infections and infestations (n = 162, 52.8%) and eczematous (85, 27.7%) and inflammatory (17, 5.5%) conditions. Fifty-three patients (17.3%) were diagnosed with a neglected tropical skin disease, including leprosy and scabies. Dermatologist advice was provided within a median of 50 minutes (interquartile range, 18-255 minutes), with 91.9% of consultations occurring within 24 hours. The diagnostic agreement level between HCWs and dermatologists significantly improved over time, from 46.9% in the first 6-month period (κ = 0.45; 95% CI, 0.37-0.54) to 77.2% in the last 6-month period (κ = 0.76; 95% CI, 0.67-0.86; global P < 0.001). The HCWs reported that the teledermatology service was extremely/very useful in supporting daily practice (100%) and improved their knowledge of skin diseases tremendously/a lot (92%). Teledermatology can improve accessibility and quality of skin services in medically underserved areas, providing opportunities for scalability and knowledge transfer to frontline HCWs.
Prospects for the development of community-based care in remote rural areas: a stakeholder analysis in Laos.
BackgroundCommunity-based health programmes have been a cornerstone of primary care in Laos for decades. The study presented here aimed to document prospects for the development of current programmes, considering perceptions about health and health care priorities in the communities, implementation challenges, the policy landscape and opportunities associated with the availability of new technologies.MethodsThe research design primarily involved qualitative in-depth interviews with stakeholders (n = 35) responsible for the planning, management, or implementation of community-based care in Laos at different levels of the health system. These included health managers at central departments or institutes of the Ministry of Health, provincial health departments, district health offices, heads of health centres, village health volunteers, community representatives, and international stakeholders.ResultsThere was consensus that service delivery is still a challenge in many areas, due to geographic inaccessibility of health facilities, communication barriers, health-seeking behaviour, trust, and gender discrimination, particularly among ethnic minorities. In these settings, community health workers have the potential to extend the reach of the formal health system, acting as cultural brokers across sectors of society, ethnicities, and worldviews. To maximise impact, planners need to carefully consider the implementation model, financing arrangements, health system integration, and changing health priorities in the communities.ConclusionsThis study examined challenges to, and opportunities for, the expansion and health system integration of community-based care in Laos. Further development and horizontal integration of community-based care remains a complex financing and governance challenge, although the renewed emphasis on primary care and the ongoing process of decentralisation provide a favourable policy environment in the country to sustain and potentially expand existing programmes.
Sepsis Mortality Prediction Using Wearable Monitoring in Low-Middle Income Countries.
Sepsis is associated with high mortality-particularly in low-middle income countries (LMICs). Critical care management of sepsis is challenging in LMICs due to the lack of care providers and the high cost of bedside monitors. Recent advances in wearable sensor technology and machine learning (ML) models in healthcare promise to deliver new ways of digital monitoring integrated with automated decision systems to reduce the mortality risk in sepsis. In this study, firstly, we aim to assess the feasibility of using wearable sensors instead of traditional bedside monitors in the sepsis care management of hospital admitted patients, and secondly, to introduce automated prediction models for the mortality prediction of sepsis patients. To this end, we continuously monitored 50 sepsis patients for nearly 24 h after their admission to the Hospital for Tropical Diseases in Vietnam. We then compared the performance and interpretability of state-of-the-art ML models for the task of mortality prediction of sepsis using the heart rate variability (HRV) signal from wearable sensors and vital signs from bedside monitors. Our results show that all ML models trained on wearable data outperformed ML models trained on data gathered from the bedside monitors for the task of mortality prediction with the highest performance (area under the precision recall curve = 0.83) achieved using time-varying features of HRV and recurrent neural networks. Our results demonstrate that the integration of automated ML prediction models with wearable technology is well suited for helping clinicians who manage sepsis patients in LMICs to reduce the mortality risk of sepsis.
The Plasma Lipidomic Landscape in Patients with Sepsis due to Community-acquired Pneumonia.
Rationale: The plasma lipidome has the potential to reflect many facets of the host status during severe infection. Previous work is limited to specific lipid groups or was focused on lipids as prognosticators.Objectives: To map the plasma lipidome during sepsis due to community-acquired pneumonia (CAP) and determine the disease specificity and associations with clinical features.Methods: We analyzed 1,833 lipid species across 33 classes in 169 patients admitted to the ICU with sepsis due to CAP, 51 noninfected ICU patients, and 48 outpatient controls. In a paired analysis, we reanalyzed patients still in the ICU 4 days after admission (n = 82).Measurements and Main Results: A total of 58% of plasma lipids were significantly lower in patients with CAP-attributable sepsis compared with outpatient controls (6% higher, 36% not different). We found strong lipid class-specific associations with disease severity, validated across two external cohorts, and inflammatory biomarkers, in which triacylglycerols, cholesterol esters, and lysophospholipids exhibited the strongest associations. A total of 36% of lipids increased over time, and stratification by survival revealed diverging lipid recovery, which was confirmed in an external cohort; specifically, a 10% increase in cholesterol ester levels was related to a lower odds ratio (0.84; P = 0.006) for 30-day mortality (absolute mortality, 18 of 82). Comparison with noninfected ICU patients delineated a substantial common illness response (57.5%) and a distinct lipidomic signal for patients with CAP-attributable sepsis (37%).Conclusions: Patients with sepsis due to CAP exhibit a time-dependent and partially disease-specific shift in their plasma lipidome that correlates with disease severity and systemic inflammation and is associated with higher mortality.
Nursing Practice of Airway Care Interventions and Prone Positioning in ICU Patients with COVID-19-A Dutch National Survey.
Background: Airway care interventions and prone positioning are used in critically ill patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) to improve oxygenation and facilitate mucus removal. At the onset of the COVID-19 pandemic, the decision-making process regarding the practice of airway care interventions and prone positioning was challenging. Objective: To provide an overview of the practice of airway care interventions and prone positioning during the second wave of the pandemic in the Netherlands. Method: Web-based survey design. Seventy ICU nurses, each representing one intensive care in the Netherlands, were contacted for participation. Potential items were generated based on a literature search and formulated by a multidisciplinary team. Questions were pilot tested for face and construct validity by four intensive care nurses from four different hospitals. Results: The response rate was 53/77 (69%). This survey revealed widespread use of airway care interventions in the Netherlands in COVID-19 patients, despite questionable benefits. Additionally, prone positioning was used in invasively and non-invasively ventilated patients. Conclusions: The use of airway care interventions and prone positioning is time consuming and comes with the production of waste. Further research is needed to assess the effectiveness, workload, and environmental impact of airway care interventions and prone positioning.
Hemolysis Index Correlations with Plasma-Free Hemoglobin and Plasma Lactate Dehydrogenase in Critically Ill Patients under Extracorporeal Membrane Oxygenation or Mechanical Circulatory Support-A Single-Center Study.
Monitoring for thrombosis and hemolysis is crucial for patients under extracorporeal or mechanical circulatory support, but it can be costly. We investigated correlations between hemolysis index (HI) and plasma-free hemoglobin (PFH) levels on one hand, and between the HI and plasma lactate dehydrogenase (LDH) levels on the other, in critically ill patients with and without extracorporeal or mechanical circulatory support. Additionally, we calculated the cost reductions if monitoring through HI were to replace monitoring through PFH or plasma LDH. In a single-center study, HI was compared with PFH and plasma LDH levels in blood samples taken for routine purposes in critically ill patients with and without extracorporeal or mechanical circulatory support. A cost analysis, restricted to direct costs associated with each measurement, was made for an average 10-bed ICU. This study included 147 patients: 56 patients with extracorporeal or mechanical circulatory support (450 measurements) and 91 patients without extracorporeal or mechanical circulatory support (562 measurements). The HI correlated well with PFH levels (r = 0.96; p < 0.01) and poorly with plasma LDH levels (r = 0.07; p < 0.01) in patients with extracorporeal or mechanical circulatory support. Similarly, HI correlated well with PFH levels (r = 0.97; p < 0.01) and poorly with plasma LDH levels (r = -0.04; p = 0.39) in patients without extracorporeal or mechanical circulatory support. ROC analyses demonstrated a strong performance of HI, with the curve indicating excellent discrimination in the whole cohort (area under the ROC of 0.969) as well as in patients under ECMO or mechanical circulatory support (area under the ROC of 0.988). Although the negative predictive value of HI for predicting PFH levels > 10 mg/dL was high, its positive predictive value was found to be poor at various cutoffs. A simple cost analysis showed substantial cost reduction if HI were to replace PFH or plasma LDH for hemolysis monitoring. In conclusion, in this cohort of critically ill patients with and without extracorporeal or mechanical circulatory support, HI correlated well with PFH levels, but poorly with plasma LDH levels. Given the high correlation and substantial cost reductions, a strategy utilizing HI may be preferable for monitoring for hemolysis compared to monitoring strategies based on PFH or plasma LDH. The PPV of HI, however, is unacceptably low to be used as a diagnostic test.
Detection of Mycoplasma pneumoniae in hospitalized children with pneumonia in Laos
Mycoplasma pneumoniae has been described worldwide as an important cause of community-acquired pneumonia. From December 2013 to December 2014, 461 children admitted to Mahosot Hospital, Vientiane, Laos, with acute respiratory infection were investigated for upper respiratory microorganisms using probe-based real-time polymerase chain reaction (PCR) (FTD33). M. pneumoniae was detected by FTD33 in the upper respiratory tract of three patients, two girls and one boy, 5.7 and 3.9 years old and 13.6 years old, respectively. They presented with clinical features compatible with M. pneumoniae infection. The two girls were also positive for other potential pathogens. The boy had abnormal pulmonary auscultation, and one of the girls had significant anaemia. These results suggest that enhancement of diagnostic systems for M. pneumoniae detection and analysis of its antibiotic resistance profile is needed to raise awareness and improve understanding of the epidemiology of M. pneumoniae infection in Laos, enable targeted therapy, and inform treatment guidelines.
Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection.
The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of BA.4/5 mAbs culminating in total loss of function with recent XBB.1.5.70 variants containing the so-called 'FLip' mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86.
Building citizen science intelligence for outbreak preparedness and response: a mixed-method study in nine countries to assess knowledge, readiness and feasibility.
IntroductionCitizen science (CS) is an emerging approach in public health to harness the collective intelligence of individuals to augment traditional scientific efforts. However, citizens' viewpoint, especially the hard-to-reach population, is lacking in current outbreak-related literature. We aim to understand the awareness, readiness and feasibility of outbreak-related CS, including digitally enabled CS, in low-income and middle-income countries.MethodsThis mixed-method study was conducted in nine countries between October 2022 and June 2023. Recruitment through civil society targeted the general population, marginalised/indigenous groups, youth and community health workers. Participants (aged ≥18 years) completed a quantitative survey, and a subset participated in focus group discussions (FGDs).Results2912 participants completed the survey and 4 FGDs were conducted in each country. Incorporating participants' perspectives, CS is defined as the practice of active public participation, collaboration and communication in all aspects of scientific research to increase public knowledge, create awareness, build trust and facilitate information flow between citizens, governments and scientists. In Bangladesh, Indonesia, the Philippines, Cameroon and Kenya, majority were unaware of outbreak-related CS. In India and Uganda, majority were aware but unengaged, while in Nepal and Zimbabwe, majority participated in CS before. Engagement approaches should consider different social and cultural contexts, while addressing incentivisation, attitudes and practicality factors. Overall, 76.0% expressed interest in digital CS but needed training to build skills and confidence. Digital CS was perceived as convenient, safer for outbreak-related activities and producing better quality and quantity of data. However, there were concerns over non-inclusion of certain groups, data security and unclear communication.ConclusionCS interventions need to be relatable and address context-specific factors influencing CS participation. Digital CS has the potential to facilitate collaboration, but capacity and access issues must be considered to ensure inclusive and sustainable engagement.
The double burden of malnutrition in individuals: Identifying key challenges and re-thinking research focus.
The 'double burden of malnutrition' is a global health challenge that increasingly affects populations in both low- and middle-income countries (LMICs). This phenomenon refers to the coexistence of undernutrition and overweight or obesity, as well as other diet-related non-communicable diseases, in the same population, household or even individual. While noteworthy progress has been made in reducing undernutrition in some parts of the world, in many of these areas, the prevalence of overweight and obesity is increasing, particularly in urban areas, resulting in greater numbers of people who were undernourished in childhood and have overweight or obesity in adulthood. This creates a complex and challenging situation for research experts and policymakers who must simultaneously address the public health burdens of undernutrition and overweight/obesity. This review identifies key challenges and limitations in the current research on the double burden of malnutrition in individuals, including the need for a more comprehensive and nuanced understanding of the drivers of malnutrition, the importance of context-specific interventions and the need for greater attention to the food environment and food systems. We advocate for the re-evaluation of research strategies and focus, with a greater emphasis on multidisciplinary and systems approaches and greater attention to the synergistic relationship between the biological, environmental, commercial and socio-economic determinants of malnutrition. Addressing these key challenges can enable us to better comprehend and tackle the multifaceted and dynamic issues of the double burden of malnutrition, particularly in individuals and work towards more effective and sustainable solutions.
Distinct transcriptomic signatures define febrile malaria depending on initial infective states, asymptomatic or uninfected.
BackgroundCumulative malaria parasite exposure in endemic regions often results in the acquisition of partial immunity and asymptomatic infections. There is limited information on how host-parasite interactions mediate the maintenance of chronic symptomless infections that sustain malaria transmission.MethodsHere, we determined the gene expression profiles of the parasite population and the corresponding host peripheral blood mononuclear cells (PBMCs) from 21 children (ResultsChildren with asymptomatic infections had a parasite transcriptional profile characterized by a bias toward trophozoite stage (~ 12 h-post invasion) parasites and low parasite levels, while early ring stage parasites were characteristic of febrile malaria. The host response of asymptomatic children was characterized by downregulated transcription of genes associated with inflammatory responses, compared with children with febrile malaria,. Interestingly, the host responses during febrile infections that followed an asymptomatic infection featured stronger inflammatory responses, whereas the febrile host responses from previously uninfected children featured increased humoral immune responses.ConclusionsThe priming effect of prior asymptomatic infection may explain the blunted acquisition of antibody responses seen to malaria antigens following natural exposure or vaccination in malaria endemic areas.