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SC Johnson Guardian™ spatial repellent shows 1-year efficacy against wild pyrethroid-resistant Anopheles arabiensis, with a similar blood-feeding inhibition efficacy to Mosquito Shield™ in a Tanzanian experimental hut trial
Get PDFBackground: Spatial repellents (SRs) that passively emanate airborne concentrations of an active ingredient within a space disrupt mosquito behaviors to reduce human-vector contact. A clinical trial of SC Johnson’s Mosquito Shield™ (Mosquito Shield) demonstrated a 33% protective efficacy against malaria in Kenya. Mosquito Shield lasts for 1 month, but a longer duration product is needed for malaria control programs. SC Johnson’s Guardian™ (Guardian) is designed to provide longer continuous protection from disease-transmitting mosquitoes.
Methods: We conducted experimental hut trials to i) evaluate the efficacy of Guardian over 12 months (between May 2022 and May 2023) and ii) assess the potential public health utility of Guardian by comparing it to Mosquito Shield over 1 month (midway through the Guardian evaluation in November 2022) against wild pyrethroid-resistant malaria vector mosquitoes. The primary endpoint was the number of blood-fed Anopheles arabiensis, while secondary endpoints were the proportion of dead An. arabiensis at 24 hours and the proportion of blood-fed mosquitoes. For Guardian, the number of mosquito landings was also evaluated by human landing catch, a method routinely used in community or implementation studies.
Results: Over 12 months of continuous use, Guardian reduced the number of An. arabiensis blood-feeding by 82.7% [95% confidence interval (78.5%–86.1%)] and landing by 65.1% (59.4%– 70.0%). Guardian also induced 20.1% mortality (18.4%–21.8%). Guardian was found to be superior to Mosquito Shield in reducing the number of blood-fed An. arabiensis with similar proportions of blood-fed and dead mosquitoes at 24 hours.
Conclusion: Guardian was effective in reducing blood-feeding and landing of wild pyrethroid-resistant malaria vectors for 12 months and shows superior protective efficacy compared to Mosquito Shield in reducing the overall number of blood-feeding mosquitoes. Experimental hut studies are suitable for comparative evaluations of new spatial repellent products because they precisely estimate entomological endpoints elicited by spatial repellents known to significantly impact vectorial capacity and disease transmission
Chikungunya in a pediatric cohort: Asymptomatic infection, seroconversion, and chronicity rates.
Get PDFChikungunya disease, caused by the chikungunya virus (CHIKV), is an acute febrile syndrome that frequently leads to chronic musculoskeletal manifestations. Little is known about the incidence, asymptomatic rate, seroconversion and chronicity after acute CHIKV infection in children and adolescents. We leveraged a nested cohort study within a phase III clinical trial of the Dengue vaccine by the Butantan Institute (DEN-03-IB), in Simões Filho (Bahia-Brazil) to characterize the dynamics of CHIKV infection in the pediatric population. 348 volunteers were included between 2018-2020 and followed for up to three years. Arbovirus surveillance was conducted during medical visits using 1) routine study visits with periodic blood collection; 2) visits due to adverse events (any symptom or illness); and 3) visits due to febrile episodes, with routine blood samples tested for chikungunya, Dengue, and Zika by viral RNA detection using RT-PCR. For cases with suspected arbovirus infection, symptoms and signs were collected with a structured questionnaire. At baseline, 7% (23/348) were positive for antichikungunya IgG. Among 311 that completed follow up (41 months, IQR 38-43), 17% tested positive for CHIKV, with 25 cases positive by RT-PCR and 28 cases by serology. 9.4% were asymptomatic and 3 (12%) developed chronic arthralgia. By the end of the study, only onefifth have been exposed to CHIKV despite several local outbreaks. Seroconversion rate among RT-PCR positive cases was 84%. Chronic arthralgia, though infrequent, was observed in the pediatric population. Our study demonstrates that, within the pediatric population, most CHIKV infections are symptomatic. We observed a small but significant frequency of negative antibody responses following acute infection and instances of chronic disease. These findings underscore the necessity for continuous surveillance and tailored interventions to tackle the unique challenges chikungunya presents in children and adolescents
Comparisons of Preferences Toward EQ-5D-Y-3L Health States Between Adult Own and Child Perspectives.
Get PDFOBJECTIVES: The international valuation protocol for EQ-5D-Y-3L recommends elicitation of utilities using adults' preference for a hypothetical 10-year-old child. Published studies have reported preference difference in adults when valuing for a child and valuing for themselves. This study aimed to obtain EQ-5D-Y-3L preferences in Hong Kong and understand the preference difference between the adult own perspective and the child perspective. METHODS: We recruited 1000 and 200 adults in Hong Kong to value EQ-5D-Y-3L health states using discrete choice experiment and composite time trade-off (cTTO), respectively. Discrete choice experiment respondents were randomized to complete tasks from either adult own perspective or child perspective. cTTO respondents completed valuation from the child perspective. Relative attribute importance scores were compared between perspectives. Utility values were obtained by anchoring on the worst health state for both perspectives. RESULTS: Both perspectives had similar relative attribute importance scores, rankings of dimensions, rescaled coefficients, and elicited values. Rank order of 5 dimensions, from highest to lowest importance, was "having pain or discomfort," "doing usual activities," "feeling worried, sad, or unhappy," "mobility," and "looking after myself" for both perspectives. The most important and least important dimensions were consistent with published EQ-5D-Y-3L value sets. CONCLUSIONS: This study revealed no remarkable difference in the relative preference for EQ-5D-Y-3L health states between the adult own and child perspectives in Hong Kong, offering insights to the development of the EQ-5D-Y-5L valuation protocol. Future research may explore the effect of perspectives on preferences elicited by cTTO in Asia
Impact of Heat on Birth Outcomes and Child Nutrition: Study Protocol using the CIDACS Birth Cohort
Get PDFBackground Pregnant individuals and children are particularly vulnerable to the adverse health consequences of exposure to heat. Leveraging the robust ecosystem of Brazilian linked administrative data, we aim to advance our understanding of how high temperatures and heatwaves influence birth outcomes and child nutrition. Objectives Investigate the association between high ambient temperatures/ heatwaves and 1) birth outcomes (low birth weight (LBW), small for gestational age (SGA), large for gestational age (LGA), and preterm birth), 2) child nutrition (growth), and 3) breastfeeding practices and complementary feeding in children. Methods We will triangulate results from complementary analytical approaches, including time-stratified case-crossover designs and time-to-event techniques. We will explore the influence of high temperatures and heatwaves at different periods (or lags) preceding the event and apply distributed lag non-linear models to account for delayed and non-linear effects. We will conduct subgroup analyses to identify the population groups most at risk. Results and Conclusions Our study will generate new insights into the relationship between heat, birth outcomes, and child nutrition in Brazil. By providing evidence from a middle-income country with diverse ecosystems and climate zones in a context of social inequalities, this research will contribute to advancing the current knowledge base. Additionally, by identifying critical windows of vulnerability and at-risk groups, our findings can potentially inform targeted and equitable climate adaptation policies.</ns3:p
Causes of hospitalisation among people living with HIV worldwide, 2014-23: a systematic review and meta-analysis.
Get PDFBACKGROUND: Despite improved access to antiretroviral therapy (ART), HIV-related morbidity and mortality remain high. A previous review (2007-14) found that AIDS-related illnesses were the leading causes of hospitalisations. We aimed to summarise the causes of hospitalisations among people living with HIV from 2014 to 2023. METHODS: For this meta-analysis we searched eight databases (Ovid Medline ALL, Ovid Embase Classic and Ovid Embase, Ovid Global Health, EBSCOhost CINAHL Complete, EBSCOhost Africa-Wide Information, Clarivate Analytics Web of Science Core Content, Clarivate Analytics Web of Science SciELO, and Global Index Medicus) on April 26, 2023. We included studies of any design that reported on the cause of admission to hospital for at least 20 people after Jan 1, 2014. We extracted summary-level data about CD4 cell counts, ART use, cause of admission, and incidence of death, and assessed risk of bias with the use of a modified Newcastle-Ottowa Scale. We constructed random effects models to estimate prevalence of various diseases as a cause of hospital admission. FINDINGS: From the 19 629 records identified, we obtained data from 110 studies representing 100 628 hospital admissions. The weighted median CD4 count was 111 cells per μL (range of medians 25-713); 60% of admissions (95% Cl 54-66) were people receiving ART. The most common cause of admission was AIDS-related illnesses (42% of admissions, 95% CI 35-49), including tuberculosis (19%, 15-23). The second most common cause was bacterial infection (26%, 20-33). AIDS-related illnesses were more common in WHO regions of South and Central America (62%, 53-71), Africa (49%, 39-60), Western Pacific (68%, 57-77), and South-East Asia (40%, 31-50) than in Europe (30%, 23-37) and North America (13%, 6-25). Wasting and parasitic infections were more common in children (malnutrition 31%, 11-63; parasitic infection 13%, 4-37) than in adults. In-hospital mortality was 17% (13-20), with substantial regional variation. INTERPRETATION: Our results indicate providing high-quality care to hospitalised people with HIV-related conditions (AIDS-related illness and severe bacterial infections) should be prioritised. FUNDING: The Bill & Melinda Gates Foundation
Pregnant and breastfeeding women concerns during a group B Streptococcus phase ll clinical trial: A qualitative study in Kampala, Uganda.
Get PDFDespite evidence that maternal vaccines can contribute to reduction of neonatal infections, vaccine hesitancy is a challenge in many low- and middle-income countries like Uganda. We conducted in-depth interviews with pregnant women and focus group discussions with breastfeeding women who were part of a Group B Streptococcus (GBS) clinical trial. We explored the women's concerns about vaccination and their reasons for being hesitant to take vaccines before they joined the trial. Women aged 18-39 were randomly selected from follow-up lists during the study period. Data were analysed thematically. All the women had been hesitant about joining the trial because of fear of possible vaccine side effects. A lack of knowledge on maternal vaccines, rumours and stigma in the community as well the need to follow study procedures were other concerns. Several women were concerned about their male partner view of their trial participation because using a trial vaccine meant taking a decision on behalf of the foetus. Pregnant women's involvement in clinical trials of maternal immunisation requires engagement with their families and community stakeholders, including local leaders and health workers, to ensure people understand what maternal vaccines are and why trials with pregnant women are required
Point-of-care testing reduces antibiotic prescribing in acute exacerbations of chronic obstructive pulmonary disease: A systematic review and meta-analysis.
Get PDFBACKGROUND: Challenges in identifying the causes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have led to overuse of antibiotics. The advantages of point-of-care testing (POCT) may help to identify pathogens and use antibiotics more appropriately. METHODS: We conducted a systematic review to evaluate the effect of POCT to guide antibiotic prescriptions for AECOPD. Adhering to a protocol (CRD42024555847), we searched eligible studies. The outcomes included antibiotic-related and clinical outcomes. We evaluated the risk of bias and performed meta-analyses with subgroup based on the type and testing timing of POCT. RESULTS: A total of 18 studies evaluating 4346 AECOPD patients were included. Overall, POCT significantly reduced the number of AECOPD patients given antibiotic prescriptions by 16% (P < 0.001). Additionally, antibiotic treatment was reduced by 1.19 days (P = 0.04). There was no detrimental impact on clinical outcomes, such as the length of hospital stay (P = 0.19). Our results proved robust to sensitivity analyses. CONCLUSION: We offered reasonable evidence for using POCT to reduce antibiotic exposure for AECOPD without adversely affecting clinical outcomes. As diagnostic techniques become increasingly important in combating antimicrobial resistance, the use of POCT should be encouraged
Primary health care data-based early warning system for dengue outbreaks: a nationwide case study in Brazil.
Get PDFBACKGROUND: Traditional surveillance presents limitations for early outbreak detection. Primary health care (PHC) administrative data applied to syndromic surveillance offers a cost-effective way to integrate early warning systems (EWS). We evaluate the potential of an EWS for dengue outbreaks using PHC data in Brazil. METHODS: We applied the Early Aberration Reporting System (EARS-C1 and EARS-C2) to arbovirus-related PHC encounters from October 1, 2022, to March 1, 2024, to establish an EWS across 5570 municipalities. We assessed EWS timeliness, sensitivity, and positive predictive value (PPV) against fixed-incidence dengue outbreak thresholds. FINDINGS: Arbovirus-related PHC encounters occurred in 5364 (96.3%) and dengue cases in 5269 (94.6%) Brazilian municipalities. PHC-based warnings anticipated 48.5% (100 cases/100,000 inhabitants), and 68.4% (300/100,000) of outbreaks detected by existing surveillance. Timeliness was higher in municipalities with over 100,000 inhabitants. INTERPRETATION: The EARS algorithm applied to PHC data anticipated outbreaks up to four weeks before suspected case reporting. Its use of routine data ensures broader coverage and scalability. This study demonstrates the feasibility of integrating PHC data into an EWS for early dengue outbreak detection in Brazil. FUNDING: Rockefeller Foundation's Health Initiative and Fundação de Amparo à Pesquisa do Estado da Bahia, Brazil
Systematic review of risk assessment tools for post-discharge mortality among children in sub-Saharan Africa.
Get PDFPost-discharge mortality is increasingly recognized as a major contributor to the high burden of childhood mortality in sub-Saharan Africa. Accurate identification of children at risk for post-discharge mortality is critically important to inform interventions to reduce deaths following hospital discharge. Our objective was to describe the current state of development, validation, or implementation for risk assessment tools for post-hospital discharge mortality (PDM) in sub-Saharan Africa. We conducted a systematic review of publications on risk assessment tools for PDM among children aged 0-18 years in sub-Saharan Africa. We searched CABI Global Health, Cochrane Reviews, Cochrane Trials, ProQuest Dissertations and Theses, Embase, PubMed, and Web of Science with no date or language restriction. We included publications if they described a tool/model with weights assigned to variables to quantify risk of PDM, included children, and were conducted in sub-Saharan Africa. We determined the level of evidence for tools using the Evidence-Based-Medicine Working Group hierarchy. Of 4,893 publications screened, 289 full texts were reviewed, and seven publications that reported 23 risk assessment tools for PDM among children in sub-Saharan Africa were identified. These studies enrolled 49,669 total participants (3.6%, n = 1,795 experienced PDM). There was substantial heterogeneity in identified risk factors, although all identified malnutrition as a risk factor for PDM. All risk assessment tools had fair (i.e., area under the receiver operating characteristic curve [AUC] ≥0.70) or good (AUC ≥ 0.80) discriminatory value in internal validation. Only two risk assessment tools had been externally validated, and none were implemented. Existing risk assessment tools to identify children at risk for PDM in sub-Saharan Africa lack broad validation and implementation. Malnutrition is a common risk factor for PDM. Further studies are needed to validate and implement such tools to reduce PDM among children
Neutrophils display antibacterial defense via non-canonical LC3 decoration of extracellular bacteria.
No full textNeutrophils play a pivotal role in the innate immune response to bacterial infection, being one of the first immune cells to reach infectious sites. Bacterial infection may induce neutrophil degranulation, production of neutrophil extracellular traps (NETs), or pathogen phagocytosis. While LC3 is typically linked to autophagy, here we observed a non-canonical role of LC3 when peripheral neutrophils interact with bacteria both in vivo and in vitro, using Shigella spp. as a model. Upon incubation with neutrophils, extracellular bacteria became labelled by LC3 (LC3+) along with granules-localised antimicrobial components, such as lactotransferrin, defensin, elastase, and myeloperoxidase, as demonstrated by mass spectrometry. Co-localisation of LC3 and plasma membrane-specific dyes indicated that neutrophil plasma membrane-derived elongated structures covering bacteria were responsible for the labelling. This phenomenon was associated with bacterial growth restriction and bacterial cell-death induction. Testing with specific inhibitors demonstrated that this labelling was dependent on functional V-type ATP synthase. Covering bacteria with membrane-derived elongated structures enhanced the subsequent phagocytosis of bacteria by neutrophils. Finally, the LC3 labelling rate increased with higher bacterial burden. In conclusion, we propose that this defense mechanism is beneficial when the burden of bacterial infection overwhelms neutrophils' capacity for phagocytosis