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EBioMedicine May 2024Dengue epidemics impose considerable strain on healthcare resources. Real-time continuous and non-invasive monitoring of patients admitted to the hospital could lead to...
BACKGROUND
Dengue epidemics impose considerable strain on healthcare resources. Real-time continuous and non-invasive monitoring of patients admitted to the hospital could lead to improved care and outcomes. We evaluated the performance of a commercially available wearable (SmartCare) utilising photoplethysmography (PPG) to stratify clinical risk for a cohort of hospitalised patients with dengue in Vietnam.
METHODS
We performed a prospective observational study for adult and paediatric patients with a clinical diagnosis of dengue at the Hospital for Tropical Disease, Ho Chi Minh City, Vietnam. Patients underwent PPG monitoring early during admission alongside standard clinical care. PPG waveforms were analysed using machine learning models. Adult patients were classified between 3 severity classes: i) uncomplicated (ward-based), ii) moderate-severe (emergency department-based), and iii) severe (ICU-based). Data from paediatric patients were split into 2 classes: i) severe (during ICU stay) and ii) follow-up (14-21 days after the illness onset). Model performances were evaluated using standard classification metrics and 5-fold stratified cross-validation.
FINDINGS
We included PPG and clinical data from 132 adults and 15 paediatric patients with a median age of 28 (IQR, 21-35) and 12 (IQR, 9-13) years respectively. 1781 h of PPG data were available for analysis. The best performing convolutional neural network models (CNN) achieved a precision of 0.785 and recall of 0.771 in classifying adult patients according to severity class and a precision of 0.891 and recall of 0.891 in classifying between disease and post-disease state in paediatric patients.
INTERPRETATION
We demonstrate that the use of a low-cost wearable provided clinically actionable data to differentiate between patients with dengue of varying severity. Continuous monitoring and connectivity to early warning systems could significantly benefit clinical care in dengue, particularly within an endemic setting. Work is currently underway to implement these models for dynamic risk predictions and assist in individualised patient care.
FUNDING
EPSRC Centre for Doctoral Training in High-Performance Embedded and Distributed Systems (HiPEDS) (Grant: EP/L016796/1) and the Wellcome Trust (Grants: 215010/Z/18/Z and 215688/Z/19/Z).
PubMed: 38815363
DOI: 10.1016/j.ebiom.2024.105164 -
PNAS Nexus May 2024C-type lectins (CTLs) are a family of carbohydrate-binding proteins and an important component of mosquito saliva. Although CTLs play key roles in immune activation and...
C-type lectins (CTLs) are a family of carbohydrate-binding proteins and an important component of mosquito saliva. Although CTLs play key roles in immune activation and viral pathogenesis, little is known about their role in regulating dengue virus (DENV) infection and transmission. In this study, we established a homozygous knockout mutant line using CRISPR/Cas9 to study the interaction between and viruses in mosquito vectors. Furthermore, mouse experiments were conducted to confirm the transmission of DENV by mutants. We found that was mainly expressed in the medial lobe of the salivary glands (SGs) in female . knockout increased DENV replication and accumulation in the SGs of female , suggesting that plays an important role in DENV transmission. We also found a reduced expression of immunodeficiency and Janus kinase/signal transducer and activator of transcription pathway components correlated with increased DENV viral titer, infection rate, and transmission efficiency in the mutant strain. The findings of this study provide insights not only for guiding future investigations on the influence of CTLs on immune responses in mosquitoes but also for developing novel mutants that can be used as vector control tools.
PubMed: 38813522
DOI: 10.1093/pnasnexus/pgae188 -
Health Science Reports Jun 2024Epidemics of the dengue virus can trigger widespread morbidity and mortality along with no specific treatment. Examining the spatial autocorrelation and variability of...
BACKGROUND
Epidemics of the dengue virus can trigger widespread morbidity and mortality along with no specific treatment. Examining the spatial autocorrelation and variability of dengue prevalence throughout Bangladesh's 64 districts was the focus of this study.
METHODS
The spatial autocorrelation is evaluated with the help of Moran and Geary . Local Moran was used to detect hotspots and cold spots, whereas local Getis Ord was used to identify only spatial hotspots. The spatial heterogeneity has been detected using various conventional and spatial models, including the Poisson-Gamma model, the Poisson-Lognormal Model, the Conditional Autoregressive (CAR) model, the Convolution model, and the BYM2 model, respectively. These models are implemented using Gibbs sampling and other Bayesian hierarchical approaches to analyze the posterior distribution effectively, enabling inference within a Bayesian context.
RESULTS
The study's findings show that Moran and Geary analysis provides a substantial clustering pattern of positive spatial autocorrelation of dengue fever (DF) rates between surrounding districts at a 90% confidence interval. The Local Indicators of Spatial Autocorrelation cluster mapped spatial clusters and outliers based on prevalence rates, while the local Getis-Ord displayed a thorough breakdown of high or low rates, omitting outliers. Although Chattogram had the most dengue cases (15,752), Khulna district had a higher prevalence rate (133.636) than Chattogram (104.796). The BYM2 model, determined to be well-fitted based on the lowest Deviance Information Criterion value (527.340), explains a significant association between spatial heterogeneity and prevalence rates.
CONCLUSION
This research pinpoints the district with the highest prevalence rate for dengue and the neighboring districts that also have high risk, allowing government agencies and communities to take the necessary precautions to mollify the risk effect of DF.
PubMed: 38812714
DOI: 10.1002/hsr2.2154 -
PloS One 2024Ae. aegypti is the vector of important μ arboviruses, including dengue, Zika, chikungunya and yellow fever. Despite not being specifically targeted by insecticide-based...
BACKGROUND
Ae. aegypti is the vector of important μ arboviruses, including dengue, Zika, chikungunya and yellow fever. Despite not being specifically targeted by insecticide-based control programs in West Africa, resistance to insecticides in Ae. aegypti has been reported in countries within this region. In this study, we investigated the status and mechanisms of Ae. aegypti resistance in Niamey, the capital of Niger. This research aims to provide baseline data necessary for arbovirus outbreak prevention and preparedness in the country.
METHODS
Ovitraps were used to collect Ae. aegypti eggs, which were subsequently hatched in the insectary for bioassay tests. The hatched larvae were then reared to 3-5-day-old adults for WHO tube and CDC bottle bioassays, including synergist tests. The kdr mutations F1534C, V1016I, and V410L were genotyped using allele-specific PCR and TaqMan qPCR methods.
RESULTS
Ae. aegypti from Niamey exhibited moderate resistance to pyrethroids but susceptibility to organophosphates and carbamates. The kdr mutations, F1534C, V1016I and V410L were detected with the resistant tri-locus haplotype 1534C+1016L+410L associated with both permethrin and deltamethrin resistance. Whereas the homozygote tri-locus resistant genotype 1534CC+1016LL+410LL was linked only to permethrin resistance. The involvement of oxidase and esterase enzymes in resistance mechanisms was suggested by partial restoration of mosquitoes' susceptibility to pyrethroids in synergist bioassays.
CONCLUSION
This study is the first report of Ae. aegypti resistance to pyrethroid insecticides in Niamey. The resistance is underpinned by target site mutations and potentially involves metabolic enzymes. The observed resistance to pyrethroids coupled with susceptibility to other insecticides, provides data to support evidence-based decision-making for Ae. aegypti control in Niger.
Topics: Animals; Aedes; Insecticide Resistance; Pyrethrins; Niger; Insecticides; Mutation; Mosquito Vectors; Genotype; Larva; Insect Proteins
PubMed: 38809933
DOI: 10.1371/journal.pone.0304550 -
Epidemiologia E Servicos de Saude :... 2024To create a protocol for performing minimally invasive autopsies (MIA) in detecting deaths from arboviruses and report preliminary data from its application in Ceará...
OBJECTIVE
To create a protocol for performing minimally invasive autopsies (MIA) in detecting deaths from arboviruses and report preliminary data from its application in Ceará state, Brazil.
METHODS
Training was provided to medical pathologists on MIA.
RESULTS
A protocol was established for performing MIA, defining criteria for sample collection, storage methods, and diagnoses to be carried out according to the type of biological sample; 43 MIAs were performed in three months. Of these, 21 (48.8%) arrived at the Death Verification Service (SVO) with arboviruses as a diagnostic hypothesis, and seven (16.3%) were confirmed (six chikungunya cases and one dengue case); cases of COVID-19 (n = 9), tuberculosis (n = 5), meningitis (n = 4), cryptococcosis (n = 1), Creutzfeldt-Jakob disease (n = 1), breast cancer (n = 1), and human rabies (n = 1) were also confirmed.
CONCLUSION
The protocol implemented enabled identification of a larger number of suspected arbovirus-related deaths, as well as confirmation of other diseases of interest for surveillance.
MAIN RESULTS
A protocol was developed to perform minimally invasive autopsies (MIAs) in Death Verification Services (SVO), capable of expanding the system's capacity to identify a greater number of deaths suspected to be due to arboviruses.
IMPLICATIONS FOR SERVICES
The experience suggests that in-service trained health professionals are able to perform MIA, and that use of this technique in SVOs has been shown to be capable of increasing the system's sensitivity in detecting deaths of interest to public health.
PERSPECTIVES
Trained professionals will be able to collect biological material in hospitals, through MIA, in cases of interest for health surveillance and when family members do not allow a complete conventional autopsy to be performed.
Topics: Humans; Brazil; Autopsy; Arbovirus Infections; Female; Sensitivity and Specificity; Male; Middle Aged; Adult; Adolescent; Young Adult; Arboviruses; Aged; Population Surveillance; Epidemiological Monitoring; Cause of Death; Child; Child, Preschool
PubMed: 38808901
DOI: 10.1590/S2237-96222024V33E2024008.en -
Open Veterinary Journal Apr 2024Dengue infection can trigger an immunological response that results in an inflammatory reaction, which acts as a defensive mechanism to protect the host. Dengue...
BACKGROUND
Dengue infection can trigger an immunological response that results in an inflammatory reaction, which acts as a defensive mechanism to protect the host. Dengue infection leads to an elevation in the release of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). These three cytokines have been shown to correlate with the development of thrombocytopenia and plasma leakage, which is related to the severity of the disease.
AIM
This study aims to investigate the effect of faloak ( R. Br) stem bark on TNF-α, IL-1β, and IL-6 levels in Wistar rats infected with dengue, specifically DENV-3.
METHODS
A group of 27 male Wistar rats () aged 2-3 months and weighting 200-300 g were divided into three distinct groups: healthy, dengue, and treatment (dengue infection and extract) groups. The rats in both the dengue and treatment groups were administered an injection of DENV-3 with a titer of 105 pfu at a dosage of 0.8 cc via the intraperitoneal route. The propagation of DENV-3 was initiated using C6/36 cells, and it underwent four passages. The extract was administered orally via a nasogastric tube at a dosage of 1,500 mg/kg body weight once daily for 7 days. The healthy group underwent blood sampling on the first day, whereas the dengue and therapy groups underwent blood sampling on the fifth and eighth, respectively.
RESULTS
Compared with the healthy group, TNF-α levels in the dengue and treatment groups showed significant differences on day 5 post-infection. The analysis revealed a statistically significant difference between the dengue-treatment and dengue-healthy groups. The IL-1β levels in the dengue and healthy groups significantly differed on days 5 and 8 post-infection compared to the healthy group. The treatment group had less of a decrease in IL-6 levels on days 5 and 8 than the dengue group. However, no statistically significant differences were observed.
CONCLUSION
The stem bark of shows potential as an anti-inflammatory agent in dengue infections, particularly in its ability to decrease levels of TNF-α and IL-1β.
Topics: Animals; Rats, Wistar; Male; Rats; Plant Bark; Tumor Necrosis Factor-alpha; Dengue; Plant Extracts; Interleukin-6; Anti-Inflammatory Agents; Interleukin-1beta; Dengue Virus
PubMed: 38808285
DOI: 10.5455/OVJ.2024.v14.i4.11 -
Lancet Regional Health. Americas Jul 2024CYD-TDV (Dengvaxia®) was the first dengue vaccine approved, launched in Brazil in 2015 for individuals aged 9-44 years. We aimed to estimate the effectiveness of...
BACKGROUND
CYD-TDV (Dengvaxia®) was the first dengue vaccine approved, launched in Brazil in 2015 for individuals aged 9-44 years. We aimed to estimate the effectiveness of CYD-TDV in preventing symptomatic dengue cases during a campaign targeting individuals aged 15-27 years in selected municipalities in Paraná, Brazil. Additionally, we examined whether a history of dengue, as recorded by the surveillance system, modified the vaccine's effectiveness.
METHODS
We conducted a case-cohort analysis comparing the frequency of vaccination, with at least one dose of CYD-TDV, in individuals with dengue confirmed by RT-PCR, identified by the surveillance system during 2019 and 2020, with the vaccination coverage in the target population. Moreover, in a case-control design using weighted controls, we assessed the documented history of dengue as a modifier of the vaccine's effectiveness. We used a logistic random-effects regression model, with data clustered in municipalities and incorporating covariates such as the incidence of dengue before the campaign, age, and sex. We calculated vaccine effectiveness (VE) as (1-relative risk) x 100%.
FINDINGS
1869 dengue cases were identified, which had a vaccination frequency significantly lower than the overall vaccination coverage in the target population (50.3% vs. 57.2%, respectively; overall VE: 21.3%; 95% confidence interval [CI]: 13.4%-28.4%). In individuals with a documented history of dengue, vaccination had a VE of 71% (95% CI: 58%-80%) in reducing the incidence of dengue. However, vaccination was not associated with a significant reduction in the overall dengue case risk in individuals without a documented history of dengue (VE: 12%; 95% CI: -21% to 36%). In this last stratum, vaccination was associated with reduced cases due to DENV-1 and DENV-4, but an excess of DENV-2 cases.
INTERPRETATION
Vaccination led to a significant reduction in reported dengue cases within the target population. The case-control design suggested that this reduction was primarily driven by the benefits observed in individuals with a documented history of dengue. In endemic regions with limited serological testing facilities, a previous history of dengue diagnosis recorded by epidemiological surveillance could be used to triage candidates for CYD-TDV vaccination.
FUNDING
Research supported by Sanofi.
PubMed: 38807985
DOI: 10.1016/j.lana.2024.100777 -
Heliyon May 2024In recent years, research on exosomal miRNAs has provided new insights into exploring the mechanism of viral infection and disease prevention. This study aimed to...
BACKGROUND
In recent years, research on exosomal miRNAs has provided new insights into exploring the mechanism of viral infection and disease prevention. This study aimed to investigate the serum exosomal miRNA expression profile of dengue-infected individuals through a community survey of dengue virus (DENV) infection.
METHODS
A seroprevalence study of 1253 healthy persons was first conducted to ascertain the DENV infection status in Baiyun District, Guangzhou. A total of 18 serum samples, including 6 healthy controls (HC), 6 asymptomatic DENV infections (AsymptDI), and 6 confirmed dengue fever patients (AcuteDI), were collected for exosome isolation and then sRNA sequencing. Through bioinformatics analysis, we discovered distinct serum exosomal miRNA profiles among the different groups and identified differentially expressed miRNAs (DEMs). These findings were further validated by qRT-PCR.
RESULTS
The community survey of DENV infection indicated that the DENV IgG antibody positivity rate among the population was 11.97 % in the study area, with asymptomatic infected individuals accounting for 93.06 % of the anti-DENV IgG positives. The age and Guangzhou household registration were associated with DENV IgG antibody positivity by logistic regression analysis. Distinct miRNA profiles were observed between healthy individuals and DENV infections. A total of 1854 miRNAs were identified in 18 serum exosome samples from the initial analysis of the sequencing data. Comparative analysis revealed 23 DEMs comprising 5 upregulated and 18 downregulated miRNAs in the DENV-infected group (mergedDI). In comparison to AcuteDI, 18 upregulated miRNAs were identified in AsymptDI. Moreover, functional enrichment of the predicted target genes of DEMs indicated that these miRNAs were involved in biological processes and pathways related to cell adhesion, focal adhesion, endocytosis, and ECM-receptor interaction. Eight DEMs were validated by qRT-PCR.
CONCLUSION
The Baiyun District of Guangzhou exhibits a notable proportion of asymptomatic DENV infections as suggested in other research, highlighting the need for enhanced monitoring and screening of asymptomatic persons and the elderly. Differential miRNA expression among healthy, symptomatic and asymptomatic DENV-infected individuals suggests their potential as biomarkers for distinguishing DENV infection and offers new avenues of investigating the mechanisms underlying DENV asymptomatic infections.
PubMed: 38807894
DOI: 10.1016/j.heliyon.2024.e31546 -
Scientific Reports May 2024The Ae. albopictus mosquito has gained global attention due to its ability to transmit viruses, including the dengue and zika. Mosquito control is the only effective way...
Resistance to pyrethroids and the relationship between adult resistance and knockdown resistance (kdr) mutations in Aedes albopictus in dengue surveillance areas of Guizhou Province, China.
The Ae. albopictus mosquito has gained global attention due to its ability to transmit viruses, including the dengue and zika. Mosquito control is the only effective way to manage dengue fever, as no effective treatments or vaccines are available. Insecticides are highly effective in controlling mosquito densities, which reduces the chances of virus transmission. However, Ae. albopictus has developed resistance to pyrethroids in several provinces in China. Pyrethroids target the voltage-gated sodium channel gene (VGSC), and mutations in this gene may result in knockdown resistance (kdr). Correlation studies between resistance and mutations can assist viruses in managing Ae. albopictus, which has not been studied in Guizhou province. Nine field populations of Ae. albopictus at the larval stage were collected from Guizhou Province in 2022 and reared to F1 to F2 generations. Resistance bioassays were conducted against permethrin, beta-cypermethrin, and deltamethrin for both larvae and adults of Ae. albopictus. Kdr mutations were characterized by PCR and sequencing. Additionally, the correlation between the kdr allele and pyrethroid resistance was analyzed. All nine populations of Ae. albopictus larvae and adults were found to be resistant to three pyrethroid insecticides. One kdr mutant allele at codon 1016, one at 1532 and three at 1534 were identified with frequencies of 13.86% (V1016G), 0.53% (I1532T), 58.02% (F1534S), 11.69% (F1534C), 0.06% (F1534L) and 0.99% (F1534P), respectively. Both V1016G and F1534S mutation mosquitoes were found in all populations. The kdr mutation F1534S was positively correlated with three pyrethroid resistance phenotypes (OR > 1, P < 0.05), V1016G with deltamethrin and beta-cypermethrin resistance (OR > 1, P < 0.05) and F1534C only with beta-cypermethrin resistance (OR > 1, P < 0.05). Current susceptibility status of wild populations of Ae. albopictus to insecticides and a higher frequency of kdr mutations from dengue-monitored areas in Guizhou Province are reported in this paper. Outcomes of this study can serve as data support for further research and development of effective insecticidal interventions against Ae. albopictus populations in Guizhou Province.
Topics: Animals; Pyrethrins; Aedes; Insecticide Resistance; China; Dengue; Mutation; Insecticides; Mosquito Vectors; Larva; Voltage-Gated Sodium Channels; Mosquito Control; Nitriles
PubMed: 38806622
DOI: 10.1038/s41598-024-63138-0 -
Nature Communications May 2024Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity...
Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity between one or more sources and a suitable local environment, but how these two factors interact at different stages of disease emergence remains largely unknown. Further, no analytical framework exists to examine their roles. Here we develop a dynamic modelling approach for infectious diseases that explicitly models both connectivity via human movement and environmental suitability interactions. We apply it to better understand recently observed (1995-2019) patterns as well as predict past unobserved (1983-2000) and future (2020-2039) spread of dengue in Mexico and Brazil. We find that these models can accurately reconstruct long-term spread pathways, determine historical origins, and identify specific routes of invasion. We find early dengue invasion is more heavily influenced by environmental factors, resulting in patchy non-contiguous spread, while short and long-distance connectivity becomes more important in later stages. Our results have immediate practical applications for forecasting and containing the spread of dengue and emergence of new serotypes. Given current and future trends in human mobility, climate, and zoonotic spillover, understanding the interplay between connectivity and environmental suitability will be increasingly necessary to contain emerging and re-emerging pathogens.
Topics: Dengue; Humans; Brazil; Mexico; Animals; Dengue Virus; Communicable Diseases, Emerging; Environment; Human Migration; Aedes
PubMed: 38806460
DOI: 10.1038/s41467-024-48465-0