Bloodmeals fuel dengue virus replication in the female mosquito Aedes aegypti.

Vector competence defines the ability of a vector to acquire, host, and transmit a pathogen. Understanding the molecular determinants of the mosquitos' competence to host dengue virus (DENV) holds promise to prevent its transmission. To this end, we employed RNA-seq to profile mRNA transcripts of the female Aedes aegypti mosquitos feeding on naïve vs viremic mouse. While most transcripts (12,634) did not change their abundances, 360 transcripts showed decreases. Biological pathway analysis revealed representatives of the decreased transcripts involved in the wnt signaling pathway and hippo signaling pathway. One thousand three hundred fourteen transcripts showed increases in abundance and participate in 21 biological pathways including amino acid metabolism, carbon metabolism, fatty acid metabolism, and oxidative phosphorylation. Inhibition of oxidative phosphorylation with antimycin A reduced oxidative phosphorylation activity and ATP concentration associated with reduced DENV replication in the Aedes aegypti cells. Antimycin A did not affect the amounts of the non-structural proteins 3 and 5, two major components of the replication complex. Ribavirin, an agent that reduces GTP concentration, recapitulated the effects of reduced ATP concentration on DENV replication. Knocking down one of the oxidative phosphorylation components, ATP synthase subunit ß, reduced DENV replication in the mosquitos. In summary, our results suggest that DENV enhances metabolic pathways in the female Aedes aegypti mosquitos to supply nutrients and energy for virus replication. ATP synthase subunit ß knockdown might be exploited to reduce the mosquitos' competence to host and transmit DENV. IMPORTANCE: Through evolution, the mosquito-borne viruses have adapted to the blood-feeding behaviors of their opportunist hosts to fulfill a complete lifecycle in humans and mosquitos. Disruption in the mosquitos' ability to host these viruses offers strategies to prevent diseases caused by them. With the advent of genomic tools, we discovered that dengue virus (DENV) benefited from the female mosquitos' bloodmeals for metabolic and energetic supplies for replication. Chemical or genetic disruption in these supplies reduced DENV replication in the female mosquitos. Our discovery can be exploited to produce genetically modified mosquitos, in which DENV infection leads to disruption in the supplies and thereby reduces replication and transmission. Our discovery might be extrapolated to prevent mosquito-borne virus transmission and the diseases they cause.

Emergence of Indigenous Dengue Fever, Niger, October 2023.

Dengue fever is a growing worldwide public health concern. In mid-October 2023, multiple cases of uncommon febrile illness were reported among patients in Niamey, Niger. Fifteen samples were tested by using molecular methods, from which 7 (46.66%) were confirmed positive for mosquitoborne dengue virus belonging to serotypes 1 and 3.

Autochthonous Dengue Fever in 2 Patients, Rome, Italy.

Since August 2023, outbreaks of dengue virus (DENV) infection have occurred in Italy. We report 2 autochthonous case-patients and their extended follow-up. Despite persistent DENV detected in blood by PCR, results for antigenomic DENV RNA were negative after day 5, suggesting that a 5-day isolation period is adequate to avoid secondary cases.

First-in-human trial evaluating safety and pharmacokinetics of AT-752, a novel nucleotide prodrug with pan-serotype activity against dengue virus.

AT-752 is a novel guanosine nucleotide prodrug inhibitor of the dengue virus (DENV) polymerase with sub-micromolar, pan-serotype antiviral activity. This phase 1, double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of ascending single and multiple oral doses of AT-752 in healthy subjects. AT-752 was well tolerated when administered as a single dose up to 1,500 mg or when administered as multiple doses up to 750 mg three times daily (TID). No serious adverse events occurred, and the majority of treatment-emergent adverse events were mild in severity and resolved by the end of the study. In those receiving single ascending doses of AT-752, no pharmacokinetic sensitivity was observed in Asian subjects, and no food effect was observed. Plasma exposure of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, increased with increasing dose levels of AT-752 and exhibited a long half-life of approximately 15-25 h. Administration of AT-752 750 mg TID led to a rapid increase in plasma levels of AT-273 exceeding the target in vitro 90% effective concentration (EC90) of 0.64 µM in inhibiting DENV replication, and maintained this level over the treatment period. The favorable safety and pharmacokinetic results support the evaluation of AT-752 as an antiviral for the treatment of dengue in future clinical studies.Registered at ClinicalTrials.gov (NCT04722627).

Proteomic investigations of dengue virus infection: key discoveries over the last 10 years.

INTRODUCTION: Dengue virus (DENV) infection remains one of the most significant infectious diseases in humans. Several efforts have been made to address its molecular mechanisms. Over the last 10 years, proteomics has been widely applied to investigate various aspects of DENV infection. AREAS COVERED: In this review, we briefly introduce common proteomics approaches using various mass spectrometric modalities followed by summarizing all the discoveries obtained from proteomic investigations of DENV infection over the last 10 years. These include the data on DENV-vector interactions and host responses to address the DENV biology and disease mechanisms. Moreover, applications of proteomics to disease prevention, diagnosis, vaccine design, development of anti-DENV agents and other new treatment strategies are discussed. EXPERT OPINION: Despite efforts on disease prevention, DENV infection is still a significant global healthcare burden that affects the general population. As summarized herein, proteomic technologies with high-throughput capabilities have provided more in-depth details of protein dynamics during DENV infection. More extensive applications of proteomics and other powerful research tools would provide a promise to better cope and prevent this mosquito-borne infectious disease.

Integrated serum proteomic and N-glycoproteomic characterization of dengue patients.

Dengue fever is a mosquito-borne viral disease caused by the dengue virus (DENV). It poses a public health threat globally and, while most people with dengue have mild symptoms or are asymptomatic, approximately 5% of affected individuals develop severe disease and need hospital care. However, knowledge of the molecular mechanisms underlying dengue infection and the interaction between the virus and its host remains limited. In the present study, we performed a quantitative proteomic and N-glycoproteomic analysis of serum from 19 patients with dengue and 11 healthy people. The results revealed distinct proteomic and N-glycoproteomic landscapes between the two groups. Notably, we report for the first time the changes in the serum N glycosylation pattern following dengue infection and provide abundant information on glycoproteins, glycosylation sites, and intact N-glycopeptides using recently developed site-specific glycoproteomic approaches. Furthermore, a series of key functional pathways in proteomic and N-glycoproteomic were identified. Collectively, our findings significantly improve understanding of host and DENV interactions and the general pathogenesis and pathology of DENV, laying a foundation for functional studies of glycosylation and glycan structures in dengue infection.

Dengue fever ophthalmic manifestations: A review and update.

Dengue fever, the most common arbovirus disease, affects an estimated 390 million people annually. Dengue virus (DENV) is an RNA virus of the Flaviviridae family with four different serotypes. Dengue haemorrhagic fever is the deadliest form of dengue infection and is characterised by thrombocytopaenia, hypotension, and the possibility of multi-system organ failure. The mechanism hypothesised for DENV viral replication is intrinsic antibody-dependent enhancement, which refers to Fcγ receptor-mediated viral amplification. This hypothesis suggests that the internalisation of DENV through the Fcγ receptor inhibits antiviral genes by suppressing type-1 interferon-mediated antiviral responses. DENV NS1 antibodies can promote the release of various inflammatory mediators in the nuclear transcription factor pathway (NF-κB-dependent), including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL-8. As a result, MCP-1 increases ICAM-1 expression and facilitates leukocyte transmigration. In addition, anti-DENV NS1 antibodies induce endothelial cell apoptosis via a nitric oxide-regulated pathway. A chain reaction involving pre-existing DENV heterotypic antibodies and innate immune cells causes dysfunction in complement system activity and contributes to the action of autoantibodies and anti-endothelial cells, resulting in endothelial cell dysfunction, blood-retinal barrier breakdown, haemorrhage, and plasma leakage. A spectrum of ocular diseases associated with DENV infection, ranging from haemorrhagic to inflammatory manifestations, has been reported in the literature. Although rare, ophthalmic manifestations can occur in both the anterior and posterior segments and are usually associated with thrombocytopenia. The most common ocular complication is haemorrhage. However, ophthalmic complications, such as anterior uveitis and vasculitis, suggest an immune-mediated pathogenesis.

Retrospective study on the dengue fever outbreak in Puntland State, Somalia.

BACKGROUND: Dengue infection is a mosquito-borne, endemic viral disease, particularly in developing countries. Here, we report the results of the clinicodemographic, serologic profile and the monthly occurrence of a recent dengue fever outbreak in Puntland State (Somalia). METHODOLOGY: We analyzed the data of 956 dengue-suspected patients who were investigated using the rapid diagnostic testing (RDT) method for detecting NS1 (dengue virus non-structural protein) and IgM antibodies employing the SD Biosensor Dengue Dou NS Ag and IgM test kit (Germany) at the Puntland Public Health Referral Laboratory from November 21, 2022, to May 27, 2023. RESULTS: We found that 118 cases were positive for dengue among the suspected patients enrolled in the present study. Of these cases, 76.2% were dengue NSI positive, 13.6% were dengue IgM positive, and 10.2% were both NSI and IgM positive. The number of females and males in the confirmed cases was equal, and most (48.3%) were aged 20 years or less. 43.1% of them lived in the Nugal region, particularly in Garowe. Clinically, fever was the most frequent symptom (88.9%). The cases peaked in December 2022 but dropped from January to March, with a slight rise in February, and then increased in April and May 2023. CONCLUSION: This study highlights the clinicodemographic characteristics, seroprevalence, and monthly occurrence of dengue in Puntland. We recommend improving vector control measures, enhancing case management, strengthening dengue surveillance, developing an early warning system, and conducting future studies to characterize the circulating strains.

Epidemiological investigation of dengue fever outbreak and its socioeconomic determinants in Banadir region, Somalia.

BACKGROUND: Dengue has become an alarming global problem and is endemic in many countries, particularly in tropical and subtropical countries. The aim of this study was to investigate dengue fever outbreak in Banadir Region, Somalia, to understand the risk factors (time, place, personal characteristics). METHODS: A descriptive cross-sectional study was undertaken to determine the levels of circulating anti-dengue virus antibodies and DENV NS1 antigen among Banadir Region residents, while a questionnaire survey was conducted to understand the clinical and demographic characteristics of the patients. RESULTS: A total of 735 febrile patients were studied, with 55.6% men and 44.3% women. The majority of the participants were children aged 14 years and younger. Among them, 10.8% tested positive for IgM antibodies against dengue virus (DENV), while the prevalence of DENV NS1 antigen was 11.8%. Fever and myalgia were the most common symptoms observed in the DENV-positive patients. CONCLUSIONS: A dengue fever outbreak has been confirmed in Banadir region, Somalia. This study provides information on the most affected districts and identifies risk factors contributing to DF outbreaks. The study recommends improving outbreak readiness and response, particularly in surveillance and laboratory diagnostics, by fostering intersectoral collaboration and establishing regulatory frameworks for financial and operational participation.

Identifying villages and breeding habitats for dengue transmission in Thailand: insights from long-term larval surveys.

BACKGROUND: In Thailand, the Department of Disease Control (DDC) regularly performs visual larval surveys throughout the country to monitor dengue fever outbreaks. Since 2016, the DDC switched from a paper-based to a digital-based larval survey process. The significant amount of larval survey data collected digitally presents a valuable opportunity to precisely identify the villages and breeding habitats that are vulnerable to dengue transmission. METHODS: The study used digitally collected larval survey data from 2017 to 2019. It employed larval indices to evaluate the risk of dengue transmission in villages based on seasonal, regional, and categorical perspectives. Furthermore, the study comprehensively scrutinized each container category by employing different measures to determine its breeding preference ratio. RESULTS: The result showed that villages with a very high-risk of dengue transmission were present year-round in all regions, with the highest proportion during the rainy season. The Southern region had more high-risk villages during the winter season due to rainfall. Slums and residential communities were more vulnerable to dengue than commercial areas. All container categories could potentially serve as breeding habitats for dengue-carrying mosquitoes, with abandoned containers being the most significant breeding sites. CONCLUSIONS: The risk of dengue transmission was present year-round throughout Thailand. This underscores the importance of community and government initiatives, along with sustained public awareness campaigns and active community engagement, to efficiently and permanently eradicate mosquito breeding habitats. It should be noted that larval indices may not strongly correlate with dengue cases, as indicated by the preliminary analysis. However, they offer valuable insights into potential breeding sites for targeted preventive measures.

Evaluation of clinical and laboratory characteristics of dengue viral infection and risk factors of dengue hemorrhagic fever: a multi-center retrospective analysis.

BACKGROUND: Dengue Viral Infection (DVI) has become endemic in Pakistan since the first major outbreak in Karachi in 1996. Despite aggressive measures taken by relevant authorities, Pakistan has been dealing with a worsening dengue crisis for the past two decades. DHF is severe form of dengue infection which is linked with significant morbidity and mortality. Early identification of severe dengue infections can reduce the morbidity and mortality. In this context we planned current study in which we find out the different factors related with DHF as well as clinical laboratory features of DHF and compare them to DF so that patients can be best evaluated for DHF and managed accordingly at admission. METHODS: Retrospective study conducted over a period of 6 years (2013-2018) in two tertiary care hospitals in Pakistan. Data were collected by using a pre-structured data collection form. Data were statistically analyzed to determine the clinical and laboratory characteristics of DVI and risk factors of dengue hemorrhagic fever (DHF). RESULTS: A total 512 dengue cases (34.05 ± 15.08 years; Male 69.53%) were reviewed. Most common clinical manifestations of DVI were fever (99.60%), headache (89.1%), chills (86.5%), rigors (86.5%), myalgia (72.3%). Less common clinical manifestations were vomiting (52.5%), arthralgia (50.2%) and skin rashes (47.5%). Furthermore, nasal bleeding (44.1%), gum bleeding (32.6%), pleural effusion (13.9%) and hematuria (13.1%) were more profound clinical presentations among DHF patients. Mortality rate was 1.5% in this study. Logistic regression analysis indicated that delayed hospitalization (OR: 2.30) and diabetes mellitus (OR:2.71), shortness of breath (OR:2.21), association with risk groups i.e., living near stagnant water, travelling to endemic areas, living in endemic regions (OR:1.95), and presence of warning signs (OR:2.18) were identified as risk factors of DHF. Statistically we found that there is strong association of diabetes mellitus (DM) with DHF while the patient suffering from DM individually had higher odds (2.71) of developing DHF than patients without disease. CONCLUSIONS: The current study demonstrated that the clinical and laboratory profiles of DF and DHF are significantly distinct. Significant predictors of DHF were advanced age, diabetes mellitus, ascites, pleural effusion, thick gallbladder and delayed hospitalization. The identification of these factors at early stage provides opportunities for the clinicians to identify high risk patients and to reduce dengue-related morbidity and mortality.

Determinants and prevalence of symptomatic dengue fever among adults in the Central Region of Burkina Faso: a hospital-based cross-sectional study.

BACKGROUND: Dengue fever (DF) is a significant public health concern in Burkina Faso, particularly in the Central Region, previously endemic for malaria. However, limited research has focused on dengue prevalence and associated factors among adult febrile patients in this region. This study aimed to estimate the prevalence of symptomatic dengue fever among adults and identify the sociodemographic and clinical determinants of the disease. METHODS: A seroepidemiological cross-sectional study was conducted in the Central Region of Burkina Faso, through a three-stage sampling. Five health facilities, one from each of the region five districts, were purposively selected. Febrile patients aged 16 and older, suspected of having dengue, were included in the study, after consenting. Bivariate analyses and multivariate binary logistic regression were done at a 5% confidence level. RESULTS: A total of 637 patients between the ages of 16 and 90 years were included. Most of the participants were females (58.71%). Most dengue cases resided in Arrondissement 4 (59.62%), or were present in the Arrondissement 4 at daytime during the previous days (51.92%). 52.90% of the participants knew of dengue. Dengue prevalence was estimated at 8.16% (95% CI: 6.16%-10.57%). The most frequent markers for dengue were immunoglobulins M detected in 4.40% (2.94%-6.29%), followed by Antigen NS1 at 4.24% (95% CI: 2.81%-6.11%). The Antigen NS1 marker was associated with myalgia (p = 0.024), vomiting (p < 0.001), hemorrhagic manifestations (p = 0.001), and anorexia (p < 0.001). Staying at Arrondissement 4 (vs staying at Saaba) during daytime (aOR = 2.36 95% CI: 1.03-5.45; p = 0.044) significantly increased the odds of dengue. Dengue cases were about 3 times more likely to have vomited (aOR = 2.99 95% CI: 1.58-5.64; p = 0.001). Participants knowing of dengue (aOR = 0.53 95% CI: 0.29-0.98; p = 0.042) and those coinfected with malaria (aOR = 0.28 95% CI: 0.14-0.57; p < 0.001) instead had reduced odds of dengue. CONCLUSION: The study revealed a relatively high prevalence of symptomatic dengue fever among adults in the Central Region of Burkina Faso in 2022. These findings emphasize the need for continuous surveillance and targeted control measures. The low coinfection of dengue and malaria warrants further investigation.

Improving dengue fever predictions in Taiwan based on feature selection and random forests.

BACKGROUND: Dengue fever is a well-studied vector-borne disease in tropical and subtropical areas of the world. Several methods for predicting the occurrence of dengue fever in Taiwan have been proposed. However, to the best of our knowledge, no study has investigated the relationship between air quality indices (AQIs) and dengue fever in Taiwan. RESULTS: This study aimed to develop a dengue fever prediction model in which meteorological factors, a vector index, and AQIs were incorporated into different machine learning algorithms. A total of 805 meteorological records from 2013 to 2015 were collected from government open-source data after preprocessing. In addition to well-known dengue-related factors, we investigated the effects of novel variables, including particulate matter with an aerodynamic diameter < 10 µm (PM10), PM2.5, and an ultraviolet index, for predicting dengue fever occurrence. The collected dataset was randomly divided into an 80% training set and a 20% test set. The experimental results showed that the random forests achieved an area under the receiver operating characteristic curve of 0.9547 for the test set, which was the best compared with the other machine learning algorithms. In addition, the temperature was the most important factor in our variable importance analysis, and it showed a positive effect on dengue fever at < 30 °C but had less of an effect at > 30 °C. The AQIs were not as important as temperature, but one was selected in the process of filtering the variables and showed a certain influence on the final results. CONCLUSIONS: Our study is the first to demonstrate that AQI negatively affects dengue fever occurrence in Taiwan. The proposed prediction model can be used as an early warning system for public health to prevent dengue fever outbreaks.

Transmission dynamics of a reaction-advection-diffusion dengue fever model with seasonal developmental durations and intrinsic incubation periods.

In this paper, we propose a reaction-advection-diffusion dengue fever model with seasonal developmental durations and intrinsic incubation periods. Firstly, we establish the well-posedness of the model. Secondly, we define the basic reproduction number ℜ 0 for this model and show that ℜ 0 is a threshold parameter: if ℜ 0 < 1 , then the disease-free periodic solution is globally attractive; if ℜ 0 > 1 , the system is uniformly persistent. Thirdly, we study the global attractivity of the positive steady state when the spatial environment is homogeneous and the advection of mosquitoes is ignored. As an example, we use the model to investigate the dengue fever transmission case in Guangdong Province, China, and explore the impact of model parameters on ℜ 0 . Our findings indicate that ignoring seasonality may underestimate ℜ 0 . Additionally, the spatial heterogeneity of transmission may increase the risk of disease transmission, while the increase of seasonal developmental durations, intrinsic incubation periods and advection rates can all reduce the risk of disease transmission.

Three Togolese aromatic plants' essential oils diurnal variations and their insecticidal activities against the dengue vector Aedesaegypti.

The present reported work deals with the ability of Togolese plants' essential oils (EOs) to act as repellents for Aedes aegypti mosquitoes in order to use them as personal protective requirements or actions against mosquito bites and therefore to drastically reduce the risk of contracting dengue or yellow fever. EOs studied here were extracted from dry leaves of Ageratum conyzoides L., Eucalyptus citriodora Hook, and Lantana camara Linn, three plants that were collected at different daytimes (7 a.m., 1 p.m., and 7 p.m.) at various locations in Togo. Using a Clevenger-type device, EOs were obtained by the hydrodistillation method (Clevenger, 1928). The physical parameters of the EOs such as density, refractive index, rotatory power, and organoleptic properties were determined. Then, the characterization of EOs using gas chromatography equipped with a flame ionization detector (GC/FID) and gas chromatography coupled to mass spectrometry (GC/MS) was conducted. Chemical analyses showed the presence of several main compounds from EO samples of the three plants. The major compounds were characterized and identified as: (i) precocene I (67.7, 70.6, and 66.9%) and ß-caryophyllene (17.4, 12.1, and 16.5%) for the EO of A. conyzoïdes; (ii) citronellal (63.3, 67.2, and 75.4%) and citronellol (24.5, 21.4, and 14.3%) for E. citriodora and (iii) ß-caryophyllene (15.3, 11.7, and 12.4%), sabinene (28.4, 35, and 33.3%) and eucalyptol (11.5, 14.1, and 15.6%) for L. camara at 7 a.m., 1 p.m., and 7 p.m., respectively. The yield and the chemical composition of the oils vary according to harvesting time and sunlight. The insecticidal activity of EOs was evaluated following the CDC bottle method on Aedes aegypti females. All the EOs tested on the female adults of Aedes aegypti showed significant insecticidal activity. The EO of A. conyzoïdes at 1 p.m. and 7 p.m. resulted in 100% mortality after 8 min of exposure time at the lowest concentration (0.0025%). At the same concentration for the EO of E. citriodora, the mortality rates were 83%, 38.8%, and 30.80% at 7 a.m., 1 p.m., and 7 p.m., respectively for an exposure time of 8 min. The EO extracted from the leaves of L. camara harvested at 7 a.m. was effective after an exposure time of 15 min for a concentration of 0.02%. For the same concentration, the mortality rates of the EO of L. camara harvested at 1 p.m. and 7 p.m., after 8 min were 62.9% and 52%, respectively. From these interesting results reported for the first time in Togo, EOs from leaves of three Togolese plants harvested at different times of the day appear to be a valuable alternative for mosquito vector control in Togo or abroad countries in which dengue and yellow fever constitute a terrible scourge.

Spatiotemporal distribution of climate-sensitive disease incidences in ethiopia: a longitudinal retrospective analysis of Malaria, Meningitis, Cholera, Dysentery, Leishmaniasis and Dengue fever between 2010 and 2022/2023.

BACKGROUND: Understanding the temporal and geographic distribution of disease incidences is crucial for effective public health planning and intervention strategies. This study presents a comprehensive analysis of the spatiotemporal distribution of disease incidences in Ethiopia, focusing on six major diseases: Malaria, Meningitis, Cholera and Dysentery, over the period from 2010 to 2022, whereas Dengue Fever and Leishmaniasis from 2018 to 2023. METHODS: Using data from Ethiopian public health institute: public health emergency management (PHEM), and Ministry of Health, we examined the occurrence and spread of each disease across different regions of Ethiopia. Spatial mapping and time series analysis were employed to identify hotspots, trends, and seasonal variations in disease incidence. RESULTS: The findings reveal distinct patterns for each disease, with varying cases and temporal dynamics. Monthly wise, Malaria exhibits a cyclical pattern with a peak during the rainy and humid season, while Dysentery, Meningitis and Cholera displays intermittent incidences. Dysentery cases show a consistent presence throughout the years, while Meningitis remains relatively low in frequency but poses a potential threat due to its severity. Dengue fever predominantly occurs in the eastern parts of Ethiopia. A significant surge in reported incident cases occurred during the years 2010 to 2013, primarily concentrated in the Amhara, Sidama, Oromia, Dire Dawa, and Benishangul-Gumuz regions. CONCLUSIONS: This study helps to a better understanding of disease epidemiology in Ethiopia and can serve as a foundation for evidence-based decision-making in disease prevention and control. By recognizing the patterns and seasonal changes associated with each disease, health authorities can implement proactive measures to mitigate the impact of outbreaks and safeguard public health in the region.

Mitigating dengue incidence through advanced Aedes larval surveillance and control: A successful experience from Pakistan.

Dengue fever is a viral disease caused by one of four dengue stereotypes (Flavivirus: Flaviviridae) that are primarily transmitted by Aedes albopictus (Skuse) and Aedes aegypti (L.). To safeguard public health, it is crucial to conduct surveys that examine the factors favouring the presence of these species. Our study surveyed 42 councils across four towns within the Bhakkar district of Punjab Province, by inspecting man-made or natural habitats containing standing water. First, door-to-door surveillance teams from the district health department were assigned to each council to surveillance Aedes species and dengue cases. Second, data collection through surveillance efforts, and validation procedures were implemented, and the verified data was uploaded onto the Dengue Tracking System by Third Party Validation teams. Third, data were analysed to identify factors influencing dengue fever cases. The findings demonstrated the following: (1) Predominantly, instances were discerned among individuals who had a documented history of having travelled beyond the confines of the province. (2) Containers associated with evaporative air coolers and tyre shops were responsible for approximately 30% of the Aedes developmental sites. (4) Variability in temperature was responsible for approximately 45% of the observed differences in the quantity of recorded Aedes mosquito developmental sites. (5) Implementation of dengue prevention initiatives precipitated a 50% reduction in Aedes-positive containers, alongside a notable 70% decline in reported cases of dengue fever during the period spanning 2019 to 2020, while the majority of reported cases were of external origin. Aedes control measures substantially curtailed mosquito populations and lowered vector-virus interactions. Notably, local dengue transmission was eliminated through advanced and effective Aedes control efforts, emphasising the need for persistent surveillance and eradication of larval habitats in affected regions.

Cytokine Storm Syndrome Associated with Hemorrhagic Fever and Other Viruses.

A wide variety of infections can trigger cytokine storm syndromes including those caused by bacteria, viruses, fungi and parasites. The most frequent viral trigger is Epstein-.Barr virus which is covered in Chapter 16. CSS associated with COVID-19 is also discussed separately (Chapter 22). This chapter will focus on other viruses including the hemorrhagic fever viruses, influenza, parainfluenza, adenovirus, parvovirus, hepatitis viruses, measles, mumps, rubella, enterovirus, parechovirus, rotavirus, human metapneumovirus and human T-lymphotropic virus. The published literature consists of many single case reports and moderate-sized case series reporting CSS, in most circumstances meeting the 2004 diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). There is no published clinical trial evidence specifically for management of HLH associated with these viruses. In some situations, patients received supportive therapy and blood product transfusions only but in most cases, they were treated with one or more of intravenous corticosteroids, intravenous immunoglobulin and/or etoposide. These were successful in many patients although in significant numbers progression of infection to CSS was associated with mortality.

Virulence and proteomic responses of Metarhizium anisopliae against Aedes albopictus larvae.

The tropical climate in Malaysia provides an ideal environment for the rapid proliferation of Aedes mosquitoes, notably Aedes aegypti and Aedes albopictus, prominent vectors of dengue fever. Alarmingly, these species are increasingly developing resistance to conventional pesticides. This study aimed to evaluate the efficacy of Metarhizium anisopliae isolate HSAH5 spores, specifically on conidia (CO) and blastospores (BL), against Ae. albopictus larvae. The study centered on evaluating their pathogenic effects and the resultant changes in protein expression. Spore suspensions with varying concentrations were prepared for larvicidal bioassays, and protein expressions were analysed using liquid chromatography-mass spectrometry. Subsequently, protein annotation and network analysis were conducted to elucidate infection mechanisms and the proteomic response. Based on the lethal concentrations and time frames, CO exhibited faster larval mortality than BL at lower concentrations. Despite this, both spore types demonstrated comparable overall pathogenic effects. Results from the proteomic profiling revealed 150 proteins with varied expressions following exposure to Ae. albopictus extract, shedding light on distinct infection strategies between the spores. Gene Ontology enrichment and network analysis illustrated the diverse metabolic adaptations of M. anisopliae and interactions with mosquito larvae. This highlighted the complexity of host-pathogen dynamics and the significance of biosynthetic processes, energy storage, and cellular interaction pathways in disease progression. The BL network, consisting 80 proteins and 74 connections, demonstrates the intricate fungal mechanisms triggered by host stimuli. Conversely, the CO network, though smaller, displayed notable interconnectivity and concentrated involvement at the cell periphery, suggesting a deliberate strategy for initial host contact. This study offers valuable insights into proteome dynamics of M. anisopliae's BL and CO for managing mosquito populations and combating disease transmission, thereby significantly advancing public health and environmental conservation efforts.

Antibody and memory B cell responses to the dengue virus NS1 antigen in individuals with varying severity of past infection.

To further understand the role of NS1-specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1-Ab levels, IgG antibody subclass profiles and NS1-specific memory B-cell responses (Bmems) in individuals, with varying severity of past dengue. Nabs (Neut50 titres) were assessed using the Foci Reduction Neutralization Test (FRNT) and in-house ELISAs were used to assess NS1-Abs and NS1-Ab subclasses for all four DENV serotypes in individuals with past DF (n = 22), those with past DHF (n = 14) and seronegative (SN) individuals (n = 7). B-cell ELISpot assays were used to assess NS1-specific Bmem responses. 15/22 (68.18%) individuals with past DF and 9/14 (64.29%) individuals with past DHF had heterotypic infections. Neut50 titres were found to be significantly higher for DENV1 than DENV2 (p = 0.0006) and DENV4 (p = 0.0127), in those with past DHF, whereas there was no significant difference seen in titres for different DENV serotypes in those with past DF. Overall NS1-Ab to all serotypes and NS1-specific IgG1 responses for DENV1, 2 and 4 serotypes were significantly higher in those with past DHF than individuals with past DF. Those with past DHF also had higher IgG1 than IgG3 for DENV1 and DENV3, whereas no differences were seen in those with past DF. Over 50% of those with past DF or DHF had NS1-specific Bmem responses to >2 DENV serotypes. There was no difference in the frequency of Bmem responses to any of the DENV serotypes between individuals with past DF and DHF. Although the frequency of Bmem responses to DENV1 correlated with DENV1-specific NS1-Abs levels (Spearman r = 0.35, p = 0.02), there was no correlation with other DENV serotypes. We found that those with past DF had broadly cross-reactive Nabs, while those with past DHF had higher NS1-Ab responses possibly with a different functionality profile than those with past DF. Therefore, it would be important to further evaluate the functionality of NS1-specific antibody and Bmem responses to find out the type of antibody repertoire that is associated with protection against severe disease.