-
Virus Research Mar 2024The immunopathogenesis of dengue severity is convoluted. The primary objective of the research was to examine the dynamics of cytokine storm and its correlation with...
The immunopathogenesis of dengue severity is convoluted. The primary objective of the research was to examine the dynamics of cytokine storm and its correlation with disease development in individuals affected by DENV infection. Additionally, the study aimed to discover potential biomarkers that could indicate severe dengue infection and determine the most suitable timeframe for predicting the severity of these biomarkers during the acute stage of dengue infections. We conducted a temporal analysis of the daily viral load and cytokine levels in 60 hospitalized dengue patients until discharge. Our findings reveal a distinct cytokine profile (elevated IL-8, IL-10, IL-6, GM-CSF, MCP-1, IL-13, and IL-4 and decreased IL-12, MIP-1β) on the third day after symptom onset is predictive of severe dengue in secondary dengue infection. The imbalanced cytokine signature may inform clinical decision-making in treating severe dengue infections.
Topics: Humans; Severe Dengue; Dengue; Dengue Virus; Cytokine Release Syndrome; Cytokines; Biomarkers
PubMed: 38176525
DOI: 10.1016/j.virusres.2023.199306 -
Frontiers in Immunology 2023Crimean-Congo hemorrhagic fever (CCHF) is the most prevalent tick-borne viral disease affecting humans. The disease is life-threatening in many regions of the developing... (Review)
Review
Crimean-Congo hemorrhagic fever (CCHF) is the most prevalent tick-borne viral disease affecting humans. The disease is life-threatening in many regions of the developing world, including Africa, Asia, the Middle East, and Southern Europe. In line with the rapidly increasing disease prevalence, various vaccine strategies are under development. Despite a large number of potential vaccine candidates, there are no approved vaccines as of yet. This paper presents a detailed comparative analysis of current efforts to develop vaccines against CCHFV, limitations associated with current efforts, and future research directions.
Topics: Humans; Hemorrhagic Fever Virus, Crimean-Congo; Hemorrhagic Fever, Crimean; Africa; Asia; Vaccine Development
PubMed: 37753088
DOI: 10.3389/fimmu.2023.1238882 -
PLoS Neglected Tropical Diseases Oct 2023Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile...
BACKGROUND
Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile patients may result in medical complications or preventable deaths. Common causes of acute undifferentiated febrile illness in Colombia include leptospirosis, rickettsioses, dengue fever, malaria, chikungunya, and Zika virus infection. In this study, we described the acute undifferentiated febrile illness in postmortem patients reported as suspected cases of leptospirosis through the national leptospirosis surveillance in Colombia, 2016-2019.
METHODOLOGY/PRINCIPAL FINDINGS
We retrospectively analyze human fresh and formalin-fixed tissue samples from fatal suspected leptospirosis cases reported by the Public Health Laboratories in Colombia. Leptospirosis confirmation was made by immunohistochemistry, real-time polymerase chain reaction (PCR) in the tissue samples. In some cases, the serum sample was used for confirmation by Microagglutination test (MAT). Simultaneously, tissue samples were tested by PCR for the most common viral (dengue, Zika, and chikungunya), bacterial (Brucella spp., and Rickettsia spp.), and parasitic (malaria). Fresh tissue samples from 92 fatal suspected leptospirosis cases were reported to the National Reference Laboratory from 22/32 departments in Colombia. We confirmed leptospirosis in 27% (25/92) of cases. Other pathogens identified by real-time PCR were Brucella spp. (10.9%), Rickettsia spp. (14.1%), and dengue (2.2%). Dengue (6.9%), hepatitis (3.5%), and Yellow Fever cases (2.2%) were detected by the pathology. All patients were negative for chikungunya and Plasmodium spp. Most cases were classified as undifferentiated febrile illnesses (45.7%; 42/92).
CONCLUSIONS/SIGNIFICANCE
This study underscores the importance of early and accurate recognition of leptospirosis to prevent mortalities. Moreover, it draws attention to the existence of other febrile syndromes in Colombia, including rickettsiosis and brucellosis, that currently lack sufficient human surveillance and regular reporting. Expanding laboratory surveillance to include viruses such as Hantavirus, Mayaro virus, Oropouche virus, and West Nile virus is crucial.
Topics: Humans; Chikungunya Fever; Retrospective Studies; Colombia; Leptospirosis; Fever; Rickettsia Infections; Rickettsia; Zika Virus; Zika Virus Infection; Real-Time Polymerase Chain Reaction; Malaria; Dengue
PubMed: 37844106
DOI: 10.1371/journal.pntd.0011683 -
PloS One 2023Although environmental and human behavioral factors in countries with Zika virus (ZIKV) outbreaks are also common in Nigeria, such an outbreak has not yet been reported...
INTRODUCTION
Although environmental and human behavioral factors in countries with Zika virus (ZIKV) outbreaks are also common in Nigeria, such an outbreak has not yet been reported probably due to misdiagnosis. The atypical symptoms of malaria and ZIKV infections at the initial phase could leverage their misdiagnosis. This study randomly recruited 496 malaria-suspected patients who visited selected health institutions in Adamawa, Bauchi, and Borno states for malaria tests. These patients' sera were analyzed for ZIKV antibodies using ELISA and plaque reduction neutralization tests (PRNT) at 90% endpoint. About 13.8% of Zika virus-neutralizing antibodies (nAb) did not cross-react with dengue, yellow fever, and West Nile viruses suggesting possible monotypic infections. However, 86% of the sera with ZIKV nAb also neutralized other related viruses at varied degrees: dengue viruses (60.7%), West Nile viruses (23.2%), yellow fever virus (7.1%) and 39.3% were co-infections with chikungunya viruses. Notably, the cross-reactions could also reflect co-infections as these viruses are also endemic in the country. The serum dilution that neutralized 90-100% ZIKV infectivity ranged from 1:8 to 1:128. Also, our findings suggest distinct protection against the ZIKV between different collection sites studied. As indicated by nAb, acute ZIKV infection was detected in 1.7% of IgM-positive patients while past infections occurred in 8.5% of IgM-negatives in the three states. In Borno State, 9.4% of IgG neutralized ZIKV denoting past infections while 13.5% were non-neutralizing IgM and IgG indicating other related virus infections. The age, gender, and occupation of the patients and ZIKV nAb were not significantly different. ZIKV nAb from samples collected within 1-7 days after the onset of symptoms was not significantly different from those of 7-10 days. A wider interval with the same techniques in this study may probably give better diagnostic outcomes. ZIKV nAb was significantly distinct among recipients and non-recipients of antibiotic/antimalaria treatments before seeking malaria tests. The inhibiting effect of these drugs on ZIKV infection progression may probably contribute to the absence of neurological disorders associated with the virus despite being endemic in the environment for several decades. Also, protection against ZIKV as marked by the nAb was different among the vaccinated and unvaccinated YF vaccine recipients. Thus, the YF vaccine may be a good alternative to the Zika vaccine in resource-constrained countries.
CONCLUSION
The cryptic ZIKV infections underscore the need for differential diagnosis of malaria-suspected febrile patients for arboviruses, especially the Zika virus. The absence of systemic surveillance for the virus is worrisome because of its association with neurological disorders in newborns. Co-infections with other arboviruses may impact adversely on the management of these diseases individually.
Topics: Humans; Infant, Newborn; Zika Virus Infection; Zika Virus; Nigeria; Coinfection; Dengue Virus; Antibodies, Viral; Arboviruses; Malaria; West Nile virus; Immunoglobulin M; Immunoglobulin G; Vaccines; Nervous System Diseases; Dengue
PubMed: 37939049
DOI: 10.1371/journal.pone.0292350 -
Virologica Sinica Feb 2024Ferroptosis is a newly discovered prototype of programmed cell death (PCD) driven by iron-dependent phospholipid peroxidation accumulation, and it has been linked to...
Ferroptosis is a newly discovered prototype of programmed cell death (PCD) driven by iron-dependent phospholipid peroxidation accumulation, and it has been linked to numerous organ injuries and degenerative pathologies. Although studies have shown that a variety of cell death processes contribute to JEV-induced neuroinflammation and neuronal injury, there is currently limited research on the specific involvement of ferroptosis. In this study, we explored the neuronal ferroptosis induced by JEV infection in vitro and in vivo. Our results indicated that JEV infection induces neuronal ferroptosis through inhibiting the function of the antioxidant system mediated by glutathione (GSH)/glutathione peroxidase 4 (GPX4), as well as by promoting lipid peroxidation mediated by yes-associated protein 1 (YAP1)/long-chain acyl-CoA synthetase 4 (ACSL4). Further analyses revealed that JEV E and prM proteins function as agonists, inducing ferroptosis. Moreover, we found that treatment with a ferroptosis inhibitor in JEV-infected mice reduces the viral titers and inflammation in the mouse brains, ultimately improving the survival rate of infected mice. In conclusion, our study unveils a critical role of ferroptosis in the pathogenesis of JEV, providing new ideas for the prevention and treatment of viral encephalitis.
Topics: Mice; Animals; Neuroinflammatory Diseases; Ferroptosis; Neurons; Encephalitis, Japanese; Apoptosis
PubMed: 38104890
DOI: 10.1016/j.virs.2023.12.004 -
Integrative and Comparative Biology Aug 2023Mosquitoes use a wide range of cues to find a host to feed on, eventually leading to the transmission of pathogens. Among them, olfactory cues (e.g., host-emitted odors,...
Mosquitoes use a wide range of cues to find a host to feed on, eventually leading to the transmission of pathogens. Among them, olfactory cues (e.g., host-emitted odors, including CO2, and skin volatiles) play a central role in mediating host-seeking behaviors. While mosquito olfaction can be impacted by many factors, such as the physiological state of the insect (e.g., age, reproductive state), the impact of environmental temperature on the olfactory system remains unknown. In this study, we quantified the behavioral responses of Aedes aegypti mosquitoes, vectors of dengue, yellow fever, and Zika viruses, among other pathogens, to host and plant-related odors under different environmental temperatures.
Topics: Animals; Dengue; Dengue Virus; Temperature; Smell; Mosquito Vectors; Zika Virus; Aedes; Zika Virus Infection
PubMed: 37309024
DOI: 10.1093/icb/icad066 -
The Lancet. Planetary Health Jan 2024Estimates of the spatiotemporal distribution of different mosquito vector species and the associated risk of transmission of arboviruses are key to design adequate... (Review)
Review
BACKGROUND
Estimates of the spatiotemporal distribution of different mosquito vector species and the associated risk of transmission of arboviruses are key to design adequate policies for preventing local outbreaks and reducing the number of human infections in endemic areas. In this study, we quantified the abundance of Aedes albopictus and Aedes aegypti and the local transmission potential for three arboviral infections at an unprecedented spatiotemporal resolution in areas where no entomological surveillance is available.
METHODS
We developed a computational model to quantify the daily abundance of Aedes mosquitoes, leveraging temperature and precipitation records. The model was calibrated on mosquito surveillance data collected in 115 locations in Europe and the Americas between 2007 and 2018. Model estimates were used to quantify the reproduction number of dengue virus, Zika virus, and chikungunya in Europe and the Americas, at a high spatial resolution.
FINDINGS
In areas colonised by both Aedes species, A aegypti was estimated to be the main vector for the transmission of dengue virus, Zika virus, and chikungunya, being associated with a higher estimate of R when compared with A albopictus. Our estimates highlighted that these arboviruses were endemic in tropical and subtropical countries, with the highest risks of transmission found in central America, Venezuela, Colombia, and central-east Brazil. A non-negligible potential risk of transmission was also estimated for Florida, Texas, and Arizona (USA). The broader ecological niche of A albopictus could contribute to the emergence of chikungunya outbreaks and clusters of dengue autochthonous cases in temperate areas of the Americas, as well as in mediterranean Europe (in particular, in Italy, southern France, and Spain).
INTERPRETATION
Our results provide a comprehensive overview of the transmission potential of arboviral diseases in Europe and the Americas, highlighting areas where surveillance and mosquito control capacities should be prioritised.
FUNDING
EU and Ministero dell'Università e della Ricerca, Italy (Piano Nazionale di Ripresa e Resilienza Extended Partnership initiative on Emerging Infectious Diseases); EU (Horizon 2020); Ministero dell'Università e della Ricerca, Italy (Progetti di ricerca di Rilevante Interesse Nazionale programme); Brazilian National Council of Science, Technology and Innovation; Ministry of Health, Brazil; and Foundation of Research for Minas Gerais, Brazil.
Topics: Humans; Animals; Arboviruses; Chikungunya Fever; Europe; Aedes; Zika Virus; Zika Virus Infection
PubMed: 38199719
DOI: 10.1016/S2542-5196(23)00252-8 -
Virology Aug 2023With no approved antiviral therapies, the continuous emergence and re-emergence of tick-borne encephalitis virus (TBEV) and yellow fever virus (YFV) is a rising concern....
With no approved antiviral therapies, the continuous emergence and re-emergence of tick-borne encephalitis virus (TBEV) and yellow fever virus (YFV) is a rising concern. We performed head-to-head comparisons of the antiviral activity of available nucleos(t)ide analogs (nucs) using relevant human cell lines. Eight existing nucs inhibited TBEV and/or YFV with differential activity between cell lines and viruses. Remdesivir, uprifosbuvir and sofosbuvir were the most potent drugs against TBEV and YFV in liver cells, but they had reduced activity in neural cells, whereas galidesivir retained uniform activity across cell lines and viruses. Ribavirin, valopicitabine, molnupiravir and GS-6620 exhibited only moderate antiviral activity. We found antiviral activity for drugs previously reported as inactive, demonstrating the importance of using human cell lines and comparative experimental assays when screening the activity of nucs. The relatively high antiviral activity of remdesivir, sofosbuvir and uprifosbuvir against TBEV and YFV merits further investigation in clinical studies.
Topics: Humans; Sofosbuvir; Encephalitis, Tick-Borne; Yellow Fever; Cell Line; Encephalitis Viruses, Tick-Borne; Yellow fever virus; Antiviral Agents
PubMed: 37356253
DOI: 10.1016/j.virol.2023.06.002 -
Frontiers in Immunology 2023Dengue virus (DENV) is responsible for approximately 100 million cases of dengue fever annually, including severe forms such as hemorrhagic dengue and dengue shock...
Dengue virus (DENV) is responsible for approximately 100 million cases of dengue fever annually, including severe forms such as hemorrhagic dengue and dengue shock syndrome. Despite intensive vaccine research and development spanning several decades, a universally accepted and approved vaccine against dengue fever has not yet been developed. The major challenge associated with the development of such a vaccine is that it should induce simultaneous and equal protection against the four DENV serotypes, because past infection with one serotype may greatly increase the severity of secondary infection with a distinct serotype, a phenomenon known as antibody-dependent enhancement (ADE). Using a lentiviral vector platform that is particularly suitable for the induction of cellular immune responses, we designed a tetravalent T-cell vaccine candidate against DENV ("LV-DEN"). This vaccine candidate has a strong CD8 T-cell immunogenicity against the targeted non-structural DENV proteins, without inducing antibody response against surface antigens. Evaluation of its protective potential in the preclinical flavivirus infection model, i.e., mice knockout for the receptor to the type I IFN, demonstrated its significant protective effect against four distinct DENV serotypes, based on reduced weight loss, viremia, and viral loads in peripheral organs of the challenged mice. These results provide proof of concept for the use of lentiviral vectors for the development of efficient polyvalent T-cell vaccine candidates against all DENV serotypes.
Topics: Animals; Mice; Vaccines, Combined; Dengue Virus; CD8-Positive T-Lymphocytes; Antibody-Dependent Enhancement; Severe Dengue
PubMed: 37654495
DOI: 10.3389/fimmu.2023.1208041 -
Pathogens and Global Health Sep 2023Ovitraps can detect Aedes vectors at an early stage and can serve as an alarm indicator for outbreak prediction. This study aimed to summarize the available literature... (Review)
Review
Ovitraps can detect Aedes vectors at an early stage and can serve as an alarm indicator for outbreak prediction. This study aimed to summarize the available literature about the ovitrap system and to determine its feasibility, required resources and costs when installing and maintaining this vector surveillance system in the municipality of Los Patios, Colombia. A scoping review to assess the role of ovitraps as a tool for Aedes vector surveillance was conducted. The subsequent fieldwork consisted of mapping the municipality, manufacturing, and installing 40 ovitraps in 10 blocks, revising them weekly for 4 weeks by two half-time employed vector control technicians, and carrying out a cost analysis. A total of 38 studies were included in this review showing that ovitraps had a better performance than other entomological surveillance methods and a positive correlation with other entomological and disease variables. From the field results over 4 weeks, a high proportion of positive ovitraps (80%, 90%, 75%, 97.5%) and positive blocks (100%) as well as a good acceptance by house owners (76.9%), were identified. Operational indicators such as average installation time of the ovitraps (10h15 m), weekly reading and reinstallation (on average 7h27 m) and the cost of the intervention (COL$1,142,304.47/US$297) were calculated. Literature shows that ovitraps are sensitive to detect the presence of Aedes mosquitoes, providing data efficiently and timely for outbreak prediction. The field testing showed it is an affordable and feasible method in the context of a Colombian municipality and similar endemic areas.
Topics: Animals; Humans; Dengue; Mosquito Vectors; Aedes; Colombia; Mosquito Control
PubMed: 36384430
DOI: 10.1080/20477724.2022.2146049