Parasites & Vectors最新文献

Background: The current therapeutic options for toxoplasmosis are limited by side effects. The development of molecules against T. gondii is urgently needed. A series of β-carboline derivatives were synthesized and examined as potential agents against toxoplasmosis.

Methods: A series of β-carboline derivatives were synthesized. To assess their potential as anti-T. gondii agents, cytotoxicity towards Vero cells was determined using the CCK-8 assay. Plaque and qPCR assays were carried out to screen for anti-T. gondii activities, providing insights into their inhibitory effects on the parasite. In vitro assays on T. gondii RH and PRU strains were conducted to evaluate proliferation, invasion, and cyst formation. Transmission electron microscopy was employed to analyze ultrastructural changes and apoptosis in T. gondii, revealing the impact of the derivatives at the cellular level. Finally, the in vivo efficacy of the derivatives was tested in a mouse model, which offered valuable information on their potential therapeutic effects in a living organism.

Results: β-carboline derivatives exhibited potent inhibitory effects on the growth and replication of both PRU and RH strains, while demonstrating low cytotoxicity to mammalian cells. It is worth noting that NBZ023 and NBZ035 exhibited optimal potency against proliferation (IC₅₀ = 2.85 and 1.6 μM) or invasion (IC₅₀ = 4.72 and 1.13 μM) of T. gondii. Importantly, NBZ023 and NBZ035 had an effect on preventing PRU cysts formation, and they markedly reduced parasite burden in the brain, spleen, and liver in mouse infection model.

Conclusions: Lead compounds NBZ023 and NBZ035 exhibited an excellent overall efficacy against the T. gondii RH and PRU strains, and were highly effective at preventing toxoplasmosis during murine infection, which are expected to be developed as new anti-toxoplasmosis drugs.

Background: Mosquito-borne diseases cause significant burdens in rural areas of Southeast Asia. The lack of data on vector bionomics hinders disease control and elimination. The objectives of this study were to assess the diversity and biting behaviours of mosquito species biting humans and their livestock in the forest hills of Karen state, Myanmar, and to assess the patterns of species co-occurrence and the effects of the environment on vector abundance.

Methods: Mosquitoes were captured over 24-h diel cycles in six villages in September 2019 using the human landing catch and cow-baited trap collection methods. Collected specimens were identified to the species level using dichotomous morphological keys. Environmental data were acquired through remote sensing. The analysis of biting times was performed with circular statistics. Species co-occurrence patterns and the effects of environmental variables on species abundance were assessed with a generalized linear latent variable model.

Results: A total of 36,607 mosquitoes were captured, and 96 species in 16 genera were identified. The most abundant genera were Anopheles, Culex and Downsiomyia. Multiple malaria, arboviruses and lymphatic filariasis vector species were detected, and their biting behaviours were reported. Generalized linear latent variable modelling revealed two clusters of species that were positively correlated with one another. The first cluster included many Culex and Anopheles species, and Mansonia annulata, which breed in shallow, stagnant or slow-moving water, such as marshes, swamps, rice fields and the margins of streams and puddles. These species were negatively associated with elevation, slopes and forests and positively associated with grasslands, shrubs and crop fields. The second cluster included many rainforest mosquitoes of the genera Armigeres, Heizmannia, Downsiomyia, Anopheles dirus, An. jeyporiensis, Culex bitaeniorhynchus and Aedes pseudoalbopictus, which breed in tree canopies and in natural surface water and containers such as bamboo stumps, tree holes and rainwater pools. These species were positively associated with elevation, slope, dense forests, surface water and wetlands and negatively associated with crop fields, grasslands and shrubs.

Conclusions: Transmission dynamics are particularly complex in this setting where people are exposed to bites of numerous vector species throughout the diel cycle. Environmental factors shape the assembly of mosquito species communities and largely determine the risk of exposure to vector bites.

Background: Oral transmission of Chagas disease has been registered in rural and periurban areas of South America. In Brazil, outbreaks have involved food, sugar cane juice, water, or soup contaminated with infected triatomines or their feces. Here, we report an investigation into an acute Chagas disease outbreak in a rural area of the municipality of Serrolândia, in the semi-arid region of Bahia, Brazil.

Methods: We conducted a descriptive study based on primary care information, epidemiological evaluation, entomological surveillance, and molecular analysis. The investigation began after the death of a 12-year-old child. The study population included triatomines, animals (one opossum, three cats, and two dogs), and a human family of five individuals. We performed serological diagnosis of family members, Trypanosoma cruzi molecular detection and genotyping in collected samples, and triatomine blood meal analysis.

Results: Among the five family members, four tested positive for acute Chagas disease. All affected individuals reported ingesting acerola juice from fruits grown on their property, except for case 5, who did not consume the juice or fresh fruit and tested negative for T. cruzi. During the investigation, we captured 21 triatomines and collected blood samples from sylvatic and domestic animals. TcI haplotypes show a close relationship between the parasites found in vectors and those detected in a single human case and in the wild reservoir captured, respectively, reinforcing the vector/oral transmission hypothesis and the maintenance of the T. cruzi anthropozoonotic cycle in the region.

Conclusions: This study describes the investigation of an acute Chagas disease outbreak in the Serrolândia municipality, and based on that, we conclude that the infection occurred through the vector/oral route via ingestion of T. cruzi-contaminated fresh acerola fruit or juice. Our findings underscore the need for improved surveillance and preventive measures in areas vulnerable to Chagas disease.

Background: Toxoplasma gondii (T. gondii) is an important apicomplexan parasite that causes zoonotic toxoplasmosis in humans and animals. Acute T. gondii infection leads to systemic immunopathology that may manifest as lung injury or pulmonary embolism. Ferroptosis is an iron-dependent regulated cell death driven by lethal lipid hydroperoxide accumulation. Emerging evidence implicates ferroptosis in infection-related tissue damage; however, the role of ferroptosis in T. gondii-induced lung injury remains to be explored.

Methods: Mice were infected with T. gondii to establish a lung injury model. The body weight changes, survival rate, inflammatory cytokines, lung histopathology, and parasite burden were assessed. The key ferroptosis-related indicators involved in antioxidant, iron metabolism, and lipid metabolism pathways were analyzed in lung tissues using techniques such as transmission electron microscopy, western blotting, and immunohistochemistry. Deferiprone (DFP), an oral iron chelator that can inhibit ferroptosis, was used to investigate the potential role of ferroptosis in T. gondii lung injury.

Results: T. gondii infection induced lung injury in mice with thickening of alveolar septa and hemorrhage in alveolar spaces, accompanied by iron deposition. Crucially, T. gondii triggered ferroptosis in lung tissues of mice, evidenced by MDA elevation, GSH depletion, total iron and Fe²⁺ overload, and mitochondrial cristae loss. Furthermore, iron metabolism pathways were disordered while antioxidant pathways were suppressed. DFP treatment reversed ferroptosis alterations, decreased inflammatory cytokines, attenuated pathological changes, reduced T. gondii burden, and prolonged survival of the infected mice.

Conclusions: Our findings revealed that T. gondii infection triggered ferroptosis by compromising dysregulated iron metabolism and antioxidant defenses, playing a key role in T. gondii-induced lung injury. DFP exhibited a promising therapy effect for toxoplasmosis.

Background: This study leveraged the Global Burden of Disease (GBD) 2021 database to comprehensively evaluate the trends in the disease burden of cystic echinococcosis (CE) in China from 1990 to 2021, situating its unique trajectory within the global context to inform targeted control strategies.

Methods: Based on data from the GBD 2021 study, the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of CE were analyzed. Joinpoint regression was applied to calculate the average annual percentage change (AAPC), decomposition analysis was conducted to identify key driving factors, and frontier analysis was used to assess reduction potential. Subgroup analyses were stratified by age, sex, and region.

Results: Globally, the age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) of CE remained relatively stable from 1990 to 2021. In contrast, China experienced sharp increases in ASIR (AAPC = 2.94%) and ASPR (AAPC = 3.13%). Age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) declined globally and in China, though China's ASDR reduction (AAPC = -2.71%) lagged behind the global rate (AAPC = -4.0%). Decomposition analysis indicated that epidemiological deterioration was the primary driver of increased cases in China, while healthcare improvements contributed to reduced deaths and DALYs. Females had higher incidence and prevalence, particularly among those aged over 35, whereas males exhibited higher mortality and DALYs. The global CE burden was negatively correlated with the Sociodemographic Index (SDI). Although China approached the efficiency frontier in disease control, elevated ASPR and ASDR indicated persistent transmission and latent infections, suggesting further reduction potential.

Conclusions: China faces rising CE incidence and prevalence despite improved outcomes, owing to delayed diagnosis and unbalanced resources. Aging and persistent exposure have worsened the burden, especially among middle-aged adults and females. Strategic priorities include enhanced prevention in the elderly, improved screening for women, intensified management of severe male cases, and balanced treatment/prevention approaches. SDI is a key determinant of CE burden, requiring focused interventions in low-SDI regions. Targeted monitoring of ASPR and ASDR is crucial to reduce the impact of historical transmission and achieve World Health Organization (WHO) targets.

Background: With the worldwide spread of the Asian tiger mosquito, Aedes albopictus, the number of autochthonous cases of exotic arboviral diseases, such as dengue or chikungunya, is increasing in temperate regions. In Europe, pyrethroids are the only insecticides allowed for the abatement of adult mosquitoes and are thus crucial for limiting ongoing arbovirus transmission. Despite this and the report of resistance rising in vector populations worldwide, information on the pyrethroid resistance status of vector populations and knowledge on resistance mechanisms is widely lacking. Genotyping of knockdown resistance (kdr) mutations situated within the target site of pyrethroids, i.e., the voltage-gated sodium channel (VGSC), and associated with pyrethroid resistance, is a cost-effective approach to investigate the spread of resistance in a population. Herein, we describe the European-wide distribution of two kdr mutations, i.e., I1532T and F1534C, in Ae. albopictus and evaluate their co-occurrence with another well-characterized kdr mutation, V1016G.

Methods: Genotyping of the kdr mutation F1534C was performed by allele-specific PCR for 1732 Ae. albopictus specimens sampled in 19 European countries; for a subset of 419 specimens mutation I1532T was also genotyped by sequencing. For all samples, information on mutation V1016G was available, allowing evaluation of the co-occurrence of kdr alleles.

Results: Mutation 1534C was detected in nine sites from six countries at an overall frequency close to 5%. Highest frequencies per site were detected in Cyprus (84%) and Greece (45%). Allele 1532 T was identified in 11 sites from 7 countries at frequencies ranging from 4% to 25% per site. Co-occurrence of different kdr alleles (1534C, 1532 T and 1016G) was observed in nine sampling sites from seven countries.

Conclusions: The present study offers the first map of the occurrence of the major Ae. albopictus kdr alleles across Europe and highlights a differential distribution of the two alleles most strongly associated with pyrethroid resistance, 1016G and 1534C. Our findings also point to the need for enhancing resistance monitoring in the Eastern Mediterranean region, where the two mutations are shown to exist in geographically close areas, with the risk of emergence of highly resistant double mutants.

Background: Insecticides remain a cornerstone in the control of vector-borne diseases. In Brazil, Alfatek 200SC-a pyrethroid (alphacypermethrin)-is recommended for controlling phlebotomine sand flies, the vectors of leishmaniases. For mosquitoes such as Aedes aegypti, a combination of deltamethrin and clothianidin (Fludora FusionPM) is endorsed. This study evaluated the efficacy of Fludora FusionPM against phlebotomine sand flies.

Methods: Laboratory bioassays were conducted using Fludora FusionPM-impregnated filter papers stored either at room temperature (25 ± 2 °C) or under cold conditions (3 ± 1 °C). In field trials, painted (PS) or unpainted (US) masonry-plastered walls in selected households were treated with the insecticide. Alfatek 200SC was used as a reference, following the same procedures. Lutzomyia longipalpis females (n = 25 per replicate, in triplicate) were exposed for 60 min using the cone test. Mortality was assessed 1 h and 24 h postexposure and quarterly over 1 year. Structured questionnaires were administered to the community endemic agent (CEA) responsible for spraying and to household residents to document perceived adverse effects.

Results: In the laboratory, the residual activity expressed by average mortality rates over 1 year of paper impregnation was of 97.6% for Fludora FusionPM) and 91.7% for Alfatek 200SC). In the field, 1-year average mortality rates were 97.3% for Fludora FusionPM and 94.6% for Alfatek 200SC for PS. On US walls, Fludora^® FusionPM maintained high mortality rate (97.8%) whereas Alfatek 200SC parameter decreased to 80.7%. Adverse effects were informed by three of five residents for Alfatek 200SC and by one of four residents for Fludora FusionPM. The CEA reported side reactions after Alfatek 200SC spraying.

Conclusions: Fludora FusionPM was highly toxic to Lu. longipalpis and outperformed Alfatek 200SC under field conditions, particularly on unpainted masonry-plastered walls. Combining insecticides with complementary modes of action may enhance rotational strategies, reduce costs and resistance risk, and optimize control of multiple vector-borne diseases simultaneously.

Background: Dengue is an acute infectious tropical disease that poses a significant public health burden in the Philippines; however, studies employing spatial distribution modeling and ecological approaches to analyze dengue occurrence data remain limited. This study aims to determine the high-risk areas suitable for dengue occurrence and its determinants in the Philippines.

Methods: Dengue case data from 2017 to 2024 were analyzed using kernel density estimation (KDE) and inverse distance weighting (IDW) spatial interpolation to characterize spatial intensity and estimate incidence in unsampled areas. An ecological niche model was developed using maximum entropy modeling, implemented through the MaxEnt software, with climatic, environmental, and socioeconomic predictors. Model performance was evaluated using the area under the curve (AUC), and predictor importance was assessed using jackknife testing.

Results: Results show highest intensity in 2019 and consistent high case density in the National Capital Region (NCR). Meanwhile, high predicted incidence rates were consistently exhibited in northern Luzon. The maximum entropy model had a strong performance in predicting the suitable areas for dengue with a mean area under curve (AUC) of 0.847. Nighttime lights (32.3%), land cover (31.1%), and population density (9.4%) significantly contributed to the model. The NCR was found to be a high-risk suitable area for dengue occurrence along with some parts of other provinces.

Conclusions: This study represents the first application of ecological niche modeling to dengue in the Philippines. The integration of KDE, IDW, and maximum entropy model provides a robust framework for identifying high-risk areas and key determinants, emphasizing the role of urbanization in dengue distribution. These findings are valuable to authorities for an informed risk-based surveillance, genotype-specific monitoring, and decision-making for geospatially targeted disease risk management.

Background: Leishmaniasis, a parasitic disease caused by Leishmania protozoa, has various clinical forms and is endemic in Brazil. Traditional experimental infection methods using intradermal and subcutaneous needles do not resemble natural sand fly transmission and are associated with risks of laboratory accidents owing to the use of low-gauge needles. In this study, we investigated the application of microneedles for transdermal (TD) infections to better replicate the deposition of parasites observed in the natural infection environment while ensuring safe handling in the laboratory.

Methods: Initial experiments involved inducing TD infections using 1-, 7- or 12-microneedle cartridges, compared with inducing conventional intradermal (ID) infections in the ears of BALB/c mice. Subsequent tests used a 12-microneedle cartridge at different tissue depths (0.25, 0.5, 0.75, 1.0 and 1.5 mm), followed by challenge with different doses of Leishmania amazonensis. In addition, histology and flow cytometry studies were performed 30 min post-infection.

Results: Transdermal infections produced similar lesion development and parasite loads as ID infections. More tissue destruction was induced using the 1- or 7-microneedle cartridge compared to the 12-microneedle cartridge and ID infection. Infection was successfully established at all microneedle depths (0.25, 0.5, 0.75 and 1.0 mm), resulting in comparable lesion thickness across the different experimental groups, with no statistically significant differences observed. The parasite load and lesion thickness were dependent on the inoculum size in the ear infection via the TD route, with efficient lesion progression using 2 × 10⁶ and 2 × 10⁵ promastigotes. Parasite loads in the ear were similar between the two approaches at the early stages, specifically at 30 min and 12 h post-infection. Thirty minutes post-infection, cytometry analysis indicated recruitment of neutrophils to the lesion site, regardless of the infection model used. The TD model specifically attracted neutrophils, independent of the presence of parasites.

Conclusions: This novel microneedle infection model enables efficient challenge and reduces risks during animal experimentation. This technique holds promise for future studies of leishmaniasis therapy and vaccine development.

Background: One of the alternatives for controlling malaria is using mosquito symbiotic bacteria to reduce Plasmodium transmission. Species of Serratia, a genus of the Enterobacteriaceae family, have been isolated from the midgut of mosquitoes and are commonly found in water, soil and plant surfaces. These bacteria have shown great promise in blocking the transmission of Plasmodium in mosquitoes. The aim of this study was to isolate and characterize the genus Serratia within the Anopheles gambiae complex from Burkina Faso.

Methods: Mosquitoes were collected in three field sites located in Houet Province in western Burkina Faso (Dioulassoba, Vallée du Kou and Soumousso), transported to the laboratory and identified morphologically. The salivary gland, midgut, spermatheca, ovary of females and testis of males were dissected and their contents ground up. Different species of Serratia were identified by PCR targeting of the luxS gene of Serratia, followed by 16S ribosomal RNA (rRNA) sequencing.

Results: Molecular analyses identified the isolates as belonging to the genus Serratia, and phylogenetic reconstruction revealed that these strains are highly similar to one another but distinct from Serratia strains previously reported in neighboring countries such as Ghana and Nigeria. The overall prevalence of Serratia among malaria vectors was 13.3%. This prevalence varied according to the development stage of mosquitoes, locality of origin and mosquito organ. Only one Anopheles coluzzii mosquito was co-infected with Serratia and Plasmodium falciparum.

Conclusions: The results of this study support the presence of Serratia spp. in wild mosquitoes from Burkina Faso, we well as their potential use in malaria control.