The epidemiology and clinical features of the neglected myiasis: A pilot surveillance study from Oman.

BACKGROUND: Myiasis is a neglected disease, characterized by ill-defined diagnostics and management protocols. Published epidemiological and clinical studies of myiasis are still scarce, although several countries, such as Oman, have reported a few cases over the past 30 years. This study explores the epidemiological profile and clinical characteristics of myiasis in South Batinah Governorate (SBG), Oman. METHODOLOGY: A prospective surveillance study was conducted in SBG from 1st November 2018 to 31st October 2019. Clinical and epidemiological data were collected using a pre-designed reporting form for suspected and confirmed cases. RESULTS: A total of 188 cases were reported, of which 81.4% were male. One-third of cases were 11-20 years old, and a quarter reported exposure inside house. The rate of exposure was 16 per 10000 in Nakhal and Wadi Mawel. About 57% patients reported multiple re-exposure. Almost 60% of patients developed nasal or oral myiasis, 25% developed myiasis in the eye, and 4% in the ear. The most common respiratory symptoms were cough (83%), runny nose (48%), and foreign body sensation (35%). Over 50% of patients with eye exposures had redness, pain, and itchiness. Most patients (89.3%) kept animals at homes. Many cases occurred between December 2018 and April 2019, with almost one-third of exposures occurring at 5 p.m. Re-exposure likelihood for patients residing in Nakhal and Wadi Mawel was high; OR = 2.49 (95% CI 1.14-5.45), with OR = 3.59 (95% CI 1.37-9.39) for 11-20-year-olds and, OR = 3.01 (95% CI 1.07-8.42) for patients ≥ 31 years. CONCLUSION: The myiasis exposure rate is high in certain areas and age groups, which is most likely associated with animal-related activities. The disease has a significant impact upon people's health in SBG. Therefore, urgent active-surveillance and clinical studies are warranted to explore possible preventive measures and treatment options. Adopting one health approach could offer an effective strategy for preventing myiasis in human and animal populations.

Visceral Leishmaniasis in Immunocompetent Hosts in Brescia: A Case Series and Analysis of Cytokine Cascade.

Visceral leishmaniasis (VL) is a parasitic zoonosis caused by Leishmania spp. that usually manifests itself in immunocompromised subjects. It is a rare and neglected disease, and it is not endemic in the province of Brescia (Italy). Three cases of human VL occurred in Brescia from October to December 2021 in immunocompetent patients. We evaluated the patients looking for signs of underlying immunodeficiencies and conducted further epidemiological evaluations in the province of Brescia without success. An analysis of the sera levels of the main cytokines involved in the immune response to VL was performed. All patients presented a significant augmentation of CXCL-10, CCL-4, and IL-6. The patients tested during the acute phase showed an elevation of IL-1α, IL-5, IL-10, and IL-12, while in the recovery phase, higher levels of TNF-α and IL-7 were detected. Altogether, a predominant activation of the T-helper-2 pathway emerged during the acute phase of the parasite infection, while the cytokines associated with the T-helper-1 pathway were less represented. This imbalanced immune response to the parasite infection might play a crucial role in the development of VL in immunocompetent patients.

Development of subunit selective proteasome substrates for Schistosoma species.

Schistosomiasis, or bilharzia, is a neglected tropical disease caused by Schistosoma spp. blood flukes that infects over 200 million people worldwide. Just one partially effective drug is available, and new drugs and drug targets would be welcome. The 20S proteasome is a validated drug target for many parasitic infections, including those caused by Plasmodium and Leishmania. We previously showed that anticancer proteasome inhibitors that act through the Schistosoma mansoni 20S proteasome (Sm20S) kill the parasite in vitro. To advance these initial findings, we employed Multiplex Substrate Profiling by Mass Spectrometry (MSP-MS) to define the substrate cleavage specificities of the three catalytic ß subunits of purified Sm20S. The profiles in turn were used to design and synthesize subunit-specific optimized substrates that performed two to eight fold better than the equivalent substrates used to measure the activity of the constitutive human proteasome (c20S). These specific substrates also eliminated the need to purify Sm20S from parasite extracts - a single step enrichment was sufficient to accurately measure substrate hydrolysis and its inhibition with proteasome inhibitors. Finally, we show that the substrate and inhibition profiles for the 20S proteasome from the three medically important schistosome species are similar, suggesting that data arising from an inhibitor development campaign that focuses on Sm20S can be extrapolated to the other two targets with consequent time and cost savings.

Fleas (Siphonaptera, Latreille, 1825) from Rio Grande do Sul State, Brazil: Species Diversity, Hosts, and One Health Approach.

Background: Fleas are ectoparasitic insects with holometabolous development. It has a hematophagous habit with mouthparts adapted to sting and suck its hosts. There are about 3000 species in the world, ∼61 in Brazil, and 19 in Rio Grande do Sul state. The objective of the research is to catalog the diversity of fleas recorded in the state, their respective hosts, and endosymbionts. Materials and Methods: To this end, a search was carried out in the scientific literature, from articles, books, to abstracts submitted to congresses. Results: The 19 species of fleas occurring in Rio Grande do Sul are divided into 7 families and 10 genera. These ectoparasites, in addition to being found in the environment, were associated with 10 different families of hosts in Rio Grande do Sul, and on the endosymbiont, agents found associated with fleas, there were 7 different species. The main agents researched in the state are Rickettsia spp. and Bartonella spp. The relationships between parasites, hosts, environment, and etiological agents present different scenarios, whether anthropized or conserved, but unknown. Sometimes, this overlap, a factor that aggravates the possibility of spillovers, either from cosmopolitan fleas in these conserved areas, or from their endosymbionts. Conclusion: Thus, it is important to characterize the environment so that the complexities of each location are known for the adoption of environmental and public health policies in each case. The challenges are extensive, but necessary in view of the One Health perspective.

Snakebites epidemiology in Mexico: a 13-year ecological analysis.

BACKGROUND: Globally, snakebites have a significant impact on public health and represent substantial costs for health services. Their severity is particularly relevant in developing countries due to the lack of resources and accessibility to health facilities. Additionally, the number of cases may be underestimated, highlighting the urgent need for improved prevention measures. METHODS: An observational ecological study was undertaken using the records identified with X200-X209 codes registered in the Ministry of Health injuries database during 2010-2022. Variables included information related to the patient, the snakebite and the healthcare provided. Statistical analysis was carried out with STATA 16 and Microsoft Excel 2020. RESULTS: A total of 10 420 snakebites were registered. The average number of cases per year was 788 (IQR 615, 875) and 82.74% occurred during the rainy season. The median age was 35 (IQR 19, 52) y and early adulthood was the most affected age group; bites were most common on the hand and in the living place. The Eastern region of Mexico registered the highest number of cases, with 3496 (33.71%) of snakebites. The lethality rate was 18.23 per 10 000. CONCLUSIONS: Snakebites are a significant health problem in Mexico. Most injuries occur among men in early adulthood, in households and in the upper extremities.

Unveiling the secrets of snakes: Analysis of environmental, socioeconomic, and spatial factors associated with snakebite risk in Paraná, Southern Brazil.

The state of Paraná is home to three out of the five medically significant snake genera in Brazil and lacks of snakebite epidemiology studies. This study aimed to ascertain the spatial, environmental, and socioeconomic factors associated with snakebite risk by analyzing notification data of cases in the state of Paraná. Notification and socioeconomic data were gathered from the online platforms of the National System of Notifiable Diseases (SINAN) and the Brazilian Institute of Geography and Statistics (IBGE). Land cover and land use maps were obtained from the Mapbiomas platform in raster format and subsequently converted into vectors using QGis software. The proportions of land use and land cover in square kilometers (km2) were then calculated. All acquired data were tabulated using Microsoft Excel 365 software. For spatial analysis, GeoDa software version 1.20 was utilized to calculate the Global and Local Moran indices, assessing spatial correlations. Between 2007 and 2021, 12,877 notifications were recorded, with an average incidence of 8.22/100,000 inhabitants in the state, 8166 (63.41%) caused by Bothrops, 1534 (11.91%) caused by Crotalus, 56 (0.43%) caused by Micrurus. 1703 (13.22%) caused by non-venomous snake species, and the remaining cases did not have the identified causative species. The incidents caused by Bothrops and Crotalus showed different distribution patterns. Spatial analysis revealed that key factors contributing to snakebite risk included the presence of native forests, mangroves, apicuns, and monospecific planted forests. The population group at the highest risk comprised rural residents and workers. Furthermore, the absence of basic sanitation and proper garbage collection and disposal exhibited positive correlations with snakebites. Conversely, intensive farming practices with substantial mechanization and pastures demonstrated negative spatial correlations. This study has enabled the identification of the primary factors associated with snakebite risk, facilitating more targeted efforts to prevent snakebite accidents among vulnerable populations.

Simple and promising paper-based electrochemical platform for serological detection of American tegumentary leishmaniasis

BACKGROUND American tegumentary leishmaniasis (ATL) is an endemic neglected tropical disease (NTD), its conventional treatment is toxic, slow, and invasive. Rapid diagnosis is crucial for the clinical management of suspected patients, so the development and use of low-cost, miniaturised and portable devices could be the key. OBJECTIVES This work aimed to develop a simple paper-based electrochemical platform for the serological detection of ATL. METHODS Platform was fabricated in Whatman N°1 paper, contains a hydrophobic zone generated by wax printing, two pencil graphite electrodes, and uses specific crude extracts (CA) antigens for ATL immuno-determination. The platform performance was analysed by measuring the relative impedance change for different antigen-antibody combinations. Then, 10 serum human samples previously diagnosed by the gold standard (five positive ATL cases and five non-ATL cases) were evaluated. FINDINGS The platform presented a linear response for the charge transfer resistance (ΔRct) and the interface reactance (ΔXc). Also, optimal working conditions were established (1/60 serum dilution and 180 µg/mL CA concentration). Then, the platform permits to distinguish between ATL and non-ATL (p < 0.05) human serum samples. MAIN CONCLUSIONS Our platform could allow the diagnosis, management, and monitoring of leishmaniasis while being an extremely simple and environmentally friendly technology.

Progress of research on the diagnosis and treatment of bone cystic echinococcosis.

Bone cystic echinococcosis (CE) is one of the most complex and dangerous of all echinococcoses. The lack of typical imaging features and clinical manifestations makes diagnosis and treatment of this disease difficult. X-ray and computed tomography (CT) images of bone CE are similar to those of bone cysts, giant-cell bone tumors, and bone metastases, but magnetic resonance imaging (MRI) shows good diagnostic value due to excellent soft-tissue imaging features. Serological tests cannot be used as a definitive diagnostic method for bone CE due to cross-reactivity, which can lead to false-positive or false-negative results. The development of novel antigens can open new frontiers in the diagnosis of the disease. Currently, views conflict on how to diagnose and treat bone CE. Both surgical and pharmacological treatments can be used, but determining which is appropriate is difficult due to the different sites and clinical manifestations of bone CE. Radical resection is not indicated for large-bone injuries, and Pharmacotherapy becomes important. This article reviews the progress of research into the pathogenesis and clinical manifestations of, and diagnostic strategies and treatment options for, bone CE. We aimed to provide a reference for clinical diagnosis and -treatment options.

Trend of pediatric leprosy in an endemic area in Northeast of Brazil, 2008-2018.

BACKGROUND: The incidence of leprosy in children is an important indicator of the disease's tendency in the general population and suggests intense circulation and transmission of Mycobacterium leprae. OBJECTIVES: To describe the clinical, epidemiological characteristics and temporal dynamics of leprosy cases in children under 15 years of age from 2008 to 2018 in an endemic municipality. METHODS: A descriptive study with an analytical approach was carried out with data from leprosy cases registered in the Brazilian Information System on Notifiable Diseases for the municipality of Cabo de Santo Agostinho, Pernambuco, Brazil. RESULTS: Between 2008 and 2018, 112 new cases of leprosy were registered. Most cases were classified as paucibacillary leprosy and occurred in children living in urban areas. There was no significant difference in the incidence of leprosy during the study period. Only 4.5% of the sample presented reactional episodes, but a high number of cases were not evaluated for the occurrence of reactions. CONCLUSIONS: The findings of this study show a high incidence of paucibacillary leprosy in children and adolescents, which reveals active transmission in the community and failures in the detection of new multibacillary cases among adults. Children between 10 and 14 years old are more vulnerable to M. leprae infection and mainly develop paucibacillary leprosy.

Phenotypic assay for cytotoxicity assessment of Balamuthia mandrillaris against human neurospheroids.

Introduction: The phenotypic screening of drugs against Balamuthia mandrillaris, a neuropathogenic amoeba, involves two simultaneous phases: an initial step to test amoebicidal activity followed by an assay for cytotoxicity to host cells. The emergence of three-dimensional (3D) cell cultures has provided a more physiologically relevant model than traditional 2D cell culture for studying the pathogenicity of B. mandrillaris. However, the measurement of ATP, a critical indicator of cell viability, is complicated by the overgrowth of B. mandrillaris in coculture with host cells during drug screening, making it challenging to differentiate between amoebicidal activity and drug toxicity to human cells. Methods: To address this limitation, we introduce a novel assay that utilizes three-dimensional hanging spheroid plates (3DHSPs) to evaluate both activities simultaneously on a single platform. Results and discussion: Our study showed that the incubation of neurospheroids with clinically isolated B. mandrillaris trophozoites resulted in a loss of neurospheroid integrity, while the ATP levels in the neurospheroids decreased over time, indicating decreased host cell viability. Conversely, ATP levels in isolated trophozoites increased, indicating active parasite metabolism. Our findings suggest that the 3DHSP-based assay can serve as an endpoint for the phenotypic screening of drugs against B. mandrillaris, providing a more efficient and accurate approach for evaluating both parasite cytotoxicity and viability.

Emerging biomedical tools for biomarkers detection and diagnostics in schistosomiasis.

Schistosomiasis is a neglected disease that strikes many people from tropical and subtropical countries where there are not satisfactory sanitation and wide access to clean water. Schistosoma spp., the causative agents of schistosomiasis, exhibit a quite complex life cycle that involves two hosts (humans and snails, respectively, the definitive and the intermediate), and five evolutive forms: cercariae (human infective form), schistosomula, adult worms, eggs, and miracidia. The techniques to diagnose schistosomiasis still have various limitations, mainly regarding low-intensity infections. Although various mechanisms associated with schistosomiasis have already been evidenced, there is still a need to fulfill the comprehension of this disease, especially to prospect for novel biomarkers to improve its diagnosis. Developing methods with more sensitivity and portability to detect the infection is valuable to reach schistosomiasis control. In this context, this review has gathered information not only on schistosomiasis biomarkers but also on emerging optical and electrochemical tools proposed in selected studies from about the last ten years. Aspects of the assays regarding the sensibility, specificity, and time needed for detecting diverse biomarkers are described. We hope this review can guide future developments in the field of schistosomiasis, contributing to improving its diagnosis and eradication.

Allergic rhinitis behavioral changes after Indonesian house dust mites allergenic extract administration as immunotherapy.

Background: Allergy is a hypersensitivity reaction that is generally mediated by Immunoglobulin E (IgE). More than 25% of the world's population is suspected of having these various diseases, and the prevalence and progression of these diseases have continued to increase significantly in recent years. Among these allergyrelated diseases, allergic rhinitis and food allergy are the types of allergies with the highest prevalence. Clinical manifestations of allergic rhinitis include sneezing, rhinorrhea, nasal itching, and nasal congestion. Objective: This study aimed to determine the behavioral changes of allergic rhinitis after Indonesian House Dust Mites (IHDM) allergenic extract administration as an immunotherapy. Methods: Eight male BALB/c mice aged 6-8 weeks in each group were treated for seven groups. The sensitization phase is given intraperitoneal, the desensitization phase is given by subcutaneous, and the challenge phase is given intranasal. The allergic parameters were observed, such as nose rubbing and sneezing. The parameters were observed for 15 minutes after the challenge administration. Results: The results showed that the administration of Indonesian House Dust Mites as immunotherapy decreased the frequency of nose rubbing and sneezing after the administration of immunotherapy compared to the allergic rhinitis model. Conclusions: The administration of the Indonesian House Dust Mites as immunotherapy decreased the allergic rhinitis immune response by altering the behavioral parameter.

An 11-year epidemiological analysis of schistosomiasis in Ecuador: Investigating a non-endemic, neglected, and challenging-to-identify parasitic disease.

Schistosomiasis is a neglected disease caused by parasites of the genus Schistosoma and transmitted by snails of the genus Biomphalaria. At least five species have the potential to infect humans living in or visiting tropical areas worldwide. In Latin America, Schistosoma mansoni is particularly common; however, it has not been reported in Ecuador. In this study, we assess the available official data on schistosomiasis in Ecuador to describe the prevalence of this neglected disease. We conducted a nationwide study to determine the demographic and spatial distribution patterns of schistosomiasis infection in Ecuador, using hospital discharge official data as a proxy for infection incidence from 2011 to 2021. We calculated crude and age-sex-adjusted morbidity and hospital admission rates by region, province, canton, and elevation. In the last decade of available data, schistosomiasis accounted for at least 551 hospital admissions in Ecuador. Women represented 53.7% (n = 296) of cases, equivalent to 3.2 cases per 1,000,000 inhabits. The highest number of cases (61.2%, n = 337) was found in the Coastal region. However, the highest incidence rates were observed in the Amazon region's provinces of Pastaza (173.44 cases/1,000,000).

Fungal Vaccine Development: State of the Art and Perspectives Using Immunoinformatics.

Fungal infections represent a serious global health problem, causing damage to health and the economy on the scale of millions. Although vaccines are the most effective therapeutic approach used to combat infectious agents, at the moment, no fungal vaccine has been approved for use in humans. However, the scientific community has been working hard to overcome this challenge. In this sense, we aim to describe here an update on the development of fungal vaccines and the progress of methodological and experimental immunotherapies against fungal infections. In addition, advances in immunoinformatic tools are described as an important aid by which to overcome the difficulty of achieving success in fungal vaccine development. In silico approaches are great options for the most important and difficult questions regarding the attainment of an efficient fungal vaccine. Here, we suggest how bioinformatic tools could contribute, considering the main challenges, to an effective fungal vaccine.

Severe Chagas disease in Ecuador: a countrywide geodemographic epidemiological analysis from 2011 to 2021.

Background: Chagas disease is a neglected and often forgotten tropical disease caused by the Trypanosoma cruzi. This parasite can be transmitted through the direct contact of human skin with feces and urine of the triatomine insect. According to the World Health Organization (WHO), an estimated 6-7 million people are infected worldwide, killing at least 14,000 every year. The disease has been reported in 20 of the 24 provinces of Ecuador, with El Oro, Guayas, and Loja being the most affected. Methodology: We analyzed the morbidity and mortality rates of severe Chagas disease in Ecuador on a nationwide, population-based level. Hospitalization cases and deaths were also examined based on altitude, including low (< 2,500 m) and high (> 2,500 m) altitudes, according to the International Society. Data was retrieved from the National Institute of Statistics and Census hospital admissions and in-hospital mortality databases from 2011 to 2021. Results: A total of 118 patients have been hospitalized in Ecuador since 2011 due to Chagas disease. The overall in-hospital mortality rate was 69.4% (N = 82). Men have a higher incidence rate (4.8/1,000,000) than women, although women have a significantly higher mortality rate than men (6.9/1,000,000). Conclusion: Chagas disease is a severe parasitic condition that primarily affects rural and poorer areas of Ecuador. Men are more likely to be infected due to differences in work and sociocultural activities. Using average elevation data, we conducted a geodemographic analysis to assess incidence rates by altitude. Our findings indicate that the disease is more common at low and moderate altitudes, but recent increases in cases at higher altitudes suggest that environmental changes, such as global warming, could be driving the proliferation of disease-carrying vectors in previously unaffected areas.

Cranial vault reduction cranioplasty for severe macrocephaly due to holoprosencephaly and subdural hygroma: a case report.

BACKGROUND: Severe macrocephaly can still be found in developing countries. This condition is usually caused by neglected hydrocephalus and can cause a lot of morbidities. Cranial vault reconstruction cranioplasty is the main treatment option for severe macrocephaly. Holoprosencephaly is often seen with features of microcephaly. Hydrocephalus should be considered as the main cause in HPE patients with features of macrocephaly. In this report, we present a rare case of cranial vault reduction cranioplasty procedure in patient with severe macrocephaly due to holoprosencephaly and subdural hygroma. CASE DESCRIPTION: A 4-year-10-month-old Indonesian boy was admitted with head enlargement since birth. He had a history of VP shunt placement when he was 3 months old. But the condition was neglected. Preoperative head CT showed massive bilateral subdural hygroma that compressed brain parenchyma caudally. From the craniometric calculation, the occipital frontal circumference was 70.5 cm with prominent vertex expansion, the distance between nasion to inion was 11.91 cm and the vertical height was 25.59 cm. The preoperative cranial volume was 24.611 cc. The patient underwent subdural hygroma evacuation and cranial vault reduction cranioplasty. The postoperative cranial volume was 10.468 cc. CONCLUSION: Subdural hygroma can be a rare cause of severe macrocephaly in holoprosencephaly patients. Cranial vault reduction cranioplasty and subdural hygroma evacuation is still the main treatment option. Our procedure successfully reduces significant cranial volume (57.46% volume reduction).

First report of acanthocephalan parasite in wild-caught Asian vine snake (Ahaetulla prasina) in Indonesia.

Background and Aim: Exotic pet snakes are more susceptible to infection, especially parasitic helminths than wild-caught. There is no comprehensive report on the prevalence of acanthocephalan parasite infection in Indonesian snakes. Therefore, this study aimed to estimate the prevalence rate and to identify the acanthocephalan infection in wild-caught Asian vine snake (Ahaetulla prasina) from the Mojokerto District, East Java, Indonesia. Materials and Methods: A total of 60 snakes were collected from the local sellers in the Mojokerto District, East Java, Indonesia. Then, snakes were euthanized and necropsied to observe various predilections of acanthocephalan larval stage (cystacanth). Morphological identification of the cystacanth was conducted using the carmine staining method and microscopic examination. Results: Acanthocephalan infection was recorded with a high prevalence rate of 80.06%. A total of 696 cystacanths were examined from the muscle, subcutaneous tissues, and visceral with 32.90, 16.37, and 50.71% intensity rates, respectively. Conclusion: Acanthocephalan prevalence rate was recorded at 80.06% in this study. Constant disease monitoring is necessary, considering wild-caught Asian vine snakes were susceptible host and lack of data regarding parasitological surveys. Therefore, further studies are needed in new areas and various species of wild-caught snakes in Indonesia, because of the potential of parasitic helminth transmission between snake and other reptiles.

Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole.

BACKGROUND: Chagas disease (CD), caused by Trypanosoma cruzi, represents a health threat to around 20 million people worldwide. Side effects of benznidazole (Bzn) cause 15-20% of patients to discontinue their treatment. Evidence has increased in favor of the use of drug combinations to improve the efficacy and tolerance of the treatment. Natural products are well known to provide structures that could serve as new drugs or scaffolds for CD treatment. Spp of the Amaryllidoideae sub family of Amaryllidaceae family are known by their bioactives alkaloids, which have been reported by their antiparasitic activities. PURPOSE: To evaluate the anti-T. cruzi activity of the isolated alkaloid candimine (Cnd) from Hippeastrum escoipense Slanis & Huaylla; and to assess the combination effect between Cnd and Bzn against different life stages of T. cruzi parasites. METHODS: The chemical profile of H. escoipense alkaloids extract (AE-H. escoipense), including quantitation of Cnd was performed through GC/MS and UPLC-MS/MS techniques. Subsequently, Cnd was isolated using Shephadex LH-20. Then, the AE-H. escoipense and Cnd were tested against T. cruzi, (epimastigotes, trypomastigotes, and amastigotes) by in vitro proliferation and viability assays. The cytotoxicity was evaluated against Vero and HepG2 mammalian cells. The ultrastructural analysis was perform by transmission electron microscopy (TEM) and mitochondrial activity was carried out by MTT assay. Drug combination assay between Cnd and Bzn was evaluated using the Chou-Talalay method. RESULTS: The AE-H. escoipense and Cnd showed high and specific anti-T. cruzi activity, comparable to Bzn. Cnd induces ultrastructural changes in T. cruzi, such as vacuolization, membrane blebs, and increased mitochondrial activity. Regarding the interaction between Cnd and Bzn, it generates synergism in the combinations of 0.25×IC50 in epimastigotes, 2×IC50 in trypomastigotes+amastigotes, and 0.25, 2, and 4×IC50 in amastigotes. CONCLUSION: The synergism between Cnd and Bzn indicates that the combination at the concentration of 4×IC50 could be useful as an effective new therapy against CD in the chronic stage. Thus, Cnd isolated from the leaves of H. escoipense emerges as potential candidate for the development of a new drug for the treatment of CD.

Phylogenetic and immunological investigations of complete TSA56 ORF of Orientia tsutsugamushi present in acute encephalitis syndrome cases from eastern Uttar Pradesh, India.

Scrub typhus (ST) caused by Orientia tsutsugamushi (OT), has long been known to cause acute encephalitis syndrome (AES) and acute febrile illness (AFI). The immunodominant 56 kDa protein of OT, which is encoded by the 56 kDa gene (1600 bp encoding 516-541 amino acids) is a commonly studied antigen for genotype and serotype assignment. Previous studies from India have utilized partial type specific antigen (TSA) 56 kDa sequences for OT strain characterisation. On the other hand, understanding the antigenic diversity of current OT strains, is critical for developing specific diagnostic tests and vaccines against ST. As a result, the current study analyses antigenic variants using the entire TSA56 ORF of OT from AES cases. Phylogenetic investigation using complete TSA56 ORF sequences revealed Karp and Gilliam were the circulating predominant strains of OT. Furthermore, Immuno-informatical analysis demonstrated that the majority of high-binding affinity CD4 TCEs against the most prevalent Indian human leukocyte antigen alleles were present in the S-VDIII/IV and S-VDIV spacer regions of TSA56 ORF. TSA56 conserved spacer is crucial for OT immunological response investigations. Further, the pathophysiological effects of spacer domains in ST require further investigation. Furthermore, the characterization of the TSA56 spacer region of the OT from different parts of India is critical for developing region-specific ST diagnostic assays and vaccines.

Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections.

Introduction: Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp., commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited efficiencies and can cause serious side effects, so there is an urgent need to develop new control strategies. Presently, the identification and prioritization of appropriate targets can be aided by integrative genomic and computational approaches. Methods: In this work, we conducted a genome-wide multidimensional data integration strategy to prioritize drug targets. We included genomic, transcriptomic, metabolic, and protein structural data sources, to delineate candidate proteins with relevant features for target selection in drug development. Results and Discussion: Our final ranked list includes proteins shared by TriTryps and covers a range of biological functions including essential proteins for parasite survival or growth, oxidative stress-related enzymes, virulence factors, and proteins that are exclusive to these parasites. Our strategy found previously described candidates, which validates our approach as well as new proteins that can be attractive targets to consider during the initial steps of drug discovery.