Advances in the study of the interaction between schistosome infections and the host's intestinal microorganisms.

Schistosomiasis, also called bilharziasis, is a neglected tropical disease induced by schistosomes that infects hundreds of millions of people worldwide. In the life cycle of schistosomiasis, eggs are regarded as the main pathogenic factor, causing granuloma formation in the tissues and organs of hosts, which can cause severe gastrointestinal and liver granulomatous immune responses and irreversible fibrosis. Increasing evidence suggests that the gut microbiome influences the progression of schistosomiasis and plays a central role in liver disease via the gut-liver axis. When used as pharmaceutical supplements or adjunctive therapy, probiotics have shown promising results in preventing, mitigating, and even treating schistosomiasis. This review elucidates the potential mechanisms of this three-way parasite-host-microbiome interaction by summarizing schistosome-mediated intestinal flora disorders, local immune changes, and host metabolic changes, and elaborates the important role of the gut microbiome in liver disease after schistosome infection through the gut-liver axis. Understanding the mechanisms behind this interaction may aid in the discovery of probiotics as novel therapeutic targets and sustainable control strategies for schistosomiasis.

In Vitro and in Vivo Study of a Photostable Quinone Compound with Enhanced Therapeutic Efficacy against Chagas Disease.

Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi poses a significant health challenge in rural areas of Latin America. The current pharmacological options exhibit notable side effects, demand prolonged administration, and display limited efficacy. Consequently, there is an urgent need to develop drugs that are safe and clinically effective. Previously, we identified a quinone compound (designated as compound 2) with potent antiprotozoal activity, based on the chemical structure of komaroviquinone, a natural product renowned for its antitrypanosomal effects. However, compound 2 was demonstrated considerably unstable to light. In this study, we elucidated the structure of the light-induced degradation products of compound 2 and probed the correlation between the quinone ring's substituents and its susceptibility to light. Our findings led to the discovery of quinones with significantly enhanced light stability, some of which exhibiting antitrypanosomal activity. The most promising compound was evaluated for drug efficacy in a mouse model of Chagas disease, revealing where a notable reduction in blood parasitemia.

MLMFNet: A multi-level modality fusion network for multi-modal accelerated MRI reconstruction.

Magnetic resonance imaging produces detailed anatomical and physiological images of the human body that can be used in the clinical diagnosis and treatment of diseases. However, MRI suffers its comparatively longer acquisition time than other imaging methods and is thus vulnerable to motion artifacts, which ultimately lead to likely failed or even wrong diagnosis. In order to perform faster reconstruction, deep learning-based methods along with traditional strategies such as parallel imaging and compressed sensing come into play in recent years in this field. Meanwhile, in order to better analyze the diseases, it is also often necessary to acquire images in the same region of interest under different modalities, which yield images with different contrast levels. However, most of these aforementioned methods tend to use single-modal images for reconstruction, neglecting the correlation and redundancy information embedded in MR images acquired with different modalities. While there are works on multi-modal reconstruction, the information is yet to be efficiently explored. In this paper, we propose an end-to-end neural network called MLMFNet, which helps the reconstruction of the target modality by using information from the auxiliary modality across feature channels and layers. Specifically, this is highlighted by three components: (I) An encoder based on UNet with a single-stream strategy that fuses auxiliary and target modalities; (II) a decoder that tends to multi-level features from all layers of the encoder, and (III) a channel attention module. Quantitative and qualitative analyses are performed on a public brain dataset and knee brain dataset, which show that the proposed method achieves satisfying results in MRI reconstruction within the multi-modal context, and also demonstrate its effectiveness and potential to be used in clinical practice.

Human and camel cystic echinococcosis - a polyclonal antibody-based sandwich ELISA for its serodiagnosis with molecular identification.

Cystic echinococcosis (CE) is an emergent neglected disease affecting human and animals in Egypt with a wide distribution and incidence. This study aimed to evaluate the use of a polyclonal antibody-based sandwich ELISA in the detection of Echinococcus granulosus antigen in human and camel sera. Hydatid cyst protoscoleces antigen (PsAg) was isolated from hydatid cysts collected from naturally infected camel livers and lungs. PsAg was used for immunization of rabbits to raise IgG polyclonal antibodies (IgG PsAb). IgG PsAb were then precipitated, purified using Protein-A Sepharose gel and labeled with horseradish peroxidase enzyme. We assayed the purity of the IgG PsAb, and the two prepared E. granulosus antigens CPsAg from camel cysts and HPsAg from human cysts by Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The resulted protein bands of the prepared CPsAg appeared at different molecular weights: 180, 90, 68, 54, 42 and 22 kDa while, HPsAg shared with it in 4 common bands at 68, 54, 42, and 22 kDa. The purified IgG PsAb had been resolved at two bands at 52 kDa and at 32 kDa. Sandwich ELISA were performed for the detection of circulating E. granulosus antigens in sera of human (n = 183) and camels (n = 190). The purified IgG PsAb showed strong reactivity against E. granulosus infected human and camel samples and no cross reactivity neither with free-healthy negative sera nor with others parasitic diseases (Schistosomiasis, Fascioliasis, Toxoplasmosis, Ancylostomiasis for human samples and Fascioliasis, ticks' infestation, Eimeriosis, Cryptosporidiosis, Nasal myiasis, Toxoplasmosis for camel samples). The sensitivity of the assay was 98.25% (56/57) and 96.9% (31/32) against human and camel samples, respectively. Specificity was 100% in both human and camel samples. Sandwich ELISA detected CE in 33.3% (24/72) and 55.6% (50/90) random human and camel samples, respectively. Indirect ELISA, using CPsAg, was used for detection of antibodies in positive human and camels' sera and detected 96.5% (55/57) and 93.8% (30/32) of human and camel samples, respectively. In our study, Genomic DNA was extracted from protoscoleces fluid of human liver hydatid cysts to identify the Echinococcus sp. isolate based on NADH dehydrogenase subunit 1 (NAD1) gene by Polymerase Chain Reaction (PCR) and the isolate (GenBank: OP785689.1) were identified as E. granulosus sensu lato genotype. In conclusion, Sandwich ELISA technique was found to be a potent and sensitive assay for detection of hydatid antigen in both human and camel samples.

The Uptake of Pneumococcal and Seasonal Influenza Vaccinations Based on Perceptions and Attitudes Toward the COVID-19 Vaccine Among Patients With Diabetes.

Objective In this study, we aimed to assess the rates of pneumococcal and seasonal influenza vaccinations among elderly and nonelderly diabetes patients and examine their perceptions and attitudes toward the coronavirus disease 2019 (COVID-19) vaccine. Methods A single-center study was conducted among patients with diabetes, employing a structured survey encompassing sociodemographic data, vaccination records, and the COVID-19 vaccine perception and attitude scale. Results Among the 280 diabetes patients in our study, the vaccination rates for COVID-19, seasonal influenza, and pneumococcal vaccines were 96.1%, 16.8%, and 17.5%, respectively. A higher cumulative dosage of the COVID-19 vaccine was associated with older age (r = 0.463; p<0.001), increased safety score (r = 0.479; p<0.001), and lower conspiracy theory score (r = -0.336; p<0.001). Participants who had received COVID-19 and influenza vaccines were observed to have significantly higher safety scores related to COVID-19 vaccines (p<0.001; d = 2.381 and p = 0.008; d = 0.525, respectively). Notably, vaccination rates for influenza and pneumococcus were significantly different between nonelderly and elderly patients (8.7% vs. 29.6%; p<0.001 and 13.4% vs. 24.1%; p = 0.022). Elderly patients with diabetes were 3.3 times more likely to receive the influenza vaccine than nonelderly participants [odds ratio (OR) = 3.319; 95% confidence interval (CI) = 1.592 - 6.920; p = 0.001] and had a higher safety score related to COVID-19 vaccines (OR = 1.076; 95% CI = 1.011 - 1.146; p = 0.021). Conclusions Both influenza and pneumococcal vaccination rates were below the desired targets in this study. The vaccination rates among the nonelderly diabetes population suggest that this group may be more likely to neglect to receive vaccination compared to the elderly diabetes population. The association between vaccination rates and post-pandemic safety perceptions highlights the critical need to implement public health strategies specifically designed to address and improve safety-related information dissemination.

Neurocysticercosis in a Nigerian woman -missed diagnosis of a neglected disease and surgical management.

Neurocysticercosis is a rarely diagnosed but significant clinical problem from infestation with taenia solium. It occurs as a result of ingestion of infested pork and the mode of transmission is usually feco-oral. It is commonly associated with non-specific neurologic manifestations expected of intracranial space-occupying lesions with its most common neurological presentation being seizures. However, its diagnosis without seizure is rarely reported. We report a recent experience in this regard and outcome of this disease which was inadvertently managed surgically. A good history and high index of suspicion especially in developing and low socioeconomic region is helpful for diagnosis in the presence of appropriate radiological findings. Prognosis is good when treatment is tailored to well selected cases. Treatment options include medical with or without surgical removal of encapsulated cyst. A high index of suspicion will be helpful in making appropriate diagnosis and proper management of this disease.

Mines of cytokine: A treasure trove in pulpal and periapical diseases.

Pulpitis is a special disease of dental pulp. It causes localized inflammation, due to various inflammatory mediators such as cytokines and chemokines. These inflammatory mediators are responsible for various reparative and resorptive processes in the dental pulp. The balance between these processes ultimately determines the viability of the tooth. Due to the important properties of various inflammatory markers, the correlation of cytokinin gene expression in various stages of inflammation becomes necessary to focus on. Several studies in the past have focused on the importance of such correlation to help in diagnostic applications. The nature of these inflammatory mediators can help us in diagnostic evaluation. Several attempts have been made to focus on these associations so that it can assist in making clinical decisions effectively. The data available are vast but are the most neglected topic. This review article briefly outlines and summarizes the importance of various inflammatory mediators such as cytokinin and chemokines in various pathways of pulpal and periapical inflammation in explanatory and diagrammatic forms. Knowledge gained about pulpal inflammatory response may aid in understanding the molecular level of inflammatory pulpal and periapical diseases, which shall modify our future diagnostic modalities. Several medicaments are used in the treatment of minimal to advanced dental caries which leads to periapical infections. Thorough understanding of these medicaments can resolve secondary infection and can improve the prognosis of the treated tooth.

Hepatic Topology of Glycosphingolipids in Schistosoma mansoni-Infected Hamsters.

Schistosomiasis is a neglected tropical disease caused by worm parasites of the genus Schistosoma. Upon infection, parasite eggs can lodge inside of host organs like the liver. This leads to granuloma formation, which is the main cause of the pathology of schistosomiasis. To better understand the different levels of host-pathogen interaction and pathology, our study focused on the characterization of glycosphingolipids (GSLs). For this purpose, GSLs in livers of infected and noninfected hamsters were studied by combining high-spatial-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) with nanoscale hydrophilic interaction liquid chromatography tandem mass spectrometry (nano-HILIC MS/MS). Nano-HILIC MS/MS revealed 60 GSL species with a distinct saccharide and ceramide composition. AP-SMALDI MSI measurements were conducted in positive- and negative-ion mode for the visualization of neutral and acidic GSLs. Based on nano-HILIC MS/MS results, we discovered no downregulated but 50 significantly upregulated GSLs in liver samples of infected hamsters. AP-SMALDI MSI showed that 44 of these GSL species were associated with the granulomas in the liver tissue. Our findings suggest an important role of GSLs during granuloma formation.

Ancestral aneuploidy and stable chromosomal duplication resulting in differential genome structure and gene expression control in trypanosomatid parasites.

Aneuploidy is widely observed in both unicellular and multicellular eukaryotes, usually associated with adaptation to stress conditions. Chromosomal duplication stability is a tradeoff between the fitness cost of having unbalanced gene copies and the potential fitness gained from increased dosage of specific advantageous genes. Trypanosomatids, a family of protozoans that include species that cause neglected tropical diseases, are a relevant group to study aneuploidies. Their life cycle has several stressors that could select for different patterns of chromosomal duplications and/or losses, and their nearly universal use of polycistronic transcription increases their reliance on gene expansion/contraction, as well as post-transcriptional control as mechanisms for gene expression regulation. By evaluating the data from 866 isolates covering seven trypanosomatid genera, we have revealed that aneuploidy tolerance is an ancestral characteristic of trypanosomatids but has a reduced occurrence in a specific monophyletic clade that has undergone large genomic reorganization and chromosomal fusions. We have also identified an ancient chromosomal duplication that was maintained across these parasite's speciation, named collectively as the trypanosomatid ancestral supernumerary chromosome (TASC). TASC has most genes in the same coding strand, is expressed as a disomic chromosome (even having four copies), and has increased potential for functional variation, but it purges highly deleterious mutations more efficiently than other chromosomes. The evidence of stringent control over gene expression in this chromosome suggests that these parasites have adapted to mitigate the fitness cost associated with this ancient chromosomal duplication.

Exploring the Midwives' Experiences of Providing Delivery Care for Women with Suspected or Confirmed COVID-19 Infection: A Qualitative Study.

Introduction: Midwives were at the forefront of caring for pregnant women during the COVID-19 pandemic, therefore, the present study was conducted with the purpose of exploring midwives' experiences of providing delivery care for women with suspected or confirmed COVID-19 infection. Methods: In this qualitative study, 18 midwives working in the public hospitals affiliated with Guilan University of Medical Sciences (Iran). Who had experience in providing delivery care to women with suspected or confirmed COVID-19 infection were selected using purposive sampling. Data were collected via individual semi-structured interviews until reaching data saturation, and analyzed through conventional content analysis. Results: Data analysis led to the extraction of three main categories and six sub-categories. The main categories included "COVID-19 and organizational support" with two sub-categories including lack of resources/neglecting the role of midwives, "COVID-19 and positive achievements" with two sub-categories including professional resilience/turning threats into opportunities, "COVID-19 and informational support" with two sub-categories, including up-to-date training/empowering pregnant women. Conclusion: According to the findings, to realize and guarantee the provision of high-quality maternity care to pregnant women in dealing with epidemic diseases such as COVID-19 in the future, the attention of policymakers and healthcare service officials to the physical and psychological needs of midwives is necessary. Also, organizational and informational support, improving job satisfaction, and paying attention to the importance of midwives' role in the medical team are recommended. Moreover, empowering pregnant women during epidemic diseases is essential.

Practical Synthesis of 6-Amino-1-hydroxy-2,1-benzoxaborolane: A Key Intermediate of DNDI-6148.

Visceral leishmaniasis (VL), a parasitic, poverty-linked, neglected disease, is endemic across multiple regions of the world and fatal if untreated. There is an urgent need for a better and more affordable treatment for VL. DNDI-6148 is a promising drug candidate being evaluated for the treatment of VL; however, the current process for producing the key intermediate of DNDI-6148, 6-amino-1-hydroxy-2,1-benzoxaborolane, is expensive and difficult to scale up. Herein, we describe two practical approaches to synthesizing 6-amino-1-hydroxy-2,1-benzoxaborolane from inexpensive and readily available raw materials. Starting with 4-tolunitrile, the first approach is a five-step sequence involving a Hofmann rearrangement, resulting in an overall yield of 40%. The second approach utilizes 2-methyl-5-nitroaniline as the starting material and features borylation of aniline and continuous flow hydrogenation as the key steps, with an overall yield of 46%. Both routes bypass the nitration of 1-hydroxy-2,1-benzoxaborolane, which is challenging and expensive to scale. In particular, the second approach is more practical and scalable because of the mild operating conditions and facile isolation process.

Multiple Behavioral Risk Factors As Assets for Chronic Disease Prevention: Observations From Urban Primary Care Settings in Crete, Greece.

AIM: This study aimed to assess the health profile of patient-attendees visiting primary healthcare (PHC) practice settings in the midst of the COVID-19 pandemic and to explore the relationships between multiple behavioral risk factors (MBRFs) and consultation-driven health information. Multiple behavioral risk factors involve a variety of unhealthy behaviors that are associated with an increased prevalence of non-communicable diseases (NCDs). SUBJECTS AND METHODS: The study design was based on a dataset analysis, afterward exploring the feasibility and diagnostic capacity of respiratory morbidity aspects from a study previously conducted. The study dataset contained information regarding socio-demographic characteristics, health habits, clinical information, and reported comorbidities from 183 primary care patient-attendees. A categorical regression analysis was performed, using as a numeric variable the multiple MBRFs (clustering of 0 to four factors) in order to examine relationships with the basic and clinical characteristics of the patient-attendees. RESULTS: Based on this secondary analysis, it was found that the prevalence of MBRFs is quite common among patient-attendees visiting urban PHC facilities. The prevalence of current smoking, sleep deprivation, increased body weight, and medium/high perceived stress levels were 33.9%, 52.5%, 83.1%, and 35.0%, respectively. An increased occurrence of MBRFs might be significantly predicted by the lower age of patient-attendees (b = -0.221, p = 0.05), by the absence of gray hair at an early age (b = -0.144, p = 0.042), by the physical discomfort during activities (b = 0.191, p = 0.017), or by the lower oxygen saturation (b = -0.184, p = 0.004). Diabetes mellitus (25.1%) was the most prevalent condition, followed by bronchial asthma (18.6%) and depression (15.8%). CONCLUSIONS: Lower age, absence of premature hair whitening, physical discomfort during activities, and lower oxygen saturation are linked with an increased occurrence of MBRFs, leading to a neglected way of living. Those factors could be used to alert researchers, policymakers, and PHC professionals to act accordingly in order to prevent or early diagnose NCDs.

Current advances in serological and molecular diagnosis of Schistosoma mekongi infection.

Schistosomiasis, a neglected tropical disease, caused by blood flukes belonging to the genus Schistosoma; it persists as a public health problem in selected regions throughout Africa, South America, and Asia. Schistosoma mekongi, a zoonotic schistosome species endemic to the Mekong River in Laos and Cambodia, is one of the significant causes of human schistosomiasis along with S. japonicum, S. mansoni, S. haematobium and S. intercalatum. Since its discovery, S. mekongi infection has been highly prevalent in communities along the Mekong River. Although surveillance and control measures have shown success in recent years, more robust diagnostic tools are still needed to establish more efficient control and prevention strategies to achieve and sustain an elimination status. Diagnosis of S. mekongi infection still relies on copro-parasitological techniques, commonly made by Kato-Katz stool examination. Serological techniques such as enzyme-linked immunosorbent assay (ELISA) may also be applicable but in a limited setting. Targeted molecular and serological tools specific to the species, on the other hand, have been limited. This is due, in part, to the limited research and studies on the molecular biology of S. mekongi since genome information of this species has not yet been released. In this review, current advances, and gaps and limitations in the molecular and immunological diagnosis of S. mekongi are discussed.

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.

Unified Convolutional Sparse Transformer for Disease Diagnosis, Monitoring, Drug Development, and Therapeutic Effect Prediction from EEG Raw Data.

Electroencephalogram (EEG) analysis plays an indispensable role across contemporary medical applications, which encompasses diagnosis, monitoring, drug discovery, and therapeutic assessment. This work puts forth an end-to-end deep learning framework that is uniquely tailored for versatile EEG analysis tasks by directly operating on raw waveform inputs. It aims to address the challenges of manual feature engineering and the neglect of spatial interrelationships in existing methodologies. Specifically, a spatial channel attention module is introduced to emphasize the critical inter-channel dependencies in EEG signals through channel statistics aggregation and multi-layer perceptron operations. Furthermore, a sparse transformer encoder is used to leverage selective sparse attention in order to efficiently process long EEG sequences while reducing computational complexity. Distilling convolutional layers further concatenates the temporal features and retains only the salient patterns. As it was rigorously evaluated on key EEG datasets, our model consistently accomplished a superior performance over the current approaches in detection and classification assignments. By accounting for both spatial and temporal relationships in an end-to-end paradigm, this work facilitates a versatile, automated EEG understanding across diseases, subjects, and objectives through a singular yet customizable architecture. Extensive empirical validation and further architectural refinement may promote broader clinical adoption prospects.

Assessing the Incidence of Snakebites in Rural Gabon-A Community-Based, Cross-Sectional Pilot Survey.

Snakebite envenoming (SBE) is a neglected tropical disease (NTD). Community-based studies from sub-Saharan Africa are urgently required as data on the incidence are scarce. This study aimed to determine the lifetime prevalence of snakebites in rural Gabon by preparing the conduct of a larger regional survey. A cross-sectional community-based epidemiological survey in Sindara, Ngounie province, was conducted. Households were interviewed about the history of snakebites of household members to calculate lifetime prevalence. In addition, the average annual incidence rate per 100,000 over the last 5 years was calculated. A total of 771 inhabitants were enrolled, of which 5 (0.65%; 95% confidence interval (95% CI: 0.2-1.5%)) were victims of snakebites. Over the past 5 years, annual incidence was 77 bites per 100,000 (95% CI: 0-620). This study provides a first rough estimate of the incidence of SBE from rural central Gabon, demonstrating the importance of this NTD. Key Contribution: The estimated annual incidence of snakebites found was 77 per 100,000. Snakebites occurred mainly during agricultural activities.

The Rapid Emergence of Hypervirulent Klebsiella Species and Burkholderia pseudomallei as Major Health Threats in Southeast Asia: The Urgent Need for Recognition as Neglected Tropical Diseases.

The World Health Organization (WHO)'s list of neglected tropical diseases (NTDs) highlights conditions that are responsible for devastating health, social and economic consequences, and yet, they are overlooked and poorly resourced. The NTD list does not include conditions caused by Gram-negative bacilli (GNB). Infections due to GNB cause significant morbidity and mortality and are prevalent worldwide. Southeast Asia is a WHO region of low- and middle-income countries carrying the largest burden of NTDs. Two significant health threats in Southeast Asia are Burkholderia pseudomallei (causing melioidosis) and hypervirulent Klebsiella pneumoniae (HvKp). Both diseases have high mortality and increasing prevalence, yet both suffer from a lack of awareness, significant under-resourcing, incomplete epidemiological data, limited diagnostics, and a lack of evidence-based treatment. Emerging evidence shows that both melioidosis and HvKp are spreading globally, including in high-income countries, highlighting the potential future global threat they pose. In this article, we review both conditions, identifying current trends and challenges in Southeast Asia and areas for future research. We also argue that melioidosis and HvKp merit inclusion as NTDs, and that mandatory global surveillance and reporting systems should be established, and we make an urgent call for research to better understand, detect, and treat these neglected diseases.

Global, Regional and National Burden of Human Cystic Echinococcosis from 1990 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Cystic echinococcosis (CE) is a neglected tropical parasitic disease that poses huge disease, social and economic burdens worldwide; however, there has been little knowledge on the global morbidity, mortality and disability-adjusted life years (DALYs) of CE until now. This study aimed to collect the most up-to-date data about the global, regional and national disease burden due to CE from 1990 to 2019 and to project trends in the next 10 years. METHODS: We measured the global, regional and national morbidity, mortality and DALYs of CE from 1990 to 2019 based on the Global Burden of Disease Study 2019 (GBD 2019) data, and we examined the correlation between socioeconomic development levels and the disease burden of CE. In addition, the disease burden due to CE was projected from 2020 to 2030. RESULTS: The age-standardized incidence rate (ASIR) of CE reduced from 2.65/105 [95% UI: (1.87/105 to 3.7/105)] in 1990 to 2.6/105 [95% UI: (1.72/105 to 3.79/105)] in 2019 (EAPC = -0.18%). The number of deaths, DALYs, age-standardized mortality rate (ASMR) and age-standardized DALY rate due to CE all showed a tendency to decline from 1990 to 2019. A higher disease burden of CE was measured in women than in men in 2019. There was a significant difference in the ASMR of CE by region according to the socio-demographic index (SDI), and lower burdens of CE were estimated in high-SDI regions. The global ASIR of CE is projected to decline from 2020 to 2030; however, the ASMR and age-standardized DALY rate are projected to rise. CONCLUSIONS: The global burden of CE remains high, and it is recommended that more health resources are allocated to low-SDI regions, women and the elderly aged 55 to 65 years to reduce the disease burden of CE.

A panel of recombinant Leishmania donovani cell surface and secreted proteins identifies LdBPK_323600.1 as a serological marker of symptomatic infection.

Visceral leishmaniasis is a deadly infectious disease and is one of the world's major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test. These tests, however, are either difficult to perform in the field (DAT) or lack specificity in some endemic regions (rK39), making the development of new tests a research priority. The availability of Leishmania spp. genomes presents an opportunity to identify new diagnostic targets. Here, we use genome data and a mammalian protein expression system to create a panel of 93 proteins consisting of the extracellular ectodomains of the Leishmania donovani cell surface and secreted proteins. We use these panel and sera from murine experimental infection models and natural human and canine infections to identify new candidates for serological diagnosis. We observed a concordance between the most immunoreactive antigens in different host species and transmission settings. The antigen encoded by the LdBPK_323600.1 gene can diagnose Leishmania infections with high sensitivity and specificity in patient cohorts from different endemic regions including Bangladesh and Ethiopia. In longitudinal sampling of treated patients, we observed reductions in immunoreactivity to LdBPK_323600.1 suggesting it could be used to diagnose treatment success. In summary, we have identified new antigens that could contribute to improved serological diagnostic tests to help control the impact of this deadly tropical infectious disease. IMPORTANCE: Visceral leishmaniasis is fatal if left untreated with patients often displaying mild and non-specific symptoms during the early stages of infection making accurate diagnosis important. Current methods for diagnosis require highly trained medical staff to perform highly invasive biopsies of the liver or bone marrow which pose risks to the patient. Less invasive molecular tests are available but can suffer from regional variations in their ability to accurately diagnose an infection. To identify new diagnostic markers of visceral leishmaniasis, we produced and tested a panel of 93 proteins identified from the genome of the parasite responsible for this disease. We found that the pattern of host antibody reactivity to these proteins was broadly consistent across naturally acquired infections in both human patients and dogs, as well as experimental rodent infections. We identified a new protein called LdBPK_323600.1 that could accurately diagnose visceral leishmaniasis infections in humans.

Review: Opportunities and challenges for the genetic selection of dairy calf disease traits.

Interest in dairy cow health continues to grow as we better understand health's relationship with production potential and animal welfare. Over the past decade, efforts have been made to incorporate health traits into national genetic evaluations. However, they have focused on the mature cow, with calf health largely being neglected. Diarrhoea and respiratory disease comprise the main illnesses with regard to calf health. Conventional methods to control calf disease involve early separation of calves from the dam and housing calves individually. However, public concern regarding these methods, and growing evidence that these methods may negatively impact calf development, mean the dairy industry may move away from these practices. Genetic selection may be a promising tool to address these major disease issues. In this review, we examined current literature for enhancing calf health through genetics and discussed alternative approaches to improve calf health via the use of epidemiological modelling approaches, and the potential of indirectly selecting for improved calf health through improving colostrum quality. Heritability estimates on the observed scale for diarrhoea ranged from 0.03 to 0.20, while for respiratory disease, estimates ranged from 0.02 to 0.24. The breadth in these ranges is due, at least in part, to differences in disease prevalence, population structure, data editing and models, as well as data collection practices, which should be all considered when comparing literature values. Incorporation of epidemiological theory into quantitative genetics provides an opportunity to better determine the level of genetic variation in disease traits, as it accounts for disease transmission among contemporaries. Colostrum intake is a major determinant of whether a calf develops either respiratory disease or diarrhoea. Colostrum traits have the advantage of being measured and reported on a continuous scale, which removes the issues classically associated with binary disease traits. Overall, genetic selection for improved calf health is feasible. However, to ensure the maximum response, first steps by any industry members should focus efforts on standardising recording practices and encouragement of uploading information to genetic evaluation centres through herd management software, as high-quality phenotypes are the backbone of any successful breeding programme.