The Cotard Delusion in a Patient With Neuropsychiatric Systemic Lupus Erythematosus: The Challenges of Autoimmune Psychosis.

The clinical features of neuropsychiatric systemic lupus erythematosus (NPSLE) are heterogeneous. Furthermore, therapeutic decision-making for NPSLE depends on the recognition of clinical syndromes that have not been sufficiently studied. This report describes the case of a 36-year-old woman with NPSLE who exhibited severe cognitive dysfunction and affective psychosis with persistent nihilistic delusions such as those described in the Cotard delusion. The patient insisted for several months that she was already dead. CSF analysis showed elevated levels of anti-ribosomal P antibodies and a positive determination of oligoclonal bands. Additionally, 18F -FDG PET/CT imaging revealed severe bilateral frontal hypermetabolism suggestive of brain inflammation and occipital hypometabolism. Results from the Systematic Lupus Erythematosus Disease Activity Index 2000 and the Systemic Lupus Erythematosus Disease Activity Score were consistent with an active state of the immunological disease. We then determined by an algorithm that this neuropsychiatric event could be attributed to the activity of the underlying immunological disease. Despite immunosuppressive and symptomatic treatment, only a partial improvement in cognition was achieved. The psychopathological features of the Cotard delusion remained unchanged 4 months after onset. However, we observed rapid remission of affective psychosis and significant improvement in cognition following electroconvulsive therapy. Subsequent follow-up examinations showed a sustained remission. This case describes a protracted form of the Cotard delusion, the diagnostic challenges that arise in the context of SLE, and treatment dilemmas that necessitate collaboration between neurology, psychiatry, and rheumatology.

Immunization of recombinant NS3 protein (protease region) of dengue virus induces high levels of CTLA-4 and apoptosis in splenocytes of BALB/c mice.

DENV infection outcomes depend on the host's variable expression of immune receptors and mediators, leading to either resolution or exacerbation. While the NS3 protein is known to induce robust immune responses, the specific impact of its protease region epitopes remains unclear. This study investigated the effect of recombinant NS3 protease region proteins from all four DENV serotypes on splenocyte activation in BALB/c mice (n = 5/group). Mice were immunized with each protein, and their splenocytes were subsequently stimulated with homologous antigens. We measured the expression of costimulatory molecules (CD28, CD80, CD86, CD152) by flow cytometry, along with IL-2 production, CD25 expression, and examined the antigen-specific activation of CD4 + and CD8 + T cells. Additionally, the expression of IL-1, IL-10, and TGF-ß1 in splenocytes from immunized animals was assessed. Apoptosis was evaluated using Annexin V/PI staining and DNA fragmentation analysis. Stimulation of splenocytes from immunized mice triggered apoptosis (phosphatidylserine exposure and caspase 3/7 activation) and increased costimulatory molecule expression, particularly CD152. Low IL-2 production and low CD25 expression, as well as sustained expression of the IL-10 gene. These results suggest that these molecules might be involved in mechanisms by which the NS3 protein contributes to viral persistence and disease pathogenesis.

CD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis.

American Tegumentary Leishmaniasis (ATL) is a disease of high severity and incidence in Brazil, in addition to being a worldwide concern in public health. Leishmania amazonensis is one of the etiological agents of ATL, and the inefficiency of control measures, associated with the high toxicity of the treatment and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present study proposes to elaborate a chimeric protein (rChiP), based on the fusion of multiple epitopes of CD4+/CD8+ T cells, identified in the immunoproteome of the parasites L. amazonensis and L. braziliensis. The designed chimeric protein was tested in the L. amazonensis murine model of infection using the following formulations: 25 µg of the rChiP in saline (rChiP group) and 25 µg of the rChiP plus 25 µg of MPLA-PHAD® (rChiP+MPLA group). After completing immunization, CD4+ and CD8+ T cells, stimulated with SLa-Antigen or rChiP, showed an increased production of nitric oxide and intracytoplasmic pro-inflammatory cytokines, in addition to the generation of central and effector memory T cells. rChiP and rChiP+MPLA formulations were able to promote an effective protection against L. amazonensis infection determined by a reduction in the development of skin lesions and lower parasitic burden. Reduction in the development of skin lesions and lower parasitic burden in the vaccinated groups were associated with an increase of nitrite, CD4+/CD8+IFN-γ+TNF-α+ and CD4+/CD8+CD44highCD62Lhigh/low T cells, IgGTotal, IgG2a, and lower rates of IgG1 and CD4+/CD8+IL-10+. This data suggests that proposed formulations could be considered potential tools to prevent ATL.

Identification of differentially expressed genes, pathways, and immune infiltration in diabetes.

This study aimed to perform exhaustive bioinformatic analysis by using GSE29221 micro-array maps obtained from healthy controls and Type 2 Diabetes (T2DM) patients. Raw data are downloaded from the Gene Expression Omnibus database and processed by the limma package in R software to identify Differentially Expressed Genes (DEGs). Gene ontology functional analysis and Kyoto Gene Encyclopedia and Genome Pathway analysis are performed to determine the biological functions and pathways of DEGs. A protein interaction network is constructed using the STRING database and Cytoscape software to identify key genes. Finally, immune infiltration analysis is performed using the Cibersort method. This study has implications for understanding the underlying molecular mechanism of T2DM and provides potential targets for further research.

Brazilian consensus recommendations on the diagnosis and treatment of autoimmune encephalitis in the adult and pediatric populations.

BACKGROUND: Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis. OBJECTIVE: With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method. METHODS: A total of 25 panelists, including adult and child neurologists, participated in the study. RESULTS: The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSION: The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system.

ANTECEDENTES: Encefalites autoimunes (EAIs) são um grupo de doenças inflamatórias caracterizadas pela presença de anticorpos contra antígenos neuronais e gliais, que ocasionam sintomas psiquiátricos subagudos, queixas de memória e distúrbios anormais do movimento. A maioria dos pacientes é jovem, e o atraso no tratamento está associado a pior prognóstico. OBJETIVO: Com o apoio da Academia Brasileira de Neurologia (ABN) e da Sociedade Brasileira de Neurologia Infantil (SBNI), desenvolvemos um consenso sobre o diagnóstico e o tratamento da EAIs no Brasil utilizando a metodologia Delphi. MéTODOS: Um total de 25 especialistas, incluindo neurologistas e neurologistas infantis, foram convidados a participar. RESULTADOS: Os especialistas concordaram que os pacientes com critérios de possíveis EAIs devem ser submetidos ao rastreio de anticorpos antineuronais no soro e no líquido cefalorraquidiano (LCR) por meio das técnicas de ensaio baseado em tecidos (tissue-based assay, TBA, em inglês) e ensaio baseado em células (cell-based assay, CBA, em inglês). As crianças também devem ser submetidas ao rastreio de de anticorpo contra a glicoproteína da mielina de oligodendrócitos (anti-myelin oligodendrocyte glycoprotein, anti-MOG, em inglês). O tratamento deve ser iniciado dentro das primeiras 4 semanas dos sintomas, sendo as opções de primeira linha metilprednisolona combinada com imunoglobulina intravenosa (IGIV) ou plasmaférese. O tratamento de segunda linha inclui rituximabe e ciclofosfamida. Bortezomib e tocilizumab são opções de tratamento de terceira linha. A maioria das crises epilépticas nas EAIs são sintomáticas, e os fármacos anticrise podem ser desmamadas após a fase aguda. Em relação à encefalite antirreceptor de N-metil-D-aspartato (anti-N-methyl-D-aspartate receptor, anti-NMDAR, em inglês), os especialistas concordaram que agentes imunossupressores orais não devem ser usados. Os pacientes devem ser avaliados na fase aguda e pós-aguda mediante escalas funcionais e cognitivas, como Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Modified Rankin Scale (mRS), e Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSãO: Esta pesquisa oferece evidências tangíveis do manejo efetivo de pacientes com EAIs no sistema de saúde Brasileiro.

α-IRAK-4 Suppresses the Activation of RANK/RANKL Pathway on Macrophages Exposed to Endodontic Microorganisms.

Periapical lesions are common pathologies affecting the alveolar bone, often initiated by intraradicular lesions resulting from microbial exposure to dental pulp. These microorganisms trigger inflammatory and immune responses. When endodontic treatment fails to eliminate the infection, periapical lesions persist, leading to bone loss. The RANK/RANKL/OPG pathway plays a crucial role in both the formation and the destruction of the bone. In this study, the objective was to inhibit the RANK/RANKL pathway in vitro within exposed Thp-1 macrophages to endodontic microorganisms, specifically Enterococcus faecalis, which was isolated from root canals of 20 patients with endodontic secondary/persistent infection, symptomatic and asymptomatic, and utilizing an α-IRAK-4 inhibitor, we introduced endodontic microorganisms and/or lipoteichoic acid from Streptococcus spp. to cellular cultures in a culture plate, containing thp-1 cells and/or PBMC from patients with apical periodontitis. Subsequently, we assessed the percentages of RANK+, RANKL+, and OPG+ cells through flow cytometry and measured the levels of several inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) in the cellular culture supernatant through a CBA kit and performed analysis by flow cytometry. A significant difference was observed in the percentages of RANK+RANKL+, OPG+ RANKL+ cells in thp-1 cells and PBMCs from patients with apical periodontitis. The findings revealed significant differences in the percentages of the evaluated cells, highlighting the novel role of the IRAK-4 inhibitor in addressing this oral pathology, apical periodontitis, where bone destruction is observed.

Single-cell transcriptomic analysis of B cells reveals new insights into atypical memory B cells in COVID-19.

Here, we performed single-cell RNA sequencing of S1 and receptor binding domain protein-specific B cells from convalescent COVID-19 patients with different clinical manifestations. This study aimed to evaluate the role and developmental pathway of atypical memory B cells (MBCs) in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The results revealed a proinflammatory signature across B cell subsets associated with disease severity, as evidenced by the upregulation of genes such as GADD45B, MAP3K8, and NFKBIA in critical and severe individuals. Furthermore, the analysis of atypical MBCs suggested a developmental pathway similar to that of conventional MBCs through germinal centers, as indicated by the expression of several genes involved in germinal center processes, including CXCR4, CXCR5, BCL2, and MYC. Additionally, the upregulation of genes characteristic of the immune response in COVID-19, such as ZFP36 and DUSP1, suggested that the differentiation and activation of atypical MBCs may be influenced by exposure to SARS-CoV-2 and that these genes may contribute to the immune response for COVID-19 recovery. Our study contributes to a better understanding of atypical MBCs in COVID-19 and the role of other B cell subsets across different clinical manifestations.

Calcium-dependent HLA-DQ epitope revealed by EDTA mediated inhibition of antibody reactions in the Luminex single antigen bead assay.

Complement mediated interference with the detection of antibodies targeting HLA is a known limitation of the single antigen bead (SAB) Luminex assay. Ethylenediaminetetraacetic acid (EDTA) is currently the serum treatment of choice in most histocompatibility laboratories to block complement activation by chelating calcium. The purpose of this study was to investigate a serum with an antibody reactivity to HLA-DQ6, 7, 8 and 9 molecules, in the Luminex SAB assay, that was inhibited by treatment with EDTA. Serum was from a 55-year-old highly sensitised female renal transplant candidate that contained, among others, antibodies to an epitope containing the 74EL eplet, shared by HLA-DQ6, DQ7, DQ8 and DQ9 molecules. Serum samples were treated with EDTA, dithiothreitol (DTT), or heat prior to testing by SAB assay. EDTA-treated serum was also tested after the addition of calcium chloride (CaCl2). HLA-DQ-specific antibodies were isolated by adsorption/elution method using three informative donor cells and were tested in the absence or presence of EDTA. The antibody reactivity against HLA-DQ6, DQ7, DQ8 and DQ9 in the SAB assay was significantly inhibited by treating serum and eluates with EDTA and was restored by addition of CaCl2. The study represents the first description of a calcium-dependent epitope in HLA molecules. The relevance of this finding is that the treatment of sera with EDTA could lead to false-negative reactions in the SAB assay, which may compromise virtual crossmatching.

Unveiling the Enigmatic nature of six neglected Amazonian Leishmania (Viannia) species using the hamster model: Virulence, Histopathology and prospection of LRV1.

American tegumentary leishmaniasis (ATL) is highly endemic in the Amazon basin and occurs in all South American countries, except Chile and Uruguay. Most Brazilian ATL cases are due to Leishmania (Viannia) braziliensis, however other neglected Amazonian species are being increasingly reported. They belong to the subgenus L. (Viannia) and information on suitable models to understand immunopathology are scarce. Here, we explored the use of the golden hamster Mesocricetus auratus and its macrophages as a model for L. (Viannia) species. We also studied the interaction of parasite glycoconjugates (LPGs and GIPLs) in murine macrophages. The following strains were used: L. (V.) braziliensis (MHOM/BR/2001/BA788), L. (V.) guyanensis (MHOM/BR/85/M9945), L. (V.) shawi (MHOM/BR/96/M15789), L. (V.) lindenbergi (MHOM/BR/98/M15733) and L. (V.) naiffi (MDAS/BR/79/M5533). In vivo infections were initiated by injecting parasites into the footpad and were followed up at 20- and 40-days PI. Parasites were mixed with salivary gland extract (SGE) from wild-captured Nyssomyia neivai prior to in vivo infections. Animals were euthanized for histopathological evaluation of the footpads, spleen, and liver. The parasite burden was evaluated in the skin and draining lymph nodes. In vitro infections used resident peritoneal macrophages and THP-1 monocytes infected with all species using a MOI (1:10). For biochemical studies, glycoconjugates (LPGs and GIPLs) were extracted, purified, and biochemically characterized using fluorophore-assisted carbohydrate electrophoresis (FACE). They were functionally evaluated after incubation with macrophages from C57BL/6 mice and knockouts (TLR2-/- and TLR4-/-) for nitric oxide (NO) and cytokine/chemokine production. All species, except L. (V.) guyanensis, failed to generate evident macroscopic lesions 40 days PI. The L. (V.) guyanensis lesions were swollen but did not ulcerate and microscopically were characterized by an intense inflammatory exudate. Despite the fact the other species did not produce visible skin lesions there was no or mild pro-inflammatory infiltration at the inoculation site and parasites survived in the hamster skin/lymph nodes and even visceralized. Although none of the species caused severe disease in the hamster, they differentially infected peritoneal macrophages in vitro. LPGs and GIPLs were able to differentially trigger NO and cytokine production via TLR2/TLR4 and TLR4, respectively. The presence of a sidechain in L. (V.) lainsoni LPG (type II) may be responsible for its higher proinflammatory activity. After Principal Component analyses using all phenotypic features, the clustering of L. (V.) lainsoni was separated from all the other L. (Viannia) species. We conclude that M. auratus was a suitable in vivo model for at least four dermotropic L. (Viannia) species. However, in vitro studies using peritoneal cells are a suitable alternative for understanding interactions of the six L. (Viannia) species used here. LRV1 presence was found in L. (V.) guyanensis and L. (V.) shawi with no apparent correlation with virulence in vitro and in vivo. Finally, parasite glycoconjugates were able to functionally trigger various innate immune responses in murine macrophages via TLRs consistent with their inflammatory profile in vivo.

Prevalence and factors associated with hepatitis B susceptibility among men who sex with men on HIV pre-exposure prophylaxis in Northeastern Brazil: a cross-sectional study.

BACKGROUND: This study aimed to determine the prevalence and factors associated with susceptibility to hepatitis B virus (HBV) among cisgender men who have sex with men (MSM) on HIV pre-exposure prophylaxis (PrEP) in Northeastern Brazil. METHODS: This was a cross-sectional, analytical study conducted between September 2021 and June 2023. Participants underwent structured interviews to collect sociodemographic and clinical information, including hepatitis B vaccination history, HIV PrEP use and sexual health history. Blood samples were collected for hepatitis B serologic testing: HBV surface antigen (HBsAg), HBV surface antibody (anti-HBs), total and IgM HBV core antibody (anti-HBc). HBV susceptibility was defined as nonreactive results for all these serological markers. RESULTS: A total of 287 participants were enrolled into the study. The median age of the individuals was 31 years (interquartile range: 27; 36). HBV susceptibility was found in 58 out 286 individuals (20.3%; 95% CI: 15.9-25.2). Seventy-six percent of the participants reported completing the three-dose hepatitis B vaccine schedule. Susceptibility was significantly associated with a monthly income ≤ 5 minimum wages (PR: 2.02; 95% CI: 1.01-4.05), lack of complete hepatitis B vaccination schedule (PR: 4.52; 95% CI: 2.89-7.06), initiation of HIV PrEP (PR: 2.18; 95% CI: 1.21-3.94), duration of six months of HIV PrEP (PR: 2.16; 95% CI: 1.19-3.91), absence of tattoos (PR: 1.55; 95% CI: 1.00-2.40) and no history of sexually transmitted infections (PR: 1.65; 95% CI: 1.07-2.54). CONCLUSION: Our findings highlight the significant burden of HBV susceptibility among MSM on HIV PrEP in Northeastern Brazil. Socioeconomic factors, vaccination status, PrEP use and sexual health behaviors play critical roles in determining susceptibility to HBV. Integrating hepatitis B screening and vaccination into PrEP services is critical for identifying and addressing HBV susceptibility among MSM. Interventions aimed at increasing vaccination coverage and promoting safer sexual practices are essential for mitigating the burden of HBV infection in this population.

Immunogenicity of a pentavalent recombinant Escherichiacoli bacterin against enterotoxemia and botulism in sheep.

INTRODUCTION: Producing commercial bacterins/toxoids against Clostridium spp. is laborious and hazardous. Conversely, developing prototype vaccines using purified recombinant toxoids, though safe and effective, is both laborious and costly for application in production animals. OBJECTIVE: Considering that inactivated recombinant Escherichiacoli (bacterin) is a simple, cost-effective, and to be safe solution, we evaluated, for the first time, a pentavalent formulation of recombinant bacterins containing the alpha, beta, and epsilon toxins of Clostridiumperfringens and C and D neurotoxins of Clostridiumbotulinum in sheep. METHODS: Subcutaneously, 18 Texel sheep received two doses (200 µg of each antigen) of recombinant bacterin (n = 7) or purified recombinant antigens (n = 6) on days 0 and 28, while the control group (n = 5) did not receive an immunization. Sera samples from days 0 (before the 1st dose), 28 (before the 2nd dose), and 56, 84, and 112 were used for measuring IgG (indirect ELISA) and neutralizing antibodies (mouse serum neutralization). RESULTS: Both formulations induced significant levels of IgG against all five toxins (p < 0.05) up to day 112, with peaks at days 28 and 56 post-immunization. The expected booster effect occurred only for the botulinum toxins. The neutralizing antibody titers were satisfactory against ETX (≥2 IU/ml for both formulations) and BoNT-D [5 IU/ml (bacterin) and 10 IU/ml (purified)]. CONCLUSION: While adjustments are required, the recombinant bacterin platform holds great potential for polyvalent vaccines due to its straightforward, safe, and cost-effective production, establishing it as a user-friendly technology for the veterinary immunobiological industry.

Development of two recombinant vaccines against Clostridioides difficile infection and immunogenicity in pregnant sows and neonatal piglets.

INTRODUCTION: Clostridioides difficile is the main cause of antibiotic-associated diarrhea in humans and is a major enteropathogen in several animal species. In newborn piglets, colonic lesions caused by C. difficile A and B toxins (TcdA and TcdB, respectively) cause diarrhea and significant production losses. OBJECTIVE: The present study aimed to develop two recombinant vaccines from immunogenic C-terminal fragments of TcdA and TcdB and evaluate the immune response in rabbits and in breeding sows. Two vaccines were produced: bivalent (rAB), consisting of recombinant fragments of TcdA and TcdB, and chimeric (rQAB), corresponding to the synthesis of the same fragments in a single protein. Groups of rabbits were inoculated with 10 or 50 µg of proteins adjuvanted with aluminum or 0.85 % sterile saline in a final volume of 1 mL/dose. Anti-TcdA and anti-TcdB IgG antibodies were detected in rabbits and sows immunized with both rAB and rQAB vaccines by ELISA. The vaccinated sows were inoculated intramuscularly with 20 µg/dose using a prime-boost approach. RESULTS: Different antibody titers (p ≤ 0.05) were observed among the vaccinated groups of sows (rAB and rQAB) and control. Additionally, newborn piglets from vaccinated sows were also positive for anti-TcdA and anti-TcdB IgGs, in contrast to control piglets (p ≤ 0.05). Immunization of sows with the rQAB vaccine conferred higher anti-TcdA and anti-TcdB responses in piglets, suggesting the superiority of this compound over rAB. CONCLUSION: The synthesized recombinant proteins were capable of inducing antibody titers against C. difficile toxins A and B in sows, and were passively transferred to piglets through colostrum.

Novel insights into the application of recombinant mutated phospholipases D as antigens for developing new strategies against Loxoscelism.

Loxoscelism is the pathological condition triggered by a brown spider bite. The venom of these spiders is rich in phospholipases D (PLDs), which can induce virtually all local and systemic manifestations. Recombinant mutated PLDs from clinically relevant Loxosceles species in South America have been investigated as potential antigens to develop novel therapeutic strategies for loxoscelism. However, certain gaps need to be addressed before a clinical approach can be implemented. In this study, we examined the potential of these recombinant mutated PLDs as antigens by testing some variations in the immunization scheme. Furthermore, we evaluated the efficacy of the produced antibodies in neutralizing the nephrotoxicity and sphingomyelinase activity of brown spider venoms. Our findings indicate that the number of immunizations has a greater impact on the effectiveness of neutralization compared to the amount of antigen. Specifically, two or three doses were equally effective in reducing dermonecrosis and edema. Additionally, three immunizations proved to be more effective in neutralizing mice lethality than one or two. Moreover, immunizations mitigated the signs of kidney injury, a crucial aspect given that acute renal failure is a serious systemic complication. In vitro inhibition of the sphingomyelinase activity of Loxosceles venoms, a key factor in vivo toxicity, was nearly complete after incubation with antibodies raised against these antigens. These findings underscore the importance of implementing an effective immunization scheme with multiple immunizations, without the need for high antigen doses, and enhances the spectrum of neutralization exhibited by antibodies generated with these antigens. In summary, these results highlight the strong potential of these antigens for the development of new therapeutic strategies against cutaneous and systemic manifestations of loxoscelism.

Attitudes of pregnant women in the Dominican Republic towards a future maternal Group B Streptococcus vaccine.

INTRODUCTION: Current protocols aim to prevent some infant GBS infection through screening and peripartum antibiotics, however such strategies cannot be widely implemented in resource-limited settings. On the other hand, maternal vaccines in development against Group B Streptococcus (GBS) can provide a feasible universal approach. The success of any vaccine will depend on uptake in the population. Rates of maternal GBS colonization in the Dominican Republic (DR) and Caribbean region are among the highest in the world, but little is known about attitudes towards maternal vaccines in this region. METHODS: A cross-sectional, multicenter, mixed-methodology survey evaluated facilitators and barriers to maternal immunization and acceptability of a hypothetical Group B Streptococcus vaccine among pregnant women in three hospitals in the DR. RESULTS: Six-hundred and fifty women completed the survey of whom 85 % had never heard of GBS. Following receipt of information about GBS and a vaccine, 94 % of women stated that they would be likely or very likely to receive a vaccine. Being 18 years or younger was associated with a lower likelihood of GBS vaccine receipt (AOR 0.32, 95 % CI 0.14-0.69). Being born in the DR was associated with a higher likelihood of GBS vaccine receipt (AOR 2.73, 95 % CI 1.25-5.97). Among women who were unlikely to receive the vaccine, uncertainty about potential harm from a novel vaccine was the prominent theme elicited from free text responses. CONCLUSION: There was a high level of acceptance of a future GBS vaccine among this sample of pregnant women in the DR. However, knowledge of vaccines and vaccine-preventable diseases was low, and most women had concerns about the safety of new vaccines. Interventions that strengthen existing maternal immunisation infrastructures, including increasing education of pregnant women about vaccines, will aid the successful implementation of a future GBS vaccine.

Spatial and seasonal distribution of Leptospira spp. seropositive horses in the Northeast region of Brazil.

Leptospirosis is an anthropozoonosis of economic and public health importance, caused by bacteria of the genus Leptospira. Horses are deemed important in its transmission chain due to their proximity to humans, and because the species is often asymptomatic, making these animals potential silent reservoirs. In this context, the objectives of this study were to determine the prevalence of seropositive horses for Leptospira spp., and to identify the presence of Leptospira spp. serogroups and antibody titers, the occurrence of areas with higher density of infection cases and demographic characteristics associated with seropositivity in the states of Paraíba (PB), Pernambuco (PE), Rio Grande do Norte (RN) and Ceará (CE), in the Northeast region of Brazil, during rainy (May and June) and dry (October and November) seasons from 2017 to 2019. Using the microscopic agglutination test (MAT), 1152 equine serum samples from 225 municipalities were analyzed. Anti-Leptospira antibodies were detected in 23.9 % (95 % CI= 21.4 - 26.3 %) of the samples in the three-year period, with a frequency of 30.4 % (95 % CI= 26.7 - 34.2 %) during the rainy period (with greater emphasis on the Ballum serogroup) and 17.4 % (95 % CI= 14.3 - 20.5 %) in the dry period (with greater emphasis on the Sejroe serogroup). Age of horses ≥ 6 years (6-10 years, 11-15 years and ≥ 16 years), rainy season, and animal belonging to Pernambuco state were factors with higher seropositivities. Regarding spatial distribution, a higher percentage of seropositive animals was observed in Pernambuco (P < 0.05), in interstate border areas, and large urban centers, with a spatial cluster detected in the dry season of 2018 with relative risk of 2.8 (P = 0.049) times higher in municipalities within the cluster. It is suggested that measures for controlling rodents and contact with wild animals in equine farming, both in rainy and dry periods, combined with care regarding the use of pastures shared with cattle and the adoption of immunoprophylaxis are important in preventing and controlling leptospirosis in horses in the Northeast region of Brazil.

Deletions of ttrA and pduA genes in Salmonella enterica affect survival within chicken-derived HD-11 macrophages.

In mammals, enteric salmonellas can use tetrathionate (ttr), formed as a by-product from the inflammatory process in the intestine, as electron acceptor in anaerobic respiration, and it can fuel its energy metabolism by degrading the microbial fermentation product 1,2-propanediol. However, recent studies have shown that this mechanism is not important for Salmonella infection in the intestine of poultry, while it prolongs the persistence of Salmonella at systemic sites in this species. In the current study, we show that ΔttrApduA strains of Salmonella enterica have lower net survival within chicken-derived HD-11 macrophages, as CFU was only 2.3% (S. Enteritidis ΔttrApduA), 2.3% (S. Heidelberg ΔttrApduA), and 3.0% (S. Typhimurium ΔttrApduA) compared to wild-type strains after 24 h inside HD-11 macrophage cells. The difference was not related to increased lysis of macrophages, and deletion of ttrA and pduA did not impair the ability of the strains to grow anaerobically. Further studies are indicated to determine the reason why Salmonella ΔttrApduA strains survive less well inside macrophage cell lines.

Navigating the landscape of food allergies: Insights and perspectives from the AMCP Market Insights Program.

AMCP convened a panel of clinical and managed care experts to identify insights regarding the prevalence, clinical manifestations, and management approaches for immunoglobulin E-mediated food allergies. This article aims to summarize expert perspectives on health care system challenges and areas of agreement concerning the management of food allergies, and to advance payers' understanding of their role in supporting health care for patients with food allergies. Food allergy management requires dietary modification and is associated with significant patient and caregiver burdens. Emerging therapies provide hope for those living with food allergies but will likely lead to a rise in health plan pharmacy expenses. In considering the value of new treatments, it is important to consider the total cost of care and the value of preventing anaphylaxis and enhancing the patient's quality of life. Several challenges remain in identifying the appropriate patient population for treatment with newer agents and in optimizing treatment outcomes. Addressing health disparities will require standardized clinical protocols, better access to specialized allergy care, and management of comorbid conditions.

Immunoproteomic profile of Malus domestica in Mexican pediatric patients. Evidence of new allergen prospects.

Background: Apple (Malus domestica) is a fruit commonly associated with allergic oral symptoms in the Mexican pediatric population; however, knowledge of its allergenic proteins is limited. This information is crucial as sensitization frequencies to specific allergens can vary among different populations. The main allergic symptomatology before apple ingestion derives from primary sensitizations induced by pollen, promoting cross-reactivity with the main allergenic protein of apple. Therefore, this study aims to identify new potential sensitizing proteins to apple using immunoproteomic techniques. Methods: We collected serum samples from 14 pediatric patients with confirmed immunoglobulin E (IgE)-mediated apple allergy and used these samples to assess immunoreactivity to apple protein extracts through 2D-western blot assays. The spots corresponding to the 2D-SDS-PAGE were analyzed using nanoLC-MS/MS. Results: We identified 11 non-redundant proteins, including Mal d 2 and Mal d 1, the latter showing a high frequency of sensitization (79%) in our patients, and being considered the main apple allergenic protein. The remaining identified proteins have not been previously described as apple allergens in the International Union of Immunological Societies databases. However, three of these may be categorized as pan-allergens. Conclusions: This study shows evidence that the repertoire of apple allergens in the Mexican population could differ from those reported internationally, highlighting the importance of studies in different countries to improve the certainty of allergy diagnosis and allow the implementation of precision medicine.

Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-ß Antibodies.

Type I IFNs play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-ß Abs from PBMCs of individuals treated with IFN-α or IFN-ß, harboring confirmed neutralizing Abs. Clones AH07856 and AH07857 were identified as neutralizing anti-IFN-α-specific with inhibition against IFN-α2a, -α2b, and -αK subtypes. Clones AH07859 and AH07866 were identified as neutralizing anti-IFN-ß1a-specific signaling and able to block lipopolysaccharide or S100 calcium-binding protein A14-induced IFN-ß signaling effects. Cloned Abs bind rhesus but not murine IFNs. The specificity of inhibition between IFN-α and IFN-ß suggests potential for diverse research and clinical applications.

Regulatory T Cell Insufficiency in Autoimmune Diabetes Is Driven by Selective Loss of Neuropilin-1 on Intraislet Regulatory T Cells.

Approaches to reverse or limit regulatory T cell (Treg) insufficiency are of great interest for development of immunotherapeutic treatments for autoimmune patients, including type 1 diabetes. Treg insufficiency is heavily implicated in the progression of autoimmune diabetes in the NOD mouse model and is characterized by defects in Treg numbers, development, and/or function. Utilizing a Treg-centric screen, we show that intraislet Tregs have a uniquely dysfunctional phenotype, hallmarked by an almost complete lack of neuropilin-1 (Nrp1), a cell surface receptor required to maintain Treg stability. Intraislet Nrp1- Tregs exhibit hallmark features of fragility, including reduced suppressive capacity, decreased CD73 and Helios, and increased Rorγt and Tbet. Intraislet Nrp1- Tregs also exhibit decreased Foxp3 expression on a per cell basis, suggesting that Nrp1 may also be required for long-term Treg stability. Mechanistically, Treg-restricted augmentation of Nrp1 expression limited the onset of autoimmune diabetes in NOD mice suggesting that Nrp1 critically impacts intraislet Treg function. Transcriptional analysis showed that Nrp1 restoration led to an increase in markers and pathways of TCR signaling, survival, and suppression, and when Nrp1 protein expression is examined by cellular indexing of transcriptomes and epitopes by sequencing, significant differences were observed between Nrp1+ and Nrp1- Tregs in all tissues, particularly in markers of Treg fragility. This translated into substantive differences between Nrp1+ and Nrp1- Tregs that afforded the former with a competitive advantage in the islets. Taken together, these data suggest that maintenance of Nrp1 expression and signaling on Tregs limits diabetes onset and may serve as a strategy to combat Treg insufficiency in autoimmune disease.