Asthma as a risk factor and allergic rhinitis as a protective factor for COVID-19 severity: a case-control study.

PURPOSE: The COVID-19 pandemic has resulted in significant global morbidity and mortality. The disease presents a broad clinical spectrum, significantly influenced by underlying comorbidities. While certain conditions are known to exacerbate COVID-19 outcomes, the role of chronic inflammatory airway diseases such as asthma and rhinitis in influencing disease severity remains controversial. This study investigates the association between asthma and allergic rhinitis and the severity of COVID-19 outcomes in a specific geographical region prior to widespread vaccine deployment. METHODS: We conducted a case-control study with unvaccinated adult patients who had laboratory-confirmed COVID-19 by polymerase chain reaction (PCR). Cases were defined as severe or critical COVID-19 patients requiring intensive care unit (ICU) admission, and controls were non-severe patients without signs of viral pneumonia or hypoxia. We utilized the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire to assess the presence of asthma and allergic rhinitis. The association between these chronic inflammatory airway diseases and the severity of COVID-19 was evaluated using multivariate logistic regression analysis. RESULTS: A total of 122 patients were analyzed, with 61 in each group. The presence of asthma (9 patients) was associated with an increased likelihood of severe COVID-19 (OR = 13.0; 95% CI 1.27-133.74), while rhinitis (39 patients) was associated with a protective effect against severe outcomes (OR = 0.36; 95% CI 0.13-0.99). No significant association was found between the frequency of asthmatic episodes or the severity of rhinitis and the severity of COVID-19 outcomes. CONCLUSION: This study underscores the divergent effects of chronic inflammatory airway diseases on COVID-19 severity, with asthma associated with a higher likelihood of severe outcomes and rhinitis potentially offering protective effects. These findings enhance our understanding of the complex interactions between respiratory allergies and COVID-19, emphasizing the importance of targeted clinical management and public health strategies.

CD4+ Th1 and Th17 responses and multifunctional CD8 T lymphocytes associated with cure or disease worsening in human visceral leishmaniasis.

Introduction: In VL, a proinflammatory phenotype is typically associated with enhanced phagocytosis and a Th1 mediated immune response resulting in infection control. In contrast, an anti-inflammatory phenotype, associated with a predominant regulatory response, typically enables intracellular multiplication of Leishmania parasites and disease progression. Methods: To investigate the impact of chemotherapy on Th2 and Th17 immune responses in patients with visceral leishmaniasis (VL), we assessed all combinations of intracellular expression of IFN-γ, IL-10, IL-4 and IL-17 in the CD4+ and CD8+ T cell populations of peripheral blood mononuclear cell (PBMC) samples from patients, after antigenic stimulation with Leishmania lysate, throughout treatment and follow-up. As increases in spleen and liver sizes and decreases in hematocrit, hemogloblin, erythrocytes, monocytes, leukocytes and platelets levels are strongly related to the disease, we studied the correlations between the frequencies of T cells producing the afore mentioned cytokines, individually and in combination, and these variables, as markers of disease or cure. Results: We found that the frequency of IFN-γ-producingCD4+ T cells increased until the end of chemotherapy with Glucantime® or AmBisome ®, while IL-10, IL-4 and IL-17-producing CD4+ T cells peaked on day 7 following the start of treatment. Although the frequency of CD4+IL-17+ cells decreased during treatment an increase was observed after clinical cure. The frequency of CD4+ T cells producing only IFN-γ or IL-17 correlated with blood monocytes levels. Frequencies of double-producers of IFN-γ and IL-10 or IL-4 correlated positively with eosinophils and platelets levels. Together, this suggest that IFN-γ drives the immune response towards Th1 at cure. In contrast, and associated with disease or Th2 response, the frequency of CD4+ IL-10+ cells correlated positively with spleen sizes and negatively with circulating monocyte levels, while the frequency of CD4+ producing both IL-4 and IL-10 correlated negatively with platelets levels. The frequency of CD8+ single-producers of IFN-γ increased from day 21 to 90 while that of single-producers of IL-10 peaked on day 7, of IL-4 on day 30 and of IL-17, on day 180. IFN-γ expression in CD8+ single- and double-producers of cytokines was indicative of an immune response associated with cure. In contrast, frequencies of CD8+ double-producers of IL-4 and IL-10, IL-4 and IL-17 and IL-10 and IL-17 and producers of three and four cytokines, were associated with disease and were low after the cure. Frequencies of CD8+ T cells producing IFN-γ alone or with IL-17 were positively correlated with platelets levels. In contrast, as markers of disease: 1) frequencies of single producers of IL-10 correlated negatively with leukocytes levels, 2) frequencies of double producers of IL-4 and IL-10 correlated negatively with platelet, leukocyte, lymphocyte and circulating monocyte levels, 3) frequencies of triple-producers of IFN-γ, IL-4 and IL-10 correlated negatively with platelet, leukocyte and neutrophil levels and 4) frequencies of producers of IFN-γ, IL-4, IL-10 and IL-17 simultaneously correlated positively with spleen size, and negatively with leukocyte and neutrophil levels. Discussion: Our results confirmed that the clinical improvement of VL patients correlates with the decrease of an IL-4 and IL-10 CD4+Th2 response, the recovery of CD4+ Th1 and Th17 responses and the frequency of CD8+ single-producers of IFN-γ and double producers of IFN-γ and IL-17.

The role of neurotrophin polymorphisms and susceptibility to neural damage in leprosy.

OBJECTIVES: Mycobacterium leprae is able to infect Schwann cells leading to neural damage. Neurotrophins are involved in nervous system plasticity and impact neural integrity during diseases. Investigate the association between single nucleotide polymorphisms in neurotrophin genes and leprosy phenotypes, especially neural damage. DESIGN: We selected single nucleotide polymorphisms in neurotrophins or their receptors genes associated with neural disorders: rs6265 and rs11030099 of brain-derived neurotrophic factor (BDNF), rs6330 of BDNF, rs6332 in NT3 and rs2072446 of P75NTR. The association of genetic frequencies with leprosy phenotypes was investigated in a case-control study. RESULTS: An association of the BDNF single nucleotide polymorphism rs11030099 with the number of affected nerves was demonstrated. The "AA+AC" genotypes were demonstrated to be protective against nerve impairment. However, this variation does not affect BDNF serum levels. BDNF is an important factor for myelination of Schwann cells and polymorphisms in this gene can be associated with leprosy outcome. Moreover, rs11030099 is located in the binding region for micro-RNA (miRNA) 26a that could be involved in control of BDNF expression. We demonstrated different expression levels of this miRNA in polar forms of leprosy. CONCLUSION: Our findings demonstrate for the first time an association between the polymorphism rs11030099 in the BDNF gene and neural commitment in leprosy and may indicate a possible role of miRNA-26a acting synergistically to these genetic variants in neural damage development.

sTREM-1 and TNF-α levels are associated with the clinical outcome of leprosy patients.

Leprosy reaction (LR) and physical disability (PD) are the most significant clinical complications of leprosy. Herein, we assessed the circulating serum-sTREM-1 and TNF-α levels and their genetic polymorphisms in leprosy. Serum-sTREM-1 and TNF-α levels were measured in leprosy patients (LP) before treatment (n = 51) and from their household contacts (HHCs; n = 25). DNA samples were genotyped using TREM-1 rs2234246 and TNF-α rs1800629-SNP in 210 LPs and 168 endemic controls. The circulating sTREM-1 and TNF-α levels are higher in the multibacillary form. The ROC curve of the serum-sTREM-1 levels was able to differentiate LR from non-LR and PD from non-PD. Similarly, LPs with serum-sTREM-1 levels >210 pg/ml have 3-fold and 6-fold higher chances of presenting with LR and PD, respectively. Genotypes CC+CT of the TREM-1 were associated with leprosy. Taken together, our analyses indicated that sTREM-1 and TNF-α play an important role in the pathogenesis of leprosy and provide promising biomarkers to assist in the diagnosis of leprosy complications.

Influence of Testosterone in Neglected Tropical Diseases: Clinical Aspects in Leprosy and In Vitro Experiments in Leishmaniasis.

Neglected tropical diseases encompass a group of chronic and debilitating infectious diseases that primarily affect marginalized populations. Among these diseases, leprosy and leishmaniasis are endemic in numerous countries and can result in severe and disfiguring manifestations. Although there have been reports indicating a higher incidence of leprosy and leishmaniasis in males, the underlying factors contributing to this observation remain unclear. Therefore, the objective of this study was to examine both clinical and experimental evidence regarding the role of testosterone in leprosy and leishmaniasis. A prospective clinical study was conducted to compare the clinical forms of leprosy and assess circulating testosterone levels. Additionally, the impact of testosterone on Leishmania amazonensis-infected macrophages was evaluated in vitro. The findings demonstrated that serum testosterone levels were higher in women with leprosy than in the control group, irrespective of the multi- or pauci-bacillary form of the disease. However, no differences in testosterone levels were observed in men when comparing leprosy patients and controls. Interestingly, increasing doses of testosterone in macrophages infected with L. amazonensis resulted in a higher proportion of infected cells, decreased CD40 expression on the cell surface, elevated expression of SOCS1, and decreased expression of IRF5. These findings provide biological evidence to support the influence of testosterone on intracellular infections, though the interpretation of clinical evidence remains limited.

COVID-19 recurrence is related to disease-early profile T cells while detection of anti-S1 IgG is related to multifunctional T cells.

COVID-19 is caused by SARS-CoV-2 infection and leads from asymptomatic to severe outcomes. The recurrence of the COVID-19 has been described, however, mechanisms involved remains unclear. Thus, the work aimed to investigate the role of multifunctional T cells in patients with recurrent COVID-19. We evaluated clinical characteristics, presence of anti-S1 and anti-Nucleocapsid IgG in patients' sera, and multifunctional T cells (for IFN-γ, IL-2, and TNF-α) in patients with multiple episodes of COVID-19 and controls. Data demonstrate that patients with recurrent COVID-19 have a T cell pattern predominantly related to IFN-γ production. Also, patients with COVID-19 history and absence of anti-S1 IgG had lower levels of CD4+ IFN + IL-2 + TNF + T cells independently of number of disease episodes. Complementary, vaccination changed the patterns of T cells phenotypes and induced IgG seroconversion, despite not induce higher levels of multifunctional T cells in all patients. In conclusion, the data suggest that recurrent disease is related to early-disease T cell profile and absence of anti-S1 IgG is related to lower multifunctional CD4 T cell response, what suggests possibility of new episodes of COVID-19 in these patients.

Co-infection of Leishmania infantum and a Crithidia-related species in a case of refractory relapsed visceral leishmaniasis with non-ulcerated cutaneous manifestation in Brazil.

We report a refractory and relapsed visceral leishmaniasis case in a male child patient followed from 2016 to 2020, whose clinical isolates from multiple relapses were analyzed at the genome level. To the best of our knowledge, it is the first report that both visceral leishmaniasis and non-ulcerated cutaneous leishmaniasis have concomitantly manifested in the same patient. Importantly, sequence analysis revealed that the patient was co-infected with Leishmania infantum and a Crithidia-related parasite, which was previously found in a fatal case of visceral leishmaniasis from the same endemic region.

Association between asthma, rhinitis and atopic dermatitis with leprosy: A case-control study.

Background Considering the cross-regulation of Th1 and Th2 responses, we hypothesised that atopic diseases (Th2) inhibit the protective Th1 immune response to Mycobacterium leprae and exacerbates leprosy. Objective In this study, we aimed to evaluate the association between leprosy and atopic diseases. Methods To evaluate the association of atopic diseases with leprosy, we conducted a case-control study that included leprosy patients (n = 333) and their household contacts (n = 93). The questionnaire from the International Study of Asthma and Allergies in Childhood, which is validated in several countries for epidemiological diagnosis of atopic diseases, was applied to determine the occurrence of atopic diseases, allergic rhinitis, asthma, and atopic dermatitis among leprosy patients and the household contacts. Results Considering clinical and epidemiological data, among the leprosy group 51.6% (n = 172) were determined to have at least one atopic disease, while atopy was observed less frequently at 40.86% among household contacts (n = 38). When two or more atopic diseases were assessed, the frequency was significantly higher among the leprosy patients than in the household contacts (21.9% vs. 11.8%; P-value = 0.03). Likewise, the frequency of asthma was significantly higher among leprosy patients (21%) than in the household contacts (10.8%; P-value = 0.02). Thus, our analyses revealed an association of atopic diseases with leprosy, with a significant linear increase in the occurrence of leprosy with an increase in the number of atopic diseases (P-value = 0.01). Limitation Due to the difficulties in recruiting household contacts that have prolonged contact with patients, but are not genetically related to the patient, the household contacts group is smaller than the leprosy patient group. Conclusion The data reveal an association between atopic diseases and leprosy outcomes. This knowledge could improve the treatment of leprosy patients with co-incident atopic diseases.

Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly.

Congenital Zika syndrome (CZS) is a cluster of malformations induced by Zika virus (ZIKV) infection and the underline mechanisms involved in its occurrence are yet not fully understood. Along with epidemiological and environmental factors, the genetic host factors are suggested as important to the CZS occurrence and development, however, few studies have evaluated this. This study enrolled a total of 245 individuals in a case-control association study compound a cohort of high specific interest constituted by 75 mothers who had delivered CZS infants, their 76 infants, and 47 mothers that had delivered healthy infants, and their 47 infants. Sixteen single-nucleotide polymorphisms on TREM1, CXCL10, IL4, CXCL8, TLR3, TLR7, IFNR1, CXCR1, IL10, CCR2 and CCR5 genes were genotyped to investigate their association as risk factors to CZS. The results show an association between C allele at TREM1 rs2234246 and C allele at IL4 rs224325 in mothers infected with ZIKV during pregnancy, with the increased susceptibility to CZS occurrence in their infants and the SNP CXCL8 rs4073 and the G allele at CXCL10 rs4508917 with presence of CZS microcephaly in the infants. Furthermore, the T allele at CXCL8 rs4073 and TRL7 rs179008 SNPs were associated with the severity of microcephaly in children with CZS. These results suggest that these polymorphisms in genes of innate immune responses addressed here are associated to increased risk of occurrence and severity of CZS in pregnant mothers infected with ZIKV and their CZS infants.

Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments.

This investigation aimed to assess the effect of N-acetylcysteine (NAC) as an adjuvant treatment to alleviate visceral leishmaniasis (VL). The present work includes both blinded randomized clinical intervention and experimental in vitro studies. The clinical trial included 60 patients with VL randomly allocated into two groups: a test group (n = 30) treated with meglumine antimoniate plus NAC (SbV + NAC) and a control group (n = 30) treated with meglumine antimoniate only (SbV). The primary outcome was clinical cure (absence of fever, spleen and liver sizes reduction, and hematological improvement) in 180 days. The cure rate did not differ between the groups; both groups had similar results in all readout indices. The immunological parameters of the patients treated with SbV + NAC showed higher sCD40L in sera during treatment, and the levels of sCD40L were negatively correlated with Interleukin-10 (IL-10) serum levels. In addition, data estimation showed a negative correlation between the sCD40L levels and the spleen size in patients with VL. For the in vitro experiments, peripheral blood mononuclear cells (PBMCs) or PBMC-derived macrophages from healthy donors were exposed to soluble Leishmania antigen (SLA) or infected with stationary promastigotes of Leishmania infantum in the presence or absence of NAC. Results revealed that NAC treatment of SLA-stimulated PBMCs reduces the frequency of monocytes producing IL-10 and lowers the frequency of CD4+ and CD8+ T cells expressing (pro-)inflammatory cytokines. Together, these results suggest that NAC treatment may modulate the immune response in patients with VL, thus warranting additional investigations to support its case use as an adjuvant to antimony therapy for VL.

Impact of the COVID-19 pandemic on the diagnosis of leprosy in Brazil: An ecological and population-based study.

BACKGROUND: The pandemic caused by COVID-19 has seriously affected global health, resulting in the suspension of many regular health services, making the diagnosis of other infections difficult. Therefore, this study aimed to assess the impact of the COVID-19 pandemic on the diagnosis of leprosy in Brazil during the year 2020. METHODS: We evaluated the monthly incidence of leprosy and calculated the percentage change to verify whether there was an increase or decrease in the number of leprosy cases in 2020, considering the monthly average of cases over the previous 5 years. We used interrupted time series analysis to assess the trend in the diagnosis of leprosy before and after the start of COVID-19 in Brazil and prepared spatial distribution maps, considering the percentage variation in each state. FINDINGS: We verified a reduction of 41.4% of leprosy cases in Brazil in 2020. Likewise, there was a reduction of leprosy notifications in children under 15 years-old (-56.82%). Conversely, the diagnosis of multibacillary leprosy increased (8.1%). There was a decreasing trend in the leprosy incidence in the general population between 2015 and 2020 in Brazil. Spatial distribution maps depicted a reduction of up to 100% in new cases of leprosy in some states. INTERPRETATION: Along with COVID-19 spread there was a reduction in leprosy diagnosis in the general population and children under 15 years-old, and also an increase in multibacillary cases diagnosed, signalling a serious impact of the pandemic on leprosy control strategies in Brazil. FUNDING: This research received no specific grants.

SARS-CoV-2 and splenic infarction: a rarely described thromboembolic presentation.

We report the case of a COVID-19 patient presenting with fever, headache and dyspnea, evolving with severe acute abdominal pain. A contrast-enhanced computed tomography (CT) scan diagnosed splenic infarction. We emphasize the importance of seeking the identification of complications of SARS-CoV-2 infection, notably thromboembolic events, with the potential to reduce the morbidity and mortality of the disease. Studies on radiological aspects involving the spleen and splenic infarctions associated with COVID-19 are rare.

Association of IL-9, IL-10, and IL-17 Cytokines With Hepatic Fibrosis in Human Schistosoma mansoni Infection.

This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP-10 µg/ml) or egg (SEA-10 µg/ml) antigens or purified protein derivative of turberculin (PPD-10 µg/ml) or phytohemagglutinin (PHA-1 µg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17, IL10, and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis.

Basic and associated causes of schistosomiasis-related mortality in Brazil: A population-based study and a 20-year time series of a disease still neglected.

BACKGROUND: Schistosomiasis is a persistent public health problem in Brazil. Regardless advances in diagnosis and mass treatment, schistosomiasis has a severe impact on morbimortality in the country and remains a neglected tropical disease. Herein, we assessed the basic and associated causes of schistosomiasis-related deaths and the temporal and spatial patterns of mortality from the disease in Brazil between 1999 and 2018. METHODS: We conducted an ecological and time series study. The segmented log-linear regression model was applied to assess time trends, considering all deaths recorded in the category B65/ICD-10. Additionally, we elaborated maps of mortality rates from schistosomiasis in Brazil. RESULTS: A total of 4168 schistosomiasis-related deaths were recorded in Brazil in this period, as an associated cause. Time trend analysis revealed an increase in the average age of deaths from schistosomiasis (annual percentage change (APC) = 0.84), and stable trend in Brazil (APC = 0.31). Concerning schistosomiasis-related deaths, we observed disorders related to the digestive system, liver diseases, septicemias, and chronic diseases. Surprisingly, there were deaths caused by non-endemic Schistosoma species in Brazil. Also, municipalities from non-endemic areas in Brazil presented schistosomiasis-related deaths. CONCLUSION: Altogether, our analyses demonstrated that schistosomiasis remains a significant cause of death in Brazil, and it is increasing in some areas, especially in the Northeast region. Additionally, women and the elderly showed a stable time trend of deaths. Thereby, it urgently requires improvements in the control programs strategies, in the sense of an effective reduction in cases and deaths from the disease in Brazil.

Association between Hypertriglyceridemia and Disease Severity in Visceral Leishmaniasis.

Visceral leishmaniasis (VL) is a tropical disease endemic to Brazil. The clinical manifestations of the infection range from asymptomatic to severe. In VL, changes in lipid metabolism, such as hypocholesterolemia and hypertriglyceridemia, occur that are believed to be related to its progression and severity. This study investigated the associations between serum levels of cholesterol, triglycerides, and lipoproteins (high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein) with clinical and hematological parameters that predict severity in a case series of 83 VL patients. Severely ill patients had higher mean serum triglyceride levels than non-severely ill patients. There was a significant positive correlation between disease severity score and serum triglyceride levels, very low-density lipoprotein, international normalized ratio for prothrombin time test, total bilirubin, and age. An inverse correlation was detected between the disease severity score and mean platelet and neutrophil counts. Hypertriglyceridemia can be a prognostic indicator of severity in patients diagnosed with VL.

Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis.

Visceral leishmaniasis (VL) is a chronic and often fatal disease caused by protozoans of the genus Leishmania that affects millions of people worldwide. Patients with symptomatic VL have an impaired anti-Leishmania-specific CD4+ T-cell response, which is reversed after clinical cure. In contrast, the quality of the CD4+ and CD8+ T-cell responses involved in resistance and/or cure of VL relies on the capability of these cells to activate polyfunctional and memory responses, which are associated with the simultaneous production of three cytokines: IFN-γ, IL-2, and TNF-α. Models for the development of CD4 and CD8 T-cell quality in memory and protection to leishmaniasis have been described previously. We aimed to assess the functionality of the T cells involved in the recovery of the immune suppression throughout the VL treatment. Therefore, we cultured peripheral blood mononuclear cells (PBMCs) from VL patients and healthy controls in vitro with soluble Leishmania antigen (SLA). Cell surface markers and intracellular cytokine production were determined on days 7, 14, 21, 30, 60, 90, and 180 after the beginning of chemotherapy. We observed that the frequencies of CD4+TNF-α+IFN-γ+ and the multifunctional CD4+IL-2+TNF-α+IFN-γ+, together with CD4+TNF-α+ and CD4+IFN-γ+ T cells, increased throughout and at the end of the treatment, respectively. In addition, enhanced frequencies of CD8+IL-2+TNF-α+IFN-γ+ and CD8+TNF-α+IFN-γ T cells were also relevant in the healing process. Noteworthy, the frequencies of the CD4+ and CD8 central-memory T cells, which produce IL-2, TNF-α, and IFN-γ and ensure the memory response against parasite reinfection, are significantly enhanced in cured patients. In addition, the subset of the non-functional CD8Low population is predominant in VL untreated patients and decreases along the chemotherapy treatment. In contrast, a CD8High subset increased towards the cure. Furthermore, the cure due to treatment with meglumine antimoniate or with liposomal amphotericin B was associated with the recovery of the T-cell immune responses. We described the evolution and participation of functional T cells during the treatment of patients with VL. Our results disclosed that the clinical improvement of patients is significantly associated with the participation of the CD4+ and CD8+ cytokine-secreting T cells.

Leishmania infantum (syn. L. chagasi) parasites affect the release of soluble CD14 by infected macrophages.

Functionally, cluster of differentiation 14 (CD14) is a co-receptor of the complex formed by lipopolysaccharide (LPS) and LPS-binding protein expressed on the membrane of a variety of cells. However, CD14 can be shed from the cell membrane into the circulation as soluble CD14 (sCD14) upon cell activation. Previously, our group reported that elevated sCD14 serum levels were associated with the clinical and laboratory findings in the context of visceral leishmaniasis (VL), but not in the context of LPS stimulation or bacterial infection. In the present study, we investigated the secretion dynamics of sCD14 in the context of Leishmania infantum (syn. L. chagasi) in vitro infection. Macrophages from treated VL patients and delayed-type hypersensitivity positive (DTH+) subjects were infected with L. infantum (syn. L. chagasi) promastigotes, and the infection index was evaluated (number of amastigotes per 100 infected macrophages). Additionally, the levels of sCD14, Inteleukin (IL)10, IL-6 and tumour necrosis factor alpha (TNF-α) were measured in the culture supernatants using the Luminex assay. Interestingly, the release of sCD14 was inversely correlated with the L. infantum (syn. L. chagasi) infection index. Of note, the release of sCD14 was upregulated and downregulated in the context of infected macrophages from DTH+ subjects and treated VL patients, respectively. Additionally, we also observed that the levels of sCD14 in the culture supernatants were positively correlated with the levels of TNF-α, IL-6 and IL-10. Therefore, our data suggest that macrophages from treated VL patients and DTH+ subjects respond differently to L. infantum (syn. L. chagasi) infection in the context of the release of sCD14; therefore, the release of sCD14 may be associated with the outcome of VL.

Antimony resistance associated with persistence of Leishmania (Leishmania) infantum infection in macrophages.

Visceral leishmaniasis is a severe disease caused by protozoan parasites that include Leishmania (L.) infantum. The disease is established when parasites subvert the immune response of the host. Notably, chemotherapy-based use of antimonial compounds can partially alleviate disease burden. Unfortunately, the resistance to drug treatments is increasing in areas endemic to the disease. In this report, we investigated immune responses within macrophages infected with antimony-resistant L. infantum isolates from patients with a relapse in the disease. Results revealed that antimony-resistant parasites persist in the first 24 h of infection. Activation of macrophage or blocking of thiol production during infection shows enhanced clearance of parasites, which is coordinately associated with increased production of pro-inflammatory cytokines. Taken together, these results suggest that the mechanism of antimony resistance in L. infantum isolates may be related to a decrease in macrophage microbicidal functions.

Case Report: Visceral Leishmaniasis and Hemophagocytic Lymphohistiocytosis: Three Clinical Cases, Three Different Patterns.

Visceral leishmaniasis (VL) is a neglected tropical disease with more than 30,000 cases annually reported worldwide. In Brazil, about 3,700 cases are annually reported. The VL clinical presentation is variable, from asymptomatic to severe cases with a high risk of death. We reported three cases of VL with clinical sign similarities but distinct development. All cases had bone marrow hemophagocytosis and hemophagocytic lymphohistiocytosis (HLH) criteria. HLH is a rare condition that may have secondary causes, including infectious and parasitic diseases, like VL. The delayed recognition of the secondary HLH (sHLH) association to VL may cause unfavorable outcomes and death.

Individuals with isolated congenital GH deficiency due to a GHRH receptor gene mutation appear to cope better with SARS-CoV-2 infection than controls.

PURPOSE: Several interactions exist between the GH/IGF axis and the immune system, including effects on innate immunity and humoral and cellular response. Acquired GH deficiency (GHD) has been recently proposed as a risk factor for severity of COVID-19 infections. However, acquired GHD is often associated to other factors, including pituitary tumors, surgery, radiotherapy, and additional pituitary hormones deficits and their replacements, which, together, may hinder an accurate analysis of the relationship between GHD and COVID-19. Therefore, we decided to assess the seroprevalence of SARS-CoV-2 antibodies and the frequency of symptomatic cases of COVID-19 in adults subjects with untreated isolated GHD (IGHD) due to a homozygous null mutation in the GHRH receptor gene. METHODS: A cross-sectional study was carried out in 27 adult IGHD subjects and 27 age- and gender-matched local controls. Interview, physical examination, bio-impedance, hematological and SARS-CoV-2 IgM and IgG antibodies were analyzed. RESULTS: There was no difference in the prevalence of positivity of anti-SARS-CoV-2 IgM and IgG antibodies between the two groups. Conversely, no IGHD individual had a previous clinical diagnosis of COVID-19 infection, while 6 control subjects did (p = 0.023). CONCLUSION: The production of anti-SARS-CoV-2 antibodies was similar between IGHD subjects due to a GHRH receptor gene mutation and controls, but the evolution to symptomatic stages of the infection and the frequency of confirmed cases was lower in IGHD subjects than in GH sufficient individuals.