Visceral Leishmaniasis Revealing Undiagnosed Inborn Errors of Immunity.

Visceral Leishmaniasis (VL) is a potentially fatal disease and may be associated with primary or acquired immunodeficiencies. There are few reports, in the literature, of inborn errors of immunity. Here, we report two cases of VL as a marker of inborn errors of immunity, namely, GATA2 and RAB27A deficiency. Our data suggest that VL patients should be screened for primary immunodeficiency, particularly in cases of VL relapse.

Visceral Leishmaniasis Revealing Undiagnosed Inborn Errors of Immunity

ABSTRACT Visceral Leishmaniasis (VL) is a potentially fatal disease and may be associated with primary or acquired immunodeficiencies. There are few reports, in the literature, of inborn errors of immunity. Here, we report two cases of VL as a marker of inborn errors of immunity, namely, GATA2 and RAB27A deficiency. Our data suggest that VL patients should be screened for primary immunodeficiency, particularly in cases of VL relapse.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and esophageal rupture by candida infection: A case report and review.

We probably describe the first report of esophageal rupture in a patient with autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy (APECED, OMIM # 240300), who had candida esophagitis as the main feature for decades. Strong evidence shows that this rupture may have been caused directly and indirectly by chronic candidiasis. In this way, we demonstrate how severe and harmful the persistent esophageal candidiasis can cause in the esophagus, especially in immunodeficient patients.

Posicionamento da ASBAI sobre a vacinação de crianças de 5 a 11 anos contra a COVID-19 com a vacina Comirnaty/ Pfizer/BioNTech ­ 27/12/2021 / ASBAI's position on vaccination of children aged 5 to 11 years against COVID-19 with the Comirnaty/Pfizer/BioNTech vaccine ­ 12/27/2021

A Associação Brasileira de Alergia e Imunologia (ASBAI) se manifesta totalmente favorável à imunização contra a COVID-19 em indivíduos entre 5 e 11 anos, para a proteção não somente deste grupo, mas também de seus conviventes. A vacinação de crianças, demonstrada sua eficácia e segurança, é fundamental para o controle da circulação do vírus e proteção de indivíduos cuja resposta vacinal pode não ocorrer de modo eficiente, como os imunocomprometidos e idosos. A imunização de pessoas entre 5 e 11 anos deve ser uma estratégia de saúde pública fundamental para o controle da pandemia que nos assola desde março de 2020 com todas as suas graves consequências para a saúde pública e a economia.

The Brazilian Association of Allergy and Immunology (ASBAI) is totally in favor of immunization against COVID-19 in individuals between 5 and 11 years old, for the protection not only of this group, but also of their cohabitants. The vaccination of children, once its efficacy and safety has been demonstrated, is essential for controlling the circulation of the virus and protecting individuals whose vaccine response may not occur efficiently, such as the immunocompromised and the elderly. The immunization of people between the ages of 5 and 11 must be a fundamental public health strategy to control the pandemic that has been plaguing us since March 2020 with all its serious consequences for public health and the economy.

Diagnosis, treatment and maxillofacial rehabilitation in rhinocerebral mucormycosis patient: A case report and review of the literature.

Mucormycosis is an aggressive, rare and opportunistic infectious disease, with a high mortality rate. Etiologic agents are filamentous fungi, and infection among humans normally occurs through spore inhalation. A 61-year-old male individual, presenting left eye amaurosis, dark epistaxis, hyperalgesia and malodor underwent clinical examination, which detected ulcerative lesion and wide bone exposure in the hard palate and alveolar ridge. Direct microbiological examination, microbiological culture and lesion biopsy were performed. Non-septate smooth fungal hyphae forming right angles with each other were observed through the direct microbiological examination. Microbiological culture revealed fast-growing fungal colonies with cottony texture, identified as Rhizopus sp. Histopathological examination exhibited necrosis areas, intense mononuclear inflammatory infiltrate and bulky hyphae, thus concluding the mucormycosis diagnosis. Amphotericin B antifungal therapy and surgical intervention were adopted as treatment. The patient was then rehabilitated with maxillofacial prosthesis, subsequently to the healing of the surgical wound.

Vacinas COVID-19 e outros imunobiológicos ­ intervalos preconizados / COVID-19 vaccines and other immunobiological drugs ­ recommended intervals

Com o início do programa de vacinação contra a COVID-19 no Brasil, surgiu uma série de questionamentos relacionados ao uso dos imunizantes. Neste documento, o grupo de estudo da COVID-19 da Associação Brasileira de Alergia e Imunologia (ASBAI) avalia as evidências científicas e se posiciona em relação aos intervalos preconizados entre a administração das vacinas contra o SARS-CoV-2 e dos imunobiológicos.

With the beginning of the COVID-19 vaccination program in Brazil, a series of questions related to the use of vaccines arose. In this document, the COVID-19 study group of the Brazilian Association of Allergy and Immunology (ASBAI) assesses the scientific evidence and takes a stand for the recommended intervals between the administration of SARS-CoV-2 vaccines and that of immunobiological drugs.

Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature.

We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient's susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient.

Alergias e vacinas contra a COVID-19 / Allergies and vaccines against COVID-19

As vacinas são reconhecidas como uma das conquistas do século passado de maior impacto em Saúde Pública, reduzindo de modo significativo a morbidade e mortalidade associadas a grande número de doenças infecciosas. No entanto, em casos raros, as vacinas podem causar doença ou eventos adversos pós-vacinação (EAPV). Os imunologistas clínicos e alergistas possuem um papel muito importante nesse momento em que mundialmente buscamos imunizar a população contra a COVID- 19. Eles devem fornecer apoio aos indivíduos orientando sobre o diagnóstico e tratamento de EAPV, incluindo anafilaxia, e, ainda, apoiar e encorajar os pacientes a se vacinarem, mesmo após eventos adversos, desde que leves ou moderados.

Vaccines are known as one of the achievements of the last century with greatest impact on public health, significantly reducing morbidity and mortality associated with a large number of infectious diseases. However, in rare cases, vaccines may cause disease or adverse events following immunization. Clinical immunologists and allergists have a very important role in the worldwide vaccination against COVID-19. They should provide support to individuals by advising on the diagnosis and treatment of adverse events following immunization, including anaphylaxis, and also support and encourage patients to be vaccinated, even after adverse events, as long as they are mild or moderate.

Vacinas contra a COVID-19 e os erros inatos da imunidade (ou imunodeficiências primárias) / COVID-19 vaccines and inborn errors of immunity (or primary immunodeficiencies)

Desde o início da pandemia de COVID-19 iniciou-se a corrida por uma imunização ativa, eficaz e segura. Todas as vacinas desenvolvidas até o momento vêm demostrando boa eficácia na prevenção de casos graves de COVID-19, de hospitalizações e mortes. Muitos pacientes com erros inatos da imunidade (EII) não terão capacidade de desenvolver uma resposta imune semelhante ao indivíduo imunocompetente. Esses pacientes foram incluídos nos grupos prioritários definidos pelo Ministério da Saúde, como pessoas entre 18 a 59 anos com uma ou mais das comorbidades, incluindo as imunodeficiências primárias. Eles podem e devem receber as vacinas em uso contra o SARS-CoV-2, mas nem sempre apresentarão uma resposta imunológica satisfatória e protetora, e, portanto, seus contactantes também devem ser vacinados.

Since the beginning of the COVID-19 pandemic, the race for an active, effective, and safe immunization has started. All vaccines developed to date have shown good efficacy in preventing serious cases of COVID-19, hospitalization, and death. Many patients with inborn errors of immunity will not be able to develop an immune response similar to that of immunocompetent individuals. These patients were included in the priority groups defined by the Brazilian Ministry of Health, as people between 18 and 59 years of age with one or more comorbidities, including primary immunodeficiencies. They can and should receive the vaccines in use against SARS-CoV-2, but they will not always have a satisfactory and protective immune response, and, therefore, those in direct contact with them should also be vaccinated.

Reinfecções pelo SARS-CoV-2: fato ou fake ? Implicações para a resposta vacinal / Reinfection with SARS-CoV-2: fact or fake? Implications for vaccine response

Há evidências atuais de que a reinfecção pelo SARS-CoV-2 é uma realidade, mas na grande maioria das situações não houve investigação que permitisse sua perfeita caracterização, sendo confirmados poucos casos. Em situações de real reinfecção, esta ocorreu, em sua grande maioria, por variantes do vírus, com diversas mutações, usualmente na proteína da espícula viral, em profissionais de saúde altamente expostos, ou em portadores de imunodeficiências, tanto primárias quanto secundárias. Ressaltamos que as vacinas podem ser modificadas com relativa facilidade, mas a capacidade de fabricação e de distribuição pelo mundo será capaz de acompanhar a demanda por vacinação em massa de forma eficiente? Neste manuscrito, a comissão de estudo da COVID-19 da ASBAI analisa criticamente o conhecimento atual sobre a reinfecção pelo SARS-CoV-2.

There is current evidence that reinfection with SARS-CoV-2 is a reality, but there is also a lack of investigation that would allow its perfect characterization, and few cases have been confirmed. Real reinfections occurred mostly with variants of the virus, with several mutations, usually in the viral spike protein, in highly exposed health professionals or in patients with immunodeficiencies, both primary and secondary. We emphasize that vaccines can be modified relatively easily, but will the manufacturing and distribution capacity around the world be able to keep up with the demand for mass vaccination efficiently? The ASBAI COVID-19 study commission critically analyzes in this manuscript the current knowledge about SARS-CoV-2 reinfection.

Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature

Abstract We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient's susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient.

Contribution of complement system pathways to the killing of leptospira spp.

The Complement System CS plays an important role in the immune response against leptospirosis and can be activated by the Alternative and Lectin Pathways (Innate Immunity) and by the Classical Pathway (Acquired Immunity). Here we analyzed a broad range of nonpathogenic and pathogenic Leptospira strains considering their interaction with each CS pathway. We determined bacterial survival rate and CS protein deposition in the presence of purified proteins, specific component depleted sera and NHS treated with the chelating agents EDTA inhibits all three activation pathways) or EGTA inhibits the Classical and Lectin Pathways. We suggest that the Lectin and the Alternative Pathways have an important role to eliminate saprophytic leptospires since i) approximately 50% survival of both saprophytic strains was observed in the presence of MBL-deficient serum; ii) approximately 50 % survival of L. biflexa Patoc I was observed in the presence of NHS – EGTA and iii) C1q-depleted serum caused significant bacterial lysis. In all serovars investigated the deposition of C5-C9 proteins on saprophytic Leptospira strains was more pronounced when compared to pathogenic species confirming previous studies in the literature. No difference on C3 deposition was observed between nonpathogenic and pathogenic strains. In conclusion, Leptospira strains interact to different degrees with CS proteins, especially those necessary to form MAC, indicating that some strains and specific ligands could favor the binding of certain CS proteins.

Unusual manifestations of visceral leishmaniasis in children: a case series and its spatial dispersion in the western region of São Paulo state, Brazil.

BACKGROUND: Visceral leishmaniasis (VL) is becoming endemic in São Paulo state, in the southeastern region of Brazil. Unusual manifestations with non-specific signs and symptoms may make diagnosis difficult and delay treatment, increasing the risk of severity and death, particularly in new endemic areas. There are few studies on patients with these characteristics in Brazil. We describe a case series of unusual manifestations of VL in children and its spatial dispersion in the western region of São Paulo state. CASES PRESENTATION: From 2009 to 2014, five clinical cases involving children treated in the Regional Hospital of Presidente Prudente (RH) were selected. Two patients had multiple relapses requiring liposomal amphotericin B; one patient had VL-cytomegalovirus-dengue co-infection and liver injury; one patient was diagnosed with X-linked agammaglobulinemia, a primary immunodeficiency; and one patient was diagnosed with VL-human immunodeficiency virus/acquired immunodeficiency syndrome (VL-HIV/AIDS) co-infection. Primary or secondary immunodeficiencies were found in four children, and associated viral infections were found in three children. Three patients were referred from other hospitals to RH. With regard to the geographic spread of VL, more cases were found in the northern area, in the epicenter of the infection where the first cases were registered, flowing south; a spatial-temporal occurrence was found. CONCLUSIONS: Primary and secondary immunodeficiencies and viral co-infectious should be considered among unusual manifestations of VL, especially in those with multiple relapses. Spatial-temporal occurrence was found. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices to stem the tide of the epidemic.

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab.

BACKGROUND: The use of rituximab (RTX) is increasing, even in developing countries. It has become the first-line therapy or adjuvant to chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) for various diseases, including B cell lymphoma and autoimmune diseases. AIM: We describe the infectious diseases and immunological markers associated with RTX treatment of patients with non-Hodgkin lymphoma (NHL). METHODS: Serum immunoglobulins were determined before and after intravenous immunoglobulin (IVIg) administration. Pneumo-23IgG-specific anti-pneumococcal antibodies were evaluated before and after vaccination. Immunophenotyping and lymphocyte proliferation were determined in the course of the treatment. RESULTS: Seven patients were followed and median age was 56.0 ± 5.0 years (range, 41.9-71.6 years). At baseline, the mean level of IgG was 333.7 ± 40.8 and IgM 40.9 ± 11.3 mg/dL, respectively; immunoglobulin A and E (IgA and IgE) were under the limit of detection. Two patients had reduced or absent B cells and T cell subsets were at normal levels in five patients. All patients failed to mount an efficient post-vaccination immune response against hepatitis B virus, tetanus, diphtheria and against the 23-valent pneumococcal polysaccharide vaccine. During RTX/CHOP treatment, human-IgG-immunoglobulin (IVIg) therapy was introduced in six patients after recurrent infections, including community-acquired pneumonia (85.7%), chronic sinusitis (85.7%) and gastroenteritis (42.9%). CONCLUSION: Poor response against pneumococcal vaccines increases the susceptibility of respiratory diseases in these patients. In patients with NHL treated with RTX, the benefits achieved with IVIg replacement for the control of recurrent infectious diseases is of paramount importance. Clinicians dealing with monoclonal antibodies against cancer therapy, especially RTX, should be aware of the increasing risks for symptomatic induced hypogammaglobulinemia and respiratory infections.

Role of T. cruzi exposure in the pattern of T cell cytokines among chronically infected HIV and Chagas disease patients.

OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.

Role of T. cruzi exposure in the pattern of T cell cytokines among chronically infected HIV and Chagas disease patients

OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.