Avian reticuloendotheliosis (RE) caused by reticuloendotheliosis virus (REV) is an important tumor and immunosuppressive disease posing a serious threat to poultry development. The REV envelope protein, glycoprotein (gp)-90, not only participates in cell receptor binding and viral assembly and release but also induces neutralizing antibody production. However, the antigenic epitope structure of gp90 has not yet been systematically understood. Therefore, in this study, the gp90 envelope protein of a predominant REV strain was prepared using a prokaryotic expression system, and a hybridoma cell line stably secreting the REV gp90 monoclonal antibody was developed via cell fusion and flow cytometry. Notably, a novel linear B-cell epitope, 195REESVRERL203, was identified for the first time in the gp90 of REV using peptide scanning. This epitope was located on the outer side of the gp90 midpiece and was conserved across REV strains. Overall, this study is of great significance for the systematic understanding of REV antigen structure and the development of virus detection methods.

Darling's disease, another name for oral histoplasmosis, is an uncommon but important form of Histoplasma capsulatum infection that can appear as oral cavity lesions that frequently mimic cancers like squamous cell carcinoma. Immunocompromised people, notably those with HIV, are most vulnerable to this fungal infection, while immunocompetent patients can still get it. Because of their appearance and chronic nature, the clinical presentation usually consists of painful, ulcerative lesions that could be mistakenly diagnosed as cancer. In the uncommon instance described in this analysis, an 80-years-old man who had no known addictions or comorbidities showed up with a non-bleeding ulcero-proliferative lesion on his tongue that had been there for two months. The lesion was eventually determined to be oral histoplasmosis after being misdiagnosed as mouth cancer. The diagnostic difficulties associated with this illness were highlighted by the histopathological investigation, which showed granulomatous inflammation and the distinctive yeast forms of Histoplasma. Inappropriate treatment plans and delays in efficient management can result from misdiagnosis. This example emphasizes how crucial it is to take oral histoplasmosis into account when making a differential diagnosis for oral lesions, especially in areas where it is endemic. To get positive results and avoid consequences from misdiagnosis, early detection and adequate antifungal medication are essential.

Histoplasmosis, also referred to as Darling's disease, is mainly caused by the thermally dimorphic fungus Histoplasma capsulatum. It is usually contracted by inhaling fungal spores found in soil contaminated with bat or bird droppings, often during activities like cave exploration. Although endemic in certain regions of India, such as the eastern part, and sporadically in southern and northern states, histoplasmosis can manifest with varied clinical presentations, ranging from asymptomatic to severe disseminated disease affecting multiple organs. Adrenal involvement, though relatively uncommon, can lead to adrenal insufficiency, especially in immunocompetent individuals, with bilateral adrenal enlargement being a characteristic feature in imaging studies. This report discusses the case of a 51-year-old farmer from Haryana, India, who was diagnosed with progressive disseminated histoplasmosis (PDH) resulting in primary adrenal insufficiency. Although tuberculosis or malignancy was initially suspected, imaging studies and biopsy results confirmed histoplasmosis as the root cause. This case emphasizes the necessity of including histoplasmosis in the differential diagnosis of primary adrenal insufficiency, especially in endemic areas, and highlights the importance of early detection and appropriate management of this potentially life-threatening disease.

DISSEMINATED HISTOPLASMOSIS IN A PATIENT WITH ACUTE KIDNEY TRANSPLANT REJECTION: A CASE REPORT OF DARLING'S DISEASE

stoplasmosis is a deep cosmopolitan mycosis due to dimorphic fungi belonging to the genus Histoplasma. We distinguish the American histoplasmosis, with small form due to Histoplasma capsulatum var. capsulatum (H. capsulatum), and large-form African histoplasmosis, due to H. duboisii. The latter is endemic in West and Central Africa and Madagascar. African histoplasmosis is a rare deep mycosis, due to Histoplasma Capsulatum var.duboisii. Clinical presentation may be localized with isolated infections of the skin, bones or lymph nodes or disseminated with multiple skin lesions present throughout the body, subcutaneous abscesses, enlarged lymph nodes, liver and spleen, and enlargement of visceral organs. It has diagnostic similarities with pathologies such as lymph node tuberculosis, cutaneous cryptococcosis and certain malignant diseases of the skeleton. The disease sometimes poses therapeutic difficulties. We report a histoplasmosis case at Histoplasma Capsulatum var.duboisii, with multiple localization in a 22-year-old student.

Definitive diagnosis of histoplasmosis relies on culture and/or cytology/histopathology; however, these procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has low sensitivity in immunocompromised individuals and uses histoplasmin (HMN), a crude antigenic extract, as reagent. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques to obtain standardized and specific reagents for diagnosing histoplasmosis. To compare the analytical performance of novel enzyme-linked immunosorbent assays (ELISAs) for antibodies testing for diagnosing histoplasmosis using different Histoplasma capsulatum antigens as reagents. The H. capsulatum 100kDa protein (Hcp100), the M antigen and its immunoreactive fragment F1 were produced by DNA-recombinant techniques. Galactomannan was purified from both the yeast and mycelial cell walls (yGM and mGM, respectively). The analytical performance of the ELISA tests for the serological detection of antibodies against these antigens was evaluated and compared with those obtained using HMN as reagent. Antibodies detection by the Hcp100 ELISA demonstrated 90.0% sensitivity and 92.0% specificity, versus 43.3% sensitivity and 95.0% specificity of the M ELISA, 33.3% sensitivity and 84.0% specificity of the F1 ELISA, 96.7% sensitivity and 94.0% specificity of the yGM ELISA, 83.3% sensitivity and 88.0% specificity of the mGM ELISA, and 70.0% sensitivity and 86.0% specificity for the HMN ELISA. In summary, Hcp100 is proposed as the most promising candidate for the serodiagnosis of histoplasmosis. The primary immunoreactive element in HMN proved to be GM rather than the M antigen. Nevertheless, a higher incidence of cross-reactions was noted with GM compared to M.

Diagnosing progressive disseminated histoplasmosis (PDH) is still challenging in many countries where this disease is highly endemic. Definitive diagnosis is established by culture and/or by cytology/histopathology but both procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has a low sensitivity in immunocompromised individuals. Commercially available antigen detection assays have high sensitivity in PDH cases; however, they are expensive and only performed in few laboratories. To describe the potential use of a novel ELISA for antibodies testing and a dot blot assay for antigen testing for diagnosing PDH using the recombinant 100 kDa protein of Histoplasma capsulatum (Hcp100) and their polyclonal antibodies as novel reagents, respectively. Serum and urine samples from a cohort of patients with HIV/AIDS and proven PDH were studied for the detection of anti-Hcp100 antibodies by ELISA and Hcp100 antigen by dot blot, respectively. Sensitivity, specificity and cross-reactions with other diseases were estimated for each assay and compared with those obtained using histoplasmin (HMN) as a reagent for antibodies detection by ELISA and immunodiffusion, and using a commercial antigenuria test. Antibodies detection by the Hcp100 ELISA demonstrated 78.6% sensitivity and 88.4% specificity, versus 85.7% sensitivity and 81.0% specificity for the HMN ELISA and 26.1% sensitivity and 100% specificity for the immunodiffusion assay. Antigen detection by the Hcp100 dot blot demonstrated 89.3% sensitivity and 97.0% specificity versus 82.1% sensitivity and 90.9% specificity for the commercial test. The immunoassays described herein based on Hcp100 would be a valuable screening tool for diagnosing PDH.

HTLV-1 and HTLV-2 infections in patients with endemic mycoses in São Paulo, Brazil: A cross-sectional, observational study

BackgroundHistoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum (Hcc) and Histoplasma capsulatum var. duboisii (Hcd) causes infection in humans and commonly termed classical or American histoplasmosis and African histoplasmosis, respectively. Histoplasma capsulatum var. farciminosum (Hcf) affects equines. In recent times, there have been heightened sensitization on fungal infections such as histoplasmosis in Africa, aimed at improving awareness among relevant stakeholders, particularly healthcare workers. This effort is expected to be paralleled with increased detection of both classical and African histoplasmosis, which has remained underdiagnosed over the years. In this narrative review, we describe the current perspectives of histoplasmosis in Africa, identify knowledge gaps, and suggest research priorities.MethodsA PubMed, Google Scholar, and Africa Journal Online (AJOL) literature search was conducted for studies on histoplasmosis in Africa between 2000 and 2020. Histoplasmosis essays in medical mycology textbooks were also consulted. This narrative review was prepared from the data gathered.FindingsIn the past 2 decades, histoplasmosis in general has seen a relative increase in case detection in some Africa countries, probably attributable to the gradually increasing medical mycology advocacy efforts in Africa. Histoplasmosis cases are dominated by African histoplasmosis mostly in Western and Central Africa, while classical histoplasmosis is more common in Southern and Northern Africa. Although both classical and African histoplasmosis are common in Africa, the latter is more restricted to Africa, and cases outside the continent usually have a travel history to the continent. Despite the clinical and laboratory difference between African histoplasmosis and classical histoplasmosis, it is not straightforward to distinguish them. The typical manifestation of African histoplasmosis is the appearance of lesions affecting the skin, bones, and lymph nodes and unusually linked to human immunodeficiency virus (HIV)/AIDS. By contrast, classical histoplasmosis mostly affects the lungs and is often associated with immunosuppression, mainly HIV/AIDS. The present perspectives of histoplasmosis in Africa highlight unclear details on the true burden, strain diversity, infection route and genetic basis of African histoplasmosis, availability of specie-specific diagnostic tools, and compliance with recommended antifungal therapy. These knowledge gaps represent research questions that require scientific exploration.ConclusionsDespite a subtle increase in identifying histoplasmosis cases in Africa, it remains underdiagnosed and neglected in some parts of the continent. Increasing awareness and training among healthcare workers, bridging diagnostic and therapeutic gaps, and encouraging more research in Africa are crucial to improve the current perspectives of histoplasmosis in Africa.

Reemergence of reticuloendotheliosis virus and Marek's disease virus co-infection in Yellow-Chickens in Southern China

Patel, Kushal; Kirsch, Nathan; Ciezki, Richard; Asad, Shadaba; Kilburn, Jeremy; Honsberg, Angelica; Modi, Kush; Dy, Rajany; Kioka, Mutsumi; Iardino, Alfredo Author Information

Objetivo: Analisar a ocorrência de Histoplasma capsulatum nas culturas para fungos que deram entrada em um Laboratório Estadual de Saúde Pública do Centro-Oeste brasileiro no período de 2016 a 2019. Metodologia: Trata-se de um estudo transversal, constituído por culturas para pesquisa de fungos que deram entrada no referido laboratório e provenientes de Hospitais de Referência do Estado. As variáveis analisadas foram gênero, faixa etária, número de positividade e negatividade das culturas para Histoplasma capsulatum e espécime clínico utilizado para análise. Resultados: No período analisado, foi dada entrada de um total de 12.476 culturas para fungos, 2.262 foram positivas, das quais 313 identificou-se a presença do Histoplasma capsulatum. A prevalência percentual desse agente entre as amostras positivas correspondeu a 13,84, nas faixas etárias de 31 a 40 anos (19,28), de 41 - 50 anos (16,83) e de 51 a 60 anos (14,60), com maior prevalência no gênero masculino e quanto aos espécimes clínicos oriundas de medula óssea (85,00), linfonodo (64,29), líquido ascítico (42,86), sangue (39,96) e abscesso (33,33). Ao analisar a razão de prevalência verificou possível associação de histoplasmose em amostras de pacientes, cujas principais matrizes biológicas foram o sangue 6,28 (6,04 – 11,89), medula óssea 5,72 (4,52 – 68,12) e linfonodo (3,15 – 28,48). Conclusão: Nota-se frente à prevalência encontrada a relevância da notificação compulsória dessa micose a nível nacional, a fim de melhorar o monitoramento para subsidiar medidas que facilitem o diagnóstico precoce e o tratamento adequado.

Клинико-эпидемио­логический анализ заболеваемости гистоплазмозом в мире

MicroRNAs (miRNAs) are a class of non-coding small RNAs that play important roles in the regulation of various biological processes including cell development and differentiation, apoptosis, tumorigenesis, immunoregulation and viral infections. Avian immunosuppressive diseases refer to those avian diseases caused by pathogens that target and damage the immune organs or cells of the host, increasing susceptibility to other microbial infections and the risk of failure in subsequent vaccination against other diseases. As such, once a disease with an immunosuppressive feature occurs in flocks, it would be difficult for the stakeholders to have an optimal economic income. Infectious bursal disease (IBD), avian leukemia (AL), Marek’s disease (MD), chicken infectious anemia (CIA), reticuloendotheliosis (RE) and avian reovirus infection are on the top list of commonly-seen avian diseases with a feature of immunosuppression, posing an unmeasurable threat to the poultry industry across the globe. Understanding the pathogenesis of avian immunosuppressive disease is the basis for disease prevention and control. miRNAs have been shown to be involved in host response to pathogenic infections in chickens, including regulation of immunity, tumorigenesis, cell proliferation and viral replication. Here we summarize current knowledge on the roles of miRNAs in avian response to viral infection and pathogenesis of avian immunosuppressive diseases, in particular, MD, AL, IBD and RE.

BackgroundThe guideline-preferred azole for histoplasmosis (HP) is itraconazole (IC). While voriconazole (VC) has shown success in in-vitro and in retrospective analyses, there has not been enough data to include newer generation azoles as first-line treatment for infections with Histoplasma capsulatum.MethodsWe conducted a single-center retrospective cohort study of adult patients diagnosed with HP from 2002 through 2017. Data included demographics, clinical features and sites of infection, immune status, treatments, and mortality. Patients were categorized into two groups based on initial choice of azole (IC or VC) and mortality was compared between these two groups. The treatment groups were defined based on the first azole received, either IC or VC, as initial or as step-down therapy from amphotericin. Patients initiated on other azoles were excluded.ResultsWe identified 263 cases of HP from 2002 to 2017. After excluding patients initiated on other azoles, 194 patients remained. 175 (90%) patients were started on IC and 19 (10%) were started on VC, either as stepdown or initial choice of antifungal. There were no significant demographic differences between patients receiving IC compared with VC as their initial azole treatment. Patients with hematologic malignancies tended to be prescribed VC more frequently but this was not statistically significant (OR 3.1 [0.77–12.4]). Death occurred in 40 (23%) patients from the IC and 5 (26%) patients from the VC group. The hazard ratio for mortality with the use of VC was 1.21 (CI 0.4–3.6, P = 0.73).ConclusionIC is the mainstay in the treatment for HP. It appears that VC has comparable outcomes to IC and can be considered an alternative treatment option for HP, at least for patients with contraindications to IC treatment.DisclosuresAll authors: No reported disclosures.

Public health surveillance for histoplasmosis is limited. Currently, fewer than 1000 cases are reported each year, but the burden of disease is likely

Histoplasmosis: Time to Redraw the Map and Up Our Game.

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum var. capsulatum and Histoplasma capsulatum var. duboisii (in Africa) [1]. These infective agents are present mainly in the soil, particularly if contaminated with bird or bat droppings. The infection, acquired via inhalation, is generally asymptomatic, but in a small percentage of cases (1%) it may result in influenza-like symptoms, often self-limiting. It affects mainly immunocompromised patients and worsens in case of high exposure level. It may involve all organs and systems, and may mimic many other infectious and non-infectious disorders, which are more frequent just in these immunocompromised hosts.

Avian reticuloendotheliosis (RE) represents an important immunosuppressive disease of poultry. The occurrence of RE in both chickens and turkeys has an immunosuppressive effect and may lead to vaccination failures. Avian reticuloendotheliosis virus (REV) is widely distributed in different kinds of birds, causing subclinical infections. Another important issue adhering to this disease is contamination of vaccines against fowl pox (FP) and Marek’s disease (MD) with REV. The capability of REV to integrate into the genome of other larger DNA viruses complicates its diagnosis and prevention. There are no efficient vaccines against RE nor treatment, which also complicates how to limit its impact on poultry farming. This paper reviews the current state of knowledge of this important immunosuppressive agent of poultry emphasising the importance of this problem in terms of diagnosis of RE.

African cutaneous histoplasmosis is a rare mycosis. It usually occurs in patients immunecompromised by HIV. The occurrence of the disease in the immune-competent is rarely described and often present with papules. The clinical aspects actually are numerous and misleading. We report 2 cases of African histoplasmosis in immune-competent children. The first case occurred in an 11-year-old child as multiple subcutaneous nodules simulating lipomas and the second case presented as multiple ulcerated lesions of the face in a 13-year-old patient.