Human Vγ9Vδ2 T cells exhibit antifungal activity against Aspergillus fumigatus and other filamentous fungi.

Invasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant Aspergillus fumigatus strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on Vγ9Vδ2 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when A. fumigatus (Af293) hyphae were challenged by Vγ9Vδ2 T cells derived from peripheral blood. In addition, Vγ9Vδ2 T cells exhibited antifungal activity against hyphae of all Aspergillus spp., Cunninghamella bertholletiae, and Rhizopus microsporus but not against their conidia. Furthermore, Vγ9Vδ2 T cells also exhibited antifungal activity against azole-resistant A. fumigatus, indicating that Vγ9Vδ2 T cells could be used for treating drug-resistant A. fumigatus. The antifungal activity of Vγ9Vδ2 T cells depended on cell-to-cell contact with A. fumigatus hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against A. fumigatus. Vγ9Vδ2 T cells could be developed as a novel modality for treating IA or mucormycosis. IMPORTANCE: Invasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of Vγ9Vδ2 T cells against various Aspergillus spp. and several Mucorales in vitro and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using Vγ9Vδ2 T cells may offer a new therapeutic approach to IA.

Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

Risk factor of non-tuberculous Mycobacterium infection in patients with rheumatoid arthritis and other autoimmune diseases receiving biologic agents: A multicenter retrospective study.

BACKGROUND: Evidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents' usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development. METHODS: This retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria. RESULTS: Of the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038). CONCLUSION: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative.

Clinical features relating to pneumococcal colony phase variation in hospitalized adults with pneumonia.

Background. Streptococcus pneumoniae is a major causative bacteria of pneumonia and invasive pneumococcal disease (IPD); however, the mechanisms underlying its severity and invasion remain to be defined. Pneumococcal colonies exhibit opaque and transparent opacity phase variations, which have been associated with invasive infections and nasal colonization, respectively, in animal studies. This study evaluated the relationship between the opacity of pneumococcal colonies and the clinical presentation of pneumococcal pneumonia.Methods. This retrospective study included adult patients hospitalized with pneumococcal pneumonia between 2012 and 2019 at four tertiary medical institutions. Pneumococcal strains from lower respiratory tract specimens were determined for their serotypes and microscopic colony opacity, and the association between the opacity phase and the severity of pneumonia was evaluated. Serotypes 3 and 37 with mucoid colony phenotypes were excluded from the study because their colony morphologies were clearly different.Results. A total of 92 patients were included. Most patients were older adults (median age: 72 years) and males (67 %), and 59 % had community-acquired pneumonia. Of the 92 patients, 41 (45 %), 12 (13 %), and 39 (42 %) patients had opaque, transparent, and mixed variants in their pneumococcal colony, respectively. The opaque and non-opaque pneumococcal variants had no statistically significant difference in patient backgrounds. Although the pneumonia severity index score did not differ between the opaque and non-opaque groups, the rate of bacteremia was significantly higher in the opaque group than in the non-opaque group. Serotype distribution was similar between the groups.Conclusions. Opaque pneumococcal variants may cause pneumonia and invasive diseases in humans. This study could help elucidate IPD, and opacity assessment may serve as a predictor for IPD.

Efficacy and safety of lascufloxacin for nursing- and healthcare-associated pneumonia: A single-arm, open-label clinical trial.

BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.

The prognostic factors for cryptococcal meningitis in non-human immunodeficiency virus patients: An observational study using nationwide database.

BACKGROUND: Cryptococcal meningitis (CM) is an invasive fungal infection with a poor prognosis that often occurs in both healthy individuals and compromised hosts, such as patients infected with human immunodeficiency virus (HIV). Unlike CM in HIV patients, evidence regarding CM in non-HIV patients is limited to small retrospective studies. OBJECTIVE: To identify the pretreatment prognostic factors for CM in non-HIV patients. METHODS: We conducted a large retrospective analysis of CM in non-HIV patients using data from a nationwide Japanese database. The study included hospitalized patients diagnosed with CM between 1 April 2010 and 31 March 2017. All-cause mortality was compared between patients with CM with and without HIV infection. Poor diagnostic factors were analysed in the non-HIV CM group. RESULTS: Overall, 533 (64 HIV and 469 non-HIV) patients met the criteria. The mortality rate at 90 days was significantly lower in the HIV group (6.3% vs. 25.4% p = .0002). In a logistic regression analysis of the non-HIV group, age ≥ 65 y (odds ratio [OR] 2.37, 95% CI 1.17-4.78), impaired consciousness (Japan Coma Scale ≥1) (OR 2.25, 95% CI 1.29-3.93), haemodialysis (OR 3.53, 95% CI 1.12-11.20) and previous corticosteroid usage (OR 2.40, 95% CI 1.37-4.19) were associated with poor prognosis at 30 days after diagnosis. CONCLUSION: More caution is suggested when treating non-HIV with CM in older patients with impaired consciousness, previous corticosteroid usage and haemodialysis.

Efficacy of Intrathecal Isoniazid and Steroid Therapy in Refractory Tuberculous Meningitis.

Tuberculous meningitis is an infectious disease with high mortality. Literature describing intrathecal therapy for tuberculous meningitis is scarce. We herein report a case of refractory tuberculous meningitis in a 52-year-old woman with underlying neuropsychiatric systemic lupus erythematosus. Despite systemic treatment with anti-tuberculosis drugs and dexamethasone, her meningeal irritation deteriorated. Intrathecal isoniazid and prednisolone administration was therefore initiated, and the symptoms of severe meningeal irritation improved along with head magnetic resonance imaging and cerebrospinal fluid findings. This case report highlights the efficacy of intrathecal isoniazid and steroid injections for refractory tuberculous meningitis, particularly in patients with severe meningeal irritation.

Rapid increase in salivary IgA and broad recognition of spike protein following SARS-CoV-2 vaccination.

Saliva is a key component of mucosal immunity, which protects the oral cavity from viral infections. However, salivary immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in terms of immunoglobulin dynamics and recognition, have not been investigated sufficiently. In this study, saliva samples were collected from individuals that received SARS-CoV-2 vaccine, and immunoglobulin G (IgG), IgM, and IgA against whole spike protein and S1 protein were measured. IgA against whole spike protein increased significantly following vaccination, while IgA against S1 protein did not. Of note, the IgA response was evident two weeks after the first vaccine dose and continued to rise thereafter. On the contrary, IgG antibodies against S1 increased significantly at four weeks after vaccination. These results reveal the dynamics and recognition antigens of immunoglobulins in saliva, indicating the function of IgA in the mucosal immune system. These findings may pave the way for further studies on mucosal immune response induced by vaccination.

The evaluation of a rapid microfluidic immunofluorescence antigen test in detecting the infectiousness of COVID-19 patients.

BACKGROUND: A test-based strategy against coronavirus disease 2019 (COVID-19) is one of the measures to assess the need for isolation and prevention of infection. However, testing with high sensitivity methods, such as quantitative RT-PCR, leads to unnecessary isolation, whereas the lateral flow antigen test shows low sensitivity and false negative results. The purpose of this study was to evaluate the performance of the LumiraDx SARS-CoV-2 Ag test (Lumira Ag), a rapid microfluidic immunofluorescence method, in assessing infectivity. METHODS: This study was performed from March 2022 to July 2022. A pair of nasopharyngeal swab samples were obtained from each patient with mild COVID-19. One swab was used for Lumira Ag testing, and the other for quantitative RT-PCR testing and virus culture. RESULTS: A total of 84 patients were included in the study. Among them, PCR, Lumira Ag test, and virus culture indicated positivity for 82, 66, and 24 patients, respectively. When comparing the Lumira Ag test to virus culture, its sensitivity was 100.0% (24/24), specificity, 30.0% (18/60); positive predictive value, 36.3% (24/66); and negative predictive value (NPV), 100.0% (18/18). The positive sample for virus culture was observed until the ninth day from the onset of symptoms, while the Lumira Ag test was observed until day 11. CONCLUSIONS: The Lumira Ag test showed high sensitivity and NPV (100% each) compared to virus culture. A test-based strategy using the Lumira Ag test can effectively exclude COVID-19 infectiousness.

Lung Involvement in Adult T-Cell Lymphoma Diagnosed Using Bronchoscopic Cryobiopsy: A Case Report and Review of the Literature.

The diagnosis of pulmonary lymphoma using small tissue samples is difficult and often requires surgical procedures; thus, a less invasive sampling method is desirable. Moreover, pulmonary involvement in adult T-cell lymphoma (ATL) is often difficult to diagnose, especially in cases without characteristic flower cells. Here, we present the case of a 78-year-old man, in whom pathological examination of the transbronchial lung biopsy (TBLB) specimen did not reveal malignant findings; therefore, transbronchial lung cryobiopsy (TBLC) in combination with endobronchial ultrasonography (EBUS) was used to diagnose ATL based on the pathological findings. A literature review identified 18 cases of pulmonary lymphomas diagnosed using TBLC. Among the 19 cases, including our own, 16 cases were of B-cell lymphoma (84.2%), and the present case is the first case of ATL diagnosed using TBLC. Eighty percent of the cases underwent a biopsy (more than two samples) of the middle or lower lobe and were diagnosed without major complications. EBUS was used with TBLC in three cases to identify the location of the pulmonary lesions. In the present case, EBUS was also useful for avoiding vascular biopsy. Although large-scale prospective studies are required to establish precise guidelines for diagnosing pulmonary lymphomas using TBLC, our case report and review contributes to a deeper understanding of the diagnosis of rare diseases.

Invasive Malassezia Infections.

The Malassezia species are dimorphic fungi that require lipids such as olive oil for their growth. They are constituents of the normal human skin microbiota and can affix to the host or other surfaces through the establishment of biofilms. Malassezia species are accountable for superficial mycoses like folliculitis. Additionally, they are capable of causing invasive infections, such as of the bloodstream, in neonates and immunocompromised patients, albeit infrequently. Catheter-associated bloodstream infections in neonates are the most commonly reported invasive cases. Remarkably, unlike other invasive fungal infections, neutropenia and the use of broad-spectrum antibiotics do not seem to contribute to the risk of invasive Malassezia infections. Nosocomial outbreaks of Malassezia infections have been reported. While most cases of invasive Malassezia infection are fungemia, they seldom give rise to disseminated lesions in various organs. The diagnosis can be confirmed by the visualization of characteristic yeasts through histologic or cytologic examination of a biopsy or needle aspiration specimen, or via positive culture results from sterile sites. The prognosis for invasive Malassezia infection is generally favorable, with few reports of treatment failure. Nevertheless, due to the limited number of cases, evidence-based treatment recommendations are wanting. Management of invasive Malassezia infections linked to central venous catheters includes removal of the catheter, cessation of intravenous lipid emulsion, and intravenous administration of appropriate antifungal agents.

A high α1-antitrypsin/interleukin-10 ratio predicts bacterial pneumonia in adults with community-acquired pneumonia: a prospective cohort study.

BACKGROUND: Current microbiological tests fail to identify the causative microorganism in more than half of all pneumonia cases. We explored biomarkers that could be used for differentiating between bacterial and viral pneumonia in patients with community-acquired pneumonia (CAP). METHODS: In this prospective cohort study conducted in Japan, data obtained from adult patients with bacterial pneumonia, including bacterial and viral coinfections (bacterial pneumonia [BP] group), and purely viral pneumonia (VP group) at diagnosis were analyzed using multivariate logistic regression analysis to identify predictors of bacterial pneumonia. Furthermore, a decision tree was developed using the predictors. RESULTS: A total of 210 patients were analyzed. The BP and VP groups comprised 108 and 18 patients, respectively. The other 84 patients had no identified causative microorganism. The two groups shared similar characteristics, including disease severity; however, a significant difference (p < 0.05) was observed between the two groups regarding sputum type; sputum volume score; neutrophil counts; and serum levels of interleukin (IL)-8, IL-10, and α1-antitrypsin (AAT). Sputum volume score (p < 0.001), IL-10 (p < 0.001), and AAT (p = 0.008) were ultimately identified as predictors of BP. The area under the curve for these three variables on the receiver operating characteristic (ROC) curve was 0.927 (95% confidence interval [CI]: 0.881-0.974). The ROC curve for sputum volume score and an AAT/IL-10 ratio showed a diagnostic cutoff of 1 + and 65, respectively. Logistic regression analysis using dichotomized variables at the cutoff values showed that the odds ratios for the diagnosis of BP were 10.4 (95% CI: 2.2-50.2) for sputum volume score (absence vs. presence) and 19.8 (95% CI: 4.7-83.2) for AAT/IL-10 ratio (< 65 vs. ≥ 65). CONCLUSIONS: Considering that obtaining a definitive etiologic diagnosis with the current testing methods is difficult and time consuming, a decision tree with two predictors, namely sputum volume and the AAT/IL-10 ratio, can be useful in predicting BP among patients diagnosed with CAP and facilitating the appropriate use of antibiotics. TRIAL REGISTRATION: UMIN000034673 registered on November 29, 2018.

Hereditary Hemorrhagic Telangiectasia in a Patient Undergoing Hemodialysis with Anticoagulants and Antiplatelets: A Case Report.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes abnormal blood vessel formation and bleeding. We herein report a 61-year-old woman with aggravated HHT symptoms after hemodialysis initiation. She was diagnosed with HHT based on her recurrent bleeding, abnormal blood vessel formation, and family history. Despite bleeding complications, the patient required anticoagulants and antiplatelet agents to treat cardiovascular complications. Eventually, the patient died of extensive cerebral hemorrhaging. Our experience suggests that special attention should be paid to bleeding complications in high-risk patients.

Pulmonary Langerhans cell histiocytosis diagnosed using transbronchial lung cryobiopsy: A case report.

A 63-year-old Japanese woman with multiple cysts in both lungs on chest computed tomography (CT) was referred to our hospital after a thorough examination, including a transbronchial lung biopsy (TBLB), failed to provide a diagnosis. Based on the findings on chest CT and pathological examination of the bronchoalveolar lavage fluid and transbronchial lung cryobiopsy (TBLC) specimen, the patient was diagnosed with pulmonary Langerhans cell histiocytosis (PLCH). TBLC may replace TBLB as the main diagnostic technique for PLCH, although further studies are required to determine the usefulness of TBLC for the diagnosis of PLCH.

Serum Cytokine Changes in a Patient with Chronic Pulmonary Aspergillosis Overlapping with Allergic Bronchopulmonary Aspergillosis: A Case Report.

Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are diseases caused by Aspergillus infection, and CPA can develop from ABPA in some cases. We herein report a patient with CPA overlapping with ABPA. Serum cytokine levels were evaluated at 4 time points: the ABPA diagnosis, CPA diagnosis, 6 months after the start of voriconazole (VRCZ), and 12 months after re-administration of VRCZ. Interleukin (IL)-13 levels decreased upon glucocorticoid treatment, whereas IL-25 and IL-33 levels decreased rapidly with the initiation of antifungals. Early antifungal therapy may be important to control disease progression and prevent CPA overlap.

Prognostic Association of Liposomal Amphotericin B Doses Above 5†mg/kg/d in Mucormycosis: A Nationwide Epidemiologic and Treatment Analysis in Japan.

Background: Mucormycosis is a potentially fatal fungal infection, and there is limited information on its precise epidemiology and treatment practices, including the optimal dosage of liposomal amphotericin B. Methods: A retrospective, multicenter, nationwide analysis of 82 proven and probable cases of mucormycosis was performed. Cases between 2015 and 2022 were collected from 51 hospitals in Japan by hematologists and infectious disease specialists. The study included the epidemiology, treatment details, and association between the dose of liposomal amphotericin B and the outcome. Results: The lungs were the most commonly involved organ (70.7% of cases), and 35.4% of patients had disseminated disease. Rhizopus spp., Cunninghamella spp., and Mucor spp. were the most common organisms. Mortality at 4 weeks was 41.5%. The survivors had a shorter duration of neutropenia (P = .006) and less persistent hyperglycemia (P = .023). The site of infection and species of Mucorales had no detectable effect on survival. Survival did not differ between patients receiving liposomal amphotericin B at 5 mg/kg/d relative to those receiving >5 mg/kg/d (P = .625). Using Cox proportional hazards models and adjusting for confounders, the hazard ratio for the influence of >5 mg/kg/d liposomal amphotericin B on 4-week survival was 0.86 (95% CI, 0.28-2.68; P = .796) compared with 5 mg/kg/d. Conclusions: This study provides important insights into the precise epidemiology and treatment practices of mucormycosis. Treatment with liposomal amphotericin B at doses higher than 5 mg/kg/d did not improve outcomes relative to 5 mg/kg/d.

Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial.

BACKGROUND: 5-aminolevulinic acid (5-ALA), a natural amino acid that is marketed alongside sodium ferrous citrate (SFC) as a functional food, blocks severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proliferation in vitro and exerts anti-inflammatory effects. In this phase II open-label, prospective, parallel-group, randomized trial, we aimed to evaluate the safety and efficacy of 5-ALA in patients with mild-to-moderate coronavirus disease 2019. METHODS: This trial was conducted in patients receiving 5-ALA/SFC (250/145 mg) orally thrice daily for 7 days, followed by 5-ALA/SFC (150/87 mg) orally thrice daily for 7 days. The primary endpoints were changes in SARS-CoV-2 viral load, clinical symptom scores, and 5-ALA/SFC safety (adverse events [AE] and changes in laboratory values and vital signs). RESULTS: A total of 50 patients were enrolled from 8 institutions in Japan. The change in SARS-CoV-2 viral load from baseline was not significantly different between the 5-ALA/SFC (n = 24) and control (n = 26) groups. The duration to improvement was shorter in the 5-ALA/SFC group than in the control group, although the difference was not significant. The 5-ALA/SFC group exhibited faster improvement rates in "taste abnormality," "cough," "lethargy," and "no appetite" than the control group. Eight AEs were observed in the 5-ALA/SFC group, with 22.7% of patients experiencing gastrointestinal symptoms (decreased appetite, constipation, and vomiting). AEs occurred with 750/435 mg/day in 25.0% of patients in the first phase and with 450/261 mg/day of 5-ALA/SFC in 6.3% of patients in the second phase. CONCLUSION: 5-ALA/SFC improved some symptoms but did not influence the SARS-CoV-2 viral load or clinical symptom scores over 14 days. The safety of 5-ALA/SFC in this study was acceptable. Further evaluation using a larger sample size or modified method is warranted.

Antifungal susceptibility profiles of Cryptococcus neoformans strains clinically isolated from non-HIV-infected patients in Nagasaki, Japan.

Data on antifungal susceptibility of Cryptococcus neoformans are limited in Japan. A total of 89 C. neoformans strains isolated from 83 non-human immunodeficiency virus-infected patients with cryptococcosis between 1997 and 2021 in Nagasaki, Japan, were investigated. Using the reference method M27-Ed4 by the Clinical and Laboratory Standards Institute, the minimum inhibitory concentration for 90% of isolates of fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine were 4, 0.125, 0.06, 0.5, and 4 µg/ml, respectively, which were below the reported epidemiological cutoff values, without any detectable non-wild-type strains. Our findings imply no increasing trend of antifungal-resistant C. neoformans in Nagasaki, Japan.

Cryptococcus neoformans strains obtained from non-human immunodeficiency virus-infected patients were observed to maintain good antifungal susceptibility to fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine over a 25-year-long period in Nagasaki, Japan.

Disseminated Mycobacterium genavense Infection Mimicking Sarcoidosis: A Case Report and Review of Literature on Japanese Patients.

Sarcoidosis is a systemic inflammatory disease characterized by noncaseating epithelioid cell granulomas. However, certain infections can exhibit similar histological findings. We present a case of a 69-year-old man who was initially diagnosed with sarcoidosis and later was confirmed, through 16S rRNA sequencing, to have disseminated Mycobacterium genavense infection. Acid-fast bacteria were detected in the bone marrow biopsy using Ziehl-Neelsen staining, but routine clinical tests did not provide a definitive diagnosis. The patient tested negative for HIV, anti-interferon-gamma antibodies, and genetic immunodeficiency disorders. He was treated with multiple drugs, including aminoglycosides and macrolides, but showed no improvement in fever and pancytopenia. However, these clinical signs responded favorably to steroid therapy. We reviewed 17 Japanese cases of M. genavense infection. All cases were in males; 7/17 (41%) were HIV-negative; and 12/17 (71%) had a decreased CD4 count. Genetic analysis confirmed M. genavense isolation, and macrolides were used universally. Mycobacterium genavense infection is challenging to identify and mimics other systemic inflammatory diseases such as sarcoidosis. There are no standard treatment protocols. Our case report and Japanese case review contribute to understanding this rare disease.