Rapid and precise diagnosis of <i>T. marneffei</i> pulmonary infection in a HIV-negative patient with autosomal-dominant <i>STAT3</i> mutation: a case report

Zhang, Wei; Ye, Jian; Qiu, Chenhui; Wang, Limin; Jin, Wu; Jiang, Chunming; Xu, Lihui; Xu, Jianping; Li, Yue; Wang, Liusheng; Jin, Hualiang

doi:10.1177/1753466620929225

Cited by 23 publications

(33 citation statements)

References 16 publications

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“…The main manifestations of T. marneffei infection are fever, weight loss, lymphadenectasis, anemia, and hepatosplenomegaly, but they are nonspecific and have no significance for differential diagnosis ( Vanittanakom and Sirisanthana, 1997 ; Li et al., 2016 ; Zhang W. et al., 2020 ). Our patient developed fever, anemia and hepatosplenomegaly.…”

Section: Resultsmentioning

confidence: 99%

“…RelB is involved in the alternative pathway of NF-κB; therefore, the patient showed CID. In addition to RELB , STAT3, STAT1, TNFSF5 (CD40L) , and IFNGR1 mutations ( Supplementary Table 4 ) are found in HIV-negative patients infected with T. marneffei ( Lee et al., 2012 ; Lee et al., 2014 ; Fan et al., 2018 ; Lee et al., 2019 ; Zhang W. et al., 2020 ). Although some patients have T. marneffei infection only after adulthood, these patients with immunodeficiency caused by gene mutations all have clinica\l symptoms in the early stage.…”

Section: Resultsmentioning

confidence: 99%

“…Roifman et al reported that 3 brothers suffered from combined immunodeficiency (CID) due to a homozygous mutation (c.C1191A/p.Y397X) in the RELB gene ( Mericoa et al., 2015 ; Sharfe et al., 2015 ; Ovadia et al., 2017 ). To date, STAT3, STAT1, TNFSF5(CD40L) , and IFNGR1 mutations have been found in HIV-negative patients with T. marneffei infection ( Lee et al., 2012 ; Lee et al., 2014 ; Fan et al., 2018 ; Lee et al., 2019 ; Zhang W. et al., 2020 ). In this study, we present a non-HIV infant infected with T. marneffei and CID carrying a homozygous private variant of RELB.…”

Section: Introductionmentioning

confidence: 99%

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Disseminated Talaromyces marneffei Infection in a Non-HIV Infant With a Homozygous Private Variant of RELB

Ding

Huang

Zhao

et al. 2021

Front. Cell. Infect. Microbiol.

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ObjectiveThis study presents a relatively rare case of disseminated Talaromyces marneffei (T. marneffei) infection in an HIV-negative patient.MethodsAn 8-month-old girl was hospitalized because of uncontrollable fever and cough for 6 days. Routine laboratory tests, biochemical detection, immunological tests, pathogenic examination, and imaging inspection were performed. Genetic tests of trio whole genome sequencing (Trio-WES), trio copy number sequencing (Trio-CNVseq), and Sanger sequencing were conducted to identify pathogenic variants. In silico analysis of the sequence alignment and structural modeling results was carried out to study the possible pathogenicity of the identified variant. Western blotting was performed to investigate the expression of the identified gene at the protein level.ResultsEnhanced CT and MRI scanning demonstrated thymic dysplasia, diffuse pulmonary and liver nodules, and many balloon-like air sacs in both lungs. The white blood cell count, neutrophil count, and neutrophil ratio were normal or elevated. The patient was HIV-negative and bone marrow and blood culture showed T. marneffei infection. Total lymphocyte count, CD3+ T lymphocyte count, CD3+CD4+ T lymphocyte count, CD3+CD8+ T lymphocyte count, and NK cell count decreased, while the number of CD19 positive B cells increased. However, the ratio of CD3+CD4+:CD3+CD8+ T cells increased. Trio-WES identified a homozygous private variant of NM_006509: c.400_c.401insAGC/p.Lys134 delinsLysGln in RELB and Sanger sequencing validated the result. Structural modeling indicated that the variant may be pathogenic. Reverse transcription-polymerase chain reaction and Western blot analysis showed that the expression of RelB in the patient was lower than that in the healthy controls at mRNA and protein levels.ConclusionThis is the first report on disseminated T. marneffei infection in a patient with a homozygous private variant of RELB.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Disseminated Talaromyces marneffei Infection in a Non-HIV Infant With a Homozygous Private Variant of RELB

Ding

Huang

Zhao

et al. 2021

Front. Cell. Infect. Microbiol.

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“…a Bronchoscopy demonstrating irregular bronchial mucosal surface, in a 34-year-old immunocompromised female with a STAT3 mutation. Tm was grown from biopsied tissue [59]. b Computed tomography (CT) angiogram of the neck demonstrating an ill-defined mass along the right lateral aspect of the hypopharynx involving the base of the tongue, right lingual tonsil, and right vallecula extending along the right palatine tonsil and into the pharyngeal space, in a 63 year-old man with HIV [27] from China, 42/61 (69%) had pleural effusions; all cases were initially misdiagnosed as tuberculosis [37].…”

Section: Lower Respiratory Tract Infectionmentioning

confidence: 99%

Pulmonary Talaromycosis: A Window into the Immunopathogenesis of an Endemic Mycosis

et al. 2021

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Talaromycosis is an invasive mycosis caused by the thermally dimorphic saprophytic fungus Talaromyces marneffei (Tm) endemic in Asia. Like other endemic mycoses, talaromycosis occurs predominantly in immunocompromised and, to a lesser extent, immunocompetent hosts. The lungs are the primary portal of entry, and pulmonary manifestations provide a window into the immunopathogenesis of talaromycosis. Failure of alveolar macrophages to destroy Tm results in reticuloendothelial system dissemination and multi-organ disease. Primary or secondary immune defects that reduce CD4+ T cells, INF-γ, IL-12, and IL-17 functions, such as HIV infection, anti-interferon-γ autoantibodies, STAT-1 and STAT-3 mutations, and CD40 ligand deficiency, highlight the central roles of Th1 and Th17 effector cells in the control of Tm infection. Both upper and lower respiratory infections can manifest as localised or disseminated disease. Upper respiratory disease appears unique to talaromycosis, presenting with oropharyngeal lesions and obstructive tracheobronchial masses. Lower respiratory disease is protean, including alveolar consolidation, solitary or multiple nodules, mediastinal lymphadenopathy, cavitary disease, and pleural effusion. Structural lung disease such as chronic obstructive pulmonary disease is an emerging risk factor in immunocompetent hosts. Mortality, up to 55%, is driven by delayed or missed diagnosis. Rapid, non-culture-based diagnostics including antigen and PCR assays are shown to be superior to blood culture for diagnosis, but still require rigorous clinical validation and commercialisation. Our current understanding of acute pulmonary infections is limited by the lack of an antibody test. Such a tool is expected to unveil a larger disease burden and wider clinical spectrum of talaromycosis.

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“…7 However, the rate of T. marneffei infection in HIV-negative patients has increased. 8,9 This current case report describes a patient with T. marneffei infection in a nonprevalent region of South China. The patient was immunocompetent and presented with diffuse ground-glass, cystic and cavitated lesions in both lungs.…”

Section: Introductionmentioning

confidence: 96%

HIV-negative case of Talaromyces marneffei pulmonary infection with a TSC2 mutation

2021

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Talaromyces marneffei is a rare dimorphic pathogenic fungus that can induce severe infections in human immunodeficiency virus (HIV)-infected patients. However, such infections have also been reported in non-HIV hosts. This current case report describes a very rare case of a T. marneffei pulmonary infection in an HIV-negative patient with a mutation in the tuberous sclerosis complex subunit 2 ( TSC2) gene. A 24-year-old male patient presented with cough and expectoration for 6 months. Computed tomography showed multiple ground-glass opacities and cystic and cavitated lesions in both lungs. Next generation sequencing (NGS) of the bronchoalveolar lavage fluid was performed to confirm T. marneffei pulmonary infection. The results were further verified using bronchoscopy specimen cultures. This was an HIV-negative patient without a travel history to endemic zones and his blood exon sequencing results showed a mutation in the TSC2 gene. To date, he has recovered well with voriconazole therapy. In summary, patients with TSC2 mutations that induce bronchopulmonary dysplasia may be potential hosts for T. marneffei. Early and timely diagnosis is important for improving prognosis. NGS plays a critical role in the diagnosis of T. marneffei pulmonary infection.

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Rapid and precise diagnosis of T. marneffei pulmonary infection in a HIV-negative patient with autosomal-dominant STAT3 mutation: a case report

Cited by 23 publications

References 16 publications

Disseminated Talaromyces marneffei Infection in a Non-HIV Infant With a Homozygous Private Variant of RELB

Disseminated Talaromyces marneffei Infection in a Non-HIV Infant With a Homozygous Private Variant of RELB

Pulmonary Talaromycosis: A Window into the Immunopathogenesis of an Endemic Mycosis

HIV-negative case of Talaromyces marneffei pulmonary infection with a TSC2 mutation

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