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Nocardiosis Associated with Primary Immunodeficiencies (Nocar-DIP): an International Retrospective Study and Literature Review

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Abstract

Purpose

Nocardiosis is a life-threatening infectious disease. We aimed at describing nocardiosis in patients with primary immunodeficiency diseases (PID).

Methods

This international retrospective cohort included patients with PID and nocardiosis diagnosed and/or published from Jan 1, 2000, to Dec 31, 2016. To identify nocardiosis cases, we analyzed PID databases from the French National Reference Center for PID (Paris, France) and the National Institute of Health (NIH, United States of America) and we performed a literature review on PubMed.

Results

Forty-nine cases of nocardiosis associated with PID were included: median age at diagnosis of nocardiosis was 19 (0–56) years and most cases were observed among chronic granulomatous disease (CGD) patients (87.8%). Median time from symptoms to diagnosis of Nocardia infection was 20 (2–257) days. Most frequent clinical nocardiosis presentation was pneumonia (86.7%). Twelve-month mortality rate was 4.2%, and 11.9% of patients experienced a possible recurrence of infection. Nocardiosis more frequently led to the diagnosis of PID among non-CGD patients than in CGD patients. Non-CGD patients experienced more cerebral nocardiosis and more disseminated infections, but mortality and recurrence rates were similar. Highest incidences of nocardiosis among PID cohorts were observed among CGD patients (0.0057 and 0.0044 cases/patient-year in the USA and in France, respectively), followed by IL-12p40 deficiency.

Conclusions

Among 49 cases of nocardiosis associated with PID, most patients had CGD and lung involvement. Both mortality and recurrence rates were low.

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Abbreviations

ABT:

Antibiotic therapy

AST:

Antibiotic susceptibility testing

ADA:

Adenosine deaminase

BAL:

Bronchoalveolar lavage

CGD:

Chronic Granulomatous Disease

CEREDIH:

Centre de Référence des Déficits Immunitaires Héréditaires

CNS:

Central nervous system

COPD:

Chronic obstructive pulmonary disease

CS:

Corticosteroids

CVID:

Common variable immunodeficiency

HIV:

Human virus immunodeficiency

HCST:

Hematopoietic stem cell transplantation

ICL:

Idiopathic CD4 Lymphocytopenia

IL12RB1:

Interleukine-12 and Interleukine-23 receptor β1 chain deficiency

IL-12p40 deficiency:

Interleukine-12p40 deficiency

NIH:

National Institute of Health

STAT1 GoF:

Signal transducer and activator of transcription 1 gain-of-function

STAT3 LoF:

Deficiency of the signal transducer and activator of transcription 3

TMP-SMX:

Trimethoprim–sulfamethoxazole

USA:

United States of America

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Acknowledgments

We wish to thank Marion Malphettes, Jean Donadieu, and all members of the CEREDIH for their help in this work.

Authorship Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Emmanuel Lafont, Beatriz Marciano, and David Lebeaux. The first draft of the manuscript was written by Emmanuel Lafont, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

Funding for this study was provided in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Author information

Author notes

  1. Olivier Lortholary and Steven M. Holland contributed equally to this work.

Authors and Affiliations

  1. Department of Infectious Diseases and Tropical Medicine, Centre d’Infectiologie Necker -Pasteur, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker-Enfants Malades University Hospital, Université de Paris, Paris, France

    Emmanuel Lafont, Olivier Lortholary & David Lebeaux

  2. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Beatriz E. Marciano & Steven M. Holland

  3. Pediatric Immuno-Haematology and Rheumatology Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Enfants Malades University Hospital, Paris, France

    Nizar Mahlaoui, Bénédicte Neven, Alain Fischer & Stéphane Blanche

  4. French National Reference Center for Primary Immune Deficiencies (CEREDIH), Assistance Publique-Hôpitaux de Paris, (AP-HP), Necker Enfants Malades University Hospital, Paris, France

    Nizar Mahlaoui, Bénédicte Neven, Alain Fischer, Stéphane Blanche & Olivier Lortholary

  5. Sorbonne Paris Cite, Imagine Institute, INSERM UMR 1163, Université de Paris, Paris, France

    Bénédicte Neven, Jacinta Bustamante, Alain Fischer & Stéphane Blanche

  6. Laboratory of Human Genetics of Infectious Diseases, INSERM U1163, Necker Enfants Malades University Hospital, Paris, France

    Jacinta Bustamante

  7. Center for the Study of Primary Immunodeficiencies (CEDI), Assistance Publique – Hôpitaux de Paris (AP-HP), Necker Enfants Malades University Hospital, Paris, France

    Jacinta Bustamante

  8. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA

    Jacinta Bustamante

  9. Research group on Bacterial Opportunistic Pathogens and Environment UMR5557 Écologie Microbienne, French Observatory of Nocardiosis, CNRS, VetAgro Sup, Université de Lyon 1, Lyon, France

    Veronica Rodriguez-Nava

  10. Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Amit Rawat

  11. Department of Microbiology, Hospital de Basurto, 48013, Bilbao, Basque Country, Spain

    Miren Josebe Unzaga

  12. Collège de France, Paris, France

    Alain Fischer

  13. Université de Paris, 75006, Paris, France

    David Lebeaux

  14. Service de Microbiologie, Unité Mobile d’Infectiologie, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015, Paris, France

    David Lebeaux

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  1. Emmanuel Lafont
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  2. Beatriz E. Marciano
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Correspondence to David Lebeaux.

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This research study was conducted retrospectively from data obtained for clinical purposes. This work was conducted in compliance with the French law “loi Jardé” (décret n°2016–1537, published on November 16, 2016). Ethical approval was waived by the local Ethics Committee of Necker-hospital and CEREES (Comité d’expertise pour les recherches, les études, et les évaluations dans le domaine de la santé). Regarding cases from the USA, the Institutional Review Board 93I0119 approved this study (IRIS Reference # 538437).

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Lafont, E., Marciano, B.E., Mahlaoui, N. et al. Nocardiosis Associated with Primary Immunodeficiencies (Nocar-DIP): an International Retrospective Study and Literature Review. J Clin Immunol 40, 1144–1155 (2020). https://doi.org/10.1007/s10875-020-00866-8

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