Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry

Waleed Al-Herz 1 2, Sahar Essa 3

Affiliations

29 May 2019

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doi: 10.3389/fimmu.2019.01231

Abstract

Objective: To present the frequency and spectrum of viral infections in primary immunodeficient children. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders (PIDs) Registry during the period of 2004-2018. Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Overall infectious complications affected 82.4% of the patients, and viral infections affected 31.7% of the registered patients. Forty-five patients (16.4%) developed viral infections caused by at least 2 organisms, among those 20 patients were affected by three or more viral infections. There was a statistically significant association between viral infections and PID category. However, there was no statistically significant association between viral infections and gender or the patients' onset age. There was a total of 170 viral infections during the study period and the causes of these infections were predominated by CMV (22.2%), adenovirus (11.7%), EBV (11.1%), and enteroviruses (7.4%). CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The most common presentation was viremia (28.8%) followed by pneumonia (28.2%) and skin infections (17.6%). The most common causes of viremia were CMV followed by adenovirus and EBV, while the most common organisms causing pneumonia were CMV followed by rhinovirus and parainfluenza. There were 80 deaths among the registered patients, 10% were caused by viral infections. Conclusions: Viral infections are common in PIDs and result into a wide-range of clinical manifestations causing significant morbidity and mortality.

Keywords: CMV; EBV; adenovirus; mortality; pneumonia; primary immunodeficiencies; viremia; virus.

Figures

Figure 1 Severe and disseminated molluscum contagiosum in a patient with dedicator of cytokinesis 8 deficiency (DOCK8) deficiency. The patient signed an informed written consent for publication of the images.

Figure 1 Severe and disseminated molluscum contagiosum in a patient with dedicator of cytokinesis 8 deficiency (DOCK8) deficiency. The patient signed an informed written consent for publication of the images.

Figure 2 The number of patients affected by different viruses according to PID categories.

Figure 2 The number of patients affected by different viruses according to PID categories.

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References

  1.  
    1. Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, et al. . International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol. (2018) 38:96–128. 10.1007/s10875-017-0464-9 - DOI - PMC - PubMed
  2.  
    1. Aghamohammadi A, Mohammadinejad P, Abolhassani H, Mirminachi B, Movahedi M, Gharagozlou M, et al. . Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry. J Clin Immunol. (2014) 34:478–90. 10.1007/s10875-014-0001-z - DOI - PubMed
  3.  
    1. Al-Herz W. Primary immunodeficiency disorders in Kuwait: first report from Kuwait National Primary Immunodeficiency Registry (2004–2006). J Clin Immunol. (2008) 28:186–93. 10.1007/s10875-007-9144-5 - DOI - PMC - PubMed
  4.  
    1. Al-Tamemi S, Naseem SU, Al-Siyabi N, El-Nour I, Al-Rawas A, Dennison D, et al. . Primary immunodeficiency diseases in Oman: 10-year experience in a tertiary care hospital. J Clin Immunol. (2016) 36:785–92. 10.1007/s10875-016-0337-7 - DOI - PubMed
  5.  
    1. Ochs HD, Hitzig WH. History of primary immunodeficiency diseases. Curr Opin Allergy Clin Immunol. (2012) 12:577–87. 10.1097/ACI.0b013e32835923a6 - DOI - PubMed
  6.  
    1. Al-Herz W, Moussa MA. Survival and predictors of death among primary immunodeficient patients: a registry-based study. J Clin Immunol. (2012) 32:467–73. 10.1007/s10875-011-9636-1 - DOI - PubMed
  7.  
    1. Odek C, Kendirli T, Doǧu F, Yaman A, Vatansever G, Cipe F, et al. . Patients with primary immunodeficiencies in pediatric intensive care unit: outcomes and mortality-related risk factors. J Clin Immunol. (2014) 34:309–15. 10.1007/s10875-014-9994-6 - DOI - PubMed
  8.  
    1. Rezaei N, Hedayat M, Aghamohammadi A, Nichols KE. Primary immunodeficiency diseases associated with increased susceptibility to viral infections and malignancies. J Allergy Clin Immunol. (2011) 127:1329–41.e2. 10.1016/j.jaci.2011.02.047 - DOI - PubMed
  9.  
    1. Aghamohammadi A, Abolhassani H, Kutukculer N, Wassilak SG, Pallansch MA, Kluglein S, et al. . Patients with primary immunodeficiencies are a reservoir of poliovirus and a risk to polio eradication. Front Immunol. (2017) 8:685. 10.3389/fimmu.2017.00685 - DOI - PMC - PubMed
  10.  
    1. Peltola V, Waris M, Kainulainen L, Kero J, Ruuskanen O. Virus shedding after human rhinovirus infection in children, adults and patients with hypogammaglobulinaemia. Clin Microbiol Infect. (2013) 19:E322–7. 10.1111/1469-0691.12193 - DOI - PubMed
  11.  
    1. Casanova JL, Abel L, Quintana-Murci L. Human TLRs and IL-1Rs in host defense: natural insights from evolutionary, epidemiological, and clinical genetics. Annu Rev Immunol. (2011) 29:447–91. 10.1146/annurev-immunol-030409-101335 - DOI - PubMed
  12.  
    1. Ruffner MA, Sullivan KE, Henrickson SE. Recurrent and sustained viral infections in primary immunodeficiencies. Front Immunol. (2017) 8:665. 10.3389/fimmu.2017.00665 - DOI - PMC - PubMed
  13.  
    1. Dropulic LK, Cohen JI. Severe viral infections and primary immunodeficiencies. Clin Infect Dis. (2011) 53:897–909. 10.1093/cid/cir610 - DOI - PMC - PubMed
  14.  
    1. Dalwai A, Ahmad S, Pacsa A, Al-Nakib W. Echovirus type 9 is an important cause of viral encephalitis among infants and young children in Kuwait. J Clin Virol. (2009) 44:48–51. 10.1016/j.jcv.2008.10.007 - DOI - PubMed
  15.  
    1. Ljungman P, Gleaves CA, Meyers JD. Respiratory virus infection in immunocompromised patients. Bone Marrow Transplant. (1989) 4:35–40. - PubMed
  16.  
    1. Zhang Q, Dove CG, Hor JL, Murdock HM, Strauss-Albee DM, Garcia JA, et al. . DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med. (2014) 211:2549–66. 10.1084/jem.20141307 - DOI - PMC - PubMed
  17.  
    1. Medical Advisory Committee of the Immune Deficiency Foundation. Shearer WT, Fleisher TA, Buckley RH, Ballas Z, Ballow M, et al. . Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol. (2014) 133:961–6. 10.1016/j.jaci.2013.11.043 - DOI - PMC - PubMed
  18.  
    1. Philip M, Rowley DA, Schreiber H. Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol. (2004) 14:433–9. 10.1016/j.semcancer.2004.06.006 - DOI - PubMed
  19.  
    1. Harris KM, Davila BJ, Bollard CM, Keller MD. Virus-specific T cells: current and future use in primary immunodeficiency disorders. J Allergy Clin Immunol Pract. (2019) 7:809–18. 10.1016/j.jaip.2018.10.049 - DOI - PMC - PubMed

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