Definition of Opportunistic Infections in Immunocompromised Children on the Basis of Etiologies and Clinical Features: A Summary for Practical Purposes

Author(s): Niccolò Riccardi*, Gioacchino Andrea Rotulo, Elio Castagnola

Journal Name: Current Pediatric Reviews

Volume 15 , Issue 4 , 2019


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Abstract:

Opportunistic Infections (OIs) still remain a major cause of morbidity and death in children with either malignant or nonmalignant disease.

OIs are defined as those infections occurring due to bacteria, fungi, viruses or commensal organisms that normally inhabit the human body and do not cause a disease in healthy people, but become pathogenic when the body's defense system is impaired. OIs can also be represented by unusually severe infections caused by common pathogens. An OI could present itself at the onset of a primary immunodeficiency syndrome as a life-threatening event. More often, OI is a therapyassociated complication in patients needing immunosuppressive treatment, among long-term hospitalised patients or in children who undergo bone marrow or solid organ transplantation.

The aim of the present review is to provide a comprehensive and ‘easy to read’ text that briefly summarises the currently available knowledge about OIs in order to define when an infection should be considered as opportunistic in pediatrics as a result of an underlying congenital or acquired immune-deficit.

Keywords: Opportunistic infections, children, immunocompromised host, etiology, pathogenic, immune-deficit, malignant.

[1]
CDC Opportunistic Infections definition. Available at:. https://www.cdc.gov/hiv/basics/livingwithhiv/opportunisticinfec-tions.html
[2]
De Rosa FG, Corcione S, Raviolo S, et al. Candidemia, and infections by Clostridium difficile and carbapenemase-producing Enterobacteriaceae: New enteropathogenetic opportunistic syndromes? Infez Med 2015; 23(2): 105-16.
[PMID: 26110290]
[3]
Nucci M, Queiroz-Telles F, Tobón AM, Restrepo A, Colombo AL. Epidemiology of opportunistic fungal infections in Latin America. Clin Infect Dis 2010; 51(5): 561-70.
[http://dx.doi.org/10.1086/655683] [PMID: 20658942]
[4]
Bottieau E. Tropical parasitic diseases and immunosuppression. Clin Microbiol Infect 2014; 20(4): 277.
[http://dx.doi.org/10.1111/1469-0691.12590] [PMID: 24529256]
[5]
Polvi EJ, Li X, O’Meara TR, Leach MD, Cowen LE. Opportunistic yeast pathogens: Reservoirs, virulence mechanisms and therapeutic strategies. Cell Mol Life Sci 2015; 72(12): 2261-87.
[http://dx.doi.org/10.1007/s00018-015-1860-z] [PMID: 25700837]
[6]
Lake MA, Ambrose LR, Lipman MC, Lowe DM. '“Why me, why now?” Using clinical immunology and epidemiology to explain who gets nontuberculous mycobacterial infection. BMC Med 2016; 14: 54.
[http://dx.doi.org/10.1186/s12916-016-0606-6] [PMID: 27007918]
[7]
B-Lajoie MR, Drouin O, Bartlett G, et al. Incidence and prevalence of opportunistic and other infections and the impact of antiretroviral therapy among HIV-infected children in low- and middle-income countries: A systematic review and meta-analysis. Clin Infect Dis 2016; 62(12): 1586-94.
[http://dx.doi.org/10.1093/cid/ciw139] [PMID: 27001796]
[8]
Winthrop KL, Novosad SA, Baddley JW, et al. Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis 2015; 74(12): 2107-16.
[http://dx.doi.org/10.1136/annrheumdis-2015-207841] [PMID: 26395500]
[9]
Ison MG, Hayden RT. Adenovirus. Microbiol Spectr 2016; 4(4)
[PMID: 27726766]
[10]
Groll AH, Castagnola E, Cesaro S, et al. Fourth european conference on infections in leukaemia; Infectious diseases working party of the European Group for Blood Marrow Transplantation (EBMT-IDWP); Infectious Diseases Group of the European Organisation for Research and Treatment of Cancer (EORTC-IDG); International Immunocompromised Host Society (ICHS); European Leukaemia Net (ELN). Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol 2014; 15(8): e327-40.
[http://dx.doi.org/10.1016/S1470-2045(14)70017-8] [PMID: 24988936]
[11]
Aguilar C, Malphettes M, Donadieu J, Chandesris O, Coignard-Biehler H. Prevention of infections during primary immunodeficiency. Clin Infect Dis 2014; 59(10): 1462-70.
[12]
Wanat KA, Reid E, Kamiyango W, El-Mallawany NK, Kovarik CL. Tumoral bacillary angiomatosis in a child with human immunodeficiency virus. JAMA Dermatol 2014; 150(9): 1015-6.
[http://dx.doi.org/10.1001/jamadermatol.2013.9128] [PMID: 25076357]
[13]
Sionean C, Le BC, Hageman K, et al. HIV Risk, prevention and testing behaviors among heterosexuals at increased risk for HIV infection--National HIV Behavioral Surveillance System, 21 U.S. cities, 2010. MMWR Surveill Summ 2014; 63(14): 1-39.
[PMID: 25522191]
[14]
Raje N, Dinakar C. Overview of immunodeficiency disorders. Immunol Allergy Clin North Am 2015; 35(4): 599-623. [Review]
[http://dx.doi.org/10.1016/j.iac.2015.07.001] [PMID: 26454309]
[15]
Siberry GK, Abzug MJ, Nachman S, et al. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. Pediatr Infect Dis J 2013; 32(Suppl. 2): i-KK4.
[http://dx.doi.org/10.1097/01.inf.0000437856.09540.11] [PMID: 24569199]
[16]
Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. John E. Bennett, Raphael Dolin and Martin J. Blaser 2014.
[17]
Lanternier F, Tubach F, Ravaud P, et al. Incidence and risk factors of Legionella pneumophila pneumonia during anti-tumor necrosis factor therapy: A prospective French study. Chest 2013; 144(3): 990-8.
[http://dx.doi.org/10.1378/chest.12-2820] [PMID: 23744173]
[18]
Buzzi E, Manzoni P, Castagnola E, Benjamin DK Jr, Beghini R, Dall’agnola A. Candida pneumonia in a term infant after prolonged use of inhaled corticosteroids for bronchopulmonary dysplasia (BPD). Early Hum Dev 2013; 89(Suppl. 1): S62-3.
[http://dx.doi.org/10.1016/S0378-3782(13)70018-5] [PMID: 23809354]
[19]
Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357(25): 2601-14.
[http://dx.doi.org/10.1056/NEJMra064928] [PMID: 18094380]
[20]
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009; 9(Suppl. 3): S1-S155.
[http://dx.doi.org/10.1111/j.1600-6143.2009.02834.x] [PMID: 19845599]
[21]
Lönnroth K, Mor Z, Erkens C, et al. Tuberculosis in migrants in low-incidence countries: epidemiology and intervention entry points. Int J Tuberc Lung Dis 2017; 21(6): 624-37.
[http://dx.doi.org/10.5588/ijtld.16.0845] [PMID: 28482956]
[22]
Norouzi S, Aghamohammadi A, Mamishi S, Rosenzweig SD, Rezaei N. Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases. J Infect 2012; 64(6): 543-54.
[http://dx.doi.org/10.1016/j.jinf.2012.03.012] [PMID: 22430715]
[23]
Sepkowitz KA. Opportunistic infections in patients with and patients without Acquired Immunodeficiency Syndrome. Clin Infect Dis 2002; 34(8): 1098-107.
[http://dx.doi.org/10.1086/339548] [PMID: 11914999]
[24]
Grandjean S, Toro A, Drancourt M. Mycobacterium iranicum bacteremia and hemophagocytic lymphohistiocytosis: a case report. BMC Res Notes 2017; 10(1): 372.
[http://dx.doi.org/10.1186/s13104-017-2684-8] [PMID: 28789664]
[25]
Green M, Michaels MG. Infections in pediatric solid organ transplant recipients. J Pediatric Infect Dis Soc 2012; 1(2): 144-51.
[http://dx.doi.org/10.1093/jpids/pir001] [PMID: 26619167]
[26]
Odio CD, Milligan KL, McGowan K, et al. Endemic mycoses in patients with STAT3-mutated hyper-IgE (Job) syndrome Allergy Clin Immunol 2015; 136(5): 1411. 3.e1-2
[27]
Köhler JR, Hube B, Puccia R, Casadevall A, Perfect JR. Fungi that infect humans. Microbiol Spectr 2017; 5(3)
[PMID: 28597822]
[28]
Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002; 34(8): 1094-7.
[http://dx.doi.org/10.1086/339329] [PMID: 11914998]
[29]
Kruisinga MD, van Tol MJD, Bekker V, et al. Risk Factors, Treatment and Immune Dysregulation in Autoimmune Cytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients. Biol Blood Marrow Transplant 2018; 24(4): 772-8.
[30]
Tangye SG. XLP: clinical features and molecular etiology due to mutations in SH2D1A encoding SAP. J Clin Immunol 2014; 34(7): 772-9.
[http://dx.doi.org/10.1007/s10875-014-0083-7] [PMID: 25085526]
[31]
Eligio P, Delia R, Valeria G. EBV Chronic Infections. Mediterr J Hematol Infect Dis 2010; 2(1)e2010022
[http://dx.doi.org/10.4084/mjhid.2010.022] [PMID: 21415952]
[32]
Okano M, Kawa K, Kimura H, et al. Proposed guidelines for diagnosing chronic active Epstein-Barr virus infection. Am J Hematol 2005; 80(1): 64-9.
[http://dx.doi.org/10.1002/ajh.20398] [PMID: 16138335]
[33]
Tavil B, Cetin M, Tuncer M, et al. The rate of hepatitis B and C virus infections and the importance of HBV vaccination in children with acute lymphoblastic leukemia. Hepatol Res 2007; 37(7): 498-502.
[http://dx.doi.org/10.1111/j.1872-034X.2007.00079.x] [PMID: 17539991]
[34]
Nimgaonkar I, Ding Q, Schwartz RE, Ploss A. Hepatitis E virus: advances and challenges. Nat Rev Gastroenterol Hepatol 2018; 15(2): 96-110.
[PMID: 29162935]
[35]
Kim DH, Messner H, Minden M, et al. Factors influencing varicella zoster virus infection after allogeneic peripheral blood stem cell transplantation: low-dose acyclovir prophylaxis and pre-transplant diagnosis of lymphoproliferative disorders. Transpl Infect Dis 2008; 10(2): 90-8.
[http://dx.doi.org/10.1111/j.1399-3062.2007.00247.x] [PMID: 17605742]
[36]
Hayden RT, Gu Z, Liu W, et al. Risk factors for hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 2015; 17(2): 234-41.
[http://dx.doi.org/10.1111/tid.12364] [PMID: 25648430]
[37]
Sujeet K, Vasudev B, Desai P, et al. Acute kidney injury requiring dialysis secondary to adenovirus nephritis in renal transplant recipient. Transpl Infect Dis 2011; 13(2): 174-7.
[http://dx.doi.org/10.1111/j.1399-3062.2010.00577.x] [PMID: 20946204]
[38]
Lagadinou ED, Marangos M, Liga M, et al. Human herpesvirus 6-related pure red cell aplasia, secondary graft failure, and clinical severe immune suppression after allogeneic hematopoietic cell transplantation successfully treated with foscarnet. Transpl Infect Dis 2010; 12(5): 437-40.
[http://dx.doi.org/10.1111/j.1399-3062.2010.00515.x] [PMID: 20561301]
[39]
El-Mallawany NK, Villiera J, Kamiyango W, et al. Increasing numbers of new kaposi sarcoma diagnoses in hiv-infected children and adolescents despite the wide availability of antiretroviral therapy in malawi. Clin Infect Dis 2017; 64(6): 818-9.
[http://dx.doi.org/10.1093/cid/ciw879] [PMID: 28077522]
[40]
Kedia S, Acharya PS, Mohammad F, et al. Infectious complications of hematopoietic stem cell transplantation. J Stem Cell Res Ther 2013; S3: 002.
[41]
Au WY, Lie AK, Shek TW. Fulminant molluscum contagiosum infection and concomitant leukaemia cutis after bone marrow transplantation for chronic myeloid leukaemia. Br J Dermatol 2000; 143(5): 1097-8.
[http://dx.doi.org/10.1046/j.1365-2133.2000.03859.x] [PMID: 11069530]
[42]
Barroso KSN, Kaufman J, Brunetta DM, de Carvalho Araújo FM, Barroso-Duarte F. Dengue encephalitis in allogenic hematopoietic stem cell transplantation recipient. Bone Marrow Transplant 2017; 52(10): 1455-6.
[http://dx.doi.org/10.1038/bmt.2017.152] [PMID: 28714943]
[43]
Girão ES, Rodrigues Dos Santos BG, do Amaral ES, et al. Chikungunya infection in solid organ transplant recipients. Transplant Proc 2017; 49(9): 2076-81.
[http://dx.doi.org/10.1016/j.transproceed.2017.07.004] [PMID: 29149964]
[44]
Gadient Hotz S, Müller DJ, Chaney M, Blum J. No fever, no malaria? A diagnostic challenge in an immunocompromised patient. Travel Med Infect Dis 2015; 13(6): 511-2.
[http://dx.doi.org/10.1016/j.tmaid.2015.11.002] [PMID: 26612047]
[45]
Genda J, Negron EA, Lotfipour M, et al. Severe babesia microti infection in an immunocompetent host in pennsylvania. J Investig Med High Impact Case Rep 2016; 4(3)2324709616663774
[http://dx.doi.org/10.1177/2324709616663774] [PMID: 27656660]
[46]
Krause PJ, Gewurz BE, Hill D, et al. Persistent and relapsing babesiosis in immunocompromised patients. Clin Infect Dis 2008; 46(3): 370-6.
[http://dx.doi.org/10.1086/525852] [PMID: 18181735]
[47]
Prigione I, Castagnola E, Imberti L, et al. Multiple relapses of visceral leishmaniasis in an adolescent with idiopathic CD4+ lymphocytopenia associated with novel immunophenotypic and molecular features. Pediatr Infect Dis J 2009; 28(2): 161-3.
[http://dx.doi.org/10.1097/INF.0b013e318185513d] [PMID: 19106781]
[48]
Antinori S, Schifanella L, Corbellino M. Leishmaniasis: new insights from an old and neglected disease. Eur J Clin Microbiol Infect Dis 2012; 31(2): 109-18.
[http://dx.doi.org/10.1007/s10096-011-1276-0] [PMID: 21533874]
[49]
Lattes R, Lasala MB. Chagas disease in the immunosuppressed patient. Clin Microbiol Infect 2014; 20(4): 300-9.
[http://dx.doi.org/10.1111/1469-0691.12585] [PMID: 24602129]
[50]
Marciano-Cabral F, Cabral G. Acanthamoeba spp. as agents of disease in humans. Clin Microbiol Rev 2003; 16(2): 273-307.
[http://dx.doi.org/10.1128/CMR.16.2.273-307.2003] [PMID: 12692099]
[51]
Baig AM. Granulomatous amoebic encephalitis: ghost response of an immunocompromised host? J Med Microbiol 2014; 63(Pt 12): 1763-6.
[http://dx.doi.org/10.1099/jmm.0.081315-0] [PMID: 25239626]
[52]
Abanyie FA, Gray EB, Delli KW, et al. Donor-derived Strongyloides stercoralis infection in solid organ transplant recipients in the United States, 2009-2013. Am J Transplant 2015; 15(5): 1369-75.
[http://dx.doi.org/10.1111/ajt.13137] [PMID: 25703251]
[53]
Koehsler M, Soleiman A, Aspöck H, Auer H, Walochnik J. Onchocerca jakutensis filariasis in humans. Emerg Infect Dis 2007; 13(11): 1749-52.
[http://dx.doi.org/10.3201/eid1311.070017] [PMID: 18217562]
[54]
Kipp W, Bamuhiiga J, Rubaale T. Simulium neavei-transmitted onchocerciasis: HIV infection increases severity of onchocercal skin disease in a small sample of patients. Trans R Soc Trop Med Hyg 2003; 97(3): 310-1.
[http://dx.doi.org/10.1016/S0035-9203(03)90157-X] [PMID: 15228250]
[55]
Heldwein K, Biedermann HG, Hamperl WD, et al. Subcutaneous Taenia crassiceps infection in a patient with non-Hodgkin’s lymphoma. Am J Trop Med Hyg 2006; 75(1): 108-11.
[http://dx.doi.org/10.4269/ajtmh.2006.75.108] [PMID: 16837716]
[56]
Venturini E, Turkova A, Chiappini E, Galli L, de Martino M, Thorne C. Tuberculosis and HIV co-infection in children. BMC Infect Dis 2014; 14(Suppl. 1): S5.
[http://dx.doi.org/10.1186/1471-2334-14-S1-S5] [PMID: 24564453]
[57]
Mody R, Naranjo A, Van Ryn C, et al. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol 2017; 18(7): 946-57.
[http://dx.doi.org/10.1016/S1470-2045(17)30355-8] [PMID: 28549783]
[58]
Riccardi N, Rotulo GA, Favilli F, et al. Pseudomonas aeruginosa severe skin infection in a toddler with X-linked agammaglobulinemia due to a novel BTK mutation. Infez Med 2019; 27(1): 73-6.
[PMID: 30882382]
[59]
Bearden D, Collett M, Quan PL, Costa-Carvalho BT, Sullivan KE. Enteroviruses in X-Linked Agammaglobulinemia: Update on Epidemiology and Therapy. J Allergy Clin Immunol Pract 2016; 4(6): 1059-65.
[http://dx.doi.org/10.1016/j.jaip.2015.12.015] [PMID: 26883540]
[60]
Parvaneh L, Sharifi N, Azizi G, et al. Infectious etiology of chronic diarrhea in patients with primary immunodeficiency diseases. Eur Ann Allergy Clin Immunol 2019; 51(1): 32-7.
[http://dx.doi.org/10.23822/EurAnnACI.1764-1489.77] [PMID: 30417635]
[61]
Flanagan SE, Haapaniemi E, Russell MA, et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet 2014; 46(8): 812-4.
[http://dx.doi.org/10.1038/ng.3040] [PMID: 25038750]
[62]
de la Morena MT. Clinical Phenotypes of Hyper-IgM Syndromes. J Allergy Clin Immunol Pract 2016; 4(6): 1023-36.
[http://dx.doi.org/10.1016/j.jaip.2016.09.013] [PMID: 27836054]
[63]
Berrington JE, Flood TJ, Abinun M, Galloway A, Cant AJ. Unsuspected Pneumocystis carinii pneumonia at presentation of severe primary immunodeficiency. Arch Dis Child 2000; 82(2): 144-7.
[http://dx.doi.org/10.1136/adc.82.2.144] [PMID: 10648370]
[64]
Marciano BE, Spalding C, Fitzgerald A, et al. Common severe infections in chronic granulomatous disease. Clin Infect Dis 2015; 60(8): 1176-83.
[http://dx.doi.org/10.1093/cid/ciu1154] [PMID: 25537876]
[65]
Maglione PJ, Simchoni N, Cunningham-Rundles C. Toll-like receptor signaling in primary immune deficiencies. Ann N Y Acad Sci 2015; 1356(1): 1-21.
[http://dx.doi.org/10.1111/nyas.12763] [PMID: 25930993]
[66]
Spinner MA, Sanchez LA, Hsu AP, et al. GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood 2014; 123(6): 809-21.
[http://dx.doi.org/10.1182/blood-2013-07-515528] [PMID: 24227816]
[67]
Vila A, Dapás JI, Rivero CV, et al. Multiple opportunistic infections in a woman with GATA2 mutation. Int J Infect Dis 2017; 54: 89-91.
[http://dx.doi.org/10.1016/j.ijid.2016.11.408] [PMID: 27894982]
[68]
Lanternier F, Mahdaviani SA, Barbati E, et al. Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, or both. J Allergy Clin Immunol 2015; 135(6): 1558-68.e2.
[http://dx.doi.org/10.1016/j.jaci.2014.12.1930] [PMID: 25702837]
[69]
Lozano ML, Rivera J, Sánchez-Guiu I, Vicente V. Towards the targeted management of Chediak-Higashi syndrome. Orphanet J Rare Dis 2014; 9: 132.
[http://dx.doi.org/10.1186/s13023-014-0132-6] [PMID: 25129365]
[70]
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(6): 1329-41.e2.
[http://dx.doi.org/10.1016/j.jaci.2011.02.047] [PMID: 21514636]
[71]
Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM. Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr 2004; 144(4): 505-11.
[http://dx.doi.org/10.1016/j.jpeds.2003.12.046] [PMID: 15069401]
[72]
Candotti F. Clinical manifestations and pathophysiological mechanisms of the wiskott-aldrich syndrome. J Clin Immunol 2018; 38(1): 13-27.
[http://dx.doi.org/10.1007/s10875-017-0453-z] [PMID: 29086100]
[73]
Al-Shaikhly T, Ochs HD. Hyper IgE syndromes: clinical and molecular characteristics. Immunol Cell Biol 2019; 97(4): 368-79.
[74]
Grimbacher B, Holland SM, Gallin JI, et al. Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med 1999; 340(9): 692-702.
[http://dx.doi.org/10.1056/NEJM199903043400904] [PMID: 10053178]
[75]
Picard C, Bobby Gaspar H, et al. International union of immunological societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol 2018; 38(1): 96-128.
[http://dx.doi.org/10.1007/s10875-017-0464-9] [PMID: 29226302]


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Article Details

VOLUME: 15
ISSUE: 4
Year: 2019
Published on: 30 December, 2019
Page: [197 - 206]
Pages: 10
DOI: 10.2174/1573396315666190617151745

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