Microbiological profile in chronic granulomatous disease patients in a single Brazilian primary immunodeficiency center

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Aimée Filippini Bifulco Oliveira
Antonio Carlos Pastorino
Mayra de Barros Dorna
Ana Paula Beltran Moschione Castro
José Roberto Mendes Pegler
Beni Morgenstern
Magda Maria Sales Carneiro-Sampaio


Chronic Granulomatous Disease, Staphylococcal Infections, Aspergillus, Mycobacterium, Abscess, Pediatrics


Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency. Infections of lung, skin, lymph nodes, and liver are the hallmark of CGD and frequently the initial manifestation of the disease. The aim of the present paper is to describe the sites of infections and their causative agents in 38 pediatric patients with CGD.

Methods: This retrospective, single-center cohort study included CGD patients followed at the allergy and immunology unit of a tertiary hospital in São Paulo, Brazil over the last 40 years. Sites of infections and their causative agents were described.

Results: Thirty-eight patients were included (36 males). The median age of onset of symptoms was 45 days (ranging from 7 days–7 years), and the median age at diagnosis was 23 months (ranging from 1 month–12 years). In all, 31.6% of the patients reported a family history of child deaths and 21% (eight cases) had another male family member with CGD. The most common infections were pneumonia (81.6%), skin infections (50.0%), adenitis (42.1%), and liver abscess (23.7%); 188 cultures were positive (85.6% bacteria; 14.4% fungi). The most prevalent bacterial agents were Staphylococcus sp. (12.4%), Staphylococcus aureus (11.2%), and Klebsiella pneumoniae (9.3%). Aspergillus sp. and Candida sp. were 56% and 22.2% of the isolated fungi, respectively. Mycobacterium tuberculosis was isolated in 5.6% and Mycobacterium bovis in one patient (0.9%).

Conclusion: Staphylococcus sp., Staphylococcus aureus, and Aspergillus sp. were the most frequent agents found in this cohort. M. tuberculosis should be considered in endemic area. Detection of infectious agents drives to the adequate treatment and benefits the evolution of patients with CGD.

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1. Holland SM. Chronic granulomatous disease. Hematol Oncol Clin North Am. 2013;27(1):89–99. doi:10.1016/j.hoc.2012.11.002.

2. Chiriaco M, Salfa I, Di Matteo G, Rossi P, Finocchi A. Chronic granulomatous disease: Clinical, molecular, and therapeutic aspects. Pediatr Allergy Immunol. 2016;27(3):242–53. doi: 10.1111/pai.12527.

3. Arnold DE, Heimall JR. A review of chronic granulomatous disease. Adv Ther. 2017;34(12):2543–57. doi: 10.1007/s12325-017-0636-2.

4. Magnani A, Brosselin P, Beauté J, de Vergnes N, Mouy R, Debré M, et al. Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease. J Allergy Clin Immunol. 2014;134(3):655–62.e8. doi: 10.1016/j.jaci.2014.04.014.

5. Gennery A. Recent advances in understanding and treating chronic granulomatous disease. F1000Res. 2017;6:1427. doi: 10.12688/f1000research.11789.1. eCollection 2017.

6. Gallin JI, Alling DW, Malech HL, Wesley R, Koziol D, Marciano B, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. N Engl J Med. 2003;348(24):2416–22. doi: 10.1056/NEJMoa021931.

7. Connelly JA, Marsh R, Parikh S, Talano JA. Allogeneic hematopoietic cell transplantation for chronic granulomatous disease: Controversies and state of the art. J Pediatric Infect Dis Soc. 2018;7(Suppl 1):S31–9. doi: 10.1093/jpids/piy015.

8. Ministry of Health. Portal da Saúde. Live births in Brazil 2017. Available from: http://tabnet.datasus.gov.br/cgi/tabcgi.exe?sinasc/cnv/nvuf.def. Accessed November 20, 2019.

9. Latin American Society for Immunodeficiencies (LASID). Statistic register of PID cases. Accessed November 20, 2019. Available from: http://www.bragid.org.br/_download/registro/estatisticas_2018_08.pdf .

10. Kutukculer N, Aykut A, Karaca NE, Durmaz A, Aksu G, Genel F, et al. Chronic granulomatous disease: Two decades of experience from a pediatric immunology unit in a country with high rate of consanguineous marriages. Scand J Immunol. 2019;89(2):e12737. doi: 10.1111/sji.12737.

11. Fattahi F, Badalzadeh M, Sedighipour L, Movahedi M, Fazlollahi MR, Mansouri SD, et al. Inheritance pattern and clinical aspects of 93 Iranian patients with chronic granulomatous disease. J Clin Immunol. 2011;31(5):792–801. doi: 10.1007/s10875-011-9567-x.

12. Al-Zadjali S, Al-Tamemi S, Elnour I, AlKindi S, Lapoumeroulie C, Al-Maamari S, et al. Clinical and molecular findings of chronic granulomatous disease in Oman: Family studies. Clin Genet. 2015;87(2):185–9. doi: 10.1111/cge.12351)

13. Gao LW, Yin QQ, Tong YJ, Gui JG, Liu XY, Feng XL, et al. Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease. Pediatr Allergy Immunol. 2019;30(3):378–86. doi: 10.1111/pai.13033.

14. Bortoletto P, Lyman K, Camacho A, Fricchione M, Khanolkar A, Katz BZ. Chronic granulomatous disease, a large, single–center US experience. Pediatr Infect Dis J. 2015;34(10):1110–4. doi: 10.1097/INF.0000000000000840.

15. Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000;79(3):155–69. doi: 10.1097/00005792-200005000-00003.

16. van den Berg JM, van Koppen E, Ahlin A, Belohradsky BH, Bernatowska E, Corbeel L, et al. Chronic granulomatous disease: The European experience. PLoS One. 2009;4(4):e5234. doi: 10.1371/journal.pone.0005234.

17. Wu J, Wang WF, Zhang YD, Chen TX. Clinical features and genetic analysis of 48 patients with chronic granulomatous disease in a single center study from Shanghai, China (2005–2015): New studies and a literature review. J Immunol Res. 2017;2017:8745254. doi: 10.1155/2017/8745254.

18. de Oliveira-Junior EB, Zurro NB, Prando C, Cabral-Marques O, Pereira PV, Schimke LF, et al. Clinical and genotypic spectrum of chronic granulomatous disease in 71 Latin American patients: First report from the LASID registry. Pediatr Blood Cancer. 2015; 62(12):2101–7. doi: 10.1002/pbc.25674.

19. Martire B, Rondelli R, Soresina A, Pignata C, Broccoletti T, Finocchi A, et al. Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: An Italian multicenter study. Clin Immunol. 2008;126(2):155–64. doi: 10.1016/j.clim.2007.09.008.

20. Conti F, Lugo–Reyes SO, Blancas Galicia L, He J, Aksu G, Borges de Oliveira E Jr, et al. Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases. J Allergy Clin Immunol. 2016;138(1):241–8. e3. doi: 10.1016/j.jaci.2015.11.041.

21. Rawat A, Vignesh P, Sharma A, Shandilya JK, Sharma M, Suri D, et al. Infection profile in chronic granulomatous disease: A 23-year experience from a tertiary care center in North India. J Clin Immunol. 2017;37(3):319–28. doi: 10.1007/s10875-017-0382-x.

22. Marciano BE, Spalding C, Fitzgerald A, Mann D, Brown T, Osgood S, et al. Common severe infections in chronic granulomatous disease. Clin Infect Dis. 2015;60(8):1176–83. doi:10.1093/cid/ciu1154.

23. Buvelot H, Posfay-Barbe KM, Linder P, Schrenzel J, Krause KH. Staphylococcus aureus, phagocyte NADPH oxidase and chronic granulomatous disease. FEMS Microbiol Rev. 2017;41(2):139–57. doi:10.1093/femsre/fuw042.

24. Argemi X, Hansmann Y, Prola K, Prévost G. Coagulase-negative staphylococci pathogenomics. Int J Mol Sci. 2019;20(5):1215. doi: 10.3390/ijms20051215.

25. King J, Henriet SSV, Warris A. Aspergillosis in chronic granulomatous disease. J Fungi (Basel). 2016;2(2). pii: E15. doi: 10.3390/jof2020015.

26. Bennett N, Maglione PJ, Wright BL, Zerbe C. Infectious complications in patients with chronic granulomatous disease. J Pediatric Infect Dis Soc. 2018;7(Suppl 1):S12–7. doi: 10.1093/jpids/piy013.

27. Blumental S, Mouy R, Mahlaoui N, Bougnoux ME, Debré M, Beauté J, et al. Invasive mold infections in chronic granulomatous disease: A 25-year retrospective survey. Clin Infect Dis. 2011;53(12):e159–69. doi: 10.1093/cid/cir731.

28. Manual of Recommendations for tuberculosis control in Brazil, 2019. 2ª ed updated. http: bvsms.saude.gov.brbvs/bvs/publicacoes/manual_recomendações_controle_tuberculose_brasil_2_ed.pdf. Accessed April 28, 2020.

29. Falcone EL, Holland SM. Invasive fungal infection in chronic granulomatous disease: Insights into pathogenesis and management. Curr Opin Infect Dis. 2012;25(6):658–69. doi:10.1097/QCO.0b013e328358b0a4.

30. Lublin M, Bartlett DL, Danforth DN, Kauffman H, Gallin JI, Malech HL, et al. Hepatic abscess in patients with chronic granulomatous disease. Ann Surg. 2002;235(3):383–91. doi: 10.1097/00000658–200203000–00010.