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Infectious causes of neutropenia

Thomas D Coates, MD
Section Editor
Laurence A Boxer, MD
Deputy Editor
Jennifer S Tirnauer, MD


Neutropenia can be caused by infection with microorganisms. Conversely, neutropenia can lead to infection, typically from bacterial organisms. A number of different mechanisms are involved, including infection of hematopoietic precursor cells, infection of endothelial cells, increased neutrophil adherence to endothelium, development of antineutrophil antibodies, and enhanced neutrophil utilization at the site of infection associated with hypersplenism. Drugs given to treat these infections may also cause neutropenia. (See "Drug-induced neutropenia and agranulocytosis".)

This review will discuss the neutropenias that can occur during bacterial, viral, parasitic, or rickettsial infections. Approaches to determining the cause of unexplained neutropenia in children and adults are presented separately. (See "Overview of neutropenia in children and adolescents" and "Approach to the adult with unexplained neutropenia".)

Infections in patients with neutropenia can range from mild to life-threatening, depending on the cause of the neutropenia. Fever in a neutropenic patient is considered a medical emergency unless the patient is known to be low risk. This issue is discussed separately.

(See "Overview of neutropenic fever syndromes".)

(See "Risk of infection in children with fever and non-chemotherapy-induced neutropenia".)


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Literature review current through: Sep 2016. | This topic last updated: Aug 16, 2016.
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  1. Abdool Gaffar MS, Seedat YK, Coovadia YM, Khan Q. The white cell count in typhoid fever. Trop Geogr Med 1992; 44:23.
  2. James J, Dutta TK, Jayanthi S. Correlation of clinical and hematologic profiles with bone marrow responses in typhoid fever. Am J Trop Med Hyg 1997; 57:313.
  3. Mallouh AA, Sa'di AR. White blood cells and bone marrow in typhoid fever. Pediatr Infect Dis J 1987; 6:527.
  4. Shin BM, Paik IK, Cho HI. Bone marrow pathology of culture proven typhoid fever. J Korean Med Sci 1994; 9:57.
  5. Sood R, Roy S, Kaushik P. Typhoid fever with severe pancytopenia. Postgrad Med J 1997; 73:41.
  6. Suyasa IG, Reka IG, Inada K, et al. Plasma endotoxin in typhoid fever. Kobe J Med Sci 1995; 41:175.
  7. Keuter M, Dharmana E, Kullberg BJ, et al. Phospholipase A2 is a circulating mediator in typhoid fever. J Infect Dis 1995; 172:305.
  8. Netea MG, Drenth JP, De Bont N, et al. A semi-quantitative reverse transcriptase polymerase chain reaction method for measurement of MRNA for TNF-alpha and IL-1 beta in whole blood cultures: its application in typhoid fever and exentric exercise. Cytokine 1996; 8:739.
  9. Keuter M, Dharmana E, Gasem MH, et al. Patterns of proinflammatory cytokines and inhibitors during typhoid fever. J Infect Dis 1994; 169:1306.
  10. Butler T, Ho M, Acharya G, et al. Interleukin-6, gamma interferon, and tumor necrosis factor receptors in typhoid fever related to outcome of antimicrobial therapy. Antimicrob Agents Chemother 1993; 37:2418.
  11. Fried D, Maytal J, Hanukoglu A. The differential leukocyte count in shigellosis. Infection 1982; 10:13.
  12. Halpern Z, Averbuch M, Dan M, et al. The differential leukocyte count in adults with acute gastroenteritis. Scand J Infect Dis 1992; 24:205.
  13. Witkowska D, Czarny A, Mulczyk M. Some biological properties of outer membrane proteins of Shigella. Arch Immunol Ther Exp (Warsz) 1987; 35:759.
  14. Azim T, Islam LN, Halder RC, et al. Peripheral blood neutrophil responses in children with shigellosis. Clin Diagn Lab Immunol 1995; 2:616.
  15. al-Eissa Y, al-Nasser M. Haematological manifestations of childhood brucellosis. Infection 1993; 21:23.
  16. Crosby E, Llosa L, Miro Quesada M, et al. Hematologic changes in brucellosis. J Infect Dis 1984; 150:419.
  17. Galanakis E, Bourantas KL, Leveidiotou S, Lapatsanis PD. Childhood brucellosis in north-western Greece: a retrospective analysis. Eur J Pediatr 1996; 155:1.
  18. al-Eissa YA, Assuhaimi SA, al-Fawaz IM, et al. Pancytopenia in children with brucellosis: clinical manifestations and bone marrow findings. Acta Haematol 1993; 89:132.
  19. Gotuzzo E, Carrillo C, Guerra J, Llosa L. An evaluation of diagnostic methods for brucellosis--the value of bone marrow culture. J Infect Dis 1986; 153:122.
  20. Kokkini G, Giotaki HG, Moutsopoulos HM. Transient hemophagocytosis in Brucella melitensis infection. Arch Pathol Lab Med 1984; 108:213.
  21. Cheers C, Young AM. Serum colony stimulating activity and colony forming cells in murine brucellosis: relationship to immunopathology. Microb Pathog 1987; 3:185.
  22. Palomera Bernal L, García Díez I, Barbudo Merino A, et al. [The reactive hemophagocytic syndrome associated with infection: a study of 3 cases]. An Med Interna 1990; 7:411.
  23. Pullen RL, Stuart BM. Tularemia. JAMA 1945; 129:495.
  24. Syrjälä H. Peripheral blood leukocyte counts, erythrocyte sedimentation rate and C-reactive protein in tularemia caused by the type B strain of Francisella tularensis. Infection 1986; 14:51.
  25. Sjöstedt A, Conlan JW, North RJ. Neutrophils are critical for host defense against primary infection with the facultative intracellular bacterium Francisella tularensis in mice and participate in defense against reinfection. Infect Immun 1994; 62:2779.
  26. Maartens G, Willcox PA, Benatar SR. Miliary tuberculosis: rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. Am J Med 1990; 89:291.
  27. Bozóky G, Ruby E, Góhér I, et al. [Hematologic abnormalities in pulmonary tuberculosiss]. Orv Hetil 1997; 138:1053.
  28. ROSE HM. The clinical manifestations and laboratory diagnosis of rickettsialpox. Ann Intern Med 1949; 31:871.
  29. Klein MB, Hayes SF, Goodman JL. Monocytic differentiation inhibits infection and granulocytic differentiation potentiates infection by the agent of human granulocytic ehrlichiosis. Infect Immun 1998; 66:3410.
  30. Dumler JS. The biological basis of severe outcomes in Anaplasma phagocytophilum infection. FEMS Immunol Med Microbiol 2012; 64:13.
  31. Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA 1996; 275:199.
  32. Fritz CL, Glaser CA. Ehrlichiosis. Infect Dis Clin North Am 1998; 12:123.
  33. Hall GW, Schwartz RP. White blood cell count and differential in Rocky Mountain spotted fever. N C Med J 1979; 40:212.
  34. Musumeci S, D'Agata A, Schiliro G, Fischer A. Studies of the neutropenia in kala-azar: results in two patients. Trans R Soc Trop Med Hyg 1976; 70:500.
  35. Rai ME, Muhammad Z, Sarwar J, Qureshi AM. Haematological findings in relation to clinical findings of visceral Leishmaniasis in Hazara Division. J Ayub Med Coll Abbottabad 2008; 20:40.
  36. Pollack S, Nagler A, Liberman D, et al. Immunological studies of pancytopenia in visceral leishmaniasis. Isr J Med Sci 1988; 24:70.
  37. Marwaha N, Sarode R, Gupta RK, et al. Clinico-hematological characteristics in patients with kala azar. A study from north-west India. Trop Geogr Med 1991; 43:357.
  38. Benjamin B, Annobil SH, Bassuni WA. Diagnostic and management problems in childhood visceral leishmaniasis in south-western Saudi Arabia. Ann Trop Paediatr 1994; 14:7.
  39. Sinha R, Datta U, Sehgal S. Importance of bone marrow culture for diagnosis of Kala azar. Scand J Infect Dis 1993; 25:787.
  40. Wickramasinghe SN, Abdalla SH, Kasili EG. Ultrastructure of bone marrow in patients with visceral leishmaniasis. J Clin Pathol 1987; 40:267.
  41. Badaró R, Nascimento C, Carvalho JS, et al. Recombinant human granulocyte-macrophage colony-stimulating factor reverses neutropenia and reduces secondary infections in visceral leishmaniasis. J Infect Dis 1994; 170:413.
  42. Weatherall DJ, Kwiatkowski D. Hematologic manifestations of systemic diseases in children of the developing world. In: Hematology of Infancy and Childhood, 5th ed, Nathan D, Orkin (Eds), WB Saunders, Philadelphia p.1902.
  43. Olliaro P, Djimdé A, Dorsey G, et al. Hematologic parameters in pediatric uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa. Am J Trop Med Hyg 2011; 85:619.
  44. Dale DC, Wolff SM. Studies of the neutropenia of acute malaria. Blood 1973; 41:197.
  45. Senaldi G, Vesin C, Chang R, et al. Role of polymorphonuclear neutrophil leukocytes and their integrin CD11a (LFA-1) in the pathogenesis of severe murine malaria. Infect Immun 1994; 62:1144.
  46. Segel GB, Halterman JS. Neutropenia in pediatric practice. Pediatr Rev 2008; 29:12.
  47. Zon LI, Arkin C, Groopman JE. Haematologic manifestations of the human immune deficiency virus (HIV). Br J Haematol 1987; 66:251.
  48. Jacobson MA, Liu RC, Davies D, Cohen PT. Human immunodeficiency virus disease-related neutropenia and the risk of hospitalization for bacterial infection. Arch Intern Med 1997; 157:1825.
  49. Moore RD, Keruly JC, Chaisson RE. Neutropenia and bacterial infection in acquired immunodeficiency syndrome. Arch Intern Med 1995; 155:1965.
  50. Murphy MF, Metcalfe P, Waters AH, et al. Incidence and mechanism of neutropenia and thrombocytopenia in patients with human immunodeficiency virus infection. Br J Haematol 1987; 66:337.
  51. Ribera E, Ocaña I, Almirante B, et al. Autoimmune neutropenia and thrombocytopenia associated with development of antibodies to human immunodeficiency virus. J Infect 1989; 18:167.
  52. Perkocha LA, Rodgers GM. Hematologic aspects of human immunodeficiency virus infection: laboratory and clinical considerations. Am J Hematol 1988; 29:94.
  53. Scadden DT, Bering HA, Levine JD, et al. Granulocyte-macrophage colony-stimulating factor mitigates the neutropenia of combined interferon alfa and zidovudine treatment of acquired immune deficiency syndrome-associated Kaposi's sarcoma. J Clin Oncol 1991; 9:802.
  54. Kuritzkes DR, Parenti D, Ward DJ, et al. Filgrastim prevents severe neutropenia and reduces infective morbidity in patients with advanced HIV infection: results of a randomized, multicenter, controlled trial. G-CSF 930101 Study Group. AIDS 1998; 12:65.
  55. Manfredi R, Mastroianni A, Coronado O, Chiodo F. Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in leukopenic patients with advanced HIV disease. J Chemother 1996; 8:214.
  56. Schooley RT, Densen P, Harmon D, et al. Antineutrophil antibodies in infectious mononucleosis. Am J Med 1984; 76:85.
  57. Guibaud S, Plumet-Leger A, Frobert Y. Transient neutrophil aggregation in a patient with infectious mononucleosis. Am J Clin Pathol 1983; 80:883.
  58. Sumaya CV, Ench Y. Epstein-Barr virus infectious mononucleosis in children. II. Heterophil antibody and viral-specific responses. Pediatrics 1985; 75:1011.
  59. Roberts WD, Weinberg KI, Kohn DB, et al. Granulocyte recovery in pediatric marrow transplant recipients treated with ganciclovir for cytomegalovirus infection. Am J Pediatr Hematol Oncol 1993; 15:320.
  60. Salzberger B, Bowden RA, Hackman RC, et al. Neutropenia in allogeneic marrow transplant recipients receiving ganciclovir for prevention of cytomegalovirus disease: risk factors and outcome. Blood 1997; 90:2502.
  61. Farrugia E, Schwab TR. Management and prevention of cytomegalovirus infection after renal transplantation. Mayo Clin Proc 1992; 67:879.
  62. HAVENS WP Jr, MARCK RE. The leukocytic response of patients with experimentally induced infectious hepatitis. Am J Med Sci 1946; 212:129.
  63. Nagaraju M, Weitzman S, Baumann G. Viral hepatitis and agranulocytosis. Am J Dig Dis 1973; 18:247.
  64. Rakela J, Wood JR, Czaja AJ, et al. Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial. Mayo Clin Proc 1990; 65:1330.
  65. Dusheiko G. Side effects of alpha interferon in chronic hepatitis C. Hepatology 1997; 26:112S.
  66. Brown KE, Tisdale J, Barrett AJ, et al. Hepatitis-associated aplastic anemia. N Engl J Med 1997; 336:1059.
  67. Mary JY, Baumelou E, Guiguet M. Epidemiology of aplastic anemia in France: a prospective multicentric study. The French Cooperative Group for Epidemiological Study of Aplastic Anemia. Blood 1990; 75:1646.
  68. Issaragrisil S, Kaufman D, Thongput A, et al. Association of seropositivity for hepatitis viruses and aplastic anemia in Thailand. Hepatology 1997; 25:1255.
  69. Linnavuori K, Peltola H, Hovi T. Serology versus clinical signs or symptoms and main laboratory findings in the diagnosis of exanthema subitum (roseola infantum). Pediatrics 1992; 89:103.
  70. Singh N, Carrigan DR, Gayowski T, Marino IR. Human herpesvirus-6 infection in liver transplant recipients: documentation of pathogenicity. Transplantation 1997; 64:674.
  71. Benjamin B, Ward SM. Leukocytic response to measles. Am J Dis Child 1932; 44:921.
  72. Abramowitz A, Tamir I, Livni N, et al. Polymorphonuclear leukocyte-associated antigenemia in measles: demonstration and significance. J Med Virol 1984; 13:293.
  73. Yetgin S, Altay C. Defective bactericidal function of polymorphonuclear neutrophils in children with measles. Acta Paediatr Scand 1980; 69:411.
  74. Thatte UM, Gangal PS, Kulkarni MR, et al. Polymorphonuclear and monocyte functions in measles. J Trop Pediatr 1991; 37:67.
  75. Anderson R, Rabson AR, Sher R, Koornhof HJ. Defective neutrophil motility in children with measles. J Pediatr 1976; 89:27.
  76. Black FL, Sheridan SR. Blood leukocyte response to live measles vaccine. Am J Dis Child 1967; 113:301.
  77. HILLENBRAND FK. The blood picture in rubella; its place in diagnosis. Lancet 1956; 271:66.
  78. Arvin AM. Varicella-Zoster virus. In: Nelson Textbook of Pediatrics, 15th ed, Behman RE, Kliegman RM, Arvin AM (Eds), WB Saunders, Philadelphia 1996.
  79. Koumbourlis AC, Heldrich FJ. Varicella infection with profound neutropenia, multisystem involvement and no sequelae. Pediatr Infect Dis J 1988; 7:429.
  80. Kalayanarooj S, Vaughn DW, Nimmannitya S, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997; 176:313.
  81. Halstead SB. Dengue: hematologic aspects. Semin Hematol 1982; 19:116.
  82. JOHNSON ES, NAPOLI VM, WHITE WC. Colorado tick fever as a hematologic problem. Am J Clin Pathol 1960; 34:118.
  83. Philipp CS, Callaway C, Chu MC, et al. Replication of Colorado tick fever virus within human hematopoietic progenitor cells. J Virol 1993; 67:2389.
  84. Oshiro LS, Dondero DV, Emmons RW, Lennette EH. The development of Colorado tick fever virus within cells of the haemopoietic system. J Gen Virol 1978; 39:73.
  85. Bartelloni PJ, Tesh RB. Clinical and serologic responses of volunteers infected with phlebotomus fever virus (Sicilian type). Am J Trop Med Hyg 1976; 25:456.
  86. Sabin AB, et al. Phlebotomus (pappataci or sandfly) liver. JAMA 1944; 125:603.