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Lymphadenopathy

Lymphadenopathy


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Shyam Patel [2];Associate Editor(s)-in-Chief: Amandeep Singh M.D.[3], Raviteja Guddeti, M.B.B.S. [4] Ogechukwu Hannah Nnabude, MD


Synonyms and keywords: Lymph nodes enlarged; Enlarged lymph nodes; Lymphadenitis; Swollen lymph nodes; Swollen/enlarged lymph nodes
For patient information, click here

Overview

Overview

Classification

Classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2], Raviteja Guddeti, M.B.B.S. [3]Delband Yekta Moazami, M.D.[4] Ogechukwu Hannah Nnabude, MD

Overview

Lymphadenopathy may be classified according to distribution into 2 groups localized lymphadenopathy and generalized lymphadenopathy.

Classification

Depending upon the involvement of the lymph nodes, lymphadenopathy is classified into 2 groups, generalized and localized:[1]

  • Localized lymphadenopathy: localized adenopathy occurs in contiguous groupings of lymph nodes. In discrete anatomical regions, lymph nodes are distributed, and their enlargement represents their location’s lymphatic drainage. Tender or non-tender, fixed or mobile, and discreet or “matted” together can be the nodes themselves. 75 percent of all lymphadenopathies are localized, with over 50% seen in the region of the head and neck.

Lymphadenopathy may be classified as follows:

Upper limit of lymph node sizes in adults
Generally 10 mm[4][5]
Inguinal 10[6] – 20 mm[7]
Pelvis 10 mm for ovoid lymph nodes, 8 mm for rounded[6]
Neck
Generally (non-retropharyngeal) 10 mm[6][8]
Jugulodigastric lymph nodes 11mm[6] or 15 mm[8]
Retropharyngeal 8 mm[8]
Mediastinum
Mediastinum, generally 10 mm[6]
Superior mediastinum and high paratracheal 7mm[9]
Low paratracheal and subcarinal 11 mm[9]
Upper abdominal
Retrocrural space 6 mm[10]
Paracardiac 8 mm[10]
Gastrohepatic ligament 8 mm[10]
Upper paraaortic region 9 mm[10]
Portacaval space 10 mm[10]
Porta hepatis 7 mm[10]
Lower paraaortic region 11 mm[10]

References

  1. ↑ Mohseni S, Shojaiefard A, Khorgami Z, Alinejad S, Ghorbani A, Ghafouri A (2014). “Peripheral lymphadenopathy: approach and diagnostic tools”. Iran J Med Sci. 39 (2 Suppl): 158–70. PMC 3993046. PMID 24753638.
  2. ↑ Ganeshalingam S, Koh DM (December 2009). “Nodal staging”. Cancer Imaging. 9: 104–11. doi:10.1102/1470-7330.2009.0017. PMC 2821588. PMID 20080453.
  3. ↑ Schmidt AF, Rodrigues OR, Matheus RS, Kim Jdu U, Jatene FB (2007). “Mediastinal lymph node distribution, size and number: definitions based on an anatomical study”. J Bras Pneumol. 33 (2): 134–40. doi:10.1590/s1806-37132007000200006. PMID 17724531.
  4. ↑ Ganeshalingam, Skandadas; Koh, Dow-Mu (2009). “Nodal staging”. Cancer Imaging. 9 (1): 104–111. doi:10.1102/1470-7330.2009.0017. ISSN 1470-7330. PMC 2821588. PMID 20080453.
  5. ↑ Schmidt Júnior, Aurelino Fernandes; Rodrigues, Olavo Ribeiro; Matheus, Roberto Storte; Kim, Jorge Du Ub; Jatene, Fábio Biscegli (2007). “Distribuição, tamanho e número dos linfonodos mediastinais: definições por meio de estudo anatômico”. Jornal Brasileiro de Pneumologia. 33 (2): 134–140. doi:10.1590/S1806-37132007000200006. ISSN 1806-3713. PMID 17724531.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Torabi M, Aquino SL, Harisinghani MG (September 2004). “Current concepts in lymph node imaging”. Journal of Nuclear Medicine. 45 (9): 1509–18. PMID 15347718.
  7. ↑ “Assessment of lymphadenopathy”. BMJ Best Practice. Retrieved 2017-03-04. Last updated: Last updated: Feb 16, 2017
  8. ↑ 8.0 8.1 8.2 Page 432 in: Luca Saba (2016). Image Principles, Neck, and the Brain. CRC Press. ISBN 9781482216202.
  9. ↑ 9.0 9.1 Sharma, Amita; Fidias, Panos; Hayman, L. Anne; Loomis, Susanne L.; Taber, Katherine H.; Aquino, Suzanne L. (2004). “Patterns of Lymphadenopathy in Thoracic Malignancies”. RadioGraphics. 24 (2): 419–434. doi:10.1148/rg.242035075. ISSN 0271-5333. PMID 15026591.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 Dorfman, R E; Alpern, M B; Gross, B H; Sandler, M A (1991). “Upper abdominal lymph nodes: criteria for normal size determined with CT”. Radiology. 180 (2): 319–322. doi:10.1148/radiology.180.2.2068292. ISSN 0033-8419. PMID 2068292.

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Pathophysiology

Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Delband Yekta Moazami, M.D.[3] Ogechukwu Hannah Nnabude, MD

Overview

Lymph nodes are part of the immune system. As such, they are most readily palpable when fighting infections. Infections can either originate from the organs that they drain or primarily within the lymph node itself, referred to as lymphadenitis.

Pathophysiology

Lymph nodes are part of the immune system. As such, they are most readily palpable when fighting infections. Infections can either originate from the organs that they drain or primarily within the lymph node itself, referred to as lymphadenitis.The pathogenesis of lymphadenopathy is characterized by the inflammation of lymph nodes. This process is primarily due to an elevated rate of trafficking of lymphocytes into the node from the blood, exceeding the rate of outflow from the node.[1]

  • The immune response between the antigen and lymphocyte that leads to cellular proliferation and enlargement of the lymph nodes.
  • Lymph nodes may also be enlarged secondarily as a result of the activation and proliferation of antigen-specific T and B cells (clonal expansion).
  • On gross pathology, characteristic findings of lymphadenopathy, include:
  • Enlarged lymph node
  • Soft greasy yellow areas within the capsule

Lymph nodes are a part of the reticuloendothelial (RES) system, which includes lymphatic vessels, the lymphatic fluid found in interstitial fluid, monocytes of the blood, macrophages of the connective tissue, bone marrow, thymus, spleen, bone, and mucosa-associated lymphoid tissue (MALT) of visceral organs [1]

Lymphatic fluid moves throughout the lymphatic system and enters lymph nodes for filtration of foreign antigen. Foreign antigens are presented to the lymphoid cells, which lead to cellular proliferation and enlargement. Under microscopy, cellular proliferation in lymphoid follicles may be identified as several mitotic figures.[2] Increased activity leads to stretching of the lymphatic capsule and this may cause localized tenderness.

The development of B-cells originates from pluripotent stem cells from the bone marrow. B cells that successfully build their immunoglobulin heavy chains migrate to the germinal centers to allow for antibody diversification by somatic hypermutation.[3] The current school of thought is that B-cell lymphomas occur as a result of alternations in chromosomal translocations and somatic hypermutation.

T-cell development also begins from pluripotent stem cells, which mature within the thymic cortex. [4] While they are in the thymic cortex, specific rearrangements occur at the T-cell receptor. It is understood that chromosomal translocations at the level of T-cell receptors lead to T-cell lymphomagenesis.

Lymph nodes follicle necrosis may occur due to inflammatory, infectious, or malignant conditions. The neutrophil-rich infiltrates suggests bacterial infection, while lymphocyte-rich predominance may suggest viral infection. However, clinicians must remember that etiologies may vary; lymphomas, leukemias, tuberculosis, or even systemic lupus erythematosus (SLE) may be more appropriate diagnoses in the appropriate clinical context [5]

Microscopic findings

  • On microscopic histopathological analysis, characteristic findings of lymphadenopathy will depend on the etiology.Common findings, include:[1]

Non-specific reactive follicular hyperplasia (NSRFH)

  • Large spaced cortical follicles
  • Tingible body macrophages, normal dark/light GC pattern

Lymph node metastasis

Toxoplasmosis

Cat-scratch disease

Dermatopathic lymphadenopathy

Systemic lupus erythematosus lymphadenopathy

  • Blue hematoxylin bodies
  • Necrosis
  • No PMNs

Histology can provide more information regarding the cause of lymphadenopathy when etiology is not clear during initial history taking, physical examination, and laboratory evaluation.

Common causes of lymphadenopathy with their associated histological findings include:

References

  1. ↑ 1.0 1.1 1.2 Mohseni S, Shojaiefard A, Khorgami Z, Alinejad S, Ghorbani A, Ghafouri A (2014). “Peripheral lymphadenopathy: approach and diagnostic tools”. Iran J Med Sci. 39 (2 Suppl): 158–70. PMC 3993046. PMID 24753638.
  2. ↑ Gowing NF (1974). “Tumours of the lymphoreticular system: nomenclature, histogenesis, and behaviour”. J Clin Pathol Suppl (R Coll Pathol). 7: 103–7. PMC 1347234. PMID 4598345.
  3. ↑ Mesin L, Ersching J, Victora GD (2016). “Germinal Center [[B Cell]] Dynamics”. Immunity. 45 (3): 471–482. doi:10.1016/j.immuni.2016.09.001. PMC 5123673. PMID 27653600. URL–wikilink conflict (help)
  4. ↑ Kumar BV, Connors TJ, Farber DL (2018) Human T Cell Development, Localization, and Function throughout Life. Immunity 48 (2):202-213. DOI:10.1016/j.immuni.2018.01.007 PMID: 29466753
  5. ↑ Strickler JG, Warnke RA, Weiss LM (1987). “Necrosis in lymph nodes”. Pathol Annu. 22 Pt 2: 253–82. PMID 3317224.
  6. ↑ Fend F, Cabecadas J, Gaulard P, Jaffe ES, Kluin P, Kuzu I; et al. (2012). “Early lesions in lymphoid neoplasia: Conclusions based on the Workshop of the XV. Meeting of the European Association of Hematopathology and the Society of Hematopathology, in Uppsala, Sweden”. J Hematop. 5 (3). doi:10.1007/s12308-012-0148-6. PMC 3845020. PMID 24307917.
  7. ↑ Elmore SA (2006) Histopathology of the lymph nodes. Toxicol Pathol 34 (5):425-54. DOI:10.1080/01926230600964722 PMID: 17067938
  8. ↑ Lucia HL, Griffith BP, Hsiung GD (1985) Lymphadenopathy during cytomegalovirus-induced mononucleosis in guinea pigs. Arch Pathol Lab Med 109 (11):1019-23. PMID: 2996461
  9. ↑ Eberle FC, Mani H, Jaffe ES (2009). “Histopathology of Hodgkin’s lymphoma”. Cancer J. 15 (2): 129–37. doi:10.1097/PPO.0b013e31819e31cf. PMID 19390308.

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Histopathology

Histopathology

Causes

Causes

Differentiating Lymphadenopathy from other Diseases

Differentiating Lymphadenopathy from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[5] Ogechukwu Hannah Nnabude, MD

Overview

Lymphadenopathy can be caused by different disease categories include: neoplasms, such as lymphoma; bacterial, viral, and parasite diseases; and inflammatory conditions, such as systemic lupus erythematosus.

Differentiating different causes of Lymphadenopathy

Lymphadenopathy can be caused by different disease categories include: neoplasms such as lymphoma; bacterial, viral, and parasites diseases; and inflammatory conditions, such as systemic lupus erythematosus.

Different causes of Lymphadenopathy can be differentiated from each other based on their different clinical manifestation such as pain, constitutional symptoms; and para clinical symptoms such as blood test and pathology on biopsy.

Diseases Clinical manifestations Para-clinical findings Pathogonomic finding
Symptoms
Lab Findings Biopsy
Painless or painful Lymphadenopathy Generalized or localized Lymphadenopathy Fever Weight loss Night Sweats Rash Other symptoms Immunochemistry Blood work
NEOPLASMS
Non-Hodgkins lymphoma Painless Generalized + + + +
  • N/A
Hodgkin’s disease[1][2][3][4] Painless Generalized + + + +
  • N/A

Fine-needle aspiration

Chronic lymphocytic leukemia[5][6][7][8] Painless Generalized + + + –

CBC

On microscopic histopathological analysis:
  • N/A
Small cell carcinoma of the lung[9][10][11][12][13] Painless Localized – – – –

Nearly all SCLC are immunoreactive for

Neuroendocrine and neural differentiation result in the expression of molecules like

  • N/A
  • N/A
Melanoma[14][15][16] Painless Localized – – – –
  • N/A
  • An excisional biopsy (either elliptical, punch, or saucerization) of the thickest portion of the lesion with 1-3 mm margins.
  • Epidermal atrophy and flattening and prominent dermal invasion
Lymphomatoid granulomatosis[17][18][19][20][21][22][23] Painless Generalized or localized + + – +
  • N/A

CBC

  • N/A
  • On chest CT scan, Halo sign is seen due to the angioinvasive nature of the disease
Angioimmunoblastic lymphadenopathy[24][25][26][27] Painless Generalized + + + +
  • Immunophenotyping
  • Fluorescence in situ hybridization (FISH)
Lymph node or extranodal tissue biopsy is diagnostic of angioimmunoblastic T-cell lymphoma.
  • Epstein–Barr virus (EBV) has been found in both reactive B-cells and the neoplastic T-cells.
  • Trisomy 3, trisomy 5, and +X are the most frequent chromosomal abnormalities found in cases.
Giant lymph node hyperplasia (Castleman disease)[28] Painless Localized + + – –
  • N/A
  • N/A
  • Hypersecretion of the cytokine IL-6.
Diseases Lymphadenopathy Fever Weight loss Night sweats Rash Other symptoms Immunochemistry Blood work Biopsy

Histopathology

Pathogonomical

findings

INFECTIONS
Bacteria Syphilis[29][30][31][32] Painless Localized + – – + Primary syphilis:
  • Chancer

Secondary syphilis:

Tertiary syphilis

  • Gumma
  • Organ system involvement
  • Darkfield microscopy to detect T. pallidum.
  • Nontreponemal tests (e.g., VDRLand RPR )
  • Treponemal tests (e.g. FTA-ABS, the TP-PA assay
  • N/A

On microscopic histopathological analysis, characteristic findings of syphilis:

  • Mononuclear leukocytic infiltration, macrophages, and lymphocytes.
  • Swelling and proliferation of small blood vessels.
  • Painless clean base chancre.
Brucellosis[33][34][35][36][37] Painful Localized + – – +
  • Brucella is most commonly isolated from blood cultures
  • N/A
  • N/A
  • Night sweats, often with characteristic smell, likened to wet hay
Viral Infectious mononucleosis[38] Painful Localized + – – +
  • A positive reaction to a mono spot test
  • Direct detection of EBV in blood or lymphoid tissues
  • N/A
CMV[39][40] Painful Localized + – – +
  • Owl Eye inclusion bodies.
HIV[41][42][43][44] Painful or painless Generalized or localized – + – –
  • Anaemia
  • Thrombocytopenia
  • Leukopenia
  • N/A
  • Plasma HIV RNA viral load
Cat scratch disease[45][46][47][48] Painful Localized + – – +
  • N/A
Mycobacteria Tuberculosis[49][50][51][52][53] Painful Generalized or localized + + + +
Parasite Toxoplasmosis[54][55][56][57] Painless Generalized or localized + – + –
  • N/A
Diseases Lymphadenopathy Fever Weight loss Night sweats Rash Other symptoms Immunochemistry Blood work Biopsy

Histopathology

Pathogonomical

findings

AUTOIMMUNE
Systemic lupus erythematosus

(SLE)[58][59][60][61]

Painless Generalized or localized + +/- – +
Sjögren’s syndrome[62][63][64][65] Painless Generalized or localized – – – +
  • N/A
Sarcoidosis[66][67][68] Painless Generalized – – – –
  • Serum ACE level
  • N/A
 Biopsy of lung

References

  1. ↑ Scientific Style and Format: The CBE Manual for Authors, Editors, and Publishers. Cambridge University Press. 1994. pp. 97–. ISBN 978-0-521-47154-1.
  2. ↑ Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. (Dec 15, 2012). “Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010”. Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. OCLC 23245604.
  3. ↑ Shishodia S, Aggarwal BB (2004). “Nuclear factor-kappaB activation mediates cellular transformation, proliferation, invasion angiogenesis and metastasis of cancer”. Cancer Treat Res. 119: 139–73. PMID 15164877.
  4. ↑ Bargou RC, Leng C, Krappmann D, Emmerich F, Mapara MY, Bommert K; et al. (1996). “High-level nuclear NF-kappa B and Oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells”. Blood. 87 (10): 4340–7. PMID 8639794.
  5. ↑ Nabhan C, Rosen ST (2014). “Chronic lymphocytic leukemia: a clinical review”. JAMA. 312 (21): 2265–76. doi:10.1001/jama.2014.14553. PMID 25461996.
  6. ↑ Hallek M (2015). “Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment”. Am J Hematol. 90 (5): 446–60. doi:10.1002/ajh.23979. PMID 25908509.
  7. ↑ Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015
  8. ↑ Hallek M (2015). “Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment”. Am J Hematol. 90 (5): 446–60. doi:10.1002/ajh.23979. PMID 25908509.
  9. ↑ Zakowski, Maureen F. (2003). “Pathology of small cell carcinoma of the lung”. Seminars in Oncology. 30 (1): 3–8. doi:10.1053/sonc.2003.50015. ISSN 0093-7754.
  10. ↑ National Cancer Institute: PDQ® Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional.
  11. ↑ Grace K. Dy & Alex A. Adjei (2002). “Novel targets for lung cancer therapy: part I”. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 20 (12): 2881–2894. PMID 12065566. Unknown parameter |month= ignored (help)
  12. ↑ K. Hibi, T. Takahashi, Y. Sekido, R. Ueda, T. Hida, Y. Ariyoshi, H. Takagi & T. Takahashi (1991). “Coexpression of the stem cell factor and the c-kit genes in small-cell lung cancer”. Oncogene. 6 (12): 2291–2296. PMID 1722571. Unknown parameter |month= ignored (help)
  13. ↑ Yuri Pekarsky, Alexey Palamarchuk, Kay Huebner & Carlo M. Croce (2002). “FHIT as tumor suppressor: mechanisms and therapeutic opportunities”. Cancer biology & therapy. 1 (3): 232–236. PMID 12432269. Unknown parameter |month= ignored (help)
  14. ↑ Miller AJ, Mihm MC (2006). “Melanoma”. N Engl J Med. 355 (1): 51–65. doi:10.1056/NEJMra052166. PMID 16822996.
  15. ↑ Schanderdorf D, Kochs C, Livingstone E (2013). Handbook of Cutaneous Melanoma: A Guide to Diagnosis and Treatment. Springer.
  16. ↑ Mooi W, Krausz T (2007). Pathology of Melanocytic Disorders 2nd Ed. CRC Press.
  17. ↑ Denburg JA, Bienenstock J (March 1979). “Physiology of the immune response”. Can Fam Physician. 25: 301–7. PMC 2382958. PMID 21297689.
  18. ↑ Jaffe ES, Wilson WH (1997). “Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications”. Cancer Surv. 30: 233–48. PMID 9547995.
  19. ↑ Schmoldt A, Benthe HF, Haberland G (1975). “Digitoxin metabolism by rat liver microsomes”. Biochem Pharmacol. 24 (17): 1639–41. PMC 5922622. PMID https://doi.org/10.1016/S0046-8177(72)80005-4 Check |pmid= value (help).
  20. ↑ Beaty MW, Toro J, Sorbara L, Stern JB, Pittaluga S, Raffeld M; et al. (2001). “Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features”. Am J Surg Pathol. 25 (9): 1111–20. PMID 11688570.
  21. ↑ Bartosik W, Raza A, Kalimuthu S, Fabre A (2012). “Pulmonary lymphomatoid granulomatosis mimicking lung cancer”. Interact Cardiovasc Thorac Surg. 14 (5): 662–4. doi:10.1093/icvts/ivr083. PMC 3329320. PMID 22361129.
  22. ↑ Colby TV (2012). “Current histological diagnosis of lymphomatoid granulomatosis”. Mod Pathol. 25 Suppl 1: S39–42. doi:10.1038/modpathol.2011.149. PMID 22214969.
  23. ↑ Hare SS, Souza CA, Bain G, Seely JM, Gomes MM; et al. (2012). “The radiological spectrum of pulmonary lymphoproliferative disease”. Br J Radiol. 85 (1015): 848–64. doi:10.1259/bjr/16420165. PMC 3474050. PMID 22745203.
  24. ↑ Swerdlow, S.H.; Campo, E.; Harris, N.L.; Jaffe, E.S.; Pileri, S.A.; Stein, H.; Thiele, J.; Vardiman, J.W (2008). “11 Mature T- and NK-cell neoplasms: Angioimmunoblastic T-cell lymphoma”. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC WHO Classification of Tumours. 2 (4th ed.). IARC. ISBN 9283224310.
  25. ↑ [1] Quintanilla-Martinez L, Fend F, Moguel LR, Spilove L, Beaty MW, Kingma DW, Raffeld M, Jaffe ES. “Peripheral T-cell lymphoma with Reed-Sternberg-like cells of B-cell phenotype and genotype associated with Epstein-Barr virus infection.” Am J Surg Pathol. 1999 Oct;23(10):1233-40. PMID: 10524524
  26. ↑ [2] Ree HJ, Kadin ME, Kikuchi M, Ko YH, Go JH, Suzumiya J, Kim DS. “Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers.” Am J Surg Pathol. 1998 Jun;22(6):643-55. PMID: 9630171
  27. ↑ [3] Kaneko Y, Maseki N, Sakurai M, Takayama S, Nanba K, Kikuchi M, Frizzera G. “Characteristic karyotypic pattern in T-cell lymphoproliferative disorders with reactive “angioimmunoblastic lymphadenopathy with dysproteinemia-type” features.” Blood. 1988 Aug;72(2):413-21. PMID: 3261178
  28. ↑ Aoki Y, Yarchoan R, Wyvill K, Okamoto S, Little RF, Tosato G. Detection of viral interleukin-6 in Kaposi sarcoma-associated herpesvirus-linked disorders. Blood 2001;97(7):2173-6.
  29. ↑ Carlson JA, Dabiri G, Cribier B, Sell S (2011). “The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity”. Am J Dermatopathol. 33 (5): 433–60. doi:10.1097/DAD.0b013e3181e8b587. PMC 3690623. PMID 21694502.
  30. ↑ Fitzgerald TJ (1992). “The Th1/Th2-like switch in syphilitic infection: is it detrimental?”. Infect Immun. 60 (9): 3475–9. PMC 257347. PMID 1386838.
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  34. ↑ Zhan Y, Liu Z, Cheers C (1996). “Tumor necrosis factor alpha and interleukin-12 contribute to resistance to the intracellular bacterium Brucella abortus by different mechanisms”. Infect Immun. 64 (7): 2782–6. PMC 174139. PMID 8698508.
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  36. ↑ Arenas GN, Staskevich AS, Aballay A, Mayorga LS (2000). “Intracellular trafficking of Brucella abortus in J774 macrophages”. Infect Immun. 68 (7): 4255–63. PMC 101738. PMID 10858243.
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  39. ↑ Griffiths P, Lumley S (2014). “Cytomegalovirus”. Curr Opin Infect Dis. 27 (6): 554–9. doi:10.1097/QCO.0000000000000107. PMID 25304390.
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  44. ↑ WHO (2007). “WHO and UNAIDS announce recommendations from expert consultation on male circumcision for HIV prevention”. WHO.int. Retrieved 2007-07-13.
  45. ↑ Chomel BB; Kasten RW; Floyd-Hawkins K; et al. (1996). “Experimental transmission of Bartonella henselae by the cat flea”. J. Clin. Microbiol. 34 (8): 1952–6. PMC 229161. PMID 8818889. Unknown parameter |month= ignored (help); Unknown parameter |author-separator= ignored (help)
  46. ↑ Higgins JA, Radulovic S, Jaworski DC, Azad AF (1996). “Acquisition of the cat scratch disease agent Bartonella henselae by cat fleas (Siphonaptera:Pulicidae)”. J. Med. Entomol. 33 (3): 490–5. PMID 8667399. Unknown parameter |month= ignored (help)
  47. ↑ Telford SR III, Wormser GP (2010). “Bartonella spp. transmission by ticks not established”. Emerg Infect Dis. 16 (3): 379–84. doi:10.3201/eid1603.090443. PMID 20202410. Unknown parameter |month= ignored (help)
  48. ↑ Foil L; Andress E; Freeland RL; et al. (1998). “Experimental infection of domestic cats with Bartonella henselae by inoculation of Ctenocephalides felis (Siphonaptera: Pulicidae) feces”. J. Med. Entomol. 35 (5): 625–8. PMID 9775583. Unknown parameter |month= ignored (help); Unknown parameter |author-separator= ignored (help)
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