Sains Malaysiana 55(8)(2026): 1296-1309
http://doi.org/10.17576/jsm-2026-5508-06
Pathological Effects of Leptospira yasudae Strain BJ3 Infection in Experimental
Golden Syrian Hamster Isolated from Perak, Malaysia
(Kesan Patologi Jangkitan Strain BJ3 Leptospira yasudae pada Hamster Syria Emas Uji Kaji yang Dipencilkan dari Perak, Malaysia)
HANI KARTINI
AGUSTAR1, NADIA AQILLA SHAMSUSAH2,*,
MAHANEM MD NOOR3 MOHD FIRDAUS-RAIH4, FAIRUZ AMRAN5,
ROZITA HOD6 & MOHD ROHAIZAT HASSAN6
1Department of Earth Sciences and Environment, Faculty of
Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia
2School of Biology, Faculty of Applied Sciences, Universiti Teknologi MARA, Negeri Sembilan Branch, Kuala Pilah Campus, 72000 Kuala Pilah, Negeri Sembilan, Malaysia
3Department of Biological Sciences and Biotechnology, Faculty
of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia
4Department of Applied Physics, Faculty of Science and
Technology, Universiti Kebangsaan Malaysia, 43600 UKM
Bangi, Selangor, Malaysia
5Bacteriology Unit, Institute for Medical Research, 50588
Kuala Lumpur, Malaysia
6Department of Public Health Medicine, Faculty of Medicine,
Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala
Lumpur, Malaysia
Received: 4 March 2025/Accepted: 5
August 2026
AbstraCT
Leptospirosis is a zoonotic disease caused by helical
bacteria of the genus Leptospira that affects animals and humans.
Recently, a newly identified isolate called Leptospira yasudae strain BJ3 has been discovered in soil samples obtained from a wildlife
conservation center located in Malaysia. Currently, data on the virulence of L. yasudae in susceptible hosts is scarce. Hence,
this study was conducted to identify the virulence of L. yasudae strain BJ3 based on the histopathological effects due to leptospirosis
infection towards susceptible hosts. The strain was inoculated
intraperitoneally in hamsters at different doses (1 × 108 cells, 2 ×
108 cells, and 3 × 108 cells). Histopathological effects
of hamsters infected with L. yasudae strain
BJ3 were compared with negative control (uninfected) and positive control
(infected with L. interrogansserovar Lai
strain Langkawi) hamsters. The results demonstrated that infection with 1 × 108 L. yasudae strain BJ3 led to noticeable weight
loss. Microscopically, pulmonary edema in the lung, sparse focal inflammatory
cells infiltration but with normal hepatocytes architecture in the liver and
mild tubular degeneration in the kidney were observed. More vital pathological
changes occurred at higher dose (3 × 108 cells). The gross
examination showed crucial weight and fur loss. Microscopic examination showed
the presence of interstitial pneumonia and lung lesions, hepatocyte expansion,
hypertrophy and hyperemia with severe lesions in kidney cells. In conclusion,
infection caused by L. yasudae strain BJ3 may
represent a noteworthy emerging local agent of leptospirosis due to its ability
to induce virulence and cause histopathological alterations in the kidneys of
susceptible hosts. To the best of our knowledge, this is the first report
demonstrating that a novel Leptospira species isolated from soil can
infect hamsters and induce histopathological changes in organs.
Keywords: Histopathology; hosts; Leptospira yasudae; Leptospirosis; virulence
Abstrak
Leptospirosis merupakan penyakit zoonotik yang disebabkan oleh bakteria heliks daripada genus Leptospira yang menjangkiti haiwan dan manusia. Terdapat satu pencilan baharu yang dikenali sebagai Leptospira yasudae strain BJ3 telah ditemui dalam sampel tanah yang diperoleh dari sebuah pusat pemuliharaan hidupan liar di Malaysia. Namun, tahap kevirulenan strain ini pada perumah yang rentan masih kurang difahami. Oleh itu, kajian ini dijalankan bagi mengenal pasti kevirulenan L. yasudae strain BJ3 berdasarkan kesan histopatologi akibat jangkitannya terhadap hos yang rentan. Strain ini diinokulasikan secara intraperitoneal kepada hamster pada dos berbeza (1 × 10⁸ sel, 2 × 10⁸ sel dan 3 ×
10⁸ sel). Kesan histopatologi pada hamster yang dijangkiti L. yasudae strain BJ3 dibandingkan dengan kumpulan kawalan negatif (tidak dijangkiti) dan kawalan positif (dijangkiti dengan L. interrogans serovar Lai strain Langkawi). Hasil kajian menunjukkan bahawa jangkitan dengan 1 × 10⁸ L. yasudae strain BJ3 menyebabkan penurunan berat badan. Secara mikroskopik, edema pulmonari pada paru-paru, penyusupan sel keradangan fokal yang jarang tetapi dengan struktur hepatosit yang masih normal
pada hati, serta degenerasi tubul yang ringan pada buah pinggang telah diperhatikan. Perubahan patologi yang lebih ketara berlaku pada dos yang lebih tinggi (3 × 10⁸ sel). Pemeriksaan makroskopik menunjukkan kehilangan berat badan dan bulu yang ketara. Pemeriksaan mikroskopik pula mendedahkan kehadiran pneumonia
interstitial dan lesion pada paru-paru, pembesaran hepatosit, hipertrofi dan hiperemia serta lesion teruk pada sel buah pinggang. Kesimpulannya, jangkitan yang disebabkan oleh L. yasudae strain BJ3 berpotensi menjadi ancaman penting sebagai agen leptospirosis tempatan yang baharu kerana keupayaannya untuk menyebabkan penyakit pada hos
yang rentan. Tambahan pula, kajian ini merupakan laporan pertama yang menunjukkan bahawa spesies Leptospira baharu yang dipencilkan daripada tanah mampu menjangkiti hamster dan menyebabkan perubahan histopatologi pada organ haiwan tersebut.
Kata kunci: Histopatologi; kevirulenan; Leptospira yasudae;
Leptospirosis; perumah
REFERENCES
Abdulkader, R.C. & Silva, M.V. 2008. The
kidney in leptospirosis. Pediatric Nephrology 23(12): 2111-2120.
https://doi.org/10.1007/s00467-008-0811-4
Almeida, D.S., Paz, L.N., de Oliveira, D.S.,
Silva, D.N., Ristow, P., Hamond, C., Costa, F., Portela, R.W., Estrela-Lima, A.
& Pinna, M.H. 2019. Investigation of chronic infection by Leptospira spp. in asymptomatic sheep slaughtered in slaughterhouse. PLoS ONE 14(5): e0217391. https://doi.org/10.1371/journal.pone.0217391
American Thoracic Society; European Respiratory
Society. 2002. American Thoracic Society/European Respiratory Society
International Multidisciplinary Consensus Classification of the Idiopathic
Interstitial Pneumonias. American Journal of Respiratory and Critical Care
Medicine 165(2): 277-304. https://doi.org/10.1164/ajrccm.165.2.ats01
Andrade, L., Rodrigues, A.C., Sanches, T.R.,
Souza, R.B. & Seguro, A.C. 2007. Leptospirosis leads to dysregulation of
sodium transporters in the kidney and lung. American Journal of
Physiology-Renal Physiology 292(2): 586-592.
https://doi.org/10.1152/ajprenal.00102.2006
Ashna, S., Devi, S.S., Sajitha, I.S., Reshma,
R.S. & Abraham, M.J. 2019. Acquired hepatic encephalopathy due to
leptospirosis in dog: A case report. Journal of Entomology and Zoology
Studies 7(2): 777-779.
Benavente, C. 2010. Morphologic and molecular
pathogenesis study of condemned kidneys in swine from Alberta. Master thesis,
University of Calgary (Unpublished).
Bharti, A.R., Nally, J.E., Ricaldi, J.N.,
Matthias, M.A., Diaz, M.M., Lovett, M.A., Levett, P.N., Gilman, R.H., Willig,
M.R., Gotuzzo, E. & Vinetz, J.M. 2003. Leptospirosis: A zoonotic disease of
global importance. The Lancet Infectious Diseases 3: 757-771.
https://doi.org/10.1016/s1473-3099(03)00830-2
Bonhomme, D. & Werts, C. 2022. Host and
species-specificities of pattern recognition receptors upon infection with Leptospira interrogans. Frontiers in Cellular and
Infection Microbiology 12: 932137.
https://doi.org/10.3389/fcimb.2022.932137
Burdin, M.L. 1963. Renal histopathology of
leptospirosis caused by Leptospira grippotyphosa in farm animals in Kenya. Research in Veterinary Science 4(3): 423-431.
Burg, N.D. & Pillinger, M.H. 2001. The
neutrophil: Function and regulation in innate and humoral immunity. Clinical
Immunology 99(1): 7-17. https://doi.org/10.1006/clim.2001.5007
Casanovas-Massana,
A., Hamond, C., Santos, L.A., de Oliveira, D., Hacker, K.P., Balassiano, I., Costa, F., Medeiros, M.A., Reis, M.G., Ko,
A.I. & Wunder, E.A. 2020. Leptospira yasudae sp. nov. and Leptospira stimsonii sp. nov., two new species of the pathogenic group
isolated from environmental sources. International Journal of Systematic and
Evolutionary Microbiology 70(3): 1450-1456.
https://doi.org/10.1099/ijsem.0.003480
Castiblanco-Valencia, M.M., Fraga, T.R., Silva,
L.B., Monaris, D., Abreu, P.A., Strobel, S., Józsi,
M., Isaac, L. & Barbosa, A.S. 2012. Leptospiral immunoglobulin-like
proteins interact with human complement regulators factor H, FHL-1, FHR-1, and
C4BP. Journal of Infectious Diseases 205(6): 995-1004.
https://doi.org/10.1093/infdis/jir875
Chacko, C.S., Lakshmi, S.S., Jayakumar, A.,
Binu, S.L., Pant, R.D., Giri, A., Chand, S. & Nandakumar, U.P. 2021. A
short review on leptospirosis: Clinical manifestations, diagnosis and
treatment. Clinical Epidemiology and Global Health 11(1): 100741.
https://doi.org/10.1016/j.cegh.2021.100741
Chancharoenthana, W., Leelahavanichkul,
A., Schultz, M.J. & Dondorp, A.M. 2022. Going
micro in leptospirosis kidney disease. Cells 11(4): 698.
https://doi.org/10.3390/cells11040698
Chen, M., Wu, H., Xie, L., Wu, M. & Lan, P.
2025. Successful management of severe pulmonary form of leptospirosis with
VV-ECMO, prone ventilation, and bronchoalveolar lavage: Two case reports. Frontiers
in Medicine 12: 1598589. https://doi.org/10.3389/fmed.2025.1598589
Chen, X., Li, S.J., Ojcius,
D.M., Sun, A.H., Hu, W.L., Lin, X. & Yan, J. 2017. Mononuclear-macrophages
but not neutrophils act as major infiltrating anti leptospiral phagocytes
during leptospirosis. PLoS ONE 12(7):
e0181014. https://doi.org/10.1371/journal.pone.0181014
Cilia, G., Bertelloni, F. & Fratini, F.
2020. Leptospira infections in domestic and wild animals. Pathogens 9(7): 573. https://doi.org/10.3390/pathogens9070573
Cordonin, C., Turpin, M., Bascands,
J.L., Dellagi, K., Mavingui,
P., Tortosa, P. & Roche, M. 2019. Three Leptospira strains from
Western Indian Ocean wildlife show highly distinct virulence phenotypes through
hamster experimental infection. Frontiers in Microbiology 10: 382.
https://doi.org/10.3389/fmicb.2019.00382
Coutinho, M.L., Matsunaga, J., Wang, L.C., de
la Peña Moctezuma, A., Lewis, M.S., Babbitt, J.T., Aleixo, J.A. & Haake,
D.A. 2014. Kinetics of Leptospira interrogans infection in hamsters after intradermal and subcutaneous challenge. PLoS Neglected Tropical Diseases 8(11):
e3307. https://doi.org/10.1371/journal.pntd.0003307
Daher, E., de Abreu, K.L. & da Silva
Junior, G.B. 2010. Leptospirosis-associated acute kidney injury. Jornal
Brasileiro de Nefrologia 32(4): 400-407.
Dash, B.R., Dhaygude, V.S., Gadhave,
P.D., Garud, K.V. & Kadam, D.P. 2018. Molecular detection of Leptospira spp. from canine kidney tissues and its association with renal lesions. Veterinary
World 11(4): 530-534. https://doi.org/10.14202/vetworld.2018.530-534
Day, N.P.J. & Edward, C.N. 2010.
Leptospirosis. In Infectious Diseases, edited by Cohen, J.,
Powderly, W.G. & Opal, S. Amsterdam: Elsevier. pp. 1241-1246.
Dimroth, P., Wang, H., Grabe, M. & Oster, G. 1999.
Energy transduction in the sodium F-ATPase of Propionigenium modestum. Proceedings of the National Academy
of Sciences of the United States of America 96: 4924-4929.
https://doi.org/10.1073/pnas.96.9.4924
Dong, W.H. & Chen, Z. 2021. Leptospirosis
with pulmonary haemorrhage and multiple organ
failure: A case report and literature review. Journal of International
Medical Research 49(5). https://doi.org/10.1177/03000605211019665
Fann, R.J., Vidya, R.R., Chong, H.E., Indralingam, V. & Christopher Chan, W.S. 2020. Clinical
presentations and predictors of mortality for leptospirosis: A study from
suburban area in Malaysia. Medical Journal of Malaysia 75(1): 52-56.
Fraser, C.M., Norris, S.J., Weinstock, G.M.,
White, O., Sutton, G.G., Dodson, R., Gwinn, M., Hickey, E.K., Clayton, R.,
Ketchum, K.A., Sodergren, E., Hardham, J.M., McLeod,
M.P., Salzberg, S., Peterson, J., Khalak, H.,
Richardson, D., Howell, J.K., Chidambaram, M., Utterback, T. & Venter, J.C.
1998. Complete genome sequence of Treponema pallidum, the syphilis
spirochete. Science 281(5375): 375-388.
https://doi.org/10.1126/science.281.5375.375
Gancheva, G. 2019. Respiratory manifestations
of leptospirosis. Journal of IMAB - Annual Proceeding (Scientific Papers) 25(3): 2622-2627. https://doi.org/10.5272/jimab.2019253.2622
Gendron, K., Christe, A., Walter, S., Schweighauser, A., Francey, T., Doherr,
M.G. & Lang, J. 2014. Serial CT features of pulmonary leptospirosis in 10
dogs. Veterinary Record 174(7): 169. https://doi.org/10.1136/vr.102046
Gomes-Solecki, M., Santecchia,
I. & Werts, C. 2017. Animal models of leptospirosis: of mice and hamsters. Frontiers
in Immunology 8: 58. https://doi.org/10.3389/fimmu.2017.00058
Gonçalves-de-Albuquerque, C.F., Burth, P.,
Silva, A.R., Morandi, V., Bozza, P.T., Younes-Ibrahim, M., de Castro Faria
Neto, H.C. & de Castro Faria, M.V. 2014. Murine lung injury caused by Leptospira interrogans glycolipoprotein,
a specific Na/K-ATPase inhibitor. Respiratory Research 15(1): 93.
https://doi.org/10.1186/s12931-014-0093-2
Guedes, I.B., de Souza, G.O., Castro, J.F.P., Cavalini, M.B., de Souza Filho, A.F. & Heinemann, M.B.
2021. Usefulness of the ranking technique in the microscopic agglutination test
(MAT) to predict the most likely infecting serogroup of Leptospira. Frontiers
in Veterinary Science 8: 654034. https://doi.org/10.3389/fvets.2021.654034
Gunasekara, C.P., Sumaiha,
M.H.F., Damayanthi, M.K.S., Weerasekera, M.M. &
Fernando, S.S.N. 2017. Utility of a modified silver staining technique for
detection of Leptospira. Sri Lankan Journal of Infectious Diseases 7(2): 85-91. https://doi.org/10.4038/sljid.v7i2.8142
Haake, D.A. 2006. Hamster model of
leptospirosis. Current Protocols in Microbiology 2: 12E.2.1-12E.2.13. https://doi.org/10.1002/9780471729259.mc12e02s02
Hagedoorn, N.N., Maze, M.J., Carugati,
M., Cash-Goldwasser, S., Allan, K.J., Chen, K., Cossic,
B., Demeter, E., Gallagher, S., German, R., Galloway, R.L., Habuš, J., Rubach,
M.P., Shiokawa, K., Sulikhan, N. & Crump, J.A.
2024. Global distribution of Leptospira serovar isolations and
detections from animal host species: A systematic review and online
database. Tropical Medicine & International Health 29(3):
161-172. https://doi.org/10.1111/tmi.13965
Hullahalli, K. & Waldor,
M. 2021. Pathogen clonal expansion underlies multiorgan dissemination and
organ-specific outcomes during murine systemic infection. eLife 10: e70910. https://doi.org/10.7554/eLife.70910
Humphryes, P.C., Weeks, M.E., AbuOun, M., Thomson, G., Núñez, A. & Coldham, N.G.
2014. Vaccination with leptospiral outer membrane lipoprotein LipL32 reduces
kidney invasion of Leptospira interrogans serovar Canicola in hamsters. Clinical and Vaccine
Immunology 21(4): 546-551. https://doi.org/10.1128/CVI.00719-13
Iqbal, M.A. & Gupta, M. 2022. Cardiogenic
Pulmonary Edema. Florida: StatPearls Publishing.
Jayakrishnan, B., Ben Abid, F., Balkhair, A., Alkaabi, J.K., Al-Rawas, O.A., George, J.
& Al-Zeedy, K. 2013. Severe pulmonary involvement
in leptospirosis: Alternate antibiotics and systemic steroids. Sultan Qaboos
University Medical Journal 13(2): 318-322. https://doi.org/10.12816/0003241
Karnik, N.D. & Patankar, A.S. 2021.
Leptospirosis in intensive care unit. Indian Journal of Critical Care
Medicine 25(3): S134-S137. https://doi.org/10.5005/jp-journals-10071-23813
Ko, A.I., Goarant, C.
& Picardeau, M. 2009. Leptospira: The dawn
of the molecular genetics era for an emerging zoonotic
pathogen. Nature Reviews Microbiology 7: 736-747.
https://doi.org/10.1038/nrmicro2208
Kohn, B., Steinicke, K., Arndt, G., Gruber,
A.D., Guerra, B., Jansen, A., Kaser-Hotz, B., Klopfleisch,
R., Lotz, F., Luge, E. & Nöckler, K. 2010.
Pulmonary abnormalities in dogs with leptospirosis. Journal of Veterinary
Internal Medicine 24(6): 1277-1282.
https://doi.org/10.1111/j.1939-1676.2010.0585.x
Krangvichian, P., Nakornpakdee,
Y., Sangjun, N., Komanee,
P., Techawiwattanaboon, T. & Patarakul,
K. 2022. Sublethal infection of C3H/HeNJ against Leptospira interrogans serovar Pomona. Acta Tropica 238: 106701. https://doi.org/10.1016/j.actatropica.2022.106701
Liu, Y.H., Chen, Y.H. & Chen, C.M. 2024.
Fulminant leptospirosis presenting with rapidly developing acute renal failure
and multiorgan failure. Biomedicines 12(2): 435.
https://doi.org/10.3390/biomedicines12020435
López-Robles, G., Córdova-Robles, F.N.,
Sandoval-Petris, E. & Montalvo-Corral, M. 2021. Leptospirosis at
human-animal-environment interfaces in Latin America: Drivers, prevention, and
control measures. División de Ciencias Biológicas y de la Salud.
https://doi.org/10.18633/biotecnia.v23i3.1442
Lunn, K.F. 2022. Leptospirosis in Animals -
Overview. https://www.msdvetmanual.com/generalizedconditions/leptospirosis/leptospiro
sis-in-animals-overview (Accessed on 1 July 2022).
Mazni Baharom, Norfazilah Ahmad, Rozita Hod, Mohd Hasni Ja'afar, Fadly Syah Arsad, Fredolin Tangang, Rohaida Ismail, Norlen Mohamed, Mohd Firdaus
Mohd Radi & Yelmizaitun Osman. 2023.
Environmental and occupational factors associated with leptospirosis: A
systematic review. Heliyon 10(1):
e23473. https://doi.org/10.1016/j.heliyon.2023.e23473
McCallum, K.E., Constantino-Casas, F., Cullen,
J.M., Warland, J.H., Swales, H., Linghley,
N., Kortum, A.J., Sterritt, A.J., Cogan, T. & Watson, P.J. 2019. Hepatic
leptospiral infections in dogs without obvious renal involvement. Journal of
Veterinary Internal Medicine 33(1): 141-150.
https://doi.org/10.1111/jvim.15340
Nair, N. & Gomes-Solecki, M. 2020. A mouse
model of sublethal leptospirosis: Protocols for infection with Leptospira through natural transmission routes, for monitoring clinical and molecular
scores of disease, and for evaluation of the host
immune response. Current Protocols in Microbiology 59(1): e127.
https://doi.org/10.1002/cpmc.127
Omar, A., Salameh, R., Zouein,
T., Charafeddine, T., Karam, K. & Hachem, N.
2025. A-not-full-blown Weil’s disease: An atypical cause of
leptospirosis-induced acute hepatitis. Medical Reports 14: 100375.
https://doi.org/10.1016/j.hmedic.2025.100375
Palaniappan, R.U., McDonough, S.P., Divers,
T.J., Chen, C.S., Pan, M.J., Matsumoto, M. & Chang, Y.F. 2006. Immunoprotection of recombinant leptospiral
immunoglobulin-like protein A against Leptospira interrogans serovar Pomona infection. Infection and Immunity 74(3): 1745-1750.
https://doi.org/10.1128/IAI.74.3.1745-1750.2006
Philip, N. & Ahmed, K. 2023. Leptospirosis
in Malaysia: Current status, insights, and future prospects. Journal of
Physiological Anthropology 42(1): 30.
https://doi.org/10.1186/s40101-023-00340-7
Philip, N., Priya, S.P., Jumah Badawi, A.H.,
Mohd Izhar, M.H., Mohtarrudin, N., Tengku Ibrahim, T.A., Sekawi,
Z. & Neela, V.K. 2022. Pulmonary haemorrhage as
the earliest sign of severe leptospirosis in hamster model challenged with Leptospira interrogans strain HP358. PLoS Neglected Tropical Diseases 16(5): e0010409.
https://doi.org/10.1371/journal.pntd.0010409
Picardeau, M. 2017. Virulence of the zoonotic
agent of leptospirosis: Still terra incognita? Nature Reviews Microbiology 15(5): 297-307. https://doi.org/10.1038/nrmicro.2017.5
Picardeau, M. 2013. Diagnosis and epidemiology
of leptospirosis. Médecine et Maladies Infectieuses 43(1): 1-9.
https://doi.org/10.1016/j.medmal.2012.11.005
Picazo, M.G., Benito, P.J. & García-Olmo,
D.C. 2009. Efficiency and safety of a technique for drawing blood from the
hamster cranial vena cava. Laboratory Animals 38(6): 211-216.
https://doi.org/10.1038/laban0609-211
Poonacha, K.B., Donahue, J.M., Giles, R.C., Hong, C.B.,
Petrites-Murphy, M.B., Smith, B.J., Swerczek, T.W., Tramontin, R.R. &
Tuttle, P.A. 1993. Leptospirosis in equine fetuses, stillborn foals, and
placentas. Veterinary Pathology 30(4): 362-369.
https://doi.org/10.1177/030098589303000405
Putz, E.J. & Nally, J.E. 2020.
Investigating the immunological and biological equilibrium of reservoir hosts
and pathogenic Leptospira: Balancing the solution to an acute problem? Frontiers
in Microbiology 11: 2005. https://doi.org/10.3389/fmicb.2020.02005
Rajapakse, S. 2022. Leptospirosis: Clinical
aspects. Clinical Medicine (London) 22(1): 14-17.
https://doi.org/10.7861/clinmed.2021-0784
Rissi, D.R. & Brown, C.A. 2014. Diagnostic
features in 10 naturally occurring cases of acute fatal canine leptospirosis. Journal
of Veterinary Diagnostic Investigation 26(6): 799-804.
https://doi.org/10.1177/1040638714553293
Shamsusah, N.A., Agustar,
H.K., Amran, F. & Hod, R. 2021. Draft genome sequence of Leptospira yasudae strain BJ3, isolated from the soil of an ex-situ wild animal conservation area. Microbiology Resource Announcements 10(39): e0072321. https://doi.org/10.1128/MRA.00723-21
Sheshachalam, A., Srivastava, N., Mitchell, T., Lacy, P.
& Eitzen, G. 2014. Granule protein processing and regulated secretion in
neutrophils. Frontiers in Immunology 5: 448.
https://doi.org/10.3389/fimmu.2014.00448
Shetty, A., Kundu, S. & Gomes-Solecki, M.
2021. Inflammatory signatures of pathogenic and non-pathogenic Leptospira infection in susceptible C3H-HeJ mice. Frontiers in Cellular and Infection
Microbiology 11: 677999. https://doi.org/10.3389/fcimb.2021.677999
Segawa, T., Nomura, K.H., Villanueva, S.Y.A.M.,
Saito, M., Nomura, K., Gloriani, N.G. & Yoshida,
S. 2014. Identification of leptospiral 3-hydroxyacyl-CoA dehydrogenase
released in the urine of infected hamsters. BMC Microbiology 14: 132.
https://doi.org/10.1186/1471-2180-14-132
Shilpa, S., Menon, K.V., Sunil, B. Jolly, D.
& Gleeja, V.L. 2024. Occurrence of Leptospira spp. in peri-domestic rats of Thrissur, Kerala. Journal of Veterinary and
Animal Sciences 55(2): 366-373.
https://doi.org/10.51966/jvas.2024.55.2.366-373
Sun, A.H., Liu, X.X. & Yan, J. 2020.
Leptospirosis is an invasive infectious and systemic inflammatory disease. Biomedical
Journal 43(1): 24-31. https://doi.org/10.1016/j.bj.2019.12.002
Suttie, A.W. 2006. Histopathology of the
spleen. Toxicologic Pathology 34(5): 466-503.
https://doi.org/10.1080/01926230600867750
Tan, J.C. 1983. Leptospirosis pathogenesis and
red cell destruction. PhD thesis, Massey University Palmerston (Unpublished).
Thibeaux, R., Iraola, G., Ferrés,
I., Bierque, E., Girault, D., Soupé-Gilbert,
M.E., Picardeau, M. & Goarant, C. 2018.
Deciphering the unexplored Leptospira diversity from soils uncovers
genomic evolution to virulence. Microbial Genomics 4(1): 144-154.
https://doi.org/10.1099/mgen.0.000144
Tyagita, H., Bahaman, A.R., Jasni,
S., Ibrahim, T.A.T. & Fuzina, N.H. 2019.
Pathogenicity of Leptospira icterohaemorrhagiae serovar Lai strain Langkawi in guinea pigs (Cavia porcellus). Jurnal Veterinar Malaysia (JVM) 31(1): 1-11. https://doi.org/10.71118/586243
Vieira, M.L., de Andrade, S.A., Morais, Z.M.,
Vasconcellos, S.A., Dagli, M.L. & Nascimento, A.L. 2017. Leptospira infection interferes with the prothrombinase complex assembly during
experimental leptospirosis. Frontiers in Microbiology 8(1): 500-510.
https://doi.org/10.3389/fmicb.2017.00500
Villanueva, S., Saito, M., Tsutsumi, Y.,
Segawa, T., Baterna, R.A., Chakraborty, A., Asoh, T.,
Miyahara, S., Yanagihara, Y., Cavinta, L.L., Gloriani, N.G. & Yoshida, S.I. 2014. High virulence in
hamsters of four dominant Leptospira serovars isolated from rats in the
Philippines. Microbiology 160(2): 418-428.
https://doi.org/10.1099/mic.0.072439-0
Vincent, A.T., Schiettekatte,
O., Goarant, C., Neela, V.K., Bernet, E., Thibeaux,
R., Ismail, N., Mohd Khalid, M., Amran, F., Masuzawa,
T., Nakao, R., Amara Korba, A., Bourhy, P., Veyrier, F.J. & Picardeau, M.
2019. Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics. PLoS Neglected Tropical Diseases 13(5): e0007270.
https://doi.org/10.1371/journal.pntd.0007270
Visith, S. & Kearkiat,
P. 2005. Nephropathy in leptospirosis. Journal of Postgraduate Medicine 51: 184-188.
Wunder Jr., E.A., Figueira, C.P., Benaroudj, N., Hu, B., Tong, B.A., Trajtenberg, F., Liu,
J., Reis, M.G., Charon, N.W., Buschiazzo, A., Picardeau,
M. & Ko, A.I. 2016a. A novel flagellar sheath protein, FcpA,
determines filament coiling, translational motility and virulence for the Leptospira spirochete. Molecular Microbiology 101(3): 457-470.
https://doi.org/10.1111/mmi.13403
Wunder, E., Figueira, C., Santos, G., Lourdault, K., Matthias, M., Vinetz, J., Ramos, E., Haake,
D., Picardeau, M., Reis, M. & Ko, A. 2016b.
Real-time PCR reveals rapid dissemination of Leptospira interrogans after intraperitoneal and conjunctival inoculation of hamsters. Infection
and Immunity 84(7): 2105-2115. https://doi.org/10.1128/IAI.00094-16
Yap, M.L., Chew, L.J., Pritpal Singh, S.S., Sekawi, Z., Chee, H.Y., Ong, H.K.O. & Neela, V.K. 2021.
Distribution of pathogenic Leptospira in environmental water and soils
of selected recreational forests in Perak, Malaysia. Tropical Biomedicine 38(2): 122-128. https://doi.org/10.47665/tb.38.2.047
Yener, Z. & Keles, H. 2001. Immunoperoxidase and histopathological examinations of
leptospiral nephritis in cattle. Journal of Veterinary Medicine 48(7):
441-447. https://doi.org/10.1046/j.1439-0442.2001.00355.x
*Corresponding author; email:
nadiaaqilla@uitm.edu.my