Clinical diagnosis of leptospirosis with negative serology: case series report

Iin Novita Nurhidayati Mahmuda; Tika Melandya Santi

doi:10.31101/ijhst.v5i2.3030

Authors

Iin Novita Nurhidayati Mahmuda Universitas Muhammadiyah Surakarta, Indonesia
Tika Melandya Santi Universitas Muhammadiyah Surakarta, Indonesia

DOI:

https://doi.org/10.31101/ijhst.v5i2.3030

Keywords:

clinical suspicion; leptospirosis; serology test

Abstract

Leptospirosis is a zoonotic disease with clinical manifestations that range from mild acute febrile illness that resolves on its own to severe, life-threatening conditions with multiple organ dysfunction. Clinical features and various diagnostic tests establish leptospirosis diagnosis, such as bacterial isolation and serological examination. Because the antibody response required for serological testing is often insufficient to detect until the second week of disease (when the immune phase begins), sensitivity, when symptoms begin, is limited. Often, patients present with obvious clinical symptoms of leptospirosis but have negative serological test results. This study aimed to determine how to establish the clinical diagnosis of leptospirosis in leptospirosis cases with negative serology test results. This study used a descriptive method with a case series research design that analyzed four series of leptospirosis cases. The result of this study is that some cases of leptospirosis have obvious symptoms, but serological examination shows negative results. This can happen because new antibodies can be detected on day 6 to day 10 of the illness and reach their peak in 3-4 weeks so that the establishment of a clinical diagnosis of leptospirosis can be established from clear clinical symptoms and other laboratory tests. Establishing the clinical diagnosis of leptospirosis with negative serology can be done with the Faine scoring system.

Author Biographies

Iin Novita Nurhidayati Mahmuda, Universitas Muhammadiyah Surakarta

faculty of medicine

Tika Melandya Santi, Universitas Muhammadiyah Surakarta

faculty of medicine

References

Alikhani, A., Salehifar, E., Zameni, F., Rafiei, A., Yazdani-Charati, J., Delavaryan, L., Akbari, A., & Babamahmoudi, F. (2018). Comparison of azithromycin vs doxycycline prophylaxis in leptospirosis, a randomized double-blind placebo-controlled trial. Journal of Infection in Developing Countries, 12(11), 991–995. https://doi.org/10.3855/jidc.10126

Bandara, K., Weerasekera, M. M., Gunasekara, C., Ranasinghe, N., Marasinghe, C., & Fernando, N. (2016). Utility of modified Faine’s criteria in the diagnosis of leptospirosis. BMC Infectious Diseases, 16(1), 1–7. https://doi.org/10.1186/s12879-016-1791-9

Becirovic, A., Numanovic, F., Dzafic, F., & Piljic, D. (2020). Analysis of Clinical and Laboratory Characteristics of Patients with Leptospirosis in Five-year Period. Materia Socio Medica, 32(1), 15. https://doi.org/10.5455/msm.2020.32.15-19

Bhatia, M., Umapathy, B., & Navaneeth, B. (2015). An evaluation of dark field microscopy, culture and commercial serological kits in the diagnosis of leptospirosis. Indian Journal of Medical Microbiology, 33(3), 416–421. https://doi.org/10.4103/0255-0857.158570

Browne, E. S., Pereira, M., Barreto, A., Zeppelini, C. G., & Oliveira, D. De. (2023). Prevalence of human leptospirosis in the Americas : a systematic review and meta-analysis. 1–8.

Budihal, S. V., & Perwez, K. (2014). Leptospirosis diagnosis: Competancy of various laboratory tests. Journal of Clinical and Diagnostic Research, 8(1), 199–202. https://doi.org/10.7860/JCDR/2014/6593.3950

Carrillo-Larco, R. M., Altez-Fernandez, C., Acevedo-Rodriguez, J. G., Ortiz-Acha, K., & Ugarte-Gil, C. (2019). Leptospirosis as a risk factor for chronic kidney disease: A systematic review of observational studies. PLoS Neglected Tropical Diseases, 13(5), 1–10. https://doi.org/10.1371/journal.pntd.0007458

CDC. (2018). Leptospirosis. CDC.

Chancharoenthana, W., Leelahavanichkul, A., Schultz, M. J., & Dondorp, A. M. (2022). Going Micro in Leptospirosis Kidney Disease. Cells, 11(4), 1–20. https://doi.org/10.3390/cells11040698

Chaudhry, R., Das, A., Premlatha, M. M., Choudhary, A., Chourasia, B. K., Chandel, D. S., & Dey, A. B. (2013). Serological & molecular approaches for diagnosis of leptospirosis in a tertiary care hospital in North India: A 10-year study. Indian Journal of Medical Research, 137(4), 785–790.

Clemente, B. M., Pineda-Cortel, M. R., & Villaflores, O. (2022). Evaluating immunochromatographic test kits for diagnosis of acute human leptospirosis: A systematic review. Heliyon, 8(11). https://doi.org/10.1016/j.heliyon.2022.e11829

Daher, E. F., Silva Junior, G. B., Silveira, C. O., Falcão, F. S., Alves, M. P., Mota, J. A. A. A., Lima, J. B., Mota, R. M. S., Vieira, A. P. F., Pires Neto, R. da J., & Libório, A. B. (2014). Factors associated with thrombocytopenia in severe leptospirosis (Weil’s disease). Clinics, 69(2), 106–110. https://doi.org/10.6061/clinics/2014(02)06

De Brito, T., da Silva, A. M. G., & Abreu, P. A. E. (2018). Pathology and pathogenesis of human leptospirosis: A commented review. Revista Do Instituto de Medicina Tropical de Sao Paulo, 60(January), 1–10. https://doi.org/10.1590/S1678-9946201860023

Dey, S., Sipani, A. K., & Das, R. (2021). Case Report of a Rare Cause of Reactive Arthritis: Leptospirosis. Journal of Orthopaedic Case Reports, 11(3), 79–84. https://doi.org/10.13107/jocr.2021.v11.i03.2098

Dreyfus, A., Ruf, M. T., Goris, M., Poppert, S., Mayer-Scholl, A., Loosli, N., Bier, N. S., Paris, D. H., Tshokey, T., Stenos, J., Rajaonarimirana, E., Concha, G., Orozco, J., Colorado, J., Aristizábal, A., Dib, J. C., & Kann, S. (2022). Comparison of the Serion IgM ELISA and Microscopic Agglutination Test for diagnosis of Leptospira spp. infections in sera from different geographical origins and estimation of Leptospira seroprevalence in the Wiwa indigenous population from Colombia. PLoS Neglected Tropical Diseases, 16(6), 1–18. https://doi.org/10.1371/journal.pntd.0009876

Forbes, A. E., Zochowski, W. J., Dubrey, S. W., & Sivaprakasam, V. (2012). Leptospirosis and weil’s disease in the UK. Qjm, 105(12), 1151–1162. https://doi.org/10.1093/qjmed/hcs145

Ghasemian, R., Shokri, M., Makhlough, A., & Suraki-Azad, M. A. (2016). The course and outcome of renal failure due to human leptospirosis referred to a hospital in North of Iran; A follow-up study. Caspian Journal of Internal Medicine, 7(1), 7–12.

Girault, D., Soupé-Gilbert, M. E., Geroult, S., Colot, J., & Goarant, C. (2017). Isolation of Leptospira from blood culture bottles. Diagnostic Microbiology and Infectious Disease, 88(1), 17–19. https://doi.org/10.1016/j.diagmicrobio.2017.01.014

Goswami, R. P., Goswami, R. P., Basu, A., Tripathi, S. K., Chakrabarti, S., & Chattopadhyay, I. (2014). Predictors of mortality in leptospirosis: An observational study from two hospitals in Kolkata, eastern India. Transactions of the Royal Society of Tropical Medicine and Hygiene, 108(12), 791–796. https://doi.org/10.1093/trstmh/tru144

Haake, D. A., & Levett, P. N. (2015). Leptospirosis in Humans. Curr Top Microbiol Immunol, 25(3), 169–172. https://doi.org/10.1080/00219266.1991.9655201

Husni, S. H., Martini, M., & Suhartono Suhartono. (2023). Risk Factors Affecting the Incidence of Malaria in Indonesia: A Literature Review. Jurnal Serambil Engineering, VIII(1), 4422–4429. https://doi.org/10.4103/NJM.NJM_138_20

Kementerian Kesehatan RI. (2017). Petunjuk Teknik Pengendalian Leptospirosis. Kemenkes RI, 126.

Khalili, M., Sakhaee, E., Bagheri Amiri, F., Safat, A. A., Afshar, D., & Esmaeili, S. (2020). Serological evidence of leptospirosis in Iran; A systematic review and meta-analysis. Microbial Pathogenesis, 138(July 2019), 103833. https://doi.org/10.1016/j.micpath.2019.103833

Khanal, S., Pokhrel, B., Pokhrel, M., Thapa, R., & Nepali, R. (2022). Anuria, an Atypical Presentation of Leptospirosis: A Case Report. Journal of the Nepal Medical Association, 60(245), 83–85. https://doi.org/10.31729/jnma.6240

Kumar Singh, B. (2018). Evaluation of Dark Field Microscopy for the Early Diagnosis of Leptospirosis- A Prospective Study. Journal of Medical Science And Clinical Research, 6(8), 798–801. https://doi.org/10.18535/jmscr/v6i8.133

Le Turnier, P., Bonifay, T., Mosnier, E., Schaub, R., Jolivet, A., Demar, M., Bourhy, P., Nacher, M., Djossou, F., & Epelboin, L. (2019). Usefulness of C-Reactive Protein in Differentiating Acute Leptospirosis and Dengue Fever in French Guiana. Open Forum Infectious Diseases, 6(9), 1–6. https://doi.org/10.1093/ofid/ofz323

Mannam, S. A. M. P. (2018). University Journal of Medicine and Medical Specialities. University Journal of Medicine and Medical Specialities ISSN, 4(2), 4–5.

Motto, S. K., Shirima, G. M., de Clare Bronsvoort, B. M., & Cook, E. A. J. (2021). Epidemiology of leptospirosis in tanzania: A review of the current status, serogroup diversity and reservoirs. PLoS Neglected Tropical Diseases, 15(11). https://doi.org/10.1371/journal.pntd.0009918

Mullan, S., & Panwala, T. H. (2016). Polymerase chain reaction: An important tool for early diagnosis of leptospirosis cases. Journal of Clinical and Diagnostic Research, 10(12), DC08-DC11. https://doi.org/10.7860/JCDR/2016/22462.9010

Munoz-Zanzi, C., Groene, E., Morawski, B. M., Bonner, K., Costa, F., Bertherat, E., & Schneider, M. C. (2020). A systematic literature review of leptospirosis outbreaks worldwide, 1970-2012. Revista Panamericana de Salud Publica/Pan American Journal of Public Health, 44, 1–9. https://doi.org/10.26633/RPSP.2020.78

Musso, D., & La Scola, B. (2013). Laboratory diagnosis of leptospirosis: A challenge. Journal of Microbiology, Immunology and Infection, 46(4), 245–252. https://doi.org/10.1016/j.jmii.2013.03.001

Muthuppalaniappan, V. M., Rajakariar, R., & Blunden, M. J. (2018). Leptospirosis presenting as haemolytic uraemic syndrome: A case report. BMC Nephrology, 19(1), 18–21. https://doi.org/10.1186/s12882-018-0817-5

Perdhana, S. A. P., Susilo, R. S. B., Arifin, Redhono, D., & Sumandjar, T. (2018). Clinical manifestation, serology marker & microscopic agglutination test (MAT) to mortality in human leptospirosis. IOP Conference Series: Earth and Environmental Science, 125(1). https://doi.org/10.1088/1755-1315/125/1/012042

Predescu, A., Diaconu, S., Tiuca, N., Purcareanu, A., Tomescu, A., Cuciureanu, D., Petruta, F., Maria, P. A., Carmen, C., & Pop, C. (2018). LEPTOSPIROSIS - A CASE REPORT. XV(4), 45–53.

Rahayu, A., Prakoso, Y. A., Desiandura, K., & Kristianingrum, Y. P. (2021). Sensitivity and Specificity of Serology, Histopathology, and Molecular Tests in the Detection of Leptospirosis from Slaughtered Cattle in Indonesia. World’s Veterinary Journal, 11(4), 556–561. https://doi.org/10.54203/scil.2021.wvj71

Rajapakse, S. (2022). Leptospirosis: Clinical aspects. Clinical Medicine, Journal of the Royal College of Physicians of London, 22(1), 14–17. https://doi.org/10.7861/clinmed.2021-0784

Rosa, M. I., dos Reis, M. F., Simon, C., Dondossola, E., Alexandre, M. C., Colonetti, T., & Meller, F. O. (2017). ELISA IgM para diagnóstico de leptospirose: Revisão sistemática e meta-análise. Ciencia e Saude Coletiva, 22(12), 4001–4012. https://doi.org/10.1590/1413-812320172212.14112016

Sembiring, E. (2018). Diagnostic approach in leptospirosis patients. IOP Conference Series: Earth and Environmental Science, 125(1). https://doi.org/10.1088/1755-1315/125/1/012089

Silva, F., Brandão, M., & Esteves, A. (2016). of Case Reports in A Rare Presentation of Leptospirosis of Case Reports in. 2–4. https://doi.org/10.12890/2016

Srisawat, N., & Sitprija, V. (2019). Leptospirosis and the Kidney: An Overview. Translational Research in Biomedicine, 7, 1–9. https://doi.org/10.1159/000500376

Sykes, J. E., Reagan, K. L., Nally, J. E., Galloway, R. L., & Haake, D. A. (2022). Role of Diagnostics in Epidemiology, Management, Surveillance, and Control of Leptospirosis. Pathogens, 11(4), 1–24. https://doi.org/10.3390/pathogens11040395

Tomacruz, I. D., Sandejas, J. C., Berba, R., & Sacdalan, D. R. (2019). Behavioural change: A rare presentation of leptospirosis. BMJ Case Reports, 12(8), 1–5. https://doi.org/10.1136/bcr-2019-230619

Venkatesan, A., Bavanandam, S., Sangaralingam, T., & Krishnamoorthy, N. (2022). Clinical spectrum and outcome of elevated serum transaminases in tropical infections among children aged one month to 18 years in an urban tertiary care centre: a prospective observational study. International Journal of Contemporary Pediatrics, 9(4), 352. https://doi.org/10.18203/2349-3291.ijcp20220761

Warnasekara, J., Koralegedara, I., & Agampodi, S. (2019). Estimating the burden of leptospirosis in Sri Lanka; A systematic review. BMC Infectious Diseases, 19(1), 1–12. https://doi.org/10.1186/s12879-018-3655-y

Washington State Department of Health. (2019). Leptospirosis. December, 1–9.

Windpessl, M., Prammer, W., Nömeyer, R., Dinkhauser, P., Wimmer, L., Müller, P., Gusenleitner, J., & Wallner, M. (2014). Leptospirosis and renal failure: A case series. Wiener Klinische Wochenschrift, 126(7–8), 238–242. https://doi.org/10.1007/s00508-014-0501-0