HEMATOLOGICAL CHARACTERISTICS OF YEMENI ADULTS AND CHILDREN WITH VISCERAL LEISHMANIASIS. COULD EOSINOPENIA BE A SUSPICION INDEX?
Main Article Content
Keywords
visceral leishmaniasis, Yemen, early diagnosis, hematological charcteristics, bone marrow eosinopenia, biomarker
Abstract
Background and objectives: Delay in the diagnosis of visceral leishmaniasis (VL) particularly in non-endemic areas is associated with higher mortality. In our experience, we found that marked bone marrow eosinopenia was a very frequent accompaniment of VL and might be a useful clue for the diagnosis, which indicates the opportunity for further morphological assessment. The aim of this study was to describe the hematological characteristics including peripheral blood and bone marrow findings of Yemeni adults and children with VL.
Methods: We conducted a descriptive analytic study to evaluate systematically peripheral blood and bone marrow findings of Yemeni adults and children with VL. Peripheral blood and bone marrow aspiration of patients with bone marrow aspirate confirmed VL were examined. Forty-seven patients with the main age (±SD) of 17.34±11.37 years (Range: 1-60) were included in the study. Fifty-one non-VL subjects with splenomegaly and pancytopenia or bicytopenia served as control group.
Results: All patients with VL had anemia, 41 (87%) leukopenia, 42 (89%) neutropenia, 44 (94%) thrombocytopenia, 42 (89%) eosinopenia, 34 (72%) pancytopenia and 13 (28%) had bicytopenia. In bone marrow examination 40 (85%) showed hypercellularity, 44 (94%) eosinopenia, 24 (51%) dyserythropoiesis, 22 (47%) lymphocytosis, 8 (17%) plasmacytosis, 27 (57%) decreased iron stores and 20 (43%) showed decreased sideroblasts. Comparison of VL patients with the control group showed significantly more frequent peripheral blood eosinopenia and lymphopenia and marrow eosinopenia. There was no significant difference between adults and children in any of the hematological features.
Conclusion: Anemia, leukopenia, neutropenia, thrombocytopenia, eosinopenia, pancytopenia and marked bone marrow eosinopenia were the most common findings. The finding of marked bone marrow eosinopenia is a significant clue for the diagnosis of visceral leishmaniasis in patients who present with splenomegaly associated with cytopenias. This finding is particularly valuable in non-endemic areas.
Keywords: Visceral Leishmaniasis, Yemen, Early Diagnosis, Hematological Features, Bone Marrow Eosinopenia.
Downloads
Abstract 2906
PDF Downloads 860
HTML Downloads 1246
References
2. Ready PD. Epidemiolgy of Visceral Leishmaniasis. Clin Epidemiol 2014; 6:147-154 https://doi.org/10.2147/CLEP.S44267 PMid:24833919 PMCid:PMC4014360
3. Abdul Hamid G, Gobah GA. Clinical and hematological manifestations of visceral leishmaniasis in Yemeni children. Turk J Hematol 2009; 26: 25–28.
4. Sarkari B, Naraki T, Ghatee MA , Abdolahi KS, Davami MH. Visceral Leishmaniasis in Southwestern Iran: A Retrospective Clinico-Hematological Analysis of 380 Consecutive Hospitalized Cases (1999-2014). PLOS ONE 2016;11(3): e0150406. doi: 10.1371/journal.pone.0150406. https://doi.org/10.1371/journal.pone.0150406
5. Agrawal Y, Sinha AK, Upadhyaya P, Kafle SU, Rijal S, Khanal B. Hematological profile in visceral leishmaniasis. Int J Infect Microbiol 2013;2(2):39-44 https://doi.org/10.3126/ijim.v2i2.8320
6. Varma N, Naseem S. Hematologic Changes in Visceral Leishmaniasis/Kala Azar. Indian J Hematol Blood Transfus 2010; 26: 78-78 https://doi.org/10.1007/s12288-010-0027-1 PMid:21886387 PMCid:PMC3002089
7. Jain A, Naniwadekar M. An etiological reappraisal of pancytopenia - largest series reported to date from a single tertiary care teaching hospital. BMC Hematol 2013;13:10. https://doi.org/10.1186/2052-1839-13-10
8. Tunccan OG, Tufan A, Telli G, Akyürek N, Pamukçuoglu M, Yilmaz Get al. Visceral Leishmaniasis Mimicking Autoimmune Hepatitis, Primary Biliary Cirrhosis, and Systemic Lupus Erythematosus Overlap. Korean J Parasitol 2012; 50 (2): 133-136 https://doi.org/10.3347/kjp.2012.50.2.133 PMid:22711924 PMCid:PMC3375451
9. Cakar M, Cinar M, Yilmaz S, Sayin S, Ozgur G, Pay S. A case of leishmaniasis with a lupus-like presentation. Seminar Arthritis Rheum. 2015;45(1):e3-4. https://doi.org/10.1016/j.semarthrit.2015.04.001 PMid:25953712
10. Prasad R, Muthusami S, Pandey N, Tilak V, Shukla J, Mishra OP. Unusual presentations of Visceral leishmaniasis. Indian J Pediatr 2009;76: 843–845. https://doi.org/10.1007/s12098-009-0148-4 PMid:19475352
11. Celik U, Alabaz D, Alhan E, Bayram I, Celik T. Diagnostic dilemma in an adolescent boy: hemophagocytic syndrome in association with kala azar. Am J Med Sci 2007;334:139–141. https://doi.org/10.1097/MAJ.0b013e31812e97f4 PMid:17700207
12. Driemeier M, de Oliveira PA, Druzian AF, Lopes Brum GF, Pontes ER, Dorval ME, Paniago AM. Late diagnosis: a factor associated with death from visceral leishmaniasis in elderly patients. Pathog Glob Health 2015;109(6): 283-9. https://doi.org/10.1179/2047773215Y.0000000029 PMid:26257311 PMCid:PMC4727583
13. Bosilkovski M, Dimozva M, Stevanovic M, Cvetkovska VS, Duganovska M. Fever of unknown origin--diagnostic methods in a European developing country. Voinosanit Pregl. 2016;73(6):553-8. https://doi.org/10.2298/VSP140827050B
14. Sakkas H, Gartzonika C, Levidiotou S. Laboratory diagnosis of human visceral leishmaniasis. J Vector Borne Dis 2016;53(1):8-16. PMid:27004573
15. Report of a meeting of the WHO Expert Committee on the control of Leishmaniasis, Geneve, 22-26 March 2010. Available at: whqlibdoc.who.int, accessed: April, 2, 2017
16. da Silva MR, Stewart JM, Costa CH. Sensitivity of bone marrow aspirates in the diagnosis of visceral leishmaniasis. AM J Trop Med Hyg 2005;72(6):811-4 PMid:15964968
17. Bhatia P, Haldar D, Varma N, Marwaha RK, Varma S. A Case Series Highlighting the Relative Frequencies of common/uncommon and Atypical/Unusual Hematological Findings on bone marrow examination in cases of Visceral Leishmaniasis. Mediterr J Hematol Infect Dis 2011; 3: e2011035. https://doi.org/10.4084/mjhid.2011.035 PMid:22084650 PMCid:PMC3212968
18. Chaufal SS, Pant P, Chachra U, Singh P, Thapliyal N, Rawat V. Role of Haematological Changes in Predicting Occurrence of Leishmaniasis- A Study in Kumaon Region of Uttarakhand. J Clin Diag Res 2016;10(5):FC39-34.
https://doi.org/10.7860/JCDR/2016/15438.7885
19. Pagliano P., Ascione T., Di Flumeri G., Boccia G., De Caro F. Visceral leishmaniasis in immunocompromised: diagnostic and therapeutic approach and evaluation of the recently released IDSA guidelines. Infez. Med 2016; 24(4): 265-271 PMid:28011960
20. Franceschini E, Puzzolante C, Menozzi M, Rossi L, Bedini A, Orlando G, Gennari W, Meacc Mi, Rugna G, Carra E, Codeluppi M, Mussini C. Clinical and Microbiological Characteristics of Visceral Leishmaniasis Outbreak in a Northern Italian Nonendemic Area: A Retrospective Observational Study. BioMed Research International Volume 2016 (2016), Article ID 6481028, 7 pages
21. Mahdy MAK, Al-Mekhlafi AM, Abdul-Ghani R, Saif-Ali R, Al-Mekhlafi HM, Al-Eryani SM, Lim YAL, Mahmud R. First Molecular Characterization of Leishmania Species causing Visceral Leishmaniasis among Childeren in Yemen. PLOS ONE 2016;11(3): e0151265.
22. Al-Ghazaly J., Al-Dubai W. The clinical and biochemical characteristics of Yemeni adults and children with visceral leishmaniasis and the differences between them: a prospective cross-sectional study before and after treatment. Trop Doct 2016;46(4): 224-231. https://doi.org/10.1177/0049475515622862 PMid:26746626
23. Bates I, Burthern J. Bone marrow biopsy In: Dacie and Lewis Practical Haematology, Bain B, Bates I, Laffan M, Lewis SM (eds), Churchill Livingstone Elsevier, 11th edition 2012. p.130.
24. Ryan DH. Examination of the marrow In: Williams Hematology, Kaushansky K, Lichtman M, Beutler E, Kipps TJ, Seligsohn U, Prchal JT (eds), McGraw Hill Medical, 8th edition 2011. p. 33. PMCid:PMC3207869
25. Collin S, Davidson R, Ritmeijer K, Keus K, Melaku Y, Kipngetich S, Davies C. Conflict and kala-azar: determinants of adverse outcomes of kala-azar among patients in southern Sudan. Clin. Infect. Dis 2004; 38 (5): 612–19. https://doi.org/10.1086/381203 PMid:14986243
26. Kopterides P, Halikias S, Tsavaris N. Visceral leishmaniasis masquerading as myelodysplasia. Am J Hematol 2003;74:198–199 https://doi.org/10.1002/ajh.10408 PMid:14587050
27. Arlet JB, Capron L, Pouchot J. Visceral leishmaniasis mimicking systemic lupus erythematosus. J Clin Rheumatol 2010; 16: 203-204. https://doi.org/10.1097/RHU.0b013e3181dfd26f PMid:20511988
28. Pagliano, P., Costantini, S., Gradoni, L., Faella, F.S., Spasiano, A., Mascarella, G., Prossomariti, L., Fusco, U., Ricchi, P. Case report: Distinguishing visceral leishmaniasis from intolerance to pegylated interferon-a in a thalassemic splenectomized patient treated for chronic hepatitis C. American Journal of Tropical Medicine and Hygiene 2008; 79(1): 9-11 PMid:18606757
29. Chakrabarti S, Sarkar S, Goswami BK, Sarkar N, Das S. Clinico-hematological profile of visceral leishmaniasis among immunocompetent patients. Southeast Asian J Trop Med Public Health. 2013;44(2):143-9. PMid:23691621
30. Bain BJ. Dyserythropoiesis in visceral leishmaniasis. American J Hematol 2010;85(10):781 https://doi.org/10.1002/ajh.21787 PMid:20652969
31. Temiz F, Gurbuz BB, Leblebisatan G, Ozkan A, Canoz PY, Harmanogullari S, Gezer H, Tumogor G, Turgut M. An association of leishmaniasis and dyserythropoiesis in children. Indian J Hematol Blood Transfus 2014; 30 (1):19-21 https://doi.org/10.1007/s12288-012-0189-0 PMid:24554815 PMCid:PMC3921338
32. Bourdoiseau G, Bonnefont C, Magnol JP, Saint-Andre I, Chabanne L (1997) Lymphocyte subset abnormalities in canine leishmaniasis. Vet ImmunolImmunopathol 1997; 56: 345–351 https://doi.org/10.1016/S0165-2427(96)05768-6
33. Reis AB, Teixeira-Carvalho A, Giunchetti RC, Guerra LL, Carvalho MG, et al. Phenotypic features of circulating leucocytes as immunological markers for clinical status and bone marrow parasite density in dogs naturally infected by Leishmania chagasi. Clin Exp Immunol 2006;146: 303–311 https://doi.org/10.1111/j.1365-2249.2006.03206.x PMid:17034583 PMCid:PMC1942052
34. Scalzone M, Ruggiero A, Mastsngelo S, Trombatore G, Ridola V, Maurii P, Riccardi R. Hemophagocytic lymphohistiocytosis and visceral leishmaniasis in children: case report and systematic review of literature. J Infect Dev Ctries 2016;10(1):103-8 https://doi.org/10.3855/jidc.6385 PMid:26829545
35. Jeronimo SMB, de Queiroz Sousa A, Pearson RD. Leishmaniasis In: Tropical infectious diseases: principles, pathogens and practice, Guerrant, RL, Walker, DH, Weller, PF (Eds), Churchill Livingstone Elsevier, Edinburgh, Scotland 2006. p. 1095-1113.
36. Houweling TA, Karim-Kos HE, Kulik Mc, Stolk WA, Haagsama JA, Lenk EJ, Richardus JH, de Vlas SJ. Socioeconomic Inequalities in Neglected Tropical Diseases: A Systematic Review. J Clin Exp Hepatol 2016;6(2):146-8.
https://doi.org/10.1371/journal.pntd.0004546
37. Nicolato RC, Abreu RT, Roatt BM, Aguiar-Soares RDO, Reis LES, Carvalho MG, Carneiro CM, Giunchetti RC et al. Clinical Forms of Canine Visceral Leishmaniasis in Naturally Leishmania infantum–Infected Dogs and Related Myelogram and Hemogram Changes. PLOS ONE 2013;8(12): e82947. https://doi.org/10.1371/journal.pone.0082947 PMid:24376612 PMCid:PMC3871677
38. Tryphonas L, Zawidzka Z, Bernard MA, Janzen EA. Visceral leishmaniasis in a dog: clinical, hematological and pathological observations. Can J Comp Med 1997;41: 1–12.
39. Salpnickova M, Volkova V, Cepickova M, Kobets T, Sima M, Svobodova M et al. Gene-specific sex effects on eosinophil infiltration in leishmaniasis Biolgy of Sex Differences 2016; 7:59.
40. Dhingra KK, Gupta P, Saroha V, Setia N,Khurana N, Singh T. Morphological findings in bone marrow biopsy and aspirate smears of visceral Kala Azar: A review. Indian J Pathol Microbiol 2010; 53 (1): 96-100. https://doi.org/10.4103/0377-4929.59193 PMid:20090232