Background: Inhabitants from malaria endemic zones often present with enlarged spleen, mainly due to hyper reactive malarial splenomegaly (HMS), and it is seen more commonly associated with elevated levels of Immunoglobulin M (IgM). Cold agglutinin disease is an acquired autoimmune hemolytic anemia (AIHA) that is usually due to cold-reacting IgM autoantibodies directed against red cell antigens. The study was conducted in response to the observed high frequency of transfusion dependent anemia in patients with splenomegaly from malaria endemic zones in southern province of Rwanda. The objectives of this study were to determine the prevalence of cold agglutinin disease and to assess the distribution of IgM antibodies among these patients. Methodology: This was a descriptive, cross-sectional study conducted over a period of six months from June 2016 to December 2016. The study enrolled adult population from malaria endemic areas of the southern province of Rwanda with unexplained splenomegaly. Blood samples for testing IgM levels, cold agglutinin, FBC, and markers of hemolysis were collected from peripheral health settings and analyzed at the laboratory of Butare University Teaching Hospital. Results: During the study period, we enrolled 188 participants with enlarged spleen. One hundred twenty-five (66%) were females and 34% were males. The mean (±SD) age of the study participants was 35.6 ± 15.2 years. Out of 188 participants, only 4.8% were found with significantly positive Cold Agglutinin Titer (CAT) (≥1:64) and 84% of participants were found to have elevated serum IgM level. Hemoglobin level, white blood count and platelets count decrease with severity of splenomegaly, while IgM level increases with spleen size. Conclusion: Among patients with splenomegaly from malaria endemic areas, IgM levels correlate with the stages of splenomegaly while cold agglutinin disease plays a small role in the etiology of anemia.
References
[1]
Rudasingwa, G. and Il Cho, S. (2020) Determinants of the Persistence of Malaria in Rwanda. Malaria Journal, 19, 1-9. https://doi.org/10.1186/s12936-020-3117-z
[2]
Kamuhanda, J.K. (2019) Review of Malaria Epidemiology in Rwanda. 4-7.
Roukhsi, R., Mouhcine, A., Atmane, E.M., Elabdi, M., El Fikri, A. and Mahfoudi, M.B. (2013) Hyper-Reactive Malarial Splenomegaly: About a Case. Medical Sciences, 2, 2-4.
[5]
Mboera, L.E.G., Mukabana, W.R. and Njunwa, K.J. (2014) Integrated Research Partnerships for Malaria Control through an Ecohealth Approach in East Africa: Kenya, Rwanda, Tanzania and Uganda Projects. 1-40.
[6]
Van Den Ende, J., Van Gompel, A., Van Den Enden, E., Taelman, H., Vanham, G. and Vervoort, T. (2000) Hyperreactive Malarial in Expatriates Returning from Sub-Saharan Africa. Tropical Medicine & International Health, 5, 607-611. https://doi.org/10.1046/j.1365-3156.2000.00619.x
[7]
Bisoffi, Z., et al. (2016) Chronic Malaria and Hyper-Reactive Malarial Splenomegaly: A Retrospective Study on the Largest Series Observed in a Non-Endemic Country. Malaria Journal, 15, Article No. 230. https://doi.org/10.1186/s12936-016-1274-x
[8]
Leoni, S., Buonfrate, D., Angheben, A., Gobbi, F. and Bisoffi, Z. (2015) The Hyper-Reactive Malarial Splenomegaly: A Systematic Review of the Literature. Malaria Journal, 14, Article No. 185. https://doi.org/10.1186/s12936-015-0694-3
[9]
Bates, I. and Bedu-Addo, G. (1997) Review of Diagnostic Criteria of Hyper-Reactive Malarial Splenomegaly. The Lancet, 349, 1178. https://doi.org/10.1016/S0140-6736(05)63061-9
[10]
Swiecicki, M.A., Hegerova, P.L. and Gertz, L.T. (2013) Cold Agglutinin Disease. Blood. American Society of Hematology, 122, 1114-1121.
[11]
Venkatesh, V.N., et al. (2014) A Study on Cold Agglutinins in Malaria from a Tertiary Care Hospital of South India. Global Journal of Medical Research: (C) Microbiology & Pathology, 14, 25.
[12]
Gertz, M.A. (2007) Management of Cold Haemolytic Syndrome. British Journal of Haematology, 138, 422-429. https://doi.org/10.1111/j.1365-2141.2007.06664.x
Berentsen, S., Beiske, K. and Tjønnfjord, G.E. (2007) Primary Chronic Cold Agglutinin Disease: An Update on Pathogenesis, Clinical Features and Therapy. Hematology, 12, 361-370. https://doi.org/10.1080/10245330701445392
[15]
Swiecicki, P.L., Hegerova, L.T. and Gertz, M.A. (2015) Cold Agglutinin Disease. Blood, 122, 1114-1122. https://doi.org/10.1182/blood-2013-02-474437
[16]
Kalyani, R., Thej, M.J., Thomas, A.K. and Raveesha, A. (2012) Chronic Cold Agglutinin Disease: A Case Report with Review of Literature. Journal of Clinical and Diagnostic Research, 6, 480-482.
[17]
Bedu-Addo, G. and Bates, I. (2002) Causes of Massive Tropical Splenomegaly in Ghana. The Lancet, 360, 449-454. https://doi.org/10.1016/S0140-6736(02)09680-0
[18]
Alkadarou, T., et al. (2014) Immunological Characteristics of Hyperreactive Malarial Splenomegaly Syndrome in Sudanese Patients. Journal of Tropical Medicine, 2013, Article ID: 961051. https://doi.org/10.1155/2013/961051
[19]
Allam, M.M., et al. (2008) Hyper-Reactive Malarial Splenomegaly (HMS) in Malaria Endemic Area in Eastern Sudan. Acta Tropica, 105, 196-199. https://doi.org/10.1016/j.actatropica.2007.10.002
[20]
Khoo, K.K. (2010) Glucose-6-dehydrogenase Deficiency and Malaria. Australasian Medical Journal, 3, 422-425. https://doi.org/10.4066/AMJ.2010.297
[21]
Army, M., Hospital, C. and Benning, F. (2005) Diagnosis and Management of G6PD Deficiency. American Family Physician, 72, 1277-1282.
[22]
Torres, J.R., et al. (2016) Low-Grade Parasitaemias and Cold Agglutinins in Patients with Hyper-Reactive Malarious Splenomegaly and Acute Haemolysis. Annals of Tropical Medicine & Parasitology, 97, 125-130.
[23]
Ziegler, J.L. and Stuiver, P.C. (1972) Tropical Splenomegaly Syndrome in a Rwandan Kindred in Uganda. British Medical Journal, 3, 79-82. https://doi.org/10.1136/bmj.3.5818.79
[24]
Vivas, L., et al. (2008) Hyperreactive Malarial Splenomegaly Is Associated with Low Levels of Antibodies against Red Blood Cell and Plasmodium falciparum Derived Glycolipids in Yanomami Amerindians from Venezuela. Acta Tropica, 105, 207-214. https://doi.org/10.1016/j.actatropica.2007.12.007
[25]
Deepak Nayak M, Belurkar, S.V., Manohar, C. and Shashikiran, U. (2014) Cold Agglutinins Associated with Plasmodium falciparum Malaria: A Case Report. International Journal of Scientific and Research Publications, 4, 4-6.
