Hyperreactive Malarial Splenomegaly (HMS) is defined as a massive enlargement of the spleen resulting from abnormal immune responses after repeated exposure to the malaria parasites. This study was carried out in Khartoum, Sudan. Sudan is considered to be one of the countries where HMS is quite prevalent. The objective of the study was to determine the incidence of HMS in patients who reported to the Omdurman Tropical Diseases Hospital (OMTDH) in Sudan and to investigate the basic laboratory and immunological characteristics of this condition in these patients. A cross-sectional study was carried out in OMTDH, and all patients with enlarged spleens were included in the study. Thirty-one out of 335 (9.3%) patients were diagnosed as having the HMS condition using international criteria for HMS diagnosis. The mean serum immunoglobulin M (IgM) levels in HMS patient groups were ？g/L, and this was significantly higher compared with geographically matched controls ( ). Immunoglobulin G (IgG) C anticircumsporozoite (CSP) antibody levels were higher in the HMS patients although the difference was not statistically significant, when compared with a group of patients with mild malaria. In comparison with na？ve European controls, both the HMS and the mild malaria groups had significantly higher antimalarial antibody levels and , respectively. Plasma levels of interleukin 10 (IL10) and interferon gamma (IFNγ) were significantly increased in the HMS patients compared with the healthy control donors ( and ) for IL10 and IFNγ, respectively. The findings of this study suggest that HMS is one of the significant causes of tropical splenomegaly in Sudan. HMS is associated with significant elevations of circulating IgM and antimalarial IgG antibodies as well as IL10 and IFNγ. 1. Introduction Hyperreactive Malarial Splenomegaly (HMS) is characterized by massive enlargement of the spleen in the tropics. The condition is prevalent in certain malarious regions of the Old World, mainly in Africa [1–5]. HMS seems to be associated with a high mortality; however, the natural history of HMS is not well documented. A 5-year-mortality rate of 50% has been reported in Uganda and New Guinea [6]. A mortality rate of 85% has been documented in hospitalized patients with gross splenomegaly. Whether HMS is responsible for this high mortality is a fact that still needs to be established [6]. Clinical Features. Symptoms of splenomegaly consist primarily of left upper quadrant pain with or without signs of hypersplenism dominating the clinical presentation of HMS. Early in the syndrome, the
References
[1]
G. M. Edington, “Pathology of malaria in West Africa,” British Medical Journal, vol. 1, no. 542, pp. 715–718, 1967.
[2]
D. A. M. Gebbie, P. J. S. Hamilton, M. S. R. Hutt, P. D. Marsden, A. Voller, and N. E. Wilks, “Malarial antibodies in idiopathic splenomegaly in Uganda,” The Lancet, vol. 2, no. 7356, pp. 392–393, 1964.
[3]
M. M. Lowenthal, “The tropical splenomegaly syndrome,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 63, no. 1, p. 151, 1969.
[4]
G. Bedu-Addo and I. Bates, “Causes of massive tropical splenomegaly in Ghana,” The Lancet, vol. 360, no. 9331, pp. 449–454, 2002.
[5]
G. Charmot, J. Demarchi, J. Orio, R. Reynaud, and R. Vargues, “New aspects of splenomegaly in African Negroes; splenomegalic syndrome with macroglobulinemia,” La Presse Médicale, vol. 67, no. 1, pp. 11–12, 1959.
[6]
B. G. Kumar, M. A. Shetty, and Chakrapani, “Splenic complications in malaria: a case series,” Southeast Asian Journal of Tropical Medicine and Public Health, vol. 39, no. 5, pp. 791–794, 2008.
[7]
Y. M. Fakunle and B. M. Greenwood, “Metabolism of IgM in the tropical splenomegaly syndrome,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 70, no. 4, pp. 346–348, 1976.
[8]
J. L. Ziegler and P. C. Stuiver, “Tropical splenomegaly syndrome in a Rwandan kindred in Uganda,” British Medical Journal, vol. 3, no. 818, pp. 79–82, 1972.
[9]
P. J. Hamilton, R. H. Morrow, J. L. Ziegler et al., “Absence of sickle trait in patients with tropical splenomegaly syndrome,” The Lancet, vol. 2, no. 7611, p. 109, 1969.
[10]
WHO, Sudan Country Cooperation Strategy 2004–2007, World Health Organization, Geneva, Switzerland, 2003.
[11]
M. M. Allam, T. A. M. Y. Alkadarou, B. G. Ahmed et al., “Hyper-reactive Malarial Splenomegaly (HMS) in malaria endemic area in Eastern Sudan,” Acta Tropica, vol. 105, no. 2, pp. 196–199, 2008.
[12]
Y. M. Fakunle, “Tropical splenomegaly. Part 1: tropical Africa,” Clinics in Haematology, vol. 10, no. 3, pp. 963–975, 1981.
[13]
G. Snounou, S. Viriyakosol, X. P. Zhu et al., “High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction,” Molecular and Biochemical Parasitology, vol. 61, no. 2, pp. 315–320, 1993.
[14]
J. V. Dacie and S. M. Lewis, Practical Haematology, Longman Group, Hong Kong, China, 8th edition, 1994.
[15]
G. Rougon, B. Ceard, J. Van Rietschoten, B. Jordan, and J. Barbet, “Induction synthetic peptide of antibodies to HLA class I C terminal intracytoplasmic region,” Molecular Immunology, vol. 21, no. 6, pp. P461–P468, 1984.
[16]
H. Perlmann, P. Perlmann, K. Berzins, et al., “Dissection of the human antibody response to the malaria antigen Pf155/RESA into epitope specific components,” Immunological Reviews, vol. 112, pp. 115–132, 1989.
[17]
H. Perlmann, P. Perlmann, K. Berzins et al., “Dissection of the human antibody response to the malaria antigen Pf155/RESA into epitope specific components,” Immunological Reviews, no. 112, pp. 115–132, 1989.
[18]
J. L. Ziegler, A. Voller, and T. Ponnudurai, “Malarial antibodies in tropical splenomegaly syndrome in Uganda,” Tropical and Geographical Medicine, vol. 25, no. 3, pp. 282–285, 1973.
[19]
G. G. Crane, A. Gardner, and P. Hudson, “Malarial antibodies in tropical splenomegaly syndrome in Papua New Guinea,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 71, no. 4, pp. 308–314, 1977.
[20]
K. M. De Cock, A. N. Hodgen, and R. A. Jupp, “Immunoglobulin M and malarial antibody levels in hyper-reactive malarial splenomegaly,” Journal of Tropical Medicine and Hygiene, vol. 89, no. 3, pp. 119–121, 1986.
[21]
S. Wallace, G. Bedu-Addo, T. R. Rutherford, and I. Bates, “Serological similarities between hyperreactive malarial splenomegaly and splenic lymphoma in West Africa,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 92, no. 4, pp. 463–467, 1998.
[22]
K. Chelimo, P. O. Sumba, J. W. Kazura, A. V. Ofula, and C. C. John, “Interferon-gamma responses to Plasmodium falciparum liver-stage antigen-1 and merozoite-surface protein-1 increase with age in children in a malaria holoendemic area of western Kenya,” Malaria Journal, vol. 2, article 37, 2003.
[23]
C. Li, L. A. Sanni, F. Omer, E. Riley, and J. Langhorne, “Pathology of Plasmodium chabaudi chabaudi infection and mortality in interleukin-10-deficient mice are ameliorated by anti-tumor necrosis factor alpha and exacerbated by anti-transforming growth factor β antibodies,” Infection and Immunity, vol. 71, no. 9, pp. 4850–4856, 2003.
[24]
R. de Waal Malefyt, H. Yssel, M. G. Roncarolo, H. Spits, and J. E. De Vries, “Interleukin-10,” Current Opinion in Immunology, vol. 4, no. 3, pp. 314–320, 1992.
[25]
E. N. Villegas, U. Wille, L. Craig et al., “Blockade of costimulation prevents infection-induced immunopathology in interleukin-10-deficient mice,” Infection and Immunity, vol. 68, no. 5, pp. 2837–2844, 2000.
