Medscape is available in 5 Language Editions – Choose your Edition here.


Tropical Splenomegaly Syndrome Follow-up

  • Author: Mundeep K Kainth, DO, MPH; Chief Editor: Robert J Arceci, MD, PhD  more...
Updated: Oct 09, 2015

Further Outpatient Care

Regular visits are essential to monitor the patient's clinical improvement and to document decreases in splenomegaly.

If chloroquine is used, monitor the patient for ophthalmologic effects with slit lamp, funduscopic, and visual field examinations.

At regular intervals, perform cardiovascular monitoring with ECG and echocardiography, along with other tests as indicated.

Further workup may be indicated to look for myopathy and peripheral neuritis.

Liver function tests may be performed regularly if the patient is receiving proguanil.

Resolution of splenomegaly is accompanied by an improvement of pancytopenia.


Further Inpatient Care

Because of the extended length of treatment often needed for hyperreactive malarial syndrome (HMS), monitoring for adverse effects is crucial.

Splenectomy is contraindicated, because of increased infection-associated mortality. However, if the patient's spleen was previously removed, guidelines for the care of asplenic patients should be followed (see Asplenia). Guidelines include the following:

  • Antibiotic prophylaxis
  • Education
  • Aggressive management of suspected episodes of fever
  • Appropriate immunizations

Inpatient & Outpatient Medications

Antimalarials are the mainstays of treatment for hyperreactive malarial syndrome (HMS) (see Medication). These drugs often need to be continued long-term (months to years). However, the exact length of treatment has not been ascertained.



Depending on the facilities available at the hospital, indications for transfer may be few. Medication can easily be started after the diagnosis is established. Supportive care, including blood transfusions and antibiotic therapy if indicated, is now commonplace in most hospitals.



For travelers to endemic areas, antimalarial prophylaxis is essential to minimize the risk of hyperreactive malarial syndrome (HMS).

Prophylaxis for residents of endemic areas is controversial and has not been shown to prevent HMS.

A study in Africa determined that the RTS,S/AS02D malaria vaccine was safe, well tolerated, and immunogenic in young infants.[31] A recent report of a phase 3 trial of RTS,S/AS01 malaria vaccine showed modest protection (50% reduction) against clinical and severe malaria in African infants.[32]

Long-term follow-up and studies are needed on whether a reduction in incidence of acute infection will lead to a decrease in the incidence of HMS.[28]



Complications of hyperreactive malarial syndrome (HMS) include infections that may be serious and that may result in death. Trapping of hematopoietic elements in the enlarged spleen may cause thrombocytopenia, anemia, and neutropenia, with resultant problems.

A predisposition to develop malignancy remains unproven.



Hyperreactive malarial syndrome (HMS) is a chronic disease with mortality rates from 20-57% based on the degree of splenomegaly.[15] Higher mortality rates are associated with treatment noncompliance.[16] Bleeding and infection are the most common complications.[15]

Splenectomy should be avoided because it increases the risk of fulminant infections.

The exact risk of development of malignancy has not been established.


Patient Education

The importance of antimalarial prophylaxis during visits to endemic areas should be emphasized to travelers.

Symptoms should be promptly attended to and evaluated, even if they occur in travelers who received prophylaxis. Hyperreactive malarial syndrome (HMS) may present months to years after leaving an endemic area.

Contributor Information and Disclosures

Mundeep K Kainth, DO, MPH City Medical Specialist, Bureau of School Health, Division of Family and Child Health, New York City Department of Health and Mental Hygiene; General Pediatrician, Island Pediatric Associates

Mundeep K Kainth, DO, MPH is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.


Mudra Kumar, MD, MRCP, FAAP Professor of Pediatrics, Course Director, Course 6 MSII, Preclerkship Director, Clinical Integration, Department of Pediatrics, University of South Florida Morsani College of Medicine

Mudra Kumar, MD, MRCP, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP Professor of Pediatrics, Albany Medical College; Chief, Division of Pediatric Hematology-Oncology, John and Anna Landis Endowed Chair for Pediatric Hematology-Oncology, Medical Director, Melodies Center for Childhood Cancer and Blood Disorders, Albany Medical Center

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, International Society of Pediatric Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD Director, Children’s Center for Cancer and Blood Disorders, Department of Hematology/Oncology, Co-Director of the Ron Matricaria Institute of Molecular Medicine, Phoenix Children’s Hospital; Editor-in-Chief, Pediatric Blood and Cancer; Professor, Department of Child Health, University of Arizona College of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Additional Contributors

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, International Society of Paediatric Oncology

Disclosure: Nothing to disclose.

  1. Pitney WR. The tropical splenomegaly syndrome. Trans R Soc Trop Med Hyg. 1968. 62(5):717-28. [Medline].

  2. Bryceson A, Fakunle YM, Fleming AF, et al. Malaria and splenomegaly. Trans R Soc Trop Med Hyg. 1983. 77(6):879. [Medline].

  3. Fakunle YM. Tropical splenomegaly. Part 1: Tropical Africa. Clin Haematol. 1981 Oct. 10(3):963-75. [Medline].

  4. Facer CA, Crane GG. Hyperreactive malarious splenomegaly. Lancet. 1991 Jul 13. 338(8759):115-6. [Medline].

  5. Bates I, Bedu-Addo G. Review of diagnostic criteria of hyper-reactive malarial splenomegaly. Lancet. 1997 Apr 19. 349(9059):1178. [Medline].

  6. Crane GG. Hyperreactive malarious splenomegaly (tropical splenomegaly syndrome). Parasitol Today. 1986 Jan. 2(1):4-9. [Medline].

  7. Hoffman SL, Piessens WF, Ratiwayanto S, et al. Reduction of suppressor T lymphocytes in the tropical splenomegaly syndrome. N Engl J Med. 1984 Feb 9. 310(6):337-41. [Medline].

  8. Piessens WF, Hoffman SL, Wadee AA, et al. Antibody-mediated killing of suppressor T lymphocytes as a possible cause of macroglobulinemia in the tropical splenomegaly syndrome. J Clin Invest. 1985 Jun. 75(6):1821-7. [Medline]. [Full Text].

  9. Alkadarou T, Musa A, Alkadarou A, Mahfouz MS, Troye-Blomberg M, Elhassan AM. Immunological characteristics of hyperreactive malarial splenomegaly syndrome in sudanese patients. J Trop Med. 2013. 2013:961051. [Medline].

  10. David-West AS. Relapses after withdrawal of proguanil treatment in tropical splenomegaly syndrome. Br Med J. 1974 Aug 24. 3(5929):499-501. [Medline].

  11. Singh RK. Hyperreactive malarial splenomegaly in expatriates. Travel Med Infect Dis. 2007 Jan. 5(1):24-9. [Medline].

  12. Pryor DS. Tropical splenomegaly in New Guinea. Q J Med. 1967 Jul. 36(143):321-36. [Medline].

  13. Lowenthal MN, Hutt MS, Jones IG, Mohelsky V, O'Riordan EC. Massive splenomegaly in Northern Zambia. I. Analysis of 344 cases. Trans R Soc Trop Med Hyg. 1980. 74(1):91-8. [Medline].

  14. Wu YH, Chuang SY, Hong WC, Lai YJ, Chang YL, Pang JH. In vivo and in vitro inhibitory effects of a traditional Chinese formulation on LPS-stimulated leukocyte-endothelial cell adhesion and VCAM-1 gene expression. J Ethnopharmacol. 2012 Mar 6. 140(1):55-63. [Medline].

  15. Crane GG, Wells JV, Hudson P. Tropical splenomegaly syndrome in New Guinea. I. Natural history. Trans R Soc Trop Med Hyg. 1972. 66(5):724-32. [Medline].

  16. Fakunle YM, Greenwood BM. Mortality in tropical splenomegaly syndrome. Trans R Soc Trop Med Hyg. 1980. 74(3):419. [Medline].

  17. Bates I, Bedu-Addo G, Bevan DH, Rutherford TR. Use of immunoglobulin gene rearrangements to show clonal lymphoproliferation in hyper-reactive malarial splenomegaly. Lancet. 1991 Mar 2. 337(8740):505-7. [Medline].

  18. De Iaco G, Saleri N, Perandin F, et al. Hyper-reactive malarial splenomegaly in a patient with human immunodeficiency virus. Am J Trop Med Hyg. 2008 Feb. 78(2):239-40. [Medline].

  19. Foca E, Zulli R, Buelli F, De Vecchi M, Regazzoli A, Castelli F. P. falciparum malaria recrudescence in a cancer patient. Infez Med. 2009 Mar. 17(1):33-4. [Medline].

  20. Martin-Peprah R, Bates I, Bedu-Addo G, Kwiatkowski DP. Investigation of familial segregation of hyperreactive malarial splenomegaly in Kumasi, Ghana. Trans R Soc Trop Med Hyg. 2006 Jan. 100(1):68-73. [Medline].

  21. Bhatia KK, Crane GG. HLA heterozygosity and hyperreactive malarious splenomegaly in the Upper Watut Valley of Papua New Guinea. P N G Med J. 1989 Dec. 32(4):277-86. [Medline].

  22. Van den Ende J, van Gompel A, van den Enden E, Taelman H, Vanham G, Vervoort T. Hyperreactive malaria in expatriates returning from sub-Saharan Africa. Trop Med Int Health. 2000 Sep. 5(9):607-11. [Medline].

  23. Allam MM, Alkadarou TA, Ahmed BG, et al. Hyper-reactive Malarial Splenomegaly (HMS) in malaria endemic area in Eastern Sudan. Acta Trop. 2008 Feb. 105(2):196-9. [Medline].

  24. Verma S, Aggarwal A. Hyper-reactive malarial splenomegaly: rare cause of pyrexia of unknown origin. Indian J Pediatr. 2007 Apr. 74(4):409-11. [Medline].

  25. Mitjà O, Hays R, Malken J, et al. HMS-related hemolysis after acute attacks of Plasmodium vivax malaria. Am J Trop Med Hyg. 2011 Oct. 85(4):616-8. [Medline]. [Full Text].

  26. Bradaschia-Correa V, Barrence FA, Ferreira LB, Massa LF, Arana-Chavez VE. Effect of alendronate on endochondral ossification in mandibular condyles of growing rats. Eur J Histochem. 2012 May 25. 56(2):e24. [Medline]. [Full Text].

  27. Mothe B, Lopez-Contreras J, Torres OH, Munoz C, Domingo P, Gurgui M. A case of hyper-reactive malarial splenomegaly. The role of rapid antigen-detecting and PCR-based tests. Infection. 2008 Mar. 36(2):167-9. [Medline].

  28. Centers for Disease Control and Prevention. Malaria Diagnosis & Treatment in the United States. Available at Accessed: March 12, 2013.

  29. Leoni S, Buonfrate D, Angheben A, Gobbi F, Bisoffi Z. The hyper-reactive malarial splenomegaly: a systematic review of the literature. Malar J. 2015 Apr 29. 14:185. [Medline].

  30. Manenti F, Porta E, Esposito R, Antinori S. Treatment of hyperreactive malarial splenomegaly syndrome. Lancet. 1994 Jun 4. 343(8910):1441-2. [Medline].

  31. Aponte JJ, Aide P, Renom M, et al. Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. Lancet. 2007 Nov 3. 370(9598):1543-51. [Medline].

  32. Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BG. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med. 2012 Dec 13. 367(24):2284-95. [Medline].

Young patient with hepatomegaly and massive splenomegaly.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.