Prednisone Plus Chloroquine for the Treatment of Hyper-reactive Malarial Splenomegaly
Prednisone Plus Chloroquine for the Treatment of Hyper-reactive Malarial Splenomegaly
This randomized clinical trial will address a complication related to recurrent episodes of
 malaria in endemic areas - hyper-reactive malarial splenomegaly. We aim to assess the
 efficacy of chloroquine after prednisone-induction therapy compared to standard treatment of
 chloroquine alone in the treatment of adult patients with newly diagnosed hyper-reactive
 malarial splenomegaly.
Hyper-reactive malarious splenomegaly (HMS) is a known chronic autoimmune complication in
 areas where malaria is endemic. Patients with HMS complain most commonly of abdominal
 swelling or pain from the enlarged spleen and the condition is defined using clear clinical
 and laboratory criteria. HMS appears benign in most patients when seen first but if
 untreated, it leads to severe anaemia and also acute bacterial infections. There is familiar
 and ethnic clustering suggesting genetic basis. High prevalence rates have been reported in
 certain areas of Papua New Guinea, and Venezuela, and HMS is also common in parts of
 sub-Saharan Africa, including Sudan and Ghana.

 The treatment of HMS is still empirical since no randomized trials have been done so far.
 Long term anti-malarial chemoprophylaxis is deemed the mainstay of therapy, but the optimal
 drug-regimen and duration are unknown. Three to six months may pass before a response is
 observed, and relapses may occur when therapy is discontinued.

 On the basis of the observed benefit in experimental studies, glucocorticoids have been used
 for severe hyper-reactive malarial splenomegaly in various case reports. Because these cases
 had a favourable outcome and the drug tolerability was good, prednisone has become an
 attractive therapeutic option for this disease. Central to the pathophysiology of HMS is the
 overproduction of Immunoglobulin M due to a functional CD8 T-cell defect and the consequent
 expansion and activation of B lymphocytes. Glucocorticoids may have an immediate effect due
 to inhibition of the sequestration of immunoglobulin coated red blood cells by the
 mononuclear phagocyte system and a later effect due to glucocorticoid-induced inhibition of
 antibody synthesis. We aim to assess the efficacy of chloroquine after prednisone-induction
 therapy compared to chloroquine alone in the treatment of adult patients with newly diagnosed
 hyper-reactive malarial splenomegaly.
Inclusion Criteria:

 -  Defining features of HMS including chronic massive splenomegaly (at least 10 cm below
 the costal margin); serum Immunoglobulin M elevated more than 3.1 g/L and high
 malarial antibody titres (above 640).

 -  Evidence of the polyclonal nature of the lymphocytes by serum immunoglobulin free
 light chains.

 -  Aged at least 18 years

 -  Haemoglobin level of > 5 mg/d

 Exclusion Criteria:

 -  known allergy to chloroquine,

 -  use of anti-malarial treatment within the preceding month,

 -  suspected coexisting diseases in which glucocorticoids are contraindicated (e.g.
 diabetes mellitus, peptic ulcer disease or any acute infection as defined clinically),
 and

 -  splenomegaly secondary to known infectious or haematological causes