Treatment with Doxycycline is Associated with Reduced Spleen Size in Hyper-Reactive Malarial Splenomegaly: A Cohort Study

Abstract Background:Hyper-reactive malarial splenomegaly (HMS)is a poorly understood sequela of chronic parasitaemia, caused by an aberrant immune response, and confers a high associated mortality. There arefew historical data on effective treatments, which are either unavailable or unaffordable in endemic areas. In Kagando, Western Uganda patients were treated with Doxycycline and followed up to measure the effect.Methods:Patients were identified by medical officers from March 2018 at Kagando Hospital who met Fakunle’s criteria for HMS; children under 12 years and pregnant women were excluded. The baseline full blood count and splenic size from the costal margin was measured and manually recorded. Patients were discharged with a 6-monthcourse of Doxycycline and asked to attend on completion for follow-up assessment. Spleenmeasurements and compliance wererecorded by medical officers, before being tabulated and analysed electronically. Results:In total 27 patients were treated for HMS over a two year period with 7 patients returning for a follow up between 6-15 months. The median age was 36 years with a near equal male to female ratio. Prior to treatment patients displayed a variable degree of pancytopenia with a median haemoglobin of 10.1, leucocytes 4.5 and platelets 82, and the median spleen size was 16cm from the costal margin. The Wilcoxon signed-rank test was used for statistical analysis. There was a significant reduction in spleen size p<0.05, with 4/7 showing complete resolution. There was a numericalimprovement in platelet count (median82 vs 125) p=0.16.Conclusions:Regular doxycycline use as malaria prophylaxis in a holoendemic area of Uganda was associated with a significant reduction in spleen size and a numerical improvement in platelet count. A larger cohort study and an improved follow-up regime is required to further characterise this effect. However, doxycyclineprovidesa practical and affordable treatment modality in a rural Ugandan population, with no current national or international guidelines. In some patients the benefit is seen up to a year from treatment completion.