title: Doxycycline improves filarial lymphedema independent of active filarial infection: a randomized controlled trial.
abstract: BACKGROUND
  The aim of this study was to determine whether improvement of filarial lymphedema (LE) by doxycycline is restricted to patients with ongoing infection (positive for circulating filarial antigen [CFA]), or whether the majority of CFA-negative patients with LE would also show a reduction in LE severity.
  
  
  METHODS
  One hundred sixty-two Ghanaian participants with LE stage 1-5 (Dreyer) were randomized blockwise into 2 groups (CFA positive or negative) and allocated to 3 treatment arms of 6 weeks: (1) amoxicillin (1000 mg/d), (2) doxycycline (200 mg/d), or (3) placebo matching doxycycline. All groups received standard hygiene morbidity management. The primary outcome was reduction of LE stages. Secondary outcomes included frequency of acute attacks and ultrasonographic assessment of skin thickness at the ankles. Parameters were assessed before treatment and after 3, 12, and 24 months.
  
  
  RESULTS
  Doxycycline-treated patients with LE stage 2-3 showed significant reductions in LE severity after 12 and 24 months, regardless of CFA status. Improvement was observed in 43.9% of doxycycline-treated patients, compared with only 3.2% and 5.6% in the amoxicillin and placebo arms, respectively. Skin thickness was correlated with LE stage improvement. Both doxycycline and amoxicillin were able to reduce acute dermatolymphangioadenitis attacks.
  
  
  CONCLUSIONS
  Doxycycline treatment improves mild to moderate LE independent of ongoing infection. This finding expands the benefits of doxycycline to the entire population of patients suffering from LE. Patients with LE stage 1-3 should benefit from a 6-week course of doxycycline every other year or yearly, which should be considered as an improved tool to manage morbidity in filarial LE. Clinical Trials Registration. ISRCTN 90861344.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mand
authors.forename: Alexander Yaw
authors.initials: AY
authors.lastname: Debrah
authors.forename: Ute
authors.initials: U
authors.lastname: Klarmann
authors.forename: Linda
authors.initials: L
authors.lastname: Batsa
authors.forename: Yeboah
authors.initials: Y
authors.lastname: Marfo-Debrekyei
authors.forename: Alexander
authors.initials: A
authors.lastname: Kwarteng
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.forename: Aurea
authors.initials: A
authors.lastname: Belda-Domene
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
authors.forename: Mark
authors.initials: M
authors.lastname: Taylor
authors.forename: Ohene
authors.initials: O
authors.lastname: Adjei
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
mesh_terms: D000293:Adolescent; D000328:Adult; D000658:Amoxicillin / Q000627:therapeutic use; D000842:Ankle / Q000000981:diagnostic imaging / Q000473:pathology; D004318:Doxycycline / Q000627:therapeutic use*; D005260:Female; D005368:Filariasis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005369:Filaricides / Q000627:therapeutic use*; D005869:Ghana; D006801:Humans; D053208:Kaplan-Meier Estimate; D007866:Leg / Q000473:pathology; D008209:Lymphedema / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000000981:diagnostic imaging / Q000473:pathology; D018709:Statistics, Nonparametric; D014463:Ultrasonography; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000097:blood
chemical_list: D005369:Filaricides; D000658:Amoxicillin; D040321:Vascular Endothelial Growth Factor Receptor-3; D004318:Doxycycline