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Title: | Doxycycline Reduces Plasma VEGF-C/sVEGFR-3 and Improves Pathology in Lymphatic Filariasis |
Authors: | Debrah, Alexander Yaw Mand, Sabine Specht, Sabine Marfo-Debrekyei, Yeboah Batsa, Linda Pfarr, Kenneth Larbi, John Lawson, Bernard Taylor, Mark Adjei, Ohene Hoerauf, Achim |
Issue Date: | Sep-2006 |
Publisher: | PLoS Pathogens |
Citation: | PLoS Pathogens, 2(9):e92 |
Abstract: | Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs
are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the
infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the
morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to
complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18
lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day
doxycycline. Four months after doxycycline treatment, all patients received 150–200 lg/kg ivermectin and 400 mg
albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS),
dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial
growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(s)VEGFR-3]). Lymphedema
patients were additionally monitored for stage (grade) of lymphedema and the circumferences of affected legs.
Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic
patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular
lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no
improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and
sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values,
whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients
significantly improved following doxycycline, with the mean stage of lymphedema in the doxycycline-treated patients
being significantly lower compared to placebo patients 12 mo after treatment. The reduction in the stages manifested
as better skin texture, a reduction of deep folds, and fewer deep skin folds. In conclusion, a 6-wk regimen of antifilarial
treatment with doxycycline against W. bancrofti showed a strong macrofilaricidal activity and reduction in plasma
levels of VEGF-C/sVEGFR-3, the latter being associated with amelioration of supratesticular dilated lymphatic vessels
and with an improvement of pathology in lymphatic filariasis patients |
Description: | This article is published by PLoS Pathogens and is also available at DOI: 10.1371/journal.ppat.0020092 |
URI: | 10.1371/journal.ppat.0020092 http://hdl.handle.net/123456789/14884 |
Appears in Collections: | College of Health Sciences
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