Affiliation:
1. Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom
2. Institut de Recherche Agricole pour le Développement, Regional Centre of Wakwa, Ngaoundéré, Adamawa Region, Cameroon
3. Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Abstract
ABSTRACT
Onchocerciasis (river blindness), caused by the filarial nematode
Onchocerca volvulus
, is a major cause of visual impairment and dermatitis in sub-Saharan Africa. As
O. volvulus
contains an obligatory bacterial symbiont (
Wolbachia
), it is susceptible to antibiotic chemotherapy, although current regimens are considered too prolonged for community-level control programs. The aim of this study was to compare the efficacies of oxytetracycline and rifampin, administered separately or in combination, against a close relative of
O. volvulus
(
Onchocerca ochengi
) in cattle. Six animals per group were treated with continuous or intermittent oxytetracycline regimens, and effects on adult worm viability, dermal microfilarial loads, and
Wolbachia
density in worm tissues were assessed. Subsequently, the efficacies of 3-week regimens of oxytetracycline and rifampin alone and a combination regimen were compared, and rifampin levels in plasma and skin were quantified. A 6-month regimen of oxytetracycline with monthly dosing was strongly adulticidal, while 3-week and 6-week regimens exhibited weaker adulticidal effects. However, all three regimens achieved >2-log reductions in microfilarial load. In contrast, rifampin monotherapy and oxytetracycline-rifampin duotherapy failed to induce substantive reductions in either adult worm burden or microfilarial load, although a borderline effect on
Wolbachia
density was observed following duotherapy. Dermal rifampin levels were maintained above the MIC for >24 h after a single intravenous dose. We conclude that oxytetracycline-rifampin duotherapy is less efficacious against
O. ochengi
than oxytetracycline alone. Further studies will be required to determine whether rifampin reduces oxytetracycline bioavailability in this system, as suggested by human studies using other tetracycline-rifampin combinations.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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