A randomized, single-ascending-dose, ivermectin-controlled, double-blind study of moxidectin in Onchocerca volvulus infection

Autor: Simon K. Attah, N. O. Opoku, Kwablah Awadzi, Annette C. Kuesel, Janis K. Lazdins-Helds
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Blood Pressure
Onchocerciasis
Ghana
Gastroenterology
law.invention
chemistry.chemical_compound
Clinical trials
Ivermectin
Randomized controlled trial
law
Microfilariae
Skin
Anthelmintics
biology
Phase I clinical investigation
lcsh:Public aspects of medicine
Middle Aged
Rash
Moxidectin
Infectious Diseases
Helminth Infections
Research Design
Female
Macrolides
Onchocerca volvulus infection
medicine.symptom
Phase II clinical investigation
Research Article
Neglected Tropical Diseases
medicine.drug
Adult
medicine.medical_specialty
lcsh:Arctic medicine. Tropical medicine
Adolescent
Clinical Research Design
lcsh:RC955-962
Research and Analysis Methods
Young Adult
Pharmacotherapy
Adverse Reactions
Double-Blind Method
Internal medicine
parasitic diseases
Parasitic Diseases
medicine
Animals
Humans
Medicine and health sciences
Pharmacology
business.industry
Pruritus
Public Health
Environmental and Occupational Health
lcsh:RA1-1270
Exanthema
Tropical Diseases
medicine.disease
biology.organism_classification
Onchocerca volvulus
Surgery
chemistry
Clinical medicine
business
Zdroj: PLoS Neglected Tropical Diseases, Vol 8, Iss 6, p e2953 (2014)
PLoS Neglected Tropical Diseases
ISSN: 1935-2735
1935-2727
Popis: Background Control of onchocerciasis as a public health problem in Africa relies on annual mass ivermectin distribution. New tools are needed to achieve elimination of infection. This study determined in a small number of Onchocerca volvulus infected individuals whether moxidectin, a veterinary anthelminthic, is safe enough to administer it in a future large study to further characterize moxidectin's safety and efficacy. Effects on the parasite were also assessed. Methodology/Principal Findings Men and women from a forest area in South-eastern Ghana without ivermectin mass distribution received a single oral dose of 2 mg (N = 44), 4 mg (N = 45) or 8 mg (N = 38) moxidectin or 150 µg/kg ivermectin (N = 45) with 18 months follow up. All ivermectin and 97%–100% of moxidectin treated participants had Mazzotti reactions. Statistically significantly higher percentages of participants treated with 8 mg moxidectin than participants treated with ivermectin experienced pruritus (87% vs. 56%), rash (63% vs. 42%), increased pulse rate (61% vs. 36%) and decreased mean arterial pressure upon 2 minutes standing still after ≥5 minutes supine relative to pre-treatment (61% vs. 27%). These reactions resolved without treatment. In the 8 mg moxidectin and ivermectin arms, the mean±SD number of microfilariae/mg skin were 22.9±21.1 and 21.2±16.4 pre-treatment and 0.0±0.0 and 1.1±4.2 at nadir reached 1 and 3 months after treatment, respectively. At 6 months, values were 0.0±0.0 and 1.6±4.5, at 12 months 0.4±0.9 and 3.4±4.4 and at 18 months 1.8±3.3 and 4.0±4.8, respectively, in the 8 mg moxidectin and ivermectin arm. The reduction from pre-treatment values was significantly higher after 8 mg moxidectin than after ivermectin treatment throughout follow up (p
Author Summary Around 100 million Africans live in onchocerciasis endemic areas. Control of onchocerciasis as a public health problem and possibly even elimination of onchocerciasis infection relies on annual community-directed mass treatment with ivermectin. Given concerns about possible emergence of ivermectin resistance of the parasite Onchocerca volvulus and elimination of infection in areas where very high numbers of vectors can result in continued parasite transmission even when only few parasites are present in only a few people, research for drugs with higher effect on the parasite remains important. A series of non-clinical and clinical studies was planned to find out whether moxidectin, a veterinary anthelminthic, is sufficiently safe for mass treatment and has a better effect on the parasite than ivermectin. We report here results from the first study in infected people conducted to assess in small numbers of individuals the adverse reactions to the killing of parasites by moxidectin. A single dose of 8 mg moxidectin reduced skin parasite numbers better and for a longer time than ivermectin. The frequency and severity of adverse reactions was so low that a larger study to better characterize the adverse reactions to moxidectin and compare its efficacy with that of ivermectin was initiated.
Databáze: OpenAIRE
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