Journal Article

The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of Fiji: A cluster randomised trial

Grobler, Anneke C., Weil, Gary J., Kaldor, John M., Whitfeld, Margot J., Hardy, Myra, Steer, Andrew C., Tuicakau, Meciusela, Romani, Lucia, Robinson, Leanne J., Samuela, Josaia, King, Christopher L., Kama, Mike

2020

Overview

Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days and then asked to seek review for the next five days if unwell. Anyone with severe symptoms were reviewed by a doctor and any serious adverse event was reported to the Medical Monitor and Data Safety Monitoring Board. Of 3612 enrolled and eligible participants, 1216 were randomised to DA and 2396 to IDA. Age and sex in both groups were representative of the population. Over 99% (3598) of participants completed 7 days follow-up. Adverse events were reported by 600 participants (16.7%), distributed equally between treatment groups, with most graded as mild (93.2%). There were three serious adverse events, all judged not attributable to treatment by an independent medical monitor. Fatigue was the most common symptom reported by 8.5%, with headache, dizziness, nausea and arthralgia being the next four most common symptoms. Adverse events were more likely in participants with microfilaremia (43.2% versus 15.7%), but adverse event frequency was not related to the presence of scabies or soil-transmitted helminth infection. IDA has comparable safety to DA with the same frequency of adverse events experienced following community mass drug administration. The presence of co-endemic infections did not increase adverse events. IDA can be used in community programs where preventative chemotherapy is needed for control of lymphatic filariasis and other neglected tropical diseases.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Age / Aged / Aged, 80 and over / Albendazole / Albendazole - administration & dosage / Albendazole - adverse effects / Antiparasitic Agents - administration & dosage / Antiparasitic Agents - adverse effects / Arthralgia / Chemotherapy / Child / Child, Preschool / Combination drug therapy / Community / Community-Acquired Infections - drug therapy / Diethylcarbamazine / Diethylcarbamazine - administration & dosage / Diethylcarbamazine - adverse effects / Dosage and administration / Drug dosages / Drug therapy / Drug Therapy, Combination - adverse effects / Drug Therapy, Combination - methods / Drug-Related Side Effects and Adverse Reactions - epidemiology / Drug-Related Side Effects and Adverse Reactions - pathology / Drugs / Earth Sciences / Elephantiasis, Filarial - drug therapy / Female / Fiji / Filariasis / Frequency / Headache / Health services / Helminthiasis - drug therapy / Hospitals / Humans / Infant / Infections / Insecticides - administration & dosage / Insecticides - adverse effects / Islands / Ivermectin / Ivermectin - administration & dosage / Ivermectin - adverse effects / Male / Medicine and Health Sciences / Middle Aged / Nausea / Neglected Diseases - drug therapy / Patient outcomes / People and Places / Public health / Randomization / Research and Analysis Methods / Rural Population / Safety / Scabies / Scabies - drug therapy / Signs and symptoms / Software / Soil / Soils / Studies / Supervision / Symptoms / Therapy / Treatment Outcome / Tropical climate / Tropical diseases / Vector-borne diseases / Young Adult