Abstract
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.
Highlights
Lymphatic filariasis is caused by the parasitic, mosquito-borne filarial round-worm Wuchereria bancrofti and has been classified by the World Health Organization (WHO) as a neglected tropical disease
Lymphatic filariasis is a parasitic infection that is spread between humans by mosquitos
The adult worms can live up to 6 years in humans causing chronic irreversible damage to lymphatic vessels resulting in permanent limb swelling known as elephantiasis
Summary
Lymphatic filariasis is caused by the parasitic, mosquito-borne filarial round-worm Wuchereria bancrofti and has been classified by the World Health Organization (WHO) as a neglected tropical disease. Three anti-parasitic drugs, albendazole, diethylcarbamazine and ivermectin, have therapeutic efficacy against lymphatic filariasis and so have been included by WHO in MDA recommendations, with the specific choice of agents dependent on the presence of other endemic pathogens.[2] The precise mechanism of action of these medications on the filarial worm are not fully understood, but efficacy studies have determined macrofilaricidal and microfilaricidal activity when used in either two drug combination. The standard MDA in the Pacific is based on the dual combination of diethylcarbamazine and albendazole (known together as DA). Eleven countries, including Egypt, Thailand and Tonga, have achieved elimination targets and are under surveillance, but others, including eight countries in the Western Pacific Region such as Samoa, Philippines and Fiji, have not done so despite multiple rounds of MDA.[1]
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