A placebo-controlled double-blind trial for the treatment of Bancroftian filariasis with ivermectin or diethylcarbamazine

Abstract

Therapeutic efficacy and clinical side-effects of ivermectin (single dose of 100 micrograms/kg) and diethylcarbamazine (DEC) (3 mg/kg for one day, then 6 mg/kg daily for 12 d) were evaluated for microfilaricidal effect in Bancroftian filariasis. Seventy-one microfilaraemic consenting adult male patients (greater than or equal to 100 microfilariae (mf)/ml) were randomly assigned to receive ivermectin, DEC or placebo and kept in hospital for 15 d. Those receiving placebo were treated with ivermectin on day 9. Ivermectin (19 'double-blinded' and 22 'unblinded' patients) caused an abrupt reduction in mf count to 1.5% of the pre-treatment level 12 h after drug administration and to 0.06% on day 14, with recrudescence to 1.8% after one month and to 9.2% after 3 months. DEC (30 patients) caused a gradual drop in mf count to 1.1% of the pre-treatment level on day 14, which increased to 2.4% after one and 3 months. The total scores of side-effects were 77 (1%), 305 (2.1%) and 311.5 (3.0%) for placebo, ivermectin and DEC respectively; the differences between DEC or ivermectin and placebo were statistically significant. Ivermectin produced lower side-reaction scores than DEC and the differences were highly significant at the 95% confidence level. Side-effects were mainly headache and body aches in the ivermectin patients, which appeared as early as 4 h after drug administration, resolved within 36 to 48 hours, and were significantly related to mf densities. Side-effects in DEC patients were mainly testicular and epididymal pain and swelling, unrelated to mf densities, which began at day 2 and continued to day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse events following single dose treatment of lymphatic filariasis: Observations from a review of the literature

“…Transient mild to moderate adverse reactions such as fever, headache, dizziness, malaise, myalgia, fatigue, and gastrointestinal upset are common after treatment of LF and are primarily related to dying Mf [ 5 , 6 , 62 ]. Less commonly reported AEs include cough and dyspnea [ 15 , 17 , 23 , 40 ] (sometimes associated with blood-tinged sputum and transient pulmonary infiltrates [ 63 ] or bronchoconstriction [ 40 , 64 ]), urticaria or other rash [ 45 , 63 , 65 ], transient proteinuria or hematuria [ 9 , 44 , 63 , 66 ], elevated alkaline phosphatase [ 63 ] or transaminase levels [ 46 , 59 , 65 ], palpebral edema (with DEC) [ 17 ], increased eosinophilia 7–14 days post-treatment [ 17 , 40 , 59 , 67 ], and postural hypotension [ 16 , 23 , 40 , 45 , 68 ]. Systemic AEs generally occur with 24–48 hours after the first dose of microfilaricidal medications (IVM or DEC) [ 23 , 24 , 29 , 30 , 40 , 43 – 45 , 54 , 56 , 64 , 67 – 75 ], including when low “clearing doses” of drugs are given before full therapeutic doses [ 14 , 15 ...…”

“…Systemic AEs generally occur with 24–48 hours after the first dose of microfilaricidal medications (IVM or DEC) [ 23 , 24 , 29 , 30 , 40 , 43 – 45 , 54 , 56 , 64 , 67 – 75 ], including when low “clearing doses” of drugs are given before full therapeutic doses [ 14 , 15 , 24 ]. Most systemic AEs resolve within 48 hours of onset, although they sometimes last longer [ 15 , 16 , 24 , 29 , 30 , 40 , 44 , 45 , 54 , 56 , 64 , 67 , 69 , 73 , 75 ].…”

“…They include the development of subcutaneous or scrotal nodules, spermatic cord swelling, new onset or increased hydrocele, dilated and inflamed lymphatic vessels (the “string sign”) [ 68 ], arthritis, lymphadenitis (sometimes with suppuration), and new onset lymphedema [ 76 ]. Local reactions may occur within 24–48 hours after treatment, but often the onset is later (1 week or more after treatment) [ 15 , 17 , 44 , 45 , 55 , 59 , 66 , 72 , 77 ]. They are generally self-limited, resolving over the course of one to several weeks.…”

“…Differences in susceptibility to treatment between brugian and bancroftian filariasis may affect AE rates among those who are Mf positive. For bancroftian filariasis, IVM appears to clear Mf more rapidly and more completely than DEC [ 14 , 16 , 17 , 25 , 30 , 45 , 93 , 94 ], but Mf counts also rebound sooner following IVM treatment. DEC induces a slower, more sustained decline, with gradual Mf reductions out to about 6 months [ 25 , 31 , 64 , 95 ].…”

“…DEC induces a slower, more sustained decline, with gradual Mf reductions out to about 6 months [ 25 , 31 , 64 , 95 ]. Over a longer period, reductions in Mf counts are equivalent [ 14 , 25 , 71 , 96 , 97 ] or slightly better with DEC [ 16 , 17 , 24 , 45 ]. For bancroftian filariasis, acute reactions tend to be higher with IVM and later (localized) reactions higher with DEC [ 17 , 45 ].…”