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

Background: WHO’s Global Programme to Eliminate Lymphatic Filariasis (LF) uses mass drug administration (MDA) of anthelmintic medications to interrupt LF transmission in endemic areas. Recently, a single dose combination of ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB) was shown to be markedly more effective than the standard two-drug regimens (DEC or IVM, plus ALB) for achieving long-term clearance of microfilaremia. Objective and methods: To provide context for the results of a large-scale, international safety trial of MDA using triple drug therapy, we searched Ovid Medline for studies published from 1985–2017 that reported adverse events (AEs) following treatment of LF with IVM, DEC, ALB, or any combination of these medications. Studies that reported AE rates by treatment group were included. Findings: We reviewed 162 published manuscripts, 55 of which met inclusion criteria. Among these, 34 were clinic or hospital-based clinical trials, and 21 were community-based studies. Reported AE rates varied widely. The median AE rate following DEC or IVM treatment was greater than 60% among microfilaremic participants and less than 10% in persons without microfilaremia. The most common AEs reported were fever, headache, myalgia or arthralgia, fatigue, and malaise. Interpretation: Mild to moderate systemic AEs related to death of microfilariae are common following LF treatment. Post-treatment AEs are transient and rarely severe or serious. Comparison of AE rates from different community studies is difficult due to inconsistent AE reporting, varied infection rates, and varied intensity of follow-up. A more uniform approach for assessing and reporting AEs in LF community treatment studies would be helpful. Author summary: WHO’s Global Programme to Eliminate Lymphatic Filariais (LF) supports annual mass drug administration to over 400 million people in LF-endemic areas each year. Two drug combinations (either DEC or ivermectin, given with albendazole) have been recommended in most endemic areas. With the exception of well-described serious adverse events (AEs) occurring in patients with high level loiasis, severe AEs due to these medications are extremely rare. Mild to moderate AEs, however, are common, particularly in patients with active filarial infection. In this manuscript we synthesize published data on AEs following single-dose treatment of LF with ivermectin, DEC, or albendazole. This provides a background against which to compare the safety of triple drug therapy (ivermectin, DEC, and albendazole) recently endorsed by WHO, and provides a useful context for evaluating safety of new treatments for LF. The compiled data illustrate that transient, mild to moderate AEs following single-dose LF treatment are common in microfilaremic patients and are much less common in amicrofilaremic patients. They also show that passive surveillance for post-treatment AEs underestimates AE incidence and suggest that adherence to common reporting standards would improve the usefulness of AE reporting in filariasis studies.