Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: A systematic review and meta‐analysis

Abstract

Objective Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis. Methods For this systematic review and meta‐analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple with dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724). Results We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; p = 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; p = 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared with the dual therapy group. Conclusion Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.

Authors’ Response to “Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: Discordance between the conclusion and the findings”

“…To clarify, triple therapy (IDA) caused more clearance of microfilaria than dual therapy (DA) in different settings, which can potentially introduce a promising mass drug administration (MDA) strategy in limiting lymphatic filariasis transmission -which persuaded us to express an effect in spite of the "very-low quality evidence" as stated by Santesso et al [3]. However, such a strategy needs more highquality randomised controlled trials (RCTs) to be certain of this effect due to the substantial level of heterogeneity and the very low-quality evidence yielded by GRADE assessment (as stated at the end of our conclusion and in our limitations section) [1].We clearly stated that IDA is still a potentially better strategy that requires more subtle RCTs in the future, for which we gave several recommendations to yield stronger evidence. Regarding CFA clearance, we stated that DA is more effective than IDA for killing the adult worms; however, microfilaria (Mf) clearance is the key endpoint based on the reproductive cycle of the parasite.…”

“…To clarify, triple therapy (IDA) caused more clearance of microfilaria than dual therapy (DA) in different settings, which can potentially introduce a promising mass drug administration (MDA) strategy in limiting lymphatic filariasis transmission -which persuaded us to express an effect in spite of the "very-low quality evidence" as stated by Santesso et al [3]. However, such a strategy needs more highquality randomised controlled trials (RCTs) to be certain of this effect due to the substantial level of heterogeneity and the very low-quality evidence yielded by GRADE assessment (as stated at the end of our conclusion and in our limitations section) [1].…”

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To the Editors, We would like to thank the authors for their comments and questions, and we appreciate their meticulous reading of our recently published article [1].The authors raised concerns about a discordance between our findings and the conclusion. Both Chapter 15 of the Cochrane Handbook for Systematic Reviews of Interventions [2] and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) interpretation reporting guidelines [3] provide two options to interpret the "very low-quality evidence": one enables the author to use the effect direction, and the other does not.

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“…To the Editors, We would like to thank the authors for their comments and questions, and we appreciate their meticulous reading of our recently published article [1].…”

Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: Discordance between conclusion and findings

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To the Editors: We read with great interest the recent meta-analysis by Abuelazm et al [1] investigating the efficacy and safety of triple therapy (ivermectin, diethylcarbamazine and albendazole) versus dual therapy (diethylcarbamazine and albendazole) for the treatment of lymphatic filariasis. The authors concluded that their results clearly show that triple therapy is more effective in clearing microfilariae from the blood and has similar safety results as dual therapy.We commend the authors for this well-conducted metaanalysis that strictly adhered to methodological guidelines.

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