Antifilarial treatment strategies: a systematic review and network meta-analysis

Abstract

Background: The World Health Organization (WHO) prescribes mass drug administration (MDA) to eradicate lymphatic filariasis within endemic populations. The WHO endorsed using ivermectin with diethylcarbamazine and albendazole (IDA) for MDA in specific settings devoid of onchocerciasis or loiasis. Still, the utilization of IDA in sub-Saharan Africa is restricted due to the potential of diethylcarbamazine to induce severe adverse ocular events in individuals with onchocerciasis.

Aim: We aim to investigate all documented combinations of antifilarial drugs available in the literature using a network meta-analysis (NWM) design, focusing specifically on the treatment of Lymphatic Filariasis (LF).

Methods: A meticulous search was conducted across four electronic databases to identify pertinent studies. Subsequently, a frequentist NWM was executed. Risk ratios (RRs) served as the effect size metric for categorical outcomes, each with a 95% confidence interval (CI).

Results: Our study encompassed 45 studies, including 61,369 patients. At six months, multiple doses of diethylcarbamazine plus albendazole (multiple DA) regimens demonstrated superior efficacy in reducing microfilaremia compared to a single intake of DA, diethylcarbamazine, ivermectin, and albendazole with RR and CI as follows: 0.37 [0.19; 0.72], 0.35 [0.17; 0.69], 0.30 [0.14; 0.64], and 0.28 [0.13; 0.57]. The combination of ivermectin plus albendazole (IA) also showed significant efficacy against the use of each of these drugs alone, with RR: 0.74 [0.57; 0.96] for ivermectin and 0.69 [0.53; 0.89] for albendazole, while diethylcarbamazine combined with albendazole showed substantial superiority over albendazole alone or placebo: RR = 0.09 [0.02; 0.36] and 0.08 [0.02; 0.34], respectively. By the twelfth month, diethylcarbamazine, followed by albendazole, ranked superior to IDA and DA: 0.12 [0.02; 0.89] and 0.11 [0.01; 0.79], respectively. At 24 months, no significant differences were found among the assessed drugs in reducing microfilaremia. The comparisons revealed no significant differences between the drug combinations we studied regarding safety and adverse events.

Conclusion: Multiple doses of the DA regimen showed superior efficacy in reducing microfilaremia compared to combinations involving IA, diethylcarbamazine, ivermectin, and albendazole at six and twelve months. However, by the twenty-four-month, no significant differences were found. Safety profiles among interventions were generally comparable, with no specific drug showing superiority in adverse events.

Keywords: Antifilarial drugs; Drug efficacy; Microfilaremia; Network Meta-Analysis; sub-Saharan Africa.

Fig. 1

mf prevalence at 6 months; (A) Network graph showing direct evidence between the evaluated interventions. (B) A forest plot comparing all interventions. (C) The league table represents the network meta-analysis estimates for all interventions’ comparisons

Fig. 2

mf prevalence at 12 months; (A) Network graph showing direct evidence between the evaluated interventions. (B) A forest plot comparing all interventions. (C) The league table represents the network meta-analysis estimates for all interventions’ comparisons

Fig. 3

mf prevalence at 24 months; (A) Network graph showing direct evidence between the evaluated interventions. (B) A forest plot comparing all interventions. (C) The league table represents the network meta-analysis estimates for all interventions’ comparisons

Fig. 4

Antigenemia at 6 months; (A) Network graph showing direct evidence between the evaluated interventions. (B) A forest plot comparing all interventions. (C) The league table represents the network meta-analysis estimates for all interventions’ comparisons

Fig. 5

Antigenemia outcome at 12 months; (A) Network graph showing direct evidence between the evaluated interventions. (B) A forest plot comparing all interventions. (C) The league table represents the network meta-analysis estimates for all interventions’ comparisons

Fig. 6

Adverse events; (A) Network graph showing direct evidence between the evaluated interventions. (B) A forest plot comparing all interventions. (C) The league table represents the network meta-analysis estimates for all interventions’ comparisons

Fig. 7

Serious adverse events; (A) Network graph showing direct evidence between the evaluated interventions. (B) A forest plot comparing all interventions. (C) The league table represents the network meta-analysis estimates for all interventions’ comparisons