Does Doxycycline Benefit Intensified Hygiene Measures in Patients with Filarial Lymphedema? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Lymphatic filariasis is a vector-borne infectious disease, most commonly caused by Wuchereria bancrofti, that affects 120 million people. It invades the lymphatic system of humans, who are the definitive hosts. We compared the administration of doxycycline with intensified hygiene measures alone in patients diagnosed with bancroftian filariasis. We searched PubMed, Scopus, and Embase and included 12 randomized controlled trials. A random-effects model was used to calculate the mean difference (MD)/risk ratio (RR) and I2 for heterogeneity. The risk of bias and GRADE evaluated the certainty of evidence. Pooled analysis showed a significant reduction in the number of Wolbachia per microfilaria (MD = -3.09; 95% CI: -3.94 to -2.25; P <0.00001, I2 = 42%). Although initial analysis suggested a reduction in microfilarial count, this finding was highly heterogeneous (I2 = 99%) and became nonsignificant upon sensitivity analysis, indicating unstable results. Regarding adverse events, vomiting was significantly more common in the doxycycline group (RR = 6.25; 95% CI: 2.14-18.24; P = 0.0008, I2 = 0%). In conclusion, doxycycline combined with intensified hygiene protocols reduces the Wolbachia burden but shows a limited role in clinically significant lymphedema reduction, and the evidence for microfilarial reduction is not robust. Large-scale trials are required to better combat this neglected tropical disease in endemic populations worldwide.