Elizabeth Tuller

Introduction: Lymphatic filariasis is a tropical parasitic disease, commonly caused by the nematode Brugia malayi and Wolbachian bacterium co-infections¹. Mosquitos acquire the nematode and bacterium from infected humans while B. malayi is in its microfilial form⁶. In the gut of the mosquito, it loses the sheath and transforms into its larval form. The larval form is able to travel up to the head of the mosquito where it can infect another human host when the mosquito feeds⁶. From there, the larvae travel to local lymph nodes where it becomes the adult worm which creates microfiliae and associated disease symptoms⁶. Mass Drug Administration has reduced numbers of new infections in these regions, but many patients still struggle with disability and disfigurement from chronic infections⁷. Current surgical treatment results in further disability and disfigurement due to low surgical standards in the lower socioeconomic regions⁷. Hypothesis: Doxycycline reduces symptoms of chronic lymphatic filariasis by altering host immune responses to the parasite.² Methods: To determine the immune responses in patients with chronic lymphatic filariasis infections, blood was drawn from patients and their levels of Chronic Filarial Antigen, IL-10, Treg cells, and Breg cells were measured⁴. Levels were compared to patients who cleared the infection to help determine the differences in immune responses which lead to lymphangiogenesis and lymphedema⁴. Levels of IL-4, IL-13, and VEGF are elevated in patients with lymphangiogenesis^1,3. Knockout mice were infected with B. mayali to determine if lymphangiogenesis still occurred¹. Remodeling did not occur¹. To determine if medications could help decrease the activity of the IL-4R pathway, healthy mice were infected with B. mayali¹. After remodeling had occurred in the mice, they were given a trial of an antibiotic: doxycycline/minocycline, amoxicillin, chloramphenicol, and rifampicin. ¹ Results: Levels of lymphangiogenesis decreases with doxycycline leading to a reduction in lymphedema.¹ Levels of VEGF, IL-4 and IL-13 decrease with administration of doxycycline, but not as significantly with amoxicillin, chloramphenicol, or rifampicin¹. There is an inverse relationship between IFN-g and IL-10⁵. High levels of IL-10 are associated with chronic infection, while IFN-g is associated with formation of antibody sheaths which are targeted by the immune system for destruction.⁵  Conclusion: Doxycycline reduces remodeling through its anti-Wolbachian properties.^1,3 Doxycycline works by directly reducing levels of VEGF in the affected lymph nodes so it can’t activate the IL-4R pathway^1,3. This leads to a reduction in lymphangiogenesis and macrophage activation¹. Since Wolbachia and B. mayali are endosymbiotically related, removal of the bacteria population results in a reduction in the nematode population leads to a reduction in chronic lymphatic filariasis symptoms⁵.

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