Dr. Sacha Horn (Munich / DE), Dr. Anja Feichtner (Munich / DE), Dr. Inge Kroidl (Munich / DE), Dr. Abdallah Ngenya (Dar es Salaam / TZ), Leonard Masagati (Dar es Salaam / TZ), Dr. Jubin Osei-Mensah (Kumasi / GH), Vera Serwaa Opoku (Kumasi / GH), Linda Batsa Debrah (Kumasi / GH), Dr. Ute Klarmann-Schulz (Bonn / DE), Dr. Janina Kuehlwein (Bonn / DE), Dr. Angelika Kellings (Bonn / DE), Prof. Dr. Michael Hoelscher (Munich / DE), Dr. Akilig Kalinga (Dar es Salaam / TZ), Prof. Dr. Alexander Y. Debrah (Kumasi / GH), Achim Hoerauf (Bonn / DE)
Abstract text
Introduction:
Lymphatic filariasis is a mosquito-transmitted helminth infection caused by Wuchereria bancrofti and Brugia species. About 30% of the 68 million infected people worldwide suffer from disfiguring pathology (e.g. lymphedema). Current treatment (200 µg/kg ivermectin (IVM) and 400 mg albendazole (ALB)) acts on microfilariae, the larval stage that is also responsible for transmission, but does not affect the adult worm. Prior studies have shown 100-200mg Doxycycline to act not only on the adult worm, but also when taken daily for 6 weeks, lead to improvement of those with early stages of lymphedema.
Materials & Methods:
A double-blind, randomized, placebo-controlled trial (LEDoxy) was conducted in Ghana and Tanzania in order to confirm the effect of 200 mg Doxycycline treatment and to test the effect of 100 mg Doxycycline per day for 6 weeks on improvement of filarial lymphedema in study participants. Participants were characterized at baseline using the Dreyer staging (Dreyer et al., 2002), circumference measurements, and the LymphaTech® infrared scanner. Over a 24-month period, changes in pathology and immunological parameters were measured (end of treatment, 6 and 24 months post-treatment). Additionally, a novel flow cytometry based whole blood method developed by us was used to characterize CD4 and CD8 T cells for a number of activation, maturation, and exhaustion markers (CD45, CD27, FoxP3, CD25, CD38, HLADR, Tbet, Eomes).
Results – Conclusion:
Flow cytometry data from the first 20 Ghanaian and 43 Tanzanian participants who completed treatment has been analyzed. When comparing individual pre- and post-treatment data from Tanzania, we see no significant difference in the frequency between various T cell subgroups (central and effector memory CD4+ T cells). Yet, we observe an overall significant decline in immune activation parameters (HLADR+/CD38+ on CD4+ T cells) over the course of treatment. Interestingly, the opposite is observed in the Ghanaian samples when examining paired values from pre- and 6 months post-treatment. Clearer conclusions as to the nature of these differing results will be able to be drawn after unblinding of the study participants.