Table 1.
Primary Variables Measured before and after Treatment in Microfilaremic Patients
Figure 1.
Flowchart of Patient Participation
(A) Trial profile of microfilaremic patients. Of the 76 patients, 33 (17 doxycycline and 16 placebo) patients were present at all time points.
(B) Trial profile of lymphedema patients. Of the 19 patients, 18 (eight doxycycline and ten placebo) patients were present at all time points.
Figure 2.
The Effect of Doxycycline Treatment on the Supratesticular Lymphatic Vessel Dilation at Various Time Points
The supratesticular lymphatic vessel dilation (mean of category ± SD) was determined before treatment, and 12 and 24 mo thereafter, using USG. The mean supratesticular lymphatic vessel dilation of doxycycline-treated (Doxy) patients improved significantly compared to pretreatment (n = 9, p = 0.0404) at 24 mo, in contrast to the placebo group (n = 8) (paired t-test).
Table 2.
State of Lymphatic Vessel Dilation of Patients before and 24 Months after Doxycycline Treatment
Figure 3.
Pretreatment Plasma Levels of VEGF-C in Filarial-Infected Patients and Endemic Controls
Plasma concentrations (mean ± SD) of VEGF-C were measured, using a commercial kit, from plasma of lymphedema patients (n = 26), microfilaremic patients (n = 76), and endemic controls (n = 23, who did not have filarial infection). Mean plasma levels of VEGF-C were significantly elevated in the microfilaremic (p < 0.0001) and lymphedema patients (p = 0.0002) compared to endemic controls (Student t-test with Bonferroni/Dunn correction). There was no difference between microfilaremic and lymphedema patients (p = 0.8033).
Figure 4.
Pretreatment Plasma Levels of sVEGFR-3 in Filaria-Infected Patients and Endemic Controls
Plasma concentrations (mean ± SD) of sVEGFR-3 were measured using a commercial kit from plasma of lymphedema patients (n = 26), microfilaremic patients (n = 76), and endemic controls (n = 23, who did not have filarial infection). Mean plasma levels of sVEGFR-3 were significantly elevated in the microfilaremic (p = 0.0006) and lymphedema patients (p = 0.0012) compared to endemic controls (Student t-test with Bonferroni/Dunn correction). sVEGFR-3 was also significantly elevated in lymphedema patients (p = 0.0024) compared to microfilaremic patients.
Figure 5.
Plasma Levels of VEGF-C of Microfilaremic Patients before and 12 Mo after Doxycycline Treatment
Plasma concentrations (mean ± SD) of VEGF-C were measured from plasma of microfilaremic patients before and 12 mo after doxycycline treatment (17 doxycycline treated, 16 placebo, see Table 1). The VEGF-C levels decreased significantly at 12 mo (preceding supratesticular lymphatic dilation, see Table 2) in the doxycycline-treated patients (p = 0.0198), but no difference in the placebo group occurred (paired t-test).
Figure 6.
Plasma Levels of sVEGFR-3 of Microfilaremic Patients before and 12 Mo after Doxycycline Treatment
Plasma concentrations (mean ± SD) of sVEGFR-3 were measured from plasma of microfilaremic patients before and 12 mo after doxycycline treatment (17 doxycycline treated, 16 placebo, see Table 1). The sVEGFR-3 levels decreased significantly at 12 mo (preceding supratesticular lymphatic dilation, see Table 2) in the doxycycline-treated patients (p = 0.0125) to a level close to that of endemic controls whereas there was no difference in the placebo group (paired t-test).
Table 3.
Primary Variables Measured before and after Treatment in Lymphedema Patients
Figure 7.
Plasma Levels of VEGF-C of Lymphedema Patients before and 12 Mo after Doxycycline Treatment
Plasma concentrations (mean ± SD) of VEGF-C were measured from plasma of lymphedema patients before and 12 mo after doxycycline treatment. The VEGF-C levels decreased significantly at 12 mo in the doxycycline-treated patients (p = 0.0499), in contrast to the placebo group (paired t-test).
Figure 8.
Plasma Levels of sVEGFR-3 of Lymphedema Patients before and 12 Mo after Doxycycline Treatment
Plasma concentrations (mean ± SD) of sVEGFR-3 were measured from plasma of lymphedema patients before and 12 mo after doxycycline treatment. The sVEGFR-3 levels decreased significantly at 12 mo in the doxycycline-treated patients (p = 0.0251) whereas there was no difference in the placebo group (paired t-test).
Figure 9.
Grading of the Supratesticular Lymphatic Vessel Dilation of Filarial-Infected Patients Displayed by USG
Dilation of the supratesticular lymphatic vessels was determined by measuring the largest diameter detectable in the two-dimensional b-mode of a portable ultrasound machine. A grading system was developed to determine the degree of lymphatic dilation as follows: (A) category 1: patients with minimal lymphatic dilation of up to 0.2 cm; (B) category 2: patients with mild dilation from 0.21–0.50 cm; (C) category 3: patients with moderate dilation from 0.51–1.0 cm; and (D) category 4: patients with severe dilation of above 1.0 cm.
Figure 10.
The lymphedema stages according to the classification by Dreyer et al. [47]; patients are from this study.
(A) Stage 2, swelling that is not reversible overnight.
(B) Stage 3, shallow skin folds at the ankle.
(C) Stage 4, alteration of skin texture and formation of knobs (arrowheads).
(D) Stage 5, presentation of deep skin folds in addition to the alterations of stage 4;
(E) Satge 6, presentation of mossy lesion in addition to the alterations of stage 5.
(F) Stage 7, inability of patient to perform daily work.