Lymphatic pathology in asymptomatic and symptomatic children with Wuchereria bancrofti infection in children from Odisha, India and its reversal with DEC and albendazole treatment

Abstract

Background: Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally.

Methods: Children aged 5-18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years.

Findings: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs.

Interpretation: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration.

Trial registration: ClinicalTrials.gov No CTRI/2013/10/004121.

Fig 1. Consort flow diagram.

Fig 2

Representative image of whole body lymphatic scan of (a) normal lymphatic flow and (b) lymphatic flow obstruction. These images are given for better understanding of the lymphoscintigraphy imaging made in the study. Subsequent figures (Figs 3–10) are provided as cross sectional images at feet, popliteal and inguino-pelvic label taken at different time points to reflect the change over time.

Fig 3. Normal images: 10, 30, 60, & 120 minute images of lymphoscintigraphy in a 14 yr male (asymptomatic and Mf positive).

In both the limbs, at 10 minutes tracer movement into the lymphatics is seen in both legs and at 30 minutes inguinal nodes are visualized, lymphatic tract not imaged and tracer uptake symmetrical hence lymphatic flow normal in both legs. Note the granular appearance in leg images is typical of background noise where there is no additional tracer image.

Fig 4. Baseline 30, 60 & 120 minute images showing lymphatic pathology in left leg of a 12 year old male (symptomatic & Mf positive).

In the left leg, the lymphatic channel well visualized, and tracer uptake at injection site is low indicating lymphatic flow obstruction in left leg.

Fig 5. Baseline 30, 60 & 120 minute images showing lymphatic pathology in left leg of a 11 year old male (symptomatic & Mf positive).

In right leg, the lymphatic channel well visualized, and tracer uptake at injection site is low indicating lymphatic flow obstruction in left leg. There is also some delay in uptake in the left leg, and both legs have evidence of lateral channel formation.

Fig 6. Baseline 30, 60, & 120 minute images of lymphoscintigraphy in a 8 year old male (asymptomatic and Mf positive).

Images show visualization of popliteal nodes and fewer inguinal nodes on right leg indicating tracer accumulation at popliteal level hence lymphatic flow obstruction.There is also delayed clearance from the injection site on the right foot.

Fig 7

a & b: Post treatment reversibility of lymphedema of left leg in a symptomatic 18 year old female. (a) Change in foot circumference (fixed point over lateral maleolus). (b) Improvement in tracer accumulation at foot level (in lymphoscintigraphy).

Fig 8. Post treatment reversibility in a 12 year old asymptomatic male.

Images show lymphatic flow obstruction on left leg at baseline, with complete reversal apparent at 1 year & sustained at 18 & 24 Months.

Fig 9

a & b: Baseline and 24 month images showing disappearance of tracer retention in popliteal lymph nodes. Lymphatic flow in both legs is improved (a) baseline. (b) 24 months.

Fig 10

a & b: Baseline and 24 month images showing disappearance of tracer retention in collateral lymphatic channels and overall improvement in lymphatic flow. Leg images are normal at 24 months. (a) baseline. (b) 24 months.