Lymphatic Pathology in Asymptomatic and Symptomatic Children with Wuchereria bancrofti Infection in Children from Odisha, India and Its Reversal with DEC and Albendazole Treatment

Citation: Kar SK, Dwibedi B, Das BK, Agrawala BK, Ramachandran CP, Horton J (2017) Lymphatic pathology in asymptomatic and symptomatic children with Wuchereria bancrofti infection in children from Odisha, India and its reversal with DEC and albendazole treatment. PLoS Negl Trop Dis 11(10): e0005631. https://doi.org/10.1371/journal.pntd.0005631
Published: October 23, 2017

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

Author summary: Infection with lymphatic filarial parasites usually occurs early in childhood in endemic areas, but clinical signs appear much later. Reversal of lymphatic pathology has been shown with the much less common Brugia malayi infection using DEC and albendazole and there is scarce evidence whether the same occurs with bancroftian filariasis using the above drugs. We designed this study to look for prevalence of lymphatic pathology in children with and without clinical signs of infection and to observe the effect on the pre-treatment pathology using DEC and albendazole given once or twice a year. We have shown, using lymphoscintigraphy, that lymphatic vessel changes occur very early in infection, and treatment can reverse these changes, even when clinical symptoms are already apparent. This has important implications for lymphedema prevention, case management and for advocacy in the Lymphatic Filariasis Elimination Program. It also strengthens the previous evidence of benefit of treatment on early lymphedema management.

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