Antifilarial drugs, in the doses employed in mass drug administrations by the Global Programme to Eliminate Lymphatic Filariasis, reverse lymphatic pathology in children withBrugia malayiinfection

Abstract

Lymphatic filariasis is increasingly viewed as the result of an infection that is often acquired in childhood. The lymphatic pathology that occurs in the disease is generally believed to be irreversible. In a recent study in India, Doppler ultrasonography and lymphoscintigraphy were used to explore subclinical pathology in 100 children from an area endemic for Brugia malayi infection. All the children investigated showed some evidence of current or previous filarial infection. Some were microfilaraemic but asymptomatic, some were amicrofilaraemic but had filarial disease or a past history of microfilaraemia and/or filarial disease, and the rest, though amicrofilaraemic, asymptomatic and without any history of microfilaraemia or filarial disease, were seropositive for antifilarial IgG(4) antibodies. All the children were treated every 6 months, with a single combined dose of diethylcarbamazine (6 mg/kg) and albendazole (400 mg), and followed up for 24 months. By the end of this period all but one of the children were amicrofilaraemic and the 'filarial dance sign' could not be detected in any of the 14 children who had initially been found positive for this sign. Although lymphoscintigraphy revealed lymph-node and lymph-vessel damage in 82% of the children at enrolment, in about 67% of the children this pathology was markedly reduced by the 24-month follow-up. These results indicate that the drug regimens used in the mass drug administrations run by the Global Programme to Eliminate Lymphatic Filariasis are capable of reversing subclinical lymphatic damage and can provide benefits other than interruption of transmission in endemic areas. The implications of these findings are presented and discussed.

A Longitudinal Analysis of the Effect of Mass Drug Administration on Acute Inflammatory Episodes and Disease Progression in Lymphedema Patients in Léogane, Haiti

“…Recent clinical research using ultrasonography and lymphoscintigraphy has documented the reversal of early lymph-vessel damage in Brugia malayi-infected children after MDA with DEC in India. 21 However, earlier studies in Brazil have failed to find a decrease in lymphatic vessel dilation after treatment with DEC in adults infected with Wuchereria bancrofti. 22,23 Of the 13 published studies assessing the effect of DEC on lymphedema-specific filarial morbidity, nine found a beneficial effect of DEC on lymphedema 20,24 -31 and the other studies demonstrated no effect.…”

Lymphatic filariasis in children: Clinical features, infection burdens and future prospects for elimination

“…Recent findings of reversibility of early lymphatic pathology in treated children provide ample proof that both the MDA strategy and 'foot-hygiene' measures can be viewed as an effective measure in preventing and managing morbidity. Programme managers should effectively utilize this information to strengthen their advocacy efforts to achieve high and sustainable coverage in MDA (Shenoy et al 2009). …”

“…Due to the adverse effects that doxycycline is known to cause, this drug is generally not used in pregnant women and children (Taylor et al 2010). It may be recalled here that in a recent study on BM infection in children the presently available anti-filarial drugs are generally well tolerated and effective in clearing microfilaraemia and the FDS indicating presence of live adult worms and also in reversing the early subclinical lymphatic pathology (Shenoy et al 2009). …”

“…Thus it was seen that 94% of the microfilaraemics, 86% of the children with live adult worm 'nests' detected on Doppler ultrasonography and 78% of the children who had abnormal lymphatics on lymphoscintigraphy (LSG) were IgG4 positive. Based on these observations it was concluded that a positive BR test is a reliable marker of B. malayi infection (Shenoy et al 2009). …”

“…Lymphoscintigraphy at the last follow-up revealed that the lymph node and vessel damage observed during enrollment had reversed in 89·6% children. They included 96% of the mf positives, 85% of those with filarial disease and 87·5% of those who were only positive for IgG4 (Shenoy et al 2009). These results suggest that MDA is effective in reversing the subclinical pathology induced by the adult worms in children, if they are treated early in LF infection.…”