Lymphatic filariasis (LF) is endemic in as many as 80 countries 12. An estimated 1.1 billion people are at risk of infection, and there are approximately 120 million people with patent infection or disease round the globe 345. In India alone, 553 million people are estimated to live in areas endemic for lymphatic filariasis and there are approximately 21 million people with symptomatic filariasis 6. Progressive lymphoedema (from the early reversible stages to irreversible and complicated stages) associated with the increase in episodic attacks of acute adenolymphangitis (ADL) 7 is the most important cause of physical suffering, permanent disability and economic loss 8910. It has been estimated that there are some 16.02 million cases of lymphoedema caused by LF globally, and of these, 7.44 million (46.4%) live in India 3.

LF is recognized as one of six potentially eradicable diseases 11 and in 1997, the World Health Assembly (WHA) passed a resolution calling for it's global elimination as a public health problem 412.

The current strategy for the global elimination of LF recommended by the Global Alliance for the Elimination of Lymphatic Filariasis (GAELF) 1 has two major components: transmission control and morbidity management 13.

A total of 26 ambulatory patients with unilateral lymphoedema, (selected as per inclusion and exclusion criteria [Table 1]), were recruited to the study; 13 in each drug group (Group A: Daflon (500 mg) + DEC (25 mg) twice a day, for 90 days; Group B: DEC (25 mg) twice a day, for 90 days). The mean age (± SD) of the patients in the Daflon + DEC group was 40 (± 11.5) years (range 20–55) and in the DEC group it was 38 (± 6.8) years (range 24–50) (P > 0.05 between the two groups). There were 12 patients with grade II oedema and one patient with grade I oedema in each drug group. There was no significant difference in the pre-treatment (day 0) mean oedema volume (± SEM) between the Daflon + DEC (198.4 ± 16.5 ml) and the DEC alone (272.9 ± 48.0 ml) groups (P > 0.05). All the 26 patients completed the full 90 day treatment schedule.

The World Health Organisation has targeted lymphatic filariasis for elimination as a public health problem by the year 2020 12. India, which has the highest burden of LF, has set a target for national elimination of LF by the year 2015 36. Although annual mass administration of single-dose anti-filarial drugs to entire endemic communities for the control of transmission of lymphatic filariasis is being implemented in many counties, including India, (under which approximately 50 million citizens are currently being covered annually) 215, morbidity management 13 aimed at the alleviation of suffering of the individual patients has, in many countires, only recently begun to be addressed.

There is no doubt that the introduction of an appropriate hygiene and skin care regimen that patients can practice in their own environment will be most important in providing long term gains in the management of their morbidity. However, realisation of this strategy in many communities (living in rural and urban settings) in different endemic countries with wide socio-economic diversity remains a major challenge 17.

While the above strategy is being implemented, it is important to develop other measures, which could reduce oedema volume in patients with filarial lymphoedema, and, which can be integrated alongside a hygiene and skin care regimen.

Although, surgical procedures have been developed for filarial lymphoedema cases 3738, these can only be performed in a few specialized centers, where expertise is available. Furthermore, it is costly and it has been observed that sustaining the gains achieved by surgery depends on the ability to prevent subsequent ADL episodes (by following a hygiene and skin care regimen) 38.

Physiotherapeutic measures such as manual massage, pneumatic compression and interferential current therapy have been found to be useful in odemea volume reduction in other secondary lymphoedema cases 394043, however, these have yet to be properly evaluated in the management of filarial lymphoedema. Interferential current therapy showed significant oedema reduction in brugian filarial lymphoedema cases 41. Although, pneumatic compression also results in oedema volume reduction, the results are not sustained 42. Manual massage could be most useful as a self-help measure 43, but objective data are yet to be generated in LF cases. Of the chemotherapeutic agents investigated previously, 5,6 benzo-alpha-pyrone was most promising. In a double-blind placebo controlled study on bancroftian filarial lymphoedma cases in south India, it was observed that 5,6 benzo-alpha-pyrone (given at the dosage of 200 mg twice daily) resulted in significant reduction in oedema volume (63% in grade II cases) at the end of a two year treatment period 44. The efficacy of this drug has also been demonstrated in a study in China 45. However, 5,6 benzo-aplha-pyrone cannot be currently recommended for use as the drug has been shown to be hepato-toxic 46.

Earlier studies have shown that DEC has limited role in the management of filarial lymphoedema. In areas endemic for burgian filariasis in Indonesia considerable improvement in lymphoedema, including reversal of elephantiasis, has been reported 47. However, these observations were based on community studies and objective measurement of oedema volume was not carried out. A significant reduction in oedema volume was reported with repeated courses of DEC along with supportive measures (such as pneumatic compression, use of crepe bandage etc.) in a study, again on brugian filarial lymphoedema cases, from south India 48. However, this was an open trial and it is not possible to differentiate the effect of DEC alone from that of the supportive measures. In bancroftian filarial lymphoedema cases, long term DEC therapy (6 mg /kg /day in two divided doses for 2 years) resulted in reduction in oedema volume ranging only between 3 to 7 % in different grades of oedema 44. A double blind clinical trial with single dose DEC (6 mg / kg body weight) or ivermectin (400 mg / kg body weight) did not show any significant change in oedema volume in bancroftian filarial lymphoedema cases over a one-year follow-up period (Vector Control Research Centre – unpublished data). In the current study, DEC treatment alone at the dosage of 25 mg twice a day for 90 days did not result in significant change oedema volume in filarial lymphoedema cases. Freedman et al., using lymphoscintigraphy did not observe any improvement in lymphatic pathology after two courses of DEC (for 12 days each) in bancroftian filarial lymphoedema cases 49. Furthermore, DEC did not reduce the incidence of episodic ADL attacks in individual lymphoedema cases 5051 as well as in the community after mass drug administration 52. These results suggest the limitations of DEC in the morbidity management in LF.

This is the first report of a clinical trial on the tolerability and efficacy of Daflon in filarial lymphoedema cases. Daflon is known to be phlebotonic, it reduces capillary permeability and has an anti-lipidaemic effect 1926. This drug is known to be safe and without any adverse reaction in the dosage of 2 tablets of 500 mg each per day, and it has been given up to one-year period 5354. The results of the current study showed that there was neither any adverse reaction during the 90 days treatment period nor any significant change between the pre-treatment (day 0) and post-treatment (day 90) haematological or biochemical parameters in any of the patients (which were within normal limits). This demonstrates that Daflon (500 mg, twice a day for 90 days) is safe, well tolerated, and can be used up to 90 days in patients with filarial lymphoedema. Furthermore, the drug is also efficacious, reflected by a significant reduction in oedema volume of 63.8% (recorded between day 0 and day 360, inclusive of 90 days of treatment period) (Figure 2). A significant reduction in oedema volume was detected by the end of day 90 (Table 2). In other clinical conditions, appreciable change has been detected between 6 weeks to 6 months 55. The pattern of change in oedema volume showed a marked reduction from day 75 until day 180 (Figure 1), after which the change was marginal (Table 2). This could suggest that repeat course(s) may be required for further decrease in oedema volume. Although Daflon was given along with DEC in the current study, since DEC alone did not show any significant reduction in oedema volume (Table 2, Figure 1), the results seen in the former group is likely to be due to Daflon.

None of the patients in either drugs group suffered from an ADL attack during the treatment and follow-up period. The reason for this, however, is not clear. Although DEC, (25 mg twice a day for 90 days), was given to all patients, it is difficult to assign this effect to DEC, as previous experience, in both hospital and community studies, did not favour this 505152. All the patients were also from a limited geographical area with similar environmental and socio-economic conditions having similar risk for ADL. None of the patients were advocated a specific hygiene and skin care regimen as a part of the protocol (since this is not yet a routine measure advocated by the National Filariasis Control Programme 56 and also as this could confound the results of effects of the drug (however, for ethical reasons all patients were educated in an appropriate hygiene and skin care regimen after completion of the study)).

We conclude that Daflon (500 mg, twice a day for 90 days) is both safe and efficacious in reducing oedema volume in filarial lymphoedema. DEC, at the dosage given, did not result in any significant change in oedema volume. However, as the current study was limited to a few patients in south India (and did not have an arm of Daflon alone) further clinical trials (preferably multi-centre) with larger numbers of patients need to be carried out (and should address the effect of Daflon on lymphatic pathology). This is essential for strengthening the evidence base on the use of Daflon in the management of filarial lymphoedema, before recommending its use in morbidity management to the Global Programme for the Elimination of Lymphatic Filariasis.

None declared

LKD; Study design, case detection, recruitment and follow-up, data analysis and manuscript preparation. GSR; Study of tolerability and efficacy in the hospital. SPP; Study concept, design, implementation and manuscript preparation.