A randomized controlled trial of increased dose and frequency of albendazole with standard dose DEC for treatment of Wuchereria bancrofti microfilaremics in Odisha, India.

Shantanu Kumar Kar,Sudanshu S Panda,Anna Salomi Kerketa,Antaryami Maharana,Bhagirathi Dwibedi,John Horton,Prafulla Chandra Mohanty,Cherubala P Ramachandran,Achim Hoerauf

doi:10.1371/journal.pntd.0003583

Abstract

Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and ‘hot spots’ of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of “nests”, all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start.

Highlights

The Global Lymphatic Filariasis Elimination Programme (GPELF) had its inception in 1998 following agreements between the World Health Organization and the international pharmaceutical companies GlaxoSmithKline (GSK) and Merck to donate supplies of, respectively, albendazole and ivermectin for the programme [1]
In order to achieve global elimination of lymphatic filariasis, it may be necessary to consider alternative approaches to mass treatment using higher or more frequent dosing with the existing drugs used in the programmes
We showed that higher doses of albendazole, or 6-monthly treatment, were more effective than the standard regimen in producing clearance of microfilaria and reductions in antigenemia

Summary

Introduction

The Global Lymphatic Filariasis Elimination Programme (GPELF) had its inception in 1998 following agreements between the World Health Organization and the international pharmaceutical companies GlaxoSmithKline (GSK) and Merck to donate supplies of, respectively, albendazole and ivermectin for the programme [1]. Pockets of infection (Hot Spots) and less than anticipated decline in microfilaria rates because of poor treatment compliance have been observed especially in large countries in Asia where programmes have found it difficult to achieve the minimum recommended (65%) epidemiological coverage. These problems are likely to prolong the time to achieve LF elimination targets [6]. Development of macrofilaricidal compounds is advancing, these are still a long way from regulatory approval let alone widespread deployment [9, 10] In such a scenario, improvement of current regimens could permit shorter periods of implementation, especially for those countries that are yet to start and bring greater effectiveness in dealing with hotspots or help accelerate sluggish programmes

Results

Discussion

Conclusion