Article type
Year
Abstract
Background: Lymphatic filariasis is a parasitic infection affecting 120 million people in over 80 countries. It rarely causes death, but can be seriously disabling, causing swelling of the extremities (lymphoedema or elephantiasis) and male genitals (hydrocele). Adult worms live in the lymphatic system and produce larvae (microfilariae, mf), which migrate to the blood and are ingested by mosquitoes. The Global Programme for the Elimination of Lymphatic filariasis aims to interrupt transmission by reducing mf in the blood through one of two drug strategies: 1. albendazole, an anti-helminth drug in combination with one of two antifilarial drugs (ivermectin or diethylcarbamazine [DEC]); annually for at least 5 years 2. DEC-fortified common table salt for 6-12 months
The first strategy has received heavy investment. GlaxoSmithKline (GSK) provide tens of millions of albendazole treatments free of charge and over US$1 million each year[1]. Similarly, free supplies of ivermectin are guaranteed by Merck,Inc. Investment in the second strategy appears more limited, though an early systematic review supports its use[2].
Objectives and Methods: To compare these strategies with current research evidence from Cochrane and other systematic reviews[2-4].
Results: Albendazole in combination with an antifilarial drug[3] (Figure 1): Evidence from observational data appears to support the addition of albendazole, but randomised controlled trial evidence is limited. Adding albendazole to ivermectin showed enhancement in one trial (RR 0.27, 95%CI 0.11 to 0.70, n=52) but not in another (RR 1.04, 95% CI 0.87 to 1.25, n=145). One trial combining albendazole with diethylcarbamazine contained insufficient data. The review identified statistical difficulties with the presentation of a primary outcome, concentration of mf in the blood.
DEC fortified salt: 21 studies were included, designs varied (mainly uncontrolled and controlled before and after )[4]. In some cases, DEC salt seemed able to reduce mf prevalence close to zero. Large percentage reductions (80-95%) were observed after 6 months in many studies, regardless of the initial mf prevalence. Where mf prevalence was low (<5%), administration of DEC fortified salt for 6 months or more has shown remarkable sustained reductions for up to 19 years. Meta-regression suggested that DEC concentration and per capita consumption independently predict reductions in mf.
Conclusions: More evidence is required to assess the efficacy of albendazole combinations. DEC salt may offer an alternative strategy, provided good compliance can be achieved. Statistical analysis and reporting of some outcomes (mf concentration) is poor and sometimes flawed. We plan to continue this work with a review of different DEC dosing schedules, and with dissemination strategies to improve statistical reporting in filarial trials.
References: 1. The Global Alliance to Eliminate Lymphatic Filariasis. http:// www.filariasis.org/index.pl 2. Gelband H. Diethylcarbamazine salt in the control of lymphatic filariasis. Am J Trop Med Hygiene. 1994;50:655-62. 3. International Filariasis Review Group. Albendazole for lymphatic filariasis (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd. 4. Gelband H. Diethylcarbamazine (DEC)-medicated salt for community-based control of lymphatic filariasis (Protocol for a Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.
The first strategy has received heavy investment. GlaxoSmithKline (GSK) provide tens of millions of albendazole treatments free of charge and over US$1 million each year[1]. Similarly, free supplies of ivermectin are guaranteed by Merck,Inc. Investment in the second strategy appears more limited, though an early systematic review supports its use[2].
Objectives and Methods: To compare these strategies with current research evidence from Cochrane and other systematic reviews[2-4].
Results: Albendazole in combination with an antifilarial drug[3] (Figure 1): Evidence from observational data appears to support the addition of albendazole, but randomised controlled trial evidence is limited. Adding albendazole to ivermectin showed enhancement in one trial (RR 0.27, 95%CI 0.11 to 0.70, n=52) but not in another (RR 1.04, 95% CI 0.87 to 1.25, n=145). One trial combining albendazole with diethylcarbamazine contained insufficient data. The review identified statistical difficulties with the presentation of a primary outcome, concentration of mf in the blood.
DEC fortified salt: 21 studies were included, designs varied (mainly uncontrolled and controlled before and after )[4]. In some cases, DEC salt seemed able to reduce mf prevalence close to zero. Large percentage reductions (80-95%) were observed after 6 months in many studies, regardless of the initial mf prevalence. Where mf prevalence was low (<5%), administration of DEC fortified salt for 6 months or more has shown remarkable sustained reductions for up to 19 years. Meta-regression suggested that DEC concentration and per capita consumption independently predict reductions in mf.
Conclusions: More evidence is required to assess the efficacy of albendazole combinations. DEC salt may offer an alternative strategy, provided good compliance can be achieved. Statistical analysis and reporting of some outcomes (mf concentration) is poor and sometimes flawed. We plan to continue this work with a review of different DEC dosing schedules, and with dissemination strategies to improve statistical reporting in filarial trials.
References: 1. The Global Alliance to Eliminate Lymphatic Filariasis. http:// www.filariasis.org/index.pl 2. Gelband H. Diethylcarbamazine salt in the control of lymphatic filariasis. Am J Trop Med Hygiene. 1994;50:655-62. 3. International Filariasis Review Group. Albendazole for lymphatic filariasis (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd. 4. Gelband H. Diethylcarbamazine (DEC)-medicated salt for community-based control of lymphatic filariasis (Protocol for a Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.