Lymphatic Filariasis (LF) in Ivory Coast
Condition: Lymphatic Filariasis
MeSH terms: Filariasis; Elephantiasis, Filarial; Elephantiasis
Study type: Interventional

Summary: 
      The recommended treatment for elimination of LF in sub-Saharan Africa is annual mass drug
      administration (MDA) with single dose Albendazole (ALB) plus Ivermectin (IVM) given for at
      least 5-7 years. However, in areas where LF is co-endemic with a related filarial parasite,
      Loa loa, co-infection with L. loa represents a serious barrier to LF elimination because IVM
      used in LF MDA can result in severe reactions and even death in individuals with high
      microfilaria (mf) levels of L. loa. Screening for heavy L. loa infection is problematic. To
      overcome this problem, monotherapy with ALB is possible, since this drug has little or no
      effect on circulating mf and thus would not cause adverse effects in people with heavy L. loa
      infections. Moreover ALB has been shown to have embryostatic or embryocidal effects in female
      adult worms resulting in decreased mf levels with time as natural attrition of circulating mf
      occurs. Thus this open-label, randomized clinical trial will examine treatment with ALB
      monotherapy administered twice per year over a period of 3 years with the primary endpoint
      being the proportion of individuals with total clearance of mf at 36 months and Alere antigen
      test negativity (a more sensitive circulating antigen test of filarial infection). Two of the
      treatment arms will include ALB at two different doses, 400mg or 800mg (fixed dose twice
      yearly) as compared to standard treatment of ALB (400 mg) plus IVM (150-200 µg/kg)
      administered annually. Observations from an ongoing clinical trial in Papua New Guinea
      suggest that a single dose of triple therapy with ALB + IVM + DEC may be highly effective in
      sterilizing adult female worms. Therefore to confirm and expand these important preliminary
      observations in a different population, a fourth arm will be included in the current clinical
      trial in which subjects will receive all three drugs. The clinical trial will be performed in
      a region of Cote d'Ivoire where onchocerciasis and loiasis are not endemic.
    

Detailed description: 
      Lymphatic filariasis (LF) is a deforming and disabling infectious disease that causes
      elephantiasis and genital deformity (especially hydroceles). The infection affects some 120
      million people in 81 countries in tropical and subtropical regions with well over 1 billion
      people at risk of acquiring the disease. LF is caused by Wuchereria bancrofti and Brugia spp.
      (B. malayi and B. timori), nematode parasites that are transmitted by mosquitoes. The World
      Health Organization (WHO) developed a plan for LF elimination that is based on using novel
      approaches to rapidly map endemic areas and 4 to 6 annual rounds of MDA with antifilarial
      medication. A recent summary from WHO reported that more than 4 billion doses of MDA were
      distributed between 2000 and 2012. Thus, the Global Program to Eliminate Lymphatic Filariasis
      (GPELF) is the largest infectious disease intervention program attempted to date based on MDA
      (Ottesen, Hooper et al.

      2008). MDA has worked better in some areas than others. There are a number of challenges
      faced by GPELF. These include (among others) inability to conduct MDA programs in areas of
      Africa where L. loa is coendemic because of the unacceptable risk of Serious Adverse Events
      (SAE's) with IVM in persons with heavy L. loa infections (Hoerauf, Pfarr et al. 2011), the
      limited macrofilaricidal activity of current MDA regimens (especially ALB + IVM) that
      necessitate repeated annual rounds of MDA (Geary and Mackenzie , Hoerauf, Pfarr et al. 2011),
      and the difficulty of achieving high compliance rates for MDA over a period of years
      (Hoerauf, Pfarr et al. 2011). It is clear that new (or reformulated) drugs and/or dosing
      schedules for LF MDA have the potential to greatly improve the number of countries that will
      successfully eliminate LF by the WHO target date of 2020. This is especially important for
      areas of Central and West Africa where MDA has not been implemented because of the possible
      co-infection with L. loa and logistical and financial challenges to delivering annual doses
      of IVM + ALB MDA to millions of individuals over multiple years.
    

Intervention name(s): Albendazole; Ivermectin; Diethylcarbamazine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Subjects in Arms 1, 2, and 4 will receive 400mg of Albendazole
Subjects in Arm 3 will receive 800mg of Albendazole; Subjects in Arms 1 and 4 will receive 200mg/kg body weight; Participants in Arm 4 will receive 6mg/kg of Diethylcarbamazine per body weight
Other intervention name(s): ALB; IVM; DEC
Intervention MeSH terms: Ivermectin; Albendazole; Diethylcarbamazine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Ivermectin; Albendazole; Diethylcarbamazine