Efficacy and tolerability of treatment with single doses of diethylcarbamazine (DEC) and DEC plus albendazole (ABZ) for three consecutive years in lymphatic filariasis: a field study in India
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Lymphatic filariasis (LF) affects 73 countries, causes morbidity and impedes socioeconomic development. We had found no difference in safety and micro (Mf) and macro filarial action of single-dose diethylcarbamazine (DEC) and DEC + albendazole (ABZ) in an F01 study done in India (year 2000). There was a programmatic need to evaluate safety and efficacy of multiple annual treatments (F02). Subjects (155) from the F01 study, meeting inclusion-exclusion criteria, were enrolled in F02 and treated with further two annual doses of DEC or DEC + ABZ. Efficacy was evaluated for Mf positivity by peripheral smear (PS) and nucleopore (NP) filter, circulating filarial antigen (CFA) and filarial dance sign (FDS) positivity and Mf count at yearly follow-up. Safety was assessed for 5 days after drug administration. Total of 139 subjects evaluated for efficacy (69 DEC and 70 DEC + ABZ group). Mf positivity prevalence declined progressively by 95% (PS), 66% (NP), and 95% (PS) and 86% (NP); CFA positivity prevalence declined by 15% and 9%; FDS by 100% each; Mf count declined by 75.5 and 76.9% with three annual treatment of DEC and DEC + ABZ, respectively. Addition of ABZ did not show any advantage over DEC given as three annual rounds for LF. DEC and DEC + ABZ were well tolerated. There was no correlation between result of CFA and FDS, (both claimed to be indicative of adult worm). Analysis of published studies and our data indicate that macrofilaricidal effect of DEC/DEC + ABZ may be seen in children and not adults, with three or more annual dosing.
KeywordsLymphatic filariasis Diethylcarbamazine Albendazole Efficacy Safety Mass drug administration Retreatments Microfilaria Circulating filarial antigen Filarial dance sign
Pravin Bhusari and other social workers, all medical officers and research staff from the Department of Clinical Pharmacology who assisted at various follow-ups. Bowalekar for statistical analysis, Cipla for Drug packaging and randomization, and Glaxo Smithkline for DEC supply.
Compliance with ethical standards
This investigation received financial support from the UNDP/World bank/WHO Special Program for Research and Training in Tropical Diseases (TDR).
- Addiss DG, Beach MJ, Streit TG, Lutwick S, LeConte FH, Lafontant JG, Hightower AW, Lammie PJ (1997) Randomised placebo-controlled comparison of ivermectin and albendazole alone and in combination for Wuchereria bancrofti microfilaraemia in Haitian children. Lancet 350:480–484CrossRefPubMedGoogle Scholar
- Guidelines on filariasis control in India and its elimination. National Vector Borne Disease Control Program; Ministry of Health and Family Welfare; Government of India; 2009. http://nvbdcp.gov.in/doc/guidelines-filariasis-elimination-india.pdf
- Ismail M, Jayakody R, Weil G, Nirmalan N, Jayasinghe K, Abeyewickrema W, Sheriff MR, Rajaratnam H, Amarasekera N, De Silva D (1998) Efficacy of single dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis. Trans R Soc Trop Med Hyg 92:94–97CrossRefPubMedGoogle Scholar
- Kshirsagar N, Gogtay N, Garg B, Deshmukh P, Rajgor D, Kadam V, Kirodian B, Ingole N, Mehendale A, Fleckenstein L (2004) Safety, tolerability, efficacy and plasma concentrations of diethylcarbamazine and albendazole co-administration in a field study in an area endemic for lymphatic filariasis in India. Trans R Soc Trop Med Hyg 98:205–217CrossRefPubMedGoogle Scholar
- Lalitha P, Ravichandran M, Suba S, Kaliraj P, Narayanan R, Jayaraman K (1998) Quantitative assessment of circulating antigens in human lymphatic filariasis: a field evaluation of monoclonal antibody-based ELISA using blood collected on filter strips. Tropical Med Int Health 3(1):41CrossRefGoogle Scholar
- Njenga SM, Mwandawiro CS, Wamae CN, Mukoko DA, Omar AA, Shimada M, Bockarie MJ, Molyneux DH (2011) Sustained reduction in prevalence of lymphatic filariasis infection in spite of missed rounds of mass drug administration in an area under mosquito nets for malaria control. Parasit Vectors 4:90CrossRefPubMedPubMedCentralGoogle Scholar
- Pani S, Das L, Vanamail P (2005) Tolerability and efficacy of a three-age class dosage schedule of Diethylcarbamazine citrate (DEC) in the treatment of microfilaria carriers of Wuchereria bancrofti and its implications in mass drug administration (MDA) strategy for elimination of lymphatic filariasis (LF). J Commun Dis 37:12–17PubMedGoogle Scholar
- Rajendran R, Sunish I, Mani T, Munirathinam A, Arunachalam N, Satyanarayana K, Dash A (2006) Community-based study to assess the efficacy of DEC plus ALB against DEC alone on bancroftian filarial infection in endemic areas in Tamil Nadu, south India. Tropical Med Int Health 11:851–861CrossRefGoogle Scholar
- Rizzo J, Belo C, Lins R, Dreyer G (2007) Children and adolescents infected with Wuchereria bancrofti in Greater Recife, Brazil: a randomized, year-long clinical trial of single treatments with diethylcarbamazine or diethylcarbamazine–albendazole. Ann Trop Med Parasitol 101:423–433CrossRefPubMedGoogle Scholar
- Simonsen PE, Derua YA, Magesa SM, Pedersen EM, Stensgaard A-S, Malecela MN, Kisinza WN (2014) Lymphatic filariasis control in Tanga region, Tanzania: status after eight rounds of mass drug administration. Parasit Vectors 7:507. Published online 2014 Nov 12. doi: 10.1186/s13071-014-0507-5
- Thomsen EK, Sanuku N, Baea M, Satofan S, Maki E, Lombore B, Schmidt MS, Siba PM, Weil GJ, Kazura JW (2015) Efficacy, safety, and pharmacokinetics of coadministered diethylcarbamazine, albendazole, and ivermectin for treatment of bancroftian filariasis. Clin Infect Dis 62:334–341CrossRefPubMedGoogle Scholar
- Washington CH, Radday J, Streit TG, Boyd HA, Beach MJ, Addiss DG, Lovince R, Lovegrove MC, Lafontant JG, Lammie PJ (2004) Spatial clustering of filarial transmission before and after a Mass Drug Administration in a setting of low infection prevalence. Filaria J 3:3CrossRefPubMedPubMedCentralGoogle Scholar
- Weerasooriya MV, Yahathugoda CT, Wickramasinghe D, Gunawardena KN, Dharmadasa RA, Vidanapathirana KK, Weerasekara SH, Samarawickrema WA (2007) Social mobilisation, drug coverage and compliance and adverse reactions in a mass drug administration (MDA) Programme for the elimination of lymphatic Filariasis in Sri Lanka. Filaria J 6:1CrossRefGoogle Scholar
- WHO (2013) Sustaining the drive to overcome the global impact of neglected tropical diseases: second WHO report on neglected diseases (WHO/HTM/NTD/2013.1)Google Scholar
- Yongyuth P, Koyadun S, Jaturabundit N, Sampuch A, Bhumiratana A (2006) Efficacy of a single-dose treatment with 300 mg diethylcarbamazine and a combination of 400 mg albendazole in reduction of Wuchereria bancrofti antigenemia and concomitant geohelminths in Myanmar migrants in southern Thailand. J Med Assoc Thail 89:1237–1248Google Scholar
- Yongyuth P, Koyadun S, Jaturabundit N, Jariyahuttakij W, Bhumiratana A (2007) Adverse reactions of 300 mg diethylcarbamazine, and in a combination of 400 mg albendazole, for a mass annual single dose treatment, in migrant workers in Phang Nga Province. J Med Assoc Thail 90:552Google Scholar