Advertisement

Parasitology Research

, Volume 116, Issue 10, pp 2683–2694 | Cite as

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

  • Nilima A. KshirsagarEmail author
  • N. J. Gogtay
  • B. S. Garg
  • P. R. Deshmukh
  • D. D. Rajgor
  • V. S. Kadam
  • P. A. Thakur
  • A. Gupta
  • N. S. Ingole
  • J. K. Lazdins-Helds
Original Paper

Abstract

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.

Keywords

Lymphatic filariasis Diethylcarbamazine Albendazole Efficacy Safety Mass drug administration Retreatments Microfilaria Circulating filarial antigen Filarial dance sign 

Notes

Acknowledgements

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

Funding

This investigation received financial support from the UNDP/World bank/WHO Special Program for Research and Training in Tropical Diseases (TDR).

References

  1. 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
  2. Babu B, Rath K, Kerketta A, Swain B, Mishra S, Kar S (2006) Adverse reactions following mass drug administration during the programme to eliminate lymphatic Filariasis in Orissa state, India. Trans R Soc Trop Med Hyg 100:464–469CrossRefPubMedGoogle Scholar
  3. Bockarie MJ, Tisch DJ, Kastens W, Alexander ND, Dimber Z, Bockarie F, Ibam E, Alpers MP, Kazura JW (2002) Mass treatment to eliminate filariasis in Papua New Guinea. N Engl J Med 347:1841–1848CrossRefPubMedGoogle Scholar
  4. Bockarie MJ, Tavul L, Ibam I, Kastens W, Hazlett F, Tisch DJ, Alpers MP, Kazura JW (2007) Efficacy of single-dose diethylcarbamazine compared with diethylcarbamazine combined with albendazole against Wuchereria bancrofti infection in Papua New Guinea. Am J Trop Med Hyg 76:62–66PubMedGoogle Scholar
  5. Dreyer G, Addiss D, Williamson J, Norões J (2006) Efficacy of co-administered diethylcarbamazine and albendazole against adult Wuchereria bancrofti. Trans R Soc Trop Med Hyg 100:1118–1125CrossRefPubMedGoogle Scholar
  6. Eberhard M, Hightower A, Addiss D, Lammie P (1997) Clearance of Wuchereria bancrofti antigen after treatment with diethylcarbamazine or ivermectin. Am J Trop Med Hyg 57(4):483CrossRefPubMedGoogle Scholar
  7. El Setouhy M, Ramzy RM, Ahmed ES, Kandil AM, Hussain O, Farid HA, Helmy H, Weil GJ (2004) A randomized clinical trial comparing single-and multi-dose combination therapy with diethylcarbamazine and albendazole for treatment of bancroftian filariasis. Am J Trop Med Hyg 70:191–196PubMedGoogle Scholar
  8. El-Setouhy M, Elaziz KMA, Helmy H, Farid HA, Kamal HA, Ramzy RM, Shannon WD, Weil GJ (2007) The effect of compliance on the impact of mass drug administration for elimination of lymphatic filariasis in Egypt. Am J Trop Med Hyg 77:1069–1073PubMedPubMedCentralGoogle Scholar
  9. Fraser M, Taleo G, Taleo F, Yaviong J, Amos M, Babu M, Kalkoa M (2005) Evaluation of the program to eliminate lymphatic filariasis in Vanuatu following two years of mass drug administration implementation: results and methodologic approach. Am J Trop Med Hyg 73:753–758PubMedGoogle Scholar
  10. 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
  11. Gunawardena G, Ismail M, Bradley M, Karunaweera N (2007) Impact of the 2004 mass drug administration for the control of lymphatic filariasis, in urban and rural areas of the western province of Sri Lanka. Ann Trop Med Parasitol 101:335–341CrossRefPubMedGoogle Scholar
  12. Helmy H, Weil GJ, Ellethy AST, Ahmed ES, El Setouhy M, Ramzy RM (2006) Bancroftian filariasis: effect of repeated treatment with diethylcarbamazine and albendazole on microfilaraemia, antigenaemia and antifilarial antibodies. Trans R Soc Trop Med Hyg 100:656–662CrossRefPubMedGoogle Scholar
  13. 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
  14. Koyadun S, Bhumiratana A, Prikchu P (2003) Wuchereria bancrofti antigenemia clearance among Myanmar migrants after biannual mass treatments with diethylcarbamazine, 300 mg oral-dose FILADEC tablet, in southern Thailand. Southeast Asian J Trop Med Public Health 34:758–767PubMedGoogle Scholar
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. Ramaiah K, Vanamail P, Pani S, Das P (2003) The prevalences of Wuchereria bancrofti antigenaemia in communities given six rounds of treatment with diethylcarbamazine, ivermectin or placebo tablets. Ann Trop Med Parasitol 97:737–741CrossRefPubMedGoogle Scholar
  21. Ramaiah K, Vanamail P, Das P (2007) Changes in Wuchereria bancrofti infection in a highly endemic community following 10 rounds of mass administration of diethylcarbamazine. Trans R Soc Trop Med Hyg 101:250–255CrossRefPubMedGoogle Scholar
  22. Ramzy RM, El Setouhy M, Helmy H, Ahmed ES, Elaziz KMA, Farid HA, Shannon WD, Weil GJ (2006) Effect of yearly mass drug administration with diethylcarbamazine and albendazole on bancroftian filariasis in Egypt: a comprehensive assessment. Lancet 367:992–999CrossRefPubMedGoogle Scholar
  23. 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
  24. Schuetz A, Addiss D, Eberhard M, Lammie P (2000) Evaluation of the whole blood filariasis ICT test for short-term monitoring after antifilarial treatment. Am J Trop Med Hyg 62:502CrossRefPubMedGoogle Scholar
  25. Simonsen PE, Magesa SM, Meyrowitsch DW, Malecela-Lazaro MN, Rwegoshora RT, Jaoko WG, Michael E (2005) The effect of eight half-yearly single-dose treatments with DEC on Wuchereria bancrofti circulating antigenaemia. Trans R Soc Trop Med Hyg 99:541–547CrossRefPubMedGoogle Scholar
  26. 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
  27. Sunish I, Rajendran R, Mani T, Munirathinam A, Reuben R, Dash A (2006) Impact of single dose of diethylcarbamazine and other antifilarial drug combinations on bancroftian filarial infection variables: assessment after 2 years. Parasitol Int 55:233–236CrossRefPubMedGoogle Scholar
  28. 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
  29. Wamae C, Njenga S, Ngugi B, Mbui J, Njaanake H (2011) Evaluation of effectiveness of diethylcarbamazine/albendazole combination in reduction of Wuchereria bancrofti infection using multiple infection parameters. Acta Trop 120:S33CrossRefPubMedGoogle Scholar
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Nilima A. Kshirsagar
    • 1
    • 2
    Email author
  • N. J. Gogtay
    • 1
  • B. S. Garg
    • 3
  • P. R. Deshmukh
    • 3
  • D. D. Rajgor
    • 1
  • V. S. Kadam
    • 1
  • P. A. Thakur
    • 1
  • A. Gupta
    • 1
  • N. S. Ingole
    • 4
  • J. K. Lazdins-Helds
    • 5
  1. 1.Department of Clinical PharmacologySeth GS Medical College and KEM HospitalMumbaiIndia
  2. 2.National Chair Clinical Pharmacology, ICMR Govt. of IndiaNational Institute for Research in Reproductive Health (NIRRH)MumbaiIndia
  3. 3.Department of Community MedicineMahatma Gandhi Institute of Medical SciencesWardhaIndia
  4. 4.Department of PathologyMahatma Gandhi Institute of Medical SciencesWardhaIndia
  5. 5.World Health Organization (WHO), Special Program for Research and Training in Tropical Diseases, Product Research and DevelopmentGenevaSwitzerland

Personalised recommendations