A Systematic Review: The Effectiveness of Triple Drug versus Dual Drug Approach Against Lymphatic Filariasis
DOI:
https://doi.org/10.22225/ijbstm.2.1.2025.7-13Keywords:
dual drug, lymphatic filariasis, triple drugsAbstract
Background: Lymphatic Filariasis (LF) is a neglected tropical disease caused by filarial nematode parasites (Wuchereria bancrofti, Brugia malayi, and B. timori), which is transmitted via mosquitoes in the form of microfilariae (Mf). The transmission cycle for each species is the same parasites or worms transmitted through the bite of all types of mosquitoes. The most severe clinical manifestations of LF are lymphedema and elephantiasis. The treatment of filariasis receives mass drug administration with a single dose of the triple-drug oral regimen. Therefore, the World Health Organization (WHO) reported that the triple-drug oral regimen was an LF treatment.
Methods: The research is in the form of systematic review research using the PRISMA (Preferred Reporting Items for Systematic Review and Meta-analysis) method, which is carried out systematically. The research was conducted in December-February with a review of articles published in the last 5 years (2018-2023). Researchers searched for literature independently through PubMed and Science Direct.
Results:Triple drug therapy or a combination of Ivermectin-Diethylcarbamazine -Albendazole (IDA) is safer and more tolerable for filariasis than dual drug (combination of Diethylcarbamazine -Albendazole/DA), according to various articles. In addition, IDA reduces microfilaria formation more than DA. Most filariasis treatment side effects are modest, such as fever and soreness.
Conclusion: In comparison to dual drug therapy, triple drug therapy exhibits a substantial advantage; however, the level of endemicity and the species of the causative agents must be considered when applying this approach.
References
Abuelazm, M. T., Abdelazeem, B., Badr, H., Gamal, M., Ashraf, M., & Abd-elsalam, S. (2022). Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: A systematic review and meta-analysis. In Tropical Medicine and International Health (Vol. 27, Issue 3, pp. 226–235). John Wiley and Sons Inc. https://doi.org/10.1111/tmi.13727
Agrawal, S., Oza, P., Kakkar, R., Tanwar, S., Jetani, V., Undhad, J., & Singh, A. (2024). Analysis and recommendation system-based on PRISMA checklist to write systematic review. Assessing Writing, 61, 100866. https://doi.org/10.1016/j.asw.2024.100866
Akl, E. A., Khabsa, J., Iannizzi, C., Piechotta, V., Kahale, L. A., Barker, J. M., McKenzie, J. E., Page, M. J., & Skoetz, N. (2024). Extension of the PRISMA 2020 statement for living systematic reviews (PRISMA-LSR): checklist and explanation. BMJ, e079183. https://doi.org/10.1136/bmj-2024-079183
Azhar, S., Naeem Muhammad Abdullah, Qamar Warda, Iqbal Muhammad Jawad, Asghar Shiza, Ajaz Rahmeen, Iqbal Hrishik, Sohail MUhammad, Tahir Saleha, Assad Muhammad Ali, & Khalid Adeel. (2023). Basic Insights into Lymphatic Filariasis. Zoonosis, 2, 73–88. https://doi.org/10.47278/book.zoon/2023.53
Beng, A. A., Esum, M. E., Deribe, K., Njouendou, A. J., Ndongmo, P. W. C., Abong, R. A., Fru, J., Fombad, F. F., Nchanji, G. T., Amambo, G., Gandjui, N. T. V., Biholong, B., Nko’Ayissi, G., Mbia, P., Akame, J., Enyong, P. I., Reid, S. D., Tougoue, J. J., Zhang, Y., & Wanji, S. (2020). Mapping lymphatic filariasis in Loa loa endemic health districts naïve for ivermectin mass administration and situated in the forested zone of Cameroon. BMC Infectious Diseases, 20(1), 284. https://doi.org/10.1186/s12879-020-05009-3
Bjerum, C. M., Koudou, B. G., Ouattara, A. F., Lew, D., Goss, C. W., Gabo, P. T., King, C. L., Fischer, P. U., Weil, G. J., & Budge, P. J. (2023). Safety and tolerability of moxidectin and ivermectin combination treatments for lymphatic filariasis in Côte d’Ivoire: A randomized controlled superiority study. PLoS Neglected Tropical Diseases, 17(9 September). https://doi.org/10.1371/journal.pntd.0011633
Boussinesq, M., Gardon, J., Gardon-Wendel, N., Kamgno, J., Ngoumou, P., & Chippaux, J. P. (1998). Three probable cases of Loa loa encephalopathy following ivermectin treatment for onchocerciasis. The American Journal of Tropical Medicine and Hygiene, 58(4), 461–469. https://doi.org/10.4269/ajtmh.1998.58.461
Budge, P. J., Herbert, C., Andersen, B. J., & Weil, G. J. (2018). Adverse events following single dose treatment of lymphatic filariasis: Observations from a review of the literature. PLOS Neglected Tropical Diseases, 12(5), e0006454. https://doi.org/10.1371/journal.pntd.0006454
Chesnais, C. B., Pion, S. D., Boullé, C., Gardon, J., Gardon-Wendel, N., Fokom-Domgue, J., Kamgno, J., & Boussinesq, M. (2020). Individual risk of post-ivermectin serious adverse events in subjects infected with Loa loa. EClinicalMedicine, 28, 100582. https://doi.org/10.1016/j.eclinm.2020.100582
Direktorat Jenderal Pencegahan dan Pengendalian Penyakit. (2022). G20 Indonesia 2022.
Edi, C., Bjerum, C. M., Ouattara, A. F., Chhonker, Y. S., Penali, L. K., Méité, A., Koudou, B. G., Weil, G. J., King, C. L., & Murry, D. J. (2019). Pharmacokinetics, safety, and efficacy of a single co-administered dose of diethylcarbamazine, albendazole and ivermectin in adults with and without wuchereria bancrofti infection in cote d’ivoire. PLoS Neglected Tropical Diseases, 13(5). https://doi.org/10.1371/journal.pntd.0007325
Gusti, I., Ari, A., Yana, K., & Salim, M. (2021). REVIWE ARTICLE COMPARISON OF TRIPLE DRUG THERAPY VERSUS DOUBLE DRUG THERAPY FOR LYMPHATIC FILARIASIS: A SYSTEMATIC REVIEW ARTICLE INFO. In MEDICAL AND HEALTH SCIENCE JOURNAL (Vol. 05, Issue 01).
Gyapong, J. O., Owusu, I. O., da-Costa Vroom, F. B., Mensah, E. O., & Gyapong, M. (2018). Elimination of lymphatic filariasis: current perspectives on mass drug administration. Research and Reports in Tropical Medicine, Volume 9, 25–33. https://doi.org/10.2147/RRTM.S125204
Hardy, M., Samuela, J., Kama, M., Tuicakau, M., Romani, L., Whitfeld, M. J., King, C. L., Weil, G. J., Grobler, A. C., Robinson, L. J., Kaldor, J. M., & Steer, A. C. (2020). The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of fiji: A cluster randomised trial. PLoS Neglected Tropical Diseases, 14(3). https://doi.org/10.1371/journal.pntd.0008106
Hardy, M., Samuela, J., Kama, M., Tuicakau, M., Romani, L., Whitfeld, M. J., King, C. L., Weil, G. J., Grobler, A. C., Robinson, L. J., Kaldor, J. M., & Steer, A. C. (2020b). The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of fiji: A cluster randomised trial. PLoS Neglected Tropical Diseases, 14(3). https://doi.org/10.1371/journal.pntd.0008106
Irvine, M. A., Stolk, W. A., Smith, M. E., Subramanian, S., Singh, B. K., Weil, G. J., Michael, E., & Hollingsworth, T. D. (2017). Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: a modelling study. The Lancet Infectious Diseases, 17(4), 451–458. https://doi.org/10.1016/S1473-3099(16)30467-4
Kamgno, J., Nguipdop-Djomo, P., Gounoue, R., Téjiokem, M., & Kuesel, A. C. (2016). Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial. PLOS Neglected Tropical Diseases, 10(3), e0004492. https://doi.org/10.1371/journal.pntd.0004492
Kanaan Al Tameemi, & Raiaan Kabakli. (2019). LYMPHATIC FILARIASIS: AN OVERVIEW. Asian Journal of Pharmaceutical and Clinical Research, 1–5. https://doi.org/10.22159/ajpcr.2019.v12i12.35646
Kar Shantanu Kumar, & Jagadish Hansa. (2018). New Perspective of Lymphatic Filariasis-Towards Elimination. Annals of the National Academy of Medical Sciences, 54(2), 106–113.
Khaemba, C., Barry, A., Omondi, W. P., Kirui, E., Oluka, M., Parthasarathi, G., Njenga, S. M., Guantai, A., & Aklillu, E. (2023). Comparative Safety Surveillance of Triple (IDA) Versus Dual Therapy (DA) in Mass Drug Administration for Elimination of Lymphatic Filariasis in Kenya: A Cohort Event Monitoring Study. Drug Safety, 46(10), 961–974. https://doi.org/10.1007/s40264-023-01338-9
King, C. L., Suamani, J., Sanuku, N., Cheng, Y.-C., Satofan, S., Mancuso, B., Goss, C. W., Robinson, L. J., Siba, P. M., Weil, G. J., & Kazura, J. W. (2018). A Trial of a Triple-Drug Treatment for Lymphatic Filariasis. New England Journal of Medicine, 379(19), 1801–1810. https://doi.org/10.1056/nejmoa1706854
Laman, M., Tavul, L., Karl, S., Kotty, B., Kerry, Z., Kumai, S., Samuel, A., Lorry, L., Timinao, L., Howard, S. C., Makita, L., John, L., Bieb, S., Wangi, J., Albert, J. M., Payne, M., Weil, G. J., Tisch, D. J., Bjerum, C. M., … King, C. L. (2022). Mass drug administration of ivermectin, diethylcarbamazine, plus albendazole compared with diethylcarbamazine plus albendazole for reduction of lymphatic filariasis endemicity in Papua New Guinea: a cluster-randomised trial. The Lancet Infectious Diseases, 22(8), 1200–1209. https://doi.org/10.1016/S1473-3099(22)00026-3
Lenk, E. J., Moungui, H. C., Boussinesq, M., Kamgno, J., Nana-Djeunga, H. C., Fitzpatrick, C., Peultier, A.-C. M. M., Klion, A. D., Fletcher, D. A., Nutman, T. B., Pion, S. D., Niamsi-Emalio, Y., Redekop, W. K., Severens, J. L., & Stolk, W. A. (2020). A Test-and-Not-Treat Strategy for Onchocerciasis Elimination in Loa loa–coendemic Areas: Cost Analysis of a Pilot in the Soa Health District, Cameroon. Clinical Infectious Diseases, 70(8), 1628–1635. https://doi.org/10.1093/cid/ciz461
Molyneux, D. H. (2018). Advancing toward the Elimination of Lymphatic Filariasis. New England Journal of Medicine, 379(19), 1871–1872. https://doi.org/10.1056/NEJMe1811455
Njenga, S. M., Kanyi, H., Okoyo, C., Githinji, E., Mwatele, C., Matendechero, H. S., Omondi, W. P., Gitahi, P. N., Owaga, C., Onsongo, J. K., & Gass, K. (2024). Triple-drug therapy with ivermectin, diethylcarbamazine and albendazole for the acceleration of lymphatic filariasis elimination in Kenya: Programmatic implementation and results of the first impact surveillance. BMJ Yale. https://doi.org/10.1101/2024.01.30.24301765
Permana, A. D., Tekko, I. A., McCrudden, M. T. C., Anjani, Q. K., Ramadon, D., McCarthy, H. O., & Donnelly, R. F. (2019). Solid lipid nanoparticle-based dissolving microneedles: A promising intradermal lymph targeting drug delivery system with potential for enhanced treatment of lymphatic filariasis. Journal of Controlled Release, 316, 34–52. https://doi.org/10.1016/j.jconrel.2019.10.004
Prada, J. M., Davis, E. L., Touloupou, P., Stolk, W. A., Kontoroupis, P., Smith, M. E., Sharma, S., Michael, E., De Vlas, S. J., & Hollingsworth, T. D. (2020). Elimination or Resurgence: Modelling Lymphatic Filariasis after Reaching the 1% Microfilaremia Prevalence Threshold. Journal of Infectious Diseases, 221, S503–S509. https://doi.org/10.1093/infdis/jiz647
Rahim, S., & Karim, M. M. (2022). Lymphatic Filariasis: A systematic review on its morbidity and road to elimination. In African Journal of Biological Sciences (South Africa) (Vol. 4, Issue 4, pp. 116–126). African Science Publications. https://doi.org/10.33472/AFJBS.4.4.2022.116-126
Supali, T., Djuardi, Y., Christian, M., Iskandar, E., Alfian, R., Maylasari, R., Destani, Y., Lomiga, A., Minggu, D., Lew, D., Bogus, J., Weil, G. J., & Fischer, P. U. (2021). An open label, randomized clinical trial to compare the tolerability and efficacy of ivermectin plus diethylcarbamazine and albendazole vs. Diethylcarbamazine plus albendazole for treatment of brugian filariasis in Indonesia. PLoS Neglected Tropical Diseases, 15(3). https://doi.org/10.1371/journal.pntd.0009294
Tripathi, B., Roy, N., & Dhingra, N. (2022). Introduction of Triple-Drug Therapy for Accelerating Lymphatic Filariasis Elimination in India: Lessons Learned. The American Journal of Tropical Medicine and Hygiene. https://doi.org/10.4269/ajtmh.21-0964
Weil, G. J., Bogus, J., Christian, M., Dubray, C., Djuardi, Y., Fischer, P. U., Goss, C. W., Hardy, M., Jambulingam, P., King, C. L., Kuttiat, V. S., Krishnamoorthy, K., Laman, M., Lemoine, J. F., O’brian, K. K., Robinson, L. J., Samuela, J., Schechtman, K. B., Sircar, A., … Subramanian, S. (2019). The safety of double-and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study. PLoS Medicine, 16(6). https://doi.org/10.1371/journal.pmed.1002839
Weil, G. J., Jacobson, J. A., & King, J. D. (2021). A triple-drug treatment regimen to accelerate elimination of lymphatic filariasis: From conception to delivery. International Health, 13, S60–S64. https://doi.org/10.1093/inthealth/ihaa046
Willis, G. A., Mayfield, H. J., Kearns, T., Naseri, T., Thomsen, R., Gass, K., Sheridan, S., Graves, P. M., & Lau, C. L. (2020). A community survey of coverage and adverse events following country-wide triple-drug mass drug administration for lymphatic filariasis elimination, samoa 2018. PLoS Neglected Tropical Diseases, 14(11), 1–18. https://doi.org/10.1371/journal.pntd.0008854
World Health Organization. (2023). Lymphatic Filariasis. World Health Organization.
Yana, I. G. A. A. K. (2021). Systematic Review: Comparison of triple drug therapy versus double drug therapy for Lymphatic Filariasis. Medical and Health Science Journal, 5(1), 34–45. https://doi.org/10.33086/mhsj.v5i1.1878
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