Cited by 116Parasitic Diseases Research and TreatmentParasites and Host InteractionsMalaria Research and Control

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Randomised placebo-controlled comparison of ivermectin and albendazole alone and in combination for Wuchereria bancrofti microfilaraemia in Haitian children

Addiss, David G, Beach, Michael J, Streit, Thomas G, Lutwick, Suzanne, LeConte, Fredrick H, Lafontant, Jack G, Hightower, Allen W, Lammie, Patrick J·1997·The Lancet

DOI 10.1016/s0140-6736(97)02231-9

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Abstract

Background Lymphatic filariasis and intestinal helminth infections are important disorders in tropical areas. Periodic treatment with albendazole is now used in many school-based intestinal helminth-control programmes. However, few such programmes exist for lymphatic filariasis, despite evidence that single-dose treatment with ivermectin can greatly reduce the concentration of Wuchereria bancrofti microfilariae in the blood for months to years. We aimed to assess the potential for school-based control of lymphatic filariasis by investigating the efficacy and tolerability or combined ivermectin and albendazole in Haitian schoolchildren. Methods In January, 1996, we collected 832 20 microL capillary blood samples for inclusion in a randomised controlled study from children aged 5-11 years, and examined them by microscopy for W bancrofti microfilariae. Infected children were randomly assigned treatment with placebo (n = 29), a single 200-400 micrograms/kg dose of ivermectin (mean, 273 micrograms/kg, n = 28), 400 mg albendazole (n = 29), or a combination of 200-400 micrograms/kg ivermectin and 400 mg albendazole (n = 24). Children with high concentrations of microfilariae in the blood were admitted to hospital and adverse reactions were monitored for 3-5 days, otherwise children were examined at school or during a visit to their home. 4 months after treatment, we examined blood samples again for microfilariae. Findings 113 microfilaraemic children were enrolled (mean age 7.8 years). 4 months after treatment, the proportion of children who remained positive for microfilariae was significantly lower in the ivermectin plus albendazole group (four [17%]), but there were no significant changes in the other three groups (20 [69%] placebo, 22 [76%] albendazole alone, 17 [61%] ivermectin alone remained positive; p = 0.004). Geometric mean microfilarial concentration decreased from 9.3 to 5.3 per 20 microL blood among children who received placebo; from 15.5 to 1.5 per 20 microL blood among those who received ivermectin only (p = 0.032); from 14.1 to 5.1 per 20 microL blood among those who received albendazole alone; and from 13.7 to 0.3 per 20 microL blood among those who received both ivermectin and albendazole (p = 0.0001). Systemic adverse reactions did not differ significantly between children who received ivermectin alone and those who were treated with ivermectin and albendazole [corrected]. Interpretation For children with W bancrofti microfilaraemia, combined treatment with ivermectin and albendazole was more effective than treatment with ivermectin only, with no measurable increase in severity of adverse reactions.

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Background
Use of high-dose, twice-yearly albendazole and ivermectin to suppress Wuchereria bancrofti microfilarial levels.
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Method
Efficacy of ivermectin in the treatment of Wuchereria bancrofti infection: a model-based analysis of trial results
Plaisier, A. P., Cao, W.-C., van Oortmarssen, G. J., & Habbema, J. D. (1999) · Parasitology · doi:10.1017/s0031182099004783 · Cited by 35
“…of other filariae and some intestinal parasites; De Silva, Guyatt & Bundy, 1997), and because combinations of DEC and ivermectin or albendazole and ivermectin show very promising results for the treatment of lymphatic filariasis (Moulia-Pelat et al. 1993; Addiss et al. 1997; Ismail et al. 1998).”
Background
Antibiotic resistance: a view from the prescriber
Finch, R. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro1049 · Cited by 34
Adverse reactions following mass drug administration during the Programme to Eliminate Lymphatic Filariasis in Orissa State, India.
Babu, B., Rath, K., Kerketta, A., Swain, B. K., Mishra, S., & Kar, S. (2006) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/j.trstmh.2005.07.016 · Cited by 33
Significant decrease in the prevalence of Wuchereria bancrofti infection in anopheline mosquitoes following the addition of albendazole to annual, ivermectin-based, mass treatments in Nigeria
Richards, F. O., Pam, D., Kal, A., Gerlong, G., Onyeka, J., Sambo, Y., Danboyi, J., Ibrahim, B., Terranella, A., Kumbak, D., et al. (2005) · Annals of Tropical Medicine and Parasitology · doi:10.1179/136485905x19838 · Cited by 32
“…donated by GlaxoSmithKline, and the ivermectin– albendazole combination appears safe (Horton et al., 2000; Makunde et al., 2003) and more effective than ivermectin (at 150 mg/kg) alone in lowering W. bancrofti microfilaraemias (Addiss et al., 1997; Ottesen et al., 1997, 1999; Ismail et al., 1998).”
BackgroundResult
Model‐based analysis of trial data: microfilaria and worm‐productivity loss after diethylcarbamazine–albendazole or ivermectin–albendazole combination therapy against Wuchereria bancrofti
de Kraker, M. E. A., Stolk, W. A., van Oortmarssen, G. J., & Habbema, J. D. F. (2006) · Tropical Medicine & International Health · doi:10.1111/j.1365-3156.2006.01606.x · Cited by 29
“Our estimates for IVM–ALB were higher, which could be explained by the added effect of ALB (Addiss et al. 1997; Dunyo et al. 2000a; Makunde et al. 2003).”
Background
Review of Dancing Parasites in Lymphatic Filariasis
Dietrich, C., Chaubal, N., Hoerauf, A., Kling, K., Piontek, M., Steffgen, L., Mand, S., & Dong, Y. (2019) · Ultrasound International Open · doi:10.1055/a-0918-3678 · Cited by 29
Anti-filarial activity of novel formulations of albendazole against experimental brugian filariasis
Gaur, R. L., Dixit, S., Sahoo, M. K., KHANNA, M., Singh, S. K., & Murthy, P. K. (2006) · Parasitology · doi:10.1017/s0031182006001612 · Cited by 28
“It has also been found to be useful as an anti-filarial agent, especially because of its macrofilaricidal activity (Ottesen and Ramachandran, 1995; Addiss et al. 1997; Ottesen et al. 1999; Beach et al. 1999 and Dunyo et al. 1999, 2000).”
Background
CLINICAL CHARACTERISTICS OF POST-TREATMENT REACTIONS TO IVERMECTIN/ALBENDAZOLE FOR WUCHERERIA BANCROFTI IN A REGION CO-ENDEMIC FOR MANSONELLA PERSTANS
Keiser, P. B., Coulibaly, Y. I., Keita, F., Traoré, D., Diallo, A. A., Diallo, D. A., Semnani, R. T., Doumbo, O. K., Traore, S. F., Klion, A. D., et al. (2003) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2003.69.331 · Cited by 27
Community-directed treatment : the way forward to eliminating lymphatic filariasis as a public-health problem in Ghana
Gyapong, M., Gyapong, J., & Owusu-Banahene, G. (2001) · doi:10.1080/00034980020035942 · Cited by 28
The antifilarial activity of a marine red alga, Botryocladia leptopoda,against experimental infections with animal and human filariae
Lakshmi, V., Kumar, R., Gupta, P., Varshney, V., Srivastava, M. N., Dikshit, M., Murthy, P., & Misra-Bhattacharya, S. (2004) · Parasitology Research · doi:10.1007/s00436-004-1159-8 · Cited by 26
“The existing antifilarials such as diethylcarbamazine (DEC) and ivermectin are principally microfilaricidal (Addiss et al. 1997), with a partial macrofilaricidal activity for DEC as assessed by ultrasonography (Dreyer et al. 1996), while ivermectin possesses an embryo static action (Reuben et al.…”
Background
Towards novel antifilarial drugs: challenges and recent developments.
Singh, P., Ajay, A., Kushwaha, S., Tripathi, R., & Misra-Bhattacharya, S. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.09.170 · Cited by 24
Crusted (Norwegian) scabies in a patient with dystrophic epidermolysis bullosa
Wal, V. B. V. D., Vader, P. C. V. V., Mandema, J., & Jonkman, M. (1999) · British Journal of Dermatology · doi:10.1046/j.1365-2133.1999.03170.x · Cited by 24
Evaluation of effectiveness of diethylcarbamazine/albendazole combination in reduction of Wuchereria bancrofti infection using multiple infection parameters.
Wamae, C., Njenga, S., Ngugi, B. M., Mbui, J., & Njaanake, H. (2011) · Acta Tropica · doi:10.1016/j.actatropica.2010.09.009 · Cited by 23
Elimination of lymphatic filariasis: Where do we stand so far?
Sinha, A., Kumar, S., Dayal, D., Yadav, V., Pramanik, A., Chaubey, K. K., & Kumar, S. (2023) · Asian Pacific Journal of Tropical Medicine · doi:10.4103/1995-7645.380729 · Cited by 23
Two decades of antifilarial drug discovery: a review
Sangshetti, J., Shinde, D., Kulkarni, A. A., & Arote, R. (2017) · doi:10.1039/c7ra01857f · Cited by 19
Recent developments in search of antifilarial agents.
Tripathi, R., Katiyar, D., Dwivedi, N., Singh, B., & Pandey, J. (2006) · Current Medicinal Chemistry · doi:10.2174/092986706778773103 · Cited by 19
Controlling lymphatic filariasis and soil-transmitted helminthiasis together in South Asia: opportunities and challenges
Padmasiri, E., Montresor, A., Biswas, G., & de Silva, N. D. (2006) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/j.trstmh.2005.12.001 · Cited by 19
“In the 1990s, research suggested that combination of albendazole with DEC or ivermectin enhanced suppression of microfilariaemia (Addiss et al., 1997; Ismail et al., 1998; Jayakody et al., 1993), and in 1998, the GPELF recommended MDA with the two-drug combination described above.”
Background
The development of albendazole for lymphatic filariasis
Horton, J. (2009) · Annals of Tropical Medicine and Parasitology · doi:10.1179/000349809x12502035776595 · Cited by 17
“Nonetheless, the inclusion of albendazole into the Global Programme to Eliminate Lymphatic Filariasis was an interesting development, beginning from simple observations and expanding to a global scale.”
BackgroundInfluential
Mass ivermectin treatment for Onchocerciasis: Lack of evidence for collateral impact on transmission of Wuchereria bancrofti in areas of co-endemicity
Richards, F. O., Eigege, A., Pam, D., Kal, A., Lenhart, A., Oneyka, J. O. A., Jinadu, M., & Miri, E. (2005) · Filaria Journal · doi:10.1186/1475-2883-4-6 · Cited by 16
“donates ivermectin (Mectizan®) to global control programmes for both these parasitic diseases, although annual ivermectin in combination with albendazole (donated by GlaxoSmithKline) is recommended by WHO for the treatment of LF in Africa, because of the presumed synergy [4,5], although this remains in debate [6].”
Background
Chemotherapy for lymphatic filariasis: progress but not perfection
Melrose, W. (2003) · Expert Review of Anti-Infective Therapy · doi:10.1586/14787210.1.4.571 · Cited by 16
Randomised controlled clinical trial of increased dose and frequency of albendazole and ivermectin on Wuchereria bancrofti microfilarial clearance in northern Malawi.
Tafatatha, T., Ngwira, B., Taegtmeyer, M., Phiri, A., Wilson, T., Banda, L., Piston, W. N., Koole, O., Horton, J., & French, N. (2015) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1093/trstmh/trv027 · Cited by 15
Ivermectin and albendazole alone and in combination for the treatment of lymphatic filariasis in Ghana: follow-up after re-treatment with the combination.
Dunyo, S., & Simonsen, P. E. (2002) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/s0035-9203(02)90300-7 · Cited by 15
Interventions for Neglected Tropical Diseases Among Children and Adolescents: A Meta-analysis
Naqvi, F. A., Das, J. K., Salam, R. A., Raza, S. F., Lassi, Z. S., & Bhutta, Z. A. (2022) · PEDIATRICS · doi:10.1542/peds.2021-053852e · Cited by 13
Pharmacovigilance through consumer feedback (reporting) in the mass treatment of lymphatic filariasis using diethylcarbamazine and albendazole in two districts of Sri Lanka
Gunawardena, S., Ranganathan, S., & Fernandopulle, R. (2008) · Tropical medicine & international health · doi:10.1111/j.1365-3156.2008.02120.x · Cited by 13
“Treated microfilaraemic persons may experience headache, fever, chills and body aches; the severity of adverse drug reactions increases with microfilarial density (Dreyer et al. 1994; Addiss et al. 1997; Ismail et al. 1998; McLaughlin et al. 2003).”
Background
Symptoms reported after mass drug administration for lymphatic filariasis in Leogane, Haiti.
Hochberg, N., Michel, M., Lammie, P., Mathieu, E., Direny, A. N., de Rochars, M. B., & Addiss, D. (2006) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2006.75.928 · Cited by 13
“The filariasis program started there in 2000, and since that time, between 55,000 and 102,000 people have been treated annually with anti-filarial mass drug administration (MDA).(4,5) By treating the entire at-risk community, the program aims to decrease the prevalence and density of circulating microfilaria (MF) and…”
BackgroundSelf-citation
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
Kshirsagar, N., Gogtay, N. J., Garg, B., Deshmukh, P., Rajgor, D., Kadam, V., Thakur, P., Gupta, A., Ingole, N., & Lazdins-Helds, J. (2017) · Parasitology Research · doi:10.1007/s00436-017-5577-9 · Cited by 9
“…and Training in Tropical Diseases, Product Research and Development, 20 Avenue Appia, Geneva 27, 1211 Geneva, CH, Switzerland Single dose of albendazole (ABZ) and diethylcarbamazine (DEC) combination clears Mf for prolonged periods in bancroftian infection (Addiss et al. 1997; Ismail et al. 1998).”
Drug Treatment of Tropical Parasitic Infections
Stephenso, I., & Wiselka, M. (2000) · Drugs · doi:10.2165/00003495-200060050-00002 · Cited by 9
“[49,53] Enhanced suppression of microfilaraemia has also been foundwith ivermectin in combination with albendazole, although the mechanism is unclear.[56] In a recent study,[56] 832 Haitian children infected with W.”
Background
Impact of single-dose ivermectin on community microfilaria load in bancroftian filariasis infection: two years post treatment.
Gyapong, J. (2000) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/s0035-9203(00)90133-0 · Cited by 9
A Qualitative Study on the Adverse Reactions of Mass Treatment for Lymphatic Filariasis in Orissa, India
Babu, B. (2010) · doi:10.1016/s1995-7645(10)60033-8 · Cited by 9
Results From 2 Cohort Studies in Central Africa Show That Clearance of Wuchereria bancrofti Infection After Repeated Rounds of Mass Drug Administration With Albendazole Alone Is Closely Linked to Individual Adherence
Campillo, J., Awaca-Uvon, N.-P., Missamou, F., Tambwe, J., Kuyangisa-Simuna, G., Weil, G., Louya, F., Boussinesq, M., Pion, S., & Chesnais, C. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1232 · Cited by 8
Translating Research into Reality: Elimination of Lymphatic Filariasis from Haiti
Lammie, P., Eberhard, M., Addiss, D., Won, K. Y., BeaudeRochars, M., Direny, A. N., Milord, M., Lafontant, J. G., & Streit, T. (2017) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.16-0669 · Cited by 8
Self-citation
A New Outlook in Lymphatic Filariasis Elimination in India
Ghosh, S. K., & Srivastava, P. K. (2020) · Parasitology and Microbiology Research · doi:10.5772/intechopen.92454 · Cited by 7
Lymphadenovarix of the head-neck region--a rare presentation of Bancroftian filariasis.
Dwivedi, R. C., Gupta, P., Dwivedi, R. C., Kishore, K., & Bhatia, N. (2009) · Journal of Tropical Pediatrics · doi:10.1093/tropej/fmn111 · Cited by 7
Hospital-based safety and tolerability study to assess efficacy of oral doxycycline in the treatment of Wuchereria bancrofti infection in north-eastern Tanzania.
Makunde, W., Kamugisha, L., Makunde, R., Malecela, M., & Kitua, A. (2009) · Tanzania Health Research Bulletin · doi:10.4314/thrb.v8i3.45109 · Cited by 5
Ivermectin in Clinical Practice
Zaha, O., Hirata, T., Kinjo, F., & Saito, A. (2003) · Elsevier eBooks · doi:10.1016/b978-012526451-8/50009-6 · Cited by 5
Post-Treatment Surveillance for Lymphatic Filariasis in Plateau and Nasarawa States, Nigeria: Results of Transmission Assessment Surveys
Eigege, A., Noland, G. S., Adelamo, S. E., Nwodu, K., Sallau, A., Umaru, J., Mancha, B. S., Davies, E., Danboyi, J., Kadimbo, J., et al. (2020) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.20-0020 · Cited by 4
“bancrofti mf in circulation.(28,29) Therefore, can areas that continue to provide ivermectin truly be considered as in the “PTS” phase? From the onchocerciasis perspective, WHO guidelines indicate that PTS for onchocerciasis cannot begin until LF MDA stops in co-endemic areas.”
Background
Another tropical-drug donation.
Sharp, D. (1998) · The Lancet · doi:10.1016/s0140-6736(05)78352-5 · Cited by 4
[Recommendations for the treatment of bancroftian filariasis in symptomless and diseased patients].
Dreyer, G., Dreyer, P., & Norões, J. (2002) · Revista da Sociedade Brasileira de Medicina Tropical · doi:10.1590/s0037-86822002000100009 · Cited by 3
296 – Antiparasitic Agents
Ryan, E. (2018) · doi:10.1016/b978-0-323-40181-4.00296-6 · Cited by 3
Pharmacokinetics of UMF-078, a candidate antifilarial drug, in infected dogs.
Theplertboon, R., Fleckenstein, L., Dzimianski, M., & McCall, J. (2000) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2000.62.86 · Cited by 3
Antifilarial treatment strategies: a systematic review and network meta-analysis
Albadrani, M., Molla, A., Elbadawy, H. M., Eltahir, H. M., Sriram, S., Abouzied, M., & Elsayed, E. (2025) · BMC Infectious Diseases · doi:10.1186/s12879-025-11105-z · Cited by 2
Utilisation de 1' ivermectine en médecine tropicale
Dupouy-Camet, J., Yéra, H., & Tourte-Schaefer, C. (2003) · doi:10.1016/s0929-693x(03)90035-2 · Cited by 2
Le prix Nobel de Médecine 2015 au service des pays tropicaux
Danis, M., & Richard-Lenoble, D. (2016) · médecine/sciences · doi:10.1051/medsci/20163201018 · Cited by 3
“Plusieurs recherches seront conduites sur des associations de l’ivermectine soit à la DEC [19] soit à l’albendazole, un anthelminthique polyvalent utilisé depuis des années pour les verminoses intestinales, dont le rôle dans le traitement de masse de la filariose lymphatique a été identifié [20, 21].”
Background
Albendazole.
Venkatesan, P. (1998) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/41.2.145 · Cited by 1
“In children infected with Wuchereria bancrofti a combination of single doses of ivermectin and albendazole (400 mg) reduces microfilaraemia significantly more than a single dose of ivermectin, alone and this combination holds promise for the future.(28) In conclusion, albendazole has an important role in the treatment…”
Les médicaments anti-infectieux non antibiotiques en urologie
Bruyère, F., Désoubeaux, G., Malavaud, S., Fourcade, C. R., Chandenier, J., Lachaud, L., Guy, L., Karsenty, G., Bastide, C., Lavigne, J.-P., et al. (2013) · The French Journal of Urology · doi:10.1016/j.purol.2013.09.003 · Cited by 1
Treatment for lymphatic filariasis and elephantiasis.
Fox, L. M., Beach, M., & Lammie, P. (2008) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.299.6.632
Self-citation
Early-Stage Elephantiasis in Bancroftian Filariasis
Grobusch, M., Göbels, K., Teichmann, D., Bergmann, F., & Suttorp, N. (2001) · European Journal of Clinical Microbiology and Infectious Diseases · doi:10.1007/s100960100619
Abstracts
(1998) · doi:10.1177/004947559802800336
Water and Lymphatic Filariasis
Misra-Bhattacharya, S., Kushwaha, S., & Bajpai, P. (2014) · Springer eBooks · doi:10.1007/978-81-322-1029-0_16

Authors: Addiss, D. G., Beach, M. J., Streit, T. G., Lutwick, S., LeConte, F. H., Lafontant, J. G., Hightower, A. W., & Lammie, P. J.
Affiliations: Centers for Disease Control and Prevention (US)
University of Georgia (US)
Maimonides Medical Center (US)
ORCID: Addiss, David G
Hightower, Allen W
Venue: The Lancet
Publisher: Elsevier BV
Published: 1997-08
Volume: 350
Issue: 9076
Pages: 480-484
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(97)02231-9
OpenAlex: W2110486035
Cited by: 116
References: 18
Citations by year: 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 2
FWCI: 5.71
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Funders: United States Agency for International Development
Topics: Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
Keywords: lymphatic filariasis, Wuchereria bancrofti, microfilaremia, ivermectin, albendazole, children, treatment efficacy, tolerability, Haiti, intestinal helminth infection, periodic treatment, adverse effects
MeSH terms: Animals, Child, Child, Preschool, Drug Therapy, Combination, Female, Filariasis, Filaricides, Haiti, Humans, Ivermectin, Male, Wuchereria bancrofti, Albendazole, Treatment Outcome, Parasitemia

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Randomised placebo-controlled comparison of ivermectin and albendazole alone and in combination for Wuchereria bancrofti microfilaraemia in Haitian children

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