Randomised placebo-controlled comparison of ivermectin and albendazole alone and in combination for Wuchereria bancrofti microfilaraemia in Haitian children
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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A single reduced dose of albendazole (400 or 600 mg) in combination with either ivermectin (200-400 μg/kg) or DEC (6 mg/kg) proved to have both long-term effectiveness and safety in decreasing microfilaremia in W. bancrofti infection.
“a single reduced dose (400 or 600 mg), in combination with either ivermectin (200–400 μg/kg) or DEC (6 mg/kg), was tried; this new regimen proved to have both long-term effectiveness and safety in decreasing microfilaremia in W. bancrofti infection [195,196]”
From Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update (2021) · cites this paper as [195]
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“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.”
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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 · see citing works
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).”
BackgroundSymptoms 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-citationKshirsagar, 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.”
BackgroundGyapong, J. (2000) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/s0035-9203(00)90133-0 · Cited by 9
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 · see citing works
Self-citationA 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 · see citing works
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
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 · see citing works
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.”
BackgroundAnother 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
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 · see citing works
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
Danis, M., & Richard-Lenoble, D. (2016) · doi:10.1051/medsci/20163201018 · Cited by 2
“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].”
BackgroundVenkatesan, 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 · see citing works
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-citationEarly-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
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)
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 1997-08
- Volume
- 350
- Issue
- 9076
- Pages
- 480-484
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- 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
- 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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