{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T18:55:00Z","timestamp":1784746500960,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"European &amp; Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["CSA2016S-1618"],"award-info":[{"award-number":["CSA2016S-1618"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swedish International Development Cooperation Agency","award":["CSA2016S-1618"],"award-info":[{"award-number":["CSA2016S-1618"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Ivermectin and albendazole (IA) combination preventive chemotherapy to all at-risk populations is deployed to eliminate lymphatic filariasis. Although safety monitoring is imperative, data from Sub-Saharan Africa is scarce. We conducted a large-scale active safety surveillance of adverse events (AEs) following IA mass drug administration (MDA) to identify the type, incidence, and associated risk factors in Tanzania. After recording sociodemographic, clinical, and medical histories, 9640 eligible residents received single-dose IA combination preventive chemotherapy. Treatment-associated AEs were actively monitored through house-to-house visits on day 1, day 2, and day 7 of MDA. Events reported before and after MDA were cross-checked and verified to identify MDA-associated AEs. 9288 participants (96.3%) completed the seven-day safety follow-up, of whom 442 reported 719 MDA-associated AEs. The incidence of experiencing one or more type of MDA-associated AE was 4.8% (95% CI = 4.3\u20135.2%); this being significantly higher among those with Pre-MDA clinical events than those without (8.5% versus 4.1%, p &lt; 0.001). AEs were mild (83.8%), moderate (15.9%), and severe (0.3%), and most resolved within 72 h. The incidence of experiencing one, two, \u2265 three types of AEs were 2.8%, 1.3%, and 0.6%, respectively. The most common AEs were headache (1.23%), drowsiness (1.15%), fever (1.12%), and dizziness (1.06%). A chronic illness, or clinical manifestation of lymphatic filariasis, or being female or pre-existing clinical symptoms were independent significant predictors of AEs. IA combination preventive chemotherapy is safe and tolerable, and associated AEs are mild-to-moderate and transient, with few severe AEs. Safety monitoring during MDA campaigns in individuals with underlying clinical conditions is recommended for timely detection and management of AEs.<\/jats:p>","DOI":"10.3390\/ph15050594","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T05:10:32Z","timestamp":1652332232000},"page":"594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Safety and Tolerability of Ivermectin and Albendazole Mass Drug Administration in Lymphatic Filariasis Endemic Communities of Tanzania: A Cohort Event Monitoring Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Adam M.","family":"Fimbo","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Huddinge, Stockholm, Sweden"},{"name":"Tanzania Medicines and Medical Devices Authority (TMDA), Dar es Salaam P.O. Box 77150, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omary Mashiku","family":"Minzi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam P.O. Box 65013, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7232-8708","authenticated-orcid":false,"given":"Bruno P.","family":"Mmbando","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, Tanga Center, Tanga P.O. Box 5004, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5997-1157","authenticated-orcid":false,"given":"Parthasarathi","family":"Gurumurthy","sequence":"additional","affiliation":[{"name":"Pharmacovigilance and Clinical Trials, Botswana Medicines Regulatory Authority, Gaborone 999106, Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Appolinary A. R.","family":"Kamuhabwa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam P.O. Box 65013, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9788-0790","authenticated-orcid":false,"given":"Eleni","family":"Aklillu","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Huddinge, Stockholm, Sweden"},{"name":"Tanzania Medicines and Medical Devices Authority (TMDA), Dar es Salaam P.O. Box 77150, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"ref_1","unstructured":"WHO (2017). Guideline: Alternative Mass Drug Administration Regimens to Eliminate Lymphatic Filariasis, World Health Organization."},{"key":"ref_2","unstructured":"WHO (2022, April 01). Lymphatic Filariasis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/lymphatic-filariasis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S0140-6736(10)60586-7","article-title":"Lymphatic filariasis and onchocerciasis","volume":"376","author":"Taylor","year":"2010","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3347\/kjp.2008.46.3.119","article-title":"Clinical and pathological aspects of filarial lymphedema and its management","volume":"46","author":"Shenoy","year":"2008","journal-title":"Korean J. Parasitol."},{"key":"ref_5","unstructured":"World Health Organization (2022, February 07). Preventive Chemotherapy in Human Helminthiasis. Coordinated Use of Anthelminthic Drugs in Control Interventions: A Manual for Health Professionals and Programme Managers. Available online: https:\/\/www.who.int\/publications\/i\/item\/9241547103."},{"key":"ref_6","unstructured":"World Health Organization (2022, March 02). Accelerating Work to Overcome the Global Impact of NTDs: 2011\u20132020 Progress Dashboard. Available online: https:\/\/www.who.int\/teams\/control-of-neglected-tropical-diseases\/overview\/progress-dashboard-2011-2020."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Budge, P.J., Herbert, C., Andersen, B.J., and Weil, G.J. (2018). Adverse events following single dose treatment of lymphatic filariasis: Observations from a review of the literature. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006454"},{"key":"ref_8","unstructured":"World Health Organization (2022, April 12). Safety in Administering Medicines for Neglected Tropical Diseases. Geneva. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240024144."},{"key":"ref_9","unstructured":"(2022, April 02). Neglected Tropical Diseases Control Program Tanzania. Lymphatic Filariasis. Available online: https:\/\/www.ntdcp.go.tz\/diseases\/lf."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kiguba, R., Olsson, S., and Waitt, C. (2021). Pharmacovigilance in low- and middle-income countries: A review with particular focus on Africa. Br. J. Clin. Pharmacol.","DOI":"10.22541\/au.163256723.39408938\/v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s40264-019-00898-z","article-title":"Comparative Assessment of the National Pharmacovigilance Systems in East Africa: Ethiopia, Kenya, Rwanda and Tanzania","volume":"43","author":"Barry","year":"2020","journal-title":"Drug Saf."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Barry, A., Olsson, S., Khaemba, C., Kabatende, J., Dires, T., Fimbo, A., Minzi, O., Bienvenu, E., Makonnen, E., and Kamuhabwa, A. (2021). Comparative Assessment of the Pharmacovigilance Systems within the Neglected Tropical Diseases Programs in East Africa-Ethiopia, Kenya, Rwanda, and Tanzania. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18041941"},{"key":"ref_13","unstructured":"World Health Organization (2022, April 12). A Practical Handbook on the Pharmacovigilance of Antiretroviral Medicines. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/44236\/9789241547949_eng.pdf?sequence=1&isAllowed=y."},{"key":"ref_14","unstructured":"World Health Organization (2022, April 02). A Practical Handbook on the Pharmacovigilance of Medicines Used in the Treatment of Tuberculosis: Enhancing the Safety of the TB Patient, World Health Organization, Geneva. Available online: https:\/\/www.who.int\/medicines\/publications\/Pharmaco_TB_web_v3.pdf."},{"key":"ref_15","unstructured":"WHO (2022, February 08). The Safety of Medicines in Public Health Programmes. Geneva. Available online: http:\/\/www.who.int\/medicines\/areas\/quality_safety\/safety_efficacy\/Pharmacovigilance_B.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1054","DOI":"10.1016\/S2214-109X(18)30415-7","article-title":"Safe mass drug administration for neglected tropical diseases","volume":"6","author":"Dorlo","year":"2018","journal-title":"Lancet Glob. Health"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Campillo, J.T., Boussinesq, M., Bertout, S., Faillie, J.L., and Chesnais, C.B. (2021). Serious adverse reactions associated with ivermectin: A systematic pharmacovigilance study in sub-Saharan Africa and in the rest of the World. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009354"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1002\/sim.1157","article-title":"On the assessment of adverse drug reactions from spontaneous reporting systems: The influence of under-reporting on odds ratios","volume":"21","year":"2002","journal-title":"Stat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Khaemba, C., Barry, A., Omondi, W.P., Bota, K., Matendechero, S., Wandera, C., Siyoi, F., Kirui, E., Oluka, M., and Nambwa, P. (2021). Safety and Tolerability of Mass Diethylcarbamazine and Albendazole Administration for the Elimination of Lymphatic Filariasis in Kenya: An Active Surveillance Study. Pharmaceuticals, 14.","DOI":"10.3390\/ph14030264"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Minzi, O.M., Mnkugwe, R.H., Ngaimisi, E., Kinung\u2019hi, S., Hansson, A., Pohanka, A., Kamuhabwa, A., and Aklillu, E. (2021). Effect of Dihydroartemisinin-Piperaquine on the Pharmacokinetics of Praziquantel for Treatment of Schistosoma mansoni Infection. Pharmaceuticals, 14.","DOI":"10.3390\/ph14050400"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"712084","DOI":"10.3389\/fphar.2021.712084","article-title":"Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania","volume":"12","author":"Mnkugwe","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1080\/17425255.2021.1971194","article-title":"The impact of catha edulis (vahl) forssk. ex endl. (celestraceae) (khat) on pharmacokinetics of clinically used drugs","volume":"17","author":"Aklillu","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12726","DOI":"10.1038\/s41598-018-31191-1","article-title":"Effects of Khat (Catha edulis) use on catalytic activities of major drug-metabolizing cytochrome P450 enzymes and implication of pharmacogenetic variations","volume":"8","author":"Bedada","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fimbo, A.M., Minzi, O.M.S., Mmbando, B.P., Barry, A., Nkayamba, A.F., Mwamwitwa, K.W., Malishee, A., Seth, M.D., Makunde, W.H., and Gurumurthy, P. (2020). Prevalence and Correlates of Lymphatic Filariasis Infection and Its Morbidity Following Mass Ivermectin and Albendazole Administration in Mkinga District, North-Eastern Tanzania. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051550"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Palmeirim, M.S., Hurlimann, E., Knopp, S., Speich, B., Belizario, V., Joseph, S.A., Vaillant, M., Olliaro, P., and Keiser, J. (2018). Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006458"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Patel, C., Hurlimann, E., Keller, L., Hattendorf, J., Sayasone, S., Ali, S.M., Ame, S.M., Coulibaly, J.T., and Keiser, J. (2019). Efficacy and safety of ivermectin and albendazole co-administration in school-aged children and adults infected with Trichuris trichiura: Study protocol for a multi-country randomized controlled double-blind trial. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-3882-x"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1473-3099(14)71050-3","article-title":"Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: A four-arm, randomised controlled trial","volume":"15","author":"Speich","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1179\/000349803235001697","article-title":"The co-administration of ivermectin and albendazole--safety, pharmacokinetics and efficacy against Onchocerca volvulus","volume":"97","author":"Awadzi","year":"2003","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tavul, L., Laman, M., Howard, C., Kotty, B., Samuel, A., Bjerum, C., O\u2019Brian, K., Kumai, S., Amuga, M., and Lorry, L. (2022). Safety and efficacy of mass drug administration with a single-dose triple-drug regimen of albendazole + diethylcarbamazine + ivermectin for lymphatic filariasis in Papua New Guinea: An open-label, cluster-randomised trial. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010096"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Edi, C., Bjerum, C.M., Ouattara, A.F., Chhonker, Y.S., Penali, L.K., Meite, A., Koudou, B.G., Weil, G.J., King, C.L., and 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\u2019Ivoire. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007325"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Weil, G.J., Bogus, J., Christian, M., Dubray, C., Djuardi, Y., Fischer, P.U., Goss, C.W., Hardy, M., Jambulingam, P., and King, C.L. (2019). The safety of double- and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study. PLoS Med., 16.","DOI":"10.1371\/journal.pmed.1002839"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2165\/00128071-200102060-00001","article-title":"Do women have more adverse drug reactions?","volume":"2","author":"Rademaker","year":"2001","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_33","first-page":"335","article-title":"Influence of age, sex and seriousness on reporting of adverse drug reactions in Sweden. Pharmacoepidemiol","volume":"26","author":"Holm","year":"2017","journal-title":"Drug Saf."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13293-020-00308-5","article-title":"Sex differences in pharmacokinetics predict adverse drug reactions in women","volume":"11","author":"Zucker","year":"2020","journal-title":"Biol. Sex Differ."},{"key":"ref_35","first-page":"581","article-title":"Female sex as a risk factor for adverse drug reactions","volume":"73","author":"Nakagawa","year":"2015","journal-title":"Nihon Rinsho"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100188","DOI":"10.1016\/j.eclinm.2019.10.001","article-title":"Reported adverse drug reactions in women and men: Aggregated evidence from globally collected individual case reports during half a century","volume":"17","author":"Watson","year":"2019","journal-title":"EClinicalMedicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1093\/infdis\/jix578","article-title":"Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis","volume":"217","author":"Andersen","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1475-2883-2-4","article-title":"Lymphoedema: Pathophysiology and management in resource-poor settings\u2014Relevance for lymphatic filariasis control programmes","volume":"2","author":"Vaqas","year":"2003","journal-title":"Filaria J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/0035-9203(95)90031-4","article-title":"Chronic pulmonary disorders, including tropical pulmonary eosinophilia, in villages with endemic lymphatic filariasis in Tanga region and in Tanga town, Tanzania","volume":"89","author":"Magnussen","year":"1995","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s12936-017-1801-4","article-title":"Ivermectin to reduce malaria transmission I. Pharmacokinetic and pharmacodynamic considerations regarding efficacy and safety","volume":"16","author":"Chaccour","year":"2017","journal-title":"Malar. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"745","DOI":"10.4269\/ajtmh.1992.46.745","article-title":"Renal abnormalities in microfilaremic patients with Bancroftian filariasis","volume":"46","author":"Dreyer","year":"1992","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.2165\/11593830-000000000-00000","article-title":"Modified prescription-event monitoring studies: A tool for pharmacovigilance and risk management","volume":"34","author":"Layton","year":"2011","journal-title":"Drug Saf."},{"key":"ref_43","unstructured":"(2022, February 14). Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, Available online: https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/ctcae_v5_quick_reference_8.5x11.pdf."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/5\/594\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:09:38Z","timestamp":1760137778000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/5\/594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,12]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ph15050594"],"URL":"https:\/\/doi.org\/10.3390\/ph15050594","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,12]]}}}