Skip to main content
Top
Published in: Malaria Journal 1/2019

Open Access 01-12-2019 | Fertility | Research

The effect of ivermectin® on fertility, fecundity and mortality of Anopheles arabiensis fed on treated men in Ethiopia

Authors: Wondemeneh Mekuriaw, Meshesha Balkew, Louisa A. Messenger, Delenasaw Yewhalaw, Adugna Woyessa, Fekadu Massebo

Published in: Malaria Journal | Issue 1/2019

Login to get access

Abstract

Background

Insecticide resistance is a growing threat to malaria vector control. Ivermectin, either administered to humans or animals, may represent an alternate strategy to reduce resistant mosquito populations. The aim of this study was to assess the residual or delayed effect of administering a single oral dose of ivermectin to humans on the survival, fecundity and fertility of Anopheles arabiensis in Ethiopia.

Methods

Six male volunteers aged 25–40 years (weight range 64–72 kg) were recruited; four of them received a recommended single oral dose of 12 mg ivermectin and the other two individuals were untreated controls. A fully susceptible insectary colony of An. arabiensis was fed on treated and control participants at 1, 4, 7, 10 and 13 days post ivermectin-administration. Daily mosquito mortality was recorded for 5 days. An. arabiensis fecundity and fertility were measured from day 7 post treatment, by dissection to examine the number of eggs per mosquito, and by observing larval hatching rates, respectively.

Results

Ivermectin treatment induced significantly higher An. arabiensis mortality on days 1 and 4, compared to untreated controls (p = 0.02 and p < 0.001, respectively). However, this effect had declined by day 7, with no significant difference in mortality between treated and control groups (p = 0.06). The mean survival time of mosquitoes fed on day 1 was 2.1 days, while those fed on day 4 survived 4.0 days. Mosquitoes fed on the treatment group at day 7 and 10 produced significantly lower numbers of eggs compared to the untreated controls (p < 0.001 and p = 0.04, respectively). An. arabiensis fed on day 7 on treated men also had lower larval hatching rates than mosquitoes fed on days 10 and 13 (p = 0.003 and p = 0.001, respectively).

Conclusion

A single oral dose of ivermectin given to humans can induce mortality and reduce survivorship of An. arabiensis for 7 days after treatment. Ivermectin also had a delayed effect on fecundity of An. arabiensis that took bloodmeals from treated individuals on day 7 and 10. Additional studies are warranted using wild, insecticide-resistant mosquito populations, to confirm findings and a phase III evaluation among community members in Ethiopia is needed to determine the impact of ivermectin on malaria transmission.
Literature
2.
go back to reference WHO. World malaria report. Geneva: World Health Organization; 2018. WHO. World malaria report. Geneva: World Health Organization; 2018.
3.
go back to reference Christian R, Koekemoer L, Fettene M, Olana D, Coetzee M. Insecticide resistance in Anopheles arabiensis from Ethiopia. African Entomol. 2013;21:89–94.CrossRef Christian R, Koekemoer L, Fettene M, Olana D, Coetzee M. Insecticide resistance in Anopheles arabiensis from Ethiopia. African Entomol. 2013;21:89–94.CrossRef
5.
go back to reference Kenea O, Balkew M, Tekie H, Gebre-Michael T, Deressa W, Loha E, et al. Human-biting activities of Anopheles species in south-central Ethiopia. Parasit Vectors. 2016;9:527.CrossRef Kenea O, Balkew M, Tekie H, Gebre-Michael T, Deressa W, Loha E, et al. Human-biting activities of Anopheles species in south-central Ethiopia. Parasit Vectors. 2016;9:527.CrossRef
6.
go back to reference WHO. Control of residual malaria parasit transmission. Geneva: World Health Organization; 2014. WHO. Control of residual malaria parasit transmission. Geneva: World Health Organization; 2014.
7.
go back to reference Massebo F, Balkew M, Gebre-Michael T, Lindtjørn B. Zoophagic behaviour of anopheline mosquitoes in southwest Ethiopia: opportunity for malaria vector control. Parasit Vectors. 2015;8:645.CrossRef Massebo F, Balkew M, Gebre-Michael T, Lindtjørn B. Zoophagic behaviour of anopheline mosquitoes in southwest Ethiopia: opportunity for malaria vector control. Parasit Vectors. 2015;8:645.CrossRef
8.
go back to reference WHO. Global technical strategy for malaria 2016–2030. Geneva: World Health Organization; 2015. WHO. Global technical strategy for malaria 2016–2030. Geneva: World Health Organization; 2015.
9.
go back to reference WHO. Ivermectin for malaria transmission control: technical consultation meeting. Geneva: World Health Organization; 2016. WHO. Ivermectin for malaria transmission control: technical consultation meeting. Geneva: World Health Organization; 2016.
10.
go back to reference Chaccour CJ, Kobylinski KC, Bassat Q, Bousema T, Drakeley C, Alonso P, et al. Ivermectin to reduce malaria transmission: a research agenda for a promising new tool for elimination. Malar J. 2013;12:153.CrossRef Chaccour CJ, Kobylinski KC, Bassat Q, Bousema T, Drakeley C, Alonso P, et al. Ivermectin to reduce malaria transmission: a research agenda for a promising new tool for elimination. Malar J. 2013;12:153.CrossRef
11.
go back to reference Chaccour CJ, Rabinovich NR, Slater H, Canavati SE, Bousema T, Lacerda M, et al. Establishment of the Ivermectin Research for Malaria Elimination Network: updating the research agenda. Malar J. 2015;14:243.CrossRef Chaccour CJ, Rabinovich NR, Slater H, Canavati SE, Bousema T, Lacerda M, et al. Establishment of the Ivermectin Research for Malaria Elimination Network: updating the research agenda. Malar J. 2015;14:243.CrossRef
12.
go back to reference Campbell WC. Ivermectin: a reflection on simplicity (Nobel lecture). Angew Chem Int Ed Engl. 2016;55:10184–9.CrossRef Campbell WC. Ivermectin: a reflection on simplicity (Nobel lecture). Angew Chem Int Ed Engl. 2016;55:10184–9.CrossRef
13.
go back to reference Thylefors B. The Mectizan donation program (MDP). Ann Trop Med Parasitol. 2008;102:39–44.CrossRef Thylefors B. The Mectizan donation program (MDP). Ann Trop Med Parasitol. 2008;102:39–44.CrossRef
14.
go back to reference Ottesen EA, Hooper PJ, Bradley M, Biswas G. The global programme to eliminate lymphatic filariasis: health impact after 8 years. PLoS Negl Trop Dis. 2008;2:e317.CrossRef Ottesen EA, Hooper PJ, Bradley M, Biswas G. The global programme to eliminate lymphatic filariasis: health impact after 8 years. PLoS Negl Trop Dis. 2008;2:e317.CrossRef
15.
go back to reference Chosidow O, Giraudeau B, Cottrell J, Izri A, Hofmann R, Mann SG, et al. Oral ivermectin versus malathion lotion for difficult-to-treat head lice. N Engl J Med. 2010;362:896–905.CrossRef Chosidow O, Giraudeau B, Cottrell J, Izri A, Hofmann R, Mann SG, et al. Oral ivermectin versus malathion lotion for difficult-to-treat head lice. N Engl J Med. 2010;362:896–905.CrossRef
16.
go back to reference Richard-Lenoble D, Chandenier J, Gaxotte P. Ivermectin and filariasis. Fundam Clin Pharmacol. 2003;17:199–203.CrossRef Richard-Lenoble D, Chandenier J, Gaxotte P. Ivermectin and filariasis. Fundam Clin Pharmacol. 2003;17:199–203.CrossRef
17.
go back to reference Kobylinski KC, Sylla M, Chapman PL, Sarr MD, Foy BD. Ivermectin mass drug administration to humans disrupts malaria parasite transmission in Senegalese villages. Am J Trop Med Hyg. 2011;85:3–5.CrossRef Kobylinski KC, Sylla M, Chapman PL, Sarr MD, Foy BD. Ivermectin mass drug administration to humans disrupts malaria parasite transmission in Senegalese villages. Am J Trop Med Hyg. 2011;85:3–5.CrossRef
18.
go back to reference Chaccour C, Lines J, Whitty CJ. Effect of ivermectin on Anopheles gambiae mosquitoes fed on humans: the potential of oral insecticides in malaria control. J Infect Dis. 2010;202:113–6.CrossRef Chaccour C, Lines J, Whitty CJ. Effect of ivermectin on Anopheles gambiae mosquitoes fed on humans: the potential of oral insecticides in malaria control. J Infect Dis. 2010;202:113–6.CrossRef
20.
go back to reference Kobylinski KC, Deus KM, Butters MP, Hongyu T, Gray M, da Silva IM, et al. The effect of oral anthelmintics on the survivorship and re-feeding frequency of anthropophilic mosquito disease vectors. Acta Trop. 2010;116:119–26.CrossRef Kobylinski KC, Deus KM, Butters MP, Hongyu T, Gray M, da Silva IM, et al. The effect of oral anthelmintics on the survivorship and re-feeding frequency of anthropophilic mosquito disease vectors. Acta Trop. 2010;116:119–26.CrossRef
21.
go back to reference Cully D. Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature. 1994;371:707–11.CrossRef Cully D. Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature. 1994;371:707–11.CrossRef
22.
go back to reference Chaccour CJ, Hammann F, Alustiza M, Castejon S, Tarimo BB, Abizanda G, et al. Cytochrome P450/ABC transporter inhibition simultaneously enhances ivermectin pharmacokinetics in the mammal host and pharmacodynamics in Anopheles gambiae. Sci Rep. 2017;7:8535.CrossRef Chaccour CJ, Hammann F, Alustiza M, Castejon S, Tarimo BB, Abizanda G, et al. Cytochrome P450/ABC transporter inhibition simultaneously enhances ivermectin pharmacokinetics in the mammal host and pharmacodynamics in Anopheles gambiae. Sci Rep. 2017;7:8535.CrossRef
23.
go back to reference Balkew M, Ibrahim M, Koekemoer LL, Brooke BD, Engers H, Aseffa A, et al. Insecticide resistance in Anopheles arabiensis (Diptera: Culicidae) from villages in central, northern and south west Ethiopia and detection of kdr mutation. Parasit Vectors. 2010;3:40.CrossRef Balkew M, Ibrahim M, Koekemoer LL, Brooke BD, Engers H, Aseffa A, et al. Insecticide resistance in Anopheles arabiensis (Diptera: Culicidae) from villages in central, northern and south west Ethiopia and detection of kdr mutation. Parasit Vectors. 2010;3:40.CrossRef
24.
go back to reference WHO. Test procedures for insecticide resistance monitoring in malaria vector mosquitoes. Geneva: World Health Organization; 2016. WHO. Test procedures for insecticide resistance monitoring in malaria vector mosquitoes. Geneva: World Health Organization; 2016.
25.
go back to reference Pampiglione S, Majori G, Petrangeli G, Romi R. Avermectins, MK-933 and MK-936, for mosquito control. Trans R Soc Trop Med Hyg. 1985;79:797–9.CrossRef Pampiglione S, Majori G, Petrangeli G, Romi R. Avermectins, MK-933 and MK-936, for mosquito control. Trans R Soc Trop Med Hyg. 1985;79:797–9.CrossRef
26.
go back to reference Derua YA, Kisinza WN, Simonsen PE. Differential effect of human ivermectin treatment on blood feeding Anopheles gambiae and Culex quinquefasciatus. Parasit Vectors. 2015;8:130.CrossRef Derua YA, Kisinza WN, Simonsen PE. Differential effect of human ivermectin treatment on blood feeding Anopheles gambiae and Culex quinquefasciatus. Parasit Vectors. 2015;8:130.CrossRef
27.
go back to reference Smit MR, Ochomo EO, Aljayyoussi G, Kwambai TK, Abong’o BO, Chen T, et al. Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2018;18:615–26.CrossRef Smit MR, Ochomo EO, Aljayyoussi G, Kwambai TK, Abong’o BO, Chen T, et al. Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2018;18:615–26.CrossRef
28.
go back to reference Foley D, Bryan J, Lawrence G. The potential of ivermectin to control the malaria vector Anopheles farauti. Trans R Soc Trop Med Hyg. 2000;94:625–8.CrossRef Foley D, Bryan J, Lawrence G. The potential of ivermectin to control the malaria vector Anopheles farauti. Trans R Soc Trop Med Hyg. 2000;94:625–8.CrossRef
29.
go back to reference Fritz M, Siegert P, Walker E, Bayoh M, Vulule J, Miller J. Toxicity of bloodmeals from ivermectin-treated cattle to Anopheles gambiae s.l. Ann Trop Med Parasitol. 2009;103:539–47.CrossRef Fritz M, Siegert P, Walker E, Bayoh M, Vulule J, Miller J. Toxicity of bloodmeals from ivermectin-treated cattle to Anopheles gambiae s.l. Ann Trop Med Parasitol. 2009;103:539–47.CrossRef
30.
go back to reference Alout H, Krajacich BJ, Meyers JI, Grubaugh ND, Brackney DE, Kobylinski KC, et al. Evaluation of ivermectin mass drug administration for malaria transmission control across different West African environments. Malar J. 2014;13:417.CrossRef Alout H, Krajacich BJ, Meyers JI, Grubaugh ND, Brackney DE, Kobylinski KC, et al. Evaluation of ivermectin mass drug administration for malaria transmission control across different West African environments. Malar J. 2014;13:417.CrossRef
31.
go back to reference Gardner K, Meisch M, Meek C, Biven W. Effects of ivermectin in canine blood on Anopheles quadrimaculatus, Aedes albopictus and Culex salinarius. J Am Mosq Control Assoc. 1993;9:400–2.PubMed Gardner K, Meisch M, Meek C, Biven W. Effects of ivermectin in canine blood on Anopheles quadrimaculatus, Aedes albopictus and Culex salinarius. J Am Mosq Control Assoc. 1993;9:400–2.PubMed
32.
go back to reference Jones J, Meisch M, Meek C, Bivin W. Lethal effects of ivermectin on Anopheles quadrimaculatus. J Am Mosq Control Assoc. 1992;8:278–80.PubMed Jones J, Meisch M, Meek C, Bivin W. Lethal effects of ivermectin on Anopheles quadrimaculatus. J Am Mosq Control Assoc. 1992;8:278–80.PubMed
33.
go back to reference Bockarie M, Hii J, Alexander N, Bockarie F, Dagoro H, Kazura J, et al. Mass treatment with ivermectin for filariasis control in Papua New Guinea: impact on mosquito survival. Med Vet Entomol. 1999;13:120–3.CrossRef Bockarie M, Hii J, Alexander N, Bockarie F, Dagoro H, Kazura J, et al. Mass treatment with ivermectin for filariasis control in Papua New Guinea: impact on mosquito survival. Med Vet Entomol. 1999;13:120–3.CrossRef
34.
go back to reference Smit MR, Ochomo EO, Waterhouse D, Kwambai TK, Abong’o BO, Bousema T, et al. Pharmacokinetics-pharmacodynamics of high-dose ivermectin with dihydroartemisinin–piperaquine on mosquitocidal activity and QT-prolongation (IVERMAL). Clin Pharmacol Ther. 2019;105:388–401.CrossRef Smit MR, Ochomo EO, Waterhouse D, Kwambai TK, Abong’o BO, Bousema T, et al. Pharmacokinetics-pharmacodynamics of high-dose ivermectin with dihydroartemisinin–piperaquine on mosquitocidal activity and QT-prolongation (IVERMAL). Clin Pharmacol Ther. 2019;105:388–401.CrossRef
35.
go back to reference Sampaio VS, Beltrán TP, Kobylinski KC, Melo GC, Lima JB, Silva SG, et al. Filling gaps on ivermectin knowledge: effects on the survival and reproduction of Anopheles aquasalis, a Latin American malaria vector. Malar J. 2016;15:491.CrossRef Sampaio VS, Beltrán TP, Kobylinski KC, Melo GC, Lima JB, Silva SG, et al. Filling gaps on ivermectin knowledge: effects on the survival and reproduction of Anopheles aquasalis, a Latin American malaria vector. Malar J. 2016;15:491.CrossRef
36.
go back to reference Chaccour C, Rabinovich NR. Ivermectin to reduce malaria transmission II. Considerations regarding clinical development pathway. Malar J. 2017;16:166.CrossRef Chaccour C, Rabinovich NR. Ivermectin to reduce malaria transmission II. Considerations regarding clinical development pathway. Malar J. 2017;16:166.CrossRef
37.
go back to reference Tesh RB, Guzman H. Mortality and infertility in adult mosquitoes after the ingestion of blood containing ivermectin. Am J Trop Med Hyg. 1990;43:229–33.CrossRef Tesh RB, Guzman H. Mortality and infertility in adult mosquitoes after the ingestion of blood containing ivermectin. Am J Trop Med Hyg. 1990;43:229–33.CrossRef
Metadata
Title
The effect of ivermectin® on fertility, fecundity and mortality of Anopheles arabiensis fed on treated men in Ethiopia
Authors
Wondemeneh Mekuriaw
Meshesha Balkew
Louisa A. Messenger
Delenasaw Yewhalaw
Adugna Woyessa
Fekadu Massebo
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2019
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-019-2988-3

Other articles of this Issue 1/2019

Malaria Journal 1/2019 Go to the issue