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Open Access 01-12-2017 | Review

Ivermectin to reduce malaria transmission II. Considerations regarding clinical development pathway

Authors: Carlos Chaccour, N. Regina Rabinovich

Published in: Malaria Journal | Issue 1/2017

Abstract

The development of ivermectin as a complementary vector control tool will require good quality evidence. This paper reviews the different eco-epidemiological contexts in which mass drug administration with ivermectin could be useful. Potential scenarios and pharmacological strategies are compared in order to help guide trial design. The rationale for a particular timing of an ivermectin-based tool and some potentially useful outcome measures are suggested.

Bhatt S, Weiss DJ, Cameron E, Bisanzio D, Mappin B, Dalrymple U, et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature. 2015;526:207–11.CrossRefPubMedPubMedCentral

The_malERA_Consultative_Group_on_Vector_Control. A research agenda for malaria eradication: vector control. PLoS Med. 2011;8:e1000401.CrossRefPubMedCentral

Ranson H, Lissenden N. Insecticide resistance in African Anopheles mosquitoes: a worsening situation that needs urgent action to maintain malaria control. Trends Parasitol. 2016;32:187–96.CrossRefPubMed

Killeen GF. Characterizing, controlling and eliminating residual malaria transmission. Malar J. 2014;13:330.CrossRefPubMedPubMedCentral

Omura S, Crump A. Ivermectin: panacea for resource-poor communities? Trends Parasitol. 2014;30:445–55.CrossRefPubMed

Vontas J, Moore S, Kleinschmidt I, Ranson H, Lindsay S, Lengeler C, et al. Framework for rapid assessment and adoption of new vector control tools. Trends Parasitol. 2014;30:191–204.CrossRefPubMed

The_malERA_Consultative_Group_on_Drugs. A research agenda for malaria eradication: drugs. PLoS Med. 2011;8:e1000402.CrossRefPubMedCentral

WHO. Single dose Primaquine as a gametocytocide in Plasmodium falciparum malaria. Geneva: World Health Organization; 2012.

Burrows JN, Duparc S, Gutteridge WE, van Huijsduijnen RH, Kaszubska W, Macintyre F, et al. New developments in anti-malarial target candidate and product profiles. Malar J. 2017;16:26.CrossRefPubMedPubMedCentral

10.

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.CrossRefPubMedPubMedCentral

11.

Foy BD, Kobylinski KC, da Silva IM, Rasgon JL, Sylla M. Endectocides for malaria control. Trends Parasitol. 2011;27:423–8.CrossRefPubMedPubMedCentral

12.

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.CrossRefPubMedPubMedCentral

13.

Fritz ML, Siegert PY, Walker ED, Bayoh MN, Vulule JR, Miller JR. Toxicity of bloodmeals from ivermectin-treated cattle to Anopheles gambiae s.l. Ann Trop Med Parasitol. 2009;103:539–47.CrossRefPubMed

14.

Gardner K, Meisch MV, Meek CL, Biven WS. Effects of ivermectin in canine blood on Anopheles quadrimaculatus, Aedes albopictus and Culex salinarius. J Am Mosq Control Assoc. 1993;9:400–2.PubMed

15.

Kobylinski KC, Foy BD, Richardson JH. Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae. Malar J. 2012;11:381.CrossRefPubMedPubMedCentral

16.

Kobylinski K, Ubalee R, Ponlawat A, McCardle W, Foy B, Szumlas D et al. Ivermectin inhibits the development of Plasmodium vivax in Anopheles dirus. In: 64th Annual meeting of the American Society of Tropical Medicine and Hygiene; 2015 Oct 25–29; Philadelphia, USA.

17.

da Cruz FP, Martin C, Buchholz K, Lafuente-Monasterio MJ, Rodrigues T, Sonnichsen B, et al. Drug screen targeted at Plasmodium liver stages identifies a potent multistage antimalarial drug. J Infect Dis. 2012;205:1278–86.CrossRefPubMedPubMedCentral

18.

Macdonald G. The analysis of equilibrium in malaria. Trop Dis Bull. 1952;49:813–29.PubMed

19.

WHO Vector Control Advisory Group on New Tools. Operational procedures. Geneva: World Health Organization. http://www.who.int/neglected_diseases/vector_ecology/Operational_procedures_for_VCAG.pdf?ua=1. Accessed 10 Apr 2017.

20.

Durnez LC, Coosemans M. Residual transmission of malaria: an old issue for new approaches. In: Manguin S, editor. Anopheles mosquitoes—new insights into malaria vectors. InTech; 2014.

21.

WHO. Technical Note: control of residual malaria parasite transmission. Geneva: World Health Organization; 2014.

22.

WHO. WHO malaria terminology. http://apps.who.int/iris/bitstream/10665/208815/1/WHO_HTM_GMP_2016.6_eng.pdf. Accessed Feb 2017. Geneva: World Health Organization; 2016.

23.

Njoroge MM, Tirados I, Lindsay SW, Vale GA, Torr SJ, Fillinger U. Exploring the potential of using cattle for malaria vector surveillance and control: a pilot study in western Kenya. Parasit Vectors. 2017;10:18.CrossRefPubMedPubMedCentral

24.

Waite JL, Swain S, Lynch PA, Sharma SK, Haque MA, Montgomery J, et al. Increasing the potential for malaria elimination by targeting zoophilic vectors. Sci Rep. 2017;7:40551.CrossRefPubMedPubMedCentral

25.

Kiware SS, Chitnis N, Devine GJ, Moore SJ, Majambere S, Killeen GF. Biologically meaningful coverage indicators for eliminating malaria transmission. Biol Lett. 2012;8:874–7.CrossRefPubMedPubMedCentral

26.

Knox TB, Juma EO, Ochomo EO, Jamet HP, Ndungo L, Chege P, et al. An online tool for mapping insecticide resistance in major Anopheles vectors of human malaria parasites and review of resistance status for the Afrotropical region. Parasit Vectors. 2014;7:76.CrossRefPubMedPubMedCentral

27.

WHO. Global plan for insecticide resistance management in malaria vectors (GPIRM). Geneva: World Health Organization; 2012.

28.

Mnzava AP, Knox TB, Temu EA, Trett A, Fornadel C, Hemingway J, et al. Implementation of the global plan for insecticide resistance management in malaria vectors: progress, challenges and the way forward. Malar J. 2015;14:173.CrossRefPubMedPubMedCentral

29.

Kleinschmidt I. Implications of insecticide resistance: key evaluation findings and implications for malaria vector control. In: Oral presentation during the 65th Annual Meeting of the ASTMH Atlanta; 2016.

30.

Pooda HS, Rayaisse JB, Hien DF, Lefevre T, Yerbanga SR, Bengaly Z, et al. Administration of ivermectin to peridomestic cattle: a promising approach to target the residual transmission of human malaria. Malar J. 2015;13(Suppl 1):496.CrossRefPubMed

31.

Meyers JI, Gray M, Kuklinski W, Johnson LB, Snow CD, Black WCt, et al. Characterization of the target of ivermectin, the glutamate-gated chloride channel, from Anopheles gambiae. J Exp Biol. 2015;218:1478–86.CrossRefPubMedPubMedCentral

32.

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, et al. SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010;38:D237–43.CrossRefPubMed

33.

Schinkel AH, Wagenaar E, van Deemter L, Mol CA, Borst P. Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest. 1995;96:1698–705.CrossRefPubMedPubMedCentral

34.

Butters MP, Kobylinski KC, Deus KM, da Silva IM, Gray M, Sylla M, et al. Comparative evaluation of systemic drugs for their effects against Anopheles gambiae. Acta Trop. 2012;121:34–43.CrossRefPubMed

35.

Moonen B, Cohen JM, Tatem AJ, Cohen J, Hay SI, Sabot O, et al. A framework for assessing the feasibility of malaria elimination. Malar J. 2010;9:322.CrossRefPubMedPubMedCentral

36.

WHO. From malaria control to malaria elimination: a manual for elimination scenario planning. Geneva: World Health Organization; 2014.

37.

Kobylinski K, Ponlawat A, Ubalee R, Schuster A, McCardle W, Foy B et al. Assessing ivermectin susceptibility of Greater Mekong Subregion malaria vectors. In: Poster session presented at: annual meeting of the American Society of Tropical Medicine and Hygiene; 2014 Nov 2–6; New Orleans, USA.

38.

Griffin JT. The interaction between seasonality and pulsed interventions against malaria in their effects on the reproduction number. PLoS Comput Biol. 2015;11:e1004057.CrossRefPubMedPubMedCentral

39.

Moonasar D, Maharaj R, Kunene S, Candrinho B, Saute F, Ntshalintshali N, et al. Towards malaria elimination in the MOSASWA (Mozambique, South Africa and Swaziland) region. Malar J. 2016;15:419.CrossRefPubMedPubMedCentral

40.

Southern African Development Community: malaria elimination 8 (E8). http://tis.sadc.int/english/sarn/elimination-eight-e8/. Accessed 02 Feb 2017.

41.

Churcher TS, Trape JF, Cohuet A. Human-to-mosquito transmission efficiency increases as malaria is controlled. Nat Commun. 2015;6:6054.CrossRefPubMedPubMedCentral

42.

Maude RJ, Pontavornpinyo W, Saralamba S, Aguas R, Yeung S, Dondorp AM, et al. The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia. Malar J. 2009;8:31.CrossRefPubMedPubMedCentral

43.

Chaccour C, Hammann F, Rabinovich NR. Ivermectin to reduce malaria transmission I. Pharmacokinetic considerations regarding efficacy and safety. Malar J. 2017. doi:10.1186/s12936-017-1801-4.

44.

Slater HC, Walker PG, Bousema T, Okell LC, Ghani AC. The potential impact of adding ivermectin to a mass treatment intervention to reduce malaria transmission: a modelling study. J Infect Dis. 2014;210:1972–80.CrossRefPubMed

45.

Ouedraogo AL, Bastiaens GJ, Tiono AB, Guelbeogo WM, Kobylinski KC, Ouedraogo A, et al. Efficacy and safety of the mosquitocidal drug ivermectin to prevent malaria transmission after treatment: a double-blind, randomized, clinical trial. Clin Infect Dis. 2015;60:357–65.CrossRefPubMed

46.

Escobedo-Vargas KS, López-Sifuentes VM, Durand S, Baldeviano GC, Gerbasi RV, Vásquez GM, et al. The effect of ivermectin on the Amazonian malaria vector Anopheles darlingi: LC50 determination. In: Poster session presented at the 65th annual meeting of the American Society of Tropical Medicine and Hygiene; 2016 Nov 11–16; Atlanta, USA. 2016.

47.

Sampaio VS, Beltran 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.CrossRefPubMedPubMedCentral

48.

Chaccour C, Killeen GF. Mind the gap: residual malaria transmission, veterinary endectocides and livestock as targets for malaria vector control. Malar J. 2016;15:24.CrossRefPubMedPubMedCentral

49.

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.CrossRefPubMedPubMedCentral

50.

Sylla M, Kobylinski KC, Gray M, Chapman PL, Sarr MD, Rasgon JL, et al. Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors. Malar J. 2010;9:365.CrossRefPubMedPubMedCentral

51.

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.CrossRefPubMedPubMedCentral

52.

IVERMAL. Study information. www.Clinicaltrials.org. http://clinicaltrials.gov/ct2/show/record/NCT02511353?term=ivermectin&rank=6. Accessed Aug 2015.

53.

RIMDAMAL. Study information. www.Clinicaltrials.org. http://clinicaltrials.gov/ct2/show/NCT02509481?term=NCT02509481&rank=1. Accessed Aug 2015.

54.

Foy BD. Results from RIMDAMAL, a pilot randomized cluster-design trial in Burkina Faso, designed to assess the safety and efficacy of repeat ivermectin mass drug administrations to control malaria and NTDs. In: Oral presentation during the 65th annual meeting of the ASTMH Atlanta; 2016.

55.

Chaccour C, Barrio A, Royo AGG, Urbistondo DM, Slater H, Hammann F, et al. Screening for an ivermectin slow-release formulation suitable for malaria vector control. Malar J. 2015;14:102.CrossRefPubMedPubMedCentral

56.

Bellinger AM, Jafari M, Grant TM, Zhang S, Slater HC, Wenger EA, et al. Oral, ultra-long-lasting drug delivery: application toward malaria elimination goals. Sci Transl Med. 2016;8:365ra157.CrossRefPubMed

57.

Chaccour C, Abizanda G, Irigoyen A, Del Pozo JL. Slow release ivermectin formulation for malaria control: a pilot study in 80-kg Pigs. Antimicrob Agents Chemother. 2017;61:pii-e02104-16.CrossRef

58.

Killeen GF, Seyoum A, Gimnig JE, Stevenson JC, Drakeley CJ, Chitnis N. Made-to-measure malaria vector control strategies: rational design based on insecticide properties and coverage of blood resources for mosquitoes. Malar J. 2014;13:146.CrossRefPubMedPubMedCentral

59.

Chaccour CJ, Rabinovich NR. Oral, slow-release ivermectin: biting back at malaria vectors. Trends Parasitol. 2017;33:156–8.CrossRefPubMed

60.

Moonen B, Cohen JM, Snow RW, Slutsker L, Drakeley C, Smith DL, et al. Operational strategies to achieve and maintain malaria elimination. Lancet. 2010;376:1592–603.CrossRefPubMedPubMedCentral

61.

Killeen GF. A second chance to tackle African malaria vector mosquitoes that avoid houses and don’t take drugs. Am J Trop Med Hyg. 2013;88:809–16.CrossRefPubMedPubMedCentral

62.

Molineaux L, Gramiccia G. The Garki project. Geneva: World Health Organization; 1980.

63.

Tusting LS, Bousema T, Smith DL, Drakeley C. Measuring changes in Plasmodium falciparum transmission: precision, accuracy and costs of metrics. Adv Parasitol. 2014;84:151–208.CrossRefPubMedPubMedCentral

64.

Pinder M, Moorthy VS, Mendis K, Brown GV, on behalf of the WHO MALVAC committee. MALVAC 2010: measures of efficacy of anti-malarial interventions against malaria transmission. Geneva: WHO; 2010.

65.

WHO. Preferred product characteristics (PPC) for malaria vaccines. Geneva: World Health Organization; 2014.

66.

Shaukat AM, Breman JG, McKenzie FE. Using the entomological inoculation rate to assess the impact of vector control on malaria parasite transmission and elimination. Malar J. 2010;9:122.CrossRefPubMedPubMedCentral

67.

Stuckey EM, Miller JM, Littrell M, Chitnis N, Steketee R. Operational strategies of anti-malarial drug campaigns for malaria elimination in Zambia’s southern province: a simulation study. Malar J. 2016;15:148.CrossRefPubMedPubMedCentral

68.

Delrieu I, Leboulleux D, Ivinson K, Gessner BD. Malaria Transmission Blocking Vaccine Technical Consultation G. Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine. Vaccine. 2015;33:1518–26.CrossRefPubMed

69.

Wilson AL, Boelaert M, Kleinschmidt I, Pinder M, Scott TW, Tusting LS, et al. Evidence-based vector control? Improving the quality of vector control trials. Trends Parasitol. 2015;31:380–90.CrossRefPubMed

70.

Nunes JK, Woods C, Carter T, Raphael T, Morin MJ, Diallo D, et al. Development of a transmission-blocking malaria vaccine: progress, challenges, and the path forward. Vaccine. 2014;32:5531–9.CrossRefPubMed

71.

Chaccour C, Rabinovich NR. Ivermectin to reduce malaria transmission III. Considerations regarding regulatory and policy pathways. Malaria J. 2017. doi:10.1186/s12936-017-1803-2.

72.

Stone WJ, Eldering M, van Gemert GJ, Lanke KH, Grignard L, van de Vegte-Bolmer MG, et al. The relevance and applicability of oocyst prevalence as a read-out for mosquito feeding assays. Sci Rep. 2013;3:3418.CrossRefPubMedPubMedCentral

73.

Blagborough AM, Churcher TS, Upton LM, Ghani AC, Gething PW, Sinden RE. Transmission-blocking interventions eliminate malaria from laboratory populations. Nat Commun. 2013;4:1812.CrossRefPubMedPubMedCentral

74.

MPAC meeting, 14–16 September 2016: Update on a proposed Ivermectin target product profile. http://www.whoint/entity/malaria/mpac/mpac-sept2016-invermectin-session9pdf?ua=1. Accessed Oct 2016.

75.

Schneider P, Wolters L, Schoone G, Schallig H, Sillekens P, Hermsen R, et al. Real-time nucleic acid sequence-based amplification is more convenient than real-time PCR for quantification of Plasmodium falciparum. J Clin Microbiol. 2005;43:402–5.CrossRefPubMedPubMedCentral

76.

Cook J, Aydin-Schmidt B, Gonzalez IJ, Bell D, Edlund E, Nassor MH, et al. Loop-mediated isothermal amplification (LAMP) for point-of-care detection of asymptomatic low-density malaria parasite carriers in Zanzibar. Malar J. 2015;14:43.CrossRefPubMedPubMedCentral

77.

Drakeley CJ, Corran PH, Coleman PG, Tongren JE, McDonald SL, Carneiro I, et al. Estimating medium- and long-term trends in malaria transmission by using serological markers of malaria exposure. Proc Natl Acad Sci USA. 2005;102:5108–13.CrossRefPubMedPubMedCentral

78.

Mueller I, Schoepflin S, Smith TA, Benton KL, Bretscher MT, Lin E, et al. Force of infection is key to understanding the epidemiology of Plasmodium falciparum malaria in Papua New Guinean children. Proc Natl Acad Sci USA. 2012;109:10030–5.CrossRefPubMedPubMedCentral

Title: Ivermectin to reduce malaria transmission II. Considerations regarding clinical development pathway
Authors: Carlos Chaccour
N. Regina Rabinovich
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Malaria Journal / Issue 1/2017
Electronic ISSN: 1475-2875
DOI: https://doi.org/10.1186/s12936-017-1802-3

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