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Published in: Malaria Journal 1/2003

Open Access 01-12-2003 | Research

Epidemiological models for the spread of anti-malarial resistance

Authors: JC Koella, R Antia

Published in: Malaria Journal | Issue 1/2003

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Abstract

Background

The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance.

Methods

We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance.

Results

In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population.

Conclusions

The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.
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Literature
1.
go back to reference Moore DV, Lanier JE: Observations on two Plasmodium falciparum infections with abnormal response to chloroquine. Am J Trop Med Hyg. 1961, 10: 5-9.PubMed Moore DV, Lanier JE: Observations on two Plasmodium falciparum infections with abnormal response to chloroquine. Am J Trop Med Hyg. 1961, 10: 5-9.PubMed
2.
go back to reference Hakim SL, Roohi SWAS, Zurkurnai Y, Rain AN, Mansor SM, Palmer K, Navaratnam V, Mak JW: Plasmodium falciparum – increased proportion of severe resistance (RII and RIII) to chloroquine and high rate of resistance to sulfadoxine-pyrimethamine in peninsular Malaysia after 2 decades. Trans R Soc Trop Med Hyg. 1996, 90: 294-297.CrossRef Hakim SL, Roohi SWAS, Zurkurnai Y, Rain AN, Mansor SM, Palmer K, Navaratnam V, Mak JW: Plasmodium falciparum – increased proportion of severe resistance (RII and RIII) to chloroquine and high rate of resistance to sulfadoxine-pyrimethamine in peninsular Malaysia after 2 decades. Trans R Soc Trop Med Hyg. 1996, 90: 294-297.CrossRef
3.
go back to reference Smithius FM, Monti F, Grundl M, Oo AZ, Kyaw TT, Phe O, White MJ: Plasmodium falciparum: sensitivity in vivo to chloroquine, pyrimethamine/sulfadoxine and mefloquine in western Myanmar. Trans R Soc Trop Med Hyg. 1997, 91: 468-472.CrossRef Smithius FM, Monti F, Grundl M, Oo AZ, Kyaw TT, Phe O, White MJ: Plasmodium falciparum: sensitivity in vivo to chloroquine, pyrimethamine/sulfadoxine and mefloquine in western Myanmar. Trans R Soc Trop Med Hyg. 1997, 91: 468-472.CrossRef
4.
go back to reference Mockenhaupt F: Mefloquine resistance in Plasmodium falciparum. Parasitol Today. 1995, 11: 248-253. 10.1016/0169-4758(95)80201-0.CrossRefPubMed Mockenhaupt F: Mefloquine resistance in Plasmodium falciparum. Parasitol Today. 1995, 11: 248-253. 10.1016/0169-4758(95)80201-0.CrossRefPubMed
5.
go back to reference Benito A, Roche J, Molina R, Amela C, Alvar J: In vitro susceptibility of Plasmodium falciparum to chloroquine, amodiaquine, quinine, mefloquine, and sulfadoxine/pyrimethamine in Equatorial Guinea. Am J Trop Med Hyg. 1995, 53: 526-531.PubMed Benito A, Roche J, Molina R, Amela C, Alvar J: In vitro susceptibility of Plasmodium falciparum to chloroquine, amodiaquine, quinine, mefloquine, and sulfadoxine/pyrimethamine in Equatorial Guinea. Am J Trop Med Hyg. 1995, 53: 526-531.PubMed
6.
go back to reference White NJ: Delaying antimalarial drug resistance with combination chemotherapy. Parassitologia. 1999, 41: 301-8.PubMed White NJ: Delaying antimalarial drug resistance with combination chemotherapy. Parassitologia. 1999, 41: 301-8.PubMed
7.
go back to reference White N: Antimalarial drug resistance and combination chemotherapy. Phil Trans R Soc London B Biol Sci. 1999, 354: 739-49. 10.1098/rstb.1999.0426.CrossRef White N: Antimalarial drug resistance and combination chemotherapy. Phil Trans R Soc London B Biol Sci. 1999, 354: 739-49. 10.1098/rstb.1999.0426.CrossRef
8.
go back to reference Bonhoeffer S, Lipsitch M, Levin BR: Evaluating treatment protocols to prevent antibiotic resistance. Proc Nat Acad Sci USA. 1997, 94: 12106-12111. 10.1073/pnas.94.22.12106.PubMedCentralCrossRefPubMed Bonhoeffer S, Lipsitch M, Levin BR: Evaluating treatment protocols to prevent antibiotic resistance. Proc Nat Acad Sci USA. 1997, 94: 12106-12111. 10.1073/pnas.94.22.12106.PubMedCentralCrossRefPubMed
9.
go back to reference Macdonald G: The Epidemiology and Control of Malaria. London: Oxford University Press. 1957 Macdonald G: The Epidemiology and Control of Malaria. London: Oxford University Press. 1957
10.
go back to reference Dietz K, Molineaux L, Thomas A: A malaria model tested in the African savannah. Bull Wrld Hlth Assoc. 1974, 50: 347-357. Dietz K, Molineaux L, Thomas A: A malaria model tested in the African savannah. Bull Wrld Hlth Assoc. 1974, 50: 347-357.
11.
go back to reference Molineaux L, Gramiccia G: The Garki Project: Research on the Epidemiology and Control of Malaria in the Sudan Savanna of West Africa. Geneva: World Health Organization. 1980 Molineaux L, Gramiccia G: The Garki Project: Research on the Epidemiology and Control of Malaria in the Sudan Savanna of West Africa. Geneva: World Health Organization. 1980
12.
go back to reference Halloran ME, Struchiner CJ: Modeling transmission dynamics of stage-specific malaria vaccines. Parasitol Today. 1992, 8: 77-85. 10.1016/0169-4758(92)90240-3.CrossRefPubMed Halloran ME, Struchiner CJ: Modeling transmission dynamics of stage-specific malaria vaccines. Parasitol Today. 1992, 8: 77-85. 10.1016/0169-4758(92)90240-3.CrossRefPubMed
13.
go back to reference Gupta S, Anderson RM: Predicting the effects of malaria vaccines on the population dynamics of infection and disease. In: Malaria Vaccine Development: A Multi-Immune Response Approach. Edited by: Hoffman SL. 1996, Washington DC: ASM Press, S24-276. Gupta S, Anderson RM: Predicting the effects of malaria vaccines on the population dynamics of infection and disease. In: Malaria Vaccine Development: A Multi-Immune Response Approach. Edited by: Hoffman SL. 1996, Washington DC: ASM Press, S24-276.
14.
go back to reference Curtis CF, Otoo LN: A simple model of the build-up of resistance to mixtures of anti-malarial drugs. Trans R Soc Trop Med Hyg. 1986, 80: 889-892.CrossRefPubMed Curtis CF, Otoo LN: A simple model of the build-up of resistance to mixtures of anti-malarial drugs. Trans R Soc Trop Med Hyg. 1986, 80: 889-892.CrossRefPubMed
15.
go back to reference Dye C, Williams BG: Multigenic drug resistance among inbred malaria parasites. Proc R Soc London Ser B Biol Sci. 1997, 264: 61-67. 10.1098/rspb.1997.0009.CrossRef Dye C, Williams BG: Multigenic drug resistance among inbred malaria parasites. Proc R Soc London Ser B Biol Sci. 1997, 264: 61-67. 10.1098/rspb.1997.0009.CrossRef
16.
go back to reference Hastings IM: A model for the origins and spread of drug resistant malaria. Parasitology. 1997, 115: 133-141. 10.1017/S0031182097001261.CrossRefPubMed Hastings IM: A model for the origins and spread of drug resistant malaria. Parasitology. 1997, 115: 133-141. 10.1017/S0031182097001261.CrossRefPubMed
17.
go back to reference Aron JL: Acquired immunity dependent upon exposure in an SIRS epidemic model. Math Biosc. 1988, 88: 37-47. 10.1016/0025-5564(88)90047-8.CrossRef Aron JL: Acquired immunity dependent upon exposure in an SIRS epidemic model. Math Biosc. 1988, 88: 37-47. 10.1016/0025-5564(88)90047-8.CrossRef
18.
go back to reference Aron JL: Mathematical modelling of immunity to malaria. Math Biosc. 1988, 90: 385-396. 10.1016/0025-5564(88)90076-4.CrossRef Aron JL: Mathematical modelling of immunity to malaria. Math Biosc. 1988, 90: 385-396. 10.1016/0025-5564(88)90076-4.CrossRef
19.
go back to reference Boyd MF: Epidemiology: factors related to the definitive host. In: Malariology. A Comprehensive Survey of All Aspects of This Group of Diseases from a Global Standpoint. Edited by: Boyd MF. 1949, Philadelphia: W.B. Saunders, 1: 608-697. Boyd MF: Epidemiology: factors related to the definitive host. In: Malariology. A Comprehensive Survey of All Aspects of This Group of Diseases from a Global Standpoint. Edited by: Boyd MF. 1949, Philadelphia: W.B. Saunders, 1: 608-697.
20.
go back to reference Aron JL, May RM: The population dynamics of malaria. In: The Population Dynamics of Infectious Diseases: Theory and Applications. Edited by: Anderson RM. 1982, London: Chapman and Hall, 139-179.CrossRef Aron JL, May RM: The population dynamics of malaria. In: The Population Dynamics of Infectious Diseases: Theory and Applications. Edited by: Anderson RM. 1982, London: Chapman and Hall, 139-179.CrossRef
21.
go back to reference Nowak MA, May RM: Superinfection and the evolution of parasite virulence. Proc R Soc London Ser B Biol Sci. 1994, 255: 81-89.CrossRef Nowak MA, May RM: Superinfection and the evolution of parasite virulence. Proc R Soc London Ser B Biol Sci. 1994, 255: 81-89.CrossRef
22.
go back to reference Comins HN: The development of insecticide resistance in the presence of migration. J theor Biol. 1977, 64: 177-197.CrossRefPubMed Comins HN: The development of insecticide resistance in the presence of migration. J theor Biol. 1977, 64: 177-197.CrossRefPubMed
23.
go back to reference Bremermann HJ, Thieme HR: A competitive-exclusion principle for pathogen virulence. J math Biol. 1989, 27: 179-190.CrossRefPubMed Bremermann HJ, Thieme HR: A competitive-exclusion principle for pathogen virulence. J math Biol. 1989, 27: 179-190.CrossRefPubMed
24.
go back to reference Wernsdorfer WH: The development and spread of drug-resistant malaria. Parasitol Today. 1991, 7: 297-303. 10.1016/0169-4758(91)90262-M.CrossRefPubMed Wernsdorfer WH: The development and spread of drug-resistant malaria. Parasitol Today. 1991, 7: 297-303. 10.1016/0169-4758(91)90262-M.CrossRefPubMed
25.
go back to reference Kilombero Malaria Project: Household based malaria control in a highly endemic area of Africa (Tanzania): determinants of transmission and disease and indicators for monitoring. Memorias do Instituto Oswaldo Cruz. 1992, 87: 121-130.CrossRef Kilombero Malaria Project: Household based malaria control in a highly endemic area of Africa (Tanzania): determinants of transmission and disease and indicators for monitoring. Memorias do Instituto Oswaldo Cruz. 1992, 87: 121-130.CrossRef
26.
go back to reference Handunnetti SM, Gunewardena DM, Pathirana PPSL, Ekanayake K, Weerasinghe S, Mendis KN: Features of recrudescent chloroquine-resistant Plasmodium falciparum infections confer a survival advantage on parasites and have implications for disease control. Trans R Soc Trop Med Hyg. 1996, 90: 563-567.CrossRefPubMed Handunnetti SM, Gunewardena DM, Pathirana PPSL, Ekanayake K, Weerasinghe S, Mendis KN: Features of recrudescent chloroquine-resistant Plasmodium falciparum infections confer a survival advantage on parasites and have implications for disease control. Trans R Soc Trop Med Hyg. 1996, 90: 563-567.CrossRefPubMed
27.
go back to reference Ichimori K, Curtis CF, Targett GAT: The effects of chloroquine on the infectivity of chloroquine-sensitive and -resistant populations of Plasmodium yoelii nigeriensis to mosquitoes. Parasitology. 1990, 100: 377-381.CrossRefPubMed Ichimori K, Curtis CF, Targett GAT: The effects of chloroquine on the infectivity of chloroquine-sensitive and -resistant populations of Plasmodium yoelii nigeriensis to mosquitoes. Parasitology. 1990, 100: 377-381.CrossRefPubMed
28.
go back to reference Robert V, Molez J-F, Trape J-F: Short report: gametocytes, chloroquine pressure, and the relative parasite survival advantage of resistant strains of falciparum malaria in West Africa. Am J Trop Med Hyg. 1996, 55: 350-351.PubMed Robert V, Molez J-F, Trape J-F: Short report: gametocytes, chloroquine pressure, and the relative parasite survival advantage of resistant strains of falciparum malaria in West Africa. Am J Trop Med Hyg. 1996, 55: 350-351.PubMed
29.
go back to reference Koella JC: Linking evolutionary ecology with epidemiology. Rév Suisse Zool. 1994, 101: 865-874.CrossRef Koella JC: Linking evolutionary ecology with epidemiology. Rév Suisse Zool. 1994, 101: 865-874.CrossRef
30.
go back to reference Peters W: Chemotherapy and Drug Resistance in Malaria. London: Academic Press. 1987 Peters W: Chemotherapy and Drug Resistance in Malaria. London: Academic Press. 1987
31.
go back to reference Molineaux L: The epidemiology of drug resistance in malaria: an unfinished conceptual model. WHO informal consultation on the epidemiology of drug resistance of malaria parasites. 1986, Working paper 2.7.1: Molineaux L: The epidemiology of drug resistance in malaria: an unfinished conceptual model. WHO informal consultation on the epidemiology of drug resistance of malaria parasites. 1986, Working paper 2.7.1:
32.
go back to reference Anderson RA, Knols BJG, Koella JC: Plasmodium falciparum sporozoites increase feeding-associated mortality of their mosquito hosts Anopheles gambiae s.l. Parasitology. 2000, 120: 329-333. 10.1017/S0031182099005570.CrossRefPubMed Anderson RA, Knols BJG, Koella JC: Plasmodium falciparum sporozoites increase feeding-associated mortality of their mosquito hosts Anopheles gambiae s.l. Parasitology. 2000, 120: 329-333. 10.1017/S0031182099005570.CrossRefPubMed
33.
go back to reference Klein TA, Harrison BA, Grove JS, Dixon SV, André RG: Correlation of survival rates of Anopheles dirus A (Diptera: Culicidae) with different infection densities of Plasmodium cynomolgi. Bull Wrld Hlth Assoc. 1986, 64: 901-907. Klein TA, Harrison BA, Grove JS, Dixon SV, André RG: Correlation of survival rates of Anopheles dirus A (Diptera: Culicidae) with different infection densities of Plasmodium cynomolgi. Bull Wrld Hlth Assoc. 1986, 64: 901-907.
34.
go back to reference Anderson RM, May RM: Infectious Diseases of Humans: Dynamics and Control. Oxford: Oxford University Press. 1991 Anderson RM, May RM: Infectious Diseases of Humans: Dynamics and Control. Oxford: Oxford University Press. 1991
35.
go back to reference Koella JC: On the use of mathematical models of malaria transmission. Acta Trop. 1991, 49: 1-25. 10.1016/0001-706X(91)90026-G.CrossRefPubMed Koella JC: On the use of mathematical models of malaria transmission. Acta Trop. 1991, 49: 1-25. 10.1016/0001-706X(91)90026-G.CrossRefPubMed
36.
go back to reference Lipsitch M, Bergstrom CT, Levin BR: The epidemiology of antibiotic resistance in hospitals: paradoxes and prescriptions. Proc Nat Acad Sci USA. 2000, 97: 1938-1943. 10.1073/pnas.97.4.1938.PubMedCentralCrossRefPubMed Lipsitch M, Bergstrom CT, Levin BR: The epidemiology of antibiotic resistance in hospitals: paradoxes and prescriptions. Proc Nat Acad Sci USA. 2000, 97: 1938-1943. 10.1073/pnas.97.4.1938.PubMedCentralCrossRefPubMed
37.
go back to reference Blower SM, Small PM, Hopewell PC: Control strategies for tuberculosis epidemics: new models for old problems. Science. 1996, 273: 497-500.CrossRefPubMed Blower SM, Small PM, Hopewell PC: Control strategies for tuberculosis epidemics: new models for old problems. Science. 1996, 273: 497-500.CrossRefPubMed
38.
go back to reference Blower SM, Aschenbach AN, Gershengorn HB, Kahn JO: Predicting the unpredictable: transmission of drug-resistant HIV. Nat Med. 2001, 7: 1016-20. 10.1038/nm0901-1016.CrossRefPubMed Blower SM, Aschenbach AN, Gershengorn HB, Kahn JO: Predicting the unpredictable: transmission of drug-resistant HIV. Nat Med. 2001, 7: 1016-20. 10.1038/nm0901-1016.CrossRefPubMed
39.
go back to reference Mercado R, Vijh S, Allen SE, Kerksiek K, Pilip IM, Pamer EG: Early programming of T cell populations responding to bacterial infection. J Immunol. 2000, 165: 6833-9.CrossRefPubMed Mercado R, Vijh S, Allen SE, Kerksiek K, Pilip IM, Pamer EG: Early programming of T cell populations responding to bacterial infection. J Immunol. 2000, 165: 6833-9.CrossRefPubMed
40.
go back to reference Gupta S, Maiden MCJ, Feavers IM, Nee S, May RM, Anderson RM: The maintenance of strain structure in populations of recombining infectious agents. Nature Med. 1996, 2: 437-442.CrossRefPubMed Gupta S, Maiden MCJ, Feavers IM, Nee S, May RM, Anderson RM: The maintenance of strain structure in populations of recombining infectious agents. Nature Med. 1996, 2: 437-442.CrossRefPubMed
41.
go back to reference Tibayrenc M, Ayala FJ: Towards a population genetic theory of micro-organisms: the clonal theory of parasitic protozoa. Parasitol Today. 1991, 7: 228-232. 10.1016/0169-4758(91)90234-F.CrossRefPubMed Tibayrenc M, Ayala FJ: Towards a population genetic theory of micro-organisms: the clonal theory of parasitic protozoa. Parasitol Today. 1991, 7: 228-232. 10.1016/0169-4758(91)90234-F.CrossRefPubMed
42.
go back to reference Cross AP, Singer B: Modelling the development of resistance of Plasmodium falciparum to anti-malarial drugs. Trans R Soc Trop Med Hyg. 1991, 85: 349-355.CrossRefPubMed Cross AP, Singer B: Modelling the development of resistance of Plasmodium falciparum to anti-malarial drugs. Trans R Soc Trop Med Hyg. 1991, 85: 349-355.CrossRefPubMed
43.
go back to reference Dye C: Population genetics of nonclonal, nonrandomly mating malaria parasites. Parasitol Today. 1991, 7: 236-240. 10.1016/0169-4758(91)90236-H.CrossRefPubMed Dye C: Population genetics of nonclonal, nonrandomly mating malaria parasites. Parasitol Today. 1991, 7: 236-240. 10.1016/0169-4758(91)90236-H.CrossRefPubMed
44.
go back to reference Dye C: Models for investigating genetic exchange in protozoan populations. In: Modelling Vector-borne and Other Parasitic Diseases. Edited by: Perry BD, Hansen JW. 1994, Nairobi: ILRAD, 165-176. Dye C: Models for investigating genetic exchange in protozoan populations. In: Modelling Vector-borne and Other Parasitic Diseases. Edited by: Perry BD, Hansen JW. 1994, Nairobi: ILRAD, 165-176.
45.
go back to reference Hastings IM, Mackinnon MJ: The emergence of drug-resistant malaria. Parasitology. 1998, 117: 411-417. 10.1017/S0031182098003291.CrossRefPubMed Hastings IM, Mackinnon MJ: The emergence of drug-resistant malaria. Parasitology. 1998, 117: 411-417. 10.1017/S0031182098003291.CrossRefPubMed
46.
go back to reference Clyde DF: Malaria in Tanzania. Oxford: Oxford Univerity Press. 1967 Clyde DF: Malaria in Tanzania. Oxford: Oxford Univerity Press. 1967
Metadata
Title
Epidemiological models for the spread of anti-malarial resistance
Authors
JC Koella
R Antia
Publication date
01-12-2003
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2003
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-2-3

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