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Published in: Malaria Journal 1/2004

Open Access 01-12-2004 | Research

Association of house spraying with suppressed levels of drug resistance in Zimbabwe

Authors: Sungano Mharakurwa, Susan L Mutambu, Robert Mudyiradima, Tawanda Chimbadzwa, Steven K Chandiwana, Karen P Day

Published in: Malaria Journal | Issue 1/2004

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Abstract

Background

Public health strategies are needed to curb antimalarial drug resistance. Theoretical argument points to an association between malaria transmission and drug resistance although field evidence remains limited. Field observations, made in Zimbabwe, on the relationship between transmission and multigenic drug resistance, typified by chloroquine, are reported here.

Methods

Periodic assessments of the therapeutic response of uncomplicated falciparum malaria to chloroquine in two selectively sprayed or unsprayed health centre catchments, from 1995 – 2003. Cross-sectional analysis of in vivo chloroquine failure events for five sites in relation to natural endemicity and spraying history.

Results

During selective house spraying, the chloroquine failure rate for the sprayed catchment decreased, such that, after four years, the odds of chloroquine failure were 4× lower than before start of spraying in the area (OR 0.2, 95% CI 0.07 – 0.75, p = 0.010, n = 100). Chloroquine failure odds for the sprayed area became 4× lower than contemporaneous failure odds for the unsprayed area (OR 0.2 95% CI 0.08 – 0.65, p = 0.003, n = 156), although the likelihood of failure was not significantly different for the two catchments before selective spraying started (OR 0.5, 95% CI 0.21 – 1.32; p = 0.170, n = 88). When spraying ended, in 1999, the drug failure odds for the former sprayed area increased back 4 fold by 2003 (OR 4.2, 95%CI 1.49 – 11.78, p = 0.004, n = 146). High altitude areas with naturally lower transmission exhibited a 6× lower likelihood of drug failure than low-lying areas (OR 0.16 95% CI 0.068 – 0.353, -2 log likelihood change 23.239, p < 0.001, n = 465). Compared to sites under ongoing annual spraying, areas that were last sprayed 3–7 years ago experienced a 4-fold higher probability of chloroquine failure (OR 4.1, 95%CI 1.84 – 9.14, -2 log likelihood change 13.956, p < 0.001).

Conclusion

Reduced transmission is associated with suppressed levels of resistance to chloroquine and presumably other regimens with multigenic drug resistance. It seems the adoption of transmission control alongside combination chemotherapy is a potent strategy for the future containment of drug-resistant malaria.
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Literature
1.
go back to reference Wernsdorfer WH, Payne D: The dynamics of drug resistance in Plasmodium falciparum. Pharmacol Ther. 1991, 50: 95-121. 10.1016/0163-7258(91)90074-V.CrossRefPubMed Wernsdorfer WH, Payne D: The dynamics of drug resistance in Plasmodium falciparum. Pharmacol Ther. 1991, 50: 95-121. 10.1016/0163-7258(91)90074-V.CrossRefPubMed
2.
go back to reference Wernsdorfer WH: Epidemiology of drug resistance in malaria. Acta Trop. 1994, 56: 143-156. 10.1016/0001-706X(94)90060-4.CrossRefPubMed Wernsdorfer WH: Epidemiology of drug resistance in malaria. Acta Trop. 1994, 56: 143-156. 10.1016/0001-706X(94)90060-4.CrossRefPubMed
3.
go back to reference D'Alessandro U, Buttiens H: History and importance of antimalarial drug resistance. Trop Med Int Health. 2001, 6: 845-848. 10.1046/j.1365-3156.2001.00819.x.CrossRefPubMed D'Alessandro U, Buttiens H: History and importance of antimalarial drug resistance. Trop Med Int Health. 2001, 6: 845-848. 10.1046/j.1365-3156.2001.00819.x.CrossRefPubMed
4.
go back to reference Trape JF: The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg. 2001, 64: 12-17.PubMed Trape JF: The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg. 2001, 64: 12-17.PubMed
5.
go back to reference Trape JF, Pison G, Spiegel A, Enel C, Rogier C: Combating malaria in Africa. Trends Parasitol. 2002, 18: 224-230. 10.1016/S1471-4922(02)02249-3.CrossRefPubMed Trape JF, Pison G, Spiegel A, Enel C, Rogier C: Combating malaria in Africa. Trends Parasitol. 2002, 18: 224-230. 10.1016/S1471-4922(02)02249-3.CrossRefPubMed
6.
go back to reference Gorissen E, Ashruf G, Lamboo M, Bennebroek J, Gikunda S, Mbaruku G, Kager PA: In vivo efficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania. Trop Med Int Health. 2000, 5: 459-463. 10.1046/j.1365-3156.2000.00570.x.CrossRefPubMed Gorissen E, Ashruf G, Lamboo M, Bennebroek J, Gikunda S, Mbaruku G, Kager PA: In vivo efficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania. Trop Med Int Health. 2000, 5: 459-463. 10.1046/j.1365-3156.2000.00570.x.CrossRefPubMed
7.
go back to reference Bijl HM, Kager J, Koetsier DW, van der Werf TS: Chloroquine- and sulfadoxine-pyrimethamine-resistant Falciparum malaria in vivo - a pilot study in rural Zambia. Trop Med Int Health. 2000, 5: 692-695. 10.1046/j.1365-3156.2000.00629.x.CrossRefPubMed Bijl HM, Kager J, Koetsier DW, van der Werf TS: Chloroquine- and sulfadoxine-pyrimethamine-resistant Falciparum malaria in vivo - a pilot study in rural Zambia. Trop Med Int Health. 2000, 5: 692-695. 10.1046/j.1365-3156.2000.00629.x.CrossRefPubMed
8.
go back to reference Bwijo B, Kaneko A, Takechi M, Zungu IL, Moriyama Y, Lum JK, Tsukahara T, Mita T, Takahashi N, Bergqvist Y, Bjorkman A, Kobayakawa T: High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi. Acta Trop. 2003, 85: 363-373. 10.1016/S0001-706X(02)00264-4.CrossRefPubMed Bwijo B, Kaneko A, Takechi M, Zungu IL, Moriyama Y, Lum JK, Tsukahara T, Mita T, Takahashi N, Bergqvist Y, Bjorkman A, Kobayakawa T: High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi. Acta Trop. 2003, 85: 363-373. 10.1016/S0001-706X(02)00264-4.CrossRefPubMed
9.
go back to reference White N: Sulfadoxine-pyrimethamine for uncomplicated falciparum malaria: sulfadoxine-pyrimethamine is not working in Malawi. Bmj. 2004, 328: 1259; author reply 1260-PubMed White N: Sulfadoxine-pyrimethamine for uncomplicated falciparum malaria: sulfadoxine-pyrimethamine is not working in Malawi. Bmj. 2004, 328: 1259; author reply 1260-PubMed
10.
11.
go back to reference Olliaro PL, Taylor WR: Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review. J Postgrad Med. 2004, 50: 40-44.PubMed Olliaro PL, Taylor WR: Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review. J Postgrad Med. 2004, 50: 40-44.PubMed
12.
go back to reference Foote SJ, Cowman AF: The mode of action and the mechanism of resistance to antimalarial drugs. Acta Trop. 1994, 56: 157-171. 10.1016/0001-706X(94)90061-2.CrossRefPubMed Foote SJ, Cowman AF: The mode of action and the mechanism of resistance to antimalarial drugs. Acta Trop. 1994, 56: 157-171. 10.1016/0001-706X(94)90061-2.CrossRefPubMed
13.
go back to reference Dua VK, Dev V, Phookan S, Gupta NC, Sharma VP, Subbarao SK: Multi-drug resistant Plasmodium falciparum malaria in Assam, India: timing of recurrence and anti-malarial drug concentrations in whole blood. Am J Trop Med Hyg. 2003, 69: 555-557.PubMed Dua VK, Dev V, Phookan S, Gupta NC, Sharma VP, Subbarao SK: Multi-drug resistant Plasmodium falciparum malaria in Assam, India: timing of recurrence and anti-malarial drug concentrations in whole blood. Am J Trop Med Hyg. 2003, 69: 555-557.PubMed
14.
go back to reference Giao PT, de Vries PJ, Hung le Q, Binh TQ, Nam NV, Kager PA: CV8, a new combination of dihydroartemisinin, piperaquine, trimethoprim and primaquine, compared with atovaquone-proguanil against falciparum malaria in Vietnam. Trop Med Int Health. 2004, 9: 209-216. 10.1046/j.1365-3156.2003.01180.x.CrossRefPubMed Giao PT, de Vries PJ, Hung le Q, Binh TQ, Nam NV, Kager PA: CV8, a new combination of dihydroartemisinin, piperaquine, trimethoprim and primaquine, compared with atovaquone-proguanil against falciparum malaria in Vietnam. Trop Med Int Health. 2004, 9: 209-216. 10.1046/j.1365-3156.2003.01180.x.CrossRefPubMed
15.
go back to reference Wattanakoon Y, Chittamas S, Pornkulprasit V, Kanda T, Thimasarn K, Rojanawatsirivej C, Looareesuwan S, Bunnag D: Six-years monitoring the efficacy of the combination of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria. Southeast Asian J Trop Med Public Health. 2003, 34: 542-545.PubMed Wattanakoon Y, Chittamas S, Pornkulprasit V, Kanda T, Thimasarn K, Rojanawatsirivej C, Looareesuwan S, Bunnag D: Six-years monitoring the efficacy of the combination of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria. Southeast Asian J Trop Med Public Health. 2003, 34: 542-545.PubMed
16.
go back to reference Peters W: The prevention of antimalarial drug resistance. Pharmacol Ther. 1990, 47: 499-508. 10.1016/0163-7258(90)90067-C.CrossRefPubMed Peters W: The prevention of antimalarial drug resistance. Pharmacol Ther. 1990, 47: 499-508. 10.1016/0163-7258(90)90067-C.CrossRefPubMed
17.
18.
go back to reference David KP, Alifrangis M, Salanti A, Vestergaard LS, Ronn A, Bygbjerg IB: Atovaquone/proguanil resistance in Africa: a case report. Scand J Infect Dis. 2003, 35: 897-898.CrossRefPubMed David KP, Alifrangis M, Salanti A, Vestergaard LS, Ronn A, Bygbjerg IB: Atovaquone/proguanil resistance in Africa: a case report. Scand J Infect Dis. 2003, 35: 897-898.CrossRefPubMed
19.
go back to reference Schwartz E, Bujanover S, Kain KC: Genetic confirmation of atovaquone-proguanil-resistant Plasmodium falciparum malaria acquired by a nonimmune traveler to East Africa. Clin Infect Dis. 2003, 37: 450-451. 10.1086/375599.CrossRefPubMed Schwartz E, Bujanover S, Kain KC: Genetic confirmation of atovaquone-proguanil-resistant Plasmodium falciparum malaria acquired by a nonimmune traveler to East Africa. Clin Infect Dis. 2003, 37: 450-451. 10.1086/375599.CrossRefPubMed
20.
go back to reference Farnert A, Lindberg J, Gil P, Swedberg G, Berqvist Y, Thapar MM, Lindegardh N, Berezcky S, Bjorkman A: Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguanil hydrochloride: case reports. Bmj. 2003, 326: 628-629. 10.1136/bmj.326.7390.628.PubMedCentralCrossRefPubMed Farnert A, Lindberg J, Gil P, Swedberg G, Berqvist Y, Thapar MM, Lindegardh N, Berezcky S, Bjorkman A: Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguanil hydrochloride: case reports. Bmj. 2003, 326: 628-629. 10.1136/bmj.326.7390.628.PubMedCentralCrossRefPubMed
21.
go back to reference Fivelman QL, Butcher GA, Adagu IS, Warhurst DC, Pasvol G: Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria. Malar J. 2002, 1: 1-10.1186/1475-2875-1-1.PubMedCentralCrossRefPubMed Fivelman QL, Butcher GA, Adagu IS, Warhurst DC, Pasvol G: Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria. Malar J. 2002, 1: 1-10.1186/1475-2875-1-1.PubMedCentralCrossRefPubMed
22.
23.
go back to reference Hastings IM: A model for the origins and spread of drug-resistant malaria. Parasitology. 1997, 115 ( Pt 2): 133-141. 10.1017/S0031182097001261.CrossRef Hastings IM: A model for the origins and spread of drug-resistant malaria. Parasitology. 1997, 115 ( Pt 2): 133-141. 10.1017/S0031182097001261.CrossRef
24.
go back to reference Hastings IM, Mackinnon MJ: The emergence of drug-resistant malaria. Parasitology. 1998, 117 ( Pt 5): 411-417. 10.1017/S0031182098003291.CrossRef Hastings IM, Mackinnon MJ: The emergence of drug-resistant malaria. Parasitology. 1998, 117 ( Pt 5): 411-417. 10.1017/S0031182098003291.CrossRef
25.
go back to reference Ariey F, Robert V: The puzzling links between malaria transmission and drug resistance. Trends Parasitol. 2003, 19: 158-60; author reply 160-1. 10.1016/S1471-4922(03)00054-0.CrossRefPubMed Ariey F, Robert V: The puzzling links between malaria transmission and drug resistance. Trends Parasitol. 2003, 19: 158-60; author reply 160-1. 10.1016/S1471-4922(03)00054-0.CrossRefPubMed
26.
27.
go back to reference Molyneux DH, Floyd K, Barnish G, Fevre EM: Transmission control and drug resistance in malaria: a crucial interaction. Parasitol Today. 1999, 15: 238-240. 10.1016/S0169-4758(99)01453-2.CrossRefPubMed Molyneux DH, Floyd K, Barnish G, Fevre EM: Transmission control and drug resistance in malaria: a crucial interaction. Parasitol Today. 1999, 15: 238-240. 10.1016/S0169-4758(99)01453-2.CrossRefPubMed
28.
go back to reference Taylor P, Mutambu SL: A review of the malaria situation in Zimbabwe with special reference to the period 1972-1981. Trans R Soc Trop Med Hyg. 1986, 80: 12-19. 10.1016/0035-9203(86)90185-9.CrossRefPubMed Taylor P, Mutambu SL: A review of the malaria situation in Zimbabwe with special reference to the period 1972-1981. Trans R Soc Trop Med Hyg. 1986, 80: 12-19. 10.1016/0035-9203(86)90185-9.CrossRefPubMed
29.
go back to reference Herd N, Jordan T: An investigation of malaria during pregnancy in Zimbabwe. Cent Afr J Med. 1981, 27: 62-68. Herd N, Jordan T: An investigation of malaria during pregnancy in Zimbabwe. Cent Afr J Med. 1981, 27: 62-68.
30.
go back to reference Taylor P, A. Taputaira: Forty years of malaria control in Zimbabwe. Proceedings of the First National Symposium of Science and Technology. 1988, Harare Taylor P, A. Taputaira: Forty years of malaria control in Zimbabwe. Proceedings of the First National Symposium of Science and Technology. 1988, Harare
31.
go back to reference WHO: Assessment of the Therapeutic Efficacy of Antimalarial Drugs for the Treatment of Uncomplicated Malaria in Africa in Areas with Intense Transmission. 1996, Geneva, World Health Organization WHO: Assessment of the Therapeutic Efficacy of Antimalarial Drugs for the Treatment of Uncomplicated Malaria in Africa in Areas with Intense Transmission. 1996, Geneva, World Health Organization
32.
go back to reference Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF: Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature. 1990, 345: 255-258. 10.1038/345255a0.CrossRefPubMed Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF: Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature. 1990, 345: 255-258. 10.1038/345255a0.CrossRefPubMed
33.
go back to reference Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LMB, Naude B, Deitsch KW, Su XZ, Wootton JC, Roepe PD, Wellems TE: Mutations in the Plasmodium falciparum digestive vacuole transmembrane protein Pfcrtand evidence for their role in chloroquine resistance. Molecular Cell. 2000, 6: 861-871.PubMedCentralCrossRefPubMed Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LMB, Naude B, Deitsch KW, Su XZ, Wootton JC, Roepe PD, Wellems TE: Mutations in the Plasmodium falciparum digestive vacuole transmembrane protein Pfcrtand evidence for their role in chloroquine resistance. Molecular Cell. 2000, 6: 861-871.PubMedCentralCrossRefPubMed
34.
go back to reference Frean JA, el Kariem FM, Warhurst DC, Miles MA: Rapid detection of pfmdr1 mutations in chloroquine-resistant Plasmodium falciparum malaria by polymerase chain reaction analysis of blood spots. Trans R Soc Trop Med Hyg. 1992, 86: 29-30. 10.1016/0035-9203(92)90426-D.CrossRefPubMed Frean JA, el Kariem FM, Warhurst DC, Miles MA: Rapid detection of pfmdr1 mutations in chloroquine-resistant Plasmodium falciparum malaria by polymerase chain reaction analysis of blood spots. Trans R Soc Trop Med Hyg. 1992, 86: 29-30. 10.1016/0035-9203(92)90426-D.CrossRefPubMed
35.
go back to reference Duraisingh MT, Drakeley CJ, Muller O, Bailey R, Snounou G, Targett GA, Greenwood BM, Warhurst DC: Evidence for selection for the tyrosine-86 allele of the pfmdr 1 gene of Plasmodium falciparum by chloroquine and amodiaquine. Parasitology. 1997, 114 ( Pt 3): 205-211. 10.1017/S0031182096008487.CrossRef Duraisingh MT, Drakeley CJ, Muller O, Bailey R, Snounou G, Targett GA, Greenwood BM, Warhurst DC: Evidence for selection for the tyrosine-86 allele of the pfmdr 1 gene of Plasmodium falciparum by chloroquine and amodiaquine. Parasitology. 1997, 114 ( Pt 3): 205-211. 10.1017/S0031182096008487.CrossRef
36.
go back to reference Dye C, Williams BG: Multigenic drug resistance among inbred malaria parasites. Proc R Soc Lond 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 Lond B Biol Sci. 1997, 264: 61-67. 10.1098/rspb.1997.0009.CrossRef
37.
go back to reference Talisuna AO, Langi P, Mutabingwa TK, Van Marck E, Speybroeck N, Egwang TG, Watkins WW, Hastings IM, D'Alessandro U: Intensity of transmission and spread of gene mutations linked to chloroquine and sulphadoxine-pyrimethamine resistance in falciparum malaria. Int J Parasitol. 2003, 33: 1051-1058. 10.1016/S0020-7519(03)00156-5.CrossRefPubMed Talisuna AO, Langi P, Mutabingwa TK, Van Marck E, Speybroeck N, Egwang TG, Watkins WW, Hastings IM, D'Alessandro U: Intensity of transmission and spread of gene mutations linked to chloroquine and sulphadoxine-pyrimethamine resistance in falciparum malaria. Int J Parasitol. 2003, 33: 1051-1058. 10.1016/S0020-7519(03)00156-5.CrossRefPubMed
38.
go back to reference Liu DQ, Liu RJ, Ren DX, Gao DQ, Zhang CY, Qui CP, Cai XZ, Ling CF, Song AH, Tang X: Changes in the resistance of Plasmodium falciparum to chloroquine in Hainan, China. Bull World Health Organ. 1995, 73: 483-486.PubMedCentralPubMed Liu DQ, Liu RJ, Ren DX, Gao DQ, Zhang CY, Qui CP, Cai XZ, Ling CF, Song AH, Tang X: Changes in the resistance of Plasmodium falciparum to chloroquine in Hainan, China. Bull World Health Organ. 1995, 73: 483-486.PubMedCentralPubMed
39.
go back to reference Mita T, Kaneko A, Lum JK, Bwijo B, Takechi M, Zungu IL, Tsukahara T, Tanabe K, Kobayakawa T, Bjorkman A: Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi. Am J Trop Med Hyg. 2003, 68: 413-415.PubMed Mita T, Kaneko A, Lum JK, Bwijo B, Takechi M, Zungu IL, Tsukahara T, Tanabe K, Kobayakawa T, Bjorkman A: Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi. Am J Trop Med Hyg. 2003, 68: 413-415.PubMed
40.
go back to reference Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimde AA, Kouriba B, Taylor TE, Plowe CV: Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis. 2003, 187: 1870-1875. 10.1086/375419.CrossRefPubMed Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimde AA, Kouriba B, Taylor TE, Plowe CV: Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis. 2003, 187: 1870-1875. 10.1086/375419.CrossRefPubMed
41.
go back to reference Talisuna AO, Langi P, Bakyaita N, Egwang T, Mutabingwa TK, Watkins W, Van Marck E, D'Alessandro U: Intensity of malaria transmission, antimalarial-drug use and resistance in Uganda: what is the relationship between these three factors?. Trans R Soc Trop Med Hyg. 2002, 96: 310-317. 10.1016/S0035-9203(02)90108-2.CrossRefPubMed Talisuna AO, Langi P, Bakyaita N, Egwang T, Mutabingwa TK, Watkins W, Van Marck E, D'Alessandro U: Intensity of malaria transmission, antimalarial-drug use and resistance in Uganda: what is the relationship between these three factors?. Trans R Soc Trop Med Hyg. 2002, 96: 310-317. 10.1016/S0035-9203(02)90108-2.CrossRefPubMed
42.
go back to reference Hastings IM: Malaria control and the evolution of drug resistance: an intriguing link. Trends Parasitol. 2003, 19: 70-73. 10.1016/S1471-4922(02)00017-X.CrossRefPubMed Hastings IM: Malaria control and the evolution of drug resistance: an intriguing link. Trends Parasitol. 2003, 19: 70-73. 10.1016/S1471-4922(02)00017-X.CrossRefPubMed
Metadata
Title
Association of house spraying with suppressed levels of drug resistance in Zimbabwe
Authors
Sungano Mharakurwa
Susan L Mutambu
Robert Mudyiradima
Tawanda Chimbadzwa
Steven K Chandiwana
Karen P Day
Publication date
01-12-2004
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2004
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-3-35

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