HIGH REINFECTION RATE AND TREATMENT FAILURES IN CHILDREN TREATED WITH AMODIAQUINE FOR FALCIPARUM MALARIA IN MUHEZA VILLAGES, NORTHEASTERN TANZANIA

MARTHA LEMNGE National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

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MICHAEL ALIFRANGIS National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

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MWANAIDI Y. KAFUYE National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

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METHOD D. SEGEJA National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

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SAMWEL GESASE National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

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DANIEL MINJA National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

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JULIUS J. MASSAGA National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

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ANITA M. RØNN National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

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IB C. BYGBJERG National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Centre for Medical Parasitology at the Institute of Medical Microbiology and Immunology and Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

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In May 2003, we studied amodiaquine (AQ) efficacy in children < 5 years of age with uncomplicated falciparum malaria in Magoda and Mpapayu (with insecticide treated nets [ITNs]) and Mgome (without ITNs) in Muheza, Tanzania. The trial involved 28 days of follow-up, and data were adjusted by polymerase chain reaction (PCR) genotyping of msp1 and msp2 genes. Additionally, Pfcrt codon 72–76 polymorphisms were studied by PCR and sequence-specific oligonucleotide probe (SSOP) ELISA. In 54 cases with complete follow-up, a significant difference in late treatment failure (LTF) rates was seen (60.7% in ITN versus 88.5% in non-ITN villages, P = 0.02) before PCR correction. However, after PCR correction, 23 cases (60.5%) were confirmed as reinfections, giving a true LTF rate of 21.4% (6/28) and 34.6% (9/26) in the above settings, respectively. Frequency of Pfcrt CVIET haplotype mutation pretreatment was high (97.0%); the remaining samples were CVMNK. We conclude that AQ alone is no longer effective in the study area.

Author Notes

Reprint requests: Martha Lemnge, Tanga Medical Research Centre, PO Box 5004, Tanga, Tanzania. E-mail: mlemnge@amani.mimcom.net or marthalemnge@yahoo.com.
  • 1

    White NJ, 2004. Antimalarial drug resistance. J Clin Invest 113 :1084–1092.

  • 2

    Adjuik M, Agnamey P, Babiker A, Borrmann S, Brasseur P, Cisse M, Cobelens F, Diallo S, Faucher JF, Garner P, Gikunda S, Kremsner PG, Krishna S, Lell B, Loolpapit M, Matsiegui PB, Missinou MA, Mwanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E, Taylor WR, 2002. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial. Lancet 359 :1365–1372.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Gorissen E, Ashruf G, Lamboo M, Bennebroek J, Gikunda S, Mbaruku G, Kager PA, 2000. In vivo efficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania. Trop Med Int Health 5 :459–463.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Watkins WM, Sixsmith DG, Spencer HC, Boriga DA, Kariuki DM, Kipingor T, Koech DK, 1984. Effectiveness of amodiaquine as treatment for chloroquine-resistant Plasmodium falciparum infections in Kenya. Lancet 1 :357–359.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Schellenberg D, Kahigwa E, Drakeley C, Malende A, Wigayi J, Msokame C, Aponte JJ, Tanner M, Mshinda H, Menendez C, Alonso PL, 2002. The safety and efficacy of sulfadoxine-pyrimethamine, amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria. Am J Trop Med Hyg 67 :17–23.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Happi CT, Gbotosho GO, Sowunmi A, Falade CO, Akinboye DO, Gerena L, Kyle DE, Milhous W, Wirth DF, Oduola AM, 2004. Molecular analysis of Plasmodium falciparum recrudescent malaria infections in children treated with chloroquine in Nigeria. Am J Trop Med Hyg 70 :20–26.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Basco LK, Ndounga M, Keundjian A, Ringwald P, 2002. Molecular epidemiology of malaria in cameroon. IX. Characteristics of recrudescent and persistent Plasmodium falciparum infections after chloroquine or amodiaquine treatment in children. Am J Trop Med Hyg 66 :117–123.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Djimde A, Doumbo OK, Steketee RW, Plowe CV, 2001. Application of a molecular marker for surveillance of chloroquine-resistant falciparum malaria. Lancet 358 :890–891.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Djimde AA, Doumbo OK, Traore O, Guindo AB, Kayentao K, Diourte Y, Niare-Doumbo S, Coulibaly D, Kone AK, Cissoko Y, Tekete M, Fofana B, Dicko A, Diallo DA, Wellems TE, Kwiatkowski D, Plowe CV, 2003. Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria. Am J Trop Med Hyg 69 :558–563.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    World Health Organization, 2003. Monitoring of Antimalarial Drug Resistance, (WHO/CDS/RBM/2002.39).

    • PubMed
    • Export Citation
  • 11

    Magesa SM, Mdira KY, Babiker HA, Alifrangis M, Farnert A, Simonsen PE, Bygbjerg IC, Walliker D, Jakobsen PH, 2002. Diversity of Plasmodium falciparum clones infecting children living in a holoendemic area in north-eastern Tanzania. Acta Trop 84 :83–92.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Djimde AA, Dolo A, Ouattara A, Diakite S, Plowe CV, Doumbo OK, 2004. Molecular diagnosis of resistance to antimalarial drugs during epidemics and in war zones. J Infect Dis 190 :853–855.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Sidhu AB, Naude B, Deitsch KW, Su XZ, Wootton JC, Roepe PD, Wellems TE, 2000. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6 :861–871.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Wellems TE, Plowe CV, 2001. Chloroquine-resistant malaria. J Infect Dis 184 :770–776.

  • 15

    Bray PG, Hawley SR, Mungthin M, Ward SA, 1996. Physico-chemical properties correlated with drug resistance and the reversal of drug resistance in Plasmodium falciparum. Mol Pharmacol 50 :1559–1566.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Hawley SR, Bray PG, Park BK, Ward SA, 1996. Amodiaquine accumulation in Plasmodium falciparum as a possible explanation for its superior antimalarial activity over chloroquine. Mol Biochem Parasitol 80 :15–25.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Warhurst DC, 2003. Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine. Malar J 2 :31.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Ochong EO, van dB IV, Keus K, Nzila A, 2003. Short report: association between chloroquine and amodiaquine resistance and allelic variation in the Plasmodium falciparum multiple drug resistance 1 gene and the chloroquine resistance transporter gene in isolates from the upper Nile in southern Sudan. Am J Trop Med Hyg 69 :184–187.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Schneider AG, Premji Z, Felger I, Smith T, Abdulla S, Beck HP, Mshinda H, 2002. A point mutation in codon 76 of pfcrt of P. falciparum is positively selected for by Chloroquine treatment in Tanzania. Infect Genet Evol 1 :183–189.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Alifrangis M, Lemnge MM, Ronn AM, Segeja MD, Magesa SM, Khalil IF, Bygbjerg IC, 2003. Increasing prevalence of wild-types in the dihydrofolate reductase gene of Plasmodium falciparum in an area with high levels of sulfadoxine/ pyrimethamine resistance after introduction of treated bed nets. Am J Trop Med Hyg 69 :238–243.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Lemnge MM, Msangeni HA, Rønn AM, Salum FM, Jakobsen PH, Mhina J, Akida JA, Bygbjerg IC, 1997. Maloprim malaria prophylaxis in children living in a holoendemic village in north-eastern Tanzania. Trans R Soc Trop Med Hyg 91 :68–73.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Rønn AM, Msangeni HA, Mhina J, Wernsdorfer WH, Bygbjerg IC, 1996. High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in children in Tanzania. Trans R Soc Trop Med Hyg 90 :179–181.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Jelinek T, Rønn AM, Curtis J, Duraisingh MT, Lemnge MM, Mhina J, Bygbjerg IC, Warhurst DC, 1997. High prevalence of mutations in the dihydrofolate reductase gene of Plasmodium falciparum in isolates from Tanzania without evidence of an association to clinical sulfadoxine/pyrimethamine resistance. Trop Med Int Health 2 :1075–1079.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Jelinek T, Rønn AM, Lemnge MM, Curtis J, Mhina J, Duraisingh MT, Bygbjerg IC, Warhurst DC, 1998. Polymorphisms in dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) genes of Plasmodium falciparum and in vivo resistance to sulfadoxine/pyrimethamine in isolates from Tanzania. Trop Med Int Health 3 :605–609.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Alifrangis M, Enosse S, Khalil IF, Tarimo DS, Lemnge MM, Thompson R, Bygbjerg IC, Ronn AM, 2003. Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity. Am J Trop Med Hyg 69 :601–606.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Wooden J, Kyes S, Sibley CH, 1993. PCR and Strain Identification in Plasmodium falciparum. Parasitol Today 9 :303–305.

  • 27

    Pearce RJ, Drakeley C, Chandramohan D, Mosha F, Roper C, 2003. Molecular Determination of Point Mutation Haplotypes in the Dihydrofolate Reductase and Dihydropteroate Synthase of Plasmodium falciparum in Three Districts of Northern Tanzania. Antimicrob Agents Chemother 47 :1347–1354.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Snounou G, Zhu X, Siripoon N, Jarra W, Thaithong S, Brown KN, Viriyakosol S, 1999. Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg 93 :369–374.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Basco LK, Ringwald P, 2000. Molecular epidemiology of malaria in Yaounde, Cameroon. VII. Analysis of recrudescence and reinfection in patients with uncomplicated falciparum malaria. Am J Trop Med Hyg 63 :215–221.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344 :257–263.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Alifrangis M, Enosse S, Pearce R, Drakeley C, Roper C, Khalil IF, Nkya WMMM, Rønn AM, Theander TG, Bygbjerg IC, 2005. A simple, high-throughput method to detect P. falciparum single nucleotide polymorphisms in dhfr, dhps and Pfcrt using PCR and ELISA based technology. Am J Trop Med Hyg 72 :155–162.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Mugittu K, Ndejembi M, Malisa A, Lemnge M, Premji Z, Mwita A, Nkya W, Kataraihya J, Abdulla S, Beck HP, Mshinda H, 2004. Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in Tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance. Am J Trop Med Hyg 71 :696–702.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Hamer DH, MacLeod WB, Addo-Yobo E, Duggan CP, Estrella B, Fawzi WW, Konde-Lule JK, Mwanakasale V, Premji ZG, Sempertegui F, Ssengooba FP, Yeboah-Antwi K, Simon JL, 2003. Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 97 :422–428.

    • PubMed
    • Search Google Scholar
    • Export Citation
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