Plasmodium vivax is highly endemic in the lowlands of Papua New Guinea and accounts for a large proportion of the malaria cases in children less than 5 years of age. We collected 2117 blood samples at 2-monthly intervals from a cohort of 268 children aged 1 to 4.5 years and estimated the diversity and multiplicity of P. vivax infection. All P. vivax clones were genotyped using the merozoite surface protein 1 F3 fragment (msp1F3) and the microsatellite MS16 as molecular markers. High diversity was observed with msp1F3 (HE = 88.1%) and MS16 (HE = 97.8%). Of the 1162 P. vivax positive samples, 74% harbored multi-clone infections with a mean multiplicity of 2.7 (IQR = 1–3). The multiplicity of P. vivax infection increased slightly with age (P = 0.02), with the strongest increase in very young children. Intensified efforts to control malaria can benefit from knowledge of the diversity and MOI both for assessing the endemic situation and monitoring the effects of interventions.
References
[1]
Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, et al. (2010) The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl Trop Dis 4: e774. doi: 10.1371/journal.pntd.0000774
[2]
Mueller I, Bockarie M, Alpers M, Smith T (2003) The epidemiology of malaria in Papua New Guinea. Trends in Parasitology 19: 253–259. doi: 10.1016/S1471-4922(03)00091-6
[3]
Karunajeewa HA, Mueller I, Senn M, Lin E, Law I, et al. (2008) A trial of combination antimalarial therapies in children from Papua New Guinea. N Engl J Med 359: 2545–2557. doi: 10.1056/NEJMoa0804915
[4]
Darlow B, Vrbova H, Gibney S, Jolley D, Stace J, et al. (1982) Sulfadoxine-pyrimethamine for the treatment of acute malaria in children of Papua New Guinea. II. Plasmodium vivax. Am J Trop Med Hyg 31: 10–13.
[5]
Mueller I, Genton B, Betuela I, Alpers MP (2010) Vaccines against malaria: perspectives from Papua New Guinea. Hum Vaccin 6: 17–20. doi: 10.4161/hv.6.1.10332
[6]
Mueller I, Widmer S, Michel D, Maraga S, McNamara DT, et al. (2009) High sensitivity detection of Plasmodium species reveals positive correlations between infections of different species, shifts in age distribution and reduced local variation in Papua New Guinea. Malar J 8: 41. doi: 10.1186/1475-2875-8-41
[7]
Muller I, Genton B, Rare L, Kiniboro B, Kastens W, et al. (2009) Three different Plasmodium species show similar patterns of clinical tolerance of malaria infection. Malar J 8: 158. doi: 10.1186/1475-2875-8-158
[8]
Lin E, Kiniboro B, Gray L, Dobbie S, Robinson L, et al. (2010) Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children. PLoS One 5: e9047. doi: 10.1371/journal.pone.0009047
[9]
Michon P, Cole-Tobian JL, Dabod E, Schoepflin S, Igu J, et al. (2007) The risk of malarial infections and disease in Papua New Guinean children. Am J Trop Med Hyg 76: 997–1008.
[10]
Paul RE, Packer MJ, Walmsley M, Lagog M, Ranford-Cartwright LC, et al. (1995) Mating patterns in malaria parasite populations of Papua New Guinea. Science 269: 1709–1711. doi: 10.1126/science.7569897
[11]
Gunawardena S, Karunaweera ND, Ferreira MU, Phone-Kyaw M, Pollack RJ, et al. (2010) Geographic structure of Plasmodium vivax: microsatellite analysis of parasite populations from Sri Lanka, Myanmar, and Ethiopia. Am J Trop Med Hyg 82: 235–242. doi: 10.4269/ajtmh.2010.09-0588
[12]
Van den Eede P, Van der Auwera G, Delgado C, Huyse T, Soto-Calle VE, et al. (2010) Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon. Malar J 9: 151. doi: 10.1186/1475-2875-9-151
Tanabe K, Escalante A, Sakihama N, Honda M, Arisue N, et al. (2007) Recent independent evolution of msp1 polymorphism in Plasmodium vivax and related simian malaria parasites. Mol Biochem Parasitol 156: 74–79. doi: 10.1016/j.molbiopara.2007.07.002
[15]
Zeyrek FY, Tachibana S, Yuksel F, Doni N, Palacpac N, et al. (2010) Limited polymorphism of the Plasmodium vivax merozoite surface protein 1 gene in isolates from Turkey. Am J Trop Med Hyg 83: 1230–1237. doi: 10.4269/ajtmh.2010.10-0353
[16]
Farooq U, Malla N, Dubey ML (2009) Polymorphism in merozoite surface protein-1 gene in north & northwest Indian field isolates of Plasmodium vivax. Indian J Med Res 130: 736–741.
[17]
Koepfli C, Mueller I, Marfurt J, Goroti M, Sie A, et al. (2008) Evaluation of Plasmodium vivax genotyping markers for molecular monitoring in clinical trials. J Infect Dis. doi: 10.1086/597303
[18]
Genton B, Al Yaman F, Beck HP, Hii J, Mellor S, et al. (1995) The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. I. Malariometric indices and immunity. Ann Trop Med Parasitol 89: 359–376.
[19]
Genton B, Al Yaman F, Beck HP, Hii J, Mellor S, et al. (1995) The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. II. Mortality and morbidity. Ann Trop Med Parasitol 89: 377–390.
[20]
Smith T, Hii JL, Genton B, Muller I, Booth M, et al. (2001) Associations of peak shifts in age–prevalence for human malarias with bednet coverage. Trans R Soc Trop Med Hyg 95: 1–6. doi: 10.1016/S0035-9203(01)90314-1
[21]
Kasehagen LJ, Mueller I, McNamara DT, Bockarie MJ, Kiniboro B, et al. (2006) Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis. Am J Trop Med Hyg 75: 588–596.
[22]
Schoepflin S, Valsangiacomo F, Lin E, Kiniboro B, Mueller I, et al. (2009) Comparison of Plasmodium falciparum allelic frequency distribution in different endemic settings by high-resolution genotyping. Malar J 8: 250. doi: 10.1186/1475-2875-8-250
[23]
McNamara DT, Kasehagen LJ, Grimberg BT, Cole-Tobian J, Collins WE, et al. (2006) Diagnosing infection levels of four human malaria parasite species by a polymerase chain reaction/ligase detection reaction fluorescent microsphere-based assay. Am J Trop Med Hyg 74: 413–421.
[24]
Havryliuk T, Ferreira MU (2009) A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences. Mem Inst Oswaldo Cruz 104: 67–73. doi: 10.1590/S0074-02762009000100011
[25]
StataCorp. College Station T (2007) Stata Statistical Software: Release 10.
[26]
Lunn DJ, Thomas A, Best N, Spiegelhalter D (2000) WinBUGS - A Bayesian modelling framework: Concepts, structure, and extensibility. Statistics and Computing 10: 13.
[27]
LIAN website. Available: http://adenine.biz.fh-weihenstephan.de/c？gi-bin/lian/lian.cgi.pl. Accessed 2011 Nov 7.
[28]
Rodulfo H, De Donato M, Mora R, Gonzalez L, Contreras CE (2007) Comparison of the diagnosis of malaria by microscopy, immunochromatography and PCR in endemic areas of Venezuela. Braz J Med Biol Res 40: 535–543. doi: 10.1590/S0100-879X2007000400012
[29]
Harris I, Sharrock WW, Bain LM, Gray KA, Bobogare A, et al. (2010) A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting. Malar J 9: 254. doi: 10.1186/1475-2875-9-254
[30]
Garnham PCC (1966) Malaria Parasites And Other Heamosporidia. Oxford: Blackwell Scientific Publications.
[31]
Koepfli C, Schoepflin S, Bretscher M, Lin E, Kiniboro B, et al. (2011) How much remains undetected? Probability of molecular detection of human plasmodia in the field. PLoS ONE 6: e19010. doi: 10.1371/journal.pone.0019010
[32]
Chen N, Auliff A, Rieckmann K, Gatton M, Cheng Q (2007) Relapses of Plasmodium vivax infection result from clonal hypnozoites activated at predetermined intervals. J Infect Dis 195: 934–941. doi: 10.1086/512242
[33]
Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JR, et al. (2007) Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. J Infect Dis 195: 927–933. doi: 10.1086/512241
[34]
Rosenberg R, Rungsiwongse J, Kangsadalampai S, Sattabongkot J, Suwanabun N, et al. (1992) Random mating of natural Plasmodium populations demonstrated from individual oocysts. Mol Biochem Parasitol 53: 129–133. doi: 10.1016/0166-6851(92)90015-C
[35]
Babiker HA, Ranford-Cartwright LC, Currie D, Charlwood JD, Billingsley P, et al. (1994) Random mating in a natural population of the malaria parasite Plasmodium falciparum. Parasitology 109(Pt 4): 413–421. doi: 10.1017/S0031182000080665
[36]
Bruce MC, Galinski MR, Barnwell JW, Donnelly CA, Walmsley M, et al. (2000) Genetic diversity and dynamics of plasmodium falciparum and P. vivax populations in multiply infected children with asymptomatic malaria infections in Papua New Guinea. Parasitology 121(Pt 3): 257–272. doi: 10.1017/S0031182099006356
[37]
Smith T, Maire N, Dietz K, Killeen GF, Vounatsou P, et al. (2006) Relationship between the entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria. Am J Trop Med Hyg 75: 11–18.
[38]
Ferreira MU, Karunaweera ND, da Silva-Nunes M, da Silva NS, Wirth DF, et al. (2007) Population structure and transmission dynamics of Plasmodium vivax in rural Amazonia. J Infect Dis 195: 1218–1226. doi: 10.1086/512685
[39]
Van den Eede P, Erhart A, Van der Auwera G, Van Overmeir C, Thang ND, et al. (2010) High complexity of Plasmodium vivax infections in symptomatic patients from a rural community in central Vietnam detected by microsatellite genotyping. Am J Trop Med Hyg 82: 223–227. doi: 10.4269/ajtmh.2010.09-0458
[40]
The malERA Consultative Group on Modeling (2011) A research agenda for malaria eradication: modeling. PLoS Med 8: e1000403. doi: 10.1371/journal.pmed.1000403
