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Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010–2012 - Volume 21, Number 5—May 2015 - Emerging Infectious Disease journal - CDC

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Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010–2012 - Volume 21, Number 5—May 2015 - Emerging Infectious Disease journal - CDC





Volume 21, Number 5—May 2015

Research

Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010–2012

G. Christian BaldevianoComments to Author , Sheila Akinyi Okoth, Nancy Arrospide, Rommell V. Gonzalez, Juan F. Sánchez, Silvia Macedo, Silvia Conde, L. Lorena Tapia, Carola Salas, Dionicia Gamboa, Yeni Herrera, Kimberly A. Edgel, Venkatachalam Udhayakumar, and Andrés G. Lescano
Author affiliations: US Naval Medical Research Unit No. 6, Callao, Peru (G.C. Baldeviano, J.F. Sánchez, S. Macedo, L.L. Tapia, C. Salas, K.A. Edgel, A.G. Lescano)Centers for Disease Control and Prevention, Atlanta, Georgia, USA (S. Akinyi Okoth, V. Udhayakumar)Instituto Nacional de Salud del Peru, Lima, Peru (N. Arrospide); Direccion Regional de Salud de Tumbes, Tumbes, Peru (R.V. Gonzalez, S. Conde)Universidad Peruana Cayetano Heredia, Lima (D. Gamboa); Ministry of Health of Peru, Lima (Y. Herrera)

Abstract

During 2010–2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998–2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events.
During the past decade, remarkable progress in malaria control has been achieved globally (1). As low-risk areas progress toward the preelimination phase of malaria elimination (http://www.who.int/malaria/areas/elimination/overview/en/), new challenges are posed by risk for reintroduction of parasites into areas where malaria transmission was interrupted (2). Human movement from malaria-endemic regions could facilitate outbreaks in areas where malaria had been eliminated (2,3). Molecular epidemiology tools have been used to investigate the sources of malaria reintroduction (4,5). Use of these tools enables rapid characterization of potentially pathogenic or multidrug-resistant strains before they become adapted and expand to other non–malaria-endemic areas where anopheline vectors are present (69).
In Peru, malaria reemerged in the 1990s and the number of cases peaked at ≈160,000 cases in 1998 (10). Most reported cases had occurred in the Amazon Basin (Loreto region) and areas in the northern Pacific coast of Peru, including the Tumbes and Piura regions. In vivo efficacy studies conducted during 1998–2000 revealed different patterns of drug resistance between parasites in the Amazon region and coastal areas (11,12). Although parasites from the eastern Amazon region were resistant to chloroquine and sulfadoxine/pyrimethamine, parasites from the northern Pacific coast were resistant to chloroquine but remained sensitive to sulfadoxine/pyrimethamine (1113). In 2001, artesunate/mefloquine combination therapy was introduced in the Peruvian Amazon while artesunate–sulfadoxine/pyrimethamine remained in use in the northern Pacific coastal region (12).
After 2005, changes in drug policy and increased vector control efforts in Peru led to a drastic reduction in the number of malaria cases in the country. A major accomplishment was the interruption of Plasmodium falciparum transmission in the northern Pacific coast; no autochthonous malaria case has been reported since 2006. However, in October of 2010, the Regional Health Directorate in Tumbes received reports of 2 cases of P. falciparum malaria. An outbreak investigation confirmed the P. falciparum malaria epidemic in Tumbes. This outbreak continued to spread through 2012, when the last case of P. falciparum malaria was reported. Epidemiology investigations identified 2 index case-patients among military personnel stationed in Tumbes; surveillance activities conducted during the outbreak investigation suggested that these patients potentially acquired P. falciparum infection while in the Peruvian Amazon. We therefore hypothesized that a detailed genetic characterization of the parasite populations isolated during this outbreak might provide a better understanding of the source and main biological features of the parasite responsible for the reintroduction of malaria into Tumbes.
Previous genetic analyses of P. falciparum strains collected at the peak of the malaria epidemic, 1999–2000, revealed at least 5 distinct clonal lineages (clonets A–E), as defined by genotyping of 7 neutral microsatellite loci (14). These clonets, which were distributed in different areas of Peru, exhibited distinct patterns of mutations based on sequencing of the Pfcrt, Pfmdr1, Pfdhpsand Pfdhfr genes (14). Considering these historical data, we tested the following hypotheses. First, if the P. falciparum outbreak in Tumbes was caused by bottlenecked parasites from the coastal region, the parasites causing this outbreak would be genetically similar or closely related to clonet E, which was the only lineage found in the northern Pacific coast during 1999–2000. Second, if the parasite was introduced from the Peruvian Amazon, then the parasites causing this outbreak would be related to clonets A, B, C, or D. Third, if these parasites were introduced from outside Peru, they may have different molecular signatures.


Dr. Baldeviano is the head of the Immunology and Vaccine Development Unit, Department of Parasitology, NAMRU-6. His research focuses on the use of genetic, immunologic, and high-throughput tools for the control and prevention of malaria.

Acknowledgments


We are grateful to all the personnel of the Ministry of Health in Tumbes and Lima who were involved in the response to the outbreak and who assisted with collection of patient information and samples. We also thank Jaime Chang and Guillermo Gonzalvez for their guidance and contributions to the control of the outbreak, and we acknowledge the assistance provided by the Center for Global Health of the Universidad Peruana Cayetano Heredia, which provided valuable logistical support to this study.
This work was funded by the US Department of Defense Armed Forces Health Surveillance Center, Global Emerging Infectious Systems Division, through the Malaria Pillar Sustainment grant awarded to A.G.L. In addition, this investigation was partly supported by the Amazon Malaria Initiative, which is financially supported by the US Agency for International Development. S.A. was supported by the American Society of Microbiology/CDC Postdoctoral Fellowship Program. The participation of A.G.L. in this investigation was sponsored by training grant NIH/FIC 2D43 TW007393 awarded to NAMRU-6 by the Fogarty International Center of the US National Institutes of Health.

References

  1. World Health Organization. Malaria; country profiles 2012 [cited 2014 Dec 1] http://www.who.int/malaria/publications/country-profiles/en/index.html
  2. Cotter CSturrock HJHsiang MSLiu JPhillips AAHwang JThe changing epidemiology of malaria elimination: new strategies for new challenges.Lancet2013;382:90011DOIPubMed
  3. Webster-Kerr KPeter Figueroa JWeir PLLewis-Bell KBaker EHorner-Bryce JSuccess in controlling a major outbreak of malaria because ofPlasmodium falciparum in Jamaica. Trop Med Int Health2011;16:298306DOIPubMed
  4. Hanna JNRitchie SAEisen DPCooper RDBrookes DLMontgomery BLAn outbreak of Plasmodium vivax malaria in Far North Queensland, 2002.Med J Aust2004;180:248 .PubMed
  5. Arez APSnounou GPinto JSousa CAModiano DRibeiro HA clonal Plasmodium falciparum population in an isolated outbreak of malaria in the Republic of Cabo Verde. Parasitology1999;118:34755DOIPubMed
  6. Djimdé AADolo AOuattara ADiakite SPlowe CVDoumbo OKMolecular diagnosis of resistance to antimalarial drugs during epidemics and in war zones. J Infect Dis2004;190:8535DOIPubMed
  7. Samudio FSantamaria AMObaldia N IIIPascale JMBayard VCalzada JEPrevalence of Plasmodium falciparum mutations associated with antimalarial drug resistance during an epidemic in Kuna Yala, Panama, Central America. Am J Trop Med Hyg2005;73:83941 .PubMed
  8. Laserson KFPetralanda IAlmera RBarker RH JrSpielman AMaguire JHGenetic characterization of an epidemic of Plasmodium falciparummalaria among Yanomami Amerindians. J Infect Dis1999;180:20815DOIPubMed
  9. Legrand EVolney BLavergne ATournegros CFlorent LAccrombessi DMolecular analysis of two local falciparum malaria outbreaks on the French Guiana coast confirms the msp1 B-K1/varD genotype association with severe malaria. Malar J2005;4:26DOIPubMed
  10. Aramburú Guarda JRamal Asayag CWitzig RMalaria reemergence in the Peruvian Amazon region. Emerg Infect Dis1999;5:20915 .DOIPubMed
  11. Durand SMarquino WCabezas CUtz GFiestas VCairo JUnusual pattern of Plasmodium falciparum drug resistance in the northwestern Peruvian Amazon region. Am J Trop Med Hyg2007;76:6148 .PubMed
  12. Ruebush TK IINeyra DCabezas CModifying national malaria treatment policies in Peru. J Public Health Policy2004;25:32845DOIPubMed
  13. Magill AJZegarra JGarcia CMarquino WRuebush TK IIEfficacy of sulfadoxine-pyrimethamine and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon basin of Peru. Rev Soc Bras Med Trop2004;37:27981DOIPubMed
  14. Griffing SMMixson-Hayden TSridaran SAlam MTMcCollum AMCabezas CSouth American Plasmodium falciparum after the malaria eradication era: clonal population expansion and survival of the fittest hybrids. PLoS ONE2011;6:e23486DOIPubMed
  15. Marquiño WYlquimiche LHermenegildo YPalacios AMFalconi ECabezas CEfficacy and tolerability of artesunate plus sulfadoxine-pyrimethamine and sulfadoxine-pyrimethamine alone for the treatment of uncomplicated Plasmodium falciparum malaria in Peru. Am J Trop Med Hyg2005;72:56872 .PubMed
  16. Bacon DJMcCollum AMGriffing SMSalas CSoberon VSantolalla MDynamics of malaria drug resistance patterns in the Amazon basin region following changes in Peruvian national treatment policy for uncomplicated malaria. Antimicrob Agents Chemother2009;53:204251.DOIPubMed
  17. Singh BBobogare ACox-Singh JSnounou GAbdullah MSRahman HAA genus- and species-specific nested polymerase chain reaction malaria detection assay for epidemiologic studies. Am J Trop Med Hyg1999;60:68792 .PubMed
  18. Anderson TJSu XZBockarie MLagog MDay KPTwelve microsatellite markers for characterization of Plasmodium falciparum from finger-prick blood samples. Parasitology1999;119:11325DOIPubMed
  19. Anderson TJHaubold BWilliams JTEstrada-Franco JGRichardson LMollinedo RMicrosatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. Mol Biol Evol2000;17:146782DOIPubMed
  20. Echeverry DFNair SOsorio LMenon SMurillo CAnderson TJLong term persistence of clonal malaria parasite Plasmodium falciparum lineages in the Colombian Pacific region. BMC Genet2013;14:2DOIPubMed
  21. McCollum AMMueller KVillegas LUdhayakumar VEscalante AACommon origin and fixation of Plasmodium falciparum dhfr and dhps mutations associated with sulfadoxine-pyrimethamine resistance in a low-transmission area in South America. Antimicrob Agents Chemother.2007;51:208591DOIPubMed
  22. Nair SNash DSudimack DJaidee ABarends MUhlemann ACRecurrent gene amplification and soft selective sweeps during evolution of multidrug resistance in malaria parasites. Mol Biol Evol2007;24:56273DOIPubMed
  23. Griffing SSyphard LSridaran SMcCollum AMMixson-Hayden TVinayak Spfmdr1 amplification and fixation of pfcrt chloroquine resistance alleles in Plasmodium falciparum in Venezuela. Antimicrob Agents Chemother2010;54:15729DOIPubMed
  24. Mejia Torres REBanegas EIMendoza MDiaz CBucheli STFontecha GAEfficacy of chloroquine for the treatment of uncomplicated Plasmodium falciparum malaria in Honduras. Am J Trop Med Hyg2013;88:8504DOIPubMed
  25. Gamboa DHo MFBendezu JTorres KChiodini PLBarnwell JWA large proportion of P. falciparum isolates in the Amazon region of Peru lackpfhrp2 and pfhrp3: implications for malaria rapid diagnostic tests. PLoS ONE2010;5:e8091DOIPubMed
  26. Hunter PRWilkinson DCLake IRHarrison FCSyed QHadfield SJMicrosatellite typing of Cryptosporidium parvum in isolates from a waterborne outbreak. J Clin Microbiol2008;46:38667DOIPubMed
  27. Zhou ZGriffing SMde Oliveira AMMcCollum AMQuezada WMArrospide NDecline in sulfadoxine-pyrimethamine-resistant alleles after change in drug policy in the Amazon region of Peru. Antimicrob Agents Chemother2008;52:73941DOIPubMed

Figures

Tables

Suggested citation for this article: Baldeviano GC, Akinyi Okoth S, Arrospide N, Gonzalez RV, Sánchez JF, Macedo S, et al. Molecular epidemiology of malaria outbreak, Tumbes, Peru, 2010–2012. Emerg Infect Dis. 2015 May [date cited]. http://dx.doi.org/10.3201/eid2105.141427
DOI: 10.3201/eid2105.141427

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