• 1.

    World Health Organization , 2020. World Malaria Report. Geneva, Switzerland: WHO.

  • 2.

    Krotoski WA, 1989. The hypnozoite and malarial relapse. Prog Clin Parasitol 1: 119.

  • 3.

    Adams JH, Mueller I, 2017. The biology of Plasmodium vivax. Cold Spring Harb Perspect Med 7: a025585.

  • 4.

    Bousema T, Drakeley C, 2011. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev 24: 377410.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Vallejo AF, García J, Amado-Garavito AB, Arévalo-Herrera M, Herrera S, 2016. Plasmodium vivax gametocyte infectivity in sub-microscopic infections. Malar J 15: 48.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Collins KA et al., 2020. A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions. J Clin Invest 130: 29202927.

  • 7.

    Smalley ME, Brown J, Bassett NM, 1981. The rate of production of Plasmodium falciparum gametocytes during natural infections. Trans R Soc Trop Med Hyg 75: 318319.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Schneider P, Greischar MA, Birget PLG, Repton C, Mideo N, Reece SE, 2018. Adaptive plasticity in the gametocyte conversion rate of malaria parasites. PLoS Pathog 14: e1007371.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Lefèvre T, Vantaux A, Dabiré KR, Mouline K, Cohuet A, 2013. Non-genetic determinants of mosquito competence for malaria parasites. PLoS Pathog 9: e1003365.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Tadesse FG, Meerstein-Kessel L, Gonçalves BP, Drakeley C, Ranford-Cartwright L, Bousema T, 2019. Gametocyte sex ratio: the key to understanding Plasmodium falciparum transmission? Trends Parasitol 35: 226238.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Boyd MF, Stratman-Thomas WK, Kitchen SF, 1935. On the relative susceptibility of Anopheles quadrimaculatus to Plasmodium vivax and Plasmodium falciparum .Am J Trop Med Hyg 15: 485493.

    • Search Google Scholar
    • Export Citation
  • 12.

    Abeles SR, Chuquiyauri R, Tong C, Vinetz JM, 2013. Human host-derived cytokines associated with Plasmodium vivax transmission from acute malaria patients to Anopheles darlingi mosquitoes in the Peruvian Amazon. Am J Trop Med Hyg 88: 11301137.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Meibalan E, Marti M, 2017. Biology of malaria transmission. Cold Spring Harb Perspect Med 7: a025452.

  • 14.

    Bennink S, Kiesow MJ, Pradel G, 2016. The development of malaria parasites in the mosquito midgut. Cell Microbiol 18: 905918.

  • 15.

    Bradley J et al., 2018. Predicting the likelihood and intensity of mosquito infection from sex specific Plasmodium falciparum gametocyte density. eLife 7: e34463.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Bansal GP, Weinstein CS, Kumar N, 2016. Insight into phagocytosis of mature sexual (gametocyte) stages of Plasmodium falciparum using a human monocyte cell line. Acta Trop 157: 96101.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Clayton AM, Dong Y, Dimopoulos G, 2014. The Anopheles innate immune system in the defense against malaria infection. J Innate Immunol 6: 169181.

  • 18.

    Molina-Cruz A, Zilversmit MM, Neafsey DE, Hartl DL, Barillas-Mury C, 2016. Mosquito vectors and the globalization of Plasmodium falciparum malaria. Annu Rev Genet 50: 447465.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Kiattibutr K et al., 2017. Infectivity of symptomatic and asymptomatic Plasmodium vivax infections to a southeast Asian vector, Anopheles dirus. Int J Parasitol 47: 163170.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Bousema T et al., 2012. Mosquito feeding assays to determine the infectiousness of naturally infected Plasmodium falciparum gametocyte carriers. PLoS One 7: e42821.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Andolina C et al., 2021. Sources of persistent malaria transmission in a setting with effective malaria control in eastern Uganda: a longitudinal, observational cohort study. Lancet Infect Dis 21: 15681578.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Muirhead-Thomson RC, 1957. The malarial infectivity of an African village population to mosquitoes (Anopheles gambiae): a random xenodiagnostic survey. Am J Trop Med Hyg 6: 971979.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Bonnet S, Gouagna C, Safeukui I, Meunier JY, Boudin C, 2000. Comparison of artificial membrane feeding with direct skin feeding to estimate infectiousness of Plasmodium falciparum gametocyte carriers to mosquitoes. Trans R Soc Trop Med Hyg 94: 103106.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Diallo M et al., 2008. Evaluation and optimization of membrane feeding compared to direct feeding as an assay for infectivity. Malar J 7: 248.

  • 25.

    Sattabongkot J, Maneechai N, Phunkitchar V, Eikarat N, Khuntirat B, Sirichaisinthop J, Burge R, Coleman RE, 2003. Comparison of artificial membrane feeding with direct skin feeding to estimate the infectiousness of Plasmodium vivax gametocyte carriers to mosquitoes. Am J Trop Med Hyg 69: 529535.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Rosas-Aguirre A, Guzman-Guzman M, Gamboa D, Chuquiyauri R, Ramirez R, Manrique P, Carrasco-Escobar G, Puemape C, Llanos-Cuentas A, Vinetz JM, 2017. Micro-heterogeneity of malaria transmission in the Peruvian Amazon: a baseline assessment underlying a population-based cohort study. Malar J 16: 312.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Rovira-Vallbona E, Contreras-Mancilla JJ, Ramirez R, Guzmán-Guzmán M, Carrasco-Escobar G, Llanos-Cuentas A, Vinetz JM, Gamboa D, Rosanas-Urgell A, 2017. Predominance of asymptomatic and sub-microscopic infections characterizes the Plasmodium gametocyte reservoir in the Peruvian Amazon. PLoS Negl Trop Dis 11: e0005674.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Lin JT, Saunders DL, Meshnick SR, 2014. The role of submicroscopic parasitemia in malaria transmission: what is the evidence? Trends Parasitol 30: 183190.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Recker M, Bull PC, Buckee CO, 2018. Recent advances in the molecular epidemiology of clinical malaria. F1000Research 7: 1159.

    • Crossref
    • Export Citation
  • 30.

    Ministerio de Salud del Perú (MINSA) , 2010. Norma Técnica de Salud para el Control de Calidad del Diagnóstico Microscópico de Malaria. Lima, Peru: MINSA.

    • Search Google Scholar
    • Export Citation
  • 31.

    Mangold KA, Manson RU, Koay ESC, Stephens L, Regner M, Thomson RB, Peterson LR, Kaul KL, 2005. Real-time PCR for detection and identification of Plasmodium spp. J Clin Microbiol 43: 24352440.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Rougemont M, Van Saanen M, Sahli R, Hinrikson HP, Bille J, Jaton K, 2004. Detection of four Plasmodium species in blood from humans by 18S rRNA gene subunit-based and species-specific real-time PCR assays. J Clin Microbiol 42: 56365643.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Ministerio de Salud del Perú (MINSA) , 2015. Norma Técnica de Salud para la Atención de la Malaria y Malaria Grave en el Perú. Lima, Perú: MINSA.

  • 34.

    Kim K, Tsuda Y, Yamada A, 2009. Bloodmeal identification and detection of avian malaria parasite from mosquitoes (Diptera: Culicidae) inhabiting coastal areas of Tokyo Bay, Japan. J Med Entomol 46: 12301234.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Vantaux A et al., 2018. Contribution to malaria transmission of symptomatic and asymptomatic parasite carriers in Cambodia. J Infect Dis 217: 15611568.

  • 36.

    Tadesse FG et al., 2018. The relative contribution of symptomatic and asymptomatic Plasmodium vivax and Plasmodium falciparum infections to the infectious reservoir in a low-endemic setting in Ethiopia. Clin Infect Dis Off Publ Infect Dis Soc Am 66: 18831891.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Alves MJCP, Mayo RC, Donalisio MR, 2004. History, epidemiology and control of malaria in Campinas Region, São Paulo State, Brazil, 1980 to 2000. Rev Soc Bras Med Trop 37: 4145.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Vallejo AF, Rubiano K, Amado A, Krystosik AR, Herrera S, Arévalo-Herrera M, 2016. Optimization of a membrane feeding assay for Plasmodium vivax infection in Anopheles albimanus. PLoS Negl Trop Dis 10: e0004807.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Lin JT et al., 2016. Microscopic Plasmodium falciparum gametocytemia and infectivity to mosquitoes in Cambodia. J Infect Dis 213: 14911494.

  • 40.

    Ouédraogo AL et al., 2009. Substantial contribution of submicroscopical Plasmodium falciparum gametocyte carriage to the infectious reservoir in an area of seasonal transmission. PLoS One 4: e8410.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41.

    Bousema T, Okell L, Felger I, Drakeley C, 2014. Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nat Rev Microbiol 12: 833840.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Mueller I, Galinski MR, Baird JK, Carlton JM, Kochar DK, Alonso PL, del Portillo HA, 2009. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect Dis 9: 555566.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    Boyd MF, Kitchen SF, 1937. On the infectiousness of patients infected with Plasmodium vivax and Plasmodium falciparum .Am J Trop Med Hyg 17: 253262.

    • Search Google Scholar
    • Export Citation
  • 44.

    McCarthy JS et al., 2013. Experimentally induced blood-stage Plasmodium vivax infection in healthy volunteers. J Infect Dis 208: 16881694.

  • 45.

    Tadesse FG et al., 2021. Anopheles stephensi mosquitoes as vectors of Plasmodium vivax and falciparum, Horn of Africa, 2019. Emerg Infect Dis 27: 603607.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46.

    Chali W et al., 2020. Comparison of infectivity of Plasmodium vivax to wild-caught and laboratory-adapted (colonized) Anopheles arabiensis mosquitoes in Ethiopia. Parasit Vectors 13: 120.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47.

    Gonçalves BP et al., 2017. Examining the human infectious reservoir for Plasmodium falciparum malaria in areas of differing transmission intensity. Nat Commun 8: 1133.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48.

    Tiono AB, Guelbeogo MW, Sagnon NF, Nébié I, Sirima SB, Mukhopadhyay A, Hamed K, 2013. Dynamics of malaria transmission and susceptibility to clinical malaria episodes following treatment of Plasmodium falciparum asymptomatic carriers: results of a cluster-randomized study of community-wide screening and treatment, and a parallel entomology study. BMC Infect Dis 13: 535.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 553 553 236
Full Text Views 30 30 19
PDF Downloads 72 72 37
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Insights into Plasmodium vivax Asymptomatic Malaria Infections and Direct Skin-Feeding Assays to Assess Onward Malaria Transmission in the Amazon

View More View Less
  • 1 Department of Biology, London School of Hygiene and Tropical Medicine, London, UK;
  • | 2 Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima, Peru;
  • | 3 Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru;
  • | 4 Laboratorio de Malaria, Parásitos y Vectores, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru;
  • | 5 Facultad de Salud Pública, Universidad Peruana Cayetano Heredia, Lima, Peru;
  • | 6 Department of Biomedical Sciences, School of Public Health, University at Albany–State University of New York, Albany, New York;
  • | 7 Wadsworth Center, New York State Department of Health, Albany, New York;
  • | 8 Departamento de Ciencias Celulares y Moleculares, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru;
  • | 9 S Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California;
  • | 10 Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
Restricted access

ABSTRACT.

Understanding the reservoir and infectivity of Plasmodium gametocytes to vector mosquitoes is crucial to align strategies aimed at malaria transmission elimination. Yet, experimental information is scarce regarding the infectivity of Plasmodium vivax for mosquitoes in diverse epidemiological settings where the proportion of asymptomatically infected individuals varies at a microgeographic scale. We measured the transmissibility of clinical and subclinical P. vivax malaria parasite carriers to the major mosquito vector in the Amazon Basin, Nyssorhynchus darlingi (formerly Anopheles). A total of 105 participants with natural P. vivax malaria infection were recruited from a cohort study in Loreto Department, Peruvian Amazon. Four of 18 asymptomatic individuals with P. vivax positivity by blood smear infected colony-grown Ny. darlingi (22%), with 2.6% (19 of 728) mosquitoes infected. In contrast, 77% (44/57) of symptomatic participants were infectious to mosquitoes with 51% (890 of 1,753) mosquitoes infected. Infection intensity was greater in symptomatic infections (mean, 17.8 oocysts/mosquito) compared with asymptomatic infections (mean, 0.28 oocysts/mosquito), attributed to parasitemia/gametocytemia level. Paired experiments (N = 27) using direct skin-feeding assays and direct membrane mosquito-feeding assays showed that infectivity to mosquitoes was similar for both methods. Longitudinal studies with longer follow-up of symptomatic and asymptomatic parasite infections are needed to determine the natural variations of disease transmissibility.

    • Supplemental Materials (PDF 179 KB)

Author Notes

Address correspondence to Katherine Torres, Malaria Laboratory, Laboratorios de Investigación y Desarrollo, Faculty of Science and Institute of Tropical Medicine Alexander von Humboldt, Universidad Peruana Cayetano Heredia, 15102, Lima, Perú. E-mail: katherine.torres.f@upch.pe

These authors contributed equally to this work.

Financial support: This research was funded by NIH National Institute of Allergy and Infectious Diseases (NIAID) (U19AI089681) to J. M. V. and was funded in part by NIH-NIAID (R01AI110112) to J. E. C.

Authors’ addresses: Marta Moreno, Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK, E-mail: marta.moreno@lshtm.ac.uk. Katherine Torres, Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima, Peru, E-mail: katherine.torres.f@upch.pe. Carlos Tong, Gerson Guedez, Lutecio Torres, Manuela Herrera-Varela, Layné Guerra, Mitchel Guzman, Daniel Wong, and Roberson Ramirez, Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mails: ctong32@gmail.com, gersonerick@hotmail.es, eddie.torres.t@upch.pe, manuelahv82@gmail.com, laygueva.12@gmail.com, guzman.mitch@gmail.com, danielantonio@outlook.com.pe, and roberson.ramirez.s@upch.pe. Stefano S. García Castillo, Laboratorio de Malaria, Parásitos y Vectores, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mail: stefano.garcia.c@upch.pe. Gabriel Carrasco-Escobar and Alejandro Llanos-Cuentas, Department of Epidemiology, University of California San Diego, La Jolla, CA, E-mails: gabriel.carrasco@upch.pe and alejandro.llanos.c@upch.pe. Jan E. Conn, Department of Biomedical Sciences, School of Public Health, University at Albany–State University of New York, Albany, NY, and Wadsworth Center, New York State Department of Health, Albany, NY, E-mail: jan.conn@health.ny.gov. Dionicia Gamboa, Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima, Peru, Laboratorio de Malaria, Parásitos y Vectores, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru, and Departamento de Ciencias Celulares y Moleculares, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mail: dionigamboa@yahoo.com. Joseph M. Vinetz, Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA, Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima, Peru, and Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, E-mail: joseph.vinetz@yale.edu.

Save