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1.
World Health Organization, 2018. World Malaria Report 2018. Geneva, Switzerland: WHO.
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2.
Smith T, Felger I, Tanner M, Beck HP, 1999. Premunition in Plasmodium falciparum infection: insights from the epidemiology of multiple infections. Trans R Soc Trop Med Hyg 93: 59–64.
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3.
Rogier C, Commenges D, Trape JF, 1996. Evidence for an age-dependent pyrogenic threshold of Plasmodium falciparum parasitemia in highly endemic populations. Am J Trop Med Hyg 54: 613–619.
-
4.
Buchwald AG et al. 2019. Clinical implications of asymptomatic Plasmodium falciparum infections in Malawi. Clin Infect Dis 68: 106–112.
-
5.
Al-Yaman F, Genton B, Reeder JC, Anders RF, Smith T, Alpers MP, 1997. Reduced risk of clinical malaria in children infected with multiple clones of Plasmodium falciparum in a highly endemic area: a prospective community study. Trans R Soc Trop Med Hyg 91: 602–605.
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6.
Müller DA, Charlwood JD, Felger I, Ferreira C, do Rosario V, Smith T, 2001. Prospective risk of morbidity in relation to multiplicity of infection with Plasmodium falciparum in São Tomé. Acta Trop 78: 155–162.
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7.
Ofosu-Okyere A, Mackinnon MJ, Sowa MP, Koram KA, Nkrumah F, Osei YD, Hill WG, Wilson MD, Arnot DE, 2001. Novel Plasmodium falciparum clones and rising clone multiplicities are associated with the increase in malaria morbidity in Ghanaian children during the transition into the high transmission season. Parasitology 123: 113–123.
-
8.
Zainabadi K, Adams M, Han ZY, Lwin HW, Han KT, Ouattara A, Thura S, Plowe CV, Nyunt MM, 2017. A novel method for extracting nucleic acids from dried blood spots for ultrasensitive detection of low-density Plasmodium falciparum and Plasmodium vivax infections. Malar J 16: 377.
-
9.
Wwarn, 2015. Molecular Testing for Malaria Standard Operating Procedure (SOP) msp1, msp2, and glurp PCR. Available at: https://www.wwarn.org/tools-resources/procedures/agarose-gel-electrophoresis-msp1-msp2-and-glurp. Accessed May 28, 2019.
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10.
Wwarn, 2015. Agarose Gel Electrophoresis of msp1, msp2 and glurp v1.1. Available at: https://www.wwarn.org/tools-resources/procedures/agarose-gel-electrophoresis-msp1-msp2-and-glurp. Accessed May 28, 2019.
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11.
Smith T, Schellenberg JA, Hayes R, 1994. Attributable fraction estimates and case definitions for malaria in endemic. Stat Med 13: 2345–2358.
-
12.
Contamin H, Fandeur T, Bonnefoy S, Skouri F, Ntoumi F, Mercereau-uijalon O, 1995. PCR typing of field isolates of Plasmodium falciparum. J Clinical Microbiol 33: 944–951.
-
13.
Farnert A et al. 2001. Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study. Trans R Soc Trop Med Hyg 95: 225–232.
-
14.
Lerch A, Koepfli C, Hofmann NE, Kattenberg JH, Rosanas-Urgell A, Betuela I, Mueller I, Felger I, 2019. Longitudinal tracking and quantification of individual Plasmodium falciparum clones in complex infections. Sci Rep 9: 3333.
-
15.
Denise LD, Carlota D, Baird JK, 2009. Acquired immunity to malaria. Clin Microbiol Rev 22: 13–36.
-
16.
Hviid L, 2005. Naturally acquired immunity to Plasmodium falciparum malaria in Africa. Acta Trop 95: 270–275.
-
17.
Pinkevych M, Petravic J, Bereczky S, Rooth I, Farnert A, Davenport MP, 2015. Understanding the relationship between Plasmodium falciparum growth rate and multiplicity of infection. J Infect Dis 211: 1121–1127.
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18.
Wright GJ, Rayner JC, 2014. Plasmodium falciparum erythrocyte invasion: combining function with immune evasion. PLoS Pathog 10: e1003943.
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19.
Pacheco MA, Lopez-Perez M, Vallejo AF, Herrera S, Arévalo-Herrera M, Escalante AA, 2016. Multiplicity of infection and disease severity in Plasmodium vivax. PLoS Negl Trop Dis 10: e0004355.
-
20.
Bei AK et al. 2018. Dramatic changes in malaria population genetic complexity in Dielmo and Ndiop, Senegal, revealed using genomic surveillance. J Infect Dis 217: 622–627.
| Past two years | Past Year | Past 30 Days | |
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Impact of Multiplicity of Plasmodium falciparum Infection on Clinical Disease in Malawi
Dominique Earland
Dominique Earland
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;
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Andrea G. Buchwald
Andrea G. Buchwald
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;
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Alick Sixpence
Alick Sixpence
Malaria Alert Centre, Communicable Disease Action Centre, University of Malawi College of Medicine, Blantyre, Malawi;
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Mabvuto Chimenya
Mabvuto Chimenya
Malaria Alert Centre, Communicable Disease Action Centre, University of Malawi College of Medicine, Blantyre, Malawi;
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Milius Damson
Milius Damson
Malaria Alert Centre, Communicable Disease Action Centre, University of Malawi College of Medicine, Blantyre, Malawi;
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Karl B. Seydel
Karl B. Seydel
College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan
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Don P. Mathanga
Don P. Mathanga
Malaria Alert Centre, Communicable Disease Action Centre, University of Malawi College of Medicine, Blantyre, Malawi;
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Terrie E. Taylor
Terrie E. Taylor
College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan
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Miriam K. Laufer
Miriam K. Laufer
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;
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Multiplicity of infection (MOI), the number of unique Plasmodium falciparum parasite genotypes found in one infected individual, may contribute to the development of clinical malaria disease. However, the independent contribution of MOI and parasite density to clinical disease has not been well characterized. We conducted a two-year longitudinal cohort study of adults and children in a high-transmission setting in Malawi to test the hypothesis that increased MOI was independently associated with clinical disease, after accounting for parasite density. Of 1,062 episodes of infection, 477 (44.9%) were associated with symptoms. After controlling for repeated measures within an individual, key demographic factors, and parasite density, there was no association between MOI and clinical disease (OR = 1.02, 95% CI: 0.70–1.51). Although the limited ability to discern MOI in low-density asymptomatic infections may have impacted our results, we conclude that MOI is not an independent risk factor for clinical disease.
Author Notes
Disclosure: The material and content in this manuscript are original. The study was approved by the ethical review committee of the University of Malawi College of Medicine and University of Maryland College of Medicine.
Financial support: This work was supported by the National Institutes of Health Malawi International Center of Excellence for Malaria Research grant [U19AI089683], the National Institute of Allergy and Infectious Disease [K24AI114996]. This research was also supported by the University of Maryland, Baltimore, Postbaccalaureate Research Education Program [R25GM113262].
Authors’ addresses: Dominique Earland, Andrea G. Buchwald, and Miriam K. Laufer, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, E-mails: dearland@som.umaryland.edu, andreabuchwald@umaryland.edu, and mlaufer@som.umaryland.edu. Alick Sixpence, Mabvuto Chimenya, Milius Damson, and Don P. Mathanga, Malaria Alert Center, University of Malawi College of Medicine, Blantyre, Malawi, E-mails: asixpence@mac.medcol.mw, mschim06@gmail.com, milliusd@gmail.com, and dmathang@mac.medcol.mw. Karl B. Seydel and Terrie E. Taylor, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, E-mails: seydel@msu.edu and ttmalawi@msu.edu.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2018. World Malaria Report 2018. Geneva, Switzerland: WHO.
-
2.
Smith T, Felger I, Tanner M, Beck HP, 1999. Premunition in Plasmodium falciparum infection: insights from the epidemiology of multiple infections. Trans R Soc Trop Med Hyg 93: 59–64.
-
3.
Rogier C, Commenges D, Trape JF, 1996. Evidence for an age-dependent pyrogenic threshold of Plasmodium falciparum parasitemia in highly endemic populations. Am J Trop Med Hyg 54: 613–619.
-
4.
Buchwald AG et al. 2019. Clinical implications of asymptomatic Plasmodium falciparum infections in Malawi. Clin Infect Dis 68: 106–112.
-
5.
Al-Yaman F, Genton B, Reeder JC, Anders RF, Smith T, Alpers MP, 1997. Reduced risk of clinical malaria in children infected with multiple clones of Plasmodium falciparum in a highly endemic area: a prospective community study. Trans R Soc Trop Med Hyg 91: 602–605.
-
6.
Müller DA, Charlwood JD, Felger I, Ferreira C, do Rosario V, Smith T, 2001. Prospective risk of morbidity in relation to multiplicity of infection with Plasmodium falciparum in São Tomé. Acta Trop 78: 155–162.
-
7.
Ofosu-Okyere A, Mackinnon MJ, Sowa MP, Koram KA, Nkrumah F, Osei YD, Hill WG, Wilson MD, Arnot DE, 2001. Novel Plasmodium falciparum clones and rising clone multiplicities are associated with the increase in malaria morbidity in Ghanaian children during the transition into the high transmission season. Parasitology 123: 113–123.
-
8.
Zainabadi K, Adams M, Han ZY, Lwin HW, Han KT, Ouattara A, Thura S, Plowe CV, Nyunt MM, 2017. A novel method for extracting nucleic acids from dried blood spots for ultrasensitive detection of low-density Plasmodium falciparum and Plasmodium vivax infections. Malar J 16: 377.
-
9.
Wwarn, 2015. Molecular Testing for Malaria Standard Operating Procedure (SOP) msp1, msp2, and glurp PCR. Available at: https://www.wwarn.org/tools-resources/procedures/agarose-gel-electrophoresis-msp1-msp2-and-glurp. Accessed May 28, 2019.
-
10.
Wwarn, 2015. Agarose Gel Electrophoresis of msp1, msp2 and glurp v1.1. Available at: https://www.wwarn.org/tools-resources/procedures/agarose-gel-electrophoresis-msp1-msp2-and-glurp. Accessed May 28, 2019.
-
11.
Smith T, Schellenberg JA, Hayes R, 1994. Attributable fraction estimates and case definitions for malaria in endemic. Stat Med 13: 2345–2358.
-
12.
Contamin H, Fandeur T, Bonnefoy S, Skouri F, Ntoumi F, Mercereau-uijalon O, 1995. PCR typing of field isolates of Plasmodium falciparum. J Clinical Microbiol 33: 944–951.
-
13.
Farnert A et al. 2001. Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study. Trans R Soc Trop Med Hyg 95: 225–232.
-
14.
Lerch A, Koepfli C, Hofmann NE, Kattenberg JH, Rosanas-Urgell A, Betuela I, Mueller I, Felger I, 2019. Longitudinal tracking and quantification of individual Plasmodium falciparum clones in complex infections. Sci Rep 9: 3333.
-
15.
Denise LD, Carlota D, Baird JK, 2009. Acquired immunity to malaria. Clin Microbiol Rev 22: 13–36.
-
16.
Hviid L, 2005. Naturally acquired immunity to Plasmodium falciparum malaria in Africa. Acta Trop 95: 270–275.
-
17.
Pinkevych M, Petravic J, Bereczky S, Rooth I, Farnert A, Davenport MP, 2015. Understanding the relationship between Plasmodium falciparum growth rate and multiplicity of infection. J Infect Dis 211: 1121–1127.
-
18.
Wright GJ, Rayner JC, 2014. Plasmodium falciparum erythrocyte invasion: combining function with immune evasion. PLoS Pathog 10: e1003943.
-
19.
Pacheco MA, Lopez-Perez M, Vallejo AF, Herrera S, Arévalo-Herrera M, Escalante AA, 2016. Multiplicity of infection and disease severity in Plasmodium vivax. PLoS Negl Trop Dis 10: e0004355.
-
20.
Bei AK et al. 2018. Dramatic changes in malaria population genetic complexity in Dielmo and Ndiop, Senegal, revealed using genomic surveillance. J Infect Dis 217: 622–627.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 43 | 43 | 5 |
| Full Text Views | 632 | 155 | 3 |
| PDF Downloads | 245 | 52 | 0 |