ProCite
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Reference Manager
BibTeX
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-
1.
Aydin-Schmidt B, Xu W, González IJ, Polley SD, Bell D, Shakely D, Msellem MI, Björkman A, Mårtensson A, 2014. Loop mediated isothermal amplification (LAMP) accurately detects malaria DNA from filter paper blood samples of low density parasitaemias. PLoS One 9: e103905–e103909.
-
2.
Cook J et al. 2015. Loop-mediated isothermal amplification (LAMP) for point-of-care detection of asymptomatic low-density malaria parasite carriers in Zanzibar. Malar J 14: 43.
-
3.
Hopkins H et al. 2013. Highly sensitive detection of malaria parasitemia in a malaria-endemic setting: performance of a new loop-mediated isothermal amplification kit in a remote clinic in Uganda. J Infect Dis 208: 645–652.
-
4.
Vallejo AF, Martínez NL, González IJ, Arévalo-Herrera M, Herrera S, 2015. Evaluation of the loop mediated isothermal DNA amplification (LAMP) kit for malaria diagnosis in P. vivax endemic settings of Colombia. PLoS Negl Trop Dis 9: e3453.
-
5.
Paris DH, Imwong M, Faiz AM, Hasan M, Yunus EB, Silamut K, Lee SJ, Day NPJ, Dondorp AM, 2007. Loop-mediated isothermal PCR (LAMP) for the diagnosis of falciparum malaria. Am J Trop Med Hyg 77: 972–976.
-
6.
Oriero EC, Jacobs J, Van geertruyden J-P, Nwakanma D, D’Alessandro U, 2015. Molecular-based isothermal tests for field diagnosis of malaria and their potential contribution to malaria elimination. J Antimicrob Chemother 70: 2–13.
-
7.
Polley SD, Mori Y, Watson J, Perkins MD, González IJ, Notomi T, Chiodini PL, Sutherland CJ, 2010. Mitochondrial DNA targets increase sensitivity of malaria detection using loop-mediated isothermal amplification. J Clin Microbiol 48: 2866–2871.
-
8.
Han E-T, Watanabe R, Sattabongkot J, Khuntirat B, Sirichaisinthop J, Iriko H, Jin L, Takeo S, Tsuboi T, 2007. Detection of four Plasmodium species by genus- and species-specific loop-mediated isothermal amplification for clinical diagnosis. J Clin Microbiol 45: 2521–2528.
-
9.
Polley SD et al. 2013. Clinical evaluation of a loop-mediated amplification kit for diagnosis of imported malaria. J Infect Dis 208: 637–644.
-
10.
Pöschl B, Waneesorn J, Thekisoe O, Chutipongvivate S, Panagiotis K, 2010. Comparative diagnosis of malaria infections by microscopy, nested PCR, and LAMP in northern Thailand. Am J Trop Med Hyg 83: 56–60.
-
11.
Gaye A, Bousema T, Libasse G, Ndiath MO, Konaté L, Jawara M, Faye O, Sokhna C, 2015. Infectiousness of the human population to Anopheles arabiensis by direct skin feeding in an area hypoendemic for malaria in Senegal. Am J Trop Med Hyg 92: 648–652.
-
12.
Ouédraogo AL et al. 2015. Dynamics of the human infectious reservoir for malaria determined by mosquito feeding assays and ultrasensitive malaria diagnosis in Burkina Faso. J Infect Dis 213: jiv370–jiv399.
-
13.
Imwong M et al. 2015. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand–Myanmar border areas, Cambodia, and Vietnam. Malar J 14: 381.
-
14.
Hofmann N, Mwingira F, Shekalaghe S, Robinson LJ, Mueller I, Felger I, 2015. Ultra-sensitive detection of Plasmodium falciparum by amplification of multi-copy subtelomeric targets. PLoS Med 12: e1001788.
-
15.
Okello PE, Van Bortel W, Byaruhanga AM, Correwyn A, Roelants P, Talisuna A, D’Alessandro U, Coosemans M, 2006. Variation in malaria transmission intensity in seven sites throughout Uganda. Am J Trop Med Hyg 75: 219–225.
-
16.
Kamya MR et al. 2015. Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control. Am J Trop Med Hyg 92: 903–912.
-
17.
Katureebe A et al. 2016. Measures of malaria burden after long-lasting insecticidal net distribution and indoor residual spraying at three sites in Uganda: a prospective observational study. PLoS Med 13: e1002167.
-
18.
Rek J et al. 2016. Characterizing microscopic and submicroscopic malaria parasitaemia at three sites with varied transmission intensity in Uganda. Malar J 15: 470.
-
19.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52: 565–568.
-
20.
Schwartz A, Baidjoe A, Rosenthal PJ, Dorsey G, Bousema T, Greenhouse B, 2015. The effect of storage and extraction methods on amplification of Plasmodium falciparum DNA from dried blood spots. Am J Trop Med Hyg 92: 922–925.
-
21.
Hsiang MS, Lin M, Dokomajilar C, Kemere J, Pilcher CD, Dorsey G, Greenhouse B, 2010. PCR-based pooling of dried blood spots for detection of malaria parasites: optimization and application to a cohort of Ugandan children. J Clin Microbiol 48: 3539–3543.
-
22.
Wu L, van den Hoogen LL, Slater H, Walker PGT, Ghani AC, Drakeley CJ, Okell LC, 2015. Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies. Nature 528: S86–S93.
-
23.
Bonnet S, Gouagna LC, Paul RE, Safeukui I, Meunier JY, Boudin C, 2003. Estimation of malaria transmission from humans to mosquitoes in two neighbouring villages in south Cameroon: evaluation and comparison of several indices. Trans R Soc Trop Med Hyg 97: 53–59.
-
24.
Bousema T et al.. 2012. Mosquito feeding assays to determine the infectiousness of naturally infected Plasmodium falciparum gametocyte carriers. PLoS One 7: e42821.
-
25.
Lin JT et al.. 2016. Microscopic Plasmodium falciparum gametocytemia and infectivity to mosquitoes in Cambodia. J Infect Dis 213: 1491–1494.
-
26.
Felger I, Maire M, Bretscher MT, Falk N, Tiaden A, Sama W, Beck H-P, Owusu-Agyei S, Smith TA, 2012. The dynamics of natural Plasmodium falciparum infections. PLoS One 7: e45542.
-
27.
Roh ME, Oyet C, Orikiriza P, Wade M, Kiwanuka GN, Mwanga-Amumpaire J, Parikh S, Boum Y II, 2016. Asymptomatic Plasmodium infections in children in low malaria transmission setting, southwestern Uganda. Emerg Infect Dis 22: 1494–1498.
-
28.
Daniels RF et al.. 2017. Evidence of non-Plasmodium falciparum malaria infection in Kédougou, Sénégal. Malar J 16: 9.
-
29.
Miller RH, Obuya CO, Wanja EW, Ogutu B, Waitumbi J, Luckhart S, Stewart VA, 2015. Characterization of Plasmodium ovale curtisi and P. ovale wallikeri in western Kenya utilizing a novel species-specific real-time PCR assay. PLoS Negl Trop Dis 9: e0003469.
-
30.
Williams J et al.. 2016. Non-falciparum malaria infections in pregnant women in West Africa. Malar J 15: 53.
-
31.
Steinhardt LC et al.. 2013. The effect of indoor residual spraying on malaria and anemia in a high-transmission area of northern Uganda. Am J Trop Med Hyg 88: 855–861.
-
32.
Tukei BB, Beke A, Lamadrid-Figueroa H, 2017. Assessing the effect of indoor residual spraying (IRS) on malaria morbidity in northern Uganda: a before and after study. Malar J 16: 4.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 293 | 238 | 30 |
| Full Text Views | 394 | 15 | 0 |
| PDF Downloads | 117 | 10 | 0 |
Performance of Loop-Mediated Isothermal Amplification for the Identification of Submicroscopic Plasmodium falciparum Infection in Uganda
Shereen Katrak
Shereen Katrak
Department of Medicine, University of California San Francisco, San Francisco, California;
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Maxwell Murphy
Maxwell Murphy
Department of Medicine, University of California San Francisco, San Francisco, California;
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Patience Nayebare
Patience Nayebare
Infectious Diseases Research Collaboration, Kampala, Uganda;
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John Rek
John Rek
Infectious Diseases Research Collaboration, Kampala, Uganda;
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Mary Smith
Mary Smith
Chicago Medical School, Rosalind Franklin University, North Chicago, Illinois;
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Emmanuel Arinaitwe
Emmanuel Arinaitwe
Infectious Diseases Research Collaboration, Kampala, Uganda;
London School of Hygiene and Tropical Medicine, London, United Kingdom;
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London School of Hygiene and Tropical Medicine, London, United Kingdom;
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Joaniter I. Nankabirwa
Joaniter I. Nankabirwa
Infectious Diseases Research Collaboration, Kampala, Uganda;
School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Moses Kamya
Moses Kamya
Infectious Diseases Research Collaboration, Kampala, Uganda;
School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Grant Dorsey
Grant Dorsey
Department of Medicine, University of California San Francisco, San Francisco, California;
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Philip J. Rosenthal
Philip J. Rosenthal
Department of Medicine, University of California San Francisco, San Francisco, California;
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Bryan Greenhouse
Bryan Greenhouse
Department of Medicine, University of California San Francisco, San Francisco, California;
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Accurately identifying and targeting the human reservoir of malaria parasitemia is critical for malaria control, and requires a reliable and sensitive diagnostic method. Loop-mediated isothermal amplification (LAMP) is increasingly used to diagnose submicroscopic parasitemia. Although most published studies report the sensitivity of LAMP compared with nested polymerase chain reaction (PCR) as ≥ 80%, they have failed to use a consistent, sensitive diagnostic as a comparator. We used cross-sectional samples from children and adults in Tororo, Uganda, a region with high but declining transmission due to indoor residual spraying, to characterize the sensitivity and specificity of pan-Plasmodium LAMP for detecting submicroscopic infections. We compared LAMP results targeting a mitochondrial DNA sequence conserved in all Plasmodium species, performed on DNA extracted from dried blood spots, to those of a gold standard quantitative PCR assay targeting the var gene acidic terminal sequence of Plasmodium falciparum (varATS qPCR), performed on DNA extracted from 200 µL of whole blood. Using LAMP and varATS qPCR increased the detection of parasitemia 2- to 5-fold, compared with microscopy. Among microscopy-negative samples, the sensitivity of LAMP was 81.5% for detecting infection ≥ 1 parasites/µL. However, low density infections were common, and LAMP failed to identify more than half of all infections diagnosed by varATS qPCR, performing with an overall sensitivity of 44.7% for detecting submicroscopic infections ≥ 0.01 parasites/µL. Thus, although the LAMP assay is more sensitive than microscopy, it missed a significant portion of the submicroscopic reservoir. These findings have important implications for malaria control, particularly in settings where low-density infections predominate.
- Supplemental Materials (PDF 173 KB)
Author Notes
Authors’ addresses: Shereen Katrak, Maxwell Murphy, Grant Dorsey, Philip J. Rosenthal, and Bryan Greenhouse, Department of Medicine, University of California, San Francisco, CA, E-mails: shereen.katrak@ucsf.edu, maxwell.murphy@ucsf.edu, grant.dorsey@ucsf.edu, philip.rosenthal@ucsf.edu, and bryan.greenhouse@ucsf.edu. Patience Nayebare, John Rek, and Emmanuel Arinaitwe, Infectious Diseases Research Collaboration, Kampala, Uganda, E-mails: pnayebare@ymail.com, jrek@idrc-uganda.org, and earinaitwe@idrc-uganda.org. Mary Smith, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, IL, E-mail: marydsmith37@yahoo.com. Joaniter I. Nankabirwa and Moses Kamya, Makerere University College of Health Sciences, Kampala, Uganda, and Infectious Disease Research Collaboration, Kampala, Uganda, E-mails: jnankabirwa@yahoo.co.uk and mkamya@idrc-uganda.org.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Aydin-Schmidt B, Xu W, González IJ, Polley SD, Bell D, Shakely D, Msellem MI, Björkman A, Mårtensson A, 2014. Loop mediated isothermal amplification (LAMP) accurately detects malaria DNA from filter paper blood samples of low density parasitaemias. PLoS One 9: e103905–e103909.
-
2.
Cook J et al. 2015. Loop-mediated isothermal amplification (LAMP) for point-of-care detection of asymptomatic low-density malaria parasite carriers in Zanzibar. Malar J 14: 43.
-
3.
Hopkins H et al. 2013. Highly sensitive detection of malaria parasitemia in a malaria-endemic setting: performance of a new loop-mediated isothermal amplification kit in a remote clinic in Uganda. J Infect Dis 208: 645–652.
-
4.
Vallejo AF, Martínez NL, González IJ, Arévalo-Herrera M, Herrera S, 2015. Evaluation of the loop mediated isothermal DNA amplification (LAMP) kit for malaria diagnosis in P. vivax endemic settings of Colombia. PLoS Negl Trop Dis 9: e3453.
-
5.
Paris DH, Imwong M, Faiz AM, Hasan M, Yunus EB, Silamut K, Lee SJ, Day NPJ, Dondorp AM, 2007. Loop-mediated isothermal PCR (LAMP) for the diagnosis of falciparum malaria. Am J Trop Med Hyg 77: 972–976.
-
6.
Oriero EC, Jacobs J, Van geertruyden J-P, Nwakanma D, D’Alessandro U, 2015. Molecular-based isothermal tests for field diagnosis of malaria and their potential contribution to malaria elimination. J Antimicrob Chemother 70: 2–13.
-
7.
Polley SD, Mori Y, Watson J, Perkins MD, González IJ, Notomi T, Chiodini PL, Sutherland CJ, 2010. Mitochondrial DNA targets increase sensitivity of malaria detection using loop-mediated isothermal amplification. J Clin Microbiol 48: 2866–2871.
-
8.
Han E-T, Watanabe R, Sattabongkot J, Khuntirat B, Sirichaisinthop J, Iriko H, Jin L, Takeo S, Tsuboi T, 2007. Detection of four Plasmodium species by genus- and species-specific loop-mediated isothermal amplification for clinical diagnosis. J Clin Microbiol 45: 2521–2528.
-
9.
Polley SD et al. 2013. Clinical evaluation of a loop-mediated amplification kit for diagnosis of imported malaria. J Infect Dis 208: 637–644.
-
10.
Pöschl B, Waneesorn J, Thekisoe O, Chutipongvivate S, Panagiotis K, 2010. Comparative diagnosis of malaria infections by microscopy, nested PCR, and LAMP in northern Thailand. Am J Trop Med Hyg 83: 56–60.
-
11.
Gaye A, Bousema T, Libasse G, Ndiath MO, Konaté L, Jawara M, Faye O, Sokhna C, 2015. Infectiousness of the human population to Anopheles arabiensis by direct skin feeding in an area hypoendemic for malaria in Senegal. Am J Trop Med Hyg 92: 648–652.
-
12.
Ouédraogo AL et al. 2015. Dynamics of the human infectious reservoir for malaria determined by mosquito feeding assays and ultrasensitive malaria diagnosis in Burkina Faso. J Infect Dis 213: jiv370–jiv399.
-
13.
Imwong M et al. 2015. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand–Myanmar border areas, Cambodia, and Vietnam. Malar J 14: 381.
-
14.
Hofmann N, Mwingira F, Shekalaghe S, Robinson LJ, Mueller I, Felger I, 2015. Ultra-sensitive detection of Plasmodium falciparum by amplification of multi-copy subtelomeric targets. PLoS Med 12: e1001788.
-
15.
Okello PE, Van Bortel W, Byaruhanga AM, Correwyn A, Roelants P, Talisuna A, D’Alessandro U, Coosemans M, 2006. Variation in malaria transmission intensity in seven sites throughout Uganda. Am J Trop Med Hyg 75: 219–225.
-
16.
Kamya MR et al. 2015. Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control. Am J Trop Med Hyg 92: 903–912.
-
17.
Katureebe A et al. 2016. Measures of malaria burden after long-lasting insecticidal net distribution and indoor residual spraying at three sites in Uganda: a prospective observational study. PLoS Med 13: e1002167.
-
18.
Rek J et al. 2016. Characterizing microscopic and submicroscopic malaria parasitaemia at three sites with varied transmission intensity in Uganda. Malar J 15: 470.
-
19.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52: 565–568.
-
20.
Schwartz A, Baidjoe A, Rosenthal PJ, Dorsey G, Bousema T, Greenhouse B, 2015. The effect of storage and extraction methods on amplification of Plasmodium falciparum DNA from dried blood spots. Am J Trop Med Hyg 92: 922–925.
-
21.
Hsiang MS, Lin M, Dokomajilar C, Kemere J, Pilcher CD, Dorsey G, Greenhouse B, 2010. PCR-based pooling of dried blood spots for detection of malaria parasites: optimization and application to a cohort of Ugandan children. J Clin Microbiol 48: 3539–3543.
-
22.
Wu L, van den Hoogen LL, Slater H, Walker PGT, Ghani AC, Drakeley CJ, Okell LC, 2015. Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies. Nature 528: S86–S93.
-
23.
Bonnet S, Gouagna LC, Paul RE, Safeukui I, Meunier JY, Boudin C, 2003. Estimation of malaria transmission from humans to mosquitoes in two neighbouring villages in south Cameroon: evaluation and comparison of several indices. Trans R Soc Trop Med Hyg 97: 53–59.
-
24.
Bousema T et al.. 2012. Mosquito feeding assays to determine the infectiousness of naturally infected Plasmodium falciparum gametocyte carriers. PLoS One 7: e42821.
-
25.
Lin JT et al.. 2016. Microscopic Plasmodium falciparum gametocytemia and infectivity to mosquitoes in Cambodia. J Infect Dis 213: 1491–1494.
-
26.
Felger I, Maire M, Bretscher MT, Falk N, Tiaden A, Sama W, Beck H-P, Owusu-Agyei S, Smith TA, 2012. The dynamics of natural Plasmodium falciparum infections. PLoS One 7: e45542.
-
27.
Roh ME, Oyet C, Orikiriza P, Wade M, Kiwanuka GN, Mwanga-Amumpaire J, Parikh S, Boum Y II, 2016. Asymptomatic Plasmodium infections in children in low malaria transmission setting, southwestern Uganda. Emerg Infect Dis 22: 1494–1498.
-
28.
Daniels RF et al.. 2017. Evidence of non-Plasmodium falciparum malaria infection in Kédougou, Sénégal. Malar J 16: 9.
-
29.
Miller RH, Obuya CO, Wanja EW, Ogutu B, Waitumbi J, Luckhart S, Stewart VA, 2015. Characterization of Plasmodium ovale curtisi and P. ovale wallikeri in western Kenya utilizing a novel species-specific real-time PCR assay. PLoS Negl Trop Dis 9: e0003469.
-
30.
Williams J et al.. 2016. Non-falciparum malaria infections in pregnant women in West Africa. Malar J 15: 53.
-
31.
Steinhardt LC et al.. 2013. The effect of indoor residual spraying on malaria and anemia in a high-transmission area of northern Uganda. Am J Trop Med Hyg 88: 855–861.
-
32.
Tukei BB, Beke A, Lamadrid-Figueroa H, 2017. Assessing the effect of indoor residual spraying (IRS) on malaria morbidity in northern Uganda: a before and after study. Malar J 16: 4.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 293 | 238 | 30 |
| Full Text Views | 394 | 15 | 0 |
| PDF Downloads | 117 | 10 | 0 |