Girma S , Cheaveau J , Mohon AN , Marasinghe D , Legese R , Balasingam N , Abera A , Feleke SM , Golassa L , Pillai DR , 2019. Prevalence and epidemiological characteristics of asymptomatic malaria based on ultrasensitive diagnostics: a cross-sectional study. Clin Infect Dis 69: 1003–1010.
Awandu SS , Raman J , Bousema T , Birkholtz LM , 2019. Ultralow-density Plasmodium falciparum infections in African settings. Clin Infect Dis 69: 1463–1464.
Taylor SM , Juliano JJ , Trottman PA , Griffin JB , Landis SH , Kitsa P , Tshefu AK , Meshnick SR , 2010. High-throughput pooling and real-time PCR-based strategy for malaria detection. J Clin Microbiol 48: 512–519.
Beshir KB , Hallett RL , Eziefula AC , Bailey R , Watson J , Wright SG , Chiodini PL , Polley SD , Sutherland CJ , 2010. Measuring the efficacy of anti-malarial drugs in vivo: quantitative PCR measurement of parasite clearance. Malar J 9: 312.
Adams M et al. 2015. An ultrasensitive reverse transcription polymerase chain reaction assay to detect asymptomatic low-density Plasmodium falciparum and Plasmodium vivax infections in small volume blood samples. Malar J 14: 520.
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.
Murphy SC et al. 2012. Real-time quantitative reverse transcription PCR for monitoring of blood-stage Plasmodium falciparum infections in malaria human challenge trials. Am J Trop Med Hyg 86: 383–394.
Bousema T , Okell L , Felger I , Drakeley C , 2014. Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nat Rev Microbiol 12: 833–840.
Gruenberg M et al. 2020. Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities. Malar J 19: 319.
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.
Hofmann NE et al. 2018. Assessment of ultra-sensitive malaria diagnosis versus standard molecular diagnostics for malaria elimination: an in-depth molecular community cross-sectional study. Lancet Infect Dis 18: 1108–1116.
Golassa L , Cheaveau J , Mohon AN , Pillai DR , 2019. Reply to Awandu et al. Clin Infect Dis 69: 1464–1465.
Dalrymple U , Arambepola R , Gething PW , Cameron E , 2018. How long do rapid diagnostic tests remain positive after anti-malarial treatment? Malar J 17: 228.
Hanron AE et al. 2017. Multiplex, DNase-free one-step reverse transcription PCR for Plasmodium 18S rRNA and spliced gametocyte-specific mRNAs. Malar J 16: 208.
Niederwieser I , Felger I , Beck HP , 2000. Plasmodium falciparum: expression of gametocyte-specific genes in monolayer cultures and malaria-positive blood samples. Exp Parasitol 95: 163–169.
Ngasala B et al. 2019. Detection of the Asymptomatic Plasmodium Falciparum Infectious Reservoir among Schoolchildren in Tanzania using Mosquito Skin Feeding Assays. Poster Presentation at the Annual Meeting of the American Society of Tropical Medicine and Hygiene, National Harbor, MD.
Lin JT , Saunders DL , Meshnick SR , 2014. The role of submicroscopic parasitemia in malaria transmission: what is the evidence? Trends Parasitol 30: 183–190.
Stone W , Gonçalves BP , Bousema T , Drakeley C , 2015. Assessing the infectious reservoir of falciparum malaria: past and future. Trends Parasitol 31: 287–296.
Slater HC et al. 2019. The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density. Nat Commun 10: 1433.
Imwong M et al. 2016. Numerical distributions of parasite densities during asymptomatic malaria. J Infect Dis 213: 1322–1329.
|Past two years||Past Year||Past 30 Days|
|Full Text Views||303||185||1|
Ultrasensitive PCR used in low-transmission malaria-endemic settings has revealed a much higher burden of asymptomatic infections than that detected by rapid diagnostic tests (RDTs) or standard PCR, but there is limited evidence as to whether this is the case in higher transmission settings. Using dried blood spots (DBS) collected among 319 schoolchildren in Bagamoyo, Tanzania, we found good correlation (Pearson’s R = 0.995) between Plasmodium falciparum parasite densities detected by a DNA-based 18s rRNA real-time PCR (qPCR) and an RNA-based ultrasensitive reverse transcriptase (RT)-PCR (usPCR) for the same target. Whereas prevalence by usPCR was higher than that found by qPCR (37% versus 32%), the proportion of additionally detected low-density infections (median parasite density < 0.050 parasites/µL) represented an incremental increase. It remains unclear to what extent these low-density infections may contribute to the infectious reservoir in different malaria transmission settings.
Authors’ addresses: Christine F. Markwalter and Tonelia Mowatt, Duke Global Health Institute, Duke University, Durham, NC, E-mails: email@example.com and firstname.lastname@example.org. Billy Ngasala and Mwajabu Loya, Department of Parasitology and Medical Entomology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, E-mails: email@example.com and firstname.lastname@example.org. Christopher Basham, Zackary Park, Meredith Muller, and Jessica T. Lin, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, E-mails: email@example.com, firstname.lastname@example.org, email@example.com, and firstname.lastname@example.org. Christopher Plowe and Myaing Nyunt, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, E-mails: email@example.com and firstname.lastname@example.org.