An Ultra-Sensitive Technique: Using -mtCOX1 QPCR to Detect Early Recurrences of in Patients in the Brazilian Amazon

Overview

Journal Pathogens

Date 2021 Jan 5

PMID 33396824

Citations 1

Authors

Laila R A Barbosa

Emanuelle L da Silva

Anne C G de Almeida

Yanka E A R Salazar

Andre M Siqueira

Maria das Gracas Costa Alecrim

Jose Luiz Fernandes Vieira

Quique Bassat

Marcus V G de Lacerda

Wuelton M Monteiro

Gisely C Melo

Affiliations

Soon will be listed here.

Abstract

Background: Early recurrence of is a challenge for malaria control in the field, particularly because this species is associated with lower parasitemia, which hinders diagnosis and monitoring through blood smear testing. Early recurrences, defined as the persistence of parasites in the peripheral blood despite adequate drug dosages, may arise from resistance to chloroquine. The objective of the study was to estimate early recurrence of in the Brazilian Amazon by using a highly-sensitive detection method, in this case, PCR.

Methods: An ultra-sensitive qPCR that targeted mitochondrial DNA was used to compare a standard qPCR that targeted 18S rDNA to detect early recurrence of in very low densities in samples from patients treated with chloroquine.

Results: Out of a total of 312 cases, 29 samples (9.3%) were characterized as recurrences, from which 3.2% (10/312) were only detected through ultra-sensitive qPCR testing.

Conclusions: Studies that report the detection of early recurrences using light microscopy may severely underestimate their true incidence.

Citing Articles

Advances in Malaria Diagnostic Methods in Resource-Limited Settings: A Systematic Review.

Yalley A, Ocran J, Cobbinah J, Obodai E, Yankson I, Kafintu-Kwashie A Trop Med Infect Dis. 2024; 9(9).

PMID: 39330879 PMC: 11435979. DOI: 10.3390/tropicalmed9090190.

References

Hwang J, Alemayehu B, Reithinger R, Tekleyohannes S, Takele Teshi , Birhanu S . In vivo efficacy of artemether-lumefantrine and chloroquine against Plasmodium vivax: a randomized open label trial in central Ethiopia. PLoS One. 2013; 8(5):e63433. PMC: 3661577. DOI: 10.1371/journal.pone.0063433. View

Dua V, Kar P, Gupta N, Sharma V . Determination of chloroquine and desethylchloroquine in plasma and blood cells of Plasmodium vivax malaria cases using liquid chromatography. J Pharm Biomed Anal. 2000; 21(1):199-205. DOI: 10.1016/s0731-7085(99)00097-7. View

Imwong M, Hanchana S, Malleret B, Renia L, Day N, Dondorp A . High-throughput ultrasensitive molecular techniques for quantifying low-density malaria parasitemias. J Clin Microbiol. 2014; 52(9):3303-9. PMC: 4313154. DOI: 10.1128/JCM.01057-14. View

Simoes de Santana Filho F, Arcanjo A, Chehuan Y, Costa M, Martinez-Espinosa F, Vieira J . Chloroquine-resistant Plasmodium vivax, Brazilian Amazon. Emerg Infect Dis. 2008; 13(7):1125-6. PMC: 2878224. DOI: 10.3201/eid1307.061386. View

Rieckmann K, Davis D, Hutton D . Plasmodium vivax resistance to chloroquine?. Lancet. 1989; 2(8673):1183-4. DOI: 10.1016/s0140-6736(89)91792-3. View

Adams M, Joshi S, Mbambo G, Mu A, Roemmich S, Shrestha B . 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. 2015; 14:520. PMC: 4690410. DOI: 10.1186/s12936-015-1038-z. View

Preiser P, Wilson R, Moore P, Mccready S, Hajibagheri M, Blight K . Recombination associated with replication of malarial mitochondrial DNA. EMBO J. 1996; 15(3):684-93. PMC: 449987. View

Almeida A, Kuehn A, Castro A, Vitor-Silva S, Figueiredo E, Brasil L . High proportions of asymptomatic and submicroscopic Plasmodium vivax infections in a peri-urban area of low transmission in the Brazilian Amazon. Parasit Vectors. 2018; 11(1):194. PMC: 5859403. DOI: 10.1186/s13071-018-2787-7. View

Gruenberg M, Moniz C, Hofmann N, Koepfli C, Robinson L, Nate E . Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities. Malar J. 2020; 19(1):319. PMC: 7469345. DOI: 10.1186/s12936-020-03374-7. View

10.

McKenzie F, Wongsrichanalai C, Magill A, Forney J, Permpanich B, Lucas C . Gametocytemia in Plasmodium vivax and Plasmodium falciparum infections. J Parasitol. 2007; 92(6):1281-5. PMC: 2500222. DOI: 10.1645/GE-911R.1. View

11.

Baird J, Leksana B, Masbar S, Fryauff D, Sutanihardja M, Suradi . Diagnosis of resistance to chloroquine by Plasmodium vivax: timing of recurrence and whole blood chloroquine levels. Am J Trop Med Hyg. 1997; 56(6):621-6. DOI: 10.4269/ajtmh.1997.56.621. View

12.

Patchen L, Mount D, Schwartz I, Churchill F . Analysis of filter-paper-absorbed, finger-stick blood samples for chloroquine and its major metabolite using high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1983; 278(1):81-9. DOI: 10.1016/s0378-4347(00)84758-1. View

13.

Gruenberg M, Moniz C, Hofmann N, Wampfler R, Koepfli C, Mueller I . Plasmodium vivax molecular diagnostics in community surveys: pitfalls and solutions. Malar J. 2018; 17(1):55. PMC: 5789620. DOI: 10.1186/s12936-018-2201-0. View

14.

Britton S, Cheng Q, Grigg M, Poole C, Pasay C, William T . Sensitive Detection of Plasmodium vivax Using a High-Throughput, Colourimetric Loop Mediated Isothermal Amplification (HtLAMP) Platform: A Potential Novel Tool for Malaria Elimination. PLoS Negl Trop Dis. 2016; 10(2):e0004443. PMC: 4752294. DOI: 10.1371/journal.pntd.0004443. View

15.

Cunha M, Medina T, Oliveira S, Marinho A, Povoa M, Ribeiro-Dos-Santos A . Development of a Polymerase Chain Reaction (PCR) method based on amplification of mitochondrial DNA to detect Plasmodium falciparum and Plasmodium vivax. Acta Trop. 2009; 111(1):35-8. DOI: 10.1016/j.actatropica.2009.02.003. View

16.

Hofmann N, Gruenberg M, Nate E, Ura A, Rodriguez-Rodriguez D, Salib M . Assessment of ultra-sensitive malaria diagnosis versus standard molecular diagnostics for malaria elimination: an in-depth molecular community cross-sectional study. Lancet Infect Dis. 2018; 18(10):1108-1116. DOI: 10.1016/S1473-3099(18)30411-0. View

17.

Alecrim M das G, Alecrim W, Macedo V . Plasmodium vivax resistance to chloroquine (R2) and mefloquine (R3) in Brazilian Amazon region. Rev Soc Bras Med Trop. 1999; 32(1):67-8. DOI: 10.1590/s0037-86821999000100013. View

18.

Lin J, Patel J, Levitz L, Wojnarski M, Chaorattanakawee S, Gosi P . Gametocyte Carriage, Antimalarial Use, and Drug Resistance in Cambodia, 2008-2014. Am J Trop Med Hyg. 2018; 99(5):1145-1149. PMC: 6221238. DOI: 10.4269/ajtmh.18-0509. View

19.

Douglas N, Simpson J, Phyo A, Siswantoro H, Hasugian A, Kenangalem E . Gametocyte dynamics and the role of drugs in reducing the transmission potential of Plasmodium vivax. J Infect Dis. 2013; 208(5):801-12. PMC: 3733516. DOI: 10.1093/infdis/jit261. View

20.

Phommasone K, van Leth F, Imwong M, Henriques G, Pongvongsa T, Adhikari B . The use of ultrasensitive quantitative-PCR to assess the impact of primaquine on asymptomatic relapse of Plasmodium vivax infections: a randomized, controlled trial in Lao PDR. Malar J. 2020; 19(1):4. PMC: 6942400. DOI: 10.1186/s12936-019-3091-5. View