Malaria Diagnostics and Surveillance in the Post-Genomic Era

Lucchi, Naomi W.; Oberstaller, Jenna; Kissinger, Jessica C.; Udhayakumar, Venkatachalam

doi:10.1159/000345607

Cited by 14 publications

(15 citation statements)

References 31 publications

(44 reference statements)

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“…Of interest, only NR-qPCR assay developed here were able to detect P. falciparum when this species was present in a proportion of 240-fold lower than P. vivax . As the sensitivity of any PCR protocol depends largely on the molecular target used [40], the high copy number of Pfr364 (around 20 copies of “subfamily 1” targeted by specific primers) probably facilitated the detection of low levels of P. falciparum in co-infections as compared to 18S rRNA (around 5–8 copies). Although different multi-copy targets have been described as sensitive for molecular diagnosis of malaria [23, 25, 36], those studies did not investigate the reliability of these targets in mixed-malaria infections, which precludes any potential comparison with results described here.…”

Section: Discussionmentioning

confidence: 99%

Ribosomal and non-ribosomal PCR targets for the detection of low-density and mixed malaria infections

Amaral

Robortella

Guimarães

et al. 2019

Malar J

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Background The unexpected high proportion of submicroscopic malaria infections in areas with low transmission intensity challenges the control and elimination of malaria in the Americas. The current PCR-based assays present limitations as most protocols still rely on amplification of few-copies target gene. Here, the hypothesis was that amplification of different plasmodial targets—ribosomal ( 18S rRNA ) and non-ribosomal multi-copy sequences (Pvr47 for Plasmodium vivax and Pfr364 for Plasmodium falciparum )—could increase the chances of detecting submicroscopic malaria infection. Methods A non-ribosomal real-time PCR assay targeting Pvr47/Pfr364 ( NR - qPCR ) was established and compared with three additional PCR protocols, two of them based on 18S rRNA gene amplification ( Nested - PCR and R - qPCR ) and one based on Pvr47/Pfr364 targets ( NR - cPCR ). The limit of detection of each PCR protocol, at single and artificial mixed P. vivax / P. falciparum infections, was determined by end-point titration curves. Field samples from clinical (n = 110) and subclinical (n = 324) malaria infections were used to evaluate the impact of using multiple molecular targets to detect malaria infections. Results The results demonstrated that an association of ribosomal and non-ribosomal targets did not increase sensitivity to detect submicroscopic malaria infections. Despite of that, artificial mixed-malaria infections demonstrated that the NR-qPCR was the most sensitive protocol to detect low-levels of P. vivax / P. falciparum co-infections. Field studies confirmed that submicroscopic malaria represented a large proportion (up to 77%) of infections among asymptomatic Amazonian residents, with a high proportion of infections (~ 20%) identified only by the NR-qPCR. Conclusions This study presents a new species-specific non-ribosomal PCR assay with potential to identify low-density P. vivax and P. falciparum infections. As the majority of subclinical infections was caused by P. vivax , the commonest form of malaria in the Amazon area, future studies should investigate the potential of Pvr47/Pfr364 to detect mixed-malaria infections in the field. Electronic supplementary material The online version of this article (10.1186/s12936-019-2781-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Ribosomal and non-ribosomal PCR targets for the detection of low-density and mixed malaria infections

Amaral

Robortella

Guimarães

et al. 2019

Malar J

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“…At least one such target from each Plasmodium species (Pfr364, Pvr47, Pkr140) was found to be suitable for molecular diagnosis with some advantages over existing molecular method targets. 133 Another rapidly emerging development in microfluidics in a lab-on-a-chip approach aims to develop POC devices to improve diagnostic capacity, and is already is being optimized for implementation for sexually transmitted infections and HIV-1 detection. 134 …”

Section: Technologies In Developmentmentioning

confidence: 99%

Malaria Diagnostics in Clinical Trials

Murphy¹,

Shott²,

Parikh³

et al. 2013

The American Journal of Tropical Medicine and Hygiene

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Abstract. Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/ malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests.

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“…Genomic data from sensitive molecular tools are capable of detecting low level parasitemia and of providing additional information on parasite genetic population structure to measure the dynamic changes in malaria transmission 10,11 . Genomic epidemiology has been used detect associations between malaria parasite genetic diversity, dynamic changes in transmission intensity, and malaria programmatic impact [12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum genomic surveillance reveals spatial and temporal trends, association of genetic and physical distance, and household clustering

Déme

Warren

et al. 2020

Preprint

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Molecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control strategies. Genomic data, coupled with geographic information systems data, can further identify clusters or hotspots of malaria transmission, parasite genetic and spatial connectivity, and parasite movement by human or mosquito mobility over time and space. In this study, we performed longitudinal genomic surveillance in a cohort of 70 participants over four years from different neighborhoods and households in Thiès, Senegal—a region of exceptionally low malaria transmission (entomological inoculation rate (EIR) less than 1). Genetic identity (identity by state) was established using a 24 single nucleotide polymorphism molecular barcode and a multivariable linear regression model was used to establish genetic and spatial relationships. Our results show clustering of genetically similar parasites within households and a decline in genetic similarity of parasites with increasing distance. One household showed extremely high diversity and warrants further investigation as to the source of these diverse genetic types. This study illustrates the utility of genomic data with traditional epidemiological approaches for surveillance and detection of trends and patterns in malaria transmission not only by neighborhood but also by household. This approach can be implemented regionally and countrywide to strengthen and support malaria control and elimination efforts.

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Malaria Diagnostics and Surveillance in the Post-Genomic Era

Cited by 14 publications

References 31 publications

Ribosomal and non-ribosomal PCR targets for the detection of low-density and mixed malaria infections

Ribosomal and non-ribosomal PCR targets for the detection of low-density and mixed malaria infections

Malaria Diagnostics in Clinical Trials

Plasmodium falciparum genomic surveillance reveals spatial and temporal trends, association of genetic and physical distance, and household clustering

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