Combination of Serological, Antigen Detection, and DNA Data for Plasmodium falciparum Provides Robust Geospatial Estimates for Malaria Transmission in Haiti

Oviedo, Adan; Knipes, Alaine; Worrell, Caitlin M.; Fox, LeAnne M.; Desir, Luccene; Fayette, Carl; Javel, Alain; Monestime, Franck; Mace, Kimberly E.; Chang, Michelle; Udhayakumar, Venkatachalam; Lemoine, Jean Frantz; Won, Kimberly Y.; Lammie, Patrick J.; Rogier, Eric

doi:10.1038/s41598-020-65419-w

Cited by 15 publications

(11 citation statements)

References 46 publications

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“…loop-mediated isothermal amplification (LAMP) is a molecular point-of-care test with high specificity and sensitivity (5 parasites/µl of blood) well below the LOD for LM/RDT [ 44 , 45 ]. Serological diagnostic assays (serosurveillance tools) that detect active or latent infection as well as past exposure may help to assess the malaria burden at a community level more accurately especially in low transmission settings where infections are rare, and surveys, therefore, require large sample sizes to confidently calculate prevalence [ 46 – 48 ].…”

Section: Discussionmentioning

confidence: 99%

Performance evaluation of RDT, light microscopy, and PET-PCR for detecting Plasmodium falciparum malaria infections in the 2018 Zambia National Malaria Indicator Survey

Mwenda

Fola

Ciubotariu

et al. 2021

Malar J

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Background Zambia continues to advance on the path to elimination with significant reductions in malaria morbidity and mortality. Crucial components that have contributed to progress thus far and are necessary for achieving the national malaria elimination goals include properly identifying and treating all malaria cases through accurate diagnosis. This study sought to compare and assess the diagnostic performance of Rapid Diagnostic Tests (RDT) and Light Microscopy (LM) with photo-induced electron transfer polymerase chain reaction (PET-PCR) as the gold standard using 2018 Malaria Indicator Survey (MIS) data across Zambia to better understand diagnostic accuracy metrics and how these vary across a transmission gradient. Methods Cross-sectional samples collected in a nationally representative survey from 7 provinces in Zambia were tested for the presence of malaria parasites by light microscopy (LM), rapid diagnostic test (RDT) and the gold standard PET-PCR. Diagnostic performance was assessed including sensitivity, specificity, negative- and positive-predictive values across a wide malaria transmission spectrum. Diagnostic accuracy metrics were measured, and statistically significant differences were calculated between test methods for different outcome variables. Results From the individuals included in the MIS, the overall prevalence of Plasmodium falciparum malaria was 32.9% by RDT, 19.4% by LM, and 23.2% by PET-PCR. Herein, RDT and LM diagnostic performance was compared against gold standard PET-PCR with LM displaying a higher diagnostic accuracy than RDTs (91.3% vs. 84.6% respectively) across the transmission spectrum in Zambia. However, the performance of both diagnostics was significantly reduced in low parasitaemia samples. Consistent with previous studies, RDT diagnostic accuracy was predominantly affected by a high rate of false positives. Conclusions RDTs and LM both perform well across a range of transmission intensities within their respective target applications, i.e., in the community, for the former, where ease of use and speed of result is critical, and at the health facility, for the latter, where accuracy is prioritized. However, the performance of both diagnostic methods is adversely affected by low parasitaemia infections. As Zambia moves towards elimination more sensitive tools may be required to identify the last cases.

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Section: Discussionmentioning

confidence: 99%

Performance evaluation of RDT, light microscopy, and PET-PCR for detecting Plasmodium falciparum malaria infections in the 2018 Zambia National Malaria Indicator Survey

Mwenda

Fola

Ciubotariu

et al. 2021

Malar J

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“…As an example, Immunofluorescence Antibody Testing (IFA) uses specific antigens for the quantification of IgG and IgM antibodies in serum samples ( Tangpukdee et al, 2009 ). Combined strategies using serological, antigen detection, and DNA data are used to estimate malaria transmission and perform epidemiological studies ( Oviedo et al, 2020 ).…”

Section: Malaria Diagnosismentioning

confidence: 99%

Advances and challenges in automated malaria diagnosis using digital microscopy imaging with artificial intelligence tools: A review

Maturana

Oliveira²,

Nadal³

et al. 2022

Front. Microbiol.

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Malaria is an infectious disease caused by parasites of the genus Plasmodium spp. It is transmitted to humans by the bite of an infected female Anopheles mosquito. It is the most common disease in resource-poor settings, with 241 million malaria cases reported in 2020 according to the World Health Organization. Optical microscopy examination of blood smears is the gold standard technique for malaria diagnosis; however, it is a time-consuming method and a well-trained microscopist is needed to perform the microbiological diagnosis. New techniques based on digital imaging analysis by deep learning and artificial intelligence methods are a challenging alternative tool for the diagnosis of infectious diseases. In particular, systems based on Convolutional Neural Networks for image detection of the malaria parasites emulate the microscopy visualization of an expert. Microscope automation provides a fast and low-cost diagnosis, requiring less supervision. Smartphones are a suitable option for microscopic diagnosis, allowing image capture and software identification of parasites. In addition, image analysis techniques could be a fast and optimal solution for the diagnosis of malaria, tuberculosis, or Neglected Tropical Diseases in endemic areas with low resources. The implementation of automated diagnosis by using smartphone applications and new digital imaging technologies in low-income areas is a challenge to achieve. Moreover, automating the movement of the microscope slide and image autofocusing of the samples by hardware implementation would systemize the procedure. These new diagnostic tools would join the global effort to fight against pandemic malaria and other infectious and poverty-related diseases.

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“…In 2019, P. falciparum was responsible for 99.7% of all malaria infections in sub-Saharan Africa (SSA) [ 7 ], and a majority of the 412 million RDTs sold in SSA in 2018 were HRP2-based [ 8 ]. In addition to the qualitative detection of HRP2 for diagnosis of active infection by RDTs, determining the concentration of HRP2 in blood samples by other laboratory assays has been used to estimate parasite density [ 9 ], attribute febrile illness to malaria [ 10 ], and provide estimates on malaria transmission intensity [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Purification of native histidine-rich protein 2 (nHRP2) from Plasmodium falciparum culture supernatant, infected RBCs, and parasite lysate

Singh

McCaffery

Kong

et al. 2021

Malar J

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Background Despite the widespread use of histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs), purified native HRP2 antigen is not standardly used in research applications or assessment of RDTs used in the field. Methods This report describes the purification of native HRP2 (nHRP2) from the HB3 Plasmodium falciparum culture strain. As this culture strain lacks pfhrp3 from its genome, it is an excellent source of HRP2 protein only and does not produce the closely-related HRP3. The nHRP2 protein was isolated from culture supernatant, infected red blood cells (iRBCs), and whole parasite lysate using nickel-metal chelate chromatography. Biochemical characterization of nHRP2 from HB3 culture was conducted by SDS-PAGE and western blotting, and nHRP2 was assayed by RDT, ELISA, and bead-based immunoassay. Results Purified nHRP2 was identified by SDS-PAGE and western blot as a − 60 kDa protein that bound anti-HRP-2 monoclonal antibodies. Mouse anti-HRP2 monoclonal antibody was found to produce high optical density readings between dilutions of 1:100 and 1:3,200 by ELISA with assay signal observed up to a 1:200,000 dilution. nHRP2 yield from HB3 culture by bead-based immunoassay revealed that both culture supernatant and iRBC lysate were practical sources of large quantities of this antigen, producing a total yield of 292.4 µg of nHRP2 from two pooled culture preparations. Assessment of nHRP2 recognition by RDTs revealed that Carestart Pf HRP2 and HRP2/pLDH RDTs detected purified nHRP2 when applied at concentrations between 20.6 and 2060 ng/mL, performing within a log-fold dilution of commercially-available recombinant HRP2. The band intensity observed for the nHRP2 dilutions was equivalent to that observed for P. falciparum culture strain dilutions of 3D7 and US06 F Nigeria XII between 12.5 and 1000 parasites/µL. Conclusions Purified nHRP2 could be a valuable reagent for laboratory applications as well as assessment of new and existing RDTs prior to their use in clinical settings. These results establish that it is possible to extract microgram quantities of the native HRP2 antigen from HB3 culture and that this purified protein is well recognized by existing monoclonal antibody lines and RDTs. Graphical Abstract

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Combination of Serological, Antigen Detection, and DNA Data for Plasmodium falciparum Provides Robust Geospatial Estimates for Malaria Transmission in Haiti

Cited by 15 publications

References 46 publications

Performance evaluation of RDT, light microscopy, and PET-PCR for detecting Plasmodium falciparum malaria infections in the 2018 Zambia National Malaria Indicator Survey

Performance evaluation of RDT, light microscopy, and PET-PCR for detecting Plasmodium falciparum malaria infections in the 2018 Zambia National Malaria Indicator Survey

Advances and challenges in automated malaria diagnosis using digital microscopy imaging with artificial intelligence tools: A review

Purification of native histidine-rich protein 2 (nHRP2) from Plasmodium falciparum culture supernatant, infected RBCs, and parasite lysate

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