Literature DB >> 33926477

HRP2 and HRP3 cross-reactivity and implications for HRP2-based RDT use in regions with Plasmodium falciparum hrp2 gene deletions.

Amy Kong1, Scott A Wilson1,2, Yong Ah1,2, Douglas Nace1, Eric Rogier1, Michael Aidoo3.   

Abstract

BACKGROUND: The Plasmodium falciparum antigen histidine rich protein 2 (HRP2) is a preferred target for malaria rapid diagnostic tests (RDTs) because of its abundant production by the parasite and thermal stability. As a result, a majority of RDTs procured globally target this antigen. However, previous reports from South America and recent reports from sub-Saharan Africa and Asia indicate that certain P. falciparum parasites have deletions of the gene coding for HRP2. The HRP2 antigen is paralogous to another P. falciparum antigen HRP3 and some antibodies to HRP2 cross-react with HRP3. Multiple parasites have been described with deletions of one or both hrp2 and hrp3 genes. It is unclear how the various combinations of hrp2 and hrp3 deletion genotypes affect clinical sensitivity of HRP2-based RDTs.
METHODS: Cross-reactivity between HRP2 and HRP3 was tested on malaria RDTs using culture-adapted P. falciparum parasites with both hrp2 and hrp3 intact or with one or both genes deleted. Ten-fold serial dilutions of four culture-adapted P. falciparum parasites [3D7 (hrp2+/hrp3+), Dd2 (hrp2-/hrp3+), HB3 (hrp2+/hrp3-) and 3BD5 (hrp2-/hrp3-)] ranging from 100,000 to 0.01 parasites/µL were prepared. HRP2, Plasmodium lactate dehydrogenase (pLDH) and aldolase concentrations were determined for the diluted samples using a multiplex bead assay. The samples were subsequently tested on three RDT products designed to detect P. falciparum by HRP2 alone or in combination with pLDH.
RESULTS: At parasite densities of approximately 1000 parasites/µL, parasites that expressed either hrp2 or hrp3 were detected by all three RDTs. Multiplex based antigen measurement using HRP2- conjugated beads demonstrated higher antigen concentration when both hrp2 and hrp3 genes were intact (3D7 parasites, 47.9 ng/ml) compared to HB3 (3.02 ng/mL) and Dd2 (0.20 ng/mL) strains that had one gene deleted. 3D7 at 10 parasites/µL (0.45 ng/mL) was reactive on all three RDT products whereas none of the other parasites were reactive at that density.
CONCLUSIONS: Above a certain antigen threshold, HRP3 cross-reactivity on HRP2-based RDTs is sufficient to mask the effects of deletions of hrp2 only. Studies of hrp2 deletion and its effects on HRP2-based RDTs must be studied alongside hrp3 deletions and include clinical sample reactivity on HRP2-based tests.

Entities:  

Keywords:  Cross-reactivity; Gene deletions; HRP2; HRP3; Malaria; RDT

Year:  2021        PMID: 33926477     DOI: 10.1186/s12936-021-03739-6

Source DB:  PubMed          Journal:  Malar J        ISSN: 1475-2875            Impact factor:   2.979


  8 in total

1.  High-throughput Plasmodium falciparum hrp2 and hrp3 gene deletion typing by digital PCR to monitor malaria rapid diagnostic test efficacy.

Authors:  Claudia A Vera-Arias; Aurel Holzschuh; Colins O Oduma; Kingsley Badu; Mutala Abdul-Hakim; Joshua Yukich; Manuel W Hetzel; Bakar S Fakih; Abdullah Ali; Marcelo U Ferreira; Simone Ladeia-Andrade; Fabián E Sáenz; Yaw Afrane; Endalew Zemene; Delenasaw Yewhalaw; James W Kazura; Guiyun Yan; Cristian Koepfli
Journal:  Elife       Date:  2022-06-28       Impact factor: 8.713

2.  Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens.

Authors:  Gonzalo J Domingo; Alfredo Mayor; Ihn Kyung Jang; Alfons Jiménez; Andrew Rashid; Rebecca Barney; Allison Golden; Xavier C Ding
Journal:  Malar J       Date:  2022-06-07       Impact factor: 3.469

Review 3.  Screening strategies and laboratory assays to support Plasmodium falciparum histidine-rich protein deletion surveillance: where we are and what is needed.

Authors:  Khalid B Beshir; Jonathan B Parr; Jane Cunningham; Qin Cheng; Eric Rogier
Journal:  Malar J       Date:  2022-06-24       Impact factor: 3.469

4.  Low prevalence of Plasmodium falciparum parasites lacking pfhrp2/3 genes among asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo.

Authors:  Sabin S Nundu; Hiroaki Arima; Shirley V Simpson; Ben-Yeddy Abel Chitama; Yannick Bazitama Munyeku; Jean-Jacques Muyembe; Toshihiro Mita; Steve Ahuka; Richard Culleton; Taro Yamamoto
Journal:  Malar J       Date:  2022-04-19       Impact factor: 3.469

5.  Deletions of the Plasmodium falciparum histidine-rich protein 2/3 genes are common in field isolates from north-eastern Tanzania.

Authors:  Robert D Kaaya; Reginald A Kavishe; Filemon F Tenu; Johnson J Matowo; Franklin W Mosha; Chris Drakeley; Colin J Sutherland; Khalid B Beshir
Journal:  Sci Rep       Date:  2022-04-06       Impact factor: 4.996

6.  Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions and Relatedness to Other Global Isolates, Djibouti, 2019-2020.

Authors:  Eric Rogier; Jessica N McCaffery; Mohamed Ali Mohamed; Camelia Herman; Doug Nace; Rachel Daniels; Naomi Lucchi; Sophie Jones; Ira Goldman; Michael Aidoo; Qin Cheng; Edie A Kemenang; Venkatachalam Udhayakumar; Jane Cunningham
Journal:  Emerg Infect Dis       Date:  2022-10       Impact factor: 16.126

7.  Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia.

Authors:  Irene Molina-de la Fuente; Mulat Yimar; Luz García; Vicenta González; Arancha Amor; Melaku Anegagrie; Agustín Benito; Javier Martínez; Marta Moreno; Pedro Berzosa
Journal:  Malar J       Date:  2022-10-08       Impact factor: 3.469

8.  Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia.

Authors:  Sindew M Feleke; Emily N Reichert; Hussein Mohammed; Bokretsion G Brhane; Kalkidan Mekete; Hassen Mamo; Beyene Petros; Hiwot Solomon; Ebba Abate; Chris Hennelly; Madeline Denton; Corinna Keeler; Nicholas J Hathaway; Jonathan J Juliano; Jeffrey A Bailey; Eric Rogier; Jane Cunningham; Ozkan Aydemir; Jonathan B Parr
Journal:  Nat Microbiol       Date:  2021-09-27       Impact factor: 17.745

  8 in total

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