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


Journal

Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802

Informations de publication

Date de publication:
19 Apr 2022
Historique:
received: 05 11 2021
accepted: 06 04 2022
entrez: 20 4 2022
pubmed: 21 4 2022
medline: 22 4 2022
Statut: epublish

Résumé

Loss of efficacy of diagnostic tests may lead to untreated or mistreated malaria cases, compromising case management and control. There is an increasing reliance on rapid diagnostic tests (RDTs) for malaria diagnosis, with the most widely used of these targeting the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). There are numerous reports of the deletion of this gene in P. falciparum parasites in some populations, rendering them undetectable by PfHRP2 RDTs. The aim of this study was to identify P. falciparum parasites lacking the P. falciparum histidine rich protein 2 and 3 genes (pfhrp2/3) isolated from asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo. The performance of PfHRP2-based RDTs in comparison to microscopy and PCR was assessed using blood samples collected and spotted on Whatman 903™ filter papers between October and November 2019 from school-age children aged 6-14 years. PCR was then used to identify parasite isolates lacking pfhrp2/3 genes. Among asymptomatic malaria carriers (N = 266), 49%, 65%, and 70% were microscopy, PfHRP2_RDT, and pfldh-qPCR positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 80% and 70% while the sensitivity and specificity of RDTs compared to microscopy were 92% and 60%, respectively. Among symptomatic malaria carriers (N = 196), 62%, 67%, and 87% were microscopy, PfHRP2-based RDT, pfldh-qPCR and positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 75% and 88%, whereas the sensitivity and specificity of RDTs compared to microscopy were 93% and 77%, respectively. Of 173 samples with sufficient DNA for PCR amplification of pfhrp2/3, deletions of pfhrp2 and pfhrp3 were identified in 2% and 1%, respectively. Three (4%) of samples harboured deletions of the pfhrp2 gene in asymptomatic parasite carriers and one (1%) isolate lacked the pfhrp3 gene among symptomatic parasite carriers in the RDT positive subgroup. No parasites lacking the pfhrp2/3 genes were found in the RDT negative subgroup. Plasmodium falciparum histidine-rich protein 2/3 gene deletions are uncommon in the surveyed population, and do not result in diagnostic failure. The use of rigorous PCR methods to identify pfhrp2/3 gene deletions is encouraged in order to minimize the overestimation of their prevalence.

Sections du résumé

BACKGROUND BACKGROUND
Loss of efficacy of diagnostic tests may lead to untreated or mistreated malaria cases, compromising case management and control. There is an increasing reliance on rapid diagnostic tests (RDTs) for malaria diagnosis, with the most widely used of these targeting the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). There are numerous reports of the deletion of this gene in P. falciparum parasites in some populations, rendering them undetectable by PfHRP2 RDTs. The aim of this study was to identify P. falciparum parasites lacking the P. falciparum histidine rich protein 2 and 3 genes (pfhrp2/3) isolated from asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo.
METHODS METHODS
The performance of PfHRP2-based RDTs in comparison to microscopy and PCR was assessed using blood samples collected and spotted on Whatman 903™ filter papers between October and November 2019 from school-age children aged 6-14 years. PCR was then used to identify parasite isolates lacking pfhrp2/3 genes.
RESULTS RESULTS
Among asymptomatic malaria carriers (N = 266), 49%, 65%, and 70% were microscopy, PfHRP2_RDT, and pfldh-qPCR positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 80% and 70% while the sensitivity and specificity of RDTs compared to microscopy were 92% and 60%, respectively. Among symptomatic malaria carriers (N = 196), 62%, 67%, and 87% were microscopy, PfHRP2-based RDT, pfldh-qPCR and positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 75% and 88%, whereas the sensitivity and specificity of RDTs compared to microscopy were 93% and 77%, respectively. Of 173 samples with sufficient DNA for PCR amplification of pfhrp2/3, deletions of pfhrp2 and pfhrp3 were identified in 2% and 1%, respectively. Three (4%) of samples harboured deletions of the pfhrp2 gene in asymptomatic parasite carriers and one (1%) isolate lacked the pfhrp3 gene among symptomatic parasite carriers in the RDT positive subgroup. No parasites lacking the pfhrp2/3 genes were found in the RDT negative subgroup.
CONCLUSION CONCLUSIONS
Plasmodium falciparum histidine-rich protein 2/3 gene deletions are uncommon in the surveyed population, and do not result in diagnostic failure. The use of rigorous PCR methods to identify pfhrp2/3 gene deletions is encouraged in order to minimize the overestimation of their prevalence.

Identifiants

pubmed: 35439987
doi: 10.1186/s12936-022-04153-2
pii: 10.1186/s12936-022-04153-2
pmc: PMC9020024
doi:

Substances chimiques

Antigens, Protozoan 0
HRP-2 antigen, Plasmodium falciparum 0
HRP3 protein, Plasmodium falciparum 0
Protozoan Proteins 0
Histidine 4QD397987E

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

126

Subventions

Organisme : Japan International Cooperation Agency and the Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University
ID : 2020-Ippan-14
Organisme : Japan International Cooperation Agency and the Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University
ID : 2020-Ippan-23

Informations de copyright

© 2022. The Author(s).

Références

Malar J. 2016 Jan 13;15:27
pubmed: 26762532
PLoS One. 2015 Mar 27;10(3):e0121763
pubmed: 25816298
J Clin Microbiol. 2021 Mar 19;59(4):
pubmed: 33148707
J Infect Dis. 2017 Jul 1;216(1):36-44
pubmed: 28177502
Malar J. 2016 Feb 18;15:101
pubmed: 26891848
J Infect Dis. 2017 Aug 15;216(4):503-504
pubmed: 28931243
Malar J. 2021 Apr 29;20(1):207
pubmed: 33926477
Infect Dis Poverty. 2021 May 25;10(1):77
pubmed: 34034827
Malar J. 2014 Dec 06;13:480
pubmed: 25481825
Clin Microbiol Infect. 2013 May;19(5):408-15
pubmed: 23373854
Am J Trop Med Hyg. 2003 Oct;69(4):372-6
pubmed: 14640495
Trans R Soc Trop Med Hyg. 2007 Apr;101(4):331-7
pubmed: 17212967
Malar J. 2013 Jan 24;12:34
pubmed: 23347727
Sci Rep. 2021 Mar 22;11(1):6495
pubmed: 33753817
Malar J. 2012 Jul 06;11:224
pubmed: 22770130
Malar J. 2014 Nov 18;13:433
pubmed: 25404207
Malar J. 2006 Oct 25;5:92
pubmed: 17062168
BMJ Glob Health. 2019 Jul 29;4(4):e001582
pubmed: 31406591
Malar J. 2021 Oct 2;20(1):389
pubmed: 34600558
J Infect Dis. 2005 Sep 1;192(5):870-7
pubmed: 16088837
Trop Med Int Health. 2007 Feb;12(2):238-44
pubmed: 17300631
J Clin Microbiol. 2006 Aug;44(8):2773-8
pubmed: 16891491
Diagn Microbiol Infect Dis. 2008 Aug;61(4):421-7
pubmed: 18455349
J Clin Microbiol. 2012 Apr;50(4):1397-405
pubmed: 22259210
J Infect Dis. 2017 Aug 15;216(4):504-506
pubmed: 28931242
Nature. 2015 Dec 3;528(7580):S86-93
pubmed: 26633770
Malar J. 2017 Apr 4;16(1):138
pubmed: 28376883
Trans R Soc Trop Med Hyg. 1999 Sep-Oct;93(5):519-20
pubmed: 10696409
Mol Biochem Parasitol. 1993 Apr;58(2):283-92
pubmed: 8479452
Malar J. 2020 May 11;19(1):179
pubmed: 32393251
Trop Med Int Health. 2000 Jan;5(1):3-8
pubmed: 10672199
Malar J. 2010 Jun 18;9:171
pubmed: 20565816
Malar J. 2018 Apr 2;17(1):137
pubmed: 29609602
Emerg Infect Dis. 2018 Mar;24(3):462-470
pubmed: 29460730
Malar J. 2016 Jul 08;15:350
pubmed: 27392905

Auteurs

Sabin S Nundu (SS)

Programme for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. bb55418104@ms.nagasaki-u.ac.jp.
Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. bb55418104@ms.nagasaki-u.ac.jp.
Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo. bb55418104@ms.nagasaki-u.ac.jp.

Hiroaki Arima (H)

Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Shirley V Simpson (SV)

Programme for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Ben-Yeddy Abel Chitama (BA)

Department of Protozoology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Yannick Bazitama Munyeku (YB)

Division of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.

Jean-Jacques Muyembe (JJ)

Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo.

Toshihiro Mita (T)

Department of Tropical Medicine and Parasitology, Faculty of Medicine, Juntendo University, Tokyo, Japan.

Steve Ahuka (S)

Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo.

Richard Culleton (R)

Department of Protozoology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. culleton.richard.oe@ehime-u.ac.jp.
Division of Molecular Parasitology, Proteo-Science Center, Ehime University, Ehime, Japan. culleton.richard.oe@ehime-u.ac.jp.

Taro Yamamoto (T)

Programme for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH