African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker
Didier Leroy
,
Fiona Macintyre
,
Yeka Adoke
(1)
,
Serge Ouoba
(2)
,
Aissata Barry
(2)
,
Ghyslain Mombo-Ngoma
(3, 4)
,
Jacques Mari Ndong Ngomo
(5)
,
Rosauro Varo
(6, 7, 8)
,
Yannelle Dossou
(9)
,
Antoinette Kitoto Tshefu
(10)
,
Tran Thanh Duong
(11)
,
Bui Quang Phuc
(11)
,
Bart Laurijssens
(12)
,
Roland Klopper
(13)
,
Nimol Khim
(14)
,
Eric Legrand
(15)
,
Didier Ménard
(15)
1
Infectious Diseases Research Collaboration [Tororo]
2 INSSA - Institut de Recherche en Sciences de la Santé Bobo Dioulasso
3 Centre de Recherches Médicales de Lambaréné
4 Institut für Tropenmedizin [Tübingen]
5 Département de Parasitologie-Mycologie [Libreville]
6 CRESIB - Barcelona Centre for International Health Research, Hospital Clinic
7 CISM - Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique]
8 ICREA - Institució Catalana de Recerca i Estudis Avançats = Catalan Institution for Research and Advanced Studies
9 CERPAGE - Centre d’Etude et de Recherche sur le Paludisme Associé à la Grossesse et l’Enfance [Cotonou, Bénin]
10 Centre de Recherche du Centre Hospitalier de Mont Amba [Kinshasa]
11 National Institute of Malariology, Parasitology and Entomology [Hanoi]
12 BEL Pharm Consulting {Nimes]
13 Clindata Pty Ltd [Bloemfontein, South Africa]
14 Institut Pasteur du Cambodge
15 Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions
2 INSSA - Institut de Recherche en Sciences de la Santé Bobo Dioulasso
3 Centre de Recherches Médicales de Lambaréné
4 Institut für Tropenmedizin [Tübingen]
5 Département de Parasitologie-Mycologie [Libreville]
6 CRESIB - Barcelona Centre for International Health Research, Hospital Clinic
7 CISM - Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique]
8 ICREA - Institució Catalana de Recerca i Estudis Avançats = Catalan Institution for Research and Advanced Studies
9 CERPAGE - Centre d’Etude et de Recherche sur le Paludisme Associé à la Grossesse et l’Enfance [Cotonou, Bénin]
10 Centre de Recherche du Centre Hospitalier de Mont Amba [Kinshasa]
11 National Institute of Malariology, Parasitology and Entomology [Hanoi]
12 BEL Pharm Consulting {Nimes]
13 Clindata Pty Ltd [Bloemfontein, South Africa]
14 Institut Pasteur du Cambodge
15 Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions
Didier Leroy
- Fonction : Auteur
Fiona Macintyre
- Fonction : Auteur
Eric Legrand
- Fonction : Auteur
- PersonId : 2337
- IdHAL : eric-legrand
- IdRef : 089315960
Didier Ménard
- Fonction : Auteur
- PersonId : 184372
- IdHAL : didier-menard
- ORCID : 0000-0003-1357-4495
- IdRef : 117629006
Résumé
Background: Today, the development of new and well-tolerated anti-malarial drugs is strongly justified by the emergence of Plasmodium falciparum resistance. In 2014–2015, a phase 2b clinical study was conducted to evaluate the efficacy of a single oral dose of Artefenomel (OZ439)–piperaquine (PPQ) in Asian and African patients presenting with uncomplicated falciparum malaria.
Methods: Blood samples collected before treatment offered the opportunity to investigate the proportion of multidrug resistant parasite genotypes, including P. falciparum kelch13 mutations and copy number variation of both P. falciparum plasmepsin 2 (Pfpm2) and P. falciparum multidrug resistance 1 (Pfmdr1) genes.
Results: Validated kelch13 resistance mutations including C580Y, I543T, P553L and V568G were only detected in parasites from Vietnamese patients. In Africa, isolates with multiple copies of the Pfmdr1 gene were shown to be more frequent than previously reported (21.1%, range from 12.4% in Burkina Faso to 27.4% in Uganda). More strikingly, high proportions of isolates with multiple copies of the Pfpm2 gene, associated with piperaquine (PPQ) resistance, were frequently observed in the African sites, especially in Burkina Faso and Uganda (> 30%).
Conclusions: These findings were considered to sharply contrast with the recent description of increased sensitivity to PPQ of Ugandan parasite isolates. This emphasizes the necessity to investigate in vitro susceptibility profiles to PPQ of African isolates with multiple copies of the Pfpm2 gene and estimate the risk of development of PPQ resistance in Africa.
Format du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker
|
Résumé |
en
Background: Today, the development of new and well-tolerated anti-malarial drugs is strongly justified by the emergence of Plasmodium falciparum resistance. In 2014–2015, a phase 2b clinical study was conducted to evaluate the efficacy of a single oral dose of Artefenomel (OZ439)–piperaquine (PPQ) in Asian and African patients presenting with uncomplicated falciparum malaria.
Methods: Blood samples collected before treatment offered the opportunity to investigate the proportion of multidrug resistant parasite genotypes, including P. falciparum kelch13 mutations and copy number variation of both P. falciparum plasmepsin 2 (Pfpm2) and P. falciparum multidrug resistance 1 (Pfmdr1) genes.
Results: Validated kelch13 resistance mutations including C580Y, I543T, P553L and V568G were only detected in parasites from Vietnamese patients. In Africa, isolates with multiple copies of the Pfmdr1 gene were shown to be more frequent than previously reported (21.1%, range from 12.4% in Burkina Faso to 27.4% in Uganda). More strikingly, high proportions of isolates with multiple copies of the Pfpm2 gene, associated with piperaquine (PPQ) resistance, were frequently observed in the African sites, especially in Burkina Faso and Uganda (> 30%).
Conclusions: These findings were considered to sharply contrast with the recent description of increased sensitivity to PPQ of Ugandan parasite isolates. This emphasizes the necessity to investigate in vitro susceptibility profiles to PPQ of African isolates with multiple copies of the Pfpm2 gene and estimate the risk of development of PPQ resistance in Africa.
|
Auteur(s) |
Didier Leroy
, Fiona Macintyre
, Yeka Adoke
1
, Serge Ouoba
2
, Aissata Barry
2
, Ghyslain Mombo-Ngoma
3, 4
, Jacques Mari Ndong Ngomo
5
, Rosauro Varo
6, 7, 8
, Yannelle Dossou
9
, Antoinette Kitoto Tshefu
10
, Tran Thanh Duong
11
, Bui Quang Phuc
11
, Bart Laurijssens
12
, Roland Klopper
13
, Nimol Khim
14
, Eric Legrand
15
, Didier Ménard
15
1
Infectious Diseases Research Collaboration [Tororo]
( 1007735 )
- Tororo Hospital, Tororo, Uganda
- Ouganda
2
INSSA -
Institut de Recherche en Sciences de la Santé Bobo Dioulasso
( 188289 )
- UNIVERSITE POLYTECHNIQUE
DE BOBO-DIOULASSO
01BP. 1091 Bobo-Dioulasso 01
- Burkina Faso
3
Centre de Recherches Médicales de Lambaréné
( 1007736 )
- Lambaréné, Gabon
- Gabon
4
Institut für Tropenmedizin [Tübingen]
( 558693 )
- Wilhelmstraße 27, 72074 Tübingen
- Allemagne
5
Département de Parasitologie-Mycologie [Libreville]
( 1007737 )
- Université des Sciences de la Santé de Libreville BP 4009 Libreville
- Gabon
6
CRESIB -
Barcelona Centre for International Health Research, Hospital Clinic
( 125182 )
- Barcelona
- Espagne
7
CISM -
Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique]
( 577821 )
- Rua 12, Cambeve, Vila de Manhiça, CP 1929 Maputo,Mozambique
- Mozambique
8
ICREA -
Institució Catalana de Recerca i Estudis Avançats = Catalan Institution for Research and Advanced Studies
( 300218 )
- Passeig Lluís Companys 23, 08010 Barcelona
- Espagne
9
CERPAGE -
Centre d’Etude et de Recherche sur le Paludisme Associé à la Grossesse et l’Enfance [Cotonou, Bénin]
( 450420 )
- Cotonou
- Bénin
10
Centre de Recherche du Centre Hospitalier de Mont Amba [Kinshasa]
( 1007740 )
- Kinshasa School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
- Congo-Kinshasa
11
National Institute of Malariology, Parasitology and Entomology [Hanoi]
( 1007741 )
- Hanoi
- Viêt Nam
12
BEL Pharm Consulting {Nimes]
( 1007742 )
- France
13
Clindata Pty Ltd [Bloemfontein, South Africa]
( 1007743 )
- Afrique du Sud
14
Institut Pasteur du Cambodge
( 54022 )
- BP 983 - 5 , Boulevard Monivong, Phnom Penh
- Cambodge
15
Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions
( 462748 )
- Département des Parasites et Insectes vecteurs, 25-28, rue du docteur Roux, 75724 Paris Cedex 15
- France
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2019
|
Volume |
18
|
Page/Identifiant |
126
|
Domaine(s) |
|
DOI | 10.1186/s12936-019-2756-4 |
Pubmed Id | 30967148 |
Origine :
Publication financée par une institution
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