Skip to main content
main-content

01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

Decreased prevalence of Plasmodium falciparum resistance markers to amodiaquine despite its wide scale use as ACT partner drug in Zanzibar

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Gabrielle Fröberg, Louise Jörnhagen, Ulrika Morris, Delér Shakely, Mwinyi I Msellem, José P Gil, Anders Björkman, Andreas Mårtensson
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-321) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

GF, JPG, AM and AB conceived and designed the study. DS, AM and MIM carried out the field work. GF, LJ and UM carried out the molecular analyses. GF, LJ, UM, JPG, AB and AM analyzed the data. GF and AM wrote the manuscript. All authors revised and approved the final manuscript.

Abstract

Background

Zanzibar has recently undergone a rapid decline in Plasmodium falciparum transmission following combined malaria control interventions with artemisinin-based combination therapy (ACT) and integrated vector control. Artesunate-amodiaquine (ASAQ) was implemented as first-line treatment for uncomplicated P. falciparum malaria in Zanzibar in 2003. Resistance to amodiaquine has been associated with the single nucleotide polymorphism (SNP) alleles pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y. An accumulation of these SNP alleles in the parasite population over time might threaten ASAQ efficacy.
The aim of this study was to assess whether prolonged use of ASAQ as first-line anti-malarial treatment selects for P. falciparum SNPs associated with resistance to the ACT partner drug amodiaquine.

Methods

The individual as well as the combined SNP allele prevalence were compared in pre-treatment blood samples from patients with uncomplicated P. falciparum malaria enrolled in clinical trials conducted just prior to the introduction of ASAQ in 2002–2003 (n = 208) and seven years after wide scale use of ASAQ in 2010 (n = 122).

Results

There was a statistically significant decrease of pfcrt 76T (96–63%), pfmdr1 86Y (75–52%), 184Y (83–72%), 1246Y (28–16%) and the most common haplotypes pfcrt/pfmdr1 TYYD (46–26%) and TYYY (17–8%), while an increase of pfcrt/pfmdr1 KNFD (0.4–14%) and KNYD (1–12%).

Conclusions

This is the first observation of a decreased prevalence of pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y in an African setting after several years of extensive ASAQ use as first-line treatment for uncomplicated malaria. This may support sustained efficacy of ASAQ on Zanzibar, although it was unexpected considering that all these SNPs have previously been associated with amodiaquine resistance. The underlying factors of these results are unclear. Genetic dilution by imported P. falciparum parasites from mainland Tanzania, a de-selection by artesunate per se and/or an associated fitness cost might represent contributing factors. More detailed studies on temporal trends of molecular markers associated with amodiaquine resistance are required to improve the understanding of this observation.
Zusatzmaterial
Authors’ original file for figure 1
12936_2012_2210_MOESM1_ESM.pdf
Authors’ original file for figure 2
12936_2012_2210_MOESM2_ESM.pdf
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2012

Malaria Journal 1/2012 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Meistgelesene Bücher aus der Inneren Medizin

2017 | Buch

Rheumatologie aus der Praxis

Entzündliche Gelenkerkrankungen – mit Fallbeispielen

Dieses Fachbuch macht mit den wichtigsten chronisch entzündlichen Gelenk- und Wirbelsäulenerkrankungen vertraut. Anhand von über 40 instruktiven Fallbeispielen werden anschaulich diagnostisches Vorgehen, therapeutisches Ansprechen und der Verlauf …

Herausgeber:
Rudolf Puchner

2016 | Buch

Ambulant erworbene Pneumonie

Was, wann, warum – Dieses Buch bietet differenzierte Diagnostik und Therapie der ambulant erworbenen Pneumonie zur sofortigen sicheren Anwendung. Entsprechend der neuesten Studien und Leitlinien aller wichtigen Fachgesellschaften.

Herausgeber:
Santiago Ewig

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise