Authors: Menegon, Michela¹; Pearce, Richard J.²; Inojosa, Walter O.³; Pisani, Vincenzo³; Abel, Paulo M.⁴; Matondo, Alexandre⁵; Bisoffi, Zeno⁶; Majori, Giancarlo¹; Ord, Rosalynn²; Warhurst, David C.²; Roper, Cally²; Severini, Carlo¹

Source: Tropical Medicine & International Health, Volume 14, Number 10, October 2009 , pp. 1251-1257(7)

Publisher: Wiley-Blackwell

Abstract:

Summary Objectives 

To assess the extent of drug resistance in Uige through molecular genetic analysis and to test whether the dhfr triple mutant alleles present in Angola are of southeast Asian origin. Methods 

Seventy-one samples of blood from children admitted to the Pediatric Emergency Unit of Uige Provincial Hospital in 2004 were screened for resistance mutations at pfcrt, pfmdr1, pfdhfr, pfdhps and pfATPase6. Results 

Mutations in pfcrt (codon76), pfmdr1 (codon86), pfdhfr (codons 51, 59, 108) and pfdhps (codons 436, 437) were common. Among the 66 isolates for which we were able to determine complete genetic information 13.7% carried all seven of these mutations. Flanking microsatellite analysis revealed the triple mutant pfdhfr was derived from the southeast Asian lineage, while the N51I+S108N double mutant pfdhfr alleles are a local origin. pfATPase6 mutations were rare and S769N was not found. Conclusion 

The parasite population of Uige Angola has high frequency mutations in pfcrt, dhfr and dhps associated with resistance to chloroquine and sulphadoxine pyrimethamine, reflecting past reliance on these two drugs which were the mainstay of treatment until recently. Our findings show that drug resistance in Uige has occurred through a combination of local drug pressure and the regional and international dispersal of resistance mutant alleles.

Keywords: Plasmodium falciparum; Angola; drug resistance molecular markers; microsatellites; pyrimethamine resistance evolution; Plasmodium falciparum; Angola; marcadores molecular de resistencia a fármacos; microsatélites; evolución resistencia pirimetamina

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-3156.2009.02369.x

Affiliations: 1:  Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy 2:  Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK 3:  CUAMM-Angola, Luanda, Angola 4:  Angotrip Project, Caritas, Luanda, Angola 5:  Provincial Hospital, Uige, Angola 6:  Centre for Tropical Diseases, S. Cuore Hospital, Negrar, Italy

Publication date: 2009-10-01

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• By this author: Menegon, Michela ;  Pearce, Richard J. ;  Inojosa, Walter O. ;  Pisani, Vincenzo ;  Abel, Paulo M. ;  Matondo, Alexandre ;  Bisoffi, Zeno ;  Majori, Giancarlo ;  Ord, Rosalynn ;  Warhurst, David C. ;  Roper, Cally ;  Severini, Carlo

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