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      Chloroquine-Resistant Haplotype Plasmodium falciparum Parasites, Haiti

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          Abstract

          Chloroquine resistance is now present in this country.

          Abstract

          Plasmodium falciparum parasites have been endemic to Haiti for >40 years without evidence of chloroquine (CQ) resistance. In 2006 and 2007, we obtained blood smears for rapid diagnostic tests (RDTs) and filter paper blots of blood from 821 persons by passive and active case detection. P. falciparum infections diagnosed for 79 persons by blood smear or RDT were confirmed by PCR for the small subunit rRNA gene of P. falciparum. Amplification of the P. falciparum CQ resistance transporter ( pfcrt) gene yielded 10 samples with amplicons resistant to cleavage by ApoI. A total of 5 of 9 samples had threonine at position 76 of pfcrt, which is consistent with CQ resistance (haplotypes at positions 72–76 were CVIET [n = 4] and CVMNT [n = 1]); 4 had only the wild-type haplotype associated with CQ susceptibility (CVMNK). These results indicate that CQ-resistant haplotype P. falciparum malaria parasites are present in Haiti.

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          A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT).

          Chansuda Wongsrichanalai, Mazie Barcus, Sinuon Muth … (2007)
          The absolute necessity for rational therapy in the face of rampant drug resistance places increasing importance on the accuracy of malaria diagnosis. Giemsa microscopy and rapid diagnostic tests (RDTs) represent the two diagnostics most likely to have the largest impact on malaria control today. These two methods, each with characteristic strengths and limitations, together represent the best hope for accurate diagnosis as a key component of successful malaria control. This review addresses the quality issues with current malaria diagnostics and presents data from recent rapid diagnostic test trials. Reduction of malaria morbidity and drug resistance intensity plus the associated economic loss of these two factors require urgent scaling up of the quality of parasite-based diagnostic methods. An investment in anti-malarial drug development or malaria vaccine development should be accompanied by a parallel commitment to improve diagnostic tools and their availability to people living in malarious areas.
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            A molecular marker for chloroquine-resistant falciparum malaria.

            Abdoulaye DJimde, Ogobara K. Doumbo, Joseph Cortese … (2001)
            Chloroquine-resistant Plasmodium falciparum malaria is a major health problem, particularly in sub-Saharan Africa. Chloroquine resistance has been associated in vitro with point mutations in two genes, pfcrt and pfmdr 1, which encode the P. falciparum digestive-vacuole transmembrane proteins PfCRT and Pgh1, respectively. To assess the value of these mutations as markers for clinical chloroquine resistance, we measured the association between the mutations and the response to chloroquine treatment in patients with uncomplicated falciparum malaria in Mali. The frequencies of the mutations in patients before and after treatment were compared for evidence of selection of resistance factors as a result of exposure to chloroquine. The pfcrt mutation resulting in the substitution of threonine (T76) for lysine at position 76 was present in all 60 samples from patients with chloroquine-resistant infections (those that persisted or recurred after treatment), as compared with a base-line prevalence of 41 percent in samples obtained before treatment from 116 randomly selected patients (P<0.001), indicating absolute selection for this mutation. The pfmdr 1 mutation resulting in the substitution of tyrosine for asparagine at position 86 was also selected for, since it was present in 48 of 56 post-treatment samples from patients with chloroquine-resistant infections (86 percent), as compared with a base-line prevalence of 50 percent in 115 samples obtained before treatment (P<0.001). The presence of pfcrt T76 was more strongly associated with the development of chloroquine resistance (odds ratio, 18.8; 95 percent confidence interval, 6.5 to 58.3) than was the presence of pfmdr 1 Y86 (odds ratio, 3.2; 95 percent confidence interval, 1.5 to 6.8) or the presence of both mutations (odds ratio, 9.8; 95 percent confidence interval, 4.4 to 22.1). This study shows an association between the pfcrt T76 mutation in P. falciparum and the development of chloroquine resistance during the treatment of malaria. This mutation can be used as a marker in surveillance for chloroquine-resistant falciparum malaria.
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              DNASTAR's Lasergene sequence analysis software.

              T G Burland (2000)
              Lasergene's eight modules provide tools that enable users to accomplish each step of sequence analysis, from trimming and assembly of sequence data, to gene discovery, annotation, gene product analysis, sequence similarity searches, sequence alignment, phylogenetic analysis, oligonucleotide primer design, cloning strategies, and publication of the results. The Lasergene software suite provides the functions and customization tools needed so that users can perform analyses the software writers never imagined.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Emerg Infect Dis
                Journal ID (publisher-id): EID
                Title: Emerging Infectious Diseases
                Publisher: Centers for Disease Control and Prevention
                ISSN (Print): 1080-6040
                ISSN (Electronic): 1080-6059
                Publication date (Print): May 2009
                Volume: 15
                Issue: 5
                Pages: 735-740
                Affiliations
                [1]Tulane University, New Orleans, Louisiana, USA (B.L. Londono, T.P. Eisele, J. Keating, A. Bennett, B. Mack, D.J. Krogstad)
                [2]University of Pamplona, Pamplona, Colombia (B.L. Londono)
                [3]Hôpital Albert Schweitzer, Deschapelles, Haiti (C. Chattopadhyay, G. Heyliger, I. Rawson)
                [4]Swiss Tropical Institute, Basel, Switzerland (C. Chattopadhyay)
                [5]Ministry of Health, Port-au-Prince, Haiti (J.-F. Vely)
                [6]US Agency for International Development, Port-au-Prince (O. Désinor)
                Author notes
                Address for correspondence: Donald J. Krogstad, Department of Tropical Medicine, Tulane University, SL 17, 1430 Tulane Ave, Rm 510, New Orleans, LA 70112-2699, USA; email: krogstad@ 123456tulane.edu
                Article
                Publisher ID: 08-1063
                DOI: 10.3201/eid1505.081063
                PMC ID: 2686998
                PubMed ID: 19402959
                SO-VID: 78f8c2c8-4677-4272-9306-a262189b47ea
                History
                Categories
                Subject: Research

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: malaria,haplotypes,chloroquine,plasmodium falciparum,parasites,haiti,research,p. falciparum chloroquine resistance transporter
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: malaria, haplotypes, chloroquine, plasmodium falciparum, parasites, haiti, research, p. falciparum chloroquine resistance transporter

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