13
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Asymptomatic malaria infections and Pfmdr1 mutations in an endemic area of Nigeria

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Malaria eradication globally is yet to be achieved and transmission is sustained in many endemic countries. Plasmodium falciparum continues to develop resistance to currently available anti-malarial drugs, posing great problems for malaria elimination. This study evaluates the frequencies of asymptomatic infection and multidrug resistance-1 ( mdr-1) gene mutations in parasite isolates, which form the basis for understanding persistently high incidence in South West, Nigeria.

          Methods

          A total of 535 individuals aged from 6 months were screened during the epidemiological survey evaluating asymptomatic transmission. Parasite prevalence was determined by histidine-rich protein II rapid detection kit (RDT) in healthy individuals. Plasmodium falciparum mdr-1 gene mutations were detected by polymerase chain reaction (PCR) followed by restriction enzyme digest and electrophoresis to determine polymorphism in parasite isolates. Sequencing was done to confirm polymorphism. Proportions were compared using Chi-square test at p value < 0.05.

          Results

          Malaria parasites were detected by RDT in 204 (38.1%) individuals. Asymptomatic infection was detected in 117 (57.3%) and symptomatic malaria confirmed in 87 individuals (42.6%). Overall, individuals with detectable malaria by RDT was significantly higher in individuals with symptoms, 87 of 197 (44.2%), than asymptomatic persons; 117 of 338 (34.6%), p = 0.02. In a sub-set of 75 isolates, 18(24%) and 14 (18.6%) individuals had Pfmdr1 86Y and 1246Y mutations.

          Conclusions

          There is still high malaria transmission rate in Nigeria with higher incidence of asymptomatic infections. These parasites harbour mutations on Pfmdr1 which contribute to artemisinin partner drug resistance; surveillance strategies to reduce the spread of drug resistance in endemic areas are needed to eliminate the reservoir of malaria parasites that can mitigate the eradication of malaria in Nigeria.

          Related collections

          Most cited references35

          • Record: found
          • Abstract: found
          • Article: not found

          Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number.

          The borders of Thailand harbour the world's most multidrug resistant Plasmodium falciparum parasites. In 1984 mefloquine was introduced as treatment for uncomplicated falciparum malaria, but substantial resistance developed within 6 years. A combination of artesunate with mefloquine now cures more than 95% of acute infections. For both treatment regimens, the underlying mechanisms of resistance are not known. The relation between polymorphisms in the P falciparum multidrug resistant gene 1 (pfmdr1) and the in-vitro and in-vivo responses to mefloquine were assessed in 618 samples from patients with falciparum malaria studied prospectively over 12 years. pfmdr1 copy number was assessed by a robust real-time PCR assay. Single nucleotide polymorphisms of pfmdr1, P falciparum chloroquine resistance transporter gene (pfcrt) and P falciparum Ca2+ ATPase gene (pfATP6) were assessed by PCR-restriction fragment length polymorphism. Increased copy number of pfmdr1 was the most important determinant of in-vitro and in-vivo resistance to mefloquine, and also to reduced artesunate sensitivity in vitro. In a Cox regression model with control for known confounders, increased pfmdr1 copy number was associated with an attributable hazard ratio (AHR) for treatment failure of 6.3 (95% CI 2.9-13.8, p<0.001) after mefloquine monotherapy and 5.4 (2.0-14.6, p=0.001) after artesunate-mefloquine therapy. Single nucleotide polymorphisms in pfmdr1 were associated with increased mefloquine susceptibility in vitro, but not in vivo. Amplification in pfmdr1 is the main cause of resistance to mefloquine in falciparum malaria. Multidrug resistant P falciparum malaria is common in southeast Asia, but difficult to identify and treat. Genes that encode parasite transport proteins maybe involved in export of drugs and so cause resistance. In this study we show that increase in copy number of pfmdr1, a gene encoding a parasite transport protein, is the best overall predictor of treatment failure with mefloquine. Increase in pfmdr1 copy number predicts failure even after chemotherapy with the highly effective combination of mefloquine and 3 days' artesunate. Monitoring of pfmdr1 copy number will be useful in epidemiological surveys of drug resistance in P falciparum, and potentially for predicting treatment failure in individual patients.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The silent threat: asymptomatic parasitemia and malaria transmission.

            Scale-up of malaria control interventions has resulted in a substantial decline in global malaria morbidity and mortality. Despite this achievement, there is evidence that current interventions alone will not lead to malaria elimination in most malaria-endemic areas and additional strategies need to be considered. Use of antimalarial drugs to target the reservoir of malaria infection is an option to reduce the transmission of malaria between humans and mosquito vectors. However, a large proportion of human malaria infections are asymptomatic, requiring treatment that is not triggered by care-seeking for clinical illness. This article reviews the evidence that asymptomatic malaria infection plays an important role in malaria transmission and that interventions to target this parasite reservoir may be needed to achieve malaria elimination in both low- and high-transmission areas.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The role of submicroscopic parasitemia in malaria transmission: what is the evidence?

              Achieving malaria elimination requires targeting the human reservoir of infection, including those with asymptomatic infection. Smear-positive asymptomatic infections detectable by microscopy are an important reservoir because they often persist for months and harbor gametocytes, the parasite stage infectious to mosquitoes. However, many asymptomatic infections are submicroscopic and can only be detected by molecular methods. Although there is some evidence that individuals with submicroscopic malaria can infect mosquitoes, transmission is much less likely to occur at submicroscopic gametocyte levels. As malaria elimination programs pursue mass screening and treatment of asymptomatic individuals, further research should strive to define the degree to which submicroscopic malaria contributes to the infectious reservoir and, in turn, what diagnostic detection threshold is needed to effectively interrupt transmission. Copyright © 2014 Elsevier Ltd. All rights reserved.
                Bookmark

                Author and article information

                Contributors
                abiodun.adebayo@covenantuniversity.edu.ng
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                27 June 2019
                27 June 2019
                2019
                : 18
                : 218
                Affiliations
                [1 ]ISNI 0000 0004 1794 8359, GRID grid.411932.c, Department of Biochemistry, , Covenant University, ; Ota, 23401 Nigeria
                [2 ]ISNI 0000 0004 1794 8359, GRID grid.411932.c, Department of Biological Sciences, , Covenant University, ; Ota, 23401 Nigeria
                [3 ]ISNI 0000 0001 0625 9425, GRID grid.412974.d, Department of Pharmacology and Therapeutics, , University of Ilorin, ; Ilorin, 24003 Nigeria
                [4 ]ISNI 0000 0004 1794 8359, GRID grid.411932.c, Demography and Social Statistics Unit, Department of Economics and Development Studies, , Covenant University, ; Ota, 23401 Nigeria
                Article
                2833
                10.1186/s12936-019-2833-8
                6598231
                31248414
                bb98049a-0986-4451-8a73-c25f22a3d617
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 February 2019
                : 9 June 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100006335, Covenant University;
                Award ID: CUCRID Publication support
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Infectious disease & Microbiology
                asymptomatic malaria,pfmdr1,drug resistance,plasmodium falciparum,nigeria

                Comments

                Comment on this article