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      Lack of effect of intermittent preventive treatment for malaria in pregnancy and intense drug resistance in western Uganda.

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          Abstract

          Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is widely implemented in sub-Saharan Africa for the prevention of malaria in pregnancy and adverse birth outcomes. However, in areas of intense SP resistance, the efficacy of IPTp may be compromised.

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          Malaria in pregnancy: pathogenesis and immunity.

          Stephen Rogerson, Lars Hviid, Patrick Duffy … (2007)
          Understanding of the biological basis for susceptibility to malaria in pregnancy was recently advanced by the discovery that erythrocytes infected with Plasmodium falciparum accumulate in the placenta through adhesion to molecules such as chondroitin sulphate A. Antibody recognition of placental infected erythrocytes is dependent on sex and gravidity, and could protect from malaria complications. Moreover, a conserved parasite gene-var2csa-has been associated with placental malaria, suggesting that its product might be an appropriate vaccine candidate. By contrast, our understanding of placental immunopathology and how this contributes to anaemia and low birthweight remains restricted, although inflammatory cytokines produced by T cells, macrophages, and other cells are clearly important. Studies that unravel the role of host response to malaria in pathology and protection in the placenta, and that dissect the relation between timing of infection and outcome, could allow improved targeting of preventive treatments and development of a vaccine for use in pregnant women.
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            Guidelines for the Treatment of Malaria

            Y-W Ho (2010)
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              Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria.

              James G. Kublin, Fraction Dzinjalamala, Deborah Kamwendo … (2002)
              Molecular assays for monitoring sulfadoxine-pyrimethamine-resistant Plasmodium falciparum have not been implemented because of the genetic and statistical complexity of the parasite mutations that confer resistance and their relation to treatment outcomes. This study analyzed pretreatment dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genotypes and treatment outcomes in a double-blind, placebo-controlled trial of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment for uncomplicated P. falciparum malaria. Multiple logistic regression was used to identify mutations that were predictive of treatment failure and to identify interactions and confounding factors. Infections caused by parasites with 3 DHFR mutations and 2 DHPS mutations (the "quintuple mutant") were associated with sulfadoxine-pyrimethamine treatment failure but not with chlorproguanil-dapsone treatment failure. The presence of a single DHFR mutation (Arg-59) with a single DHPS mutation (Glu-540) accurately predicted the presence of the quintuple mutant. If this model is validated in other populations, it will finally be possible to use molecular markers for surveillance of antifolate-resistant P. falciparum malaria in Africa.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Malar. J.
                Title: Malaria journal
                Publisher: Springer Nature
                ISSN (Electronic): 1475-2875
                ISSN (Print): 1475-2875
                Publication date (Electronic): Sep 26 2015
                Volume: 14
                Affiliations
                [1 ] Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Berlin, Germany. verabraun@gmail.com.
                [2 ] Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Berlin, Germany. Eva.Rempis@gmx.de.
                [3 ] Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Berlin, Germany. alexandra.schnack@charite.de.
                [4 ] Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Berlin, Germany. sarah.decker@gmail.com.
                [5 ] Public Health Department, Mountains of the Moon University, Fort Portal, Uganda. rubaihayoj@yahoo.co.uk.
                [6 ] School of Public Health, College of Health Sciences, Makerere University, Kampala, Uganda. naz@musph.ac.ug.
                [7 ] Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Berlin, Germany. stefanie.theuring@charite.de.
                [8 ] Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Berlin, Germany. gundel.harms@charite.de.
                [9 ] Holy Family Virika Hospital, Fort Portal, Uganda. holyface03@gmail.com.
                [10 ] Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Berlin, Germany. frank.mockenhaupt@charite.de.
                Article
                Publisher Item ID: 10.1186/s12936-015-0909-7
                DOI: 10.1186/s12936-015-0909-7
                PMC ID: 4583758
                PubMed ID: 26410081
                SO-VID: 81ce9a58-2026-4f4a-a85d-82e707d6227d
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