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      A Genotyping Study in Benin Comparing the Carriage of Plasmodium falciparum Infections Before Pregnancy and in Early Pregnancy: Story of a Persistent Infection

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          Abstract

          Background

          Malaria infections in the first trimester of pregnancy are frequent and deleterious for both mother and child health. To investigate if these early infections are newly acquired or already present in the host, we assessed whether parasites detected before pregnancy and those detected in early pregnancy are the same infection.

          Methods

          We used data from the preconceptional “RECIPAL” study (Benin, 2014–2017). Sixty-three pregnant women of 411 included who had a malaria infection detected by quantitative polymerase chain reaction both before pregnancy and at the first antenatal care (ANC) visit were selected for this study. Two highly polymorphic markers, msp-2 and glurp, and a fragment-analysis method were used to enumerate the Plasmodium falciparum genotypes and to quantify their proportions within isolates. An infection was considered as persistent when identical msp-2 and glurp genotypes were found in the corresponding prepregnancy and early-pregnancy samples.

          Results

          The median time between the 2 malaria screenings was 3 months. The median gestational age at the first ANC visit was 6.4 weeks. Most infections before pregnancy were submicroscopic infections. Based on both msp-2 and glurp genotyping, the infection was similar before and in early pregnancy in 46% (29/63) of cases.

          Conclusions

          Almost half of P. falciparum infections detected in the first trimester originate before pregnancy. Protecting young women from malaria infection before pregnancy might reduce the prevalence of malaria in early pregnancy and its related poor maternal and birth outcomes.

          Abstract

          To distinguish between new and persistent malaria infection in early pregnancy, we enumerated and compared Plasmodium falciparum genotypes in isolates both before and in the first weeks of pregnancy. Persistent infections from preconception accounted for half the cases.

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          Most cited references39

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          Burden, pathology, and costs of malaria in pregnancy: new developments for an old problem.

          Over the past 10 years, knowledge of the burden, economic costs, and consequences of malaria in pregnancy has improved, and the prevalence of malaria caused by Plasmodium falciparum has declined substantially in some geographical areas. In particular, studies outside of Africa have increased the evidence base of Plasmodium vivax in pregnancy. Rapid diagnostic tests have been poor at detecting malaria in pregnant women, while PCR has shown a high prevalence of low density infection, the clinical importance of which is unknown. Erythrocytes infected with P falciparum that express the surface protein VAR2CSA accumulate in the placenta, and VAR2CSA is an important target of protective immunity. Clinical trials for a VAR2CSA vaccine are ongoing, but sequence variation needs to be carefully studied. Health system and household costs still limit access to prevention and treatment services. Within the context of malaria elimination, pregnant women could be used to monitor malaria transmission. This Series paper summarises recent progress and highlights unresolved issues related to the burden of malaria in pregnancy.
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            Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study

            Summary Background The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern. We aimed to assess the outcome of malaria-exposed and malaria-unexposed first-trimester pregnancies of women from the Thai–Burmese border and compare outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments. Methods We analysed all antenatal records of women in the first trimester of pregnancy attending Shoklo Malaria Research Unit antenatal clinics from May 12, 1986, to Oct 31, 2010. Women without malaria in pregnancy were compared with those who had a single episode of malaria in the first trimester. The association between malaria and miscarriage was estimated using multivariable logistic regression. Findings Of 48 426 pregnant women, 17 613 (36%) met the inclusion criteria: 16 668 (95%) had no malaria during the pregnancy and 945 (5%) had a single episode in the first trimester. The odds of miscarriage increased in women with asymptomatic malaria (adjusted odds ratio 2·70, 95% CI 2·04–3·59) and symptomatic malaria (3·99, 3·10–5·13), and were similar for Plasmodium falciparum and Plasmodium vivax. Other risk factors for miscarriage included smoking, maternal age, previous miscarriage, and non-malaria febrile illness. In women with malaria, additional risk factors for miscarriage included severe or hyperparasitaemic malaria (adjusted odds ratio 3·63, 95% CI 1·15–11·46) and parasitaemia (1·49, 1·25–1·78 for each ten-fold increase in parasitaemia). Higher gestational age at the time of infection was protective (adjusted odds ratio 0·86, 95% CI 0·81–0·91). The risk of miscarriage was similar for women treated with chloroquine (92 [26%] of 354), quinine (95 [27%) of 355), or artesunate (20 [31%] of 64; p=0·71). Adverse effects related to antimalarial treatment were not observed. Interpretation A single episode of falciparum or vivax malaria in the first trimester of pregnancy can cause miscarriage. No additional toxic effects associated with artesunate treatment occurred in early pregnancy. Prospective studies should now be done to assess the safety and efficacy of artemisinin combination treatments in early pregnancy. Funding Wellcome Trust and Bill & Melinda Gates Foundation.
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              Malaria in pregnancy: small babies, big problem.

              Placental malaria is hypothesized to lead to placental insufficiency, which causes fetal growth restriction (FGR). In this review, recent discoveries regarding the mechanisms of pathogenesis by which malaria causes FGR are discussed in the wider context of placental function and fetal growth. Placental malaria and associated host responses can induce changes in placental structure and function, affecting pregnancy-associated growth-regulating hormones and predisposing the offspring to hypertension and vascular dysfunction. Risk factors associated with FGR are highlighted, and potential interventions and studies to uncover remaining mechanisms of pathogenesis are proposed. Together, these strategies aim to decrease the burden of FGR associated with malaria in pregnancy. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin Infect Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                15 July 2021
                22 June 2020
                22 June 2020
                : 73
                : 2
                : e355-e361
                Affiliations
                [1 ] Université de Paris, UMR261-MERIT, Institut de Recherche pour le Développement , Paris, France
                [2 ] Clinical Research Institute of Benin (IRCB) , Abomey-Calavi, Benin
                [3 ] Faculty of Infectious and Tropical Diseases, Disease Control Department, London School of Hygiene and Tropical Medicine , London, United Kingdom
                [4 ] FIND , Geneva, Switzerland
                [5 ] University of Bordeaux, Inserm, Institut de Recherche pour le Développement, Inserm, University of Bordeaux , UMR, Bordeaux, France
                Author notes
                Correspondence: V. Briand, University of Bordeaux, Inserm, Institut de Recherche pour le Développement (IRD), UMR 1219, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France ( valerie.briand@ 123456ird.fr ).
                Article
                ciaa841
                10.1093/cid/ciaa841
                8282262
                32569359
                b8c80f90-e9a5-4c10-9ff2-5a18566373a1
                © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 March 2020
                : 16 May 2020
                : 17 June 2020
                : 21 July 2020
                Page count
                Pages: 7
                Funding
                Funded by: Bill and Melinda Gates Foundation, DOI 10.13039/100000865;
                Award ID: OPP1169555
                Funded by: Agence Nationale de la Recherche, DOI 10.13039/501100001665;
                Award ID: ANR-13-JSV1-0004
                Funded by: Fondation de France, DOI 10.13039/501100004431;
                Award ID: 00074147
                Categories
                Online Only Articles
                Major Articles and Commentaries
                AcademicSubjects/MED00290

                Infectious disease & Microbiology
                malaria,pregnancy,africa,genotyping techniques,polymerase chain reaction

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