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      Impact of Malaria at the End of Pregnancy on Infant Mortality and Morbidity

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          Abstract

          Background.  There is some consensus that malaria in pregnancy may negatively affect infant's mortality and malaria morbidity, but there is less evidence concerning the factors involved.

          Methods.  A total of 1030 Mozambican pregnant women were enrolled in a randomized, placebo-controlled trial of intermittent preventive treatment with sulfadoxine-pyrimethamine, and their infants were followed up throughout infancy. Overall mortality and malaria morbidity rates were recorded. The association of maternal and fetal risk factors with infant mortality and malaria morbidity was assessed.

          Results.  There were 58 infant deaths among 997 live-born infants. The risk of dying during infancy was increased among infants born to women with acute placental infection (odds ratio [OR], 5.08 [95% confidence interval (CI), 1.77–14.53)], parasitemia in cord blood (OR, 19.31 [95% CI, 4.44–84.02]), low birth weight (OR, 2.82 [95% CI, 1.27–6.28]) or prematurity (OR, 3.19 [95% CI, 1.14–8.95]). Infants born to women who had clinical malaria during pregnancy (OR, 1.96 [95% CI, 1.13–3.41]) or acute placental infection (OR, 4.63 [95% CI, 2.10–10.24]) had an increased risk of clinical malaria during infancy.

          Conclusions.  Malaria infection at the end of pregnancy and maternal clinical malaria negatively impact survival and malaria morbidity in infancy. Effective clinical management and prevention of malaria in pregnancy may improve infant's health and survival.

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          Most cited references50

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          WHO estimates of the causes of death in children.

          Child survival efforts can be effective only if they are based on accurate information about causes of deaths. Here, we report on a 4-year effort by WHO to improve the accuracy of this information. WHO established the external Child Health Epidemiology Reference Group (CHERG) in 2001 to develop estimates of the proportion of deaths in children younger than age 5 years attributable to pneumonia, diarrhoea, malaria, measles, and the major causes of death in the first 28 days of life. Various methods, including single-cause and multi-cause proportionate mortality models, were used. The role of undernutrition as an underlying cause of death was estimated in collaboration with CHERG. In 2000-03, six causes accounted for 73% of the 10.6 million yearly deaths in children younger than age 5 years: pneumonia (19%), diarrhoea (18%), malaria (8%), neonatal pneumonia or sepsis (10%), preterm delivery (10%), and asphyxia at birth (8%). The four communicable disease categories account for more than half (54%) of all child deaths. The greatest communicable disease killers are similar in all WHO regions with the exception of malaria; 94% of global deaths attributable to this disease occur in the Africa region. Undernutrition is an underlying cause of 53% of all deaths in children younger than age 5 years. Achievement of the millennium development goal of reducing child mortality by two-thirds from the 1990 rate will depend on renewed efforts to prevent and control pneumonia, diarrhoea, and undernutrition in all WHO regions, and malaria in the Africa region. In all regions, deaths in the neonatal period, primarily due to preterm delivery, sepsis or pneumonia, and birth asphyxia should also be addressed. These estimates of the causes of child deaths should be used to guide public-health policies and programmes.
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            Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial.

            Development of an effective malaria vaccine could greatly contribute to disease control. RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on Plasmodium falciparum circumsporozoite surface antigen. We aimed to assess vaccine efficacy, immunogenicity, and safety in young African children. We did a double-blind, phase IIb, randomised controlled trial in Mozambique in 2022 children aged 1-4 years. The study included two cohorts of children living in two separate areas which underwent different follow-up schemes. Participants were randomly allocated three doses of either RTS,S/AS02A candidate malaria vaccine or control vaccines. The primary endpoint, determined in cohort 1 (n=1605), was time to first clinical episode of P falciparum malaria (axillary temperature > or =37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) over a 6-month surveillance period. Efficacy for prevention of new infections was determined in cohort 2 (n=417). Analysis was per protocol. 115 children in cohort 1 and 50 in cohort 2 did not receive all three doses and were excluded from the per-protocol analysis. Vaccine efficacy for the first clinical episodes was 29.9% (95% CI 11.0-44.8; p=0.004). At the end of the 6-month observation period, prevalence of P falciparum infection was 37% lower in the RTS,S/AS02A group compared with the control group (11.9% vs 18.9%; p=0.0003). Vaccine efficacy for severe malaria was 57.7% (95% CI 16.2-80.6; p=0.019). In cohort 2, vaccine efficacy for extending time to first infection was 45.0% (31.4-55.9; p<0.0001). The RTS,S/AS02A vaccine was safe, well tolerated, and immunogenic. Our results show development of an effective vaccine against malaria is feasible.
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              The burden of malaria in pregnancy in malaria-endemic areas.

              Pregnant women in malarious areas may experience a variety of adverse consequences from malaria infection including maternal anemia, placental accumulation of parasites, low birth weight (LBW) from prematurity and intrauterine growth retardation (IUGR), fetal parasite exposure and congenital infection, and infant mortality (IM) linked to preterm-LBW and IUGR-LBW. We reviewed studies between 1985 and 2000 and summarized the malaria population attributable risk (PAR) that accounts for both the prevalence of the risk factors in the population and the magnitude of the associated risk for anemia, LBW, and IM. Consequences from anemia and human immunodeficiency virus infection in these studies were also considered. Population attributable risks were substantial: malaria was associated with anemia (PAR range = 3-15%), LBW (8-14%), preterm-LBW (8-36%), IUGR-LBW (13-70%), and IM (3-8%). Human immunodeficiency virus was associated with anemia (PAR range = 12-14%), LBW (11-38%), and direct transmission in 20-40% of newborns, with direct mortality consequences. Maternal anemia was associated with LBW (PAR range = 7-18%), and fetal anemia was associated with increased IM (PAR not available). We estimate that each year 75,000 to 200,000 infant deaths are associated with malaria infection in pregnancy. The failure to apply known effective antimalarial interventions through antenatal programs continues to contribute substantially to infant deaths globally.
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                Author and article information

                Journal
                J Infect Dis
                jinfdis
                jinfdis
                The Journal of Infectious Diseases
                Oxford University Press
                0022-1899
                1537-6613
                01 March 2011
                03 January 2011
                03 January 2011
                : 203
                : 5
                : 691-699
                Affiliations
                [1 ]Barcelona Centre for International Health Research and Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdicas August Pi i Sunyer, Universitat de Barcelona, Spain
                [2 ]Manhiça Health Research Centre, Mozambique
                [3 ]National Institute of Health, Ministry of Health, Maputo, Mozambique
                [4 ]National Directorate of Health and National Malaria Control Program, Ministry of Health, Maputo, Mozambique
                Author notes
                Reprints or correspondence: Azucena Bardají, MD, MSc, Barcelona Centre for International Health Research, Hospital Clinic, Universitat de Barcelona, Villarroel, 170, 08036 Barcelona, Spain ( abardaji@ 123456clinic.ub.es ).

                Potential conflicts of interest: none reported.

                Presented in part: Fifth Pan-African Conference on Malaria, Nairobi, Kenya, November 2009.

                Trial registration number, NCT00209781. Registry's URL: http://clinicaltrials.gov/ct2/show/NCT00209781?term=NCT00209781&;rank=

                Article
                10.1093/infdis/jiq049
                3071276
                21199881
                1962b056-6774-4e36-900b-0fdef64402b8
                © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 May 2010
                : 25 October 2010
                Categories
                Major Articles and Brief Reports
                Parasites

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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