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      Impact of Intermittent Preventive Treatment With Dihydroartemisinin-Piperaquine on Malaria in Ugandan Schoolchildren: A Randomized, Placebo-Controlled Trial

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          Abstract

          Dihydroartemisinin-piperaquine administered at monthly intervals, but not that dosed once a school term, is a remarkably effective measure for the prevention of incidence of malaria, prevalence of parasitemia, and prevalence of anemia in schoolchildren living in a high-transmission setting.

          Abstract

          Background.  Intermittent preventive treatment (IPT) in schoolchildren offers a promising option for malaria control. However, the optimal drug and dosing regimens for IPT remain to be determined.

          Methods.  We conducted a randomized, double-blind, placebo-controlled trial in 740 schoolchildren aged 6–14 years living in a setting of high malaria transmission in Uganda. Enrolled children were randomized to dihydroartemisinin-piperaquine (DP) given once a month (IPTm), DP given once a school term (4 treatments over 12 months, IPTst), or placebo and followed for 12 months. The primary outcome was the incidence of malaria over 12 months. Secondary outcomes included parasite prevalence and anemia over 12 months. Analyses were conducted on an intention-to-treat basis.

          Results.  In the placebo arm, the incidence of malaria was 0.34 episodes per person-year and the prevalence of parasitemia and anemia was 38% and 20%, respectively. IPTm reduced the incidence of malaria by 96% (95% confidence interval [CI], 88%–99%, P < .0001), the prevalence of asymptomatic parasitemia by 94% (95% CI, 92%–96%, P < .0001), and the prevalence of anemia by 40% (95% CI, 19%–56%, P < .0001). IPTst had no significant effect on the incidence of symptomatic malaria or the prevalence of anemia, but reduced the prevalence of asymptomatic parasitemia by 54% (95% CI, 47%–60%, P < .0001).

          Conclusions.  Monthly IPT with DP offered remarkable protection against clinical malaria, parasitemia, and anemia in schoolchildren living in a high-malaria-transmission setting.

          Clinical Trials Registration.   NCT01231880.

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          Most cited references31

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          Variation in malaria transmission intensity in seven sites throughout Uganda.

          Knowledge of the baseline malaria transmission in a given environment is important to guide malaria control interventions. However, in Uganda, recent information on malaria transmission intensity is lacking. Therefore, a 1-year entomological study was conducted in seven ecologically different sites throughout the country to assess spatial and temporal patterns in malaria transmission intensity. Anopheles gambiae sensu stricto was the main vector in five of the seven study sites, and An. funestus was the most important vector in the two other sites. In a peri-urban village, An. arabiensis contributed substantially to malaria transmission. Clear differences in annual entomological inoculation rates (AEIR) were observed between the study sites, ranging from 4 infective bites per person per year in the southwestern part of the country to >1,500 infective bites per person per year in a swampy area near the Nile River. Between villages with parasite prevalences of >or= 80% in children between 1 and 9 years old, a 4-fold difference in AEIR was observed. Based on the observed behavior of the vectors, insecticide-treated bed nets will be highly effective in controlling malaria. However, in the high transmission areas, additional measures will be needed to reduce the malaria burden to acceptable levels.
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            Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control.

            Human co-infection with Plasmodium falciparum and helminths is ubiquitous throughout Africa, although its public health significance remains a topic for which there are many unknowns. In this review, we adopted an empirical approach to studying the geography and epidemiology of co-infection and associations between patterns of co-infection and hemoglobin in different age groups. Analysis highlights the extensive geographic overlap between P. falciparum and the major human helminth infections in Africa, with the population at coincident risk of infection greatest for hookworm. Age infection profiles indicate that school-age children are at the highest risk of co-infection, and re-analysis of existing data suggests that co-infection with P. falciparum and hookworm has an additive impact on hemoglobin, exacerbating anemia-related malarial disease burden. We suggest that both school-age children and pregnant women--groups which have the highest risk of anemia--would benefit from an integrated approach to malaria and helminth control.
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              Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials.

              Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa. We pooled data from six double-blind, randomised, placebo-controlled trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all trials, IPTi or placebo was given to infants at the time of routine vaccinations delivered by WHO's Expanded Program on Immunization. Data from the trials for incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in infants up to 12 months of age were reanalysed by use of standard outcome definitions and time periods. Analysis was by modified intention to treat, including all infants who received at least one dose of IPTi or placebo. The six trials provided data for 7930 infants (IPTi, n=3958; placebo, n=3972). IPTi had a protective efficacy of 30.3% (95% CI 19.8-39.4, p<0.0001) against clinical malaria, 21.3% (8.2-32.5, p=0.002) against the risk of anaemia, 38.1% (12.5-56.2, p=0.007) against hospital admissions associated with malaria parasitaemia, and 22.9% (10.0-34.0, p=0.001) against all-cause hospital admissions. There were 56 deaths in the IPTi group compared with 53 in the placebo group (rate ratio 1.05, 95% CI 0.72-1.54, p=0.79). One death, judged as possibly related to IPTi because it occurred 19 days after a treatment dose, was subsequently attributed to probable sepsis. Four of 676 non-fatal hospital admissions in the IPTi group were deemed related to study treatment compared with five of 860 in the placebo group. None of three serious dermatological adverse events in the IPTi group were judged related to study treatment compared with one of 13 in the placebo group. IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control. Bill & Melinda Gates Foundation.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                1058-4838
                1537-6591
                15 May 2014
                12 March 2014
                12 March 2014
                : 58
                : 10
                : 1404-1412
                Affiliations
                [1 ]Department of Medicine, Makerere University College of Health Sciences
                [2 ]Infectious Disease Research Collaboration
                [3 ]Department of Epidemiology and Biostatistics, School of Public Health, Makerere University College of Health Sciences , Kampala, Uganda
                [4 ]Department of Medicine, San Francisco General Hospital, University of California , San Francisco
                [5 ]Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , United Kingdom
                [6 ]Malaria Public Health and Epidemiology Group, Kenya Medical Research Institute–Wellcome Trust Collaborative Programme , Nairobi, Kenya
                Author notes
                Correspondence: Joaniter Nankabirwa, MBChB, MSc, Department of Medicine, Makerere University College of Health Sciences, PO Box 7475, Kampala, Uganda ( jnankabirwa@ 123456yahoo.co.uk ).
                Article
                ciu150
                10.1093/cid/ciu150
                4001293
                24621953
                76755749-3485-430a-ae48-7353728852b7
                © The Author 2014. Published by Oxford University Press on behalf of 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/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 December 2013
                : 1 March 2014
                Categories
                Articles and Commentaries

                Infectious disease & Microbiology
                malaria,intermittent preventive treatment,schoolchildren
                Infectious disease & Microbiology
                malaria, intermittent preventive treatment, schoolchildren

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