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      Malaria in rural Mozambique. Part I: Children attending the outpatient clinic

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          Abstract

          Background

          Malaria represents a huge burden for the health care services across Africa. Describing malaria attending health services contributes to quantify the burden and describe the epidemiology and clinical presentation.

          Methods

          Retrospective analysis of data collected through the Manhiça morbidity surveillance system (Mozambique) on all paediatric visits (<15 years) to the outpatient clinic from June 2003 to May 2005. Age-specific minimum community-based incidence rates (MCBIRs) of malaria were calculated using demographic surveillance system data. Malaria was defined as fever or history of fever in the preceding 24 hours with asexual Plasmodium falciparum parasitaemia of any density in the blood smear.

          Results

          A total of 94,941 outpatient visits were seen during the study period, of which 30.5% had malaria. Children younger than three years accounted for almost half of the total malaria cases and children aged ≥ 5 years represented 36.4% of the cases. Among children who presented with malaria, 56.7% had fever and among children who presented with fever or a history of fever only 37.2% had malaria. The geometric mean parasitaemia in malaria cases was 8582.2 parasites/μL, peaking in children aged two to three years. 13% of malaria cases had a PCV<25% and the mean PCV in malaria cases increased gradually with age, ranging from 27.8% in children aged 2–12 months to 34.4% in ≥ 5 years. The percentage of cases admitted or transferred showed a clear decreasing trend with age. MCBIRs of outpatient malaria per 1,000 child years at risk for the whole study period were of 394 in infants, 630 in children aged 1 to <5 years and 237 in children aged five years or more. A clustering of the cases was observed, whereby most children never had malaria, some had a few episodes and very few had many episodes.

          Conclusion

          Preventive measures should be targeted at children younger than three years, as they carry the highest burden of malaria. Children aged 5–15 years represent around a third of the malaria cases and should also be included in control programmes. Concern should be raised about presumptive treatment of fever cases with artemisinin-combination therapies, as many children will, according to IMCI guidelines, receive treatment unnecessarily.

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          Most cited references26

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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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            Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial.

            RTS,S/AS02A is a pre-erythrocytic stage malaria vaccine that provides partial protection against infection in malaria-naive adult volunteers and hyperimmune adults. A previous report showed that this vaccine reduced risk of clinical malaria, delayed time to new infection, and reduced episodes of severe malaria over 6 months in African children. An important remaining issue is the durability of protection against clinical disease in these children. We did a randomised, controlled, phase IIb trial of RTS,S/AS02A given at 0, 1, and 2 months in 2022 Mozambican children aged 1-4 years. We previously determined vaccine efficacy (VE) against clinical malaria in a double-blind phase that included study months 2.5-8.5 (VE(2.5-8.5)). We now report VE in a single-blind phase up to month 21 (VE(8.5-21)). The primary endpoint was time to first or only clinical episode of Plasmodium falciparum malaria (axillary temperature 37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) detected through a passive case detection system. We also determined VE for other case definitions and for episodes of severe malaria. This study is registered with the ClinicalTrials.gov identifier NCT00197041. During the single-blind phase, VE(8.5-21) was 28.9% (95% CI 8.4-44.8; p=0.008). At month 21, prevalence of P falciparum infection was 29% lower in the RTS,S/AS02A group than in the control (p=0.017). Considering the entire study period, VE(2.5-21) was 35.3% (95% CI 21.6-46.6; p<0.0001) and VE(2.5-21) for severe malaria was 48.6% (95% CI 12.3-71.0; p=0.02). These results show that RTS,S/AS02A confers partial protection in African children aged 1-4 years living in rural endemic areas against a range of clinical disease caused by P falciparum for at least 18 months, and confirm the potential of malaria vaccines to become credible control tools for public-health use.
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              African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death.

              Malaria remains the most important parasitic cause of mortality in humans. Its presentation is thought to vary according to the intensity of Plasmodium falciparum transmission. However, detailed descriptions of presenting features and risk factors for death are only available from moderate transmission settings. Such descriptions help to improve case management and identify priority research areas. Standardized systematic procedures were used to collect clinical and laboratory data on 6,624 children admitted to hospital over a 1-year period in an intensely malarious part of Tanzania. Frequencies of signs and symptoms were calculated and their association with a fatal outcome was assessed using multivariate logistic regression. There were 72 deaths among 2,432 malaria cases (case fatality rate [CFR] = 3.0%); 44% of the cases and 54% of the deaths were in individuals less than 1 year of age. There was no association between level of parasitemia and CFR. Increased risk of dying was independently found in all children with hypoglycemia (odds ratio [OR] = 6.7, 95% confidence interval [CI] = 3.9-11.7), in children 1-7 months of age with tachypnea (OR = 8.8, 95% CI = 2.6-30.5) and dehydration (OR = 5.0, 95% CI = 1.9-14.2), and in children 8 months to 4 years of age with chest indrawing (OR = 4.7, 95% CI = 2.0-11.2) and inability to localize a painful stimulus (OR = 6.9, 95% CI = 2.9-16.5). Children in the bottom quartile of weight-for-age were more likely to die (OR = 2.1, 95% CI = 1.3-3.5). Eight percent of the malaria cases had severe anemia (packed cell volume < 15%) but 24% received a blood transfusion. The epidemiology of malaria disease may be more complex than previously thought. Improved case management in a wide variety of health facilities may result from adequate identification and treatment of dehydration and hypoglycemia. Transfusion-requiring anemia is a major problem and sustainable, effective preventive measures are urgently needed.
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                Author and article information

                Journal
                Malar J
                Malaria Journal
                BioMed Central
                1475-2875
                2008
                26 February 2008
                : 7
                : 36
                Affiliations
                [1 ]Barcelona Center for International Health Research (CRESIB), Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Rosselló 132, E-08036 Barcelona, Spain
                [2 ]Centro de Investigação em Saúde de Manhiça (CISM), Manhiça, CP 1929, Maputo, Mozambique
                [3 ]Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique
                [4 ]Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique
                [5 ]Direcção Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique
                Article
                1475-2875-7-36
                10.1186/1475-2875-7-36
                2268704
                18302770
                dee32ee2-109f-47c5-bb2d-b2470d110ae0
                Copyright © 2008 Guinovart et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 August 2007
                : 26 February 2008
                Categories
                Research

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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