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      Predicting the Clinical Outcome of Severe Falciparum Malaria in African Children: Findings From a Large Randomized Trial

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      1 , , 2 , 3 , 4 , 4 , 5 , 6 , 6 , 2 , 3 , 1 , 6 , 4 , 7 , 7 , 8 , 9 , 10 , 10 , 5 , 11 , 13 , 12 , 13 , 4 , 14 , 12 , 4 , 4 , 14 , 9 , 8 , 4 , 4 , 4
      Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
      Oxford University Press

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          Abstract

          Four predictors were independently associated with an increased risk of death: acidosis, cerebral manifestations of malaria, elevated blood urea nitrogen, or signs of chronic illness. The standard base deficit was found to be the single most relevant predictor of death.

          Abstract

          Background.  Data from the largest randomized, controlled trial for the treatment of children hospitalized with severe malaria were used to identify such predictors of a poor outcome from severe malaria.

          Methods.  African children (<15 years) with severe malaria participated in a randomized comparison of parenteral artesunate and parenteral quinine in 9 African countries. Detailed clinical assessment was performed on admission. Parasite densities were assessed in a reference laboratory. Predictors of death were examined using a multivariate logistic regression model.

          Results.  Twenty indicators of disease severity were assessed, out of which 5 (base deficit, impaired consciousness, convulsions, elevated blood urea, and underlying chronic illness) were associated independently with death. Tachypnea, respiratory distress, deep breathing, shock, prostration, low pH, hyperparasitemia, severe anemia, and jaundice were statistically significant indicators of death in the univariate analysis but not in the multivariate model. Age, glucose levels, axillary temperature, parasite density, heart rate, blood pressure, and blackwater fever were not related to death in univariate models.

          Conclusions.  Acidosis, cerebral involvement, renal impairment, and chronic illness are key independent predictors for a poor outcome in African children with severe malaria. Mortality is markedly increased in cerebral malaria combined with acidosis.

          Clinical Trial Registration.  ISRCTN50258054.

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          Most cited references79

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          Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study.

          To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission. Prospective observational study of children and adults over the course a year. 10 hospitals in north east Tanzania. 17,313 patients were admitted to hospital; of these 4474 (2851 children aged under 5 years) fulfilled criteria for severe disease. Details of the treatment given and outcome. Altitudes of residence (a proxy for transmission intensity) measured with a global positioning system. Blood film microscopy showed that 2062 (46.1%) of people treated for malaria had Plasmodium falciparum (slide positive). The proportion of slide positive cases fell with increasing age and increasing altitude of residence. Among 1086 patients aged > or = 5 years who lived above 600 metres, only 338 (31.1%) were slide positive, while in children < 5 years living in areas of intense transmission (< 600 metres) most (958/1392, 68.8%) were slide positive. Among 2375 people who were slide negative, 1571 (66.1%) were not treated with antibiotics and of those, 120 (7.6%) died. The case fatality in slide negative patients was higher (292/2412, 12.1%) than for slide positive patients (142/2062, 6.9%) (P < 0.001). Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children. In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults. This is associated with a failure to treat alternative causes of severe infection. Diagnosis needs to be improved and syndromic treatment considered. Routine hospital data may overestimate mortality from malaria by over twofold.
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            Clinical review: Severe malaria

            Malaria represents a medical emergency because it may rapidly progress to complications and death without prompt and appropriate treatment. Severe malaria is almost exclusively caused by Plasmodium falciparum. The incidence of imported malaria is increasing and the case fatality rate remains high despite progress in intensive care and antimalarial treatment. Clinical deterioration usually appears 3–7 days after onset of fever. Complications involve the nervous, respiratory, renal, and/or hematopoietic systems. Metabolic acidosis and hypoglycemia are common systemic complications. Intravenous quinine and quinidine are the most widely used drugs in the initial treatment of severe falciparum malaria, whereas artemisinin derivatives are currently recommended for quinine-resistant cases. As soon as the patient is clinically stable and able to swallow, oral treatment should be given. The intravascular volume should be maintained at the lowest level sufficient for adequate systemic perfusion to prevent development of acute respiratory distress syndrome. Renal replacement therapy should be initiated early. Exchange blood transfusion has been suggested for the treatment of patients with severe malaria and high parasitemia. For early diagnosis, it is paramount to consider malaria in every febrile patient with a history of travel in an area endemic for malaria.
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              Vertical transmission of HIV-1 infection.

              M-L Newell (2015)
              Vertical transmission is the dominant mode of acquisition of infection for HIV infection in children, and about 1600 infants are newly infected each day worldwide. Without interventions the risk of transmission is between 15% and 35%, and associated with maternal disease progression, prematurity, duration of rupture of membranes, length of labour, and vaginal delivery. Breastfeeding approximately doubles the risk of vertical transmission; the additional risk of transmission through breastfeeding is approximately 15-20%, with about one-third of this accounted for by late postnatal transmission after 3 months of age. Current strategies to reduce the risk of transmission include a short course of anti-retroviral therapy, avoidance of breastfeeding and Caesarean section delivery. However, even if interventions late in pregnancy or around the time of delivery are highly effective in preventing perinatal infection, it is likely that as a public health policy they are of interest only if alternatives to breastfeeding are feasible, affordable, safe and available.
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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 April 2012
                15 April 2012
                : 54
                : 8
                : 1080-1090
                Affiliations
                [1 ]Department of Global Health, Menzies School of Health Research, Casuarina, Northern Territory, Australia
                [2 ]Royal Victoria Teaching Hospital
                [3 ]MRC laboratories, Banjul, The Gambia
                [4 ]Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
                [5 ]University of Ilorin Teaching Hospital, Nigeria
                [6 ]Komfo Anokye Teaching Hospital, Kumasi, Ghana
                [7 ]Hospital Central da Beira, Mozambique
                [8 ]Magunga District Hospital, NIMR-Korogwe Research Laboratory, Tanzania
                [9 ]Rwamagana Hospital and Nyanza Hospital, Rwanda
                [10 ]Kilifi District General Hospital, Kenya
                [11 ]Teule District Hospital, Muheza, Tanzania
                [12 ]Department of Infectious and Tropical Diseases, London School of Tropical Medicine and Hygiene, United Kingdom
                [13 ]Mbarara Teaching Hospital, Uganda
                [14 ]Kingasani Health Centre, Kinshasa, Democratic Republic of the Congo
                Author notes
                Correspondence: Lorenz von Seidlein, MD, PhD, Dept of Global Health, Menzies School of Health Research, John Mathews Bldg (58), PO Box 41096, Casuarina, NT 0810, Australia ( lseidlein@ 123456gmail.com ).
                Article
                10.1093/cid/cis034
                3309889
                22412067
                b84fe767-f9b9-4247-bd28-6a4d0a19989d
                © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please email:journals.permissions@oup.com.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 September 2011
                : 6 December 2011
                Page count
                Pages: 11
                Categories
                Articles and Commentaries

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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