Inter-relationships of cardinal features and outcomes of symptomatic pediatric Plasmodium falciparum MALARIA in 1,933 children in Kampala, Uganda - PubMed (original) (raw)

Clinical Trial

Inter-relationships of cardinal features and outcomes of symptomatic pediatric Plasmodium falciparum MALARIA in 1,933 children in Kampala, Uganda

Christine M Cserti-Gazdewich et al. Am J Trop Med Hyg. 2013 Apr.

Abstract

Malaria remains a challenging diagnosis with variable clinical presentation and a wide spectrum of disease severity. Using a structured case report form, we prospectively assessed 1,933 children at Mulago Hospital in Kampala, Uganda with acute Plasmodium falciparum malaria. Children with uncomplicated malaria significantly differed from those with severe disease for 17 features. Among 855 children with severe disease, the case-fatality rate increased as the number of severity features increased. Logistic regression identified five factors independently associated with death: cerebral malaria, hypoxia, severe thrombocytopenia, leukocytosis, and lactic acidosis. Cluster analysis identified two groups: one combining anemia, splenomegaly, and leukocytosis; and a second group centered on death, severe thrombocytopenia, and lactic acidosis, which included cerebral malaria, hypoxia, hypoglycemia, and hyper-parasitemia. Our report updates previous clinical descriptions of severe malaria, quantifies significant clinical and laboratory inter-relationships, and will assist clinicians treating malaria and those planning or assessing future research (NCT00707200) (www.clinicaltrials.gov).

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Figures

Figure 1.

Figure 1.

Age distribution of children les than five years of age with severe malaria, Kampala, Uganda. A, Age distribution among children with uncomplicated versus severe malaria. B, Age distribution among children with cerebral malaria or severe anemia.

Figure 2.

Figure 2.

Cerebral malaria according to platelet count at presentation, Kampala. Uganda.

Figure 3.

Figure 3.

Increase in case-fatality rate (CFR) with increasing number of severe malaria features, Kampala, Uganda. CFRs are shown for 855 children with one or more combinations of the following features: cerebral malaria, lactic acidosis, severe anemia, severe thrombocytopenia, or hyper-parasitemia. The x-axis separates children into five groups based on an increasing number of co-existing severe malaria features present in combination. The groups show an increasing median CFR. The size of each bubble indicates the number of persons ranging from n = 558 for the single feature of severe anemia (lower left) to n = 4 for all five features simultaneously present (upper right).

Figure 4.

Figure 4.

Inter-relationships of clinical and laboratory findings in 855 children with severe malaria, Kampala, Uganda. The odds ratios for association between pairs of clinical and laboratory findings were determined for 855 children with severe malaria. Those features with a statistically significant positive odds ratio of association are shown. The reciprocal of the loge of the odds ratio defines the relative distance between spheres, and the number of persons with each feature defines the volume of each sphere. Two clusters of associations were observed. A, Cluster centered on severe malaria anemia (SMA). B, Cluster of seven features. CM = cerebral malaria; LA = lactic acidosis. Thrombocytopenia = platelet count < 50,000/μL.

Figure 5.

Figure 5.

Possible pathophysiologic pathways in fatal Plasmodium falciparum malaria, Kampala, Uganda. The inter-relationships of clinical features of malaria and the identification of factors with significant odds ratios for fatal outcomes suggest distinct pathophysiologic pathways in children with severe disease.

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