Prognostic value of circulating pigmented cells in African children with malaria

Abstract

Background: Plasmodium falciparum malaria is a common cause of morbidity in African children, but identifying those who are likely to die is problematic. Previous studies suggested that circulating malarial pigment might be a useful predictor of severity, but none were large enough to detect any association with mortality.

Methods: We used thick blood smears performed on admission for 26,296 children hospitalized with P. falciparum at 1 of 6 hospitals in the Severe Malaria in African Children network to assess the prognostic value of pigment-containing granulocytes, monocytes, and parasites.

Results: Although at all but one of the study sites the risk of mortality for subjects presenting with >5 pigmented granulocytes per 200 white blood cells was higher than in subjects with no pigmented granulocytes, adjusted odds ratios estimated through logistic regression, which included other established markers of severe malaria, suggested that associations between pigmented cells and mortality were moderate to nonexistent in most sites. The predictive ability of pigmented cells was low, as measured by the change in the area under the receiver operating characteristic curve of logistic regression models.

Conclusions: Although high levels of pigmented cells were associated with a fatal outcome in some study sites, they were not useful predictors of outcome across Africa.

Figure 1

Distribution of malaria pigment in granulocytes, mononuclear leukocytes, and parasitized erythrocytes from African children who survived or died from malaria. Comparisons between children who survived and those who died reached statistical significance in each group (P<.001 for each comparison). Solid bars, median values; upper hinges, 75th percentiles; lower hinges, 25th percentiles; whiskers, most-extreme values within 1.5 × interquartile range; stars, 95th percentiles.

Figure 2

Receiver operating characteristic curves assessing pigment and other predictors as prognostic factors for mortality. Predictions were based on site-specific logistic regression models using only pigmented granulocytes (PG; A), only pigmented mononuclear leukocytes (PM; B), other relevant predictors but no pigment variables (C), and including PG, PM, plus other relevant predictors (D). Other relevant predictors included hyperlactatemia, coma, deep breathing, prostration, hypoglycemia, and weight-for-age z scores (table 4). · · · ·, Banjul; — – —, Blantyre; — · · · —, Kilifi; — —— —, Kumasi; ———, Lambarene; — · —, Libreville.

Table 1

Demographic, clinical, and laboratory characteristics and outcomes of African children with malaria

Table 2

Spearman rank correlation coefficients for associations between pigmented cells and other disease markers in African children with malaria by site.

Table 3

Mortality risk and distribution of cells with malaria pigment among African children with malaria.

Table 4

Findings of logistic regression analysis to determine adjusted odds ratios (ORs) of the associations between pigmented cells and mortality among African children with malaria.