54 research outputs found

    Clinical Features and Outcome in Children with Severe <i>Plasmodium falciparum</i> Malaria: A Meta-Analysis

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    <div><p>Background</p><p>Although global malaria mortality is declining, estimates may not reflect better inpatient management of severe malaria (SM) where reported case fatality rates (CFRs) vary from 1–25%.</p><p>Methods</p><p>A meta-analysis of prospective studies of SM was conducted to examine i) whether hypothesized differences between clinical features and outcome in Melanesian compared with African or Asian children really exist, and ii) to explore temporal changes in overall and complication-specific CFRs. The proportions of different SM complications and, overall and complication-specific CFRs were incorporated into the meta-analysis. Adjustments were made for study-level covariates including geographic region, SM definition, artemisinin treatment, median age of participants and time period.</p><p>Findings</p><p>Sixty-five studies were included. Substantial heterogeneity (<i>I</i><sup>2</sup>>80%) was demonstrated for most outcomes. SM definition contributed to between-study heterogeneity in proportions of cerebral malaria (CM), metabolic acidosis (MA), severe anemia and overall CFR, whilst geographic region was a significant moderator in for CM and hypoglycemia (HG) rates. Compared with their African counterparts, Melanesian children had lower rates of HG (10% [CI95 7–13%] versus 1% [0–3%], <i>P</i><0.05), lower overall CFR (2% [0–4%] versus 7% [6–9%], <i>P</i><0.05) and lower CM-specific CFR (8% [0–17%] versus 19% [16–21%], <i>P</i><0.05). There was no temporal trend for overall CFR and CM-specific CFR but declining HG- and MA- specific CFRs were observed.</p><p>Interpretation</p><p>These data highlight that recent estimates of declining global malaria mortality are not replicated by improved outcomes for children hospitalized with SM. Significant geographic differences in the complication rates and subsequent CFRs exist and provide the first robust confirmation of lower CFRs in Melanesian children, perhaps due to less frequent HG.</p></div

    Forest plot showing random effects model of overall mortality due to severe malaria according to region.

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    <p>Forest plot showing random effects model of overall mortality due to severe malaria according to region.</p

    Heterogeneity and the effect of moderators for proportions and case fatality rates according to Blantyre Coma Score in deeply comatose children from descriptive studies of severe <i>Plasmodium falciparum</i> malaria.

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    <p>BCS, Blantyre Coma Score; CFR, Case Fatality Rate; NS, No statistically significant contribution to overall heterogeneity; * and **, <i>P</i>-values<0.05 and <0.01, respectively.</p

    Heterogeneity and the effect of moderators on heterogeneity for overall and clinical feature-specific case fatality rates in descriptive studies of severe <i>Plasmodium falciparum</i> malaria.

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    <p>NS, No statistically significant contribution to overall heterogeneity; Def, Definition; *, ** and ***, <i>P</i>-values<0.05, <0.01 and <0.0001, respectively.</p>a<p>Includes 7 studies where overall case fatality rates are calculated according to treatment regimen.</p>b<p>Includes 9 studies where case fatality rates due to deep coma are calculated separately according to treatment regimen.</p>c<p>Children with overlapping syndrome comprising coma, severe anemia and any of: metabolic acidosis, respiratory distress or hyperlactatemia.</p

    Enhancement of B19V transcription, replication and protein expression by CQ in UT7/Epo cells.

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    <p>Panel A shows the quantification of viral RNA synthesis 24 h after infection with B19V in the presence of increasing CQ concentrations. The results are the average of three independent experiments. SD bars are shown. Panel B shows the quantification of viral DNA replication at increasing post-infection times in untreated and CQ-treated (25 µM) cells. Values shown represent the average of two independent experiments. SD bars are shown. Panel C shows the kinetics of B19V structural protein expression in untreated and CQ-treated (25 µM) cells. Panel D shows the detection of viral protein expression by immunofluorescence in untreated and CQ-treated (25 µM) cells.</p

    Mechanism of enhancement of B19V infection by 4-aminoquinolines.

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    <p>Panel A shows the decreasing boosting effect of CQ when added at increasing post-infection times. UT7/Epo cells were infected with B19V at 4°C for 2 h. The cells were washed with PBS to remove unbound virus and incubated at 37°C. At progressive post-infection times, CQ (25 µM) was added to the cells. After 24 h post-infection, the viral NS1 RNA was quantified. Results represent mean values from three independent experiments. SD bars are shown. Panel B shows the effect of CQ (25 µM) and AQ (20 µM) on the integrity of the intracellular viral DNA. UT7/Epo cells were infected with B19V. At increasing post-internalization times from 1 to 7 h, the cells were washed and the viral DNA was extracted and quantified. A trendline was plotted using the average values from two independent experiments. SD bars are shown.</p

    Hemoglobin concentrations in case and control children.

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    <p>Scatter plot showing hemoglobin concentrations in case and control children from a study of severe pediatric infections in PNG. The data are categorised by parvovirus IgM/PCR positivity and prior 4-aminoquinoline (4AQ) use confirmed by drug and metabolite assay. In patients who were either IgM or PCR positive (but not both), 4-aminoquinoline use was associated with a lower hemoglobin (*<i>P</i> = 0.037 by Mann-Whitney U test). The two patients with evidence of treatment with AQ alone are indicated by open circles – all other children received CQ alone or had serum concentrations suggesting recent prior treatment with both CQ and AQ.</p

    Effect of different antimalarial drugs on B19V infection.

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    <p>UT7/Epo cells were infected with B19V at 4°C for 2 h. The cells were washed with PBS to remove unbound virus and incubated at 37°C in the presence of different drugs. All drugs were used in concentrations ranging from 0 to 100 µM. After 24 h, the amount of B19V NS1 RNA was quantified. The data are expressed as the percentage of the value obtained in untreated cells (dotted line) averaged for two independent experiments. SD bars are shown.</p
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