Dataset Information

Clinical features and outcome in children with severe Plasmodium falciparum malaria: a meta-analysis.

ABSTRACT:

Background

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%.

Methods

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.

Findings

Sixty-five studies were included. Substantial heterogeneity (I(2)>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%], P<0.05), lower overall CFR (2% [0-4%] versus 7% [6-9%], P<0.05) and lower CM-specific CFR (8% [0-17%] versus 19% [16-21%], P<0.05). There was no temporal trend for overall CFR and CM-specific CFR but declining HG- and MA- specific CFRs were observed.

Interpretation

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.

SUBMITTER: Manning L

PROVIDER: S-EPMC3916300 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical features and outcome in children with severe Plasmodium falciparum malaria: a meta-analysis.

Manning Laurens L Laman Moses M Davis Wendy A WA Davis Timothy M E TM

PloS one 20140206 2

<h4>Background</h4>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%.<h4>Methods</h4>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-specif ...[more]

PMID: 24516538

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Project description:The clinical presentation of severe Plasmodium falciparum malaria differs between children and adults, but the mechanistic basis for this remains unclear. Contributing factors to disease severity include total parasite biomass and the diverse cytoadhesive properties mediated by the polymorphic var gene parasite ligand family displayed on infected erythrocytes. To explore these factors, we performed a multicohort analysis of the contribution of var expression and parasite biomass to severe malaria in two previously published pediatric cohorts in Tanzania and Malawi and an adult cohort in India. Machine learning analysis revealed independent and complementary roles for var adhesion types and parasite biomass in adult and pediatric severe malaria and showed that similar var profiles, including upregulation of group A and DC8 var, predict severe malaria in adults and children. Among adults, patients with multiorgan complications presented infections with significantly higher parasite biomass without significant differences in var adhesion types. Conversely, pediatric patients with specific complications showed distinct var signatures. Cerebral malaria patients showed broadly increased expression of var genes, in particular group A and DC8 var, while children with severe malaria anemia were classified based on high transcription of DC8 var only. This study represents the first large multisite meta-analysis of var expression, and it demonstrates the presence of common var profiles in severe malaria patients of different ages across distant geographical sites, as well as syndrome-specific disease signatures. The complex associations between parasite biomass, var adhesion type, and clinical presentation revealed here represent the most comprehensive picture so far of the relationship between cytoadhesion, parasite load, and clinical syndrome.IMPORTANCE P. falciparum malaria can cause multiple disease complications that differ by patient age. Previous studies have attempted to address the roles of parasite adhesion and biomass in disease severity; however, these studies have been limited to single geographical sites, and there is limited understanding of how parasite adhesion and biomass interact to influence disease manifestations. In this meta-analysis, we compared parasite disease determinants in African children and Indian adults. This study demonstrates that parasite biomass and specific subsets of var genes are independently associated with detrimental outcomes in both childhood and adult malaria. We also explored how parasite var adhesion types and biomass play different roles in the development of specific severe malaria pathologies, including childhood cerebral malaria and multiorgan complications in adults. This work represents the largest study to date of the role of both var adhesion types and biomass in severe malaria.

Project description:The understanding of platelet biology under physiological and pathological conditions like malaria infection is critical importance in the context of the disease outcome or model systems used. The importance of severe thrombocytopenia (platelet count < 50,000 cells (µL) and profound thrombocytopenia (platelet count < 20,000 cells/µL) in malaria patients remains unclear. This study aimed to synthesize evidence regarding the risks of severe and profound thrombocytopenia in patients with severe non-Plasmodium falciparum malaria. Our overall aim was to identify potential indicators of severe non-P. falciparum malaria and the Plasmodium species that cause severe outcomes. This systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under registration ID CRD42020196541. Studies were identified from previous systematic reviews (n = 5) and the MEDLINE, Scopus, and Web of Science databases from 9 June 2019 to 9 June 2020. Studies were included if they reported the outcome of severe non-Plasmodium species infection, as defined by the World Health Organization (WHO) criteria, in patients with known platelet counts and/or severe and profound thrombocytopenia. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Data were pooled, and pooled prevalence (PP) and pooled odds ratios (ORs) were calculated using random effects models. Of the 118 studies identified from previous meta-nalyses, 21 met the inclusion criteria. Of the 4807 studies identified from the databases, three met the inclusion criteria. Nine studies identified from reference lists and other sources also met the inclusion criteria. The results of 33 studies reporting the outcomes of patients with severe P. vivax and P. knowlesi infection were pooled for meta-analysis. The PP of severe thrombocytopenia (reported in 21 studies) was estimated at 47% (95% confidence interval (CI): 33-61%, I2: 96.5%), while that of profound thrombocytopenia (reported in 13 studies) was estimated at 20% (95% CI: 14-27%, 85.2%). The pooled weighted mean difference (WMD) in platelet counts between severe uncomplicated Plasmodium infections (reported in 11 studies) was estimated at -28.51% (95% CI: -40.35-61%, I2: 97.7%), while the pooled WMD in platelet counts between severe non-Plasmodium and severe P. falciparum infections (reported in eight studies) was estimated at -3.83% (95% CI: -13.90-6.25%, I2: 85.2%). The pooled OR for severe/profound thrombocytopenia comparing severe to uncomplicated Plasmodium infection was 2.92 (95% CI: 2.24-3.81, I2: 39.9%). The PP of death from severe and profound thrombocytopenia was estimated at 11% (95% CI: 0-22%). These results suggest that individuals with severe non-P. falciparum infection (particularly P. vivax and P. knowlesi) who exhibit severe or profound thrombocytopenia should be regarded as high risk, and should be treated for severe malaria according to current WHO guidelines. In addition, severe or profound thrombocytopenia coupled with other clinical and microscopic parameters can significantly improve malaria diagnosis, enhance the timely treatment of malaria infections, and reduce the morbidity and mortality of severe non-P. falciparum malaria.

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Dataset Information

Clinical features and outcome in children with severe Plasmodium falciparum malaria: a meta-analysis.

Background

Methods

Findings

Interpretation

Publications

Clinical features and outcome in children with severe Plasmodium falciparum malaria: a meta-analysis.

Similar Datasets

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