Dataset Information

Severe malarial anemia is associated with long-term neurocognitive impairment.

ABSTRACT:

Background

Cerebral malaria (CM) is associated with long-term neurocognitive impairment in children ?5 years of age. No prospective studies to date have assessed neurocognitive impairment in children with CM <5 years of age, or in children with severe malarial anemia (SMA), a form of severe malaria estimated to affect as many as 5 million children annually.

Methods

Children <5 years of age presenting to Mulago Hospital, Kampala, Uganda, with CM (n = 80) or SMA (n = 86) were assessed for overall cognitive ability, attention, and associative memory 1 week after discharge and 6 and 12 months later. The z scores for each domain were computed based on scores of 61 healthy community children (CC), who were also tested at enrollment and 6 and 12 months later. Groups were compared using mixed linear models, adjusted for age, weight for age, and child's education.

Results

At 12 months, children with CM had lower adjusted scores than CC in cognitive ability (P < .001), attention (P = .02), and associative memory, (P = .002). Children with SMA had lower scores than CC in cognitive ability (P = .01) but not attention or associative memory. Cognitive ability scores in children with CM and SMA did not differ significantly.

Conclusions

In children <5 years of age, SMA is associated with long-term impairment in cognitive ability, whereas CM is associated with additional impairment in the areas of attention and associative memory. SMA may be a major contributor to long-term neurocognitive impairment in children in sub-Saharan Africa.

SUBMITTER: Bangirana P

PROVIDER: S-EPMC4155441 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

Severe malarial anemia is associated with long-term neurocognitive impairment.

Bangirana Paul P Opoka Robert O RO Boivin Michael J MJ Idro Richard R Hodges James S JS Romero Regilda A RA Shapiro Elsa E John Chandy C CC

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20140424 3

<h4>Background</h4>Cerebral malaria (CM) is associated with long-term neurocognitive impairment in children ≥5 years of age. No prospective studies to date have assessed neurocognitive impairment in children with CM <5 years of age, or in children with severe malarial anemia (SMA), a form of severe malaria estimated to affect as many as 5 million children annually.<h4>Methods</h4>Children <5 years of age presenting to Mulago Hospital, Kampala, Uganda, with CM (n = 80) or SMA (n = 86) were assess ...[more]

PMID: 24771329

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Project description:Cognitive impairment and functional disability are major determinants of caregiving needs and societal health care costs. Although the incidence of severe sepsis is high and increasing, the magnitude of patients' long-term cognitive and functional limitations after sepsis is unknown.To determine the change in cognitive impairment and physical functioning among patients who survive severe sepsis, controlling for their presepsis functioning.A prospective cohort involving 1194 patients with 1520 hospitalizations for severe sepsis drawn from the Health and Retirement Study, a nationally representative survey of US residents (1998-2006). A total of 9223 respondents had a baseline cognitive and functional assessment and had linked Medicare claims; 516 survived severe sepsis and 4517 survived a nonsepsis hospitalization to at least 1 follow-up survey and are included in the analysis.Personal interviews were conducted with respondents or proxies using validated surveys to assess the presence of cognitive impairment and to determine the number of activities of daily living (ADLs) and instrumental ADLs (IADLs) for which patients needed assistance.Survivors' mean age at hospitalization was 76.9 years. The prevalence of moderate to severe cognitive impairment increased 10.6 percentage points among patients who survived severe sepsis, an odds ratio (OR) of 3.34 (95% confidence interval [CI], 1.53-7.25) in multivariable regression. Likewise, a high rate of new functional limitations was seen following sepsis: in those with no limits before sepsis, a mean 1.57 new limitations (95% CI, 0.99-2.15); and for those with mild to moderate limitations before sepsis, a mean of 1.50 new limitations (95% CI, 0.87-2.12). In contrast, nonsepsis general hospitalizations were associated with no change in moderate to severe cognitive impairment (OR, 1.15; 95% CI, 0.80-1.67; P for difference vs sepsis = .01) and with the development of fewer new limitations (mean among those with no limits before hospitalization, 0.48; 95% CI, 0.39-0.57; P for difference vs sepsis <.001 and mean among those with mild to moderate limits, 0.43; 95% CI, 0.23-0.63; P for difference = .001). The declines in cognitive and physical function persisted for at least 8 years.Severe sepsis in this older population was independently associated with substantial and persistent new cognitive impairment and functional disability among survivors. The magnitude of these new deficits was large, likely resulting in a pivotal downturn in patients' ability to live independently.

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Project description:BackgroundWHO guidelines recommend concurrent iron and antimalarial treatment in children with malaria and iron deficiency, but iron may not be well absorbed or utilized during a malaria episode.ObjectivesWe aimed to determine whether starting iron 28 d after antimalarial treatment in children with severe malaria and iron deficiency would improve iron status and lower malaria risk.MethodsWe conducted a randomized clinical trial on the effect of immediate compared with delayed iron treatment in Ugandan children 18 mo-5 y of age with 2 forms of severe malaria: cerebral malaria (CM; n = 79) or severe malarial anemia (SMA; n = 77). Asymptomatic community children (CC; n = 83) were enrolled as a comparison group. Children with iron deficiency, defined as zinc protoporphyrin (ZPP) ≥ 80 µmol/mol heme, were randomly assigned to receive a 3-mo course of daily oral ferrous sulfate (2 mg · kg-1 · d-1) either concurrently with antimalarial treatment (immediate arm) or 28 d after receiving antimalarial treatment (delayed arm). Children were followed for 12 mo.ResultsAll children with CM or SMA, and 35 (42.2%) CC, were iron-deficient and were randomly assigned to immediate or delayed iron treatment. Immediate compared with delayed iron had no effect in any of the 3 study groups on the primary study outcomes (hemoglobin concentration and prevalence of ZPP ≥ 80 µmol/mol heme at 6 mo, malaria incidence over 12 mo). However, after 12 mo, children with SMA in the delayed compared with the immediate arm had a lower prevalence of iron deficiency defined by ZPP (29.4% compared with 65.6%, P = 0.006), a lower mean concentration of soluble transferrin receptor (6.1 compared with 7.8 mg/L, P = 0.03), and showed a trend toward fewer episodes of severe malaria (incidence rate ratio: 0.39; 95% CI: 0.14, 1.12).ConclusionsIn children with SMA, delayed iron treatment did not increase hemoglobin concentration, but did improve long-term iron status over 12 mo without affecting malaria incidence.This trial was registered at clinicaltrials.gov as NCT01093989.

Project description:Severe malarial anemia (SMA) is a leading cause of morbidity and mortality in children residing in regions where Plasmodium falciparum transmission is holoendemic. Although largely unexplored in children with SMA, interleukin-18 (IL-18) is important for regulating innate and acquired immunity in inflammatory and infectious diseases. As such, we selected two functional single-nucleotide polymorphisms (SNPs) in the IL-18 promoter (-137G?C [rs187238] and -607C?A [rs1946518]) whose haplotypes encompass significant genetic variation due to the presence of strong linkage disequilibrium among these variants. The relationship between the genotypes/haplotypes, SMA (hemoglobin [Hb], <5.0 g/dl], and longitudinal clinical outcomes were then investigated in Kenyan children (n = 719). Multivariate logistic regression analyses controlling for age, gender, sickle cell trait, glucose-6-phosphate dehydrogenase (G6PD) deficiency, HIV-1, and bacteremia revealed that carriage of the -607AA genotype was associated with protection against SMA (odds ratio [OR] = 0.440 [95% confidence interval {CI} = 0.21 to 0.90], P = 0.031) in children with acute infection. In contrast, carriers of the -137G/-607C (GC) haplotype had increased susceptibility to SMA (OR = 2.050 [95% CI = 1.04 to 4.05], P = 0.039). Measurement of IL-18 gene expression in peripheral blood leukocytes demonstrated that elevated IL-18 transcripts were associated with reduced hemoglobin concentrations (? = -0.293, P = 0.010) and that carriers of the "susceptible" GC haplotype had elevated IL-18 transcripts (P = 0.026). Longitudinal investigation of clinical outcomes over a 3-year follow-up period revealed that carriers of the rare CC haplotype (?1% frequency) had 5.76 times higher mortality than noncarriers (P = 0.001). Results presented here demonstrate that IL-18 promoter haplotypes that condition elevated IL-18 gene products during acute infection are associated with increased risk of SMA. Furthermore, carriage of the rare CC haplotype significantly increases the risk of childhood mortality.

Dataset Information

Severe malarial anemia is associated with long-term neurocognitive impairment.

Background

Methods

Results

Conclusions

Publications

Severe malarial anemia is associated with long-term neurocognitive impairment.

Similar Datasets

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