Malaria-associated hypoglycaemia in children

Madrid, Lola; Lanaspa, Miguel; Maculuve, Sónia Amós; Bassat, Quique

doi:10.1586/14787210.2015.995632

Cited by 28 publications

(27 citation statements)

References 83 publications

(153 reference statements)

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“…In patients with malaria, decreased levels of glycaemia are common and secondary to the consumption of glucose by the Plasmodium parasite, hyperinsulinism caused by quinine (whenever used), and lack of adequate supplementation/oral intake in cases of severe malaria, especially in cerebral malaria [9, 10, 12, 13]. Its impact can be easily understood when assessing the mortality risk in patients with malaria.…”

Section: Introductionmentioning

confidence: 99%

Continuous determination of blood glucose in children admitted with malaria in a rural hospital in Mozambique

Madrid

Sitoe

Varo

et al. 2017

Malar J

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BackgroundHypoglycaemia is a frequent complication among admitted children, particularly in malaria-endemic areas. This study aimed to estimate the occurrence of hypoglycaemia not only upon admission but throughout the first 72 h of hospitalization in children admitted with malaria.MethodsA simple pilot study to continuously monitor glycaemia in children aged 0–10 years, admitted with malaria in a rural hospital was conducted in Southern Mozambique by inserting continuous glucose monitors (CGMs) in subcutaneous tissue of the abdominal area, producing glycaemia readings every 5 min.ResultsGlucose was continuously monitored during a mean of 48 h, in 74 children. Continuous measurements of blood glucose were available for 72/74 children (97.3%). Sixty-five of them were admitted with density-specific malaria diagnosis criteria (17 severe, 48 uncomplicated). Five children (7.7%) had hypoglycaemia (<54 mg/dL) on admission as detected by routine capillary determination. Analysing the data collected by the CGMs, hypoglycaemia episodes (<54 mg/dL) were detected in 10/65 (15.4%) of the children, of which 7 (10.8%) could be classified as severe (≤45 mg/dL). No risk factors were independently associated with the presence of at least one episode of hypoglycaemia (<54 mg/dL) during hospitalization. Only one death occurred among a normoglycaemic child. All episodes of hypoglycaemia detected by CGMs were subclinical episodes or not perceived by caregivers or clinical staff.ConclusionsHypoglycaemia beyond admission in children with malaria appears to be much more frequent than what had been previously described. The clinical relevance of these episodes of hypoglycaemia in the medium or long term remains to be determined.

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Section: Introductionmentioning

confidence: 99%

Continuous determination of blood glucose in children admitted with malaria in a rural hospital in Mozambique

Madrid

Sitoe

Varo

et al. 2017

Malar J

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“…Similarly, and as anticipated for a paediatric non-diabetic patient population treated with a short course (4 days) of rosiglitazone, no cardiovascular adverse events were observed in this study. Additionally, some oral artemisinin-based combinations have been reported to induce prolongation of the electrocardiogram’s QT interval, while malaria infection itself can increase the sympathetic tone of the heart, which manifests as a shortening of the QT interval in ECG traces [40]. Repeated ECG measurements detected only a few electrocardiographic abnormalities, none of which were deemed related to the investigational drug.…”

Section: Discussionmentioning

confidence: 99%

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria

Varo

Crowley

Sitoe

et al. 2017

Malar J

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BackgroundDespite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention.MethodsIn this study, the safety and tolerability of adjunctive rosiglitazone in paediatric uncomplicated malaria infection was evaluated in Mozambique, as a prelude to its evaluation in a randomized controlled trial in paediatric severe malaria. The study was a prospective, randomized, double-blind, placebo-controlled, phase IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4 days versus placebo as adjunctive treatment in addition to Mozambican standard of care (artemisinin combination therapy Coartem®) in children with uncomplicated malaria. The primary outcomes were tolerability and safety, including clinical, haematological, biochemical, and electrocardiographic evaluations.ResultsThirty children were enrolled: 20 were assigned to rosiglitazone and 10 to placebo. Rosiglitazone treatment did not induce hypoglycaemia nor significantly alter clinical, biochemical, haematological, or electrocardiographic parameters.ConclusionsAdjunctive rosiglitazone was safe and well-tolerated in children with uncomplicated malaria, permitting the extension of its evaluation as adjunctive therapy for severe malaria.The trial is registered with Clinicaltrials.gov, NCT02694874

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“…Hypo-and hyperglycemia (reviewed in Madrid et al 2015) and other metabolic disturbances also occur in malaria, but are out of the scope of this review.…”

Section: Metabolic Changesmentioning

confidence: 99%

The immunological balance between host and parasite in malaria

Deroost

Pham

Opdenakker

et al. 2015

FEMS Microbiology Reviews

107

143

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One sentence summary: The intricate balance between anti-malarial immunity and parasite virulence factors including immune evasion mechanisms determine the outcome of malaria infections, as imbalances resulting in exaggerated parasite growth, excessive inflammation or the combination of both result in severe pathology. Editor: Christian van Ooij ABSTRACTCoevolution of humans and malaria parasites has generated an intricate balance between the immune system of the host and virulence factors of the parasite, equilibrating maximal parasite transmission with limited host damage. Focusing on the blood stage of the disease, we discuss how the balance between anti-parasite immunity versus immunomodulatory and evasion mechanisms of the parasite may result in parasite clearance or chronic infection without major symptoms, whereas imbalances characterized by excessive parasite growth, exaggerated immune reactions or a combination of both cause severe pathology and death, which is detrimental for both parasite and host. A thorough understanding of the immunological balance of malaria and its relation to other physiological balances in the body is of crucial importance for developing effective interventions to reduce malaria-related morbidity and to diminish fatal outcomes due to severe complications. Therefore, we discuss in this review the detailed mechanisms of anti-malarial immunity, parasite virulence factors including immune evasion mechanisms and pathogenesis. Furthermore, we propose a comprehensive classification of malaria complications according to the different types of imbalances.

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Malaria-associated hypoglycaemia in children

Cited by 28 publications

References 83 publications

Continuous determination of blood glucose in children admitted with malaria in a rural hospital in Mozambique

Continuous determination of blood glucose in children admitted with malaria in a rural hospital in Mozambique

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria

The immunological balance between host and parasite in malaria

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