Effects of chloroquine treatment on circulating erythropoietin and inflammatory cytokines in acute Plasmodium falciparum malaria

Ballal, Adil; Saeed, Amal; Rouina, Patricia; Jelkmann, Wolfgang

doi:10.1007/s00277-008-0636-z

Cited by 11 publications

(15 citation statements)

References 20 publications

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“…Of potential relevance, in this regard, is the observation that the pro-inflammatory cytokine interleukin-6 is elevated in malaria and also implicated in the non-osmotic release of AVP [21,22]. The delayed normalization of serum sodium concentration, as was observed in the present study, might be the consequence of the persistent elevation of pro-inflammatory cytokines, as has been shown for patients with severe malaria [23]. Previously, a relationship between a rise in CRP and the development of in-hospital hyponatraemia was demonstrated [24].…”

Section: Discussionsupporting

confidence: 64%

Hyponatraemia in imported malaria: the pathophysiological role of vasopressin

Hoorn

Wolfswinkel

Hesselink

et al. 2012

Malar J

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BackgroundIn the pathophysiology of hyponatraemia in malaria, the relative contribution of appropriate and inappropriate arginine vasopressin (AVP) release is unknown; the trigger for inappropriate AVP release is also unknown.MethodsSerum copeptin, a stable and sensitive marker for AVP release, was analysed in a large cohort of patients with imported malaria (204 patients) and in a small prospective substudy (23 patients) in which urine sodium and osmolality were also available. Hyponatraemia was classified as mild (serum sodium 131-134 mmol/l) and moderate-to-severe (< 131 mmol/l).ResultsSerum copeptin on admission was higher in patients with moderate-to-severe hyponatraemia (median 18.5 pmol/L) compared with normonatraemic patients (12.7 pmol/L, p < 0.05). Despite prompt fluid resuscitation, the time to normalization of serum sodium was longer in patients with moderate-to-severe hyponatraemia (median 2.9 days) than in patients with mild hyponatraemia (median 1.7 days, p < 0.001). A poor correlation was found between serum sodium and copeptin levels on admission (rs = -0.17, p = 0.017). Stronger correlations were identified between serum C-reactive protein and copeptin (rs = -0.36, p < 0.0001) and between serum C-reactive protein and sodium (rs = 0.33, p < 0.0001). Data from the sub-study suggested inappropriate AVP release in seven of 13 hyponatraemic malaria patients; these patients had significantly higher body temperatures on admission.ConclusionsIn hyponatraemic patients with imported malaria, AVP release was uniformly increased and was either appropriate or inappropriate. Although the exact trigger for inappropriate AVP release remains unknown, the higher body temperatures, correlations with C-reactive protein and long normalization times of serum sodium, suggest an important role of the host inflammatory response to the invading malaria parasite.

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Section: Discussionsupporting

confidence: 64%

Hyponatraemia in imported malaria: the pathophysiological role of vasopressin

Hoorn

Wolfswinkel

Hesselink

et al. 2012

Malar J

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“…It is certainly interesting to note that the pro-inflammatory cytokine interleukin-6 is elevated in malaria and also implicated in the non-osmotic release of vasopressin [28,29]. The delayed normalization of serum sodium concentration as was observed in the present study, might reflect the persistent elevation of inflammatory cytokines, which are known to remain increased for several weeks in some patients with severe malaria [30]. Previously, a relationship between the development of in-hospital hyponatraemia and a rise in CRP was demonstrated, which is not only another illustration of this mechanism [20] but also in line with the observed correlation between sodium levels and CRP levels in patients with imported malaria in the present study.…”

Section: Discussionmentioning

confidence: 80%

Hyponatraemia in imported malaria is common and associated with disease severity

Wolfswinkel

Hesselink

Zietse

et al. 2010

Malar J

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BackgroundHyponatraemia (serum sodium < 135 mmol/L) has long been recognized as a complication of malaria. However, few studies have been done in non-immune adult populations. It has not been investigated previously how hyponatraemia is distributed among the various Plasmodium species, and its association with malaria severity is unknown.The aim of this retrospective cohort study was to determine the prevalence of hyponatraemia and its association with malaria severity in a large cohort of patients with imported malaria caused by various Plasmodium species.MethodsAll patients that were diagnosed with malaria in the Harbour Hospital and Institute for Tropical Diseases in Rotterdam in the period 1999-2009 and who had available serum sodium on admission were included. Severe malaria was defined according to the modified WHO criteria. Prevalence of hyponatraemia and its association with malaria severity were investigated by univariate comparison, ROC analysis and multivariate logistic regression analysis.ResultsA total of 446 patients with malaria (severe falciparum malaria n = 35, non-severe falciparum malaria n = 280, non-falciparum malaria n = 131) was included. Hyponatraemia was present in 207 patients (46%). Prevalence and severity of hyponatraemia were greatest in severe falciparum malaria (77%, median serum sodium 129 mmol/L), followed by non-severe falciparum malaria (48%, median serum sodium 131 mmol/L), and non-falciparum malaria (34%, median serum sodium 132 mmol/L). Admission serum sodium < 133 mmol/L had a sensitivity of 0.69 and a specificity of 0.76 for predicting severe malaria. Multivariate logistic regression showed that serum sodium < 131 mmol/L was independently associated with severe falciparum malaria (odds ratio 10.4, 95% confidence interval 3.1-34.9). In patients with hyponatraemia, hypovolaemia did not appear to play a significant role in the development of hyponatraemia when prerenal azotaemia and haematocrit were considered as surrogate markers for hypovolaemia.ConclusionsHyponatraemia is common in imported malaria and is associated with severe falciparum malaria. From a clinical point of view, the predictive power of hyponatraemia for severe malaria is limited. The precise pathophysiological mechanisms of hyponatraemia in malaria require further study.

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“…It was found that CQ-treated mice showed a significant increase in reticulocytes when compared with the healthy and untreated groups. It has been reported that CQ could result in increased erythropoietin levels in association with its anti-inflammation, resulting from an increase in reticulocytes [ 25 ]. However, it appeared that the activity of the lower doses of GIE (100 and 250 mg/kg) was not strong enough to protect hemolysis and anemia during PbANKA infection in mice.…”

Section: Discussionmentioning

confidence: 99%

The Potential Role of Gymnema inodorum Leaf Extract Treatment in Hematological Parameters in Mice Infected with Plasmodium berghei

Ounjaijean

Sukati

Somsak

et al. 2021

Journal of Tropical Medicine

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Malaria remains a significant cause of death in tropical and subtropical regions by serious complications with hematological abnormalities consistent with high parasitemia. Hence, this study aimed to determine the efficacy of the Gymnema inodorum leaf extract (GIE) on hematological alteration in Plasmodium berghei infection in mice. Groups of ICR mice were infected intraperitoneally with parasitized red blood cells of P. berghei ANKA (PbANKA). They were administered orally by gavage of 100, 250, and 500 mg/kg of GIE for 4 consecutive days. Healthy and untreated groups were given distilled water, while 10 mg/kg of chloroquine was treated as the positive control. Hematological parameters including RBC count, hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), RBC distribution width (RDW), white blood cell (WBC) count, and WBC differential count were measured. The results showed that significant decreases of RBC count, Hb, Hct, MCV, MCH, MCHC, and reticulocytes were observed in the untreated group, while RDW was significantly increased compared with the healthy control. Furthermore, the WBC, neutrophil, monocyte, basophil, and eosinophil of untreated mice increased significantly, while the lymphocyte was significantly decreased compared with the healthy control. Interestingly, GIE normalized the hematological alteration induced by PbANKA infection in GIE-treated groups compared with healthy and untreated groups. The highest efficacy of GIE was observed at a dose of 500 mg/kg. Our results confirmed that GIE presented the potential role in the treatment of hematological alteration during malaria infection.

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Effects of chloroquine treatment on circulating erythropoietin and inflammatory cytokines in acute Plasmodium falciparum malaria

Cited by 11 publications

References 20 publications

Hyponatraemia in imported malaria: the pathophysiological role of vasopressin

Hyponatraemia in imported malaria: the pathophysiological role of vasopressin

Hyponatraemia in imported malaria is common and associated with disease severity

The Potential Role of Gymnema inodorum Leaf Extract Treatment in Hematological Parameters in Mice Infected with Plasmodium berghei

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