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Background: In a previous study, severe and cerebral malaria have been connected with acute cochlear malfunction in children, demonstrated by a decrease of transitory evoked otoacoustic emissions (TEOAEs) reproducibility. This study aims to determine whether cochlear malfunction persists for 4 years after recovery from severe malaria in a subset of the previous study's collective. Follow-up TEOAEs were performed on site (CERMEL, Hôpital Albert Schweitzer, Lambaréné, Gabon) or at the participants' homes; 33 out of 90 participants included in the initial investigation by Schmutzhard et al. could be retrieved and were re-examined, 31/33 could be included. Of the 57 missing participants, 51 could not be contacted, 1 had moved away, 4 refused to cooperate, and 1 had died. Methods: As in the initial investigation, participants of this prospective follow-up study were subjected to TEOAE examination on both ears separately. A wave correlation rate of > 60% on both ears was considered a "pass"; if one ear failed to pass, the examination was considered a "fail". The results were compared to the primary control group. Additionally, a questionnaire has been applied focusing on subsequent malaria infections between the primary inclusion and follow-up and subjective impairment of hearing and/or understanding. Results: The cohort's mean age was 9 years, 14 children were female, 18 male. 31 had been originally admitted with severe, one with cerebral malaria. 83.8% of participants (n = 26) presented with a TEOAE correlation rate of > 60% on both ears (the cut-off for good cochlear function); in the control group, 92.2% (n = 83) had passed TEOAE examination on both ears. Recurrent severe malaria was associated with a worse TEOAE correlation rate. Age at infection and gender had no influence on the outcome. Conclusions: Cochlear malfunction seems to be persistent after 4 years in more than 16% of children hospitalized for malaria. In a healthy control group, this proportion was 7.8%. Yet, the severity of the initial TEOAE-decrease did not predict a worse outcome. [ABSTRACT FROM AUTHOR]

Background. Molecular mechanisms involved in the pathogenesis of severe Plasmodium falciparum malaria—specifically, cerebral malaria—are still unclear. Transforming growth factor b (TGF-b) family members are important regulators of inflammation that influence malaria pathogenesis. The soluble form of the auxiliary receptor endoglin (sEng) may play a role in malaria pathogenesis. Methods. Serum levels of sEng were measured using enzyme-linked immunosorbent-assay in Gabonese children with cerebral malaria (n = 7), severe malaria (n = 43), or uncomplicated malaria (n = 43) and were compared with levels in healthy control subjects (n = 25) and in another infectious disease group (n = 8). Results. Serum sEng levels were higher in patients with cerebral malaria and all patients with severe malaria when compared with levels in patients in the other infection group and the healthy control group. Furthermore, sEng correlated significantly with disease severity. Only 7% of patients with uncomplicated malaria and none of the control patients (patients in the other infection group or the healthy control group) had serum levels higher than 12 ng/mL, whereas this was found in 85.7% of patients with cerebral malaria and 46.5% of patients with severe malaria. Conclusions. High sEng levels may attenuate anti-inflammatory response resulting in clinical deterioration of patients with P. falciparum malaria. Our results further corroborate the role of the vascular compartment, especially the endothelium, in severe malaria pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Plasmodium falciparum malaria accounts for >1 million deaths annually, mostly among young children in sub-Saharan Africa. Identifying those individuals who are likely to die is crucial. Several factors have been independently associated with death. Because malaria is a systemic disease, a quantitative score combining such risk factors may be superior., Methods: We used both forward and backward stepwise logistic regression to select the best predictors of death, as evaluated for 23,890 African children with severe P. falciparum malaria. The study was conducted from December 2000 through May 2005 in 6 hospital-based research units (in Banjul in the Gambia, Blantyre in Malawi, Kilifi in Kenya, Kumasi in Ghana, and Lambaréné and Libreville in Gabon) in a network established to study severe malaria in African children (ie, the SMAC Network)., Results: The Lambaréné Organ Dysfunction Score (LODS) combines 3 variables: coma, prostration, and deep breathing. A LODS >0 (odd ratio, 9.6; 95% confidence interval, 8.0-11.4) has 85% sensitivity to predict death, and a LODS <3 is highly (98%) specific for survival., Conclusions: The LODS is a simple clinical predictor of fatal malaria in African children. This score provides accurate and rapid identification of children needing either referral or increased attention.

Background: Molecular mechanisms involved in the pathogenesis of severe Plasmodium falciparum malaria (SM), are not yet fully understood. Both endothelin-1 (ET-1) and C-type natriuretic peptide (CNP) are produced by vascular endothelium and act locally as paracrine regulators of vascular tone, ET-1 being a potent vasoconstrictor and CNP having strong vasorelaxant properties., Methods: Plasma levels of ET-1 and N-terminal fragments of CNP (NT-proCNP) were studied on admission and after 24 hours of treatment, using enzyme-linked-immunosorbent-assay (ELISA) technique, in Gabonese children with severe falciparum malaria (SM, n = 50), with uncomplicated malaria (UM, n = 39) and healthy controls (HC, n = 25)., Results: Compared to HC, malaria patients had significantly higher plasma levels of ET-1 and significantly lower levels of NT-proCNP (p < 0.001 and p < 0.024 respectively). Plasma levels of NT-proCNP were additionally decreased in SM patients compared to HC (p = 0.034), whereas UM was not significantly different to HC. In the SM group we found a trend towards lower ET-1 levels compared to UM (p = 0.085)., Conclusion: In the present study, an imbalance between the vasoconstricitve and vasorelaxant endothelium-derived substances ET-1 and CNP in the plasma of children with falciparum malaria is demonstrated, presumably in favor of vasoconstrictive and pro-inflammatory effects. These results may indicate involvement of ET-1 and CNP in malaria pathogenesis. Furthermore, results of lower ET-1 and CNP levels in SM may reflect endothelial cell damage.

Background: Molecular mechanisms involved in the pathogenesis of severe malaria caused by Plasmodium falciparum are not fully understood. Matrix metalloproteinases (MMPs) are enzymes that proteolytically degrade both the extracellular matrix and nonmatrix substances with various functions in the modulation of immune response. The key inhibitors of MMPs are the tissue inhibitors of metalloproteinases (TIMPs)., Methods: We studied levels of MMP-8, MMP-9, TIMP-1, and TIMP-2 on admission and after 24 h, using an enzyme-linked immunosorbent assay, in serum specimens from 50 Gabonese children with severe malaria, 43 children with uncomplicated malaria, and 27 healthy control children., Results: Serum MMP-8 and TIMP-1 levels were significantly higher in the severe malaria and uncomplicated malaria groups, compared with those in the control group (P < .001). TIMP-1 levels were significantly higher in patients with severe malaria, compared with those in patients with uncomplicated malaria (P < .001). High TIMP-1 levels were significantly correlated with malaria severity, as determined by the simplified multiorgan dysfunction score (Spearman rank-correlation coefficient, 0.55; P < .001)., Conclusions: TIMP-1 is associated with signs and symptoms of severe malaria. MMP-8 levels are elevated in patients with severe or uncomplicated P. falciparum malaria. MMPs and TIMPs may be relevant in the pathogenesis of severe malaria, either as proteolytic enzymes that degrade the extracellular matrix or as effectors and regulators of the immune response.