Trends in the knowledge, attitudes and practices of travel risk groups towards prevention of malaria: Results from the Dutch Schiphol airport survey 2002 to 2009

Background: Previous studies investigating the travellers knowledge, attitudes and practices (KAP) profile indicated an important educational need among those travelling to risk destinations. Initiatives to improve such education should target all groups of travellers, including business travellers, those visiting friends and relatives (VFRs), and elderly travellers. Methods: In the years 2002 to 2009, a questionnaire-based survey was conducted at the Dutch Schiphol Airport with the aim to study trends in KAP of travel risk groups towards prevention of malaria. The risk groups last-minute travellers, solo-travellers, business travellers, VFRs and elderly travellers were specifically studied. Results: A total of 3,045 respondents were included in the survey. Travellers to destinations with a high risk for malaria had significantly more accurate risk perceptions (knowledge) than travellers to low-risk destinations. The relative risk for malaria in travellers to high-risk destinations was probably mitigated by higher protection rates against malaria as compared with travellers to low risk destinations. There were no significant differences in intended risk-taking behaviour. Trend analyses showed a significant change over time in attitude towards more risk-avoiding behaviour and towards higher protection rates against malaria in travellers to high-risk destinations. The KAP profile of last-minute travellers substantially increased their relative risk for malaria, which contrasts to the slight increase in relative risk of solo travellers, business travellers and VFRs for malaria. Conclusions: The results of this sequential cohort survey in Dutch travellers suggest an annual 1.8% increase in protection rates against malaria coinciding with an annual 2.5% decrease in intended risk-seeking behaviour. This improvement may reflect the continuous efforts of travel health advice providers to create awareness and to propagate safe and healthy travel. The KAP profile of last-minute travellers, in particular, substantially increased their relative risk for malaria, underlining the continuous need for personal protective measures and malaria chemoprophylaxis for this risk group

Hyponatraemia in imported malaria is common and associated with disease severity

<p>Abstract</p> <p>Background</p> <p>Hyponatraemia (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 <it>Plasmodium </it>species, and its association with malaria severity is unknown.</p> <p>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 <it>Plasmodium </it>species.</p> <p>Methods</p> <p>All 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.</p> <p>Results</p> <p>A 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.</p> <p>Conclusions</p> <p>Hyponatraemia 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.</p

Procalcitonin as a biomarker for severe Plasmodium falciparum disease: a critical appraisal of a semi-quantitative point-of-care test in a cohort of travellers with imported malaria

Background. Imported malaria occurs as a relatively rare event in developed countries. As a consequence, most clinicians have little experience in making clinical assessments of disease severity and decisions regarding the need for parenteral therapy or high-level monitoring. In this study, the diagnostic accuracy of procalcitonin (PCT) for severe Plasmodium falciparum disease was assessed in a cohort of 100 consecutive travellers with various species of imported malaria. Methods and results. In all patients, PCT was measured on admission with a semi-quantitative 'point-of-care' test. Patients with severe P. falciparum malaria had significantly higher median PCT levels on admission as compared with patients with uncomplicated P. falciparum disease. In addition, PCT levels in patients with non-falciparum malaria were also higher compared with patients with non-severe f

Severity of imported malaria: protective effect of taking malaria chemoprophylaxis

BACKGROUND: Although chemoprophylaxis remains an important strategy for preventing malaria in travellers, its effectiveness may be compromised by lack of adherence. Inappropriate use of chemoprophylaxis is likely to increase the risk of acquiring malaria, but may probably also worsen the severity of imported cases. The aim of this study was to assess the impact of use of malaria chemoprophylaxis on clinical features and outcome of imported malaria. METHODS: Demographic, clinical and laboratory data of patients included in the Rotterdam Malaria Cohort between 1998 and 2011 were systematically collected and analysed. Patients were classified as self-reported compliant or non-compliant users or as non-users of chemoprophylaxis. Severe malaria was defined using the 2010 WHO criteria. RESULTS: Details on chemoprophylaxis were available for 559 of the 604 patients, of which 64.6% were non-users, 17.9% were inadequate users and 17.5% reported to be adequate users. The group of non-users was predominated by patients with African ethnicity, partial immunity and people visiting friends and relatives. The majority contracted Plasmodium falciparum malaria. In contrast, compliant users acquired non-falciparum malaria more frequently, had significant lower P. falciparum loads on admission, shorter duration of hospitalization and significant lower odds for severe malaria as compared with non-users. Patients with P. falciparum malaria were more likely to have taken their chemoprophylaxis less compliantly than those infected with non-P. falciparum species. Multivariate analysis showed that self-reported adequate prophylaxis and being a partially immune traveller visiting friends and relatives was associated with significantly lower odds ratio of severe malaria. In contrast, age, acquisition of malaria in West-Africa and being a non-immune tourist increased their risk significantly. CONCLUSIONS: Compliant use of malaria chemoprophylaxis was associated with significantly lower odds ratios for severe malaria as compared with non-compliant users and non-users of chemoprophylaxis. After correction for age, gender and immunity, this protective effect of malaria chemoprophylaxis was present only in individuals who adhered compliantly to use of chemoprophylaxis. Patients with P. falciparum malaria were more likely to have used their chemoprophylaxis less compliantly than patients with non-P. falciparum malaria who were more likely to have contracted malaria in spite of compliant use of chemoprophylaxis

Copeptin does not accurately predict disease severity in imported malaria

<p>Abstract</p> <p>Background</p> <p>Copeptin has recently been identified to be a stable surrogate marker for the unstable hormone arginine vasopressin (AVP). Copeptin has been shown to correlate with disease severity in leptospirosis and bacterial sepsis. Hyponatraemia is common in severe imported malaria and dysregulation of AVP release has been hypothesized as an underlying pathophysiological mechanism. The aim of the present study was to evaluate the performance of copeptin as a predictor of disease severity in imported malaria.</p> <p>Methods</p> <p>Copeptin was measured in stored serum samples of 204 patients with imported malaria that were admitted to our Institute for Tropical Diseases in Rotterdam in the period 1999-2010. The occurrence of WHO defined severe malaria was the primary end-point. The diagnostic performance of copeptin was compared to that of previously evaluated biomarkers C-reactive protein, procalcitonin, lactate and sodium.</p> <p>Results</p> <p>Of the 204 patients (141 <it>Plasmodium falciparum</it>, 63 non-falciparum infection), 25 had severe malaria. The Area Under the ROC curve of copeptin for severe disease (0.66 [95% confidence interval 0.59-0.72]) was comparable to that of lactate, sodium and procalcitonin. C-reactive protein (0.84 [95% CI 0.79-0.89]) had a significantly better performance as a biomarker for severe malaria than the other biomarkers.</p> <p>Conclusions</p> <p>C-reactive protein but not copeptin was found to be an accurate predictor for disease severity in imported malaria. The applicability of copeptin as a marker for severe malaria in clinical practice is limited to exclusion of severe malaria.</p

A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

Background: Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. Methods. In this study the Binax NOW® Malaria Test, an easy-to-perform rapid diagnostic test, with Histidine Rich Protein-2 (HRP-2) and aldolase as diagnostic markers, was used for semi-quantitative assessment of parasitaemia of P. faciparum. Results: In 257 patients with imported P. falciparum malaria, reactivity of aldolase increased with higher parasitaemia. In all patients with a parasitaemia above 50,000 asexual parasites/l (> 1%) co-reactivity of HRP-2 and aldolase was observed. Absence of aldolase reactivity in the presence of HRP-2 was a reliable predictive marker to exclude high (> 1%) parasitaemia in P. falciparum malaria. Conclusions: Assessment of HRP-2 and aldolase co-reactivity can be of help in clinical decision making in the acute care setting of returning travellers suspected of having malaria

Neopterin and procalcitonin are suitable biomarkers for exclusion of severe Plasmodium falciparum disease at the initial clinical assessment of travellers with imported malaria

Background. Most clinicians in developed, non-malaria endemic countries have limited or no experience in making clinical assessments of malaria disease severity and subsequent decisions regarding the need for parenteral therapy or high-level monitoring in febrile patients with imported malaria. In the present study, the diagnostic accuracy of plasma soluble Triggering Receptor Expressed on Myeloid cells 1 (TREM-1), neopterin and procalcitonin levels as biomarkers for severe Plasmodium falciparum disease was evaluated in 104 travellers with imported malaria (26 patients with non-P. falciparum malaria, 64 patients with uncomplicated P. falciparum malaria and 14 patients with severe P. falciparum malaria). Methods. TREM-1, neopterin and procalcitonin were determined in serum using commercially available ELISA or EIA tests. The diagnostic performance of these biomarkers for severe disease was compared with plasma lactate, a well-validated parameter for disease severity in patients with malaria, as reference. Severe malaria was defined according to the modified WHO criteria. Results. No significant differences in TREM-1 levels were detected between the different patient groups. Patients with severe P. falciparum malaria had significantly higher neopterin and procalcitonin levels on admission when compared to patients with uncomplicated P. falciparum malaria or non-P. falciparum malaria. Receiver Operating Characteristic (ROC) curve analysis showed that neopterin had the highest Area-Under-the-ROC curve (AUROC 0.85) compared with plasma lactate (AUROC 0.80) and procalcitonin (AUROC 0.78). At a cut-off point of 10.0 ng/ml, neopterin had a positive and negative predictive value of 0.38 and 0.98 whereas procalcitonin, at a cut-off point of 0.9 ng/ml, had a positive and negative predictive value of 0.30 and 1.00. Conclusion. Although the diagnostic value of neopterin and procalcitonin is limited, the high negative predictive value of both neopterin and procalcitonin may be helpful for a rapid exclusion of severe malaria disease on admission. This may be a valuable tool for physicians only occasionally dealing with ill-returned travellers from malaria-endemic regions and who need to decide on subsequent oral anti-malarial treatment or timely referral to a specialized centre for high-level monitoring and intensified parenteral treatment

Odours of Plasmodium falciparum-infected participants influence mosquito-host interactions.

Malaria parasites are thought to influence mosquito attraction to human hosts, a phenomenon that may enhance parasite transmission. This is likely mediated by alterations in host odour because of its importance in mosquito host-searching behaviour. Here, we report that the human skin odour profile is affected by malaria infection. We compared the chemical composition and attractiveness to Anopheles coluzzii mosquitoes of skin odours from participants that were infected by Controlled Human Malaria Infection with Plasmodium falciparum. Skin odour composition differed between parasitologically negative and positive samples, with positive samples collected on average two days after parasites emerged from the liver into the blood, being associated with low densities of asexual parasites and the absence of gametocytes. We found a significant reduction in mosquito attraction to skin odour during infection for one experiment, but not in a second experiment, possibly due to differences in parasite strain. However, it does raise the possibility that infection can affect mosquito behaviour. Indeed, several volatile compounds were identified that can influence mosquito behaviour, including 2- and 3-methylbutanal, 3-hydroxy-2-butanone, and 6-methyl-5-hepten-2-one. To better understand the impact of our findings on Plasmodium transmission, controlled studies are needed in participants with gametocytes and higher parasite densities