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Background Malaria presents with unspecific clinical symptoms that frequently overlap with other infectious diseases and is also a risk factor for coinfections, such as non-Typhi Salmonella. Malaria rapid diagnostic tests are sensitive but unable to distinguish between an acute infection requiring treatment and asymptomatic malaria with a concomitant infection. We set out to test whether cytokine profiles could predict disease status and allow the differentiation between malaria and a bacterial bloodstream infection. Methods We created a classification model based on cytokine concentration levels of pediatric inpatients with either Plasmodium falciparum malaria or a bacterial bloodstream infection using the Luminex platform. Candidate markers were preselected using classification and regression trees, and the predictive strength was calculated through random forest modeling. Results Analyses revealed that a combination of 7–15 cytokines exhibited a median disease prediction accuracy of 88% (95th percentile interval, 73%–100%). Haptoglobin, soluble Fas-Ligand, and complement component C2 were the strongest single markers with median prediction accuracies of 82% (with 95th percentile intervals of 71%–94%, 62%–94%, and 62%–94%, respectively). Conclusions Cytokine profiles possess good median disease prediction accuracy and offer new possibilities for the development of innovative point-of-care tests to guide treatment decisions in malaria-endemic regions.

A better understanding of disease-specific biomarker profiles during acute infections could guide the development of innovative diagnostic methods to differentiate between malaria and alternative causes of fever. We investigated autoantibody (AAb) profiles in febrile children (≤ 5 years) admitted to a hospital in rural Ghana. Serum samples from 30 children with a bacterial bloodstream infection and 35 children with Plasmodium falciparum malaria were analyzed using protein microarrays (Protoplex Immune Response Assay, ThermoFisher). A variable selection algorithm was applied to identify the smallest set of AAbs showing the best performance to classify malaria and bacteremia patients. The selection procedure identified 8 AAbs of which IFNGR2 and FBXW5 were selected in repeated model run. The classification error was 22%, which was mainly due to non-Typhi Salmonella (NTS) diagnoses being misclassified as malaria. Likewise, a cluster analysis grouped patients with NTS and malaria together, but separated malaria from non-NTS infections. Both current and recent malaria are a risk factor for NTS, therefore, a better understanding about the function of AAb in disease-specific immune responses is required in order to support their application for diagnostic purposes.

SummaryBackground Influenza surveillance data from Africa indicate a substantial disease burden with high mortality. However local influenza data from district hospitals with limited laboratory facilities are still scarce. Objectives To identify the frequency and seasonal distribution of influenza among hospitalized febrile children in a rural hospital in Ghana and to describe differential diagnoses to other severe febrile infections. Methods Between January 2014 and April 2015 all children with a temperature of ≥38°C admitted to a district hospital in Ghana were screened for influenza A and B by RT-PCR and differentiated to subtypes A(H1N1)pdm09 and A(H3N2). Malaria microscopy and blood cultures were performed for each patient. Results A total of 1,063 children with a median age of 2 years (IQR: 1–4 years) were recruited. Of those, 271 (21%) were classified as severe acute respiratory infection (SARI) and 47 (4%) were positive for influenza, namely 26 (55%) influenza B, 15 (32%) A(H1N1)pdm09 and 6 (13%) A(H3N2) cases. Influenza predominantly occurred in children aged 3–5 years and was more frequently detected in the major rainy season (OR=2.9; 95%CI: 1.47–6.19) during the first half of the year. Two (4%) and seven (15%) influenza-positive children were co-diagnosed with an invasive bloodstream infection or malaria respectively. Conclusion Influenza contributes substantially to the burden of hospitalized febrile children in Ghana being strongly dependent on age and corresponds with the major rainy season during the first half-year. This article is protected by copyright. All rights reserved.