Intermittent fever is a historical diagnosis with a contested meaning. Historians have associated it with both benign malaria and severe epidemics during the Early Modern Era and early nineteenth century. Where other older medical diagnoses perished under changing medical paradigms, intermittent fever ‘survived’ into the twentieth century. This article studies the development in how intermittent fever was framed in Denmark between 1826 and 1886 through terminology, clinical symptoms and aetiology. In the 1820s and 1830s, intermittent fever was a broad disease category, which the diagnosis ‘koldfeber’. Danish physicians were inspired by Hippocratic teachings in the early nineteenth century, and patients were seen as having unique constitutions. For that reason, intermittent fevers presented itself as both benign and severe with a broad spectrum of clinical symptoms. As the Parisian school gradually replaced humoral pathology in the mid-nineteenth century, intermittent fever and koldfeber became synonymous for one disease condition with a nosography that resembles modern malaria. The nosography of intermittent fever remained consistent throughout the second half of the nineteenth century. Although intermittent fever was conceptualized as caused by miasmas throughout most of the nineteenth century, the discovery of the Plasmodium parasite in 1880 led to a change in the conceptualization of what miasmas were. The article concludes that the development of how intermittent fever was framed follows the changing scientific paradigms that shaped Danish medicine in the nineteenth century.

Increases in bed net coverage and antimalarial treatment have reduced the risk of malaria in sub-Saharan Africa. However, the pace of reduction has slowed, and new tools are needed to reverse this trend. We evaluated houses screened with insecticide-treated ceiling nets using a cluster randomized-controlled trial in western Kenya. The primary endpoints were Plasmodium falciparum PCR-positive prevalence (PCRPfPR) of children from 7 months to 10 years old and anopheline density. Ceiling nets and bed nets were provided to 1073 houses, and 1162 houses were provided with bed nets only. The treatment and control arms each had four clusters. We conducted three epidemiological and entomological post-intervention surveys over the course of a year and a half. Each epidemiological survey targeted 150 children per cluster, and entomological surveys targeted 25 houses. When the three surveys were combined, the median PCRPfPRs were 23% (IQR 8%) in the intervention arm and 42% (IQR 12%) in the control arm. The adjusted risk ratio (RR) was 0.53 [95% confidence interval (CI) 0.41–0.71; P = 0.029]. The median anopheline densities were 0.4 (IQR 0.4) and 2.0 (IQR 1.4), respectively. The adjusted RR was 0.41 (95% CI 0.29–0.90; P = 0.029). The present study indicates additional protection from insecticide-screened ceilings over the current best practice.

The article de-centres the global history of disease by examining the agency of Eastern European expertise at international organizations and during decolonization. It challenges accounts of anti-malaria policies at the League of Nations Health Organization and at the World Health Organization written from a Western, particularly North American perspective, or on the basis of local reactions to Western interventions. The contribution proposes an analysis of circulations and ideas across multiple cultural, social and political spaces: post-imperial European states, (post)colonial territories and bureaucracies of international organizations. From the 1920s to the 1960s, Eastern European experts played a crucial role in the transformation of malaria from an imperial disease that tested governance over ‘tropical’ peoples into an issue of global health and nation-state building. However, regional representatives reproduced civilizational hierarchies intrinsic to North–South biomedical relations. The global entanglements of Eastern European malariology show that liberation from disease was less about communism or liberalism, and more about national renewal, statehood and world hierarchies.

Inflammation and infections such as malaria affect estimates of micronutrient status. Medline, Embase, Web of Science, Scopus and the Cochrane library were searched to identify studies reporting mean concentrations of ferritin, hepcidin, retinol or retinol binding protein in individuals with asymptomatic or clinical malaria and healthy controls. Study quality was assessed using the US National Institute of Health tool. Random effects meta-analyses were used to generate summary mean differences. In total, forty-four studies were included. Mean ferritin concentrations were elevated by: 28·2 µg/l (95 % CI 15·6, 40·9) in children with asymptomatic malaria; 28·5 µg/l (95 % CI 8·1, 48·8) in adults with asymptomatic malaria; and 366 µg/l (95 % CI 162, 570) in children with clinical malaria compared with individuals without malaria infection. Mean hepcidin concentrations were elevated by 1·52 nmol/l (95 % CI 0·92, 2·11) in children with asymptomatic malaria. Mean retinol concentrations were reduced by: 0·11 µmol/l (95 % CI −0·22, −0·01) in children with asymptomatic malaria; 0·43 µmol/l (95 % CI −0·71, −0·16) in children with clinical malaria and 0·73 µmol/l (95 % CI −1·11, −0·36) in adults with clinical malaria. Most of these results were stable in sensitivity analyses. In children with clinical malaria and pregnant women, difference in ferritin concentrations were greater in areas with higher transmission intensity. We conclude that biomarkers of iron and vitamin A status should be statistically adjusted for malaria and the severity of infection. Several studies analysing asymptomatic infections reported elevated ferritin concentrations without noticeable elevation of inflammation markers, indicating a need to adjust for malaria status in addition to inflammation adjustments.

Infection by malaria parasites (Plasmodium spp.) remains one of the leading causes of morbidity and mortality, especially in tropical regions of the world. Despite the availability of malaria control tools such as integrated vector management and effective therapeutics, these measures have been continuously undermined by the emergence of vector resistance to insecticides or parasite resistance to frontline antimalarial drugs. Whilst the recent pilot implementation of the RTS,S malaria vaccine is indeed a remarkable feat, highly effective vaccines against malaria remain elusive. The barriers to effective vaccines result from the complexity of both the malaria parasite lifecycle and the parasite as an organism itself with consequent major gaps in our understanding of their biology. Historically and due to the practical and ethical difficulties of working with human malaria infections, research into malaria parasite biology has been extensively facilitated by animal models. Animals have been used to study disease pathogenesis, host immune responses and their (dys)regulation and further disease processes such as transmission. Moreover, animal models remain at the forefront of pre-clinical evaluations of antimalarial drugs (drug efficacy, mode of action, mode of resistance) and vaccines. In this review, we discuss commonly used animal models of malaria, the parasite species used and their advantages and limitations which hinder their extrapolation to actual human disease. We also place into this context the most recent developments such as organoid technologies and humanized mice.

The association between the ABO blood group and the risk of malaria during pregnancy has not been clearly established. The present study summarised relevant knowledge and reassessed the association through meta-analysis. Articles in MEDICINE and PubMed published before 30 November 2021 were searched. Five studies satisfied the inclusion criteria and were enrolled in the meta-analysis. It was shown that primiparae with different ABO blood group, multiparae with blood group A and non-A, AB and non-AB had a comparable risk of malaria. However, multiparae with blood group B had a significantly higher risk than non-B group [odds ratio (OR) = 1.23, 95% confidence interval (CI) was 1.01 to 1.50, P = 0.04], while multiparae with blood group O had a significantly lower risk than non-O group (OR = 0.78, 95% CI was 0.63 to 0.97, P = 0.03). Therefore, the ABO blood group may not result in a different risk of malaria in primiparae. Blood group B is potentially a risk factor while blood group O is a protective factor for multiparae.

From nearly any perspective and metric, the effects of malaria on the African continent have been persistent and deep. By focusing on the malady of malaria and the last century of biomedical interventions, Graboyes and Alidina raise critical historical, ethical, and scientific questions related to truth telling, African autonomy, and the obligations of foreign researchers. They provide a condensed history of malaria activities on the continent over the past 120 years, highlighting the overall history of failures to eliminate or control the disease. A case study of the risks of rebound malaria illustrates the practical and moral problems that abound when historical knowledge is ignored. In light of current calls for renewed global eradication efforts, Graboyes and Alidina provide evidence for why historical knowledge must be better integrated into global health epistemic realms.

Plasmodium coatneyi has been proposed as an animal model for human Plasmodium falciparum malaria as it appears to replicate many aspects of pathogenesis and clinical symptomology. As part of the ongoing evaluation of the rhesus macaque model of severe malaria, a detailed ultrastructural analysis of the interaction between the parasite and both the host erythrocytes and the microvasculature was undertaken. Tissue (brain, heart and kidney) from splenectomized rhesus macaques and blood from spleen-intact animals infected with P. coatneyi were examined by electron microscopy. In all three tissues, similar interactions (sequestration) between infected red blood cells (iRBC) and blood vessels were observed with evidence of rosette and auto-agglutinate formation. The iRBCs possessed caveolae similar to P. vivax and knob-like structures similar to P. falciparum. However, the knobs often appeared incompletely formed in the splenectomized animals in contrast to the intact knobs exhibited by spleen intact animals. Plasmodium coatneyi infection in the monkey replicates many of the ultrastructural features particularly associated with P. falciparum in humans and as such supports its use as a suitable animal model. However, the possible effect on host–parasite interactions and the pathogenesis of disease due to the use of splenectomized animals needs to be taken into consideration.

This research aims to determine whether the combination of epidemiological and clinical features can predict malaria. Diagnostic investigation detected 22.3% of individuals with Plasmodium vivax (P. vivax) malaria, with significant predominance of the male gender. The malaria triad (fever, chills and headache) had a more expressive frequency (81.1%) in individuals with positive thick blood than those with negative thick blood smear (65.1%), although there was no statistical significance. Among the variables analysed as predictive for positive thick blood smear, it was observed that personal history of travel to an endemic malaria area and past malaria infection (PMI) were significantly associated with malaria, even in multiple logistic regression. Fever had the higher sensitivity (94.6%) and past malaria history had the greater specificity (68.2%), with accuracy of 23.5% and 67.5%, respectively. In combined analysis, fever with chills had the highest sensitivity (91.9%), but low accuracy (38.5%). High specificity (91.5%) was found in the association of malaria triad, PMI and history of travel to endemic malaria area (which along with anorexia, was higher 94.6%), with good accuracy (80.7%), suggesting that the screening of patients for performing thick blood smear can be based on these data. The epidemiological features and the malaria triad (fever, chills and headache) can be predictors for identification of malaria patients, concurring to precocious diagnosis and immediate treatment of individuals with malaria.