Malaria, historically a significant health burden in temperate Europe, particularly in the low-lying marshy areas, is often poorly represented in discussions of health in the pre-modern Netherlands. Although malaria does not produce pathognomonic skeletal lesions, the haemolytic anaemia associated with repeated infection is thought to contribute to the development of cribra orbitalia, making population-level patterns in this non-specific skeletal marker informative for exploring past malaria burden. This study applied a spatial epidemiological approach, which investigated (1) the spatial distribution of cribra orbitalia prevalence across 28 archaeological medieval sites in the Netherlands, and (2) whether this distribution can be explained by underlying environmental features consistent with malaria transmission and historical mosquito density. Global Moran’s I revealed a significant positive spatial autocorrelation in prevalence. Local Indicator of Spatial Association (LISA) analysis confirmed this, identifying distinct High–High clusters in the Southwest and Low–Low clusters in the East of the Netherlands. However, linear regression models using broad-scale environmental variables failed to explain these spatial patterns. This likely reflects their inability to capture the specific ecology of the local malaria mosquito, Anopheles atroparvus, which preferentially breeds in brackish environments. Consistent with this interpretation, cribra orbitalia prevalence was significantly positively correlated with historical (1938) estimates of A. atroparvus density. The observed clustering and correlation with mosquito density suggest that malaria contributed to cribra orbitalia prevalence and may have been an important disease in certain regions of the medieval Netherlands; however, interpretation is constrained by small non-adult sample sizes as well as uneven preservation across the Netherlands.

Plasmodium simium, a parasite of platyrrhine monkeys, is known to cause human malaria outbreaks in Southeast Brazil. It has been hypothesized that, upon the introduction of Plasmodium vivax into the Americas at the time of the European colonization, the human parasite adapted to neotropical anophelines of the Kerteszia subgenus and to local monkeys, along the Atlantic coast of Brazil, to give rise to a sister species, P. simium. Here, to obtain new insights into the origins and adaptation of P. simium to new hosts, we analysed whole-genome sequence (WGS) data from 31 P. simium isolates together with a global sequence dataset of 1086 P. vivax isolates. Population genomic analyses revealed that P. simium comprises a discrete parasite lineage with greatest genetic similarity to P. vivax populations from Latin America – especially those from the Amazon Basin of Brazil – and to ancient European P. vivax isolates, consistent with Brazil as the most likely birthplace of the species. We show that P. simium displays half the amount of nucleotide diversity of P. vivax from Latin America, as expected from its recent origin. We identified pairs of sympatric P. simium isolates from monkeys and from humans as closely related as meiotic half-siblings, revealing ongoing zoonotic transmission of P. simium. Most critically, we show that P. simium currently causes most, and possibly all, malarial infections usually attributed to P. vivax along the Serra do Mar Mountain Range of Southeast Brazil.

Sulfadoxine-pyrimethamine (SP) is the standard of care for Plasmodium falciparum malaria chemoprevention among pregnant women, infants and children. Developing alternative chemoprevention products and other prevention products, such as vaccines and monoclonal antibodies, requires significant investment. However, knowledge gaps surrounding the activity of SP and resistance put these investments at risk. Therefore, we reviewed SP’s combined antimalarial action, including the individual antiplasmodial components, other antimicrobial effects, impact on malaria immunity development and continued effectiveness in settings with high SP resistance. We created a roadmap of non-clinical and clinical evidence to better understand the effectiveness of SP for chemoprevention and inform the development of new prevention tools.

Naturally acquired immunity to the different types of malaria in humans occurs in areas of endemic transmission and results in asymptomatic infection of peripheral blood. The current study examined the possibility of naturally acquired immunity in Bornean orangutans, Pongo pygmaeus, exposed to endemic Plasmodium pitheci malaria. A total of 2140 peripheral blood samples were collected between January 2017 and December 2022 from a cohort of 135 orangutans housed at a natural forested Rescue and Rehabilitation Centre in West Kalimantan, Indonesia. Each individual was observed for an average of 4.3 years during the study period. Blood samples were examined by microscopy and polymerase chain reaction for the presence of plasmodial parasites. Infection rates and parasitaemia levels were measured among age groups and all 20 documented clinical malaria cases were reviewed to estimate the incidence of illness and risk ratios among age groups. A case group of all 17 individuals that had experienced clinical malaria and a control group of 34 individuals having an event of >2000 parasites μL−1 blood but with no outward or clinical sign of illness were studied. Immature orangutans had higher-grade and more frequent parasitaemia events, but mature individuals were more likely to suffer from clinical malaria than juveniles. The case orangutans having patent clinical malaria were 256 times more likely to have had no parasitaemia event in the prior year relative to asymptomatic control orangutans. The findings are consistent with rapidly acquired immunity to P. pitheci illness among orangutans that wanes without re-exposure to the pathogen.

Invertebrate host–parasite associations are one of the keystones in order to understand vector-borne diseases. The study of these specific interactions provides information not only about how the vector is affected by the parasite at the gene-expression level, but might also reveal mosquito strategies for blocking the transmission of the parasites. A very well-known vector for human malaria is Anopheles gambiae. This mosquito species has been the main focus for genomics studies determining essential key genes and pathways over the course of a malaria infection. However, to-date there is an important knowledge gap concerning other non-mammophilic mosquito species, for example some species from the Culex genera which may transmit avian malaria but also zoonotic pathogens such as West Nile virus. From an evolutionary perspective, these 2 mosquito genera diverged 170 million years ago, hence allowing studies in both species determining evolutionary conserved genes essential during malaria infections, which in turn might help to find key genes for blocking malaria cycle inside the mosquito. Here, we extensively review the current knowledge on key genes and pathways expressed in Anopheles over the course of malaria infections and highlight the importance of conducting genomic investigations for detecting pathways in Culex mosquitoes linked to infection of avian malaria. By pooling this information, we underline the need to increase genomic studies in mosquito–parasite associations, such as the one in Culex–Plasmodium, that can provide a better understanding of the infection dynamics in wildlife and reduce the negative impact on ecosystems.