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The merozoite stage of the malaria parasite that infects erythrocytes and causes the symptoms of the disease is initially formed inside host hepatocytes. However, the mechanism by which hepatic merozoites reach blood vessels (sinusoids) in the liver and escape the host immune system before invading erythrocytes remains unknown. Here, we show that parasites induce the death and the detachment of their host hepatocytes, followed by the budding of parasite-filled vesicles (merosomes) into the sinusoid lumen. Parasites simultaneously inhibit the exposure of phosphatidylserine on the outer leaflet of host plasma membranes, which act as \"eat me\" signals to phagocytes. Thus, the hepatocyte-derived merosomes appear to ensure both the migration of parasites into the bloodstream and their protection from host immunity.

Key Points Malaria is the most deadly parasitic infection of humans, killing up to 1 million people per year. No vaccine is currently available, and the development of drug-resistant Plasmodium spp. is of increasing concern. The first phase of infection, the pre-erythrocytic (PE) phase, is clinically asymptomatic. Only after parasite replication in the liver and infection of large numbers of erythrocytes do symptoms arise. The PE phase comprises sporozoites (the infectious stage) and the liver stages. Once injected by a mosquito, the sporozoites can remain in the skin, be transported in lymph vessels to draining lymph nodes or travel through the bloodstream to the liver. In the liver, sporozoites undergo an elaborate replication and developmental programme and transform into the merozoites that are released from the liver to infect erythrocytes. The PE phase of infection is a formidable window of opportunity for therapeutic interventions owing to the small number of parasites present. Thus, targeting this 'bottleneck' of Plasmodium spp. infection with vaccines is an attractive strategy. Live attenuated parasites mimicking the PE phase of infection can be used as vaccines. Attenuation is achieved by radiation, genetic alterations or drug-mediated developmental arrest. The symptoms of malaria are associated with the erythrocytic phase of Plasmodium spp. infection, but the pre-erythrocytic (PE) phase, which is clinically silent, has long been of interest as a potential vaccination target. Robert Ménard and colleagues review how our understanding of the PE phase has changed over the past decade and how this in turn has informed our understanding of the host immune response. Malaria, which is caused by Plasmodium spp., starts with an asymptomatic phase, during which sporozoites, the parasite form that is injected into the skin by a mosquito, develop into merozoites, the form that infects erythrocytes. This pre-erythrocytic phase is still the most enigmatic in the parasite life cycle, but has long been recognized as an attractive vaccination target. In this Review, we present what has been learned in recent years about the natural history of the pre-erythrocytic stages, mainly using intravital imaging in rodents. We also consider how this new knowledge is in turn changing our understanding of the immune response mounted by the host against the pre-erythrocytic forms.

Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein–encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.

Since 2015, India has coordinated the largest school-based deworming program globally, targeting soil-transmitted helminths (STH) in ~250 million children aged 1 to 19 years twice yearly. Despite substantial progress in reduction of morbidity associated with STH, reinfection rates in endemic communities remain high. We conducted a community based parasitological survey in Tamil Nadu as part of the DeWorm3 Project—a cluster-randomised trial evaluating the feasibility of interrupting STH transmission at three geographically distinct sites in Africa and Asia—allowing the estimation of STH prevalence and analysis of associated factors. In India, following a comprehensive census, enumerating 140,932 individuals in 36,536 households along with geospatial mapping of households, an age-stratified sample of individuals was recruited into a longitudinal monitoring cohort (December 2017-February 2018) to be followed for five years. At enrolment, a total of 6089 consenting individuals across 40 study clusters provided a single adequate stool sample for analysis using the Kato-Katz method, as well as answering a questionnaire covering individual and household level factors. The unweighted STH prevalence was 17.0% (95% confidence interval [95%CI]: 16.0–17.9%), increasing to 21.4% when weighted by age and cluster size. Hookworm was the predominant species, with a weighted infection prevalence of 21.0%, the majority of which (92.9%) were light intensity infections. Factors associated with hookworm infection were modelled using mixed-effects multilevel logistic regression for presence of infection and mixed-effects negative binomial regression for intensity. The prevalence of both Ascaris lumbricoides and Trichuris trichiura infections were rare ( < 1%) and risk factors were therefore not assessed. Increasing age (multivariable odds ratio [mOR] 21.4, 95%CI: 12.3–37.2, p<0.001 for adult age-groups versus pre-school children) and higher vegetation were associated with an increased odds of hookworm infection, whereas recent deworming (mOR 0.3, 95%CI: 0.2–0.5, p<0.001) and belonging to households with higher socioeconomic status (mOR 0.3, 95%CI: 0.2–0.5, p<0.001) and higher education level of the household head (mOR 0.4, 95%CI: 0.3–0.6, p<0.001) were associated with lower odds of hookworm infection in the multilevel model. The same factors were associated with intensity of infection, with the use of improved sanitation facilities also correlated to lower infection intensities (multivariable infection intensity ratio [mIIR] 0.6, 95%CI: 0.4–0.9, p<0.016). Our findings suggest that a community-based approach is required to address the high hookworm burden in adults in this setting. Socioeconomic, education and sanitation improvements alongside mass drug administration would likely accelerate the drive to elimination in these communities. Trial Registration: NCT03014167 .

Ticks transmit a wide range of protozoan, bacterial, and viral pathogens to humans and animals globally. However, data on ticks infesting domestic ruminants and the pathogens they carry are scarce in Malawi. In this study, we examined ticks collected from domestic ruminants and screened them for selected veterinary and medically important protozoan and bacterial pathogens. A total of 964 ticks were collected from 202 cattle, 63 goats, and 16 sheep across eleven districts in Malawi. Ticks were morphologically identified to species level using taxonomical keys, with molecular confirmation by PCR amplification and sequencing of the 12S ribosomal RNA (12S rDNA) and cytochrome c oxidase subunit I ( COI ) genes. Tick DNA was further screened for tick-borne pathogens using species-specific PCR assays. Identified tick species included Rhipicephalus microplus (30.5%), Rhipicephalus appendiculatus (23.3%), Rhipicephalus decoloratus (13.2%), Rhipicephalus evertsi (9.8%), Hyalomma rufipes (7.5%), Amblyomma variegatum (6.3%), Rhipicephalus sanguineus sensu lato (tropical lineage) (3.6%), Hyalomma truncatum (2.8%), Rhipicephalus simus (2.0%), Rhipicephalus pravus (0.6%), and Rhipicephalus annulatus (0.4%). Overall, 37.0% of ticks carried at least one tick-borne pathogen, with Theileria parva being the most prevalent (34.7%), followed by Anaplasma marginale (17.4%), Babesia bigemina (14.9%), Anaplasma ovis (11.2%), Ehrlichia ruminantium (9.2%) , Theileria mutans (8.4%), Babesia bovis (2.2%), and Anaplasma bovis (2.0%). This study provides the first molecular identification of ticks infesting domestic ruminants in Malawi and documents associated tick-borne pathogens. Notably, Rhipicephalus appendiculatus was identified for the first time in southern Malawi, refining current understanding of East Coast fever epidemiology and highlighting the need for updated surveillance approaches. Les tiques transmettent un large éventail d'agents pathogènes protozoaires, bactériens et viraux aux humains et aux animaux à l'échelle mondiale. Cependant, les données sur les tiques infestant les ruminants domestiques et les agents pathogènes qu'elles transportent sont rares au Malawi. Cette étude a examiné des tiques prélevées sur des ruminants domestiques et a recherché certains agents pathogènes protozoaires et bactériens d'importance vétérinaire et médicale. Au total, 964 tiques ont été collectées sur 202 bovins, 63 chèvres et 16 moutons dans onze districts du Malawi. Les tiques ont été identifiées morphologiquement jusqu'à l'espèce à l'aide de clés taxonomiques, avec confirmation moléculaire par amplification PCR et séquençage des gènes de l'ARN ribosomique 12S (ADNr 12S) et de la sous-unité I de la cytochrome c oxydase ( COI ). L’ADN des tiques a ensuite été analysé à la recherche d’agents pathogènes transmis par les tiques à l’aide de tests PCR spécifiques à l’espèce. Les espèces de tiques identifiées comprenaient Rhipicephalus microplus (30,5 %), Rhipicephalus appendiculatus (23,3 %), Rhipicephalus decoloratus (13,2 %), Rhipicephalus evertsi (9,8 %), Hyalomma rufipes (7,5 %), Amblyomma variegatum (6,3 %), Rhipicephalus sanguineus sensu lato (lignée tropicale) (3,6 %), Hyalomma truncatum (2,8 %), Rhipicephalus simus (2,0 %), Rhipicephalus pravus (0,6 %) et Rhipicephalus annulatus (0,4 %). Au total, 37 % des tiques étaient porteuses d'au moins un agent pathogène transmis par les tiques, Theileria parva étant le plus fréquent (34,7 %), suivi d' Anaplasma marginale (17,4 %), Babesia bigemina (14,9 %), Anaplasma ovis (11,2 %), Ehrlichia ruminantium (9,2 %), Theileria mutans (8,4 %), Babesia bovis (2,2 %) et Anaplasma bovis (2 %). Cette étude fournit la première identification moléculaire des tiques infestant les ruminants domestiques au Malawi et documente les agents pathogènes transmis par les tiques associés. Notamment, Rhipicephalus appendiculatus a été identifié pour la première fois dans le sud du Malawi, ce qui affine les connaissances actuelles sur l'épidémiologie de la fièvre de la côte Est et souligne la nécessité de mettre à jour les méthodes de surveillance.