Inferring malaria parasite population structure from serological networks

The malaria parasite Plasmodium falciparum is characterized by high levels of genetic diversity at antigenic loci involved in virulence and immune evasion. Knowledge of the population structure and dynamics of these genes is important for designing control programmes and understanding the acquisition of immunity to malaria; however, high rates of homologous and non-homologous recombination as well as complex patterns of expression within hosts have hindered attempts to elucidate these structures experimentally. Here, we analyse serological data from Kenya using a novel network technique to deconstruct the relationships between patients' immune responses to different parasite isolates. We show that particular population structures and expression patterns produce distinctive signatures within serological networks of parasite recognition, which can be used to discriminate between competing hypotheses regarding the organization of these genes. Our analysis suggests that different levels of immune selection occur within different groups of the same multigene family leading to mixed population structures

Refuge sharing network predicts ectoparasite load in a lizard

Living in social groups facilitates cross-infection by parasites. However, empirical studies on indirect transmission within wildlife populations are scarce. We investigated whether asynchronous overnight refuge sharing among neighboring sleepy lizards, Tiliqua rugosa, facilitates indirect transmission of its ectoparasitic tick, Amblyomma limbatum. We fitted 18 neighboring lizards with GPS recorders, observed their overnight refuge use each night over 3 months, and counted their ticks every fortnight. We constructed a transmission network to estimate the cross-infection risk based on asynchronous refuge sharing frequencies among all lizards and the life history traits of the tick. Although self-infection was possible, the network provided a powerful predictor of measured tick loads. Highly connected lizards that frequently used their neighbors’ refuges were characterized by higher tick loads. Thus, indirect contact had a major influence on transmission pathways and parasite loads. Furthermore, lizards that used many different refuges had lower cross- and self-infection risks and lower tick loads than individuals that used relatively fewer refuges. Increasing the number of refuges used by a lizard may be an important defense mechanism against ectoparasite transmission in this species. Our study provides important empirical data to further understand how indirectly transmitted parasites move through host populations and influence individual parasite loads

Serological Conservation of Parasite-Infected Erythrocytes Predicts Plasmodium falciparum Erythrocyte Membrane Protein 1 Gene Expression but Not Severity of Childhood Malaria.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on P. falciparum-infected erythrocytes, is a major family of clonally variant targets of naturally acquired immunity to malaria. Previous studies have demonstrated that in areas where malaria is endemic, antibodies to infected erythrocytes from children with severe malaria tend to be more seroprevalent than antibodies to infected erythrocytes from children with nonsevere malaria. These data have led to a working hypothesis that PfEMP1 variants associated with parasite virulence are relatively conserved in structure. However, the longevity of such serologically conserved variants in the parasite population is unknown. Here, using infected erythrocytes from recently sampled clinical P. falciparum samples, we measured serological conservation using pools of antibodies in sera that had been sampled 10 to 12 years earlier. The serological conservation of infected erythrocytes strongly correlated with the expression of specific PfEMP1 subsets previously found to be associated with severe malaria. However, we found no association between serological conservation per se and disease severity within these data. This contrasts with the simple hypothesis that P. falciparum isolates with a serologically conserved group of PfEMP1 variants cause severe malaria. The data are instead consistent with periodic turnover of the immunodominant epitopes of PfEMP1 associated with severe malaria.Wellcome Trust (084535, 077092, 084538, and 098635)This is the final version of the article. It first appeared from the American Society for Microbiology via http://dx.doi.org/10.1128/IAI.00772-1

Mapping of DBLα Sequence Tags of Field Isolates from Two Malaria Endemic Sites in Kenya

Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) found on the surface of infected erythrocytes (IEs) mediate antigenic variation during P. falciparum infection enabling the parasite evade host immune responses and prolong infection. These molecules mediate binding of IEs to host endothelial cells and uninfected erythrocytes. Cytoadhesion of IE to host cells leads to sequestration in tissues and PfEMP1 is thought to play an important role in parasite virulence. Here we analysed 1725 sequence tags sampled from the DBLa region of PfEMP1 encoding “var” genes from 27 patients in two different geographical regions in Kenya, Mbita in Western Kenya and Twiga on the Kenyan coast. The objective of this study was to construct a network to assess the extent of shared position specific polymorphic blocks (PSPBs) in sequences isolated from genomic DNA of field isolates from the two malaria endemic sites in Kenya.. Sequences from Mbita study site and those from Tiwi largely clustered into separate giant networks with only a limited number of sequences from the two sites linking to each other. This observation suggests that the parasite populations from the two endemic sites could be genetically varied and that PfEMP1 sequencing could be a useful tool of understanding the genetics of parasite populations. Thus the network approach of studying relationships between DBLα sequences is a useful tool of uncovering the genetic structure of parasite populations circulating in different malaria endemic regions. Keywords: PfEMP1, Networks, Position Specific Polymorphic Groups, DBLα, Malaria, P. falciparu

Plasmodium falciparum Variant Surface Antigen Expression Patterns during Malaria

The variant surface antigens expressed on Plasmodium falciparum–infected erythrocytes are potentially important targets of immunity to malaria and are encoded, at least in part, by a family of var genes, about 60 of which are present within every parasite genome. Here we use semi-conserved regions within short var gene sequence “tags” to make direct comparisons of var gene expression in 12 clinical parasite isolates from Kenyan children. A total of 1,746 var clones were sequenced from genomic and cDNA and assigned to one of six sequence groups using specific sequence features. The results show the following. (1) The relative numbers of genomic clones falling in each of the sequence groups was similar between parasite isolates and corresponded well with the numbers of genes found in the genome of a single, fully sequenced parasite isolate. In contrast, the relative numbers of cDNA clones falling in each group varied considerably between isolates. (2) Expression of sequences belonging to a relatively conserved group was negatively associated with the repertoire of variant surface antigen antibodies carried by the infected child at the time of disease, whereas expression of sequences belonging to another group was associated with the parasite “rosetting” phenotype, a well established virulence determinant. Our results suggest that information on the state of the host–parasite relationship in vivo can be provided by measurements of the differential expression of different var groups, and need only be defined by short stretches of sequence data

More Collaboration - More Power in Combating Ill Health

This symposium highlighted the position of physical activity as one of the most important factors causally related to common non-communicable diseases (NCDs), and discussed the need for including physical activity in comprehensive prevention strategies and policies to combat the major NCDs. Lifestyle factors such as smoking, physical inactivity, and obesity are all major risk factors for ischemic heart disease, cerebrovascular disease, and several cancers, and physical inactivity globally ranks as the fourth leading risk factor for mortality. Despite the solid evidence that physical activity is related to several NCDs, stronger advocacy actions are required because physical activity is not viewed as a national priority in most countries. Much progress has been made on physical activity surveillance as well as the development of national policies, action plans and physical activity guidelines. However, in most countries there is a need for more workforce development across all sectors and robust evaluation of actions to build the evidence base on program effectiveness

Differential Plasmodium falciparum surface antigen expression among children with Malarial Retinopathy

Retinopathy provides a window into the underlying pathology of life-threatening malarial coma (“cerebral malaria”), allowing differentiation between 1) coma caused by sequestration of Plasmodium falciparum-infected erythrocytes in the brain and 2) coma with other underlying causes. Parasite sequestration in the brain is mediated by PfEMP1; a diverse parasite antigen that is inserted into the surface of infected erythrocytes and adheres to various host receptors. PfEMP1 sub-groups called “DC8” and “DC13” have been proposed to cause brain pathology through interactions with endothelial protein C receptor. To test this we profiled PfEMP1 gene expression in parasites from children with clinically defined cerebral malaria, who either had or did not have accompanying retinopathy. We found no evidence for an elevation of DC8 or DC13 PfEMP1 expression in children with retinopathy. However, the proportional expression of a broad subgroup of PfEMP1 called “group A” was elevated in retinopathy patients suggesting that these variants may play a role in the pathology of cerebral malaria. Interventions targeting group A PfEMP1 may be effective at reducing brain pathology

Robert James Baker (1942-2018), Obituary

First paragraph: On 30 March 2018, the science of mammalogy and the American Society of Mammalogists lost one of the most influential figures of the last half-century. Robert James Baker died quietly at his home in Lubbock, Texas (Fig. 1). He was born on 8 April 1942 to James Simeon Baker and Laura Cooper in Warren, Arkansas. His father was killed during World War II and his mother remarried, resulting in his growing up with six half-siblings. According to Robert’s autobiography in Going afield (330—number refers to specific publication in “Bibliography”), he spent a good deal of his youth with his grandparents on a 100-acre farm in the West Gulf Coastal Plain of southeastern Arkansas. He identified his maternal grandmother, “Grandma Rosie,” as his best friend and his greatest influence during these years. His marriage to Jean Joyner on 19 August 1961 ended in divorce in 1975, but the marriage resulted in a daughter, April Baker-Padilla, and two grandchildren, Jason Baker and Faith Padilla. Robert was married to his wife of 39 years, Laura Kyle (M.D.), on 28 May 1978 in Lubbock. Their son, Robert Kyle Baker, preceded his father in death, which was a tragedy from which neither Robert nor Laura ever completely recovered

Non-Native Salmonids Affect Amphibian Occupancy at Multiple Spatial Scales

Aim The introduction of non-native species into aquatic environments has been linked with local extinctions and altered distributions of native species. We investigated the effect of non-native salmonids on the occupancy of two native amphibians, the long-toed salamander (Ambystoma macrodactylum) and Columbia spotted frog (Rana luteiventris), across three spatial scales: water bodies, small catchments and large catchments. Location Mountain lakes at ≥ 1500 m elevation were surveyed across the northern Rocky Mountains, USA. Methods We surveyed 2267 water bodies for amphibian occupancy (based on evidence of reproduction) and fish presence between 1986 and 2002 and modelled the probability of amphibian occupancy at each spatial scale in relation to habitat availability and quality and fish presence. Results After accounting for habitat features, we estimated that A. macrodactylum was 2.3 times more likely to breed in fishless water bodies than in water bodies with fish. Ambystoma macrodactylum also was more likely to occupy small catchments where none of the water bodies contained fish than in catchments where at least one water body contained fish. However, the probability of salamander occupancy in small catchments was also influenced by habitat availability (i.e. the number of water bodies within a catchment) and suitability of remaining fishless water bodies. We found no relationship between fish presence and salamander occupancy at the large-catchment scale, probably because of increased habitat availability. In contrast to A. macrodactylum, we found no relationship between fish presence and R. luteiventris occupancy at any scale. Main conclusions Our results suggest that the negative effects of non-native salmonids can extend beyond the boundaries of individual water bodies and increase A. macrodactylum extinction risk at landscape scales. We suspect that niche overlap between non-native fish and A. macrodactylum at higher elevations in the northern Rocky Mountains may lead to extinction in catchments with limited suitable habitat