Parasite Movement Research Articles

Phytohormones regulate asexual Toxoplasma gondii replication.

The protozoan Toxoplasma gondii (T. gondii) is a zoonotic disease agent causing systemic infection in warm-blooded intermediate hosts including humans. Duringthe acute infection, the parasite infects host cells and multiplies intracellularly in the asexual tachyzoite stage. In this stage of the life cycle, invasion, multiplication, and egress are themost critical events in parasite replication. T. gondii features diverse cell organelles to support these processes, including the apicoplast, an endosymbiont-derived vestigial plastid originating from an alga ancestor. Previous studies have highlighted that phytohormones can modify the calcium-mediated secretion, e.g., of adhesins involved in parasite movement and cell invasion processes. The present study aimed to elucidate the influence of different plant hormones on the replication of asexual tachyzoites in a human foreskin fibroblast (HFF) host cell culture. T. gondii replication was measured by the determination of T. gondii DNA copies via qPCR. Three selected phytohormones, namely abscisic acid (ABA), gibberellic acid (GIBB), and kinetin (KIN) as representatives of different plant hormone groups were tested. Moreover, the influence of typical cell culture media components on the phytohormone effects was assessed. Our results indicate that ABA is able to induce a significant increase of T. gondii DNA copies in atypical supplemented cell culture medium when applied in concentrations of 20 ng/μl or 2 ng/μl, respectively. In contrast, depending on the culture medium composition, GIBB may potentially serve as T. gondii growth inhibitor and may be further investigated as a potential treatment for toxoplasmosis.

Isolation, Characterization and Evaluation of Anti-schistosomal Activity of triterpenes from crude ethyl acetate extract of the Rhizome of Dolichos pachyrhizus

Schistosomiasis is a neglected tropical disease caused by helminth flatworms of the genus Schistosoma. Currently, praziquantel is the only medication available. Schistosomiasis is the second most deadly parasitic infection after malaria. Dolichos pachyrhizus's (Fabaceae) rhizome is commonly utilized as an antihelmintic. In this study, the in vitro antischistosomal activity of D. pachyrhizus crude extract and isolated compounds were examined against S. mansoni immature worms. All mature and immature worms were killed by C1, C2 and ethyl acetate extract at 500 mg/mL after 24 h incubation. Additionally, all the examined compounds and extract at 500 mg/mL exponentially reduced the parasite's movement; (70-90 %) shrinkage, viability (10-30 %) and mortality (70-90 %) rates.

Clinical and therapeutic management of erratic movement of parasites in young dogs

Parasitic infection (both ecto – endo parasites) causes greater economic losses to Live Stock and Poultry. Young puppies suffered with Toxocara canis infection. Totally 32 numbers of puppies at the age group of 2-5 months showed symptomatic worm infestation with bot belly appearance and few of them showed adult ascaris worms in vomit and few of the showed unilateral nasal sneezing. Presence of worms in vomitus may be associated with their erratic movements, some round worms may enter in to stomach and may be vomited and some worms may enter the bile ducts and produce obstructive jaundice and cholangitis. Prenatal and trans mammary route of infection play a major role for transmission of infection.

The effect of the COVID-19 lockdown on malaria transmission in South Africa

BackgroundFor a country such as South Africa which is targeting malaria elimination, mobile and migrant populations pose a substantial risk to importation of malaria parasites. It has been hypothesized that halting cross-border movement of mobile and migrant populations will decrease the importation of malaria, however this option is not a politically, operationally, and financially viable prospect. It has social impacts as well, since families live on either side of the border and preventing travel will challenge family ties. Due to the COVID-19 pandemic and closure of ports of entry (land and air) for non-essential travel into South Africa, a unique opportunity arose to test the hypothesis.MethodologyAn interrupted time series analysis was done to assess whether the post-lockdown trends (April–December 2020) in monthly reported imported and local cases differed from the pre-lockdown trends (January 2015–March 2020). The analysis was conducted separately for KwaZulu-Natal, Mpumalanga, and Limpopo provinces.ResultsOn average, imported cases were lower in the post-intervention period in all three provinces, and local cases were lower in Mpumalanga and Limpopo, though no results were statistically significant.ConclusionSince population movement continued after the travel restrictions were lifted, border screening with testing and treating should be considered for reducing parasite movement. Another option is reducing malaria cases at the source in neighbouring countries by implementing proven, effective vector and parasite control strategies and through a downstream effect reduce malaria entering South Africa.

Trypanosoma cruzi-specific CD8+ T cells and other immunological hallmarks in chronic Chagas cardiomyopathy: Two decades of research.

Trypanosoma cruzi, the causal agent of Chagas disease, has coexisted with humans for thousands of years. Therefore, the parasite has developed several mechanisms of antigenic variability that has allowed it to live inside the cells and evade the host immune response. SinceT. cruzidisplays an intracellular cycle-stage, our research team focused on providing insights into the CD8+T cells immune response in chronic Chagas cardiomyopathy. We began our work in the 2000s studying parasite antigens that induce natural immune responses such as the KMP11 protein and TcTLE, its N-terminal derived peptide. Different approaches allowed us to reveal TcTLE peptide as a promiscuous CD8+ T cell epitope, able of inducing multifunctional cellular immune responses and eliciting a humoral response capable of decreasing parasite movement and infective capacity. Next, we demonstrated that as the disease progresses, total CD8+T cells display a dysfunctional state characterized by a prolonged hyper-activation state along with an increase of inhibitory receptors (2B4, CD160, PD-1, TIM-3, CTLA-4) expression, an increase of specific terminal effector T cells (TTE), a decrease of proliferative capacity, a decrease of stem cell memory (TSCM) frequency, and a decrease of CD28 and CD3ζexpression. Thus, parasite-specific CD8+ T cells undergo clonal exhaustion, distinguished by an increase in late-differentiated cells, a mono-functional response, and enhanced expression of inhibitory receptors. Finally, it was found that anti-parasitic treatment induces an improved CD8+T cell response in asymptomatic individuals, and a mouse animal model led us to establish a correlation between the quality of the CD8+ T cell responses and the outcome of chronic infection. In the future, using OMICs strategies, the identification of the specific cellular signals involved in disease progression will provide an invaluable resource for discovering new biomarkers of progression or new vaccine and immunotherapy strategies. Also, the inclusion of the TcTLE peptide in the rational design of epitope-based vaccines, the development of immunotherapy strategies using TSCMor the blocking of inhibitory receptors, and the use of the CD8+T cell response quality to follow treatments, immunotherapies or vaccines, all are alternatives than could be explored in the fight against Chagas disease.

Diversity, prevalence, and intensity of gastrointestinal helminth infections in migratory, resident, and sedentary plains zebras (Equus quagga) in Masai Mara National Reserve and Lake Nakuru National Park, Kenya.

The diversity, prevalence and intensity of parasitic infections are influenced by factors such as movement patterns and land area available to the host. Zebras are known to harbour various genera of gastrointestinal helminths and facilitate parasite movement across large geographic areas through migration. Despite the harmful effects of helminths and their consequences on host population dynamics, little is known regarding helminth infection patterns in migratory, resident, and sedentary zebras. This study compared the diversity, prevalence, and intensity of helminth infections in zebras with different host movement patterns and space availability. Faecal samples were collected from migratory, resident, and sedentary groups of zebras between 2014 and 2015 and screened for helminth infection. They were infected by diverse groups of helminths including nematodes, trematodes and cestodes with the most prevalent being strongyle type nematodes. No significant difference in the diversity and prevalence was observed between the "three groups". Larvae were also recovered and identified species, cyathostomes, Strongylus edentatus, S.vulgaris, S. equinus, and Trichostronglus in order of abundance. The intensity of infection with the strongyle type nematodes, was highest in the migratory, then sedentary and lowest in resident zebras. It is plausible that the migratory zebras have higher energy demands and poor nutrition, resulting in reduced immune function hence high nematode burdens. Similarly, the sedentary population had high nematode burdens possibly due to high pasture contamination and depressed immunity due to the artificially restricted movement. The latter observation is particularly important in the design and size of sanctuaries in relation to parasitism.

Molecular characterization of the serotonergic transporter from the cestode Echinococcus granulosus: pharmacology and potential role in the nervous system.

Echinococcus granulosus, the etiological agent of human cystic echinococcosis (formerly known as hydatid disease), represents a serious worldwide public health problem with limited treatment options. The essential role played by the neuromuscular system in parasite survival and the relevance of serotonin (5-HT) in parasite movement and development make the serotonergic system an attractive source of drug targets. In this study, we cloned and sequenced a cDNA coding for the serotonin transporter from E. granulosus (EgSERT). Bioinformatic analyses suggest that EgSERT has twelve transmembrane domains with highly conserved ligand and ionic binding sites but a less conserved allosteric site compared with the human orthologue (HsSERT). Modeling studies also suggest a good degree of conservation of the overall structure compared with HsSERT. Functional and pharmacological studies performed on the cloned EgSERT confirm that this protein is indeed a serotonin transporter. EgSERT is specific for 5-HT and does not transport other neurotransmitters. Typical monoamine transport inhibitors also displayed inhibitory activities towards EgSERT, but with lower affinity than for the human SERT (HsSERT), suggesting a high divergence of the cestode transporter compared with HsSERT. In situ hybridization studies performed in the larval protoscolex stage suggest that EgSERT is located in discrete regions that are compatible with the major ganglia of the serotonergic nervous system. The pharmacological properties, the amino acidic substitutions at important functional regions compared with the HsSERT, and the putative role of EgSERT in the nervous system suggest that it could be an important target for pharmacological intervention.

Plasmodium falciparum genomic surveillance reveals spatial and temporal trends, association of genetic and physical distance, and household clustering

Molecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control strategies. Genomic data, coupled with geographic information systems data, can further identify clusters or hotspots of malaria transmission, parasite genetic and spatial connectivity, and parasite movement by human or mosquito mobility over time and space. In this study, we performed longitudinal genomic surveillance in a cohort of 70 participants over four years from different neighborhoods and households in Thiès, Senegal—a region of exceptionally low malaria transmission (entomological inoculation rate less than 1). Genetic identity (identity by state, IBS) was established using a 24-single nucleotide polymorphism molecular barcode, identity by descent was calculated from whole genome sequence data, and a hierarchical Bayesian regression model was used to establish genetic and spatial relationships. Our results show clustering of genetically similar parasites within households and a decline in genetic similarity of parasites with increasing distance. One household showed extremely high diversity and warrants further investigation as to the source of these diverse genetic types. This study illustrates the utility of genomic data with traditional epidemiological approaches for surveillance and detection of trends and patterns in malaria transmission not only by neighborhood but also by household. This approach can be implemented regionally and countrywide to strengthen and support malaria control and elimination efforts.

Schistosoma mansoni α-N-acetylgalactosaminidase (SmNAGAL) regulates coordinated parasite movement and egg production.

α-galactosidase (α-GAL) and α-N-acetylgalactosaminidase (α-NAGAL) are two glycosyl hydrolases responsible for maintaining cellular homeostasis by regulating glycan substrates on proteins and lipids. Mutations in the human genes encoding either enzyme lead to neurological and neuromuscular impairments seen in both Fabry- and Schindler/Kanzaki- diseases. Here, we investigate whether the parasitic blood fluke Schistosoma mansoni, responsible for the neglected tropical disease schistosomiasis, also contains functionally important α-GAL and α-NAGAL proteins. As infection, parasite maturation and host interactions are all governed by carefully-regulated glycosylation processes, inhibiting S. mansoni's α-GAL and α-NAGAL activities could lead to the development of novel chemotherapeutics. Sequence and phylogenetic analyses of putative α-GAL/α-NAGAL protein types showed Smp_089290 to be the only S. mansoni protein to contain the functional amino acid residues necessary for α-GAL/α-NAGAL substrate cleavage. Both α-GAL and α-NAGAL enzymatic activities were higher in females compared to males (p<0.05; α-NAGAL > α-GAL), which was consistent with smp_089290's female biased expression. Spatial localisation of smp_089290 revealed accumulation in parenchymal cells, neuronal cells, and the vitellaria and mature vitellocytes of the adult schistosome. siRNA-mediated knockdown (>90%) of smp_089290 in adult worms significantly inhibited α-NAGAL activity when compared to control worms (siLuc treated males, p<0.01; siLuc treated females, p<0.05). No significant reductions in α-GAL activities were observed in the same extracts. Despite this, decreases in α-NAGAL activities correlated with a significant inhibition in adult worm motility as well as in egg production. Programmed CRISPR/Cas9 editing of smp_089290 in adult worms confirmed the egg reduction phenotype. Based on these results, Smp_089290 was determined to act predominantly as an α-NAGAL (hereafter termed SmNAGAL) in schistosome parasites where it participates in coordinating movement and oviposition processes. Further characterisation of SmNAGAL and other functionally important glycosyl hydrolases may lead to the development of a novel anthelmintic class of compounds.

Risk of Infection, Local Prevalence and Seasonal Changes in an Avian Malaria Community Associated with Game Bird Releases

Anthropogenic activities, such as the translocation or introduction of animals, may cause a parallel movement of exotic parasites harboured by displaced animals. Although introduction and/or relocation of animals for hunting purposes is an increasingly common management technique, the effects of gamebird release as a major vehicle for the introduction of parasites into new geographic regions have rarely been reported. We examined the prevalence and distribution of avian malaria parasites infecting resident avian hosts (red-legged partridge Alectoris rufa) at a local scale, with a particular emphasis on the effects of releasing farm-reared birds for hunting on the spatial and temporal structure of the parasite community. We collected blood samples from adult partridges from two game estates with partridge releases and two sites without releases over two periods (spring and autumn). We tested the probability of infection and differences in the parasite community in relation to the management model (releases vs. non releases) and sampling period, comparing autumn (when farm-reared birds are released) and spring (after hunting season, when mostly wild birds can be found in the population). We found a high prevalence (54%) of Plasmodium spp., and substantial differences in the spatial and temporal distribution of parasite lineages among the populations studied. Some parasite lineages occurred at high frequencies in game estates without introduction of farm-reared partridges, while other lineages were more abundant in game estates with releases than in those without releases. Overall, the prevalence of avian malaria was similar between spring and autumn at non-release sites, whereas in sites with releases, it was higher in autumn than in spring—probably due to artificial restocking with infected farm-reared birds at the onset of the hunting season. In short, humans may be an important agent driving the alteration of the spatial structure of local parasite fauna via the introduction of exotic parasites by gamebird release, which could cause avian malaria outbreaks with severe repercussions for native avifauna.

Skin-penetrating nematodes exhibit life-stage-specific interactions with host-associated and environmental bacteria

BackgroundSkin-penetrating nematodes of the genus Strongyloides infect over 600 million people, posing a major global health burden. Their life cycle includes both a parasitic and free-living generation. During the parasitic generation, infective third-stage larvae (iL3s) actively engage in host seeking. During the free-living generation, the nematodes develop and reproduce on host feces. At different points during their life cycle, Strongyloides species encounter a wide variety of host-associated and environmental bacteria. However, the microbiome associated with Strongyloides species, and the behavioral and physiological interactions between Strongyloides species and bacteria, remain unclear.ResultsWe first investigated the microbiome of the human parasite Strongyloides stercoralis using 16S-based amplicon sequencing. We found that S. stercoralis free-living adults have an associated microbiome consisting of specific fecal bacteria. We then investigated the behavioral responses of S. stercoralis and the closely related rat parasite Strongyloides ratti to an ecologically diverse panel of bacteria. We found that S. stercoralis and S. ratti showed similar responses to bacteria. The responses of both nematodes to bacteria varied dramatically across life stages: free-living adults were strongly attracted to most of the bacteria tested, while iL3s were attracted specifically to a narrow range of environmental bacteria. The behavioral responses to bacteria were dynamic, consisting of distinct short- and long-term behaviors. Finally, a comparison of the growth and reproduction of S. stercoralis free-living adults on different bacteria revealed that the bacterium Proteus mirabilis inhibits S. stercoralis egg hatching, and thereby greatly decreases parasite viability.ConclusionsSkin-penetrating nematodes encounter bacteria from various ecological niches throughout their life cycle. Our results demonstrate that bacteria function as key chemosensory cues for directing parasite movement in a life-stage-specific manner. Some bacterial genera may form essential associations with the nematodes, while others are detrimental and serve as a potential source of novel nematicides.

Moving apart together: co-movement of a symbiont community and their ant host, and its importance for community assembly

BackgroundSpecies interactions may affect spatial dynamics when the movement of one species is determined by the presence of another one. The most direct species-dependence of dispersal is vectored, usually cross-kingdom, movement of immobile parasites, diseases or seeds by mobile animals. Joint movements of species should, however, not be vectored by definition, as even mobile species are predicted to move together when they are tightly connected in symbiont communities.MethodsWe studied concerted movements in a diverse and heterogeneous community of arthropods (myrmecophiles) associated with red wood ants. We questioned whether joint-movement strategies eventually determine and speed-up community succession.ResultsWe recorded an astonishingly high number of obligate myrmecophiles outside red wood ant nests. They preferentially co-moved with the host ants as the highest densities were found in locations with the highest density of foraging red wood ants, such as along the network of ant trails. These observations suggest that myrmecophiles resort to the host to move away from the nest, and this to a much higher extent than hitherto anticipated. Interestingly, functional groups of symbionts displayed different dispersal kernels, with predatory myrmecophiles moving more frequently and further from the nest than detritivorous myrmecophiles. We discovered that myrmecophile diversity was lower in newly founded nests than in mature red wood ant nests. Most myrmecophiles, however, were able to colonize new nests fast suggesting that the heterogeneity in mobility does not affect community assembly.ConclusionsWe show that co-movement is not restricted to tight parasitic, or cross-kingdom interactions. Movement in social insect symbiont communities may be heterogeneous and functional group-dependent, but clearly affected by host movement. Ultimately, this co-movement leads to directional movement and allows a fast colonisation of new patches, but not in a predictable way. This study highlights the importance of spatial dynamics of local and regional networks in symbiont metacommunities, of which those of symbionts of social insects are prime examples.

Eliminating malaria from the margins of transmission in Southern Africa through the Elimination 8 Initiative

Four southern Africa countries, namely, Botswana, Eswatini, Namibia and South Africa, were identified by the World Health Organization as having the potential to eliminate malaria in the near future. However, the extreme interconnectedness of southern African countries facilitates the constant movement of malaria parasites across country-borders, predominately from higher-burden “source” countries to lower-burden “sink” countries, reinforcing the notion that malaria elimination in any southern African country would not be possible without regional cooperation and collaboration. The Elimination 8 initiative (E8) was therefore, created by Health Ministers from eight countries (Angola, Botswana, Eswatini, Mozambique, Namibia, South Africa, Zambia and Zimbabwe) to coordinate the implementation of a regional malaria elimination strategy. The E8 supported the implementation of five cross-border malaria control initiatives and the deployment of malaria health units at strategic points along shared borders. These units have contributed to a 30% and 46% reduction in malaria incidence and mortality, respectively, in the E8 border regions. The Situation Room, a novel data sharing platform developed and supported by the E8, has allowed for the early detection of and prompt response to malaria outbreaks. This platform played a vital role in identifying resources gaps due to the COVID-19 pandemic. Despite advancing the elimination agenda, the E8 region faces challenges which include, significant increases in malaria in certain member states, limited domestic funding and health system bottlenecks. These must be urgently addressed if the gains made through the E8 are to be sustained and malaria elimination is to be achieved across southern Africa.

Right place, right time: Environmental sensing and signal transduction directs cellular differentiation and motility in Trypanosoma brucei.

Trypanosoma brucei and other African trypanosomes are vector-borne parasites that cause substantial human suffering across sub-Saharan Africa. The T. brucei life cycle is punctuated by numerous developmental stages, each occurring in a specific environmental niche and characterized by a unique morphology, metabolism, surface protein coat, and gene expression profile. The environmental cues and signaling pathways that drive transitions between these stages remain incompletely understood. Recent studies have started to fill this gap in knowledge. Likewise, several new studies have expanded our understanding of parasite movement through specific tissues and the parasite's ability to alter movement in response to external cues. Life cycle stage differentiation and motility are intimately integrated phenomena, as parasites must be at the right place (i.e., within a specific environmental milieu) at the right time (i.e., when they are appropriately staged and preadapted for perceiving and responding to signals) in order to complete their life cycle. In this review, we highlight some of the recent work that has transformed our understanding of signaling events that control parasite differentiation and motility. Increased knowledge of T. brucei environmental sensing and signal transduction advances our understanding of parasite biology and may direct prospective chemotherapeutic and transmission blockade strategies that are critical to eradication efforts.

Genetic analysis reveals unique characteristics of Plasmodium falciparum parasite populations in Haiti

BackgroundWith increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian population remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies.MethodsThis study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand’Anse, and Sud) in 2016.ResultsAssessment of the parasite genetic relatedness revealed evidence of clonal expansion within Nippes and the exchange of parasite lineages between Nippes, Sud, and Grand'Anse. Furthermore, 437 of the 462 samples shared high levels of genetic similarity–at least 20 of 21 SNPS–with at least one other sample in the dataset.ConclusionsThese results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.

Molecular characterisation and vaccine efficacy of two novel developmentally regulated surface tegument proteins of Fasciola hepatica

The surface tegument of Fasciola hepatica is a crucial tissue due to its key role at the host-parasite interface. We characterised three novel proteins, termed Fhteg1, Fhteg5 and Fhteg8, that are found in the tegument membrane fraction of adult F. hepatica. Bioinformatic analysis of proteomic datasets identified Fhteg5 and Fhteg8 as tegumental glycoproteins and revealed that Fhteg1, Fhteg5 and Fhteg8 are associated with exosomes of adult F. hepatica. Fhteg1, Fhteg5 and Fhteg8 appear to be related to uncharacterised sequences in F. gigantica, Fasciolopsis buski, Echinostoma caproni, Clonorchis sinensis, Opisthorchis viverrini, Schistosoma japonicum and S. mansoni, although F. hepatica appears to have expanded this family. Fhteg1 and Fhteg5 were characterised in detail. The Fhteg1 and Fhteg5 gene transcripts each demonstrate significant upregulation in juvenile fluke 2–4 days post-excystment, with transcript levels maintained during development over 3 weeks in vitro. RNAseq data showed that both Fhtegs are expressed in the adult life stage, although the transcript levels were about 8 fold lower than those in juveniles (3 week post infection). Using immunocytochemistry, Fhteg1 and Fhteg5 were each shown to be expressed in cells adjacent to the muscle layer as well as on the surface of 1 week old juveniles, whilst Fhteg5 was also present in cells at the base of the pharynx. RNAi mediated knockdown of Fhteg1 and Fhteg5 transcripts in 4–10 day old juveniles had no effect on parasite survival, movement or growth in vitro. Although no IgG responses were observed for Fhteg1 or Fhteg5 during infection in sheep and cattle, both proteins elicited a low IgG response in a proportion of infected rats. Rats vaccinated with Fhteg1 and Fhteg5 showed good IgG responses to both proteins and a mean 48.2 % reduction in worm burden following parasite challenge. Although vaccination of cattle with both proteins induced a range of IgG responses, no protection was observed against parasite challenge. This is the first study to provide insights into the molecular properties of two novel, developmentally regulated surface tegument proteins in F. hepatica.

Rainfall as a driver of seasonality in parasitism

Parasite burdens are known to vary seasonally in wildlife, and rainfall is one key aspect of seasonality that has been linked to parasitism in a range of systems. Rainfall can have immediate effects on parasitism rates by affecting parasite survival and movement in the environment, or it can have delayed effects by affecting host susceptibility to parasites through changes in host body condition or immune function. In this study, we examined how helminth infection in a wild ungulate (Grant's gazelle, Nanger granti) is impacted by seasonal changes in rainfall. We looked at how the burdens of three helminth parasites varied in relation to current (immediate effect) and prior (delayed effect) rainfall by comparing parasite fecal egg and larval counts to rainfall 0, 1, and 2 months prior to parasite sampling. We found burdens of all three parasites to be negatively associated with rainfall, and that delayed effects were stronger than immediate effects. Our findings implicate rainfall as a driver of seasonal variation in infection and suggest one important mechanism may be through delayed effects on host susceptibility.

A molecular barcode to inform the geographical origin and transmission dynamics of Plasmodium vivax malaria

Although Plasmodium vivax parasites are the predominant cause of malaria outside of sub-Saharan Africa, they not always prioritised by elimination programmes. P. vivax is resilient and poses challenges through its ability to re-emerge from dormancy in the human liver. With observed growing drug-resistance and the increasing reports of life-threatening infections, new tools to inform elimination efforts are needed. In order to halt transmission, we need to better understand the dynamics of transmission, the movement of parasites, and the reservoirs of infection in order to design targeted interventions. The use of molecular genetics and epidemiology for tracking and studying malaria parasite populations has been applied successfully in P. falciparum species and here we sought to develop a molecular genetic tool for P. vivax. By assembling the largest set of P. vivax whole genome sequences (n = 433) spanning 17 countries, and applying a machine learning approach, we created a 71 SNP barcode with high predictive ability to identify geographic origin (91.4%). Further, due to the inclusion of markers for within population variability, the barcode may also distinguish local transmission networks. By using P. vivax data from a low-transmission setting in Malaysia, we demonstrate the potential ability to infer outbreak events. By characterising the barcoding SNP genotypes in P. vivax DNA sourced from UK travellers (n = 132) to ten malaria endemic countries predominantly not used in the barcode construction, we correctly predicted the geographic region of infection origin. Overall, the 71 SNP barcode outperforms previously published genotyping methods and when rolled-out within new portable platforms, is likely to be an invaluable tool for informing targeted interventions towards elimination of this resilient human malaria.

Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago

BackgroundTanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malaria’s persistence, but this paradigm has not been studied using modern genetic tools.MethodsWhole-genome sequencing (WGS) was used to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. Ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations were assessed by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections.ResultsSignificant decreases in the effective population sizes were inferred in both populations that coincide with a period of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared long segments of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling, two of isolates between the mainland and Zanzibar were identified that are related at the expected level of half-siblings, consistent with recent importation.ConclusionsThese findings suggest that importation plays an important role for malaria incidence on Zanzibar and demonstrate the value of genomic approaches for identifying corridors of parasite movement to the island.

Microsatellite analysis reveals connectivity among geographically distant transmission zones of Plasmodium vivax in the Peruvian Amazon: A critical barrier to regional malaria elimination.

Despite efforts made over decades by the Peruvian government to eliminate malaria, Plasmodium vivax remains a challenge for public health decision-makers in the country. The uneven distribution of its incidence, plus its complex pattern of dispersion, has made ineffective control measures based on global information that lack the necessary detail to understand transmission fully. In this sense, population genetic tools can complement current surveillance. This study describes the genetic diversity and population structure from September 2012 to March 2015 in three geographically distant settlements, Cahuide (CAH), Lupuna (LUP) and Santa Emilia (STE), located in the Peruvian Amazon. A total 777 P. vivax mono-infections, out of 3264, were genotyped. Among study areas, LUP showed 19.7% of polyclonal infections, and its genetic diversity (Hexp) was 0.544. Temporal analysis showed a significant increment of polyclonal infections and Hexp, and the introduction and persistence of a new parasite population since March 2013. In STE, 40.1% of infections were polyclonal, with Hexp = 0.596. The presence of four genetic clusters without signals of clonal expansion and infections with lower parasite densities compared against the other two areas were also found. At least four parasite populations were present in CAH in 2012, where, after June 2014, malaria cases decreased from 213 to 61, concomitant with a decrease in polyclonal infections (from 0.286 to 0.18), and expectedly variable Hexp. Strong signals of gene flow were present in the study areas and wide geographic distribution of highly diverse parasite populations were found. This study suggests that movement of malaria parasites by human reservoirs connects geographically distant malaria transmission areas in the Peruvian Amazon. The maintenance of high levels of parasite genetic diversity through human mobility is a critical barrier to malaria elimination in this region.