Perspectives of vector management in the control and elimination of vector-borne zoonoses

The complex transmission profiles of vector-borne zoonoses (VZB) and vector-borne infections with animal reservoirs (VBIAR) complicate efforts to break the transmission circuit of these infections. To control and eliminate VZB and VBIAR, insecticide application may not be conducted easily in all circumstances, particularly for infections with sylvatic transmission cycle. As a result, alternative approaches have been considered in the vector management against these infections. In this review, we highlighted differences among the environmental, chemical, and biological control approaches in vector management, from the perspectives of VZB and VBIAR. Concerns and knowledge gaps pertaining to the available control approaches were discussed to better understand the prospects of integrating these vector control approaches to synergistically break the transmission of VZB and VBIAR in humans, in line with the integrated vector management (IVM) developed by the World Health Organization (WHO) since 2004

The role of rosette formation in pathogenesis of vivax malaria / Lee Wenn Chyau

Rosette formation is one of the unique biological phenomena that have been linked to pathobiology of malaria. It is believe to be associated with the severe outcomes of falciparum malaria. Most of the knowledge about rosetting is obtained from in-depth studies conducted on Plasmodium falciparum. However, the rosetting phenomenon and pathobiology of vivax malaria is not well studied. This research project aimed at deciphering the unknown aspects behind rosetting phenomenon of P. vivax, and investigating the role of rosette formation in pathobiology of vivax malaria. In total, 121 fresh P. vivax isolates, 48 cryopreserved P. vivax isolates, 122 fresh P. falciparum isolates and 5 cryopreserved P. falciparum isolates were recruited into this research project. A novel technique suitable for reticulocyte characterization and rosetting assay in field setting was developed from this research project. Based on the field studies conducted, rosette formation is common in P. vivax. However, rosetting is not significantly correlated to clinical parameters such as reticulocyte count and parasitaemia. Besides, cryopreservation and thawing processes affect the rosetting capability of P. vivax isolates. Rosette formation was found to be initiated at the early trophozoite stage of P. vivax and the rosetting development reached plateau at the end of the erythrocytic maturation. Giant rosettes were found more frequently in P. vivax than P. falciparum. In addition, gametocytes were found to be involved in rosette formation. Unlike P. falciparum, the rosetting phenomenon of P. vivax is independent of human ABO blood groups and complement receptor 1 (CR1/CD35). However, rosetting phenomena of P. vivax and P. falciparum are dependent on the BRIC4 region of human glycophorin C (CD236R), strongly indicating the BRIC4 region of CD236R as another rosetting coreceptor for P. vivax and P. falciparum. On elucidating the roles of rosette formation in pathobiology of malaria, the significantly high preference for normocytes instead of reticulocytes in rosette formation clearly shows that rosetting is iii unlikely to assist merozoite reinvasion in vivax malaria. Furthermore, increased rosetting rates upon exposure to anti-malaria drug compounds and human white blood cells suggest that the rosetting phenomenon may serve as an intrinsic protective mechanism of the malaria parasites against their environmental threats

The Impact of Geographical Variation in <i>Plasmodium knowlesi</i> Apical Membrane Protein 1 (PkAMA-1) on Invasion Dynamics of <i>P. knowlesi</i>

Plasmodium knowlesi has emerged as an important zoonotic parasite that causes persistent symptomatic malaria in humans. The signs and symptoms of malaria are attributed to the blood stages of the parasites, which start from the invasion of erythrocytes by the blood stage merozoites. The apical membrane protein 1 (AMA-1) plays an important role in the invasion. In this study, we constructed and expressed recombinant PkAMA-1 domain II (PkAMA-1-DII) representing the predominant haplotypes from Peninsular Malaysia and Malaysian Borneo and raised specific antibodies against the recombinant proteins in rabbits. Despite the minor amino acid sequence variation, antibodies raised against haplotypes from Peninsular Malaysia and Malaysian Borneo demonstrated different invasion inhibition (46.81% and 39.45%, respectively) to P. knowlesi A1-H.1, a reference strain derived from Peninsular Malaysia. Here, we demonstrated how a minor variation in a conserved parasite protein could cast a significant impact on parasite invasion biology, suggesting a complex host-switching of P. knowlesi from different locations. This may challenge the implementation of a standardized One Health approach against the transmission of knowlesi malaria

Cytoadherence properties of Plasmodium knowlesi-infected erythrocytes

Plasmodium knowlesi is responsible for zoonotic malaria infections that are potentially fatal. While the severe pathology of falciparum malaria is associated with cytoadherence phenomena by Plasmodium falciparum-infected erythrocytes (IRBC), information regarding cytoadherence properties of P. knowlesi-IRBC remained scarce. Here, we characterized the cytoadherence properties of RBC infected with the laboratory-adapted P. knowlesi A1-H.1 strain. We found that late-stage IRBC formed rosettes in a human serum-dependent manner, and rosettes hampered IRBC phagocytosis. IRBC did not adhere much to unexposed (unstimulated) human endothelial cell lines derived from the brain (hCMEC/D3), lungs (HPMEC), and kidneys (HRGEC). However, after being "primed" with P. knowlesi culture supernatant, the IRBC-endothelial cytoadherence rate increased in HPMEC and HRGEC, but not in hCMEC/D3 cells. Both endothelial cytoadherence and rosetting phenomena were abrogated by treatment of P. knowlesi-IRBC with trypsin. We also found that different receptors were involved in IRBC cytoadherence to different types of endothelial cells. Although some of the host receptors were shared by both P. falciparum- and P. knowlesi-IRBC, the availability of glycoconjugates on the receptors might influence the capacity of P. knowlesi-IRBC to cytoadhere to these receptors.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Published versionW-CL, SN, and LR were supported by core funding from A ∗ STAR. W-CL was funded by the Open Fund-Young Individual Research Grant (OF-YIRG NMRC/OFYIRG/0070/2018). LR was funded by A∗ STAR grant (JCO-DP BMSI/15-800006-SIGN) and Singapore Ministry of Education AcRF Tier 3 grant (MOE2019- T3-1-007). SN was also supported by a postgraduate scholarship from the Yong Loo Lin School of Medicine, NUS

Digital microscope-assisted photography improves the accuracy of mosquito wing measurement

Wing measurement is an important parameter in many entomological studies. However, the methods of measuring wings vary with studies, and a gold standard method was not available for this procedure. This in turn limits researchers from confidently comparing their research findings with published data collected by other means of measurement. This study investigated the interchangeability of three commonly available methods for wing measurement, namely the calliper method, stereomicroscope-assisted photography method, and digital microscope-assisted photography method, using the laboratory colony of Aedes aegypti. It was found that the calliper method and the photography-based methods yielded similar results, hence the good interchangeability of these methods. Nevertheless, the digital microscope-assisted photography method yielded more accurate measurements, due to the higher resolution of the captured photos, and minimal technical bias during the data collection, as compared to the calliper-based and stereomicroscope-assisted photography methods. This study served as a reference for researchers to select the most suitable measurement method in future studies

Draft genome of Brugia pahangi: high similarity between B. pahangi and B. malayi

BACKGROUND: Efforts to completely eradicate lymphatic filariasis from human population may be challenged by the emergence of Brugia pahangi as another zoonotic lymphatic filarial nematode. In this report, a genomic study was conducted to understand this species at molecular level. METHODS: After blood meal on a B. pahangi-harbouring cat, the Aedes togoi mosquitoes were maintained to harvest infective third stage larvae, which were then injected into male Mongolian gerbils. Subsequently, adult B. pahangi were obtained from the infected gerbil for genomic DNA extraction. Sequencing and subsequently, construction of genomic libraries were performed. This was followed by genomic analyses and gene annotation analysis. By using archived protein sequences of B. malayi and a few other nematodes, clustering of gene orthologs and phylogenetics were conducted. RESULTS: A total of 9687 coding genes were predicted. The genome of B. pahangi shared high similarity to that B. malayi genome, particularly genes annotated to fundamental processes. Nevertheless, 166 genes were considered to be unique to B. pahangi, which may be responsible for the distinct properties of B. pahangi as compared to other filarial nematodes. In addition, 803 genes were deduced to be derived from Wolbachia, an endosymbiont bacterium, with 44 of these genes intercalate into the nematode genome. CONCLUSIONS: The reporting of B. pahangi draft genome contributes to genomic archive. Albeit with high similarity to B. malayi genome, the B. pahangi-unique genes found in this study may serve as new focus to study differences in virulence, vector selection and host adaptability among different Brugia spp. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1064-2) contains supplementary material, which is available to authorized users

Plasmodium falciparum rosetting protects schizonts against artemisinin

Background Artemisinin (ART) resistance in Plasmodium falciparum is thought to occur during the early stage of the parasite's erythrocytic cycle. Here, we identify a novel factor associated with the late stage parasite development that contributes to ART resistance. Methods Rosetting rates of clinical isolates pre- and post- brief (one hour) exposure to artesunate (AS, an ART derivative) were evaluated. The effects of AS-mediated rosetting on the post-AS-exposed parasite's replication and survival, as well as the extent of protection by AS-mediated rosetting on different parasite stages were investigated. The rosetting ligands, mechanisms, and gene mutations involved were studied. Findings Brief AS exposure stimulated rosetting, with AS-resistant isolates forming more rosettes in a more rapid manner. AS-mediated rosetting enabled infected erythrocytes (IRBC) to withstand AS exposure for several hours and protected the IRBC from phagocytosis. When their rosetting ability was blocked experimentally, the post-AS exposure survival advantage by the AS-resistant parasites was abrogated. Deletions in two genes coding for PfEMP1 exon 2 (PF3D7_0200300 and PF3D7_0223300) were found to be associated with AS-mediated rosetting, and these mutations were significantly selected through time in the parasite population under study, along with the K13 mutations, a molecular marker of ART-resistance. Interpretation Rapid ART parasite clearance is driven by the direct oxidative damages on IRBC by ART and the phagocytic destruction of the damaged IRBC. Rosetting serves as a rapid ‘buying time’ strategy that allows more parasites to complete schizont maturation, reinvasion and subsequent development into the intrinsically less ART-susceptible ring stage. Funding A*STAR, NMRC-OF-YIRG, HRC e-ASIA, Wellcome