Genetic and genomic approaches for the discovery of parasite genes involved in antimalarial drug resistance

The biggest threat to the war on malaria is the continued evolution of drug resistance by the parasite. Resistance to almost all currently available antimalarials now exists in Plasmodium falciparum which causes the most suffering among all human malaria parasites. Monitoring of antimalarial efficacy and the development and subsequent spread of resistance has become an important part in the treatment and control of malaria. With recent reports of reduced efficacy of artemisinin, the current recommended treatment for uncomplicated malaria, there is urgent need for better methods to recognize and monitor drug resistance for effective treatment. Molecular markers have become a welcome addition to complement the more laborious and costly in vitro and in vivo methods that have traditionally been used to monitor drug resistance. However, there are currently no molecular markers for resistance to some antimalarials. This review highlights the role of the various genetic and genomic approaches that have been used in identifying the molecular markers that underlie drug resistance in P. falciparum. These approaches include; candidate genes, genetic linkage and genome-wide association studies. We discuss the requirements and limitations of each approach and use various examples to illustrate their contributions in identifying genomic regions of the parasite associated with antimalarial drug responses

Developing a workbook for primary care nursing students

There is a continuing need to prepare a nursing workforce that is adaptable within a range of care settings. The faculty of health at Staffordshire University seconded a lecturer practitioner for a 12-month period to conduct an audit on primary care placements. Mentors were involved in the audit in order to include their views and opinions alongside those of students

Uptake of purines in <i>Plasmodium falciparum</i>-infected human erythrocytes is mostly mediated by the human Equilibrative Nucleoside Transporter and the human Facilitative Nucleobase Transporter

&lt;b&gt;Background&lt;/b&gt;: Plasmodium parasites are unable to synthesize purines de novo and have to salvage them from the host. Due to this limitation in the parasite, purine transporters have been an area of focus in the search for anti-malarial drugs. Although the uptake of purines through the human equilibrative nucleoside transporter (hENT1), the human facilitative nucleobase transporter (hFNT1) and the parasite-induced new permeation pathway (NPP) has been studied, no information appears to exist on the relative contribution of these three transporters to the uptake of adenosine and hypoxanthine. Using the appropriate transporter inhibitors, the role of each of these salvage pathways to the overall purine transport in intraerythrocytic Plasmodium falciparum was systematically investigated. &lt;b&gt;Methods&lt;/b&gt;: The transport of adenosine, hypoxanthine and adenine into uninfected and P. falciparum-infected human erythrocytes was investigated in the presence or absence of classical inhibitors of the hFNT1, hENT1 and NPP. The effective inhibition of the various transporters by the classical inhibitors was verified using appropriate known substrates. The ability of high concentration of unlabelled substrates to saturate these transporters was also studied. &lt;b&gt;Results&lt;/b&gt;: Transport of exogenous purine into infected or uninfected erythrocytes occurred primarily through saturable transporters rather than through the NPP. Hypoxanthine and adenine appeared to enter erythrocytes mainly through the hFNT1 nucleobase transporter whereas adenosine entered predominantly through the hENT1 nucleoside transporter. The rate of purine uptake was approximately doubled in infected cells compared to uninfected erythrocytes. In addition, it was found that the rate of adenosine uptake was considerably higher than the rate of hypoxanthine uptake in infected human red blood cells (RBC). It was also demonstrated that furosemide inhibited the transport of purine bases through hFNT1. &lt;b&gt;Conclusion&lt;/b&gt;: Collectively, the data obtained in this study clearly show that the endogenous host erythrocyte transporters hENT1 and hFNT1, rather than the NPP, are the major route of entry of purine into parasitized RBC. Inhibitors of hENT1 and hFNT1, as well as the NPP, should be considered in the development of anti-malarials targeted to purine transport

The impact of uniform and mixed species blood meals on the fitness of the mosquito vector Anopheles gambiae s.s: does a specialist pay for diversifying its host species diet?

We investigated the fitness consequences of specialization in an organism whose host choice has an immense impact on human health: the African malaria vector Anopheles gambiae s.s. We tested whether this mosquito’s specialism on humans can be attributed to the relative fitness benefits of specialist vs. generalist feeding strategies by contrasting their fecundity and survival on human-only and mixed host diets consisting of blood meals from humans and animals. When given only one blood meal, An. gambiae s.s. survived significantly longer on human and bovine blood, than on canine or avian blood. However, when blood fed repeatedly, there was no evidence that the fitness of An. gambiae s.s. fed a human-only diet was greater than those fed generalist diets. This suggests that the adoption of generalist host feeding strategies in An. gambiae s.s. is not constrained by intraspecific variation in the resource quality of blood from other available host species

Radical popular education today. Popular education in populist times

Popular education is more needed than ever. The Covid 19 pandemic has been highlighting the challenges of widening inequalities, increasing exploitation and oppression, along with persistent xenophobia and violence against women and minority communities. Yet popular education faces threats of its own, and resources have been on the decline, precisely when they have become so urgently required in the contemporary context. Whilst acknowledging these threats, the article goes on to focus on some of the ways in which popular education initiatives have continued to be promoted despite these wider challenges. ‘The World Transformed’ (TWT) has provided evidence of just such initiatives in Britain.The conclusions of TWT’s research resonate with Paulo Freire’s own reflections in the final section of ‘The Pedagogy of Hope’. Despite the challenges he continued to look forward to the future with hope. (DIPF/Orig.

Characterisation of species and diversity of Anopheles gambiae Keele Colony

Anopheles gambiae sensu stricto was recently reclassified as two species, An. coluzzii and An. gambiae s.s., in wild-caught mosquitoes, on the basis of the molecular form, denoted M or S, of a marker on the X chromosome. The An. gambiae Keele line is an outbred laboratory colony strain that was developed around 12 years ago by crosses between mosquitoes from 4 existing An. gambiae colonies. Laboratory colonies of mosquitoes often have limited genetic diversity because of small starting populations (founder effect) and subsequent fluctuations in colony size. Here we describe the characterisation of the chromosomal form(s) present in the Keele line, and investigate the diversity present in the colony using microsatellite markers on chromosome 3. We also characterise the large 2La inversion on chromosome 2. The results indicate that only the M-form of the chromosome X marker is present in the Keele colony, which was unexpected given that 3 of the 4 parent colonies were probably S-form. Levels of diversity were relatively high, as indicated by a mean number of microsatellite alleles of 6.25 across 4 microsatellites, in at least 25 mosquitoes. Both karyotypes of the inversion on chromosome 2 (2La/2L+a) were found to be present at approximately equal proportions. The Keele colony has a mixed M- and S-form origin, and in common with the PEST strain, we propose continuing to denote it as an An. gambiae s.s. line

Bis(thio­semicarbazide)nickel(II) bis­[2-(thio­semicarbazonometh­yl)benzene­sulfonate] dihydrate

In the title compound, [Ni(CH5N3S)2](C8H8N3O3S2)2·2H2O, the NiII atom lies on a inversion centre and is four-coordinated by two N and two S atoms of two thio­semicarbazide ligands in an almost square-planar coordination. In the crystal structure, the molecules are linked into a three-dimensional network via C—H⋯O, C—H⋯N, N—H⋯O, N—H⋯S and O—H⋯O hydrogen bonds

Diaqua­bis(5-methyl­pyridine-2-carboxyl­ato-κ2 N,O)zinc(II)

In the title compound, [Zn(C7H6NO2)2(H2O)2], the Zn atom (site symmetry ) adopts a distorted trans-ZnN2O4 octa­hedral coordination arising from two N,O-bidentate 5-methyl­pyridine-2-carboxyl­ate ligands and two water mol­ecules. In the crystal structure, mol­ecules form a layered network linked by O—H⋯O hydrogen bonds

Editorial: Special issue avian malaria

Avian malaria parasites or haemosporidia are found in bird species worldwide. This special issue focusses on three most commonly studied genera: Haemoproteus, Plasmodium and Leucocytozoon. Seven research articles and reviews are provided to illustrate the breadth of knowledge of the diversity of avian malaria parasites in different regional habitats and across bird species, and the use of avian haemosporidian systems to examine host-parasite ecoevolutionary questions