Willingness-to-Pay for Halal and Branded Poultry in Northern Mozambique

While price typically drives consumers’ food purchasing decisions in low-income countries, religious attributes associated with food production and corporate branding could influence buying patterns. In Mozambique more than 46% of people were living below the poverty line of ($0.31 USD) per day in 2018. That being said, in the Nampula Province (the location of this study), which is the second poorest province in the country, over 25% of the population is Muslim and may be willing-to-pay (WTP) a premium for Halal meat products to uphold Islamic beliefs. Like many parts of sub-Saharan Africa, poultry is the fastest growing source of protein. Since large-scale domestic poultry industries are relatively new in Mozambique, brand loyalty is a new concept that has not empirically analyzed before in the literature. In this study we survey 312 consumers in Nampula, Mozambique using a Choice Based Modeling approach to estimate if consumers are WTP for chicken which was slaughtered according to Halal laws and chicken which branded by New Horizons (the largest chicken producer in Nampula). The results of this study are important as they show if consumers in low-income countries are WTP a premium for branded commodities and if consumers are WTP for religious production attributes. Following data collection using a researcher-developed survey instrument, logistic regression models were estimated using maximum-likelihood techniques to evaluate poultry-attribute preferences (independence was rejected). A random parameters logit (RPL) model estimated the mean and standard deviation associated with each attribute’s effect on the probability of purchasing poultry. Marginal WTP values were computed with respect to the price coefficient. Results of our sample could indicate that even in low-income countries like Mozambique, consumers are WTP a premium for branding. This would signal a need for further research in the future to determine if these results are generalizable to countries with similar economic structure. In communities like Nampula, this branding could be a proxy for food safety concerns, and these results are important as in many low-income countries commodities (such as live/processed chickens) have no branding associated with them. Even in the poorest part of Mozambique, Muslims are WTP a premium for Halal produced meat. This should signal to meat producers to market appropriately (via the Halal logo) in order to increase market share and overall sales without the exploitation (via price increases) of consumers. Interestingly, across the sample Halal was not a signal for food safety or quality, it was viewed simply as a religious attribute. These data are applicable to a real-world problem; the study was built around a real company in Mozambique, and the data will be shared with New Horizons to improve marketing efforts and hopefully increase accessibility and education about commodity products in third-world countries

Willingness-to-Pay for Halal and Branded Poultry in Northern Mozambique

While price typically drives consumers’ food-purchasing decisions in low-income countries, religious attributes associated with food production and corporate branding could influence buying patterns. In Mozambique, more than 46% of people were living below the poverty line of ($0.31 USD) per day in 2018. That being said, in the Nampula Province (the location of this study), which is the second poorest province in the country, over 25% of the population is Muslim and may be willing-to-pay (WTP) a premium for Halal meat products to uphold Islamic beliefs. Like many parts of sub-Saharan Africa, poultry is the fastest-growing source of protein. Since large-scale domestic poultry industries are relatively new in Mozambique, brand loyalty is a new concept that has not been empirically analyzed before in the literature. In this study, we surveyed 312 consumers in Nampula, Mozambique, using a choice-based modeling approach to estimate if consumers were WTP for chicken that was slaughtered according to Halal laws and chicken which was branded by New Horizons (the largest chicken producer in Nampula). Results from the small sample in this study indicated that even in low-income countries like Mozambique, consumers are WTP a premium for branding. Specifically, Muslim consumers were WTP a premium for Halal-produced meat with branding. While non-Muslims did associate Halal poultry with being safer (69%) and of better quality (64%), but they were not found to be WTP a premium for these attributes

Quantitative genome re-sequencing defines multiple mutations conferring chloroquine resistance in rodent malaria

<p>Abstract</p> <p>Background</p> <p>Drug resistance in the malaria parasite <it>Plasmodium falciparum </it>severely compromises the treatment and control of malaria. A knowledge of the critical mutations conferring resistance to particular drugs is important in understanding modes of drug action and mechanisms of resistances. They are required to design better therapies and limit drug resistance.</p> <p>A mutation in the gene (<it>pfcrt</it>) encoding a membrane transporter has been identified as a principal determinant of chloroquine resistance in <it>P</it>. <it>falciparum</it>, but we lack a full account of higher level chloroquine resistance. Furthermore, the determinants of resistance in the other major human malaria parasite, <it>P. vivax</it>, are not known. To address these questions, we investigated the genetic basis of chloroquine resistance in an isogenic lineage of rodent malaria parasite <it>P. chabaudi </it>in which high level resistance to chloroquine has been progressively selected under laboratory conditions.</p> <p>Results</p> <p>Loci containing the critical genes were mapped by Linkage Group Selection, using a genetic cross between the high-level chloroquine-resistant mutant and a genetically distinct sensitive strain. A novel high-resolution quantitative whole-genome re-sequencing approach was used to reveal three regions of selection on chr11, chr03 and chr02 that appear progressively at increasing drug doses on three chromosomes. Whole-genome sequencing of the chloroquine-resistant parent identified just four point mutations in different genes on these chromosomes. Three mutations are located at the foci of the selection valleys and are therefore predicted to confer different levels of chloroquine resistance. The critical mutation conferring the first level of chloroquine resistance is found in <it>aat1</it>, a putative aminoacid transporter.</p> <p>Conclusions</p> <p>Quantitative trait loci conferring selectable phenotypes, such as drug resistance, can be mapped directly using progressive genome-wide linkage group selection. Quantitative genome-wide short-read genome resequencing can be used to reveal these signatures of drug selection at high resolution. The identities of three genes (and mutations within them) conferring different levels of chloroquine resistance generate insights regarding the genetic architecture and mechanisms of resistance to chloroquine and other drugs. Importantly, their orthologues may now be evaluated for critical or accessory roles in chloroquine resistance in human malarias <it>P. vivax </it>and <it>P. falciparum</it>.</p

Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites

<p>Abstract</p> <p>Background</p> <p>Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine <it>in vivo </it>experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, <it>Plasmodium chabaudi</it>. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, <it>P. falciparum</it>.</p> <p>Results</p> <p>A lineage of isogenic <it>in vivo </it>drug-selected mutant <it>P. chabaudi </it>parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an <it>in vivo </it>artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (Illumina^®Solexa) defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme.</p> <p>Conclusions</p> <p>This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations.</p

Unstructured proteins of the malaria parasite Plasmodium falciparum as vaccine candidates

Malaria vaccine research has been battling with persistent challenges, including polymorphisms of vaccine antigens, difficulties with production processes, and limited immune protection against the disease. Intrinsically unstructured proteins (IUPs) are a fairly newly classified group of proteins that have no stable 3D structure and are generally heat-resistant. They usually contain low complexity regions and repetitive sequences, both of which are distinct characteristics of the malaria proteome. Surprisingly, some of the vaccine candidates that have been extensively studied were later reported to have unstructured regions, some of which serve as targets of protective immunity. In keeping with their interesting immunological profiles and their unique properties, which are exceptionally beneficial for vaccine production, malarial IUP antigens may be good vaccine candidates. This PhD project has the following aims:- 1) to develop a synthetic unstructured protein antigen based on the Block 2 region of MSP-1, named the MSP-1 hybrid 2) to characterize a novel vaccine antigen derived from the MSP-3.3 protein, namely an IUP region of PF10_0347 gene product, for its potential as a vaccine candidate 3) to develop a second-generation vaccine by combining the MSP-1 hybrid, with two allelic variants of MSP-2, to overcome antigenic polymorphism and strain-specific immune responses 4) to validate protocols for IUP identification from proteins extracted from the malaria parasite. This study showed that 1) MSP-1 hybrid production was scalable, yielding high protein yields with comparable immunological properties to small-scale production. MSP-1 hybrid was shown to be compatible with different adjuvants, and elicited specific antibodies covering the whole range of Block 2 allelic diversities. 2) A novel antigen, MSP-3.3C, an IUP based on the 3’ region of the PF10_0347 gene, was cloned, expressed and purified. Anti-MSP3.3C antibodies showed very strong parasite growth inhibitory effects in vitro. 3) The MSP-multihybrid antigen was expressed using simple techniques, but only at low levels. It contains epitopes from all three parasite antigen components, and is recognized by specific naturally acquired antibodies. 4) an unconventional 2D gel technique was tested as a method of malaria parasite IUP identification. Plans for further validation of this technique were discussed

Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A real‐world intention‐to‐treat analysis

Brexucabtagene autoleucel (brexu‐cel) is an autologous CD19 CAR T‐cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA‐2, brexu‐cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real‐world intention‐to‐treat (ITT) outcomes for brexu‐cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu‐cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow‐up of 13.3 months, median progression‐free survival (PFS) for infused patients was 21 months (10.1–NA) with a 6‐ and 12‐month PFS of 82% (95% confidence interval [CI], 71–89) and 62% (95% CI, 49–73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non‐relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA‐2 and other real‐world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention

A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens

Gene encoding a deubiquitinating enzyme is mutated in artesunate- and chloroquine-resistant rodent malaria parasites§

Artemisinin- and artesunate-resistant Plasmodium chabaudi mutants, AS-ART and AS-ATN, were previously selected from chloroquine-resistant clones AS-30CQ and AS-15CQ respectively. Now, a genetic cross between AS-ART and the artemisinin-sensitive clone AJ has been analysed by Linkage Group Selection. A genetic linkage group on chromosome 2 was selected under artemisinin treatment. Within this locus, we identified two different mutations in a gene encoding a deubiquitinating enzyme. A distinct mutation occurred in each of the clones AS-30CQ and AS-ATN, relative to their respective progenitors in the AS lineage. The mutations occurred independently in different clones under drug selection with chloroquine (high concentration) or artesunate. Each mutation maps to a critical residue in a homologous human deubiquitinating protein structure. Although one mutation could theoretically account for the resistance of AS-ATN to artemisinin derivates, the other cannot account solely for the resistance of AS-ART, relative to the responses of its sensitive progenitor AS-30CQ. Two lines of Plasmodium falciparum with decreased susceptibility to artemisinin were also selected. Their drug-response phenotype was not genetically stable. No mutations in the UBP-1 gene encoding the P. falciparum orthologue of the deubiquitinating enzyme were observed. The possible significance of these mutations in parasite responses to chloroquine or artemisinin is discussed

Structural models for the protein family characterized by gamete surface protein Pfs230 of Plasmodium falciparum

Ps230 is the largest representative of a 10-member family of proteins found in all Plasmodium species. The family is defined by partially conserved, cysteine-rich double domains that are ≈350 aa in length and have one to three predicted disulfide bridges in each half. In Plasmodium falciparum, the most dangerous human malaria, Pf12 is the smallest member of the family, comprising just one double domain. Pfs230, with 7 double domains, and Pfs48/45 and Pfs47, with 1.5 double domains each, are found on the gamete surfaces and are thus potential candidates for a transmission-blocking vaccine. Fold prediction analyses of the double domains in Pfs230 reveal structural resemblance to SAG1 (surface antigen 1), a surface protein with a double β-sandwich structure from another apicomplexan parasite, Toxoplasma gondii. Template-directed modeling onto SAG1 clearly establishes the structural link between SAG1 and Pfs230 and produces positions for the cysteines that accord with the disulfide-bonding arrangement predicted for the Pfs230 family in earlier work. A highly clustered region of polymorphisms within the second double domain in Pfs230 maps to one side of the sandwich surface. This observation suggests that this region may be functional and reinforces the validity of these molecular models for the core domains of the Pfs230 family of proteins