Inclusion of marginalized populations in HPV vaccine modeling: A systematic review.

OBJECTIVE: Models simulating the potential impacts of Human Papillomavirus (HPV) vaccine have been used globally to guide vaccination policies and programs. We sought to understand how and why marginalized populations have been incorporated into HPV vaccine simulation models. METHODS: We conducted a systematic search of PubMed, CINAHL, Scopus, and Embase to identify studies using simulation models of HPV vaccination incorporating one or more marginalized population through stratification or subgroup analysis. We extracted data on study characteristics and described these overall and by included marginalized groups. RESULTS: We identified 36 studies that met inclusion criteria, which modeled vaccination in 21 countries. Models included men who have sex with men (MSM; k = 16), stratification by HIV status (k = 9), race/ethnicity (k = 6), poverty (k = 5), rurality (k = 4), and female sex workers (k = 1). When evaluating for a marginalized group (k = 10), HPV vaccination was generally found to be cost-effective, including for MSM, individuals living with HIV, and rural populations. In studies evaluating equity in cancer prevention (k = 9), HPV vaccination generally advanced equity, but this was sensitive to differences in HPV vaccine uptake and use of absolute or relative measures of inequities. Only one study assessed the impact of an intervention promoting HPV vaccine uptake. DISCUSSION: Incorporating marginalized populations into decision models can provide valuable insights to guide decision making and improve equity in cancer prevention. More research is needed to understand the equity impact of HPV vaccination on cancer outcomes among marginalized groups. Research should emphasize implementation - including identifying and evaluating specific interventions to increase HPV vaccine uptake.

Educational and economic returns to cognitive ability in low- and middle-income countries: A systematic review.

There is growing interest to use early cognitive ability to predict schooling and employment outcomes in low- and middle-income countries (LMICs). Rather than using educational attainment and school enrollment as predictors of future economic growth or of improving an individual's earning potential, mounting evidence suggests that cognitive ability may be a better predictor. The relationship between cognitive ability, education, and employment are essential to predict future development in LMICs. We performed a systematic literature review and meta-analysis of the evidence regarding the relationship between cognitive ability and educational outcomes, and between cognitive ability and economic outcomes across LMICs. We searched peer-reviewed studies since 2000 that quantitatively measured these relationships. Based on an initial search of 3,766 records, we identified 14 studies, including 8 studies that examined the cognition-education link and 8 studies that assessed cognition-employment returns in LMICs. Identified studies showed that higher cognitive ability increased the probability of school enrollment, academic achievement, and educational attainment across LMICs. A meta-analysis of returns to wages from cognitive ability suggested that a standard deviation increase in cognitive test scores was associated with a 4.5% (95% CI 2.6%-9.6%) increase in wages. Investments into early cognitive development could play a critical role in improving educational and economic outcomes in LMICs. Further research should focus particularly in low-income countries with the least evidence, and examine the impact on education and economic outcomes by cognitive domains to provide more robust evidence for policy makers to take action.

Impact of substandard and falsified antimalarials in Zambia: application of the SAFARI model.

BACKGROUND: Many countries are striving to become malaria-free, but global reduction in case estimates has stagnated in recent years. Substandard and falsified medicines may contribute to this lack of progress. Zambia aims to eliminate their annual burden of 1.2 million pediatric malaria cases and 2500 child deaths due to malaria. We examined the health and economic impact of poor-quality antimalarials in Zambia. METHODS: An agent-based model, Substandard and Falsified Antimalarial Research Impact (SAFARI), was modified and applied to Zambia. The model was developed to simulate population characteristics, malaria incidence, patient care-seeking, disease progression, treatment outcomes, and associated costs of malaria for children under age five. Zambia-specific demographic, epidemiological, and cost inputs were extracted from the literature. Simulations were run to estimate the health and economic impact of poor-quality antimalarials, the effect of potential artemisinin resistance, and six additional malaria focused policy interventions. RESULTS: We simulated annual malaria cases among Zambian children under five. At baseline, we found 2610 deaths resulting in $141.5 million in annual economic burden of malaria. We estimated that elimination of substandard and falsified antimalarials would result in an 8.1% (n = 213) reduction in under-five deaths, prevent 937 hospitalizations, and realize $8.5 million in economic savings, annually. Potential artemisinin resistance could further increase deaths by 6.3% (n = 166) and cost an additional $9.7 million every year. CONCLUSIONS: Eliminating substandard and falsified antimalarials is an important step towards a malaria-free Zambia. Beyond the dissemination of insecticide-treated bed nets, indoor residual spraying, and other malaria control measures, attention must also be paid to assure the quality of antimalarial treatments.

Development of an agent-based model to assess the impact of substandard and falsified anti-malarials: Uganda case study.

BACKGROUND: Global efforts to address the burden of malaria have stagnated in recent years with malaria cases beginning to rise. Substandard and falsified anti-malarial treatments contribute to this stagnation. Poor quality anti-malarials directly affect health outcomes by increasing malaria morbidity and mortality, as well as threaten the effectiveness of treatment by contributing to artemisinin resistance. Research to assess the scope and impact of poor quality anti-malarials is essential to raise awareness and allocate resources to improve the quality of treatment. A probabilistic agent-based model was developed to provide country-specific estimates of the health and economic impact of poor quality anti-malarials on paediatric malaria. This paper presents the methodology and case study of the Substandard and Falsified Antimalarial Research Impact (SAFARI) model developed and applied to Uganda. RESULTS: The total annual economic impact of malaria in Ugandan children under age five was estimated at US$614 million. Among children who sought medical care, the total economic impact was estimated at $403 million, including $57.7 million in direct costs. Substandard and falsified anti-malarials were a significant contributor to this annual burden, accounting for $31 million (8% of care-seeking children) in total economic impact involving $5.2 million in direct costs. Further, 9% of malaria deaths relating to cases seeking treatment were attributable to poor quality anti-malarials. In the event of widespread artemisinin resistance in Uganda, we simulated a 12% yearly increase in costs associated with paediatric malaria cases that sought care, inflicting $48.5 million in additional economic impact annually. CONCLUSIONS: Improving the quality of treatment is essential to combat the burden of malaria and prevent the development of drug resistance. The SAFARI model provides country-specific estimates of the health and economic impact of substandard and falsified anti-malarials to inform governments, policy makers, donors and the malaria community about the threat posed by poor quality medicines. The model findings are useful to illustrate the significance of the issue and inform policy and interventions to improve medicinal quality.

Complete genome sequence of maize sterile stunt virus.

Based on serology, cytopathology, cereal host range and leafhopper vector, maize sterile stunt virus (MSSV) has been regarded as a strain of the cytorhabdovirus barley yellow striate mosaic virus (BYSMV). Here, we report the first-ever sequence of MSSV, comprising the complete genome of 12,561 nucleotides. Detailed analysis of genome organization, coding and non-coding sequences, and phylogeny confirms the close relationship to BYSMV and supports classification of this virus a strain of BYSMV.

First complete genome sequence of vanilla mosaic strain of Dasheen mosaic virus isolated from the Cook Islands.

We present the first complete genome of vanilla mosaic virus (VanMV). The VanMV genomic structure is consistent with that of a potyvirus, containing a single open reading frame (ORF) encoding a polyprotein of 3139 amino acids. Motif analyses indicate the polyprotein can be cleaved into the expected ten individual proteins; other recognised potyvirus motifs are also present. As expected, the VanMV genome shows high sequence similarity to the published Dasheen mosaic virus (DsMV) genome sequences; comparisons with DsMV continue to support VanMV as a vanilla infecting strain of DsMV. Phylogenetic analyses indicate that VanMV and DsMV share a common ancestor, with VanMV having the closest relationship with DsMV strains from the South Pacific.

Taxonomy of the order Mononegavirales: update 2017.

In 2017, the order Mononegavirales was expanded by the inclusion of a total of 69 novel species. Five new rhabdovirus genera and one new nyamivirus genus were established to harbor 41 of these species, whereas the remaining new species were assigned to already established genera. Furthermore, non-Latinized binomial species names replaced all paramyxovirus and pneumovirus species names, thereby accomplishing application of binomial species names throughout the entire order. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Diversity and evolutionary history of lettuce necrotic yellows virus in Australia and New Zealand.

Lettuce necrotic yellows virus (LNYV) is the type member of the genus Cytorhabdovirus, family Rhabdoviridae, and causes a severe disease of lettuce (Lactuca sativa L.). This virus has been described as endemic to Australia and New Zealand, with sporadic reports of a similar virus in Europe. Genetic variability studies of plant-infecting rhabdoviruses are scarce. We have extended a previous study on the variability of the LNYV nucleocapsid gene, comparing sequences from isolates sampled from both Australia and New Zealand, as well as analysing symptom expression on Nicotiana glutinosa. Phylogenetic and BEAST analyses confirm separation of LNYV isolates into two subgroups (I and II) and suggest that subgroup I is slightly older than subgroup II. No correlation was observed between isolate subgroup and disease symptoms on N. glutinosa. The origin of LNYV remains unclear; LNYV may have moved between native and weed hosts within Australia or New Zealand before infecting lettuce or may have appeared as a result of at least two incursions, with the first coinciding with the beginning of European agriculture in the region. The apparent extinction of subgroup I in Australia may have been due to less-efficient dispersal than that which has occurred for subgroup II - possibly a consequence of suboptimal interactions with plant and/or insect hosts. Introduction of subgroup II to New Zealand appears to be more recent. More-detailed epidemiological studies using molecular tools are needed to fully understand how LNYV interacts with its hosts and to determine where the virus originated.

Complete genome sequence of Colocasia bobone disease-associated virus, a putative cytorhabdovirus infecting taro.

We report the first genome sequence of a Colocasia bobone disease-associated virus (CBDaV) derived from bobone-affected taro [Colocasia esculenta L. Schott] from Solomon Islands. The negative-strand RNA genome is 12,193 nt long, with six major open reading frames (ORFs) with the arrangement 3'-N-P-P3-M-G-L-5'. Typical of all rhabdoviruses, the 3' leader and 5' trailer sequences show complementarity to each other. Phylogenetic analysis indicated that CBDaV is a member of the genus Cytorhabdovirus, supporting previous reports of virus particles within the cytoplasm of bobone-infected taro cells. The availability of the CBDaV genome sequence now makes it possible to assess the role of this virus in bobone, and possibly alomae disease of taro and confirm that this sequence is that of Colocasia bobone disease virus (CBDV).

First complete genome sequence of a capsicum chlorosis tospovirus isolate from Australia with an unusually large S RNA intergenic region.

The first complete genome sequence of capsicum chlorosis virus (CaCV) from Australia was determined using a combination of Illumina HiSeq RNA and Sanger sequencing technologies. Australian CaCV had a tripartite genome structure like other CaCV isolates. The large (L) RNA was 8913 nucleotides (nt) in length and contained a single open reading frame (ORF) of 8634 nt encoding a predicted RNA-dependent RNA polymerase (RdRp) in the viral-complementary (vc) sense. The medium (M) and small (S) RNA segments were 4846 and 3944 nt in length, respectively, each containing two non-overlapping ORFs in ambisense orientation, separated by intergenic regions (IGR). The M segment contained ORFs encoding the predicted non-structural movement protein (NSm; 927 nt) and precursor of glycoproteins (GP; 3366 nt) in the viral sense (v) and vc strand, respectively, separated by a 449-nt IGR. The S segment coded for the predicted nucleocapsid (N) protein (828 nt) and non-structural suppressor of silencing protein (NSs; 1320 nt) in the vc and v strand, respectively. The S RNA contained an IGR of 1663 nt, being the largest IGR of all CaCV isolates sequenced so far. Comparison of the Australian CaCV genome with complete CaCV genome sequences from other geographic regions showed highest sequence identity with a Taiwanese isolate. Genome sequence comparisons and phylogeny of all available CaCV isolates provided evidence for at least two highly diverged groups of CaCV isolates that may warrant re-classification of AIT-Thailand and CP-China isolates as unique tospoviruses, separate from CaCV.

Calcium-dependent protein kinases in plants: evolution, expression and function.

Calcium-dependent protein kinases (CPKs) are plant proteins that directly bind calcium ions before phosphorylating substrates involved in metabolism, osmosis, hormone response and stress signaling pathways. CPKs are a large multigene family of proteins that are present in all plants studied to date, as well as in protists, oomycetes and green algae, but are not found in animals and fungi. Despite the increasing evidence of the importance of CPKs in developmental and stress responses from various plants, a comprehensive genome-wide analysis of CPKs from algae to higher plants has not been undertaken. This paper describes the evolution of CPKs from green algae to plants using a broadly sampled phylogenetic analysis and demonstrates the functional diversification of CPKs based on expression and functional studies in different plant species. Our findings reveal that CPK sequence diversification into four major groups occurred in parallel with the terrestrial transition of plants. Despite significant expansion of the CPK gene family during evolution from green algae to higher plants, there is a high level of sequence conservation among CPKs in all plant species. This sequence conservation results in very little correlation between CPK evolutionary groupings and functional diversity, making the search for CPK functional orthologs a challenge.

Identification of the Microbiota in Coconut Water, Kefir, Coconut Water Kefir and Coconut Water Kefir-Fermented Sourdough Using Culture-Dependent Techniques and Illumina-MiSeq Sequencing.

The principal objective of this study was to isolate and identify the microorganisms present in commercial kefir grains, a novel kefir-fermented coconut water (CWK) and a novel coconut water kefir-fermented sourdough using phenotypic identification and Sanger sequencing and examine the microbial diversity of CWK and CWK-fermented sourdough throughout the fermentation process using the MiSeq Illumina sequencing method. The phenotypic characterisation based on morphology identified ten isolates of LAB, five AAB and seven yeasts from kefir (K), CWK and CWK-fermented sourdough (CWKS). The results confirm the presence of the LAB species Limosilactobacillus fermentum, Lactobacillus. plantarum, L. fusant, L. reuteri and L. kunkeei; the AAB species Acetobacter aceti, A. lovaniensis and A. pasteurianus; and the yeast species Candida kefyr, Rhodotorula mucilaginosa, Saccharomyces cerevisiae, C. guilliermondii and C. colliculosa. To the best of our knowledge, the identification of Rhodotorula from kefir is being reported for the first time. This study provides important insights into the relative abundances of the microorganisms in CWKS. A decrease in pH and an increase in the titratable acidity for CWK- and CWK-fermented sourdough corresponded to the increase in D- and L-lactic acid production after 96 h of fermentation. Significant reductions in the pHs of CWK and CWKS were observed between 48 and 96 h of fermentation, indicating that the kefir microorganisms were able to sustain highly acidic environments. There was also increased production of L-lactic acid with fermentation, which was almost twice that of D-lactic acid in CWK.

Benefits, challenges, and strategies related to using presumptive recommendations for HPV vaccination: A qualitative study with rural and non-rural-serving primary care professionals.

HPV vaccination coverage remains far below the national target of 80% among US adolescents, particularly in rural areas, which have vaccine uptake rates that are 10% points lower than non-rural areas on average. Primary care professionals (PCPs) can increase coverage by using presumptive recommendations to introduce HPV vaccination in a way that assumes parents want to vaccinate. Through semi-structured interviews, we explored PCPs' experiences and perceptions of using presumptive recommendations in rural- and non-rural-serving primary care clinics in North Carolina. Thematic analysis revealed that most PCPs in rural and non-rural contexts used presumptive recommendations and felt the strategy was an effective and concise way to introduce the topic of HPV vaccination to parents. At the same time, some PCPs raised concerns about presumptive recommendations potentially straining relationships with certain parents, including those who had previously declined HPV vaccine or who distrust medical authority due to their past experiences with the healthcare system. PCPs dealt with these challenges by using a more open-ended approach when introducing HPV vaccination to parents. In conclusion, our findings suggest that PCPs in both rural and non-rural settings see value in using presumptive recommendations to introduce HPV vaccination, but to adequately address concerns and ensure increased HPV vaccine uptake, PCPs can use simple and culturally sensitive language to ensure fully informed consent and to maintain parental trust. And to further strengthen HPV vaccine discussions, PCPs can utilize other effective HPV communication techniques, like the Announcement Approach, in discussing HPV vaccinations with hesitant parents.

Modeling the economic burden of postpartum hemorrhage due to substandard uterotonics in Ghana.

Uterotonics are essential in preventing postpartum hemorrhage (PPH), the leading direct cause of maternal death worldwide. However, uterotonics are often substandard in low- and middle-income countries, contributing to poor maternal health outcomes. This study examines the health and economic impact of substandard uterotonics in Ghana. A decision-tree model was built to simulate vaginal and cesarean section births across health facilities, uterotonic quality and utilization, PPH risk and diagnosis, and resulting health and economic outcomes. We utilized delivery data from Ghana's maternal health survey, risks of health outcomes from a Cochrane review, and E-MOTIVE trial data for health outcomes related to oxytocin quality. We compared scenarios with and without substandard uterotonics, as well as scenarios altering uterotonic use and care-seeking behaviors. We found that substandard uterotonic use contributes to $18.8 million in economic burden annually, including $6.3 million and $4.8 million in out-of-pocket expenditures in public and private sectors, respectively. Annually, the National Health Insurance Scheme bears $1.6 million in costs due to substandard uterotonic use. Substandard uterotonics contribute to $6 million in long-term productivity losses from maternal mortality annually. Improving the quality of uterotonics could reduce 20,000 (11%) PPH cases, 5,000 (11%) severe PPH cases, and 100 (11%) deaths due to PPH annually in Ghana. Ensuring the quality of uterotonics would result in millions of dollars in cost savings and improve maternal health outcomes for the government and families in Ghana. Cost savings from improving uterotonic quality would provide financial protection and help Ghana advance toward Universal Health Coverage.

Comparing the return on investment of technologies to detect substandard and falsified amoxicillin: A Kenya case study.

The prevalence of substandard and falsified medicines in low- and middle-income countries (LMICs) is a major global public health concern. Multiple screening technologies for post-market surveillance of medicine quality have been developed but there exists no clear guidance on which technology is optimal for LMICs. This study examined the return on investment (ROI) of implementing a select number of screening technologies for post-market surveillance of amoxicillin quality in a case study of Kenya. An agent-based model, Examining Screening Technologies using Economic Evaluations for Medicines (ESTEEM), was developed to estimate the costs, benefits, and ROI of implementing screening technologies for post-market surveillance of substandard and falsified amoxicillin for treatment of pediatric pneumonia in Kenya. The model simulated sampling, testing, and removal of substandard and falsified amoxicillin from the Kenyan market using five screening technologies: (1) Global Pharma Health Fund's GPHF-Minilab, (2) high-performance liquid chromatography (HPLC), (3) near-infrared spectroscopy (NIR), (4) paper analytical devices / antibiotic paper analytical devices (PADs/aPADs), and (5) Raman spectroscopy. The study team analyzed the population impact of utilizing amoxicillin for the treatment of pneumonia in children under age five in Kenya. We found that the GPHF-Minilab, NIR, and PADs/aPADs were similar in their abilities to rapidly screen for and remove substandard and falsified amoxicillin from the Kenyan market resulting in a higher ROI compared to HPLC. NIR and PADs/aPADs yielded the highest ROI at $21 (90% Uncertainty Range (UR) $5-$51) each, followed by GPHF-Minilab ($16, 90%UR $4 - $38), Raman ($9, 90%UR $2 - $21), and HPLC ($3, 90%UR $0 - $7). This study highlights screening technologies that can be used to reduce costs, speed up the removal of poor-quality medicines, and consequently improve health and economic outcomes in LMICs. National medicine regulatory authorities should adopt these fast, reliable, and low-cost screening technologies to better detect substandard and falsified medicines, reserving HPLC for confirmatory tests.

Modeling the Health and Economic Impact of Substandard and Falsified Medicines: A Review of Existing Models and Approaches.

Substandard and falsified medicines are harmful to patients, causing prolonged illness, side effects, and preventable deaths. Moreover, they have an impact on the health system and society more broadly by leading to additional care, higher disease burden, productivity losses and loss of trust in health care. Models that estimate the health and economic impacts of substandard and falsified medicines can be useful for regulators to contextualize the problem and to make an economic case for solutions. Yet these models have not been systematically catalogued to date. We reviewed existing models that estimate the health and economic impact of substandard and falsified medicines to describe the varying modeling approaches and gaps in knowledge. We compared model characteristics, data sources, assumptions, and limitations. Seven models were identified. The models assessed the impact of antimalarial (n = 5) or antibiotic (n = 2) quality at a national (n = 4), regional (n = 2), or global (n = 1) level. Most models conducted uncertainty analysis and provided ranges around potential outcomes. We found that models are lacking for other medicines, few countries' data have been analyzed, and capturing population heterogeneity remains a challenge. Providing the best estimates of the impact of substandard and falsified medicines on a level that is actionable for decision-makers is important. To enable this, research on the impact of substandard and falsified medicines should be expanded to more medicine types and classes and tailored to more countries that are affected, with greater specificity.

Characterizing Medicine Quality by Active Pharmaceutical Ingredient Levels: A Systematic Review and Meta-Analysis across Low- and Middle-Income Countries.

Substandard and falsified medicines are often reported jointly, making it difficult to recognize variations in medicine quality. This study characterized medicine quality based on active pharmaceutical ingredient (API) amounts reported among substandard and falsified essential medicines in low- and middle-income countries (LMICs). A systematic review and meta-analysis was conducted using PubMed, supplemented by results from a previous systematic review, and the Medicine Quality Scientific Literature Surveyor. Study quality was assessed using the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). Random-effects models were used to estimate the prevalence of medicines with < 50% API. Among 95,520 medicine samples from 130 studies, 12.4% (95% confidence interval [CI]: 10.2-14.6%) of essential medicines tested in LMICs were considered substandard or falsified, having failed at least one type of quality analysis. We identified 99 studies that reported API content, where 1.8% (95% CI: 0.8-2.8%) of samples reported containing < 50% of stated API. Among all failed samples (N = 9,724), 25.9% (95% CI: 19.3-32.6%) reported having < 80% API. Nearly one in seven (13.8%, 95% CI: 9.0-18.6%) failed samples were likely to be falsified based on reported API amounts of < 50%, whereas the remaining six of seven samples were likely to be substandard. Furthermore, 12.5% (95% CI: 7.7-17.3%) of failed samples reported finding 0% API. Many studies did not present a breakdown of actual API amount of each tested sample. We offer suggested improved guidelines for reporting poor-quality medicines. Consistent data on substandard and falsified medicines and medicine-specific tailored interventions are needed to ensure medicine quality throughout the supply chain.

The Potential of Molecular Indicators of Plant Virus Infection: Are Plants Able to Tell Us They Are Infected?

To our knowledge, there are no reports that demonstrate the use of host molecular markers for the purpose of detecting generic plant virus infection. Two approaches involving molecular indicators of virus infection in the model plant Arabidopsis thaliana were examined: the accumulation of small RNAs (sRNAs) using a microfluidics-based method (Bioanalyzer); and the transcript accumulation of virus-response related host plant genes, suppressor of gene silencing 3 (AtSGS3) and calcium-dependent protein kinase 3 (AtCPK3) by reverse transcriptase-quantitative PCR (RT-qPCR). The microfluidics approach using sRNA chips has previously demonstrated good linearity and good reproducibility, both within and between chips. Good limits of detection have been demonstrated from two-fold 10-point serial dilution regression to 0.1 ng of RNA. The ratio of small RNA (sRNA) to ribosomal RNA (rRNA), as a proportion of averaged mock-inoculation, correlated with known virus infection to a high degree of certainty. AtSGS3 transcript decreased between 14- and 28-days post inoculation (dpi) for all viruses investigated, while AtCPK3 transcript increased between 14 and 28 dpi for all viruses. A combination of these two molecular approaches may be useful for assessment of virus-infection of samples without the need for diagnosis of specific virus infection.

Is the Glycoprotein Responsible for the Differences in Dispersal Rates between Lettuce Necrotic Yellows Virus Subgroups?

Lettuce necrotic yellows virus is a type of species in the Cytorhabdovirus genus and appears to be endemic to Australia and Aotearoa New Zealand (NZ). The population of lettuce necrotic yellows virus (LNYV) is made up of two subgroups, SI and SII. Previous studies demonstrated that SII appears to be outcompeting SI and suggested that SII may have greater vector transmission efficiency and/or higher replication rate in its host plant or insect vector. Rhabdovirus glycoproteins are important for virus-insect interactions. Here, we present an analysis of LNYV glycoprotein sequences to identify key features and variations that may cause SII to interact with its aphid vector with greater efficiency than SI. Phylogenetic analysis of glycoprotein sequences from NZ isolates confirmed the existence of two subgroups within the NZ LNYV population, while predicted 3D structures revealed the LNYV glycoproteins have domain architectures similar to Vesicular Stomatitis Virus (VSV). Importantly, changing amino acids at positions 244 and 247 of the post-fusion form of the LNYV glycoprotein altered the predicted structure of Domain III, glycosylation at N248 and the overall stability of the protein. These data support the glycoprotein as having a role in the population differences of LNYV observed between Australia and New Zealand.