Dispersal of engineered male Aedes aegypti mosquitoes

BACKGROUND:Aedes aegypti, the principal vector of dengue fever, have been genetically engineered for use in a sterile insect control programme. To improve our understanding of the dispersal ecology of mosquitoes and to inform appropriate release strategies of 'genetically sterile' male Aedes aegypti detailed knowledge of the dispersal ability of the released insects is needed. METHODOLOGY/PRINCIPAL FINDINGS:The dispersal ability of released 'genetically sterile' male Aedes aegypti at a field site in Brazil has been estimated. Dispersal kernels embedded within a generalized linear model framework were used to analyse data collected from three large scale mark release recapture studies. The methodology has been applied to previously published dispersal data to compare the dispersal ability of 'genetically sterile' male Aedes aegypti in contrasting environments. We parameterised dispersal kernels and estimated the mean distance travelled for insects in Brazil: 52.8 m (95% CI: 49.9 m, 56.8 m) and Malaysia: 58.0 m (95% CI: 51.1 m, 71.0 m). CONCLUSIONS/SIGNIFICANCE:Our results provide specific, detailed estimates of the dispersal characteristics of released 'genetically sterile' male Aedes aegypti in the field. The comparative analysis indicates that despite differing environments and recapture rates, key features of the insects' dispersal kernels are conserved across the two studies. The results can be used to inform both risk assessments and release programmes using 'genetically sterile' male Aedes aegypti

Health inequities and clustering of fever, acute respiratory infection, diarrhoea and wasting in children under five in low- and middle-income countries: a Demographic and Health Surveys analysis

BACKGROUND: Pneumonia, diarrhoea and malaria are responsible for over one third of all deaths in children under the age of 5 years in low and middle sociodemographic index countries; many of these deaths are also associated with malnutrition. We explore the co-occurrence and clustering of fever, acute respiratory infection, diarrhoea and wasting and their relationship with equity-relevant variables. METHODS: Multilevel, multivariate Bayesian logistic regression models were fitted to Demographic and Health Survey data from over 380,000 children in 39 countries. The relationship between outcome indicators (fever, acute respiratory infection, diarrhoea and wasting) and equity-relevant variables (wealth, access to health care and rurality) was examined. We quantified the geographical clustering and co-occurrence of conditions and a child's risk of multiple illnesses. RESULTS: The prevalence of outcomes was very heterogeneous within and between countries. There was marked spatial clustering of conditions and co-occurrence within children. For children in the poorest households and those reporting difficulties accessing healthcare, there were significant increases in the probability of at least one of the conditions in 18 of 21 countries, with estimated increases in the probability of up to 0.23 (95% CrI, 0.06-0.40). CONCLUSIONS: The prevalence of fever, acute respiratory infection, diarrhoea and wasting are associated with equity-relevant variables and cluster together. Via pathways of shared aetiology or risk, those children most disadvantaged disproportionately suffer from these conditions. This highlights the need for horizontal approaches, such as integrated community case management, with a focus on equity and targeted to those most at need

Assessing the impact of intervention strategies against Taenia solium cysticercosis using the EPICYST transmission model

Background The pork tapeworm, Taenia solium, and associated human infections, taeniasis, cysticercosis and neurocysticercosis, are serious public health problems, especially in developing countries. The World Health Organization (WHO) has set goals for having a validated strategy for control and elimination of T. solium taeniasis/cysticercosis by 2015 and interventions scaled-up in selected countries by 2020. Timely achievement of these internationally-endorsed targets requires that the relative benefits and effectiveness of potential interventions be explored rigorously within a quantitative framework. Methods A deterministic, compartmental transmission model (EPICYST) was developed to capture the dynamics of the taeniasis/cysticercosis disease system in the human and pig hosts. Cysticercosis prevalence in humans, an outcome of high epidemiological and clinical importance, was explicitly modelled. A next generation matrix approach was used to derive an expression for the basic reproduction number, R 0. A full sensitivity analysis was performed using a methodology based on Latin-hypercube sampling partial rank correlation coefficient index. Results EPICYST outputs indicate that chemotherapeutic intervention targeted at humans or pigs would be highly effective at reducing taeniasis and cysticercosis prevalence when applied singly, with annual chemotherapy of humans and pigs resulting, respectively, in 94 and 74% of human cysticercosis cases averted. Improved sanitation, meat inspection and animal husbandry are less effective but are still able to reduce prevalence singly or in combination. The value of R 0 for taeniasis was estimated at 1.4 (95% Credible Interval: 0.5–3.6). Conclusions Human- and pig-targeted drug-focussed interventions appear to be the most efficacious approach from the options currently available. The model presented is a forward step towards developing an informed control and elimination strategy for cysticercosis. Together with its validation against field data, EPICYST will be a valuable tool to help reach the WHO goals and to conduct economic evaluations of interventions in varying epidemiological settings

False-negative malaria rapid diagnostic test results and their impact on community-based malaria surveys in sub- Saharan Africa

Surveillance and diagnosis of Plasmodium falciparum malaria relies predominantly on rapid diagnostic tests (RDTs). However, false-negative RDT results are known to occur for a variety of reasons, including operator error, poor storage conditions, pfhrp2/3 gene deletions, poor performance of specific RDT brands and lots, and low-parasite-density infections. We used RDT and microscopy results from 85,000 children enrolled in Demographic Health Surveys and Malaria Indicator Surveys from 2009 to 2015 across 19 countries to explore the distribution of and risk factors for false-negative RDTs in Sub40 Saharan Africa, where malaria’s impact is greatest. We sought to (i) identify spatial and demographic patterns of false-negative RDT (FN-RDT) results, defined as a negative RDT but positive gold-standard microscopy test, and (ii) estimate the percentage of infections missed within community-based malaria surveys due to FN-RDT results. Across all studies, 19.9% [95% CI: 19.0 – 20.9] of microscopy-positive subjects were negative by RDT. The distribution of FN-RDT results was spatially heterogeneous. The variance in FN-RDT results was best explained by the prevalence of malaria, with an increase in FN46 RDT results observed at lower transmission intensities, among younger subjects, and in urban areas. The observed proportion of FN-RDT results was not predicted by differences in RDT brand or lot performance alone. These findings characterise how the probability of detection by RDTs varies in different transmission settings and emphasize the need for careful interpretation of prevalence estimates based on surveys employing RDTs alone. Further studies are needed to characterise the cost-effectiveness of improved malaria diagnostics (e.g. PCR or highly sensitive RDTs) in community52 based surveys, especially in regions of low transmission intensity or high urbanicity

Report 43: Quantifying the impact of vaccine hesitancy in prolonging the need for Non-Pharmaceutical Interventions to control the COVID-19 pandemic

Vaccine hesitancy – a delay in acceptance or refusal of vaccines despite availability 1 – has the potential to threaten the successful roll-out of SARS-CoV-2 vaccines globally 2 . Here, we evaluate the potential impact of vaccine hesitancy on the control of the pandemic and the relaxation of non-pharmaceutical interventions (NPIs) by combining an epidemiological model of SARS-CoV-2 transmission 3 with data on vaccine hesitancy from population surveys. Our findings suggest that the mortality over a 2-year period could be up to 8 times higher in countries with high vaccine hesitancy compared to an ideal vaccination uptake if NPIs are relaxed. Alternatively, high vaccine hesitancy could prolong the need for NPIs to remain in place. Addressing vaccine hesitancy with behavioural interventions is therefore an important priority in the control of the COVID-19 pandemic

Assessment of the Impact of Potential Tetracycline Exposure on the Phenotype of Aedes aegypti OX513A: Implications for Field Use

Aedes aegypti is the primary vector of dengue fever, a viral disease which has an estimated incidence of 390 million infections annually. Conventional vector control methods have been unable to curb the transmission of the disease. We have previously reported a novel method of vector control using a tetracycline repressible self-limiting strain of Ae. aegypti OX513A which has achieved >90% suppression of wild populations.We investigated the impact of tetracycline and its analogues on the phenotype of OX513A from the perspective of possible routes and levels of environmental exposure. We determined the minimum concentration of tetracycline and its analogues that will allow an increased survivorship and found these to be greater than the maximum concentration of tetracyclines found in known Ae. aegypti breeding sites and their surrounding areas. Furthermore, we determined that OX513A parents fed tetracycline are unable to pre-load their progeny with sufficient antidote to increase their survivorship. Finally, we studied the changes in concentration of tetracycline in the mass production rearing water of OX513A and the developing insect.Together, these studies demonstrate that potential routes of exposure of OX513A individuals to tetracycline and its analogues in the environment are not expected to increase the survivorship of OX513A

Board Ethics and Auditor Choice – International Evidence

2 Board Ethics and Auditor Choice – International Evidence ABSTRACT This study examines whether firms‟ auditor choice relates reflects the strength of board ethics. Using a large sample of firms 132,853 firm year observations from forty-six countries around the globe. and controlling for a number of firm- and country-level factors, we find that firms in countries where “high board ethical values” prevail are more likely to hire a Big 4 auditor. We also find that the relation between board ethical values and auditor choice is mitigated by the firm‟s board size. These results establish an indirect link between board ethics and financial reporting quality through the firm‟s choice of auditor

Seasonal use case for the RTS,S/AS01 malaria vaccine: a mathematical modelling study

BACKGROUND: A 2021 clinical trial of seasonal RTS,S/AS01E (RTS,S) vaccination showed that vaccination was non-inferior to seasonal malaria chemoprevention (SMC) in preventing clinical malaria. The combination of these two interventions provided significant additional protection against clinical and severe malaria outcomes. Projections of the effect of this novel approach to RTS,S vaccination in seasonal transmission settings for extended timeframes and across a range of epidemiological settings are needed to inform policy recommendations. METHODS: We used a mathematical, individual-based model of malaria transmission that was fitted to data on the relationship between entomological inoculation rate and parasite prevalence, clinical disease, severe disease, and deaths from multiple sites across Africa. The model was validated with results from a phase 3b trial assessing the effect of SV-RTS,S in Mali and Burkina Faso. We developed three intervention efficacy models with varying degrees and durations of protection for our population-level modelling analysis to assess the potential effect of an RTS,S vaccination schedule based on age (doses were delivered to children aged 6 months, 7·5 months, and 9 months for the first three doses, and at 27 months of age for the fourth dose) or season (children aged 5-17 months at the time of first vaccination received the first three doses in the 3 months preceding the transmission season, with any subsequent doses up to five doses delivered annually) in seasonal transmission settings both in the absence and presence of SMC with sulfadoxine-pyrimethamine plus amodiaquine. This is modelled as a full therapeutic course delivered every month for four or five months of the peak in transmission season. Estimates of cases and deaths averted in a population of 100 000 children aged 0-5 years were calculated over a 15-year time period for a range of levels of malaria transmission intensity (Plasmodium falciparum parasite prevalence in children aged 2-10 years between 10% and 65%) and over two west Africa seasonality archetypes. FINDINGS: Seasonally targeting RTS,S resulted in greater absolute reductions in malaria cases and deaths compared with an age-based strategy, averting an additional 14 000-47 000 cases per 100 000 children aged 5 years and younger over 15 years, dependent on seasonality and transmission intensity. We predicted that adding seasonally targeted RTS,S to SMC would reduce clinical incidence by up to an additional 42 000-67 000 cases per 100 000 children aged 5 years and younger over 15 years compared with SMC alone. Transmission season duration was a key determinant of intervention effect, with the advantage of adding RTS,S to SMC predicted to be smaller with shorter transmission seasons. INTERPRETATION: RTS,S vaccination in seasonal settings could be a valuable additional tool to existing interventions, with seasonal delivery maximising the effect relative to an age-based approach. Decisions surrounding deployment strategies of RTS,S in such settings will need to consider the local and regional variations in seasonality, current rates of other interventions, and potential achievable RTS,S coverage. FUNDING: UK Medical Research Council, UK Foreign Commonwealth & Development Office, The Wellcome Trust, and The Royal society