The scientific community recognizes that molecular xenomonitoring (MX) can allow infected mosquitoes to serve as a proxy for human infection in vector-borne disease surveillance, but developing ...reliable MX systems for programmatic use has been challenging. The primary aim of this article is to examine the available evidence to recommend how MX can best be used for various purposes. Although much of the literature published within the last 20 years focuses on using MX for lymphatic filariasis elimination, a growing body of evidence supports its use in early warning systems for emerging infectious diseases (EIDs). An MX system design must consider the goal and target (e.g. diseases targeted for elimination versus EIDs), mosquito and pathogen characteristics, and context (e.g. setting and health system). MX is currently used as a 'supplement' to human surveillance and will not be considered as a 'replacement' until the correlation between pathogen-infection rates in human and mosquito populations is better understood. Establishing such relationships may not be feasible in elimination scenarios, due to increasingly dwindling human infection prevalence after successful control, but may still be possible for EIDs and in integrated disease surveillance systems. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.
Objectives
To determine the capacity of black soldier fly larvae (BSFL) (Hermetia illucens) to convert fresh human faeces into larval biomass under different feeding regimes, and to determine how ...effective BSFL are as a means of human faecal waste management.
Methods
Black soldier fly larvae were fed fresh human faeces. The frequency of feeding, number of larvae and feeding ratio were altered to determine their effects on larval growth, prepupal weight, waste reduction, bioconversion and feed conversion rate (FCR).
Results
The larvae that were fed a single lump amount of faeces developed into significantly larger larvae and prepupae than those fed incrementally every 2 days; however, the development into pre‐pupae took longer. The highest waste reduction was found in the group containing the most larvae, with no difference between feeding regimes. At an estimated 90% pupation rate, the highest bioconversion (16–22%) and lowest, most efficient FCR (2.0–3.3) occurred in groups that contained 10 and 100 larvae, when fed both the lump amount and incremental regime.
Conclusion
The prepupal weight, bioconversion and FCR results surpass those from previous studies into BSFL management of swine, chicken manure and municipal organic waste. This suggests that the use of BSFL could provide a solution to the health problems associated with poor sanitation and inadequate human waste management in developing countries.
ObjectifsDéterminer la capacité de la larve de la mouche soldat noir (LMSN) (Hermetia illucens) à convertir les matières fécales humaines fraîches en biomasse larvaire sous différents régimes d'alimentation et déterminer dans quelle mesure la LMNS peut être efficace comme moyen de gestion des déchets fécaux humains.MéthodesDes larves de la mouche soldat noir ont été nourries avec des matières fécales humaines fraîches. La fréquence d'alimentation, le nombre de larves et le taux d'alimentation ont été modifiés afin de déterminer leurs effets sur la croissance larvaire, le poids pré‐pupal, la réduction des déchets, la bioconversion et le taux de conversion alimentaire (TCA).RésultatsLes larves qui ont été nourries avec une quantité forfaitaire unique de selles se sont développées de façon beaucoup plus importante en larves et pré‐pupes que celles nourries progressivement tous les deux jours. Cependant, le développement en pré‐pupes a pris plus de temps. La réduction la plus élevée des déchets a été constatée dans le groupe contenant plus de larves, sans différence entre les régimes alimentaires. À un taux estimé à 90% de pupes, la plus haute bioconversion (16–22%) et la plus faible, plus efficace TCA (2.0–3.3) sont survenues dans les groupes qui contenaient 10 et 100 larves, nourries soit avec une quantité forfaitaire ou selon un régime progressif.ConclusionLes résultats sur le poids pré‐pupal, la bioconversion et le TCA dépassent ceux des études précédentes sur la gestion de déchets de porcs, de fumier de poulet et organiques municipaux en utilisant la LMSN. Ceci suggère que l'utilisation de la LMSN pourrait apporter une solution aux problèmes de santé liés à l'insalubrité et à la mauvaise gestion des déchets humains dans les pays en développement.
ObjetivosDeterminar la capacidad de las larvas de la mosca soldado negra (LMSN) (Hermetia illucens) de convertir heces humanas frescas en biomasa larval bajo diferentes regímenes de alimentación, y determinar que tan efectivas son las LMSN como instrumento para el manejo de residuos de heces humanas.MétodosLas larvas de la mosca soldado negra fueron alimentadas con heces humanas frescas. La frecuencia con la que eran alimentadas, el número de larvas y la tasa de alimentación fueron alteradas para determinar sus efectos sobre el crecimiento de las larvas, el peso de la prepupa, la reducción de los desechos, la bioconversión y el índice de conversión del alimento (ICA).ResultadosLas larvas que fueron alimentadas con una única cantidad de heces se desarrollaron en larvas y prepupas significativamente más grandes que aquellas alimentadas de forma incremental cada dos días; sin embargo, el desarrollo en prepupas tomó más tiempo. La mayor reducción de se observó en el grupo que contenía más larvas, sin diferencia entre los regímenes de alimentación. Con una tasa estimada de pupación del 90%, la mayor bioconversión (16–22%) y la menor, más eficiente ICA (2.0–3.3), ocurrió en grupos que contenían 10 y 100 larvas, cuando se alimentaban tanto con una cantidad única como con el régimen incremental.ConclusiónEl peso de la prepupa, la bioconversión y los resultados del ICA sobrepasan aquellos de estudios previos en el manejo de desechos orgánicos municipales, o provenientes del ganado o las gallinas con LMSN. Esto sugiere que el uso de LMSN podría ofrecer una solución a los problemas de salud asociados con unas condiciones sanitarias pobres y al manejo inadecuado de desechos humanos en países en vías de desarrollo.
Novel control strategies for mosquito-borne diseases Jones, Robert T; Ant, Thomas H; Cameron, Mary M ...
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
02/2021, Letnik:
376, Številka:
1818
Journal Article
Recenzirano
Odprti dostop
Mosquito-borne diseases are an increasing global health challenge, threatening over 40% of the world's population. Despite major advances in malaria control since 2000, recent progress has stalled. ...Additionally, the risk of
-borne arboviruses is rapidly growing, with the unprecedented spread of dengue and chikungunya viruses, outbreaks of yellow fever and the 2015 epidemic of Zika virus in Latin America. To counteract this growing problem, diverse and innovative mosquito control technologies are currently under development. Conceptually, these span an impressive spectrum of approaches, from invasive transgene cassettes with the potential to crash mosquito populations or reduce the vectorial capacity of a population, to low-cost alterations in housing design that restrict mosquito entry. This themed issue will present articles providing insight into the breadth of mosquito control research, while demonstrating the requirement for an interdisciplinary approach. The issue will highlight mosquito control technologies at varying stages of development and includes both opinion pieces and research articles with laboratory and field-based data on control strategy development. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.
Tisagenlecleucel is a CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and ...adults with non-Hodgkin lymphoma (NHL). The initial experience with tisagenlecleucel in a real-world setting from a cellular therapy registry is presented here. As of January 2020, 511 patients were enrolled from 73 centers, and 410 patients had follow-up data reported (ALL, n = 255; NHL, n = 155), with a median follow-up of 13.4 and 11.9 months for ALL and NHL, respectively. Among patients with ALL, the initial complete remission (CR) rate was 85.5%. Twelve-month duration of response (DOR), event-free survival, and overall survival (OS) rates were 60.9%, 52.4%, and 77.2%, respectively. Among adults with NHL, the best overall response rate was 61.8%, including an initial CR rate of 39.5%. Six-month DOR, progression-free survival, and OS rates were 55.3%, 38.7%, and 70.7%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 11.6% and 7.5% of all patients, respectively. Similar outcomes were observed in patients with in-specification and out-of-specification products as a result of viability <80% (range, 61% to 79%). This first report of tisagenlecleucel in the real-world setting demonstrates outcomes with similar efficacy and improved safety compared with those seen in the pivotal trials.
•Represents the largest set of safety and efficacy data for tisagenlecleucel.•Outcomes in the real-world setting are similar to results in the pivotal trials.
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To assess the effectiveness of community-wide deployment of insecticide-impregnated collars for dogs- the reservoir of Leishmania infantum-to reduce infantile clinical visceral leishmaniasis (VL).
A ...pair matched-cluster randomised controlled trial involving 40 collared and 40 uncollared control villages (161 95% C.L.s: 136, 187 children per cluster), was designed to detect a 55% reduction in 48 month confirmed VL case incidence. The intervention study was designed by the authors, but implemented by the Leishmaniasis Control Program in NW Iran, from 2002 to 2006.
The collars provided 50% (95% C.I. 17·8%-70·0%) protection against infantile VL incidence (0·95/1000/yr compared to 1·75/1000/yr). Reductions in incidence were observed across 76% (22/29) of collared villages compared to pair-matched control villages, with 31 fewer cases by the end of the trial period. In 11 paired villages, no further cases were recorded post-intervention, whereas in 7 collared villages there were 9 new clinical cases relative to controls. Over the trial period, 6,835 collars were fitted at the beginning of the 4 month sand fly season, of which 6.9% (95% C.I. 6.25%, 7.56%) were lost but rapidly replaced. Collar coverage (percent dogs collared) per village varied between 66% and 100%, with a mean annual coverage of 87% (95% C.I. 84·2, 89·0%). The variation in post-intervention clinical VL incidence was not associated with collar coverage, dog population size, implementation logistics, dog owner compliance, or other demographic variables tested. Larger reductions and greater persistence in incident case numbers (indicative of transmission) were observed in villages with higher pre-existing VL case incidence.
Community-wide deployment of collars can provide a significant level of protection against infantile clinical VL, achieved in this study by the local VL Control Program, demonstrating attributes desirable of a sustainable public health program. The effectiveness is not dissimilar to the community-level protection provided against human and canine infection with L. infantum.
Background The kala-azar elimination programme has resulted in a significant reduction in visceral leishmaniasis (VL) cases across the Indian Subcontinent. To detect any resurgence of transmission, a ...sensitive cost-effective surveillance system is required. Molecular xenomonitoring (MX), detection of pathogen DNA/RNA in vectors, provides a proxy of human infection in the lymphatic filariasis elimination programme. To determine whether MX can be used for VL surveillance in a low transmission setting, large numbers of the sand fly vector Phlebotomus argentipes are required. This study will determine the best method for capturing P. argentipes females for MX. Methodology/Principal findings The field study was performed in two programmatic and two non-programmatic villages in Bihar, India. A total of 48 households (12/village) were recruited. Centers for Disease Control and Prevention light traps (CDC-LTs) were compared with Improved Prokopack (PKP) and mechanical vacuum aspirators (MVA) using standardised methods. Four 12x12 Latin squares, 576 collections, were attempted (12/house, 144/village,192/method). Molecular analyses of collections were conducted to confirm identification of P. argentipes and to detect human and Leishmania DNA. Operational factors, such as time burden, acceptance to householders and RNA preservation, were also considered. A total of 562 collections (97.7%) were completed with 6,809 sand flies captured. Females comprised 49.0% of captures, of which 1,934 (57.9%) were identified as P. argentipes. CDC-LTs collected 4.04 times more P. argentipes females than MVA and 3.62 times more than PKP (p<0.0001 for each). Of 21,735 mosquitoes in the same collections, no significant differences between collection methods were observed. CDC-LTs took less time to install and collect than to perform aspirations and their greater yield compensated for increased sorting time. No significant differences in Leishmania RNA detection and quantitation between methods were observed in experimentally infected sand flies maintained in conditions simulating field conditions. CDC-LTs were favoured by householders. Conclusions/Significance CDC-LTs are the most useful collection tool of those tested for MX surveillance since they collected higher numbers of P. argentipes females without compromising mosquito captures or the preservation of RNA. However, capture rates are still low.
This is the first study to show that enjoyment for high-intensity interval exercise increases with chronic training. Prior acute studies typically report high-intensity interval training (HIT) as ...being more enjoyable than moderate continuous training (MCT) unless the high-intensity intervals are too strenuous or difficult to complete. It follows that exercise competency may be a critical factor contributing to the enjoyment of HIT, and therefore building competency through chronic training may be one way to increase its enjoyment. To test this, we randomly assigned sedentary young adults to six weeks of HIT or MCT, and tracked changes in their enjoyment for the exercise. Enjoyment for HIT increased with training whereas enjoyment for MCT remained constant and lower. Changes in exercise enjoyment were predicted by increases in workload, suggesting that strength adaptions may be important for promoting exercise enjoyment. The results point to HIT as a promising protocol for promoting exercise enjoyment and adherence in sedentary young adults.
Background The elimination programme for visceral leishmaniasis (VL) in India has seen great progress, with total cases decreasing by over 80% since 2010 and many blocks now reporting zero cases from ...year to year. Prompt diagnosis and treatment is critical to continue progress and avoid epidemics in the increasingly susceptible population. Short-term forecasts could be used to highlight anomalies in incidence and support health service logistics. The model which best fits the data is not necessarily most useful for prediction, yet little empirical work has been done to investigate the balance between fit and predictive performance. Methodology/Principal findings We developed statistical models of monthly VL case counts at block level. By evaluating a set of randomly-generated models, we found that fit and one-month-ahead prediction were strongly correlated and that rolling updates to model parameters as data accrued were not crucial for accurate prediction. The final model incorporated auto-regression over four months, spatial correlation between neighbouring blocks, and seasonality. Ninety-four percent of 10-90% prediction intervals from this model captured the observed count during a 24-month test period. Comparison of one-, three- and four-month-ahead predictions from the final model fit demonstrated that a longer time horizon yielded only a small sacrifice in predictive power for the vast majority of blocks. Conclusions/Significance The model developed is informed by routinely-collected surveillance data as it accumulates, and predictions are sufficiently accurate and precise to be useful. Such forecasts could, for example, be used to guide stock requirements for rapid diagnostic tests and drugs. More comprehensive data on factors thought to influence geographic variation in VL burden could be incorporated, and might better explain the heterogeneity between blocks and improve uniformity of predictive performance. Integration of the approach in the management of the VL programme would be an important step to ensuring continued successful control.
As of 2021, the National Kala-azar Elimination Programme (NKAEP) in India has achieved visceral leishmaniasis (VL) elimination (<1 case / 10,000 population/year per block) in 625 of the 633 endemic ...blocks (subdistricts) in four states. The programme needs to sustain this achievement and target interventions in the remaining blocks to achieve the WHO 2030 target of VL elimination as a public health problem. An effective tool to analyse programme data and predict/ forecast the spatial and temporal trends of VL incidence, elimination threshold, and risk of resurgence will be of use to the programme management at this juncture.
We employed spatiotemporal models incorporating environment, climatic and demographic factors as covariates to describe monthly VL cases for 8-years (2013-2020) in 491 and 27 endemic and non-endemic blocks of Bihar and Jharkhand states. We fitted 37 models of spatial, temporal, and spatiotemporal interaction random effects with covariates to monthly VL cases for 6-years (2013-2018, training data) using Bayesian inference via Integrated Nested Laplace Approximation (INLA) approach. The best-fitting model was selected based on deviance information criterion (DIC) and Watanabe-Akaike Information Criterion (WAIC) and was validated with monthly cases for 2019-2020 (test data). The model could describe observed spatial and temporal patterns of VL incidence in the two states having widely differing incidence trajectories, with >93% and 99% coverage probability (proportion of observations falling inside 95% Bayesian credible interval for the predicted number of VL cases per month) during the training and testing periods. PIT (probability integral transform) histograms confirmed consistency between prediction and observation for the test period. Forecasting for 2021-2023 showed that the annual VL incidence is likely to exceed elimination threshold in 16-18 blocks in 4 districts of Jharkhand and 33-38 blocks in 10 districts of Bihar. The risk of VL in non-endemic neighbouring blocks of both Bihar and Jharkhand are less than 0.5 during the training and test periods, and for 2021-2023, the probability that the risk greater than 1 is negligible (P<0.1). Fitted model showed that VL occurrence was positively associated with mean temperature, minimum temperature, enhanced vegetation index, precipitation, and isothermality, and negatively with maximum temperature, land surface temperature, soil moisture and population density.
The spatiotemporal model incorporating environmental, bioclimatic, and demographic factors demonstrated that the KAMIS database of the national programmme can be used for block level predictions of long-term spatial and temporal trends in VL incidence and risk of outbreak / resurgence in endemic and non-endemic settings. The database integrated with the modelling framework and a dashboard facility can facilitate such analysis and predictions. This could aid the programme to monitor progress of VL elimination at least one-year ahead, assess risk of resurgence or outbreak in post-elimination settings, and implement timely and targeted interventions or preventive measures so that the NKAEP meet the target of achieving elimination by 2030.
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