As malaria declines in many African countries there is a growing realization that new interventions need to be added to the front-line vector control tools of long-lasting impregnated nets (LLINs) ...and indoor residual spraying (IRS) that target adult mosquitoes indoors. Larval source management (LSM) provides the dual benefits of not only reducing numbers of house-entering mosquitoes, but, importantly, also those that bite outdoors. Large-scale LSM was a highly effective method of malaria control in the first half of the twentieth century, but was largely disbanded in favour of IRS with DDT. Today LSM continues to be used in large-scale mosquito abatement programmes in North America and Europe, but has only recently been tested in a few trials of malaria control in contemporary Africa. The results from these trials show that hand-application of larvicides can reduce transmission by 70-90% in settings where mosquito larval habitats are defined but is largely ineffectual where habitats are so extensive that not all of them can be covered on foot, such as areas that experience substantial flooding. Importantly recent evidence shows that LSM can be an effective method of malaria control, especially when combined with LLINs. Nevertheless, there are a number of misconceptions or even myths that hamper the advocacy for LSM by leading international institutions and the uptake of LSM by Malaria Control Programmes. Many argue that LSM is not feasible in Africa due to the high number of small and temporary larval habitats for Anopheles gambiae that are difficult to find and treat promptly. Reference is often made to the Ross-Macdonald model to reinforce the view that larval control is ineffective. This paper challenges the notion that LSM cannot be successfully used for malaria control in African transmission settings by highlighting historical and recent successes, discussing its potential in an integrated vector management approach working towards malaria elimination and critically reviewing the most common arguments that are used against the adoption of LSM.
Identifying neuromuscular screening factors for anterior cruciate ligament (ACL) injury is a critical step toward large-scale deployment of effective ACL injury-prevention programs. The Landing Error ...Scoring System (LESS) is a valid and reliable clinical assessment of jump-landing biomechanics.
To investigate the ability of the LESS to identify individuals at risk for ACL injury in an elite-youth soccer population.
Cohort study.
Field-based functional movement screening performed at soccer practice facilities.
A total of 829 elite-youth soccer athletes (348 boys, 481 girls; age = 13.9 ± 1.8 years, age range = 11 to 18 years), of whom 25% (n = 207) were less than 13 years of age.
Baseline preseason testing for all participants consisted of a jump-landing task (3 trials). Participants were followed prospectively throughout their soccer seasons for diagnosis of ACL injuries (1217 athlete-seasons of follow-up).
Landings were scored for "errors" in technique using the LESS. We used receiver operator characteristic curves to determine a cutpoint on the LESS. Sensitivity and specificity of the LESS in predicting ACL injury were assessed.
Seven participants sustained ACL injuries during the follow-up period; the mechanism of injury was noncontact or indirect contact for all injuries. Uninjured participants had lower LESS scores (4.43 ± 1.71) than injured participants (6.24 ± 1.75; t1215 = -2.784, P = .005). The receiver operator characteristic curve analyses suggested that 5 was the optimal cutpoint for the LESS, generating a sensitivity of 86% and a specificity of 64%.
Despite sample-size limitations, the LESS showed potential as a screening tool to determine ACL injury risk in elite-youth soccer athletes.
Abstract
DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express ...elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies.
Results will provide a benchmark for subsequent trials in which combinations of interventions are assessed.\n Ignoring human movement during study design considerations would require an artificial ...increase in the expected effectiveness to achieve adequate power because every individual in a treatment cluster will be predicted to have the "maximum" effect. Insights from such trials will help guide the scaling up of effective dengue control strategies, whether vector control alone or in combination with vaccines, and will be applicable to other Ae. aegypti-borne viral infections of current public health concern, such as chikungunya and Zika viruses.
Background
Malaria is an important cause of illness and death in people living in many parts of the world, especially sub‐Saharan Africa. Long‐lasting insecticide treated bed nets (LLINs) and indoor ...residual spraying (IRS) reduce malaria transmission by targeting the adult mosquito vector and are key components of malaria control programmes. However, mosquito numbers may also be reduced by larval source management (LSM), which targets mosquito larvae as they mature in aquatic habitats. This is conducted by permanently or temporarily reducing the availability of larval habitats (habitat modification and habitat manipulation), or by adding substances to standing water that either kill or inhibit the development of larvae (larviciding).
Objectives
To evaluate the effectiveness of mosquito LSM for preventing malaria.
Search methods
We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CABS s; and LILACS up to 24 October 2012. We handsearched the Tropical Diseases Bulletin from 1900 to 2010, the archives of the World Health Organization (up to 11 February 2011), and the literature database of the Armed Forces Pest Management Board (up to 2 March 2011). We also contacted colleagues in the field for relevant articles.
Selection criteria
We included cluster randomized controlled trials (cluster‐RCTs), controlled before‐and‐after trials with at least one year of baseline data, and randomized cross‐over trials that compared LSM with no LSM for malaria control. We excluded trials that evaluated biological control of anopheline mosquitoes with larvivorous fish.
Data collection and analysis
At least two authors assessed each trial for eligibility. We extracted data and at least two authors independently determined the risk of bias in the included studies. We resolved all disagreements through discussion with a third author. We analyzed the data using Review Manager 5 software.
Main results
We included 13 studies; four cluster‐RCTs, eight controlled before‐and‐after trials, and one randomized cross‐over trial. The included studies evaluated habitat modification (one study), habitat modification with larviciding (two studies), habitat manipulation (one study), habitat manipulation plus larviciding (two studies), or larviciding alone (seven studies) in a wide variety of habitats and countries.
Malaria incidence
In two cluster‐RCTs undertaken in Sri Lanka, larviciding of abandoned mines, streams, irrigation ditches, and rice paddies reduced malaria incidence by around three‐quarters compared to the control (RR 0.26, 95% CI 0.22 to 0.31, 20,124 participants, two trials, moderate quality evidence). In three controlled before‐and‐after trials in urban and rural India and rural Kenya, results were inconsistent (98,233 participants, three trials, very low quality evidence). In one trial in urban India, the removal of domestic water containers together with weekly larviciding of canals and stagnant pools reduced malaria incidence by three quarters. In one trial in rural India and one trial in rural Kenya, malaria incidence was higher at baseline in intervention areas than in controls. However dam construction in India, and larviciding of streams and swamps in Kenya, reduced malaria incidence to levels similar to the control areas. In one additional randomized cross‐over trial in the flood plains of the Gambia River, where larval habitats were extensive and ill‐defined, larviciding by ground teams did not result in a statistically significant reduction in malaria incidence (2039 participants, one trial).
Parasite prevalence
In one cluster‐RCT from Sri Lanka, larviciding reduced parasite prevalence by almost 90% (RR 0.11, 95% CI 0.05 to 0.22, 2963 participants, one trial, moderate quality evidence). In five controlled before‐and‐after trials in Greece, India, the Philippines, and Tanzania, LSM resulted in an average reduction in parasite prevalence of around two‐thirds (RR 0.32, 95% CI 0.19 to 0.55, 8041 participants, five trials, moderate quality evidence). The interventions in these five trials included dam construction to reduce larval habitats, flushing of streams, removal of domestic water containers, and larviciding. In the randomized cross‐over trial in the flood plains of the Gambia River, larviciding by ground teams did not significantly reduce parasite prevalence (2039 participants, one trial).
Authors' conclusions
In Africa and Asia, LSM is another policy option, alongside LLINs and IRS, for reducing malaria morbidity in both urban and rural areas where a sufficient proportion of larval habitats can be targeted. Further research is needed to evaluate whether LSM is appropriate or feasible in parts of rural Africa where larval habitats are more extensive.
16 April 2019
Update pending
Studies awaiting assessment
The CIDG is currently examining a new search conducted up to 15 Aug, 2018 for potentially relevant studies. These studies have not yet been incorporated into this Cochrane Review.
To assess the contributions of both microbial larvicides and insecticide-treated nets (ITNs) in terms of reducing malaria incidence in an integrated vector management programme in an area moderately ...endemic for malaria in the western Kenyan highlands.
A pre-post, control group design was used. Larval and adult vector populations were surveyed weekly in six separate valley communities. The incidence of Plasmodium infections in children 6 months to 13 years of age was measured during the long and short rainy seasons each year. Baseline data were collected for 17 months, after which Bacillus-based larvicides were applied weekly to aquatic habitats in three of the valleys for another 19 months. At around the same time the larviciding was initiated, ITNs were introduced gradually into all study communities by the National Malaria Control Programme. The effect of larviciding, ITNs and other determinants of malaria risk was assessed by means of generalized estimating equations.
The risk of acquiring new parasite infections in children was substantially and independently reduced by ITN use (odds ratio, OR: 0.69; 95% confidence interval, CI: 0.48-0.99) and larvicide application (OR: 0.44; 95% CI: 0.23-0.82), after adjusting for confounders.
Vector control with microbial larvicides enhanced the malaria control achieved with ITNs alone. Anti-larval measures are a promising complement to ITN distribution in the economically important highland areas and similar transmission settings in Africa.
Larviciding is an effective supplementary tool for malaria vector control, but the identification and accessibility of aquatic habitats impedes application. Dissemination of the insect growth ...regulator, pyriproxyfen (PPF), by gravid Anopheles might constitute a novel application strategy. This study aimed to explore the feasibility of using an attractive bait-station to contaminate gravid Anopheles gambiae sensu stricto with PPF and subsequently transfer PPF to larval habitats.
A bait-station was developed comprising of an artificial pond containing water treated with 20 ppm cedrol, an oviposition attractant, and a netting-cover treated with PPF. Three identical semi-field cages were used to assess the potential of gravid Anopheles to transfer PPF from the bait-station to ponds. Gravid females were released in two semi-field cages, one with PPF on its bait-station (test) and one without PPF (control). No mosquitoes were released in the third cage with a PPF-treated station (control). Transfer of PPF to open ponds was assessed by monitoring emergence of late instar insectary-reared larvae introduced into the ponds. The amount of PPF carried by a mosquito and transferred to water was quantified using liquid chromatography-mass spectrometry.
In the controls, 86% (95% CI 81-89%) of larvae introduced into open ponds developed into adults, indicating that wind did not distribute PPF in absence of mosquitoes. Emergence inhibition was observed in the test cage but was dependent on the distance between pond and bait-station. Only 25% (95% CI 22-29%) of larvae emerged as adults from ponds 4 m from the bait-station, but 92% (95% CI 89-94%) emerged from ponds 10 m away. Each mosquito was contaminated on average with 112 μg (95% CI 93-123 μg) PPF resulting in the transfer of 230 ng/L (95% CI 180-290 ng/L) PPF to 100 ml volumes of water.
The bait-stations successfully attracted gravid females which were subsequently dusted with effective levels of PPF. However, in this study design, attraction and dissemination was limited to short distances. To make this approach feasible for malaria vector control, stronger attractants that lure gravid females from longer distances, in landscapes with many water bodies, and better PPF delivery systems are needed.
Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the ...Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.
Heterogeneity in transmission is a challenge for infectious disease dynamics and control. An 80-20 "Pareto" rule has been proposed to describe this heterogeneity whereby 80% of transmission is ...accounted for by 20% of individuals, herein called super-spreaders. It is unclear, however, whether super-spreading can be attributed to certain individuals or whether it is an unpredictable and unavoidable feature of epidemics. Here, we investigate heterogeneous malaria transmission at three sites in Uganda and find that super-spreading is negatively correlated with overall malaria transmission intensity. Mosquito biting among humans is 90-10 at the lowest transmission intensities declining to less than 70-30 at the highest intensities. For super-spreaders, biting ranges from 70-30 down to 60-40. The difference, approximately half the total variance, is due to environmental stochasticity. Super-spreading is thus partly due to super-spreaders, but modest gains are expected from targeting super-spreaders.
Insecticide-treated nets (ITNs) are one of the main interventions used for malaria control. However, these nets may also be effective against other vector borne diseases (VBDs). We conducted a ...systematic review and meta-analysis to estimate the efficacy of ITNs, insecticide-treated curtains (ITCs) and insecticide-treated house screening (ITS) against Chagas disease, cutaneous and visceral leishmaniasis, dengue, human African trypanosomiasis, Japanese encephalitis, lymphatic filariasis and onchocerciasis.
MEDLINE, EMBASE, LILACS and Tropical Disease Bulletin databases were searched using intervention, vector- and disease-specific search terms. Cluster or individually randomised controlled trials, non-randomised trials with pre- and post-intervention data and rotational design studies were included. Analysis assessed the efficacy of ITNs, ITCs or ITS versus no intervention. Meta-analysis of clinical data was performed and percentage reduction in vector density calculated.
Twenty-one studies were identified which met the inclusion criteria. Meta-analysis of clinical data could only be performed for four cutaneous leishmaniasis studies which together showed a protective efficacy of ITNs of 77% (95%CI: 39%-91%). Studies of ITC and ITS against cutaneous leishmaniasis also reported significant reductions in disease incidence. Single studies reported a high protective efficacy of ITS against dengue and ITNs against Japanese encephalitis. No studies of Chagas disease, human African trypanosomiasis or onchocerciasis were identified.
There are likely to be considerable collateral benefits of ITN roll out on cutaneous leishmaniasis where this disease is co-endemic with malaria. Due to the low number of studies identified, issues with reporting of entomological outcomes, and few studies reporting clinical outcomes, it is difficult to make strong conclusions on the effect of ITNs, ITCs or ITS on other VBDs and therefore further studies be conducted. Nonetheless, it is clear that insecticide-treated materials such as ITNs have the potential to reduce pathogen transmission and morbidity from VBDs where vectors enter houses.
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