遗传不育技术在蚊媒疾病防控中的应用

疟疾、登革热等重大传染性蚊媒疾病严重危害人类健康,且目前缺乏有效的药物和疫苗,防治埃及伊蚊、冈比亚按蚊等媒介昆虫是控制和消除这些疾病的有效手段。化学杀虫剂的大规模使用在一定程度上控制了疾病的传播,但其抗药性和环境污染等问题也随之而来。分子生物学的飞速发展为昆虫不育技术(SIT)的更新及害虫防治提供了新的策略,由此发展起来的以释放携带显性致死基因昆虫(RIDL)为代表的一系列遗传不育技术为蚊虫种群防控提供了更加有效的选择。本文概述了遗传技术在蚊虫防控中的应用进展,包括蚊虫遗传防治的历史和策略,阐述了RIDL技术体系的原理,同时介绍了相关遗传控制品系和已经开展的田间释放研究,展示了遗传修饰不育技术在蚊媒疾病防治中的巨大潜力。     

Genetic elimination of field-cage populations of Mediterranean fruit flies

The Mediterranean fruit fly (medfly, Ceratitis capitata Wiedemann) is a pest of over 300 fruits, vegetables and nuts. The sterile insect technique (SIT) is a control measure used to reduce the reproductive potential of populations through the mass release of sterilized male insects that mate with wild females. However, SIT flies can display poor field performance, due to the effects of mass-rearing and of the irradiation process used for sterilization. The development of female-lethal RIDL (release of insects carrying a dominant lethal) strains for medfly can overcome many of the problems of SIT associated with irradiation. Here, we present life-history characterizations for two medfly RIDL strains, OX3864A and OX3647Q. Our results show (i) full functionality of RIDL, (ii) equivalency of RIDL and wild-type strains for life-history characteristics, and (iii) a high level of sexual competitiveness against both wild-type and wild-derived males. We also present the first proof-of-principle experiment on the use of RIDL to eliminate medfly populations. Weekly releases of OX3864A males into stable populations of wild-type medfly caused a successive decline in numbers, leading to eradication. The results show that genetic control can provide an effective alternative to SIT for the control of pest insects.     

Costs of Dengue Control Activities and Hospitalizations in the Public Health Sector during an Epidemic Year in Urban Sri Lanka

Background

Reported as a public health problem since the 1960s in Sri Lanka, dengue has become a high priority disease for public health authorities. The Ministry of Health is responsible for controlling dengue and other disease outbreaks and associated health care. The involvement of large numbers of public health staff in dengue control activities year-round and the provision of free medical care to dengue patients at secondary care hospitals place a formidable financial burden on the public health sector.

Methods

We estimated the public sector costs of dengue control activities and the direct costs of hospitalizations in Colombo, the most heavily urbanized district in Sri Lanka, during the epidemic year of 2012 from the Ministry of Health’s perspective. The financial costs borne by public health agencies and hospitals are collected using cost extraction tools designed specifically for the study and analysed retrospectively using a combination of activity-based and gross costing approaches.

Results

The total cost of dengue control and reported hospitalizations was estimated at US$3.45 million (US$1.50 per capita) in Colombo district in 2012. Personnel costs accounted for the largest shares of the total costs of dengue control activities (79%) and hospitalizations (46%). The results indicated a per capita cost of US$0.42 for dengue control activities. The average costs per hospitalization ranged between US$216–609 for pediatric cases and between US$196–866 for adult cases according to disease severity and treatment setting.

Conclusions

This analysis is a first attempt to assess the economic burden of dengue response in the public health sector in Sri Lanka. Country-specific evidence is needed for setting public health priorities and deciding about the deployment of existing or new technologies. Our results suggest that dengue poses a major economic burden on the public health sector in Sri Lanka.     

Economic and Disease Burden of Dengue in Southeast Asia

Background

Dengue poses a substantial economic and disease burden in Southeast Asia (SEA). Quantifying this burden is critical to set policy priorities and disease-control strategies.

Methods and Findings

We estimated the economic and disease burden of dengue in 12 countries in SEA: Bhutan, Brunei, Cambodia, East-Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Viet Nam. We obtained reported cases from multiple sources—surveillance data, World Health Organization (WHO), and published studies—and adjusted for underreporting using expansion factors from previous literature. We obtained unit costs per episode through a systematic literature review, and completed missing data using linear regressions. We excluded costs such as prevention and vector control, and long-term sequelae of dengue. Over the decade of 2001–2010, we obtained an annual average of 2.9 million (m) dengue episodes and 5,906 deaths. The annual economic burden (with 95% certainty levels) was US$950m (US$610m–US$1,384m) or about US$1.65 (US$1.06–US$2.41) per capita. The annual number of disability-adjusted life years (DALYs), based on the original 1994 definition, was 214,000 (120,000–299,000), which is equivalent to 372 (210–520) DALYs per million inhabitants.

Conclusion

Dengue poses a substantial economic and disease burden in SEA with a DALY burden per million inhabitants in the region. This burden is higher than that of 17 other conditions, including Japanese encephalitis, upper respiratory infections, and hepatitis B.     

Pair of lice lost or parasites regained: the evolutionary history of anthropoid primate lice

Background

Reduction or elimination of vector populations will tend to reduce or eliminate transmission of vector-borne diseases. One potential method for environmentally-friendly, species-specific population control is the Sterile Insect Technique (SIT). SIT has not been widely used against insect disease vectors such as mosquitoes, in part because of various practical difficulties in rearing, sterilization and distribution. Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality.

Results

We investigated by mathematical modeling the effect of manipulating the stage of development at which death occurs (lethal phase) in an SIT program against a density-dependence-limited insect population. We found late-acting lethality to be considerably more effective than early-acting lethality. No such strains of a vector insect have been described, so as a proof-of-principle we constructed a strain of the principal vector of the dengue and yellow fever viruses, Aedes (Stegomyia) aegypti, with the necessary properties of dominant, repressible, highly penetrant, late-acting lethality.

Conclusion

Conventional SIT induces early-acting (embryonic) lethality, but genetic methods potentially allow the lethal phase to be tailored to the program. For insects with strong density-dependence, we show that lethality after the density-dependent phase would be a considerable improvement over conventional methods. For density-dependent parameters estimated from field data for Aedes aegypti, the critical release ratio for population elimination is modeled to be 27% to 540% greater for early-acting rather than late-acting lethality. Our success in developing a mosquito strain with the key features that the modeling indicated were desirable demonstrates the feasibility of this approach for improved SIT for disease control.     

High-throughput sorting of mosquito larvae for laboratory studies and for future vector control interventions

ABSTRACT: BACKGROUND: Mosquito transgenesis offers new promises for the genetic control of vector-borne infectious diseases such as malaria and dengue fever. Genetic control strategies require the release of large number of male mosquitoes into field populations, whether they are based on the use of sterile males (sterile insect technique, SIT) or on introducing genetic traits conferring refractoriness to disease transmission (population replacement). However, the current absence of high-throughput techniques for sorting different mosquito populations impairs the application of these control measures. METHODS: A method was developed to generate large mosquito populations of the desired sex and genotype. This method combines flow cytometry and the use of Anopheles gambiae transgenic lines that differentially express fluorescent markers in males and females. RESULTS: Fluorescence-assisted sorting allowed single-step isolation of homozygous transgenic mosquitoes from a mixed population. This method was also used to select wild-type males only with high efficiency and accuracy, a highly desirable tool for genetic control strategies where the release of transgenic individuals may be problematic. Importantly, sorted males showed normal mating ability compared to their unsorted brothers. CONCLUSIONS: The developed method will greatly facilitate both laboratory studies of mosquito vectorial capacity requiring high-throughput approaches and future field interventions in the fight against infectious disease vectors.     

Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore

Background

Dengue illness causes 50–100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact of dengue in higher resourced countries or the cost-effectiveness of potential dengue vaccines in such settings.

Methods and Findings

We estimate the direct and indirect costs of dengue from hospitalized and ambulatory cases in Singapore. We consider inter alia the impacts of dengue on the economy using the human-capital and the friction cost methods. Disease burden was estimated using disability-adjusted life years (DALYs) and the cost-effectiveness of a potential vaccine program was evaluated. The average economic impact of dengue illness in Singapore from 2000 to 2009 in constant 2010 US$ ranged between $0.85 billion and $1.15 billion, of which control costs constitute 42%–59%. Using empirically derived disability weights, we estimated an annual average disease burden of 9–14 DALYs per 100 000 habitants, making it comparable to diseases such as hepatitis B or syphilis. The proportion of symptomatic dengue cases detected by the national surveillance system was estimated to be low, and to decrease with age. Under population projections by the United Nations, the price per dose threshold for which vaccines stop being more cost-effective than the current vector control program ranged from $50 for mass vaccination requiring 3 doses and only conferring 10 years of immunity to $300 for vaccination requiring 2 doses and conferring lifetime immunity. The thresholds for these vaccine programs to not be cost-effective for Singapore were $100 and $500 per dose respectively.

Conclusions

Dengue illness presents a serious economic and disease burden in Singapore. Dengue vaccines are expected to be cost-effective if reasonably low prices are adopted and will help to reduce the economic and disease burden of dengue in Singapore substantially.     

Large-scale use of mosquito larval source management for malaria control in Africa: a cost analysis

Background

At present, large-scale use of two malaria vector control methods, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) is being scaled up in Africa with substantial funding from donors. A third vector control method, larval source management (LSM), has been historically very successful and is today widely used for mosquito control globally, except in Africa. With increasing risk of insecticide resistance and a shift to more exophilic vectors, LSM is now under re-evaluation for use against afro-tropical vector species. Here the costs of this intervention were evaluated.

Methods

The 'ingredients approach' was used to estimate the economic and financial costs per person protected per year (pppy) for large-scale LSM using microbial larvicides in three ecologically diverse settings: (1) the coastal metropolitan area of Dar es Salaam in Tanzania, (2) a highly populated Kenyan highland area (Vihiga District), and (3) a lakeside setting in rural western Kenya (Mbita Division). Two scenarios were examined to investigate the cost implications of using alternative product formulations. Sensitivity analyses on product prices were carried out.

Results

The results show that for programmes using the same granular formulation larviciding costs the least pppy in Dar es Salaam (US$0.94), approximately 60% more in Vihiga District (US$1.50) and the most in Mbita Division (US$2.50). However, these costs are reduced substantially if an alternative water-dispensable formulation is used; in Vihiga, this would reduce costs to US$0.79 and, in Mbita Division, to US$1.94. Larvicide and staff salary costs each accounted for approximately a third of the total economic costs per year. The cost pppy depends mainly on: (1) the type of formulation required for treating different aquatic habitats, (2) the human population density relative to the density of aquatic habitats and (3) the potential to target the intervention in space and/or time.

Conclusion

Costs for LSM compare favourably with costs for IRS and LLINs, especially in areas with moderate and focal malaria transmission where mosquito larval habitats are accessible and well defined. LSM presents an attractive tool to be integrated in ongoing malaria control effort in such settings. Further data on the epidemiological health impact of larviciding is required to establish cost effectiveness.     

Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases

Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication) can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted). We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences—consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even modest perturbations induced by weak interventions can exhibit strong, albeit transient, epidemiological effects. This, together with our finding that under some conditions combining strategies could have transient adverse epidemiological effects suggests that a relatively long time horizon may be necessary to discern the efficacy of alternative intervention strategies.     

Emergence and prevalence of human vector-borne diseases in sink vector populations

Vector-borne diseases represent a major public health concern in most tropical and subtropical areas, and an emerging threat for more developed countries. Our understanding of the ecology, evolution and control of these diseases relies predominantly on theory and data on pathogen transmission in large self-sustaining 'source' populations of vectors representative of highly endemic areas. However, there are numerous places where environmental conditions are less favourable to vector populations, but where immigration allows them to persist. We built an epidemiological model to investigate the dynamics of six major human vector borne-diseases in such non self-sustaining 'sink' vector populations. The model was parameterized through a review of the literature, and we performed extensive sensitivity analysis to look at the emergence and prevalence of the pathogen that could be encountered in these populations. Despite the low vector abundance in typical sink populations, all six human diseases were able to spread in 15-55% of cases after accidental introduction. The rate of spread was much more strongly influenced by vector longevity, immigration and feeding rates, than by transmission and virulence of the pathogen. Prevalence in humans remained lower than 5% for dengue, leishmaniasis and Japanese encephalitis, but substantially higher for diseases with longer duration of infection; malaria and the American and African trypanosomiasis. Vector-related parameters were again the key factors, although their influence was lower than on pathogen emergence. Our results emphasize the need for ecology and evolution to be thought in the context of metapopulations made of a mosaic of sink and source habitats, and to design vector control program not only targeting areas of high vector density, but working at a larger spatial scale.     

Dynamic Epidemiological Models for Dengue Transmission: A Systematic Review of Structural Approaches

Dengue is a vector-borne disease recognized as the major arbovirose with four immunologically distant dengue serotypes coexisting in many endemic areas. Several mathematical models have been developed to understand the transmission dynamics of dengue, including the role of cross-reactive antibodies for the four different dengue serotypes. We aimed to review deterministic models of dengue transmission, in order to summarize the evolution of insights for, and provided by, such models, and to identify important characteristics for future model development. We identified relevant publications using PubMed and ISI Web of Knowledge, focusing on mathematical deterministic models of dengue transmission. Model assumptions were systematically extracted from each reviewed model structure, and were linked with their underlying epidemiological concepts. After defining common terms in vector-borne disease modelling, we generally categorised fourty-two published models of interest into single serotype and multiserotype models. The multi-serotype models assumed either vector-host or direct host-to-host transmission (ignoring the vector component). For each approach, we discussed the underlying structural and parameter assumptions, threshold behaviour and the projected impact of interventions. In view of the expected availability of dengue vaccines, modelling approaches will increasingly focus on the effectiveness and cost-effectiveness of vaccination options. For this purpose, the level of representation of the vector and host populations seems pivotal. Since vector-host transmission models would be required for projections of combined vaccination and vector control interventions, we advocate their use as most relevant to advice health policy in the future. The limited understanding of the factors which influence dengue transmission as well as limited data availability remain important concerns when applying dengue models to real-world decision problems.     

害虫遗传不育技术中致死基因的研究与应用

基于遗传修饰手段的昆虫不育技术(SIT)作为一类物种特异、环境友好、科学高效的新兴策略,在害虫防治中具有广阔的应用前景。释放携带显性致死基因昆虫的技术(RIDL)是改进传统SIT的重要手段之一,主要包括四环素调控系统、特异性启动子、性别特异剪接系统和特异性致死基因等重要元件,其中根据不同昆虫的特点选择合适的特异性致死基因对于构建遗传不育品系至关重要。这些致死基因或受到阻遏调控系统的控制、或特异的在雌虫中表达、亦或直接作用于X染色体,导致后代在特定发育阶段或特定性别中条件致死。本文综述了RHG家族(reapr、hid、grim、michelob_x)细胞凋亡基因、转录激活因子t TA及Nipp1Dm、归巢内切酶基因等在害虫遗传不育技术中的研究和应用,讨论了特定致死基因的效应机理和应用特点,并对其可能的发展方向进行了展望。由于不同效应基因的致死作用和调控机理尚未完全明晰,因此深入研究特异致死基因的凋亡机制和在不同物种中的兼容作用,将为害虫遗传防控提供更多的研究思路和手段。     

The Costs of Preventing and Treating Chagas Disease in Colombia

Background

The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy.

Methods

Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation.

Findings

The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between $46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is $1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care.

Conclusion

Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.     

Enhancing vector refractoriness to trypanosome infection: achievements,challenges and perspectives

With the absence of effective prophylactic vaccines and drugs against African trypanosomosis, control of this group of zoonotic neglected tropical diseases depends the control of the tsetse fly vector. When applied in an area-wide insect pest management approach, the sterile insect technique (SIT) is effective in eliminating single tsetse species from isolated populations. The need to enhance the effectiveness of SIT led to the concept of investigating tsetse-trypanosome interactions by a consortium of researchers in a five-year (2013–2018) Coordinated Research Project (CRP) organized by the Joint Division of FAO/IAEA. The goal of this CRP was to elucidate tsetse-symbiome-pathogen molecular interactions to improve SIT and SIT-compatible interventions for trypanosomoses control by enhancing vector refractoriness. This would allow extension of SIT into areas with potential disease transmission. This paper highlights the CRP’s major achievements and discusses the science-based perspectives for successful mitigation or eradication of African trypanosomosis.     

Cost-Effectiveness of Chagas Disease Vector Control Strategies in Northwestern Argentina

Background

Control and prevention of Chagas disease rely mostly on residual spraying of insecticides. In Argentina, vector control shifted from a vertical to a fully horizontal strategy based on community participation between 1992 and 2004. The effects of such strategy on Triatoma infestans, the main domestic vector, and on disease transmission have not been assessed.

Methods and Findings

Based on retrospective (1993–2004) records from the Argentinean Ministry of Health for the Moreno Department, Northwestern Argentina, we performed a cost-effectiveness (CE) analysis and compared the observed CE of the fully horizontal vector control strategy with the expected CE for a vertical or a mixed (i.e., vertical attack phase followed by horizontal surveillance) strategy. Total direct costs (in 2004 US$) of the horizontal and mixed strategies were, respectively, 3.3 and 1.7 times lower than the costs of the vertical strategy, due to reductions in personnel costs. The estimated CE ratios for the vertical, mixed and horizontal strategies were US$132, US$82 and US$45 per averted human case, respectively. When per diems were excluded from the costs (i.e., simulating the decentralization of control activities), the CE of vertical, mixed and horizontal strategies was reduced to US$60, US$42 and US$32 per averted case, respectively.

Conclusions and Significance

The mixed strategy would have averted between 1.6 and 4.0 times more human cases than the fully horizontal strategy, and would have been the most cost-effective option to interrupt parasite transmission in the Department. In rural and dispersed areas where waning vertical vector programs cannot accomplish full insecticide coverage, alternative strategies need to be developed. If properly implemented, community participation represents not only the most appealing but also the most cost-effective alternative to accomplish such objectives.     

Oral Ingestion of Transgenic RIDL Ae. aegypti Larvae Has No Negative Effect on Two Predator Toxorhynchites Species

Dengue is the most important mosquito-borne viral disease. No specific treatment or vaccine is currently available; traditional vector control methods can rarely achieve adequate control. Recently, the RIDL (Release of Insect carrying Dominant Lethality) approach has been developed, based on the sterile insect technique, in which genetically engineered ‘sterile’ homozygous RIDL male insects are released to mate wild females; the offspring inherit a copy of the RIDL construct and die. A RIDL strain of the dengue mosquito, Aedes aegypti, OX513A, expresses a fluorescent marker gene for identification (DsRed2) and a protein (tTAV) that causes the offspring to die. We examined whether these proteins could adversely affect predators that may feed on the insect. Aedes aegypti is a peri-domestic mosquito that typically breeds in small, rain-water-filled containers and has no specific predators. Toxorhynchites larvae feed on small aquatic organisms and are easily reared in the laboratory where they can be fed exclusively on mosquito larvae. To evaluate the effect of a predator feeding on a diet of RIDL insects, OX513A Ae. aegypti larvae were fed to two different species of Toxorhynchites (Tx. splendens and Tx. amboinensis) and effects on life table parameters of all life stages were compared to being fed on wild type larvae. No significant negative effect was observed on any life table parameter studied; this outcome and the benign nature of the expressed proteins (tTAV and DsRed2) indicate that Ae. aegypti OX513A RIDL strain is unlikely to have any adverse effects on predators in the environment.     

The Sterile Insect Technique for Controlling Populations of Aedes albopictus (Diptera: Culicidae) on Reunion Island: Mating Vigour of Sterilized Males

Reunion Island suffers from high densities of the chikungunya and dengue vector Aedes albopictus. The sterile insect technique (SIT) offers a promising strategy for mosquito-borne diseases prevention and control. For such a strategy to be effective, sterile males need to be competitive enough to fulfil their intended function by reducing wild mosquito populations in natura. We studied the effect of irradiation on sexual maturation and mating success of males, and compared the sexual competitiveness of sterile versus wild males in the presence of wild females in semi-field conditions. For all untreated or sterile males, sexual maturation was completed within 13 to 20 h post-emergence and some males were able to inseminate females when 15 h old. In the absence of competition, untreated and sterile males were able to inseminate the same number of virgin females during 48 h, in small laboratory cages: an average of 93% of females was inseminated no matter the treatment, the age of males, and the sex ratio. Daily mating success of single sterile males followed the same pattern as for untreated ones, although they inseminated significantly fewer females after the ninth day. The competitiveness index of sterile males in semi-field conditions was only 0.14 when they were released at 1-day old, but improved to 0.53 when the release occurred after a 5-day period in laboratory conditions. In SIT simulation experiments, a 5∶1 sterile to wild male ratio allowed a two-fold reduction of the wild population’s fertility. This suggests that sterile males could be sufficiently competitive to mate with wild females within the framework of an SIT component as part of an AW-IPM programme for suppressing a wild population of Ae. albopictus in Reunion Island. It will be of interest to minimise the pre-release period in controlled conditions to ensure a good competitiveness without increasing mass rearing costs.     

High Dengue Case Capture Rate in Four Years of a Cohort Study in Nicaragua Compared to National Surveillance Data

Dengue is a major public health problem in tropical and subtropical regions; however, under-reporting of cases to national surveillance systems hinders accurate knowledge of disease burden and costs. Laboratory-confirmed dengue cases identified through the Nicaraguan Pediatric Dengue Cohort Study (PDCS) were compared to those reported from other health facilities in Managua to the National Epidemiologic Surveillance (NES) program of the Nicaraguan Ministry of Health. Compared to reporting among similar pediatric populations in Managua, the PDCS identified 14 to 28 (average 21.3) times more dengue cases each year per 100,000 persons than were reported to the NES. Applying these annual expansion factors to national-level data, we estimate that the incidence of confirmed pediatric dengue throughout Nicaragua ranged from 300 to 1000 cases per 100,000 persons. We have estimated a much higher incidence of dengue than reported by the Ministry of Health. A country-specific expansion factor for dengue that allows for a more accurate estimate of incidence may aid governments and other institutions calculating disease burden, costs, resource needs for prevention and treatment, and the economic benefits of drug and vaccine development.     

害虫遗传防治的研究历史与现状

作为防治或根除重大害虫最为有效的手段之一,害虫遗传防治在世界范围内被广泛采用并取得了巨大成功。本文综述了不育昆虫技术、雌性致死系统和昆虫显性致死技术等经典害虫遗传防治策略的发展历史、技术特点和应用情况。近年来,许多新的分子生物手段被不断提出并整合到害虫遗传防治策略中,包括归巢核酸内切酶基因、锌指核酸酶、转录激活因子样效应因子核酸酶、CRISPR/Cas9系统、Medea元件、Killer-Rescue系统、Wolbachia-细胞质不亲和性系统等。基于这些新的工具手段,许多国家已经在不同程度上启动了下一代害虫遗传防治项目。而我国在该领域的研究相对薄弱,需要在借鉴国外成功经验的同时,进一步加强害虫遗传防治的基础和应用研究,从而实现本地有害生物的可持续治理和外来入侵生物的有效狙击,确保我国未来的粮食和生态安全。     

Association of insecticide use and alteration on Aedes aegypti susceptibility status

Dengue and dengue hemorrhagic fever, vector-borne diseases transmitted by the mosquito Aedes aegypti, are presently important public health problems in Brazil. As the strategy for disease control is based on vector control through the use of insecticides, the development of resistance is a threat to programs efficacy. The objective of this study was to compare the Aedes aegypti susceptibility in nine vector populations from the state of S?o Paulo and seven from Northeast region of Brazil, since there was a difference on group of insecticide used between the areas. Bioassays with larvae and adult were performed according to the World Health Organization methods. The results showed higher resistance levels to organophosphates group in populations from the Northeast region where this group was used for both larvae and adult control than in S?o Paulo where organophosphates were used for larvae and pyretroids for adult control. Resistance to pyretroids in adults was widespread in S?o Paulo after ten years of use of cypermethrin while in vector populations from the Northeast region it was punctual. The difference in resistance profile between the areas is in accordance to the group of insecticide used.