Contained semi-field environments for ecological studies on transgenic African malaria vectors: benefits and constraints

New interventions are needed to reduce the burden of vector-borne diseases like malaria and dengué, which are among the most serious and prevalent infectious diseases worldwide. The release of genetically modified (GM) mosquitoes may offer an alternative strategy to do so while circumventing the pitfalls of current vector control methods. Current methodologies are stalling because of drug resistance, absence of vaccines and inadequate mosquito control techniques. GM mosquitoes have been developed that are resistant to pathogen infection and transmission, but the public-health and environmental consequences of releasing such insects are unclear, mainly because of a lack of knowledge of the ecology and population biology of mosquitoes. This book is the reflection of a workshop, held in June 2002, that addressed these issues. Experts on mosquito ecology met for the first time to discuss the current knowledge of mosquito ecology with respect to GM-insect technology. Emphasis of the workshop was on evaluating how human health and natural ecosystems, including target wild-mosquito populations, will respond to the invasion of GM vectors. This volume will stimulate discussion by clearly showing the importance of vector ecology for prevention of vector-borne disease

Linking individual phenotype to density-dependent population growth: the influence of body size on the population dynamics of malaria vectors

Understanding the endogenous factors that drive the population dynamics of malaria mosquitoes will facilitate more accurate predictions about vector control effectiveness and our ability to destabilize the growth of either low- or high-density insect populations. We assessed whether variation in phenotypic traits predict the dynamics of Anopheles gambiae sensu lato mosquitoes, the most important vectors of human malaria. Anopheles gambiae dynamics were monitored over a six-month period of seasonal growth and decline. The population exhibited density-dependent feedback, with the carrying capacity being modified by rainfall (97% wAICc support). The individual phenotypic expression of the maternal (p = 0.0001) and current (p = 0.040) body size positively influenced population growth. Our field-based evidence uniquely demonstrates that individual fitness can have population-level impacts and, furthermore, can mitigate the impact of exogenous drivers (e.g. rainfall) in species whose reproduction depends upon it. Once frontline interventions have suppressed mosquito densities, attempts to eliminate malaria with supplementary vector control tools may be attenuated by increased population growth and individual fitness

Contained semi-field environments for ecological studies on transgenic African malaria vectors: benefits and constraints

Recent successful genetic transformation of disease-transmitting insects has fuelled enthusiasm towards its potential application for disease control in the future. However, advances to date have been confined to laboratory settings and many questions relating to the fitness, behaviour, ecology and phenotypic characteristics of transformed insects remain unanswered. Spread of desired traits, such as refractoriness to Plasmodium infection, will depend on the reproductive fitness and manifestation of life-history behaviours, such as dispersal and mating, by engineered specimens. These should preferably be similar to those displayed by their wild conspecifics but may be compromised by genetic modification and difficult to assess realistically under standard laboratory conditions. Contained semi-field environments that mimic a near-natural environment and are exposed to ambient climatic conditions may serve to verify laboratory findings and yield valuable insights into transgene fixation processes prior to field releases of transgenic specimens into the wild. Here we describe the constraints and benefits of this approach with respect to containment stringency, facility design and operational guidelines for studies involving genetically-engineered malaria vectors. We also report on our initial success with such semi-field systems in West Kenya, using non-transgenic mosquitoes in a variety of behavioural and ecological studies. Successful completion of the Anopheles gambiae life cycle, and thus expression of all major life-history behaviours, occurred in three separate trials. However, our results show that the sustenance of successive and overlapping generations in such systems may be difficult. Considering the frequently expressed and explicit need for contained semi-field trials with engineered insects prior to field releases, this calls for intensified development of improved semifield systems, preferably in field sites earmarked for future release

Artemisinin-based combination therapy does not measurably reduce human infectiousness to vectors in a setting of intense malaria transmission

<p>Background: Artemisinin-based combination therapy (ACT) for treating malaria has activity against immature gametocytes. In theory, this property may complement the effect of terminating otherwise lengthy malaria infections and reducing the parasite reservoir in the human population that can infect vector mosquitoes. However, this has never been verified at a population level in a setting with intense transmission, where chronically infectious asymptomatic carriers are common and cured patients are rapidly and repeatedly re-infected.</p> <p>Methods: From 2001 to 2004, malaria vector densities were monitored using light traps in three Tanzanian districts. Mosquitoes were dissected to determine parous and oocyst rates. Plasmodium falciparum sporozoite rates were determined by ELISA. Sulphadoxinepyrimethamine(SP) monotherapy was used for treatment of uncomplicated malaria in the contiguous districts of Kilombero and Ulanga throughout this period. In Rufiji district, the standard drug was changed to artesunate co-administered with SP (AS + SP) in March 2003. The effects of this change in case management on malaria parasite infection in the vectors were analysed.</p> <p>Results: Plasmodium falciparum entomological inoculation rates exceeded 300 infective bites per person per year at both sites over the whole period. The introduction of AS + SP in Rufiji was associated with increased oocyst prevalence (OR [95%CI] = 3.9 [2.9-5.3], p < 0.001), but had no consistent effect on sporozoite prevalence (OR [95%CI] = 0.9 [0.7-1.2], p = 0.5). The estimated infectiousness of the human population in Rufiji was very low prior to the change in drug policy. Emergence rates and parous rates of the vectors varied substantially throughout the study period, which affected estimates of infectiousness. The latter consequently cannot be explained by the change in drug policy.</p> <p>Conclusions: In high perennial transmission settings, only a small proportion of infections in humans are symptomatic or treated, so case management with ACT may have little impact on overall infectiousness of the human population. Variations in infection levels in vectors largely depend on the age distribution of the mosquito population. Benefits of ACT in suppressingtransmission are more likely to be evident where transmission is already low or effective vector control is widely implemented.</p&gt

Habitat characterization and spatial distribution of Anopheles sp. mosquito larvae in Dar es Salaam (Tanzania) during an extended dry period

Introduction: By 2030, more than 50% of the African population will live in urban areas. Controlling malaria reduces the disease burden and further improves economic development. As a complement to treated nets and prompt access to treatment, measures targeted against the larval stage of Anopheles sp. mosquitoes are a promising strategy for urban areas. However, a precise knowledge of the geographic location and potentially of ecological characteristics of breeding sites is of major importance for such interventions. Methods: In total 151 km2 of central Dar es Salaam, the biggest city of Tanzania, were systematically searched for open mosquito breeding sites. Ecologic parameters, mosquito larvae density and geographic location were recorded for each site. Logistic regression analysis was used to determine the key ecological factors explaining the different densities of mosquito larvae. Results: A total of 405 potential open breeding sites were examined. Large drains, swamps and puddles were associated with no or low Anopheles sp. larvae density. The probability of Anopheles sp. larvae to be present was reduced when water was identified as turbid . Small breeding sites were more commonly colonized by Anopheles sp. larvae. Further, Anopheles gambiae s.l. larvae were found in highly organically polluted habitats. Conclusions: Clear ecological characteristics of the breeding requirements of Anopheles sp. larvae could not be identified in this setting. Hence, every stagnant open water body, including very polluted ones, have to be considered as potential malaria vector breeding sites. © 2005 Sattler et al; licensee BioMed Central Ltd

Extent of digestion affects the success of amplifying human DNA from blood meals of Anopheles gambiae (Diptera: Culicidae)

The success of distinguishing blood meal sources of Anopheles gambiae Giles through deoxyribonucleic acid (DNA) profiling was investigated by polymerase chain reaction (PCR) amplification at the TC-11 and VWA human short tandem repeats (STR) loci. Blood meal size and locus had no significant effect on the success of amplifying human DNA from blood meals digested for 0, 8, 16, 24 and 32 h (P = 0.85 and 0.26 respectively). However, logistic regression found a significant negative relationship between time since ingestion and the success probability of obtaining positive PCR products among meals digested for between 8 and 32 h (P = 0.001). Approximately 80 f fresh blood meals were successfully profiled. After 8 h, the proportion of blood meals that could be successfully profiled decreased slowly with time after ingestion, dropping to below 50 fter approximately 15 h. There was no significant difference in the success of amplifying human DNA from blood meals of mosquitoes killed at time 0 and 8 h after ingestion (P = 0.272)

Spatial repellents: from discovery and development to evidence based validation

International public health workers are challenged by a burden of arthropod-borne disease that remains elevated despite best efforts in control programmes. With this challenge comes the opportunity to develop novel vector control paradigms to guide product development and programme implementation. The role of vector behaviour modification in disease control was first highlighted several decades ago but has received limited attention within the public health community. This paper presents current evidence highlighting the value of sub-lethal agents, specifically spatial repellents, and their use in global health, and identifies the primary challenges towards establishing a clearly defined and recommended role for spatial repellent products in disease control

Cost-sharing strategies combining targeted public subsidies with private-sector delivery achieve high bednet coverage and reduced malaria transmission in Kilombero Valley, southern Tanzania

Background: Cost-sharing schemes incorporating modest targeted subsidies have promoted insecticide-treated nets (ITNs) for malaria prevention in the Kilombero Valley, southern Tanzania, since 1996. Here we evaluate resulting changes in bednet coverage and malaria transmission. Methods: Bednets were sold through local agents at fixed prices representing a 34% subsidy relative to full delivery cost. A further targeted subsidy of 15% was provided to vulnerable groups through discount vouchers delivered through antenatal clinics and regular immunizations. Continuous entomological surveys (2,376 trap nights) were conducted from October 2001 to September 2003 in 25 randomly-selected population clusters of a demographic surveillance system which monitored net coverage. Results: Mean net usage of 75 % (11,982/16,086) across all age groups was achieved but now-obsolete technologies available at the time resulted in low insecticide treatment rates. Malaria transmission remained intense but was substantially reduced: Compared with an exceptionally high historical mean EIR of 1481, even non-users of nets were protected (EIR [fold reduction] = 349 infectious bites per person per year [×4]), while the average resident (244 [×6]), users of typical nets (210 [×7]) and users of insecticidal nets (105 [×14]) enjoyed increasing benefits. Conclusion: Despite low net treatment levels, community-level protection was equivalent to the personal protection of an ITN. Greater gains for net users and non-users are predicted if more expensive long-lasting ITN technologies can be similarly promoted with correspondingly augmented subsidies. Cost sharing strategies represent an important option for national programmes lacking adequate financing to fully subsidize comprehensive ITN coverage