Field Evaluation of a Push-Pull System to Reduce Malaria Transmission

Malaria continues to place a disease burden on millions of people throughout the tropics, especially in sub-Saharan Africa. Although efforts to control mosquito populations and reduce human-vector contact, such as long-lasting insecticidal nets and indoor residual spraying, have led to significant decreases in malaria incidence, further progress is now threatened by the widespread development of physiological and behavioural insecticide-resistance as well as changes in the composition of vector populations. A mosquito-directed push-pull system based on the simultaneous use of attractive and repellent volatiles offers a complementary tool to existing vector-control methods. In this study, the combination of a trap baited with a five-compound attractant and a strip of net-fabric impregnated with micro-encapsulated repellent and placed in the eaves of houses, was tested in a malaria-endemic village in western Kenya. Using the repellent delta-undecalactone, mosquito house entry was reduced by more than 50%, while the traps caught high numbers of outdoor flying mosquitoes. Model simulations predict that, assuming area-wide coverage, the addition of such a push-pull system to existing prevention efforts will result in up to 20-fold reductions in the entomological inoculation rate. Reductions of such magnitude are also predicted when mosquitoes exhibit a high resistance against insecticides. We conclude that a push-pull system based on non-toxic volatiles provides an important addition to existing strategies for malaria prevention.     

Effects of blood-feeding on olfactory sensitivity of the malaria mosquito Anopheles gambiae: Application of mixed linear models to account for repeated measurements

Olfaction plays an important role in the host-seeking behavior of the malaria mosquito Anopheles gambiae. After a complete blood meal, female mosquitoes will not engage in host-seeking behavior until oviposition has occurred. We investigated if peripheral olfactory sensitivity changed after a blood meal by recording electroantennograms (EAGs) of female mosquitoes at three time points (2 h, 48 h and 72 h) to 15 volatile kairomones of either human origin or documented to emanate from oviposition sites. The EAG-sensitivity was compared with that of females of similar age post eclosion. As is common practice in electrophysiological studies, the EAG recordings were obtained by repeated stimulation of the same antennal preparations. We introduce mixed linear modeling as an improved statistical analysis for electrophysiological data. Two hours after blood ingestion, olfactory sensitivity as quantified through EAG-recording increased significantly and selectively, i.e. for seven compounds, compared to unfed females of the same age. Such short-term electrophysiological sensitization in the olfactory system as a result of feeding has not been documented before for insects. Sensitization to six compounds persisted until 48 h or 72 h post-blood meal at one or more concentrations. Desensitization was observed at 48 and 72 h pbm in response to two and three kairomones, respectively. For several compounds, sensitization at the EAG-level corresponded with sensitization found previously in single sensillum studies on olfactory neurons in antennal sensilla trichodea of An. gambiae females. These effects are likely to reflect sensitization to oviposition cues, as eggs have matured 48–72 h pbm. Knowledge of changes in olfactory sensitivity to kairomones can be applied to increase trap catches of malaria mosquitoes that have taken a blood meal and need to locate oviposition sites.     

Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency

Rhabdomyolysis is common in very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and other metabolic myopathies, but its pathogenic basis is poorly understood. Here, we show that prolonged bicycling exercise against a standardized moderate workload in VLCADD patients is associated with threefold bigger changes in phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations in quadriceps muscle and twofold lower changes in plasma acetyl-carnitine levels than in healthy subjects. This result is consistent with the hypothesis that muscle ATP homeostasis during exercise is compromised in VLCADD. However, the measured rates of PCr and Pi recovery post-exercise showed that the mitochondrial capacity for ATP synthesis in VLCADD muscle was normal. Mathematical modeling of oxidative ATP metabolism in muscle composed of three different fiber types indicated that the observed altered energy balance during submaximal exercise in VLCADD patients may be explained by a slow-to-fast shift in quadriceps fiber-type composition corresponding to 30% of the slow-twitch fiber-type pool in healthy quadriceps muscle. This study demonstrates for the first time that quadriceps energy balance during exercise in VLCADD patients is altered but not because of failing mitochondrial function. Our findings provide new clues to understanding the risk of rhabdomyolysis following exercise in human VLCADD.     

Odor coding in the maxillary palp of the malaria vector mosquito Anopheles gambiae

BACKGROUND: Many species of mosquitoes, including the major malaria vector Anopheles gambiae, utilize carbon dioxide (CO(2)) and 1-octen-3-ol as olfactory cues in host-seeking behaviors that underlie their vectorial capacity. However, the molecular and cellular basis of such olfactory responses remains largely unknown. RESULTS: Here, we use molecular and physiological approaches coupled with systematic functional analyses to define the complete olfactory sensory map of the An. gambiae maxillary palp, an olfactory appendage that mediates the detection of these compounds. In doing so, we identify three olfactory receptor neurons (ORNs) that are organized in stereotyped triads within the maxillary-palp capitate-peg-sensillum population. One ORN is CO(2)-responsive and characterized by the coexpression of three receptors that confer CO(2) responses, whereas the other ORNs express characteristic odorant receptors (AgORs) that are responsible for their in vivo olfactory responses. CONCLUSIONS: Our results describe a complete and highly concordant map of both the molecular and cellular olfactory components on the maxillary palp of the adult female An. gambiae mosquito. These results also facilitate the understanding of how An. gambiae mosquitoes sense olfactory cues that might be exploited to compromise their ability to transmit malaria.     

Cardiopulmonary exercise testing in congenital heart disease: equipment and test protocols

Cardiopulmonary exercise testing (CPET) in paediatric cardiology differs in many aspects from the tests as performed in adult cardiology. Children's cardiovascular responses during exercise testing present different characteristics, particularly oxygen uptake, heart rate and blood pressure response, which are essential in interpreting haemodynamic data. Diseases that are associated with myocardial ischaemia are very rare in children. The main indications for CPET in children are evaluation of exercise capacity and the identification of exercise-induced arrhythmias. In this article we will review exercise equipment and test protocols for CPET in children with congenital heart disease. (Neth Heart J 2009;17:339–44.)     

Chromosome analysis of five Brazilian species of poison frogs (Anura: Dendrobatidae)

Dendrobatid frogs have undergone an extensive systematic reorganization based on recent molecular findings. The present work describes karyotypes of the Brazilian species Adelphobates castaneoticus, A. quinquevittatus, Ameerega picta, A. galactonotus and Dendrobates tinctorius which were compared to each other and with previously described related species. All karyotypes consisted of 2n = 18 chromosomes, except for A. picta which had 2n = 24. The karyotypes of the Adelphobates and D. tinctorius species were highly similar to each other and to the other 2n = 18 previously studied species, revealing conserved karyotypic characteristics in both genera. In recent phylogenetic studies, all Adelphobates species were grouped in a clade separated from the Dendrobates species. Thus, we hypothesized that their common karyotypic traits may have a distinct origin by chromosome rearrangements and mutations. In A. picta, with 2n = 24, chromosome features of pairs from 1 to 8 are shared with other previously karyotyped species within this genus. Hence, the A. picta data reinforced that the C-banding pattern and the NOR location are species-specific traits in the genus Ameerega. Moreover, the Ameerega monophyletism proposed by previous phylogenetic studies indicates that the karyotypic differences among species in this genus result from a long divergence time.     

Efficacy of aquatain, a monomolecular film, for the control of malaria vectors in rice paddies

Background

Rice paddies harbour a large variety of organisms including larvae of malaria mosquitoes. These paddies are challenging for mosquito control because their large size, slurry and vegetation make it difficult to effectively apply a control agent. Aquatain, a monomolecular surface film, can be considered a suitable mosquito control agent for such breeding habitats due to its physical properties. The properties allow Aquatain to self-spread over a water surface and affect multiple stages of the mosquito life cycle.

Methodology/Principal Findings

A trial based on a pre-test/post-test control group design evaluated the potential of Aquatain as a mosquito control agent at Ahero rice irrigation scheme in Kenya. After Aquatain application at a dose of 2 ml/m² on rice paddies, early stage anopheline larvae were reduced by 36%, and late stage anopheline larvae by 16%. However, even at a lower dose of 1 ml/m² there was a 93.2% reduction in emergence of anopheline adults and 69.5% reduction in emergence of culicine adults. No pupation was observed in treated buckets that were part of a field bio-assay carried out parallel to the trial. Aquatain application saved nearly 1.7 L of water in six days from a water surface of 0.2 m² under field conditions. Aquatain had no negative effect on rice plants as well as on a variety of non-target organisms, except backswimmers.

Conclusions/Significance

We demonstrated that Aquatain is an effective agent for the control of anopheline and culicine mosquitoes in irrigated rice paddies. The agent reduced densities of aquatic larval stages and, more importantly, strongly impacted the emergence of adult mosquitoes. Aquatain also reduced water loss due to evaporation. No negative impacts were found on either abundance of non-target organisms, or growth and development of rice plants. Aquatain, therefore, appears a suitable mosquito control tool for use in rice agro-ecosystems.     

Laboratory studies on the olfactory behaviour of Anopheles quadriannulatus

The host preference of Anopheles quadriannulatus Theobald (Diptera: Culicidae), the zoophilic member of the malaria mosquito complex Anopheles gambiae Giles, was investigated in a dual‐choice olfactometer. Naïve female mosquitoes were exposed to CO₂, acetone, 1‐octen‐3‐ol, and skin emanations from cows and humans in various combinations. Their behavioural responses were recorded when they had entered one of either upwind traps from where the odours were being released. The mosquitoes did not respond to CO₂ when released at human or cattle equivalent concentrations. Too few mosquitoes responded to acetone to allow for a statistical analysis. The combination of CO₂+ 1‐octen‐3‐ol was repellent. Cow odour alone was slightly attractive, but there was a synergistic attractive effect of cow odour + CO₂. Surprisingly, the mosquitoes were attracted to human odour, and in a choice situation human odour was selected above cow odour + CO₂. Anthropophilic An. gambiae Giles s.s. was repelled by cow odour + CO₂ in contrast to An. quadriannulatus. In a choice situation, both mosquito species selected human odour above cow odour + CO₂. The implications of these results are discussed in the light of recent behavioural data from the field.