Adherence to Chemoprophylaxis and Plasmodium falciparum Anti-Circumsporozoite Seroconversion in a Prospective Cohort Study of Dutch Short-Term Travelers

Background

We conducted a prospective study in a cohort of short-term travelers assessing the incidence rate of anti-circumsporozoite seroconversion, adherence to chemoprophylaxis, symptoms of malaria during travel, and malaria treatment abroad.

Methods

Adults were recruited from the travel clinic of the Public Health Service Amsterdam. They kept a structured daily travel diary and donated blood samples before and after travel. Blood samples were serologically tested for the presence of Plasmodium falciparum anti-circumsporozoite antibodies.

Results

Overall, the incidence rate (IR) of anti-circumsporozoite seroconversion was 0.8 per 100 person-months. Of 945 travelers, 620 (66%) visited high-endemic areas and were advised about both chemoprophylaxis and preventive measures against mosquito bites. Most subjects (520/620 = 84%) took at least 75% of recommended prophylaxis during travel. Travel to Africa, use of mefloquine, travel duration of 14–29 days in endemic areas, and concurrent use of DEET (N,N-diethyl-meta-toluamide) were associated with good adherence practices. Four travelers without fever seroconverted, becoming anti-circumsporozoite antibody-positive. All four had been adherent to chemoprophylaxis; two visited Africa, one Suriname, one India. Ten subjects with fever were tested for malaria while abroad and of these, three received treatment. All three were adherent to chemoprophylaxis and tested negative for anti-circumsporozoite antibodies.

Conclusion

Travel to Africa, using mefloquine, travel duration of 14–29 days in endemic areas, and use of DEET were associated with good adherence to chemoprophylaxis. The combination of chemoprophylaxis and other preventive measures were sufficient to protect seroconverting travelers from clinical malaria. Travelers who were treated for malaria abroad did not seroconvert.     

Novel benzimidazole-based MCH R1 antagonists

The identification of an MCH R1 antagonist screening hit led to the optimization of a class of benzimidazole-based MCH R1 antagonists. Structure-activity relationships and efforts to optimize pharmacokinetic properties are detailed along with the demonstration of the effectiveness of an MCH R1 antagonist in an animal model of obesity.     

Mosquito and biting fly surveillance on Camp Zama Army Base,Kanagawa Prefecture,Japan

Camp Zama, Japan, and the associated military housing and depot storage areas have been occupied by the US military for over 50 years. The military base has experienced less urbanization and development during those 50 years when compared to the surrounding cities of Zama and Sagamihara. We present an annotated comparative checklist of historical records of biting flies (mosquitoes, black flies, biting midges, stable flies, and horse flies) with recent collections. Overall 24 species of biting flies have been reported from Camp Zama, with 17 of these species collected during the last 5 years. Vectors of human and veterinary pathogens were collected including Anopheles sinensis, Aedes albopictus, Culex tritaeniorhynchus, and Simulium bidentatum.     

An anthocyanin/polyphenolic-rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands

Oxidative cell damage is involved in the pathogenesis of atherosclerosis, cancer, diabetes and other diseases. Uptake of fruit juice with especially high content of antioxidant flavonoids/polyphenols, might reduce oxidative cell damage. Therefore, an intervention study was performed with a red mixed berry juice [trolox equivalent antioxidative capacity (TEAC): 19.1 mmol/L trolox] and a corresponding polyphenol-depleted juice (polyphenols largely removed, TEAC 2.4 mmol/L trolox), serving as control. After a 3-week run-in period, 18 male probands daily consumed 700 mL juice, and 9 consumed control juice, in a 4-week intervention, followed by a 3-week wash-out. Samples were collected weekly to analyze DNA damage (comet assay), lipid peroxidation (plasma malondialdehyde: HPLC/fluorescence; urinary isoprostanes: GC-MS), blood glutathione (photometrically), DNA-binding activity of nuclear factor-kappaB (ELISA) and plasma carotenoid/alpha-tocopherol levels (HPLC-DAD). During intervention with the fruit juice, a decrease of oxidative DNA damage (p<5x10(-4)) and an increase of reduced glutathione (p<5x10(-4)) and of glutathione status (p<0.05) were observed, which returned to the run-in levels in the subsequent wash-out phase. The other biomarkers were not significantly modulated by the juice supplement. Intervention with the control juice did not result in reduction of oxidative damage. In conclusion, the fruit juice clearly reduces oxidative cell damage in healthy probands.     

Noise, predation risk compensation and vigilance in the chaffinch Fringilla coelebs

Background noise should in theory hinder detection of auditory cues associated with approaching danger. We tested whether foraging chaffinches Fringilla coelebs responded to background noise by increasing vigilance, and examined whether this was explained by predation risk compensation or by a novel stimulus hypothesis. The former predicts that only inter-scan interval should be modified in the presence of background noise, not vigilance levels generally. This is because noise hampers auditory cue detection and increases perceived predation risk primarily when in the head-down position, and also because previous tests have shown that only interscan interval is correlated with predator detection ability in this system. Chaffinches only modified interscan interval supporting this hypothesis. At the same time they made significantly fewer pecks when feeding during the background noise treatment and so the increased vigilance led to a reduction in intake rate, suggesting that compensating for the increased predation risk could indirectly lead to a fitness cost. Finally, the novel stimulus hypothesis predicts that chaffinches should habituate to the noise, which did not occur within a trial or over 5 subsequent trials. We conclude that auditory cues may be an important component of the trade-off between vigilance and feeding, and discuss possible implications for anti-predation theory and ecological processes.     

Assessment of drug-induced mitochondrial dysfunction via altered cellular respiration and acidification measured in a 96-well platform

High-throughput applicable screens for identifying drug-induced mitochondrial impairment are necessary in the pharmaceutical industry. Hence, we evaluated the XF96 Extracellular Flux Analyzer, a 96-well platform that measures changes in the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of cells. The sensitivity of the platform was bench-marked with known modulators of oxidative phosphorylation and glycolysis. Sixteen therapeutic agents were screened in HepG2 cells for mitochondrial effects. Four of these compounds, thiazolidinediones, were also tested in primary feline cardiomyocytes for cell-type specific effects. We show that the XF96 platform is a robust, sensitive system for analyzing drug-induced mitochondrial impairment in whole cells. We identified changes in cellular respiration and acidification upon addition of therapeutic agents reported to have a mitochondrial effect. Furthermore, we show that respiration and acidification changes upon addition of the thiazoldinediones were cell-type specific, with the rank order of mitochondrial impairment in whole cells being in accord with the known adverse effects of these drugs.     

Tunable pores for measuring concentrations of synthetic and biological nanoparticle dispersions

Scanning ion occlusion sensing (SIOS), a technique that uses a tunable pore to detect the passage of individual nano-scale objects, is applied here for the rapid, accurate and direct measurement of synthetic and biological nanoparticle concentrations. SIOS is able to characterize smaller particles than other direct count techniques such as flow cytometry or Coulter counters, and the direct count avoids approximations such as those necessary for turbidity measurements. Measurements in a model system of 210-710 nm diameter polystyrene particles demonstrate that the event frequency scales linearly with applied pressure and concentration, and that measured concentrations are independent of particle type and size. Both an external-calibration and a calibration-free measurement method are demonstrated. SIOS is then applied to measure concentrations of Baculovirus occlusion bodies, with a diameter of ~1 μm, and the marine photosynthetic cyanobacterium Prochlorococcus, with a diameter of ~600 nm. The determined concentrations agree well with results from counting with microscopy (a 17% difference between the mean concentrations) and flow cytometry (6% difference between the mean concentrations), respectively.     

Mentalizing deficits constrain belief in a personal God

Religious believers intuitively conceptualize deities as intentional agents with mental states who anticipate and respond to human beliefs, desires and concerns. It follows that mentalizing deficits, associated with the autistic spectrum and also commonly found in men more than in women, may undermine this intuitive support and reduce belief in a personal God. Autistic adolescents expressed less belief in God than did matched neuro-typical controls (Study 1). In a Canadian student sample (Study 2), and two American national samples that controlled for demographic characteristics and other correlates of autism and religiosity (Study 3 and 4), the autism spectrum predicted reduced belief in God, and mentalizing mediated this relationship. Systemizing (Studies 2 and 3) and two personality dimensions related to religious belief, Conscientiousness and Agreeableness (Study 3), failed as mediators. Mentalizing also explained the robust and well-known, but theoretically debated, gender gap in religious belief wherein men show reduced religious belief (Studies 2-4).