Trajectories of body mass index and waist circumference in four Peruvian settings at different level of urbanisation: the CRONICAS Cohort Study

BACKGROUND: Studies have reported the incidence/risk of becoming obese, but few have described the trajectories of body mass index (BMI) and waist circumference (WC) over time, especially in low/middle-income countries. We assessed the trajectories of BMI and WC according to sex in four sites in Peru. METHODS: Data from the population-based CRONICAS Cohort Study were analysed. We fitted a population-averaged model by using generalised estimating equations. The outcomes of interest, with three data points over time, were BMI and WC. The exposure variable was the factorial interaction between time and study site. RESULTS: At baseline mean age was 55.7 years (SD: 12.7) and 51.6% were women. Mean follow-up time was 2.5 years (SD: 0.4). Over time and across sites, BMI and WC increased linearly. The less urbanised sites showed a faster increase than more urbanised sites, and this was also observed after sex stratification. Overall, the fastest increase was found for WC compared with BMI. Compared with Lima, the fastest increase in WC was in rural Puno (coefficient=0.73, P<0.001), followed by urban Puno (coefficient=0.59, P=0.001) and Tumbes (coefficient=0.22, P=0.088). CONCLUSIONS: There was a linear increase in BMI and WC across study sites, with the greatest increase in less urbanised areas. The ongoing urbanisation process, common to Peru and other low/middle-income countries, is accompanied by different trajectories of increasing obesity-related markers

Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs

We have previously shown that genetic disruption of Toxoplasma gondii calcium-dependent protein kinase 3 (TgCDPK3) affects calcium ionophore-induced egress. We examined whether Plasmodium falciparum CDPK1 (PfCDPK1), the closest homolog of TgCDPK3 in the malaria parasite P. falciparum, could complement a TgCDPK3 mutant strain. PfCDPK1 is essential and plays critical roles in merozoite development, motility, and secretion. We show that expression of PfCDPK1 in the TgCDPK3 mutant strain rescues the egress defect. This phenotypic complementation requires the localization of PfCDPK1 to the plasma membrane and kinase activity. Interestingly, PfCDPK1-expressing Toxoplasma becomes more sensitive to egress inhibition by purfalcamine, a potent inhibitor of PfCDPK1 with low activity against TgCDPK3. Based on this result, we tested eight small molecules previously determined to inhibit the kinase activity of recombinant PfCDPK1 for their abilities to inhibit ionophore-induced egress in the PfCDPK1-expressing strain. While two of these chemicals did not inhibit egress, we found that six drugs affected this process selectively in PfCDPK1-expressing Toxoplasma. Using mutant versions of PfCDPK1 and TgCDPK3, we show that the selectivities of dasatinib and PLX-4720 are regulated by the gatekeeper residue in the ATP binding site. Importantly, we have confirmed that the three most potent inhibitors of egress in the PfCDPK1-expressing strain effectively kill P. falciparum. Thus, we have established and validated a recombinant strain of Toxoplasma that can be used as a surrogate for the discovery and analysis of PfCDPK1-specific inhibitors that can be developed as antimalarials

Humidity and gravimetric equivalency adjustments for nephelometer-based particulate matter measurements of emissions from solid biomass fuel in cookstoves

Great uncertainty exists around indoor biomass burning exposure-disease relationships due to lack of detailed exposure data in large health outcome studies. Passive nephelometers can be used to estimate high particulate matter (PM) concentrations during cooking in low resource environments. Since passive nephelometers do not have a collection filter they are not subject to sampler overload. Nephelometric concentration readings can be biased due to particle growth in high humid environments and differences in compositional and size dependent aerosol characteristics. This paper explores relative humidity (RH) and gravimetric equivalency adjustment approaches to be used for the pDR-1000 used to assess indoor PM concentrations for a cookstove intervention trial in Nepal. Three approaches to humidity adjustment performed equivalently (similar root mean squared error). For gravimetric conversion, the new linear regression equation with log-transformed variables performed better than the traditional linear equation. In addition, gravimetric conversion equations utilizing a spline or quadratic term were examined. We propose a humidity adjustment equation encompassing the entire RH range instead of adjusting for RH above an arbitrary 60% threshold. Furthermore, we propose new integrated RH and gravimetric conversion methods because they have one response variable (gravimetric PM2.5 concentration), do not contain an RH threshold, and is straightforward

Cutaneous Larva Migrans Presenting with Folliculitis.

No abstract available

Bacterial genomics reveal the complex epidemiology of an emerging pathogen in Arctic and boreal ungulates

Northern ecosystems are currently experiencing unprecedented ecological change, largely driven by a rapidly changing climate. Pathogen range expansion, and emergence and altered patterns of infectious disease, are increasingly reported in wildlife at high latitudes. Understanding the causes and consequences of shifting pathogen diversity and host-pathogen interactions in these ecosystems is important for wildlife conservation, and for indigenous populations that depend on wildlife. Among the key questions are whether disease events are associated with endemic or recently introduced pathogens, and whether emerging strains are spreading throughout the region. In this study, we used a phylogenomic approach to address these questions of pathogen endemicity and spread for Erysipelothrix rhusiopathiae, an opportunistic multi-host bacterial pathogen associated with recent mortalities in arctic and boreal ungulate populations in North America. We isolated E. rhusiopathiae from carcasses associated with large-scale die-offs of muskoxen in the Canadian Arctic Archipelago, and from contemporaneous mortality events and/or population declines among muskoxen in northwestern Alaska and caribou and moose in western Canada. Bacterial genomic diversity differed markedly among these locations; minimal divergence was present among isolates from muskoxen in the Canadian Arctic, while in caribou and moose populations, strains from highly divergent clades were isolated from the same location, or even from within a single carcass. These results indicate that mortalities among northern ungulates are not associated with a single emerging strain of E. rhusiopathiae, and that alternate hypotheses need to be explored. Our study illustrates the value and limitations of bacterial genomic data for discriminating between ecological hypotheses of disease emergence, and highlights the importance of studying emerging pathogens within the broader context of environmental and host factors

A cross-sectional study of determinants of indoor environmental exposures in households with and without chronic exposure to biomass fuel smoke

BACKGROUND: Burning biomass fuels indoors for cooking is associated with high concentrations of particulate matter (PM) and carbon monoxide (CO). More efficient biomass-burning stoves and chimneys for ventilation have been proposed as solutions to reduce indoor pollution. We sought to quantify indoor PM and CO exposures in urban and rural households and determine factors associated with higher exposures. A secondary objective was to identify chronic vs. acute changes in cardiopulmonary biomarkers associated with exposure to biomass smoke. METHODS: We conducted a census survey followed by a cross-sectional study of indoor environmental exposures and cardiopulmonary biomarkers in the main household cook in Puno, Peru. We measured 24-hour indoor PM and CO concentrations in 86 households. We also measured PM(2.5) and PM(10) concentrations gravimetrically for 24 hours in urban households and during cook times in rural households, and generated a calibration equation using PM(2.5) measurements. RESULTS: In a census of 4903 households, 93% vs. 16% of rural vs. urban households used an open-fire stove; 22% of rural households had a homemade chimney; and <3% of rural households participated in a national program encouraging installation of a chimney. Median 24-hour indoor PM(2.5) and CO concentrations were 130 vs. 22 μg/m(3) and 5.8 vs. 0.4 ppm (all p<0.001) in rural vs. urban households. Having a chimney did not significantly reduce median concentrations in 24-hour indoor PM(2.5) (119 vs. 137 μg/m(3); p=0.40) or CO (4.6 vs. 7.2 ppm; p=0.23) among rural households with and without chimneys. Having a chimney did not significantly reduce median cook-time PM(2.5) (360 vs. 298 μg/m(3), p=0.45) or cook-time CO concentrations (15.2 vs. 9.4 ppm, p=0.23). Having a thatched roof (p=0.007) and hours spent cooking (p=0.02) were associated with higher 24-hour average PM concentrations. Rural participants had higher median exhaled CO (10 vs. 6 ppm; p=0.01) and exhaled carboxyhemoglobin (1.6% vs. 1.0%; p=0.04) than urban participants. CONCLUSIONS: Indoor air concentrations associated with biomass smoke were six-fold greater in rural vs. urban households. Having a homemade chimney did not reduce environmental exposures significantly. Measures of exhaled CO provide useful cardiopulmonary biomarkers for chronic exposure to biomass smoke

Comparison of next-generation portable pollution monitors to measure exposure to PM2.5 from household air pollution in Puno, Peru.

Assessment of personal exposure to PM2.5 is critical for understanding intervention effectiveness and exposure-response relationships in household air pollution studies. In this pilot study, we compared PM2.5 concentrations obtained from two next-generation personal exposure monitors (the Enhanced Children MicroPEM or ECM; and the Ultrasonic Personal Air Sampler or UPAS) to those obtained with a traditional Triplex Cyclone and SKC Air Pump (a gravimetric cyclone/pump sampler). We co-located cyclone/pumps with an ECM and UPAS to obtain 24-hour kitchen concentrations and personal exposure measurements. We measured Spearmen correlations and evaluated agreement using the Bland-Altman method. We obtained 215 filters from 72 ECM and 71 UPAS co-locations. Overall, the ECM and the UPAS had similar correlation (ECM ρ = 0.91 vs UPAS ρ = 0.88) and agreement (ECM mean difference of 121.7 µg/m3 vs UPAS mean difference of 93.9 µg/m3 ) with overlapping confidence intervals when compared against the cyclone/pump. When adjusted for the limit of detection, agreement between the devices and the cyclone/pump was also similar for all samples (ECM mean difference of 68.8 µg/m3 vs UPAS mean difference of 65.4 µg/m3 ) and personal exposure samples (ECM mean difference of -3.8 µg/m3 vs UPAS mean difference of -12.9 µg/m3 ). Both the ECM and UPAS produced comparable measurements when compared against a cyclone/pump setup

Size distribution and lung‐deposited doses of particulate matter from household exposure to biomass smoke

Exposure to high concentrations of particulate matter (PM) is associated with a number of adverse health effects. However, it is unclear which aspects of PM are most hazardous, and a better understanding of particle sizes and personal exposure is needed. We characterized particle size distribution (PSD) from biomass‐related pollution and assessed total and regional lung‐deposited doses using multiple‐path deposition modeling. Gravimetric measurements of kitchen and personal PM2.5 (< 2.5 µm in size) exposures were collected in 180 households in rural Puno, Peru. Direct‐reading measurements of number concentrations were collected in a subset of 20 kitchens for particles 0.3–25 µm, and the continuous PSD was derived using a nonlinear least‐squares method. Mean daily PM2.5 kitchen concentration and personal exposure was 1205±942 µg/m3 and 115±167 µg/m3 respectively, and the mean mass concentration consisted of a primary accumulation mode at 0.21 µm and a secondary coarse mode at 3.17 µm. Mean daily lung‐deposited surface area (LDSA) and LDSA during cooking were 1009.6±1469.8 µm2/cm3 and 10,552.5±8261.6 µm2/cm3, respectively. This study presents unique data regarding lung deposition of biomass smoke that could serve as a reference for future studies, and provides a novel, more biologically‐relevant metric for exposure‐response analysis compared to traditional size‐based metrics

Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in sea-level and high-altitude settings.

AIM: Higher haemoglobin levels and differences in glucose metabolism have been reported among high-altitude residents, which may influence the diagnostic performance of HbA1c . This study explores the relationship between HbA1c and fasting plasma glucose (FPG) in populations living at sea level and at an altitude of > 3000 m. METHODS: Data from 3613 Peruvian adults without a known diagnosis of diabetes from sea-level and high-altitude settings were evaluated. Linear, quadratic and cubic regression models were performed adjusting for potential confounders. Receiver operating characteristic (ROC) curves were constructed and concordance between HbA1c and FPG was assessed using a Kappa index. RESULTS: At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05) for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA1c ; and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The adjusted relationship between HbA1c and FPG was quadratic at sea level and linear at high altitude. Adjusted models showed that, to predict an HbA1c value of 48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA1c cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95% confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to 63.6) at high altitude. CONCLUSION: The relationship between HbA1c and FPG is less clear at high altitude than at sea level. Caution is warranted when using HbA1c to diagnose diabetes mellitus in this setting

Indoor air pollution concentrations and cardiometabolic health across four diverse settings in Peru: a cross-sectional study.

BACKGROUND: Indoor air pollution is an important risk factor for health in low- and middle-income countries. METHODS: We measured indoor fine particulate matter (PM2.5) and carbon monoxide (CO) concentrations in 617 houses across four settings with varying urbanisation, altitude, and biomass cookstove use in Peru, between 2010 and 2016. We assessed the associations between indoor pollutant concentrations and blood pressure (BP), exhaled carbon monoxide (eCO), C-reactive protein (CRP), and haemoglobin A1c (HbA1c) using multivariable linear regression among all participants and stratifying by use of biomass cookstoves. RESULTS: We found high concentrations of indoor PM2.5 across all four settings (geometric mean ± geometric standard deviation of PM2.5 daily average in μg/m3): Lima 41.1 ± 1.3, Tumbes 35.8 ± 1.4, urban Puno 14.1 ± 1.7, and rural Puno 58.8 ± 3.1. High indoor CO concentrations were common in rural households (geometric mean ± geometric standard deviation of CO daily average in ppm): rural Puno 4.9 ± 4.3. Higher indoor PM2.5 was associated with having a higher systolic BP (1.51 mmHg per interquartile range (IQR) increase, 95% CI 0.16 to 2.86), a higher diastolic BP (1.39 mmHg higher DBP per IQR increase, 95% CI 0.52 to 2.25), and a higher eCO (2.05 ppm higher per IQR increase, 95% CI 0.52 to 3.57). When stratifying by biomass cookstove use, our results were consistent with effect measure modification in the association between PM2.5 and eCO: among biomass users eCO was 0.20 ppm higher per IQR increase in PM2.5 (95% CI - 2.05 to 2.46), and among non-biomass users eCO was 5.00 ppm higher per IQR increase in PM2.5 (95% CI 1.58 to 8.41). We did not find associations between indoor air concentrations and CRP or HbA1c outcomes. CONCLUSIONS: Excessive indoor concentrations of PM2.5 are widespread in homes across varying levels of urbanisation, altitude, and biomass cookstove use in Peru and are associated with worse BP and higher eCO